bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse moment of the Bs-meson distribution amplitude from QCD sum rule
Authors: Khodjamirian Alexander , Mandal Rusa , Mannel Thomas
Published: October 2020

Abstract

We derive a QCD sum rule for the inverse moment of the Bs-meson light-cone distribution amplitude in HQET. Within this method, the SU(3)f l symmetry violation is traced to the strange quark mass and to the difference between strange and nonstrange quark condensate densities. We predict the ratio of inverse moments λBs/λB = 1.19 ± 0.14 which can be used in various applications of these distribution amplitudes to the analyses of Bs-meson decays, provided an accurate value of λB is available from other sources, such as the B → ℓνℓγ decay.
Ruelle Zeta Function from Field Theory
Authors: Hadfield Charles , Kandel Santosh , Schiavina Michele
Published: October 2020

We propose a field-theoretic interpretation of Ruelle zeta function and show how it can be seen as the partition function forBFtheory when an unusual gauge-fixing condition on contact manifolds is imposed. This suggests an alternative rephrasing of a conjecture due to Fried on the equivalence between Ruelle zeta function and analytic torsion, in terms of homotopies of Lagrangian submanifolds.
Technological Solutions and Contested Interpretations of Scientific Results: Risk Assessment of Diesel Emissions in the United States and in West Germany, 1977–1995
Authors: Neumaier Christopher
Published: October 2020

This article traces the different classifications of diesel emissions either as “safe” or as “hazardous” in the US and in West Germany between 1977 and 1995. It argues that the environmental regulation of diesel emissions was a political threshold. It contributes to our general understanding of how politicians, environmental lobbyists, scientists, and engineers constructed the standards and norms that defined the “safe” limit of environmental pollutants. After discussing how diesel emissions came under review as a potential carcinogen, I will show that the coding as “safe” or as “hazardous” resulted from negotiations that were entirely dependent on the temporal, geographical, and intellectual contexts in which diesel technology, scientific research on their emissions, and political regulation were embedded. In particular, I trace the differences in German and US regulatory policy. While US regulation relied more on epidemiology that provided only weak data on the carcinogenicity of diesel particulates in the early 1980s, German government agencies tended to base their policy around the mid-1980s more on the results of animal tests and shortly afterwards also on epidemiology. Furthermore, the article reveals how US and German automakers tried to foster doubt on the carcinogenicity of diesel emissions and how their approaches differed and shifted. Thereby, it sheds light on the triangular relationship between technology, science, and politics in regulatory processes by analyzing the different roles of the state, automakers, scientists, and environmental agencies in Germany and in the United States.
Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases
Authors: Salminen Antero
Published: October 2020

Chronic low-grade inflammation is a common hallmark of the aging process and many age-related diseases. There is substantial evidence that persistent inflammation is associated with a compensatory anti-inflammatory response which prevents excessive tissue damage. Interestingly, the inflammatory state encountered with aging, called inflammaging, is associated with the anti-inflammaging process. The age-related activation of immunosuppressive network includes an increase in the numbers of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and macrophages (Mreg/M2c). Immunosuppressive cells secrete several anti-inflammatory cytokines, e.g., TGF-β and IL-10, as well as reactive oxygen and nitrogen species (ROS/RNS). Moreover, immunosuppressive cells suppress the function of effector immune cells by catabolizingl-arginine and tryptophan through the activation of arginase 1 (ARG1) and indoleamine 2,3-dioxygenase (IDO), respectively. Unfortunately, the immunosuppressive armament also induces harmful bystander effects in neighboring cells by impairing host tissue homeostasis. For instance, TGF-β signaling can trigger many age-related degenerative changes, e.g., cellular senescence, fibrosis, osteoporosis, muscle atrophy, and the degeneration of the extracellular matrix. In addition, changes in the levels of ROS, RNS, and the metabolites of the kynurenine pathway can impair tissue homeostasis. This review will examine in detail the harmful effects of the immunosuppressive cells on host tissues. It seems that this age-related immunosuppression prevents inflammatory damage but promotes the tissue degeneration associated with aging and age-related diseases.

Key messages

• Low-grade inflammation is associated with the aging process and age-related diseases.

• Persistent inflammation activates compensatory immunosuppression with aging.

• The numbers of immunosuppressive cells increase with aging and age-related diseases.

• Immunosuppressive mechanisms evoke harmful bystander effects in host tissues.

