Miracle-dz/UniFAR-FTUs huggingface dataset:
The Efficacy and Safety of Cytarabine on Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

Background: The role of cytarabine on newly diagnosed primary central nervous system lymphoma (PCNSL) remains controversial. The present study mainly aimed to assess the efficacy and safety of cytarabine in the induction treatment of PCNSL. Methods: We systematically searched PubMed, Embase, and the Cochrane library for randomized controlled trials comparing treatment of PCNSL patients with or without cytarabine. A meta-analysis was conducted to compare the odds ratios (ORs) with corresponding 95% confidence intervals (95% CI) for complete remission (CR) rate, overall response rate (ORR), grade 3–4 toxic effects, hazard ratios (HRs) with 95% CIs for progression-free survival (PFS), and overall survival (OS) using Stata 12.0. Results: In total, three randomized clinical trials were analyzed in this study. The result of our statistical analysis demonstrated that the application of cytarabine was closely correlated with a higher CR (OR: 2.27, 95% CI: 1.29–3.99, P < 0.01) and ORR (OR: 2.11, 95% CI: 1.14–3.93, P = 0.02). No significant difference was found in OS (HR: 0.75, 95% CI: 0.50–1.13, P = 0.17), but PFS had been improved (HR: 0.66, 95% CI: 0.45–0.97, P = 0.04) when cytarabine was added to the treatment regimen. The grade 3–4 side effect rate of the cytarabine group was higher (overall OR: 2.95, 95% CI: 1.37–6.34, P < 0.01) than that of the cytarabine-free group. Conclusions: This meta-analysis verifies that adding cytarabine to the therapeutic regimen is helpful for newly diagnosed PCNSL patients in terms of CR, ORR, and PFS. Moreover, it should be noted that the grade 3–4 toxic effects, especially hematological toxicity, are higher in the cytarabine group than in the cytarabine-free group. The results indicate that cytarabine plays an important role in the induction therapy of PCNSL. Large-sample and high-quality RCTs should be conducted to verify our results and confirm the effects of cytarabine on newly diagnosed PCNSL.
Will Sirtuins Be Promising Therapeutic Targets for TBI and Associated Neurodegenerative Diseases?

Traumatic brain injury (TBI), a leading cause of morbidity worldwide, induces mechanical, persistent structural, and metabolic abnormalities in neurons and other brain-resident cells. The key pathological features of TBI include neuroinflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. These pathological processes persist for a period of time after TBIs. Sirtuins are evolutionarily conserved nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylases and mono-ADP-ribosyl transferases. The mammalian sirtuin family has seven members, referred to as Sirtuin (SIRT) 1–7. Accumulating evidence suggests that SIRT1 and SIRT3 play a neuroprotective role in TBI. Although the evidence is scant, considering the involvement of SIRT2, 4–7 in other brain injury models, they may also intervene in similar pathophysiology in TBI. Neurodegenerative diseases are generally accepted sequelae of TBI. It was found that TBI and neurodegenerative diseases have many similarities and overlaps in pathological features. Besides, sirtuins play some unique roles in some neurodegenerative diseases. Therefore, we propose that sirtuins might be a promising therapeutic target for both TBI and associated neurodegenerative diseases. In this paper, we review the neuroprotective effects of sirtuins on TBI as well as related neurodegeneration and discuss the therapeutic potential of sirtuin modulators.
Activated Oxytocin Neurons in the PVN-DVC Pathway in Asthmatic Rats

