bluuebunny/crossref_metadata_2025_split huggingface dataset:
An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer
Authors: Xu Jing , Gao Yi , Luan Xiaotian , Li Ke , Wang Jing , Dai Yilin , Kang Mingyi , Lu Chong , Zhang Minhua , Lu Chris X. , Kang Yu , Xu Congjian 
Published: April 2022

Abstract
Background
Although the use of PARP inhibitor has received considerable amount of attention in ovarian cancer, PARP inhibitor resistance still emerges with disease progression. PI3K/AKT pathway inhibitors have been proposed to synergize with PARP inhibition to slow tumor growth, but the exact molecular mechanisms are still elusive.

Methods
Utilizing tumor samples from recurrent EOC patients with platinum resistance and prior PARP inhibitor use, Mini PDX and PDX models were established to study the anti-tumor effect of AKT inhibitor (LAE003) and LAE003/PARP inhibitor (Olaparib) in combination. Five ovarian cancer cell lines were treated with Olaparib or LAE003 or in combination in vitro. Cell viability and apoptosis rate were measured after the treatments. Combination index by the Chou–Talalay was used to evaluate in vitro combination effect of Olaparib and LAE003. The protein expression level of PARP1 and PAR was measured by Western blot in cell lines and by immunohistochemistry in PDX tumor tissues.

Results
Tumor cells from two out of five platinum-resistant ovarian cancer patients previously treated with PARP inhibitor were sensitive to AKT inhibition in Mini-PDX study. Inhibition of AKT further increased the response of tumor cells to Olaparib in a PDX model derived from a recurrent platinum-resistant ovarian cancer patient. Additive anti-proliferation effect of LAE003 and Olaparib was also observed in three ovarian cancer cell lines with high PARP1 protein level. Interestingly, mechanism study revealed that AKT inhibition decreased PARP enzyme activity as measured by PAR level and/or reduced PARP1 protein level in the tumor cell lines and PDX tumor tissues, which may explain the observed combined anti-tumor effect of LAE003 and Olaparib.

Conclusion
Collectively, our results suggest that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients.
Characterization and Genomic Analysis of Bacteriophage vB_KpnM_IME346 Targeting Clinical Klebsiella pneumoniae Strain of the K63 Capsular Type
Authors: Gao Mingming , Yi Lingxian , Wang Yuan , Gao Jie , Liu Huiying , Zhang Xianglilan , Pei Guangqian , Tong Yigang , Bai Changqing 
Published: April 2022

AbstractA Klebsiella pneumoniae bacteriophage (vB_KpnM_IME346) was isolated from a hospital sewage sample. This bacteriophage specifically infects a clinical K. pneumoniae strain with a K63 capsular polysaccharide structure. The phage genome was evaluated by next-generation sequencing, which revealed a linear double-stranded DNA genome consisting of 49,482 base pairs with a G+C content of 49.1%. The latent period of vB_KpnM_IME346 was shown to be 20 min, and the burst size was 25–30 pfu (plaque-forming units)/infected cell. Transmission electron microscopy and phylogenetic analysis showed that the JD001-like phage belongs to the genus Jedunavirus of the family Myoviridae. The newly isolated vB_KpnM_IME346 shows infectivity in the clinical host K. pneumoniae KP576 strain, indicating that it is a promising alternative to antibacterial agents for removing K. pneumoniae from patients.
The water mass transformation framework and variability in hurricane activity
Authors: Harris Elizabeth A. , Marsh Robert , Grist Jeremy. P. , McCarthy Gerard. D. 
Published: April 2022