• Immunosuppression promotes tissue degeneration with aging and age-related diseases.
Immuntherapie und Tyrosinkinaseinhibitoren beim metastasierten Nierenzellkarzinom in der First-line-Therapie – Wann welche Strategie?
Authors: Mickisch G. , Peters I. , Grüllich C. , Mudra T. , Doehn C.
Published: October 2020

Immuntherapien mit Checkpoint-Inhibitoren haben beim metastasierten klarzelligen Nierenzellkarzinom (mRCC) zu einem Paradigmenwechsel geführt und einen neuen Standard in der Erstlinie etabliert. Einschließlich der bekannten Monotherapie mit Tyrosinkinaseinhibitoren ist das Spektrum an medikamentösen Therapieoptionen somit breiter geworden. In diesem Beitrag sollen anhand der aktuellen Studiendaten sowie Leitlinienempfehlungen mögliche Faktoren zur individuellen Therapieplanung in der Erstlinie des mRCC diskutiert werden. Hierbei ist das wichtigste Leitkriterium das Risikoprofil. Daneben sind Effektivität und Verträglichkeit der Substanzen, sowie Tumorlast, Alter und Präferenzen der Patienten sowie Überlegungen zur Sequenztherapie für die Therapiewahl ausschlaggebend. Real-world-Daten für die neuen Kombinationstherapien, Biomarker für eine personalisierte Medizin sowie Studien zur optimalen Sequenztherapie beim mRCC werden benötigt.
Type 1 diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta cells
Authors: Johnson Matthew B. , Patel Kashyap A. , De Franco Elisa , Hagopian William , Killian Michael , McDonald Timothy J. , Tree Timothy I. M. , Domingo-Vila Clara , Hudson Michelle , Hammersley Suzanne , Dobbs Rebecca ,   EXE-T1D Consortium, Ellard Sian , Flanagan Sarah E. , Hattersley Andrew T. , Oram Richard A.
Published: October 2020

Aims/hypothesis

Diabetes diagnosed at <6 months of age is usually monogenic. However, 10–15% of affected infants do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed at <6 months of age without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at early ages.

Methods

We studied 166 infants diagnosed with type 1 diabetes at <6 months of age in whom pathogenic variants in all 26 known genes had been excluded and compared them with infants with monogenic neonatal diabetes (n = 164) or children with type 1 diabetes diagnosed at 6–24 months of age (n = 152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features.

Results

We found an excess of infants with high T1D-GRS: 38% (63/166) had a T1D-GRS >95th centile of healthy individuals, whereas 5% (8/166) would be expected if all were monogenic (p < 0.0001). Individuals with a high T1D-GRS had a similar rate of autoantibody positivity to that seen in individuals with type 1 diabetes diagnosed at 6–24 months of age (41% vs 58%, p = 0.2), and had markedly reduced C-peptide levels (median <3 pmol/l within 1 year of diagnosis), reflecting rapid loss of insulin secretion. These individuals also had reduced birthweights (median z score −0.89), which were lowest in those diagnosed with type 1 diabetes at <3 months of age (median z score −1.98).

Conclusions/interpretation

We provide strong evidence that type 1 diabetes can present before the age of 6 months based on individuals with this extremely early-onset diabetes subtype having the classic features of childhood type 1 diabetes: high genetic risk, autoimmunity and rapid beta cell loss. The early-onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes at <6 months of age.
Indirect cutting tool wear classification using deep learning and chip colour analysis
Authors: Pagani Luca , Parenti Paolo , Cataldo Salvatore , Scott Paul J. , Annoni Massimiliano
Published: October 2020

In the growing Industry 4.0 market, there is strong need to implement automatic inspection methods to support manufacturing processes. Tool wear in turning is one of the biggest concerns that most expert operators are able to indirectly infer through the analysis of the removed chips. Automatising this operation would enable developing more efficient cutting processes that turns in easier process planning management toward the Zero Defect Manufacturing paradigm. This paper presents a deep learning approach, based on image processing applied to turning chips for indirectly identifying tool wear levels. The procedure extracts different indicators from the RGB and HSV image channels and instructs a neural network for classifying the chips, based on tool state conditions. Images were collected with a high-resolution digital camera during an experimental cutting campaign involving tool wear analysis with direct microscope imaging. The sensitivity analysis confirmed that the most sensible image channels are the hue valueHthat were used to teach the network, leading to performances in the range of 95 of proper classification. The feasibility of the deep learning approach for indirectly understanding the tool wear from the chip colour characterisation is confirmed. However, due to the big effects on chip colours of variables as the workpiece material and cutting process parameters, the applicability is limited to stable production flows. An industrial implementation can be foreseen by populating proper large databases and by implementing real-time chip segmentation analysis.
A thermomechanically motivated approach for identification of flow stress properties in metal cutting
Authors: Ertürk Ahmet Semih , Malakizadi Amir , Larsson Ragnar
Published: October 2020

The paper presents a novel thermomechanically coupled distributed primary deformation zone model to assist the inverse identification of Johnson-Cook material parameters to be used for machining simulations. A special feature of the enhanced model is that the assumed stress field is temperature-dependent, where the thermomechanical coupling governs the stress and temperature distributions across the primary shear zone to describe the thermal softening effect. By using stress, strain, strain rate, and temperature distributions from the thermomechanically enhanced model, Johnson-Cook material parameters are calibrated for orthogonal cutting tests of C38, 42CrMo4, and AA6082 materials where continuous chip formation prevails. The performance of the parameters is compared with that of a wider set of cutting tests using finite element simulations. The results show that the thermomechanically motivated model yields closer results to experiments in terms of cutting force and chip thickness (9% and 34% difference, respectively) compared with the original thermally uncoupled model (47% and 92% difference, respectively). Identification of the material parameters by this method focuses directly on the orthogonal cutting test and it does not require many experiments or simulations. In fact, the proposed methodology is computationally robust and cost-efficient which makes it preferable compared with other methods which are more accurate but highly time-consuming.
Bleeding and thromboembolism due to drug-drug interactions with non-vitamin K antagonist oral anticoagulants—a Swedish, register-based cohort study in atrial fibrillation outpatients
Authors: Holm Johan , Mannheimer Buster , Malmström Rickard E , Eliasson Erik , Lindh Jonatan D
Published: October 2020

Purpose

To study the association between interacting drugs and bleeding or thromboembolism in atrial fibrillation outpatients treated with non-vitamin K antagonist oral anticoagulants (NOACs).

