Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and toxicity of CLAG combined with pegylated liposomal doxorubicin in the treatment of refractory or relapsed acute myeloid leukemia

Refractory and relapsed acute myeloid leukemia (r/rAML) is associated with a difficult prognosis; clinical trials are typically suggested despite lack of a recognized standard of care. Combinatorial chemotherapy regimens utilized for r/rAML salvage play a crucial role in battling this invasive phase. Although it is characterized by a low response rate, CLAG is a traditional regimen used in r/rAML. We aimed to compare the efficacy and toxicity of CLAG+PLD to explore whether there was any improvement with the addition of pegylated liposomal doxorubicin (PLD) to CLAG
Diabetestherapie bei herzkranken Patienten

ZUSAMMENFASSUNG Wenn es nicht möglich ist, die glykämischen Behandlungsziele mit nicht-medikamentösen Maßnahmen zu erreichen, soll innerhalb weniger Monate – oder bei Stoffwechseldekompensation sofort – mit einer medikamentösen Diabetestherapie begonnen werden. Dabei müssen individualisierte Therapieziele unter Einbezug des individuellen kardiovaskulären und renalen Risikos definiert werden.
Therapie und Training bei Tendinopathien

Tendinopathien sind ein häufiges Krankheitsbild in der physiotherapeutischen Praxis, und es stellt sich die Frage, wie wirksam trotz der Schmerzsymptomatik Therapie und Training sind. Dies vor allem auch vor dem Hintergrund, dass der genaue Mechanismus für das Entstehen einer Tendinopathie nicht vollständig geklärt ist. Dieser Refresher-Artikel erklärt die aktuellen Hypothesen zur Entstehung einer Tendinopathie und zeigt Therapieansätze sowie Trainingsprinzipien für das im Wesentlichen überlastungsinduzierte Beschwerdebild.
FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke

Introduction Comprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, the FIND Stroke Recovery Study. We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery. Methods and analysis We recruit individuals with first-ever stroke at the stroke unit at the Sahlgrenska University Hospital, Sweden, to FIND. The inclusion started early 2018 and we aim to enrol minimum 500 patients. Neurological and cognitive impairments across multiple domains are assessed using validated clinical assessment methods, advanced neuroimaging is performed and blood samples for biomarker measuring (protein, RNA and DNA) at inclusion and follow-up visits at 3 months, 6 months, 1 year, 2 years and 5 years poststroke. At baseline and at each follow-up visit, we also register clinical variables known to influence outcomes such as prestroke functioning, stroke severity, acute interventions, rehabilitation, other treatments, socioeconomic status, infections (including COVID-19) and other comorbidities. Recurrent stroke and other major vascular events are identified continuously in national registers. Ethics and dissemination FIND composes a unique stroke cohort with detailed phenotyping, repetitive assessments of outcomes across multiple neurological and cognitive domains and patient-reported outcomes as well as blood and imaging biomarker profiling. Ethical approval for the FIND study has been obtained from the Regional Ethics Review Board in Gothenburg and the Swedish Ethics Review Board. The results of this exploratory study will provide novel data on the time course of recovery and biomarkers after stroke. The description of this protocol will inform the stroke research community of our ongoing study and facilitate comparisons with other data sets. Trial registration number The protocol is registered at http://www.clinicaltrials. gov, Study ID: NCT05708807.
Performance Control for Nonlinear Hadoop-Mapreduce Computing Systems

Abstract This paper addresses the issue of model establishment and performance control for nonlinear computing systems based on Hadoop-Mapreduce platform. The parameter mapred.map. tasks is selected as the control input data and the CPU usage is selected as the output data. By using least-squares principle, a Hammerstein model for this relationship is identified and validated. The control law consists of a nonlinear compensator and a PID feedback. By testing in Simulink, the Hammerstein model is verified appropriate and the designed nonlinear control drives the CPU usage to achieve the target value asymptotically.
Performance evaluation of Standardized Copula‐based Drought Index with Reconnaissance Drought Index and Standardized Precipitation Temperature Index using severity–duration frequency curves over Balochistan, Pakistan