AbstractHurricane activity has been higher since 1995 than in the 1970s and 1980s. This rise in activity has been linked to a warming Atlantic. In this study, we consider variability of the volume of water warmer than 26.5 ºC, considered widely to be the temperature threshold crucial to hurricane development. We find the depth of the 26.5 ºC isotherm better correlated with seasonal hurricane counts than SST in the early part of the Atlantic hurricane season in some regions. The volume of water transformed by surface heat fluxes to temperatures above 26.5 ºC is directly calculated using the Water Mass Transformation framework. This volume is compared with the year-to-year changes in the volume of water of this temperature to see how much of the volume can be explained using this calculation. In some years, there is notable correspondence between transformed and observed volume anomalies, but anomalies in other years must be largely associated with other processes, such as the divergence of horizontal heat transport associated with the AMOC. This technique provides evidence that, in a given year, coordinated physical mechanisms are responsible for the build-up of anomalous ocean heat; not only net surface heat exchange but also the convergence of horizontal heat transport from ocean currents, to provide fuel for larger numbers of intense hurricanes.
Multicenter cohort study on the presentation and treatment of acute appendicitis during the COVID-19 pandemic
Authors: Huijgen Demi , de Wijkerslooth Elisabeth M. L. , Janssen Josephine C. , Beverdam Frédérique H. , Boerma Evert-Jan G. , Dekker Jan Willem T. , Kitonga Sophia , van Rossem Charles C. , Schreurs Wilhelmina H. , Toorenvliet Boudewijn R. , Vermaas Maarten , Wijnhoven Bas P. L. , van den Boom Anne Loes 
Published: April 2022

Abstract

Purpose
Current studies have demonstrated conflicting results regarding surgical care for acute appendicitis during the COVID-19 pandemic. This study aimed to assess trends in diagnosis as well as treatment of acute appendicitis in the Netherlands during the first and second COVID-19 infection wave.

Methods
All consecutive patients that had an appendectomy for acute appendicitis in nine hospitals from January 2019 to December 2020 were included. The primary outcome was the number of appendectomies for acute appendicitis. Secondary outcomes included time between onset of symptoms and hospital admission, proportion of complex appendicitis, postoperative length of stay and postoperative infectious complications. Outcomes were compared between the pre-COVID group and COVID group.

Results
A total of 4401 patients were included. The mean weekly rate of appendectomies during the COVID period was 44.0, compared to 40.9 in the pre-COVID period. The proportion of patients with complex appendicitis and mean postoperative length of stay in days were similar in the pre-COVID and COVID group (respectively 35.5% vs 36.8%, p = 0.36 and 2.0 ± 2.2 vs 2.0 ± 2.6, p = 0.93). There were no differences in postoperative infectious complications. A computed tomography scan was used more frequently as a diagnostic tool after the onset of COVID-19 compared to pre-COVID (13.8% vs 9.8%, p < 0.001, respectively).

Conclusion
No differences were observed in number of appendectomies, proportion of complex appendicitis, postoperative length of stay or postoperative infectious complications before and during the COVID-19 pandemic. A CT scan was used more frequently during the COVID-19 pandemic.
Expression of DNA mismatch repair proteins in melanoma patients treated with immune checkpoint inhibitors
Authors: Gambichler T. , Finis C. , Abu Rached N. , Scheel C. H. , Becker J. C. , Lang K. , Käfferlein H. U. , Brüning T. , Abolmaali N. , Susok L. 
Published: April 2022

Abstract
Purpose
To investigate the protein expression of DNA mismatch repair (MMR) proteins in patients with cutaneous melanoma (CM) under immune checkpoint inhibitor (ICI) therapy.

Methods
Immunohistochemistry was performed on tumor tissue for MMR proteins MLH1, MSH2, MSH6, and PMS2 in 50 metastatic CM patients treated with ICI (ipilimumab, nivolumab, pembrolizumab).

Results
Best overall response (BOR) rate was 48% (24/50). Reduced MMR protein expression (nuclear expression in < 80% of tumor cells) was observed in 8 patients (16%). Compared to other clinical parameters, baseline neutrophil/lymphocyte ratio and reduced intratumoral MMR protein expression (P = 0.0033) were determined as the only parameters significantly associated with favorable BOR. However, in this small study population, reduced MMR protein expression did not reach statistical significance in multivariate analysis.

Conclusion
Reduced MMR protein expression is observed in CM and might predict favorable BOR in patients treated with ICI, as was observed for other entities. However, these findings need to be substantiated in larger patient cohorts.
Levamisole causes a transient increase in plasma creatinine levels but does not affect kidney function based on cystatin C
Authors: Veltkamp Floor , Bökenkamp Arend , Slaats Jeroen , Hamer Henrike , Bouts Antonia H. M. ,   on behalf of the LEARNS consortium
Published: April 2022

Abstract
Background
In pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms — nephrotoxicity and interference with the analytical assay for creatinine — have never been thoroughly investigated.