Asthma is a heterogeneous disease, and the central nervous system (CNS) also participates in the pathogenesis of asthma. We previously reported the amygdala might regulate asthmatic attacks via projecting to the paraventricular hypothalamic nucleus (PVN). The dorsal vagal complex (DVC) is a crucial region that modulates respiratory. This study aimed to observe the activity in both PVN and DVC and the connection between PVN and DVC in asthmatic rats. Immunohistochemistry was conducted to observe the changes in Fos and oxytocin (OT) expression. Retrograde tracing using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and double immunohistochemistry for OT and Fos was used to observe the HRP/OT/Fos positive neurons distribution in the PVN. The results showed that during an asthma attack, the Fos positive neurons increased in both PVN and DVC over time. The expression of OT positive neurons in PVN showed a similar trend in parallel to the c-Fos positive neurons in PVN. The HRP retrograde-labeled neurons were densely distributed in the medial and lateral subnucleus in the PVN. OT+/HRP+ and Fos+/OT+/HRP+ accounted for 18.14%, and 2.37% of HRP-labeled neurons, respectively. Our study showed PVN and DVC were activated and the expression of OT positive neurons in PVN were increased over time during an asthma attack. The existence of connection between PVN and DVC suggested the OT neurons in PVN might project to DVC which might be involved in the pathogenesis of asthma.
Transcriptome Analysis of the Clostridioides difficile Response to Different Doses of Bifidobacterium breve

Probiotics are widely used in the prevention of Clostridioides difficile infection (CDI). The precise dosage of probiotics is a challenge. In this study, Clostridioides difficile ATCC 9689 (CD) was exposed to different doses of Bifidobacterium breve (YH68). A transcriptomic analysis was performed on CD cells that were separately exposed to low or high doses of YH68 cell-free culture supernatant (CFCS; CDL; or CDH, respectively). The results showed that the inhibitory effect of YH68 (cell pellets or CFCS) on the growth and the damage to the cell membrane integrity of CD exhibited a dose-response relationship at the physiological level. At the transcriptional level, a large number of differentially expressed genes (DEGs) were concentrated in amino acid, carbohydrate, energy metabolism and membrane transport in CDL and CDH cells, suggesting that both doses of YH68-CFCS triggered a significant change in activities in these metabolic pathways. Importantly, a significant stimulation or suppression was found in the pathogenic pathways (quorum sensing, signal transduction, flagellar assembly, biofilm formation, and drug resistance) of CDL and CDH cells, whereas there were some differences between the two doses. For example, the expression levels of genes related to quorum sensing and signal transduction in CDH cells were suppressed significantly, whereas genes encoding toxin production and sporulation factors were enhanced; in CDL cells, the expression levels of genes associated with flagellar assembly and biofilm formation were suppressed, whereas genes associated with drug resistance were upregulated significantly. These results indicated that the inhibitory effect of YH68-CFCS against CD, especially in pathogenic and metabolic aspects, did not demonstrate a dose-response relationship at the transcriptional level.
Analysis of Resistance to Florfenicol and the Related Mechanism of Dissemination in Different Animal-Derived Bacteria

Bacterial resistance to antibiotics has become an important concern for public health. This study was aimed to investigate the characteristics and the distribution of the florfenicol-related resistance genes in bacteria isolated from four farms. A total of 106 florfenicol-resistant Gram-negative bacilli were examined for florfenicol-related resistance genes, and the positive isolates were further characterized. The antimicrobial sensitivity results showed that most of them (100, 94.33%) belonged to multidrug resistance Enterobacteriaceae. About 91.51% of the strains carried floR gene, while 4.72% carried cfr gene. According to the pulsed-field gel electrophoresis results, 34 Escherichia coli were subdivided into 22 profiles, the genetic similarity coefficient of which ranged from 80.3 to 98.0%. The multilocus sequence typing (MLST) results revealed 17 sequence types (STs), with ST10 being the most prevalent. The genome sequencing result showed that the Proteus vulgaris G32 genome consists of a 4.06-Mb chromosome, a 177,911-bp plasmid (pG32-177), and a 51,686-bp plasmid (pG32-51). A floR located in a drug-resistant region on the chromosome of P. vulgaris G32 was with IS91 family transposase, and the other floR gene on the plasmid pG32-177 was with an ISCR2 insertion sequence. The cfr gene was located on the pG32-51 flanked by IS26 element and TnpA26. This study suggested that the mobile genetic elements played an important role in the replication of resistance genes and the horizontal resistance gene transfer.
Regulation of COP1 Function by Brassinosteroid Signaling