Methods

Population-based cohort study of outpatients treated with NOACs in Sweden from 2008 to 2017. Patients with atrial fibrillation and newly initiated NOAC treatment were identified in the Prescribed Drug Register. Comorbidities and outcome data were retrieved from the Patient Register and the Cause of Death Register. Cox-regression analyses were performed to evaluate the primary endpoints any severe bleed and ischemic stroke/transient ischemic attack/stroke unspecified during the first six months of treatment. Secondary endpoints were gastrointestinal bleeding, intracranial bleeding, ischemic stroke, and venous thromboembolism.

Results

Increased risk of any severe bleed was found when NOAC treatment, and drugs with pharmacodynamic effect on bleeding were combined, compared to NOAC only. An increased risk with these combinations was evident for apixaban (hazard ratio (HR) 1.47; 95% CI 1.33–1.63), rivaroxaban (HR 1.7; 95% CI 1.49–1.92), and dabigatran (HR 1.26; 95% CI 1.05–1.52). For apixaban, there was an increased risk of any severe bleed when combined with CYP3A4 and/or P-glycoprotein (P-gp) inhibitors (HR 1.23; 95% CI 1.01–1.5). The use of inducers of CYP3A4 and/or P-gp was low in this cohort, and effects on ischemic stroke/TIA/stroke unspecified could not be established.

Conclusion

Increased risk of bleeding was seen for pharmacodynamic and pharmacokinetic interactions with NOACs. Prescribers need to be vigilant of the effect of interacting drugs on the risk profile of patients treated with NOACs.
Brain metabolic changes across King’s stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-d-glucose-positron emission tomography study
Authors: Canosa Antonio , Calvo Andrea , Moglia Cristina , Manera Umberto , Vasta Rosario , Di Pede Francesca , Cabras Sara , Nardo Davide , Arena Vincenzo , Grassano Maurizio , D’Ovidio Fabrizio , Van Laere Koen , Van Damme Philip , Pagani Marco , Chiò Adriano
Published: October 2020

Purpose

To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King’s staging system, using brain 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET).

Methods

Three hundred ninety ALS cases with King’s stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King’s stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King’s 1, King’s 2, King’s 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates.

Results

Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3.

Conclusions

Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.
Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives
Authors: Qu Jingjing , Mei Quanhui , Chen Lijun , Zhou Jianying
Published: October 2020

There has been a rapid progress in developing genetically engineered T cells in recent years both in basic and clinical cancer studies. Chimeric antigen receptor (CAR)-T cells exert an immune response against various cancers, including the non-small-cell lung cancer (NSCLC). As novel agents of immunotherapy, CAR-T cells show great promise for NSCLC. However, targeting specific antigens in NSCLC with engineered CAR-T cells is complicated because of a lack of tumor-specific antigens, the immunosuppressive tumor microenvironment, low levels of infiltration of CAR-T cells into tumor tissue, and tumor antigen escape. Meanwhile, the clinical application of CAR-T cells remains limited due to the cases of on-target/off-tumor and neurological toxicity, as well as cytokine release syndrome. Hence, optimal CAR-T-cell design against NSCLC is urgently needed. In this review, we describe the basic structure and generation of CAR-T cells and summarize the common tumor-associated antigens targeted in clinical trials on CAR-T-cell therapy for NSCLC, as well as point out current challenges and novel strategies. Although many obstacles remain, the new/next generation of CARs show much promise. Taken together, research on CAR-T cells for the treatment of NSCLC is underway and has yielded promising preliminary results both in basic and pre-clinical medicine. More pre-clinical experiments and clinical trials are, therefore, warranted.
Psychotherapiemotivation von „Pseudogesunden“
Authors: Braungardt Tanja , Goldmann Marie , Schneider Wolfgang , Spitzer Carsten
Published: October 2020

Hintergrund

Als „pseudogesund“ gelten Patienten, deren Testwerte in symptombezogenen Selbstbeurteilungsverfahren sich nicht von Personen der Allgemeinbevölkerung unterscheiden. Dennoch nehmen die „Pseudogesunden“ psychotherapeutische Behandlungen in Anspruch. Die vorliegende Studie geht daher der Frage nach, ob, und ggf. wie, sich „pseudogesunde“ Patienten in ihrer Psychotherapiemotivation von jenen mit hoher Symptombelastung unterscheiden.