Methods
In three steroid-sensitive nephrotic syndrome (SSNS) patients with elevated plasma creatinine levels, treated with levamisole 2.5 mg/kg every other day, serum cystatin C was determined. The glomerular filtration rate (GFR) was estimated using the full age spectrum for creatinine and the full age spectrum for cystatin C equations. Interference of levamisole with the enzymatic creatinine assay was tested using spare human plasma of different creatinine concentrations spiked with levamisole (4, 20, and 100 µM).

Results
Three patients who received levamisole with elevated plasma creatinine levels had normal serum cystatin C levels and corresponding estimated GFR. There was no assay interference.

Conclusion
Levamisole increases plasma creatinine levels, which is most probably due to impaired tubular secretion of creatinine since there was no assay interference and patients had normal eGFR based on serum cystatin C. However, interference of metabolites of levamisole could not be excluded. To monitor GFR, cystatin C in addition to creatinine should be used and be measured before and during levamisole use.
Psychotherapeutische Versorgung in Österreich: Kassenfinanzierte Psychotherapie für Menschen mit chronisch psychischen Erkrankungen im Jahresvergleich 2017 bis 2020
Authors: Riffer Friedrich , Knopp Magdalena , Oppenauer Claudia , Sprung Manuel 
Published: April 2022

ZusammenfassungIn Österreich wird die psychotherapeutische Versorgung im niedergelassenen Bereich finanziell über die Kostenzuschussregelung und kassenfinanzierten Psychotherapiestunden geregelt. Die vorliegende Studie untersucht, inwiefern sich der Anteil an selbstfinanzierten und kassenfinanzierten Psychotherapieeinheiten über die Jahre 2017–2020 unter Berücksichtigung des sozioökonomischen/krankheitsbezogenen und behandlungsbezogenen Status verändert hat. Hierfür wurde eine Stichprobe von 6387 Patient*innen mit psychischen Störungen im Rahmen einer stationären Behandlung befragt.Der größte Teil (70 %) der Patient*innen ist seit mehr als zwei Jahren an einer psychischen Störung erkrankt und hatte bereits einen stationären Aufenthalt (46 %) oder ambulante psychotherapeutische Behandlung (82 %) in Anspruch genommen. Im Zuge der ambulanten psychotherapeutischen Vorbehandlung haben 45 % der Patient*innen einen Kassenplatz für Psychotherapie erhalten. Von den Patient*innen, die die Psychotherapie privat finanziert haben, hat der Großteil der Patient*innen (72 %) für eine psychotherapeutische Behandlung bis zu 100 € bezahlt – bei einem Anteil von 70 % von Patient*innen, die vor der stationären Behandlung arbeitsunfähig waren und 39 % von Patient*innen, deren monatliches Einkommen weniger als 1000 € ausmacht. Die Studiendaten zeigen auch, dass sich der Anteil der Patient*innen, die eine kassenfinanzierte Psychotherapie in Anspruch nehmen konnten seit 2017 nicht erhöht hat.Die vorliegende Studie verdeutlicht, dass die Inanspruchnahme von ambulanter Psychotherapie und Kassenplätzen für Psychotherapie bei Patient*innen mit chronisch psychischen Erkrankungen in den letzten vier Jahren, trotz Erhöhung des Kassenzuschuss im Jahr 2018 und etwaiger Aufstockungen an Kassenplätzen, unverändert geblieben ist. Angesichts der limitierten Kassenplätze ist deshalb ein transparentes System für die Zuteilung von Kassenplätzen zu fordern, um die Inanspruchnahme von ambulanter Psychotherapie bei allen Patient*innen mit chronischen psychischen Erkrankungen zu ermöglichen.
Systemischer Kompetenzerwerb durch das Transkribieren und Interpretieren psychotherapeutischer Sitzungen
Authors: Ahlers Corina , Kristandl Susanna , Walch Kathrin 
Published: April 2022