Small increases in temperature result in enhanced elongation of the hypocotyl and petioles and hyponastic growth, in an adaptive response directed to the cooling of the leaves and to protect the shoot meristem from the warm soil. This response, collectively termed as thermomorphogenesis, relies on the faster reversion of phyB Pfr at warmer temperatures, which leads to enhanced activity of the basic-helix-loop-helix PHYTOCHROME INTERACTING FACTOR 4 (PIF4). PIF4 acts as a molecular hub integrating light and temperature cues with endogenous hormonal signaling, and drives thermoresponsive growth by directly activating auxin synthesis and signaling genes. Growth promotion by PIF4 depends on brassinosteroid (BR) signaling, as indicated by the impaired thermoresponse of BR-defective mutants and the partial restoration of pifq thermoresponsive defects by brassinolide (BL) application. Also, phyB limits thermomorphogenic elongation through negative regulation of the E3 ubiquitin ligase COP1 that triggers nuclear degradation of multiple photomorphogenesis-promoting factors acting antagonistically to PIF4. COP1 is indeed observed to accumulate in the nucleus in darkness, or in response to warm temperatures, with constitutive photomorphogenic cop1 mutants failing to respond to temperature. Here we explored the role of BR signaling on COP1 function, by growing cop1 seedlings on BL or the inhibitor brassinazole (BRZ), under different light and temperature regimes. We show that weak cop1 alleles exhibit a hyposensitive response to BL. Furthermore, while cop1-6 mutants display as described a wild-type response to temperature in continuous darkness, this response is abolished by BRZ. Application of this inhibitor likewise suppressed temperature-induced COP1 nuclear accumulation in N. benthamiana leaves. Overall these results demonstrate that cop1-6 is not a temperature-conditional allele, but this mutation allows for a partially active protein which unveils a pivotal role of active BR signaling in the control of COP1 activity.
Hallmarks of Life in Single Cell Contact Mechanics: Outstanding Challenges and Perspectives

Cell mechanics is a fascinating subject that has witnessed a boost of scientific interest in the most diverse disciplines. Evidence of its biological relevance is continuously mounting, unveiling a real-life scenario ever more intricate and complex, and ever less universal. This review revisits the topic at the same time that appraises routine approaches and the synchronous combination of experimental methodologies to tackle cell mechanics in all its dimensionality and complexity. The focus is placed on cultured mammalian cells and on highly sensitive experimental techniques that rely on contact mechanics, namely scanning-probe and traction force microscopies. The importance of time as key variable in theory and experiment is particularly highlighted, together with the need to unambiguously identify the active and physiological contributions to cell behavior, and provide suitable mechanisms that dynamically interconnect relevant events, cellular structures and organelles to thoroughly understand the mechanobiology of cells. A special consideration is given to the role of friction and the importance of cell-cell interactions in scaling up the mechanical behavior from single cells to tissues. The topic is in constant demand of crossdisciplinarity, and in that sense, this review also serves the purpose of bringing the subject nearer to the mechanical physics and engineering community.
How Team Structure Can Enhance Performance: Team Longevity’s Moderating Effect and Team Coordination’s Mediating Effect

Teams are more or less structured in function. Whether team structure is beneficial or harmful for the teams entail debates in current literature. Past studies mainly investigate the effects of team structure through learning or creativity. In this study, we tend to examine the effect of team structure on team performance through team coordination. We conducted two independent field studies with samples of 56 and 67 work teams to test our hypotheses. In both two substudies, we found team structure positively affect team performance by improving team coordination. Moreover, we found team longevity was able to moderate the relationship between team structure and team performance through team coordination, such that the positive relationship between team structure and team coordination were more significant when team longevity was high rather than low.
Comparative microRNA Transcriptomes in Domestic Goats Reveal Acclimatization to High Altitude