Drought and aridity are good measures to study climate change that are measured using several indices. In this study, the performance of Standardized Copula‐based Drought Index (SCDI) is compared with Standardized Precipitation Temperature Index (SPTI) and Reconnaissance Drought Index (RDI) for measuring drought in Balochistan province of Pakistan. These standardized drought indices combine the outcomes of De‐Martone Aridity Index (DAI) and UNEP Aridity Index (UAI). SCDI is calculated using probability distributions and copula models that combine the outcomes of UAI and DAI utilizing data of precipitation, potential evapotranspiration (PE), and temperature. Climate data from nine including arid and humid metrological stations are used to study drought conditions in Balochistan province. SCDI outcomes are graphically and numerically compared with SPTI and RDI. Selected drought indices are compared based on frequency of drought and wet events occurred in moderate, severe, and extreme drought categories, which indicate that SCDI has maximum number of events in these categories. It gives better results due to the utilization of more climate data as compared to RDI and SPTI. Severity–duration frequency curves are used to find future projections which shows that drought severity and drought duration have increasing trend with the passage of time. The indices have more differences in results of arid stations. The results indicate that there are no significant chances of drought at lower time scales, but the chances increase with the increase in time scale. The SCDI may also be more useful for agricultural and hydrological droughts due to temperature and PE variables. This study's results will be helpful for climate planning in Balochistan province.
The Optimization of EIGRP Algorithm Based on Particle Swarm and Qos Constraint

Against the shortcomings that EIGRP protocol can not adapt to the complex network of high-speed,and does not consider quality of service,we proposed an algorithm of the optimization of EIGRP mixed measure based on particle swarm and Qos Constraint-Based Routing.Analysis of the five indicators in the application characteristics of EIGRP protocol overhead mainly based on calculating the path.On this basis,we established a model,put the particle swarm algorithm applied to the model,and achieved the path optimization.Simulation results show that it can be a very good convergence speed and optimization results.
Editorial: Novel biomarkers for predicting response to cancer immunotherapy

COPYRIGHT © 2023 Huangfu and Pan. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 11 May 2023 DOI 10.3389/fimmu.2023. 1179913
Editorial: Abiotic stress and plant immunity – a challenge in climate change

COPYRIGHT © 2023 Tanaka, Mudgil and Tunc-Ozdemir. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 10 May 2023 DOI 10.3389/fpls.2023. 1197435
Viral infection in chronic otitis media with effusion in children

Background The role of respiratory viruses in chronic otitis media with effusion (COME) in children is not clearly defined. In our study we aimed to investigate the detection of respiratory viruses in middle ear effusions (MEE) as well as the association with local bacteria, respiratory viruses in the nasopharynx and cellular immune response of children with COME. Methods This 2017–2019 cross-sectional study included 69 children aged 2–6 undergoing myringotomy for COME. MEE and nasopharyngeal swabs were analyzed via PCR and CT-values for the genome and loads of typical respiratory viruses. Immune cell populations and exhaustion markers in MEE related to respiratory virus detection were studied via FACS. Clinical data including the BMI was correlated. Results Respiratory viruses were detected in MEE of 44 children (64%). Rhinovirus (43%), Parainfluenzavirus (26%) and Bocavirus (10%) were detected most frequently. Average Ct values were 33.6 and 33.5 in MEE and nasopharynx, respectively. Higher detection rates correlated with elevated BMI. Monocytes were elevated in MEE (9.5 ± 7.3%/blood leucocytes). Exhaustion markers were elevated on CD4+ and CD8+ T cells and monocytes in MEE. Conclusion Respiratory viruses are associated with pediatric COME. Elevated BMI was associated with increased rates of virus associated COME. Changes in cell proportions of innate immunity and expression of exhaustion markers may be related to chronic viral infection.
Numerical Analysis of Grounding Resistance of Buried Thin Wires by the FDTD Method

For the analysis of grounding resistance with the finite-difference time-domain (FDTD) method for solving Maxwell’s equations, an equivalent radius of a naked thin wire in a lossy medium is derived by means of the static-field approximation proposed for derivation of that of an aerial thin wire. It is 0.23 times the side of cells employed, which is the same as that of an aerial thin wire. The validity is tested by comparing the grounding-resistance values obtained through FDTD simulations on simple buried structures with the theoretical values.
Recent and projected changes in water scarcity and unprecedented drought events over Southern Pakistan

In recent decades, water scarcity is a significant constraint for socioeconomic development and threatens livelihood in an agriculture-based developing country like Pakistan. The water crisis in the country is projected to exacerbate in the coming years, especially in the southern parts. This dire situation calls for an investigation of major droughts, associated water scarcity, and changes in teleconnection patterns over Southern Pakistan. Moderate to low Southeastern monsoon (SEM) precipitation triggered the extreme drought episode (2017–2020) over Southern Pakistan and intensified the water scarcity. This study explored the severity of the respective drought event, underlying mechanisms, and changes in water scarcity over Southern Pakistan. To investigate the future changes (1980–2050) in water scarcity, coupling models (global hydrological models (GHMs)-global climate models (GCMs)) have been used to achieve the interannual performance of water availability and total water consumption. Besides, future scenarios used in this study are the combinations of SSPs and RCPs, including middle-of-the-road (SSP1-RCP4.5) and fossil-fueled development (SSP2-RCP8.5). The findings indicated a precipitation deficit of 45% during the 4-year (2017–2020), depicting the worst events in the past 50 years. South Pakistan observed the worst SEM droughts over the last 50 years, as 2000–2005 was the worst drought (precipitation deficit of 75%), followed by 2017–2020 with a 49% of precipitation deficit. Water scarcity was exacerbated by the extreme dry spells that developed over most of southern Pakistan between 2017 and 2020 as a result of moderate-to-exceptionally low SEM precipitation. Furthermore, this drought episode was accompanied by the cool phase in the Pacific and equatorial Indian Oceans. The future changes in water scarcity over the southern regions of Pakistan present a sharp increase under the SSP2-RCP8.5 scenario and are anticipated to be intensified in already stressed regions. This research is essential for environmentalists, and water resources managers, and provided crucial information to identify the hot spot areas in the target region so that water scarcity problems could be reduced in the future.
CCN2/CTGF tip the balance of growth factors towards TGF-β2 in primary open-angle glaucoma