Material und Methoden

Es wurden 1883 voll- und teilstationäre behandelte Patienten einer universitären Klinik für psychosomatische Medizin untersucht. Neben der Selbstbeurteilung mithilfe des „Fragebogen zur Messung der Psychotherapiemotivation“ (FMP) erfolgte die Fremdeinschätzung durch die Bezugstherapeuten auf Grundlage der Achse I „Krankheitserleben und Behandlungsvoraussetzungen“ der Operationalisierten Psychodynamischen Diagnostik (OPD-2).

Ergebnisse

Der Anteil der „Pseudogesunden“ betrug knapp 26 %. In dieser Gruppe waren somatoforme Störungen überzufällig häufig vertreten. „Pseudogesunde“ zeichneten sich im Vergleich zu den „belasteten“ Patienten sowohl in der Selbst- als auch in der Fremdbeurteilung durch einen geringeren Leidensdruck, eine an somatischen Ursachen orientierte Laienätiologie und eine insgesamt geringere Psychotherapiemotivation aus.

Diskussion

Die erhobenen Befunde deuten darauf hin, dass psychotherapiemotivierende Interventionen vor oder zu Beginn der Behandlung bei „pseudogesunden“ Patienten in erster Linie auf die Förderung eines angemessenen Krankheitsverständnisses abzielen sollten, auch um Therapieabbrüche zu vermeiden.
Diagnostic value of ultrasonography in acute lateral and syndesmotic ligamentous ankle injuries
Authors: Baltes Thomas P. A. , Arnáiz Javier , Geertsema Liesel , Geertsema Celeste , D’Hooghe Pieter , Kerkhoffs Gino M. M. J. , Tol Johannes L.
Published: October 2020

Objectives

To determine the diagnostic value of ultrasonography for complete discontinuity of the anterior talofibular ligament (ATFL), the calcaneofibular ligament (CFL) and the anterior inferior tibiofibular ligament (AITFL).

Methods

All acute ankle injuries in adult athletes (> 18 years old) presenting to the outpatient department of a specialised Orthopaedic and Sports Medicine Hospital within 7 days post-injury were assessed for eligibility. Using ultrasonography, one musculoskeletal radiologist assessed the ATFL, CFL and AITFL for complete discontinuity. Dynamic ultrasound measurements of the tibiofibular distance (mm) in both ankles (injured and contralateral) were acquired in the neutral position (N), during maximal external rotation (Max ER), and maximal internal rotation (Max IR). MR imaging was used as a reference standard.

Results

Between October 2017 and July 2019, 92 acute ankle injuries were included. Ultrasound diagnosed complete discontinuity of the ATFL with 87% (CI 74–95%) sensitivity and 69% (CI 53–82%) specificity. Discontinuity of the CFL was diagnosed with 29% (CI 10–56%) sensitivity and 92% (CI 83–97%) specificity. Ultrasound diagnosed discontinuity of the AITFL with 100% (CI 74–100%) sensitivity and 100% (CI 95–100%) specificity. Of the dynamic measurements, the side-to-side difference in external rotation had the highest diagnostic value for complete discontinuity of the AITFL (sensitivity 82%, specificity 86%; cut-off 0.93 mm).

Conclusions

Ultrasound has a good to excellent diagnostic value for complete discontinuity of the ATFL and AITFL. Therefore, ultrasound can be used to screen for injury of the ATFL and AITFL. Compared with ultrasound, dynamic ultrasound has inferior diagnostic value for complete discontinuity of the AITFL.

Key Points

• Ultrasound has a good to excellent diagnostic value for complete discontinuity of the anterior talofibular ligament (ATFL) and anterior inferior tibiofibular ligament (AITFL).

• Ultrasound can be used to screen for injury of the ATFL and AITFL.

• Compared with ultrasound, dynamic ultrasound has inferior diagnostic value for complete discontinuity of the AITFL.
Reducing host DNA contamination in 16S rRNA gene surveys of anthozoan microbiomes using PNA clamps
Authors: Reigel Alicia M. , Owens Sarah M. , Hellberg Michael E.
Published: October 2020

Efforts to study the microbial communities associated with corals can be limited by inefficiencies in the sequencing process due to high levels of host amplification by universal bacterial 16S rRNA gene primers. Here, we develop an inexpensive peptide nucleic acid (PNA) clamp that binds to a target sequence of host DNA during PCR and blocks amplification. We then test the ability of this PNA clamp to mitigate host contamination and increase overall microbial sequence coverage on samples from three coral species: the gorgonians Eunicea flexuosa and Gorgonia ventalina, and the scleractinian Porites panamensis. The 20-bp PNA clamp was designed using DNA from E. flexuosa. Adding the PNA clamp during PCR increased the percentage of microbial reads in E. flexuosa samples more than 11-fold. Microbial community diversity was similar without- and with-PNA clamps, as were the relative frequencies of the ten most abundant ASVs (amplicon sequence variants), indicating that the clamps successfully blocked host DNA amplification while simultaneously increasing microbial DNA amplification proportionally across the most abundant taxa. The reduction of E. flexuosa DNA correlated with an increase in the abundance of rarer taxa. The clamp also increased the average percentage of microbial reads in another gorgonian, G. ventalina, by 8.6-fold without altering the microbial community beta diversity, and in a distantly related scleractinian coral, P. panamensis, by nearly double. The reduction of host contamination correlated with the number of nucleotide mismatches between the host amplicon and the PNA clamp. The PNA clamp costs as little as $0.48 per sample, making it an efficient and cost-effective solution to increase microbial sequence coverage for high-throughput sequencing of coral microbial communities.
An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment
Authors: Binz Camilla , Schreiber-Katz Olivia , Kumpe Mareike , Ranxha Gresa , Siegler Hannah , Wieselmann Gary , Petri Susanne , Osmanovic Alma
Published: October 2020