High-altitude acclimatization is a representative example of vertebrates’ acclimatization to harsh and extreme environments. Previous studies reported sufficient evidence for a molecular genetic basis of high-altitude acclimatization, and genomic patterns of genetic variation among populations and species have been widely elucidated in recent years. However, understanding of the miRNA role in high-altitude acclimatization have lagged behind, especially in non-model species. To investigate miRNA expression alterations of goats that were induced by high-altitude stress, we performed comparative miRNA transcriptome analysis on six hypoxia-sensitive tissues (heart, kidney, liver, lung, skeletal muscle, and spleen) in two goat populations from distinct altitudes (600 and 3000 m). We obtained the expression value of 1391 mature miRNAs and identified 138 differentially expressed (DE) miRNAs between high and low altitudes. Combined with tissue specificity analysis, we illustrated alterations of expression levels among altitudes and tissues, and found that there were coexisting tissue-specific and -conserved mechanisms for hypoxia acclimatization. Notably, the interplay between DE miRNA and DE target genes strongly indicated post-transcriptional regulation in the hypoxia inducible factor 1, insulin, and p53 signaling pathways, which might play significant roles in high-altitude acclimatization in domestic goats. It’s also worth noting that we experimentally confirmed miR-106a-5p to have a negative regulation effect on angiogenesis by directly targeting FLT-1. These results provide insight into the complicated miRNA expression patterns and regulatory mechanisms of high-altitude acclimatization in domestic goats.
Is There a Role for Vitamin D in Amyotrophic Lateral Sclerosis? A Systematic Review and Meta-Analysis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3–5 years after diagnosis from respiratory failure. Several studies investigated the role of vitamin D as a biomarker or a therapeutic option for ALS patients. To clarify the scientific evidence, we performed a systematic review and different meta-analyses regarding the potential role of vitamin D in ALS. Methods: We performed a systematic review of clinical trials, cohorts, and case–control studies retrieved from PubMed, EMBASE, and Cochrane databases reporting vitamin D levels as a putative biomarker for ALS diagnosis or prognosis or the effect of vitamin D supplementation in ALS patients. Whenever possible, data were pooled using a random-effects model, with an assessment of heterogeneity. Results: Out of 2,996 articles retrieved, we finally included 13 research articles, 12 observational studies (50% prospective), and 1 clinical trial. We found that ALS patients had slightly lower levels of vitamin D than controls (mean difference −6 ng/ml, 95% CI [−10.8; −1.3]), but important confounding factors were not considered in the studies analyzed. We found no relationship between vitamin D levels and ALS functional rate score—revised (ALSFRS-R), with highly heterogeneous results. Discordant results were reported in three studies regarding survival. Finally, five studies reported the effects of vitamin D supplementation with discordant results. Two of them showed a small improvement, whereas two others showed a deleterious effect on ALSFRS-R. One very small clinical trial with important methodological limitations showed some improvement in ALSFRS-R with high doses of vitamin D compared with normal doses. Conclusions: Our review did not find evidence to support the role of vitamin D on ALS diagnosis, prognosis, or treatment. Most studies had important limitations, mostly regarding the risk of bias for not considering confounding factors. Vitamin D supplementation should be offered to ALS patients to avoid other health issues related to vitamin D deficiency, but there is not enough evidence to support the use of vitamin D as a therapy for ALS.
Brain Tumors and Electroconvulsive Therapy: A Literature Overview of the Last 80 Years

The safety and efficacy of electroconvulsive therapy (ECT) in patients with a brain tumor have been debated in the past without a clear conclusion. In the last large review published by Maltbie et al. in 1980, it was concluded that the presence of an intracranial mass should be considered an absolute contraindication to ECT. In our updated review, we investigated a total of 33 published and indexed case reports, case report series, and reviews of 75 individual patients who underwent ECT in the presence of a brain tumor over the last 80 years. Mounting case reports after the original Maltbie et al. review show that it is feasible to apply this method safely in patients with benign or otherwise clinically insignificant lesions. Certain precautionary measures, such as dexamethasone or phenytoin application before ECT, could lead to a further minimalization or even absence of adverse effects, particularly in higher risk individuals.
Shifting in the Dominant Bacterial Group Endozoicomonas Is Independent of the Dissociation With Coral Symbiont Algae