TGF-β2 is the predominant TGF-β isoform within the eye. One function of TGF-β2 is to provide the eye with immune protection against intraocular inflammation. The beneficial function of TGF-β2 within the eye must be under tight control of a network of different factors. A disbalance of the network can result in different eye diseases. In Primary Open-Angle Glaucoma (POAG), one of the leading causes of irreversible blindness worldwide, TGF-β2 is significantly elevated in the aqueous humor and antagonistic molecules like BMPs are reduced. The changes provoke an altering of the quantity and quality of the extracellular matrix and the actin cytoskeleton in the outflow tissues, leading to an increased outflow resistance and thereby to an increased intraocular pressure (IOP), the major risk factor for primary open-angle glaucoma. The pathologic effect of TGF-β2 in primary open-angle glaucoma is mainly meditated by CCN2/CTGF. CCN2/CTGF can modulate TGF-β and BMP signaling by direct binding. The eye specific overexpression of CCN2/CTGF caused an increase in IOP and led to a loss of axons, the hallmark of primary open-angle glaucoma. CCN2/CTGF appears to play a critical role in the homeostatic balance of the eye, so we investigated if CCN2/CTGF can modulate BMP and TGF-β signaling pathways in the outflow tissues. To this end, we analyzed the direct effect of CCN2/CTGF on both signaling pathways in two transgenic mouse models with a moderate (βB1-CTGF1) and a high CCN2/CTGF (βB1-CTGF6) overexpression and in immortalized human trabecular meshwork (HTM) cells. Additionally, we investigate whether CCN2/CTGF mediates TGF-β effects via different pathways. We observed developmental malformations in the ciliary body in βB1-CTGF6 caused by an inhibition of the BMP signaling pathway. In βB1-CTGF1, we detected a dysregulation of the BMP and TGF-β signaling pathways, with reduced BMP activity and increased TGF-β signaling. A direct CCN2/CTGF effect on BMP and TGF-β signaling was shown in immortalized HTM cells. Finally, CCN2/CTGF mediated its effects on TGF-β via the RhoA/ROCK and ERK signaling in immortalized HTM cells. We conclude that CCN2/CTGF functions as a modulator of the homeostatic balance of BMP and TGF-β signaling pathways, which is shifted in primary open-angle glaucoma.
Role of Astrophorina sponges (Demospongiae) in food-web interactions at the Flemish Cap (NW Atlantic)

Deep-sea sponges are important contributors to carbon and nitrogen cycling due to their large filtration capacity. Species of the suborder Astrophorina form dense sponge grounds in the North Atlantic, where they serve as prey for spongivores, but also have non-trophic interactions with commensal epi- and endobionts. At the Flemish Cap (NW Atlantic) Astrophorina sponges are present in four previously described deep-sea epifaunal assemblages: the deep-sea coral assemblage, the lower slope assemblages 1 and 2, and the deep-sea sponge assemblage. To investigate their role in trophic and non-trophic interactions at the Flemish Cap, we developed trophic-/ non-trophic interaction web models for each of the four faunal assemblages using the published literature. By excluding the sponges from the models, we estimated how many trophic, facultative and obligatory non-trophic links would be lost, and how this removal affected food-web properties (number of compartments, links, link density, and connectance). Astrophorina sponges were mostly linked via facultative non-trophic links to 60, 59, 86, and 92 compartments in the deep-sea coral, the lower slope 1 and 2, and the deep-sea sponge assemblages, respectively. Direct trophic links only existed to Echinasteridae and Pterasteridae. As removing Astrophorina sponges from the interaction webs of the different assemblages had the highest impact on food-web properties compared to removing any other fauna present, these sponges were considered “highest impact taxa”. They were also identified, along with sea pens, as “structural species”/ “habitat formers” and “foundation species” based on non-trophic interactions in the deep-sea coral and deep-sea sponge assemblages.
Exploration biases how forelimb reaches to a spatial target are learned