Background

Efficacy of nusinersen in adult 5q-spinal muscular atrophy (SMA) patients regarding motor function has recently been demonstrated. However, additional outcome measures are needed to capture non-motor improvements. Fatigue is a common and disabling symptom in neurologic diseases, but little is known about its frequency, characteristics and associated factors in SMA.

Objective

To characterize fatigue in SMA patients receiving nusinersen, identify associated factors and evaluate fatigue as potential patient-reported outcome measure (PRO).

Methods

We assessed fatigue in adults with genetically confirmed 5q-SMA in a prospective longitudinal monocentric study using the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Factors associated with fatigue including health-related quality of life (HRQOL) were evaluated.

Results

75% of participants were abnormally fatigued with highest scores in the dimensions physical, followed by general fatigue and reduced activity. 53% agreed that fatigue was among their three most disabling symptoms. Reduced activity was reported more extensively by participants with ≥ 4 copies of the survival of motor neuron 2 gene and better motor function. General and mental fatigue correlated positively with age and disease duration. HRQOL was inversely correlated with physical fatigue, which was not associated with disease or participant characteristics. During 14 months of nusinersen treatment, fatigue measures remained mostly stable with a trend towards improvement in reduced activity, general and physical fatigue.

Conclusion

Fatigue is a frequent and relevant complaint in adult SMA patients. Fatigue should be taken into consideration as additional outcome measure, but needs further evaluation in a larger patient cohort over a longer observation period.
Health-related quality of life after Gamma Knife radiosurgery in patients with 1–10 brain metastases
Authors: Verhaak Eline , Schimmel Wietske C. M. , Gehring Karin , Emons Wilco H. M. , Hanssens Patrick E. J. , Sitskoorn Margriet M.
Published: October 2020

Purpose

Increasingly more patients with multiple (> 4) brain metastases (BM) are being treated with stereotactic radiosurgery (SRS). Preserving patients’ health-related quality of life (HRQoL) is an important treatment goal. The aim of this study was to assess (individual) changes in HRQoL in patients with 1–10 BM over time.

Methods

A total of 92 patients were assessed before (n = 92) and at 3 (n = 66), 6 (n = 53), and 9 (n = 41) months after Gamma Knife radiosurgery (GKRS), using the Functional Assessment of Cancer Therapy-Brain (FACT-Br). The course of HRQoL was analyzed using linear mixed models. Clinical minimally important differences were used to evaluate individual changes.

Results

At group level, patients’ physical well-being worsened, whereas emotional well-being improved over 9 months. Scores on other HRQoL subscales did not change significantly. Number (1–3 versus 4–10) and volume (small, medium, and large) of BM did not influence HRQoL over time, except for the subscale additional concerns; medium intracranial tumor volume was associated with less additional concerns. On the individual level as well, physical well-being declined while emotional well-being improved in most patients over 9 months after GKRS. At patient level, however, most patients had both declines as well as improvements in the different HRQoL aspects.

Conclusion

Our results indicate that even in patients with up to 10 BM, both at group and individual subscale level, aspects of HRQoL remained stable over nine months after GKRS, except for an improvement in emotional well-being and a decline in physical well-being. Nevertheless, HRQoL scores varied considerably at the individual patient level.

Trail registration number

ClinicalTrials.gov Identifier: NCT02953756, November 3, 2016.
Apicomplexan co-infections impair with phagocytic activity in avian macrophages
Authors: Zhang Runhui , Zheng Wanpeng , Daugschies Arwid , Bangoura Berit
Published: October 2020

Mixed infections of Toxoplasma gondii and Eimeria tenella are likely to occur frequently due to the high prevalence of both pathogens in free-ranging chickens. In this study, we investigated the co-occurrence of the two parasites in the same immune-competent host cell towards altered patterns of parasite-host interactions. Chicken blood monocyte–derived macrophages were co-infected with T. gondii RH tachyzoites and E. tenella Houghton sporozoites in vitro for 24 h. Through monitoring the uptake of pH-sensitive pHrodo™ Zymosan BioParticles (“Zymosan”) by macrophages, we created a three-dimensional model and to analyze quantitatively phagocytosis using confocal laser scanning microscopy. Assessments of parasite populations were performed by qPCR at 2, 6, 12, and 24 h post-infection (hpi). At 6 hpi, phagocytosis was inhibited in the E. tenella–infected cultures while no inhibition of phagocytosis was observed due to T. gondii. Phagocytosis activity revealed more complex interactions during co-infection. At 12 and 24 hpi, phagocytosis response to “Zymosan” was distinctly weaker in co-infected cells than in all other groups except for cells mono-infected with high doses of E. tenella at 24 hpi. By qPCR, significantly reduced numbers of both intracellular parasites were recorded (10-fold) in all infected groups at 2 hpi. At 12 hpi, the T. gondii population reached lowest values but dramatically increased by 24 hpi. Our data confirm that macrophage phagocytosis is involved in the control of invasion by apicomplexan parasites in chicken which particularly applies to E. tenella infection and it was able to be altered by the co-existing parasites.
The effect of preferred music on mental workload and laparoscopic surgical performance in a simulated setting (OPTIMISE): a randomized controlled crossover study
Authors: Fu Victor X. , Oomens Pim , Kleinrensink Vincent E. E. , Sleurink Karel J. , Borst Willemijn M. , Wessels Pascale E. , Lange Johan F. , Kleinrensink Gert-Jan , Jeekel Johannes
Published: October 2020