ZusammenfassungStudierende transkribierten Psychotherapiesitzungen an der Ambulanz der ÖAS. Schlüsselszenen wurden in Interpretationsgruppen und mit der Projektleitung analysiert. Didaktische Effekte zeigen sich in der spezifischen Medialität der Textanalyse und dadurch vielseitigen Konstrukten zur therapeutischen Performanz, oder als Erwerb einer „Fehlerkultur“ und im Erkennen „besonderer Momente“ der therapeutischen Beziehung, v. a. im Vergleich der Kommunikation in Dyaden bzw. in Mehrpersonensystemen.
Consistency management in industrial continuous model-based development settings: a reality check
Authors: Jongeling Robbert , Ciccozzi Federico , Carlson Jan , Cicchetti Antonio 
Published: April 2022

AbstractThis article presents the state of practice of consistency management in thirteen industrial model-based development settings. Our analysis shows a tight coupling between adopting shorter development cycles and increasingly pressing consistency management challenges. We find that practitioners desire to adopt shorter development cycles, but immature modeling practices slow them down. We describe the different patterns that emerge from the various industrial settings. There is an opportunity for researchers to provide practitioners with a migration path toward practices that enable more automated consistency management, and ultimately, continuous model-based development.
KIT is dispensable for physiological organ vascularisation in the embryo
Authors: Tacconi Carlotta , Plein Alice , Colletto Chiara , Villa Emanuela , Denti Laura , Barone Cristiana , Javanmardi Yousef , Moeendarbary Emad , Azzoni Emanuele , Fantin Alessandro , Ruhrberg Christiana 
Published: April 2022

AbstractBlood vessels form vast networks in all vertebrate organs to sustain tissue growth, repair and homeostatic metabolism, but they also contribute to a range of diseases with neovascularisation. It is, therefore, important to define the molecular mechanisms that underpin blood vessel growth. The receptor tyrosine kinase KIT is required for the normal expansion of hematopoietic progenitors that arise during embryogenesis from hemogenic endothelium in the yolk sac and dorsal aorta. Additionally, KIT has been reported to be expressed in endothelial cells during embryonic brain vascularisation and has been implicated in pathological angiogenesis. However, it is neither known whether KIT expression is widespread in normal organ endothelium nor whether it promotes blood vessel growth in developing organs. Here, we have used single-cell analyses to show that KIT is expressed in endothelial cell subsets of several organs, both in the adult and in the developing embryo. Knockout mouse analyses revealed that KIT is dispensable for vascularisation of growing organs in the midgestation embryo, including the lung, liver and brain. By contrast, vascular changes emerged during late-stage embryogenesis in these organs from KIT-deficient embryos, concurrent with severe erythrocyte deficiency and growth retardation. These findings suggest that KIT is not required for developmental tissue vascularisation in physiological conditions, but that KIT deficiency causes foetal anaemia at late gestation and thereby pathological vascular remodelling.
Does a Carbon Tax Reduce CO2 Emissions? Evidence from British Columbia
Authors: Pretis Felix 
Published: April 2022

AbstractUsing difference-in-differences, synthetic control, and introducing a new break-detection approach, I show that the introduction of North America’s first major carbon tax has reduced transportation emissions but not ‘yet’ led to large statistically significant reductions in aggregate CO2emissions. Proposing a new method to assess policy based on breaks in difference-in-differences using machine learning, I demonstrate that neither carbon pricing nor trading schemes in other provinces are detected as large and statistically significant interventions. Instead, closures and efficiency-improvements in emission-intense industries in untaxed provinces have reduced emissions. Overall, the results show that existing carbon taxes (and prices) are likely too low to be effective in the time frame since their introduction.
Movement patterns of juvenile green sturgeon (Acipenser medirostris) in the San Francisco Bay Estuary
Authors: Thomas Michael J. , Rypel Andrew L. , Singer Gabriel P. , Klimley A. Peter , Pagel Matthew D. , Chapman Eric D. , Fangue Nann A. 
Published: April 2022