The brain can learn to generate actions, such as reaching to a target, using different movement strategies. Understanding how different variables bias which strategies are learned to produce such a reach is important for our understanding of the neural bases of movement. Here we introduce a novel spatial forelimb target task in which perched head-fixed mice learn to reach to a circular target area from a set start position using a joystick. These reaches can be achieved by learning to move into a specific direction or to a specific endpoint location. We find that mice gradually learn to successfully reach the covert target. With time, they refine their initially exploratory complex joystick trajectories into controlled targeted reaches. The execution of these controlled reaches depends on the sensorimotor cortex. Using a probe test with shifting start positions, we show that individual mice learned to use strategies biased to either direction or endpoint-based movements. The degree of endpoint learning bias was correlated with the spatial directional variability with which the workspace was explored early in training. Furthermore, we demonstrate that reinforcement learning model agents exhibit a similar correlation between directional variability during training and learned strategy. These results provide evidence that individual exploratory behavior during training biases the control strategies that mice use to perform forelimb covert target reaches.
Invariant relationship unites REM and NonREM sleep

Establishing structural and functional links between two distinct types of sleep, rapid-eye-movement (REM) and non-REM (NREM), that alternate and form several sleep cycles per night, has posed a significant challenge. Here we demonstrate a simple invariant relationship where the product of the duration of NREM sleep episode and intensity of subsequent REM sleep episode remains constant over successive sleep cycles of normal human sleep. This Sleep Cycle Invariant (SCI), previously predicted by a quantitative model of sleep dynamics, supports the structural and functional unity of NREM and REM sleep. The significance of SCI for understanding normal sleep and sleep disorders is highlighted by alterations in REM sleep intensity and NREM sleep episode duration being a hallmark of major depression. One-Sentence Summary The duration of NREM sleep and intensity of REM sleep have an invariant relationship across normal sleep cycles of one night.
Nonviral PDMAEMA Vectors Efficiently Express PDE6β in a Mouse Model of Retinitis Pigmentosa

Retinitis Pigmentosa (RP) is one of main causes of inherited blindness, with about 6% of cases caused by a single mutation in the PDE6β gene, making it an ideal candidate for a gene therapy intervention. Gene therapy has been shown to restore normal retinal and visual function in other monogenic diseases, such as Lebers’ Congenital Amaurosis and choroideremia, and RP could benefit from a similar therapeutic approach. Our goal was to combine efficient nonviral vectors and gene expression systems to express the PDE6β gene in the retina of a mouse model of Retinitis Pigmentosa. We have firstly validated the potential of PDMAEMA polyplexes as a nonviral vector by subretinal injection, which were shown to efficiently promote gene expression in the RPE layer of the adult mouse retina. We have then produced polyplexes of PDMAEMA with a replicating plasmid expressing the PDE6β gene and administered the polyplexes via subretinal injection in the rd10 mouse. We have observed that PDMAEMA polyplexes were able to efficiently enter the target retinal pigment epithelium cells and rapidly express the PDE6β gene in the mouse retina, thus confirming their potential as nonviral vectors for retinal gene therapy.
The development of resistance to an inhibitor of a cellular protein reveals a critical interaction between the enterovirus protein 2C and a small GTPase Arf1

The cellular protein GBF1, an activator of Arf GTPases (ArfGEF: Arf guanine nucleotide exchange factor), is recruited to the replication organelles of enteroviruses through interaction with the viral protein 3A, and its ArfGEF activity is required for viral replication. Here, we investigated the development of resistance of poliovirus, a prototype enterovirus, to increasing concentrations of brefeldin A (BFA), an inhibitor of GBF1. High level of resistance required a gradual accumulation of multiple mutations in the viral protein 2C. The 2C mutations conferred BFA resistance even in the context of a 3A mutant previously shown to be defective in the recruitment of GBF1 to replication organelles, and in cells depleted of GBF1, suggesting a GBF1-independent replication mechanism. Still, activated Arfs accumulated on the replication organelles of this mutant even in the presence of BFA, its replication was inhibited by a pan-ArfGEF inhibitor LM11, and the BFA-resistant phenotype was compromised in Arf1-knockout cells. Importantly, the mutations strongly increased the interaction of 2C with the activated form of Arf1. Analysis of other enteroviruses revealed a particularly strong interaction of 2C of human rhinovirus 1A with activated Arf1. Accordingly, the replication of this virus was significantly less sensitive to BFA than that of poliovirus. Thus, our data demonstrate that enterovirus 2Cs may behave like Arf1 effector proteins and that GBF1 but not Arf activation can be dispensable for enterovirus replication. These findings have important implications for the development of host-targeted anti-viral therapeutics.