Background

Worldwide, music is commonly played in the operation room. The effect of music on surgical performance reportedly has varying results, while its effect on mental workload and key surgical stressor domains has only sparingly been investigated. Therefore, the aim is to assess the effect of recorded preferred music versus operating room noise on laparoscopic task performance and mental workload in a simulated setting.

Methods

A four-sequence, four-period, two-treatment, randomized controlled crossover study design was used. Medical students, novices to laparoscopy, were eligible for inclusion. Participants were randomly allocated to one of four sequences, which decided the exposure order to music and operation room noise during the four periods. Laparoscopic task performance was assessed through motion analysis with a laparoscopic box simulator. Each period consisted of ten alternating peg transfer tasks. To account for the learning curve, a preparation phase was employed. Mental workload was assessed using the Surgery Task Load Index. This study was registered with the Netherlands Trial Register (NL7961).

Results

From October 29, 2019 until March 12, 2020, 107 participants completed the study, with 97 included for analyzation. Laparoscopic task performance increased significantly during the preparation phase. No significant beneficial effect of music versus operating room noise was observed on time to task completion, path length, speed, or motion smoothness. Music significantly decreased mental workload, reflected by a lower score of the total weighted Surgery Task Load Index in all but one of the six workload dimensions.

Conclusion

Music significantly reduced mental workload overall and of several previously identified key surgical stressor domains, and its use in the operating room is reportedly viewed favorably. Music did not significantly improve laparoscopic task performance of novice laparoscopists in a simulated setting. Although varying results have been reported previously, it seems that surgical experience and task demand are more determinative.
Extrahepatic biliary tract visualization using near-infrared fluorescence imaging with indocyanine green: optimization of dose and dosing time
Authors: Chen Qiangxing , Zhou Rou , Weng Jiefeng , Lai Yueyuan , Liu Hui , Kuang Jiao , Zhang Shuai , Wu Zhaofeng , Wang Wen , Gu Weili
Published: October 2020

Background

The dose and dosing time of indocyanine green (ICG) vary among fluorescence cholangiography (FC) studies. The purpose of this prospective, randomized, exploratory clinical trial was to optimize the dose and dosing time of ICG.

Methods

PubMed was searched to determine the optimal dose. To optimize the dosing time of ICG, a clinical trial was designed with two parts. The first part included patients with T tubes for more than 1 month. After the patient was injected with ICG, bile was collected at 10 time points to explore the change and trends of bile fluorescence intensity (FI). In addition, the results of the first experiment were used to setup a randomized controlled trial (RCT) that aimed to find the optimal dosing timing for ICG injections for laparoscopic cholecystectomy (LC). During surgery, imaging data were collected for analysis.

Results

After performing a systematic review, the ICG injection dose for each patient in the clinical trial was 10 mg. Five patients were included in the first part of the study. Bile collected 8 h after ICG injection had a higher FI than bile collected at other time points (p < 0.05), and the FI of bile collected 20 h after ICG injection was nearly zero. In the second part of the experiment, 4 groups of patients (6 patients per group) were injected with 10 mg ICG at 8, 10, 12 and 14 h prior to surgery. The distribution of bile duct FI (p = 0.001), liver FI (p < 0.001), and common bile duct (CBD)-to-liver contrast (p = 0.001) were not the same in each group. Further analysis with the Bonferroni method revealed the following: (1) the FI of the CBD in the 8 h group was significantly different from that in the 14 h group (adjustedp < 0.001); (2) the liver FI of the 8 h group was higher than that of the 10 h group (adjustedp = 0.042) and the 14 h group (adjustedp < 0.001); and (3) the CBD-to-liver contrast of the 8 h group was lower than that of the 10 h group (adjustedp = 0.013) and the 14 h group (adjustedp = 0.001).