The coral-associated Endozoicomonas are dominant bacteria in the coral holobiont. Their relative abundance usually decreases with heat-induced coral bleaching and is proposed to be positively correlated with Symbiodiniaceae abundance. It remains unclear whether this phenomenon of decreased Endozoicomonas abundance is caused by temperature stress or a decreased abundance of Symbiodiniaceae. This study induced bleaching in the coral Euphyllia glabrescens using a dark treatment over 15 weeks. We examined shifts in Endozoicomonas abundance and experimentally reduced Symbiodiniaceae density. 16S rRNA gene amplicon sequencing was used to characterize the changes in bacterial community (incl. Endozoicomonas) over time, and the 16S rRNA gene copy number of Endozoicomonas was quantified by qPCR. We detected a high abundance of Endozoicomonas in E. glabrescens that underwent dark-induced bleaching. The results reveal that changes in the relative abundance of Endozoicomonas are unrelated to Symbiodiniaceae abundance, indicating that Endozoicomonas can be independent of Symbiodiniaceae in the coral holobiont.
Effect of Capacity to Undertake Instrumental Activities of Daily Living on Entry to Aged Residential Care in Older People With Heart Failure

Background: Heart failure is a common condition in older people with complex medical needs. A key factor in resilience after heart failure is the capacity to perform the instrumental activities of daily living (IADLs). Knowing the association between capacity to perform IADLs and entry into aged residential care will help health professionals plan interventions that will allow older people to remain independent longer. Methods: We analyzed the association between the capacity to perform eight IADLs and entry into ARC. Participants included New Zealanders aged ≥65 years with a diagnosis of heart failure, and who had an InterRAI 9.1 Home Care assessment between July 2012 and June 2018. A multivariable competing risks regression model for entry to ARC with death as the competing risks was used to establish sub-hazard ratios (SHR) for IADL capacity. Co-variates included demographic variables, co-morbidities, living arrangements, cognitive performance, depression, timed walk, alcohol use, smoking, activities of daily living, recent hospitalization and history of falls. Results: There were 13,220 participants with heart failure who were followed for a median 1.69 (0.70–3.17) years. There were 3,177 (24.0%) participants who entered aged residential care and 5,714 (43.2%) who died without having first entered residential care. Overall capacity to perform specific IADLs was “very poor” for housework (85.5%), shopping (68.0%), stairs (61.7%), meal preparation (53.0%), and transportation (52.2%). In the multivariable model, compared to adequate capacity (the reference) poorer capacity for managing finance, managing medications, meal preparation and transport were all associated with increased risk of entering aged residential care, with SHR from 1.05 to 1.18. Overall, the IADL capacity explained ~10% of the risk of entering aged residential care. Conclusion: Capacity to perform IADL is a key factor in maintaining resilience in older people with heart failure. Capacity to manage finances, transport and medications, prepare meals, and transport oneself with minimal supervision could reduce the risk of entry into aged residential care. Developing early interventions and support for people with poor capacity to perform their IADL may help reduce admission into aged residential care.
Learning to Close the Gap: Combining Task Frame Formalism and Reinforcement Learning for Compliant Vegetable Cutting

Compliant manipulation is a crucial skill for robots when they are supposed to act as helping hands in everyday household tasks. Still, nowadays, those skills are hand-crafted by experts which frequently requires labor-intensive, manual parameter tuning. Moreover, some tasks are too complex to be specified fully using a task specification. Learning these skills, by contrast, requires a high number of costly and potentially unsafe interactions with the environment. We present a compliant manipulation approach using reinforcement learning guided by the Task Frame Formalism, a task specification method. This allows us to specify the easy to model knowledge about a task while the robot learns the unmodeled components by reinforcement learning. We evaluate the approach by performing a compliant manipulation task with a KUKA LWR 4+ manipulator. The robot was able to learn force control policies directly on the robot without using any simulation.
Overview on Modeling for Control of Autonomous Road Vehicles Platoon

This is an overview on the models used to control fleets of road vehicles. In general, simplified vehicle models are used and their coupling features are introduced through the (individual) controllers. The robustness and precision of motion control needs geometric, kinematic and dynamic descriptions. We propose a modeling methodology for robots platooning to introduce specific features in the platoon behavior. This overview proposes reference models to link the fleet vehicles and assign a character to the group independent from control.