AbstractLittle is known about the distribution and ecology of juvenile green sturgeon throughout their range and specifically within California’s Central Valley and the San Francisco Bay Estuary. The objective of our study was to identify rearing movement patterns of juvenile green sturgeon and their interaction with Delta and Bay habitats. Acoustic biotelemetry was used to record juvenile movements and residence within different regions of this highly modified watershed. We document a diversity of movements exhibited by 31 acoustically tagged juvenile green sturgeon monitored over a 9-month period. The juvenile sturgeon either (1) remained in the Delta or moved (2) into the Carquinez Straits, (3) into San Pablo Bay, (4) into San Pablo Bay but returned to Delta, (5) through the estuary and likely left through the mouth of the bay, (6) or left the estuary only to return later. Spatiotemporal habitat quality varies within and between Delta and Bay habitats. Variation in water year and hydrologic connectivity are likely to influence habitat quality and quantity, and behaviors may be differentially optimized for fitness in response to environmental variation. Our results provide initial evidence supporting multiple behavioral movement patterns and a broad use of regional habitats for green sturgeon in the California Central Valley. This apparent behavioral diversity observed through movement patterns may ensure long-term success of all population segments over time in an extremely variable environment, ultimately supporting overall population stability (i.e., the portfolio effect). Enhanced conservation efforts may be needed to protect juvenile green sturgeon and the habitats they rely upon.
Assessment of microalgae species, biomass, and distribution from spectral images using a convolution neural network
Authors: Salmi Pauliina , Calderini Marco , Pääkkönen Salli , Taipale Sami , Pölönen Ilkka 
Published: April 2022

AbstractEffective monitoring of microalgae growth is crucial for environmental observation, while the applications of this monitoring could also be expanded to commercial and research-focused microalgae cultivation. Currently, the distinctive optical properties of different microalgae groups are targeted for monitoring. Since different microalgae can grow together, their spectral signals are mixed with ambient properties, making estimations of species biomasses a challenging task. In this study, we cultured five different microalgae and monitored their growth with a mobile spectral imager in three separate experiments. We trained and validated a one-dimensional convolution neural network by introducing absorbance spectra of the cultured microalgae and simulated pairwise mixtures of them. We then tested the model with samples of microalgae (monocultures and their pairwise mixtures) that were not part of the training or validation data. The convolution neural network classified microalgae accurately in the monocultures (test accuracy = 95%, SD = 4) and in the pairwise mixtures (test accuracy = 100%, SD = 0). Median prediction errors for biomasses were 17% (mean = 22%, SD = 18) for the monocultures and 17% (mean 24%, SD = 28) for the pairwise mixtures. As the spectral camera produced spatial information of the imaged target, we also demonstrated here the spatial distribution of microalgae biomass by applying the model across 5 × 5 pixel areas of the spectral images. The results of this study encourage the application of a one-dimensional convolution neural network to solve classification, regression, and distribution problems related to microalgae observation, simultaneously.
Cutting tool condition monitoring using eigenfaces
Authors: König Wolfgang , Möhring Hans-Christian 
Published: April 2022

AbstractEffective monitoring of the tool wear condition within a machining process can be very challenging. Depending on the sensors used, often only a part of the relevant wear information can be detected. In the case of milling processes data acquisition is made even more difficult by the fact that the process working point is inaccessible for sensor applications due to the physical tool, the machining process itself, the chipping and used cooling-lubricants. By using a variety of sensors and different measuring principles, sensor data fusion strategies can counteract this problem. An approach to this is the eigenface algorithm. This approach, a face recognition technique, is tested for its suitability on tool condition monitoring in milling processes by using multi-sensor process data.
Parity and the Resolution of Value Conflicts in Design
Authors: Kozlovski Atay 
Published: April 2022

AbstractRecent developments in theories for responsible innovation have focused on the importance of actively accounting for values in our technological designs. Leading among these theories is that of Value Sensitive Design (VSD) which attempts to guide the design process on the basis of evaluative analysis. However, values often come into conflict and VSD has been criticized for not providing a proper method to resolve such inevitable conflicts. This paper examines three such methods and argues that although each has its merits, they all fail to account for a common source of value conflicts known as value incommensurability. Drawing on literature from the field of axiology, this paper argues that by incorporating the evaluative relation of ‘parity’ each of these three methods, and the VSD framework in general, will be able to properly understand the relation which holds between conflicting design options stemming from the incommensurable of values and be able to guide designers in making rational decision in the face of such conflicts.