Conclusion

ICG FC enables the real-time identification of extrahepatic bile ducts. The optimal effect of FC can be achieved by performing 10 mg ICG injections 10 to 12 h prior to surgery.
Outcomes of primary versus revisional robotically assisted laparoscopic Roux-en-Y gastric bypass: a multicenter analysis of ten-year experience
Authors: Iranmanesh Pouya , Fam John , Nguyen Thomas , Talarico David , Chandwani Kavita D. , Bajwa Kulvinder S. , Felinski Melissa M. , Katz Leon V. , Mehta Sheilendra S. , Myers Stephan R. , Snyder Brad E. , Walker Peter A. , Wilson Todd D. , Rivera Angielyn R. , Klein Connie L. , Shah Shinil K. , Wilson Erik B.
Published: October 2020

Background

Postoperative morbidity after laparoscopic bariatric surgery is considered higher for patients undergoing revisional versus primary procedures. The objective of this retrospective cohort study was to compare outcomes between patients undergoing primary versus revisional robotically assisted laparoscopic (RAL) Roux-en-Y gastric bypass (RYGB).

Methods

Data of all patients who underwent RAL primary and revisional RYGB between 2009 and 2019 at two accredited, high-volume bariatric surgery centers—the Memorial Hermann – Texas Medical Center, Houston, TX, and the Tower Health, Reading Hospital, Reading, PA, were analyzed. Primary outcomes were early (< 30 days) and overall postoperative complications. Secondary outcomes included intraoperative complications, operative times, conversions to laparotomy, length of hospital stay, early (< 30 days) postoperative readmissions and deaths.

Results

Data of 1072 patients were analyzed, including 806 primary and 266 revisional RAL RYGB procedures. Longer operative times (203 versus 154 min, P < 0.001), increased number of readmissions for oral intolerance (10.5% versus 6.7%, P = 0.046) and higher rate of gastrojejunal stricture (6.4% versus 2.7%, P = 0.013) were found in the revisional group. Gastrointestinal leak rates were 0.2% for the primary versus 1.1% for the revisional group (P = 0.101). Early (< 30 days) reoperations rates were 2.2% for the primary versus 1.1% for the revisional group (P = 0.318). There were no statistically significant differences between groups in overall and severe complication rates.

Conclusion

Patients undergoing RAL primary and revisional RYGB had comparable overall outcomes, with a non-significant higher early complication rate in the revisional group. Despite the study being underpowered to detect differences in specific complication rates, the morbidity seen in the revisional RYGB group remains markedly below literature reports of revisional laparoscopic RYGB and might suggest a benefit of robotic assistance. Further prospective studies are needed to confirm these results.
Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge
Authors: Hansen Niels , Timäus Charles
Published: October 2020

Our review aims to delineate the psychiatric spectrum of autoantibody-associated autoimmune encephalitis over time through its discoveries of antibodies. We searched in PubMed for appropriate articles depicting the first appearance and spectrum of psychiatric symptomatology in autoantibody-positive encephalitis for this narrative review. Memory impairment was first associated with autoantibodies against intracellular antigens such as anti-HuD antibodies in 1993. 8 years later, autoantibodies against cell membrane surface antigens such as voltage-gated potassium channels were described in conjunction with memory dysfunction. The spectrum of psychiatric syndromes was amplified between 1990 and 2020 to include disorientation, behavior, cognitive dysfunction, obsessive compulsive behavior and suicidality in encephalitis patients occurring together mainly with antibodies against surface antigens, less so against intracellular antigens. In general, we found no specific psychiatric symptoms underlying specific autoantibody-associated encephalitis. As fundamental data on this issue have not been systemically assessed to date, we cannot know whether our specific findings would remain from systematic studies, i.e., on the association between cerebrospinal fluid N-methyl-D-aspartate receptor antibodies in catatonia. The psychiatric symptomatology overlaps between psychiatric domains and occurs frequently in antibody-positive encephalitis. No specific psychiatric symptoms imply an underlying, specifically autoantibody-associated encephalitis. The psychiatric phenotypology associated with antibody-positive encephalitis has evolved tremendously recently, and this new evidence reveals its relevance for future diagnostic and treatment aspects of autoimmune encephalitis patients.
Groundwater recharge processes in an Asian mega-delta: hydrometric evidence from Bangladesh
Authors: Nowreen Sara , Taylor R. G. , Shamsudduha M. , Salehin M. , Zahid A. , Ahmed K. M.
Published: October 2020

Groundwater is used intensively in Asian mega-deltas yet the processes by which groundwater is replenished in these deltaic systems remain inadequately understood. Drawing insight from hourly monitoring of groundwater levels and rainfall in two contrasting settings, comprising permeable surficial deposits of Holocene age and Plio-Pleistocene terrace deposits, together with longer-term, lower-frequency records of groundwater levels, river stage, and rainfall from the Bengal Basin, conceptual models of recharge processes in these two depositional environments are developed. The representivity of these conceptual models across the Bengal Basin in Bangladesh is explored by way of statistical cluster analysis of groundwater-level time series data. Observational records reveal that both diffuse and focused recharge processes occur in Holocene deposits, whereas recharge in Plio-Pleistocene deposits is dominated by indirect leakage from river channels where incision has enabled a direct hydraulic connection between river channels and the Plio-Pleistocene aquifer underlying surficial clays. Seasonal cycles of recharge and discharge including the onset of dry-season groundwater-fed irrigation are well characterised by compiled observational records. Groundwater depletion, evident from declining groundwater levels with a diminished seasonality, is pronounced in Plio-Pleistocene environments where direct recharge is inhibited by the surficial clays. In contrast, intensive shallow groundwater abstraction in Holocene environments can enhance direct and indirect recharge via a more permeable surface geology. The vital contributions of indirect recharge of shallow groundwater identified in both depositional settings in the Bengal Basin highlight the critical limitation of using models that exclude this process in the estimation of groundwater recharge in Asian mega-deltas.
Clean manufacturing powered by biology: how Amyris has deployed technology and aims to do it better
Authors: Hill Paul , Benjamin Kirsten , Bhattacharjee Binita , Garcia Fernando , Leng Joshua , Liu Chi-Li , Murarka Abhishek , Pitera Douglas , Rodriguez Porcel Elisa Maria , da Silva Iris , Kraft Chuck
Published: October 2020

Amyris is a fermentation product company that leverages synthetic biology and has been bringing novel fermentation products to the market since 2009. Driven by breakthroughs in genome editing, strain construction and testing, analytics, automation, data science, and process development, Amyris has commercialized nine separate fermentation products over the last decade. This has been accomplished by partnering with the teams at 17 different manufacturing sites around the world. This paper begins with the technology that drives Amyris, describes some key lessons learned from early scale-up experiences, and summarizes the technology transfer procedures and systems that have been built to enable moving more products to market faster. Finally, the breadth of the Amyris product portfolio continues to expand; thus the steps being taken to overcome current challenges (e.g. automated strain engineering can now outpace the rest of the product commercialization timeline) are described.
Effect of aluminum and sodium on the sorption of water and methanol in microporous MFI-type zeolites and mesoporous SBA-15 materials
Authors: Li Zheng , Rieg Carolin , Beurer Ann-Katrin , Benz Michael , Bender Johannes , Schneck Christof , Traa Yvonne , Dyballa Michael , Hunger Michael
Published: October 2020

The interaction and nature of surface sites for water and methanol sorption on MFI-type zeolites and mesoporous SBA-15 were investigated by solid-state NMR spectroscopy and correlated with the desorption enthalpies determined via TGA/DSC. For siliceous Silicalite-1, 29Si CPMAS NMR studies support stronger methanol than water interactions with SiOH groups of Q3-type. On siliceous SBA-15, SiOH groups of Q2-type are accompanied by an enhanced hydrophilicity. In aluminum-containing Na-ZSM-5, Na+ cations are strong adsorption sites for water and methanol as evidenced by 23Na MAS NMR in agreement with high desorption enthalpies of ΔH = 66–74 kJ/mol. Solid-state NMR of aluminum-containing Na-[Al]SBA-15, in contrast, has shown negligible water and methanol interactions with sodium and aluminum. Desorption enthalpies of ΔH = 44–60 kJ/mol hint at adsorption sites consisting of SiOH groups influenced by distant framework aluminum. On H-ZSM-5, Brønsted acidic OH groups are strong adsorption sites as indicated by partial protonation of water and methanol causing low-field shifts of their 1H MAS NMR signals and enhanced desorption enthalpies. Due to the small number of Brønsted acid sites in aluminum-containing H-[Al]SBA-15, water and methanol adsorption on this material is suggested to mainly occur at SiOH groups with distant framework aluminum species, as in the case of Na-[Al]SBA-15.
Exploring the extremes: applying high concentration of yeast extract leads to drastic morphological changes and elimination of (+)-geodin and asterric acid production in Aspergillus terreus submerged cultures
Authors: Boruta Tomasz , Górnicka Adrianna , Grzybowska Iwona , Stefaniak Ida , Bizukojć Marcin
Published: October 2020

Objective

Evaluation of morphology and secondary metabolites production in Aspergillus terreus ATCC 20542 cultures over a wide range of lactose and yeast extract concentrations from 0.2 up to an extremely high level of 200 g l−l.

Results

The morphological differences of mycelial objects were quantified with the use of morphological parameters calculated by applying the tools of digital image analysis. At 200 g l−l of yeast extract clumps and loose hyphae were recorded instead of pellets commonly observed in submerged cultures of A. terreus. Under these conditions the biosynthesis of (+)-geodin and asterric acid was totally blocked, lovastatin formation was found to be at a relatively low level and biomass production turned out to be greater than in the remaining variants, where the pelleted growth was observed. At 200 g l−l of lactose the production of lovastatin, (+)-geodin and asterric acid was visibly stimulated compared to the media containing 0.2, 2 and 20 g l−l of the sugar substrate, but at the same time no traces of butyrolactone I could be detected in the broth. Lactose at the extremely high concentration of 200 g l−l did not induce the drastic morphological changes observed in the case of 200 g l-1 of yeast extract. It was proved that at the C/N values as low as 4 and as high as 374 A. terreus not only continued to display growth but also exhibited the production of secondary metabolites. The use of cultivation media representing the equivalent C/N ratios led to different metabolic and morphological outcomes depending on the concentration of lactose and yeast extract that contributed to the given C/N value.

Conclusion

The extremely high concentration of yeast extract leads to marked morphological changes of A. terreus and the elimination of (+)-geodin and asterric production, while applying the excess of lactose is stimulatory in terms of lovastatin production.