An In-Vitro Study of the Expansion and Transcriptomics of CD4+ and CD8+ Naïve and Memory T Cells Stimulated by IL-2, IL-7 and IL-15.

The growth of T cells ex vivo for the purpose of T cell therapies is a rate-limiting step in the overall process for cancer patients to achieve remission. Growing T cells is a fiscally-, time-, and resource-intensive process. Cytokines have been shown to accelerate the growth of T cells, specifically IL-2, IL-7, and IL-15. Here a design of experiments was conducted to optimize the growth rate of different naïve and memory T cell subsets using combinations of cytokines. Mathematical models were developed to study the impact of IL-2, IL-7, and IL-15 on the growth of T cells. The results show that CD4+ and CD8+ naïve T cells grew effectively using moderate IL-2 and IL-7 in combination, and IL-7, respectively. CD4+ and CD8+ memory cells favored moderate IL-2 and IL-15 in combination and moderate IL-7 and IL-15 in combination, respectively. A statistically significant interaction was observed between IL-2 and IL-7 in the growth data of CD4+ naïve T cells, while the interaction between IL-7 and IL-15 was found for CD8+ naïve T cells. The important genes and related signaling pathways and metabolic reactions were identified from the RNA sequencing data for each of the four subsets stimulated by each of the three cytokines. This systematic investigation lays the groundwork for studying other T cell subsets.

Ride-hailing with kids: Who's got their back?

INTRODUCTION: As transportation network companies (TNC) are on the rise, assessing the safety of children traveling in these vehicles is imperative. For this reason, this study developed and adopted a scoring system to assess states' safety standards for children traveling in TNC vehicles. METHODS: The scoring was based on two parameters pertaining to child car seat laws for TNCs: clarity and stringency. For each parameter, three criteria that could impact child safety in TNC vehicles were formulated. If a state met a certain criterion it got 1 point and 0 otherwise. The authors gathered all the necessary information by reviewing state statutes in Nexus Uni, a legal research database. These reviews took place between December 2019 and October 2020, and this study evaluated state laws in effect on October 28, 2020. RESULTS: During this assessment, the authors observed a lack of clarity in state child car seat laws, which could compromise safety of children traveling in TNC vehicles. For clarity of laws, Georgia and Indiana received the highest scores (3 out of 3 points), while 16 states scored only 1 point, which was the lowest score in this category. In terms of stringency of laws, Pennsylvania received the highest score (3 out of 3 points), while Indiana scored the least (0 points). CONCLUSIONS: Besides one state (Oregon), all other states defined TNCs in their state laws. All states except for Indiana and Washington required child car seats in TNC vehicles. The responsibility for child car seat use was clearly defined in 35 states. The fine for child car seat violation was $50 or more in 28 states. Practical Application: This study will help TNCs, policymakers, and stakeholders identify states that need to improve their standards for child safety in TNC vehicles, and comprehensively address the issue.

Mixing and oxygen transfer characteristics of a microplate bioreactor with surface-attached microposts.

Bioprocess optimization for cell-based therapies is a resource heavy activity. To reduce the associated cost and time, process development may be carried out in small volume systems, with the caveat that such systems be predictive for process scale-up. The transport of oxygen from the gas phase into the culture medium, characterized using the volumetric mass transfer coefficient, kL a, has been identified as a critical parameter for predictive process scale-up. Here, we describe the development of a 96-well microplate with integrated Redbud Posts to provide mixing and enhanced kL a. Mixing in the microplate is characterized by observation of dyes and analyzed using the relative mixing index (RMI). The kL a is measured via dynamic gassing out method. Actuating Redbud Posts are shown to increase rate of planar homogeneity (2 min) verse diffusion alone (120 min) and increase oxygenation, with increasing stirrer speed (3500-9000 rpm) and decreasing fill volume (150-350 µL) leading to an increase in kL a (4-88 h-1 ). Significant increase in Chinese Hamster Ovary growth in Redbud Labs vessel (580,000 cells mL-1 ) versus the control (420,000 cells mL-1 ); t(12.814) = 8.3678, p ≤ .001), and CD4+ Naïve cell growth in the microbioreactor indicates the potential for this technology in early stage bioprocess development and optimization.

Landscape genetics reveal broad and fine-scale population structure due to landscape features and climate history in the northern leopard frog (Rana pipiens) in North Dakota.

Prehistoric climate and landscape features play large roles structuring wildlife populations. The amphibians of the northern Great Plains of North America present an opportunity to investigate how these factors affect colonization, migration, and current population genetic structure. This study used 11 microsatellite loci to genotype 1,230 northern leopard frogs (Rana pipiens) from 41 wetlands (30 samples/wetland) across North Dakota. Genetic structure of the sampled frogs was evaluated using Bayesian and multivariate clustering methods. All analyses produced concordant results, identifying a major east-west split between two R. pipiens population clusters separated by the Missouri River. Substructuring within the two major identified population clusters was also found. Spatial principal component analysis (sPCA) and variance partitioning analysis identified distance, river basins, and the Missouri River as the most important landscape factors differentiating R. pipiens populations across the state. Bayesian reconstruction of coalescence times suggested the major east-west split occurred ~13-18 kya during a period of glacial retreat in the northern Great Plains and substructuring largely occurred ~5-11 kya during a period of extreme drought cycles. A range-wide species distribution model (SDM) for R. pipiens was developed and applied to prehistoric climate conditions during the Last Glacial Maximum (21 kya) and the mid-Holocene (6 kya) from the CCSM4 climate model to identify potential refugia. The SDM indicated potential refugia existed in South Dakota or further south in Nebraska. The ancestral populations of R. pipiens in North Dakota may have inhabited these refugia, but more sampling outside the state is needed to reconstruct the route of colonization. Using microsatellite genotype data, this study determined that colonization from glacial refugia, drought dynamics in the northern Great Plains, and major rivers acting as barriers to gene flow were the defining forces shaping the regional population structure of R. pipiens in North Dakota.

District-level explanations for supporter involvement in political parties: The importance of electoral factors.

Traditional analyses of grass roots involvement in political parties have focussed almost exclusively on formal members. However, recent analyses across a range of democracies have shown that non-members (supporters) are playing important roles within political parties, including election campaigning, candidate and leader selection, online policy deliberations and even policy formation. The growing literature on this topic suggests that the involvement of supporters may be a function of party structure and availability of online recruitment. Using new data collected at the 2015 British general election, this article extends the examination of supporter involvement but challenges these assumptions. It shows that supporter activity is better explained by responses to electoral factors and that the focus on online recruitment seriously underplays the enduring importance of human contact.

New Food and Drug Administration-Approved and Emerging Novel Treatment Options for Acute Myeloid Leukemia.

Advancements in the treatment of acute myeloid leukemia (AML) have been sparse during the past several decades, and the disease continues to have a poor prognosis. However, in 2017 alone, four new medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of AML reached the market. Midostaurin, liposomal cytarabine and daunorubicin, enasidenib, and gemtuzumab ogozamicin all showed benefit in respective clinical trials to gain approval for the treatment of AML in various patient populations. Additionally, many phase II and III clinical trials are currently ongoing to assess the safety and efficacy of other potential therapies for the treatment of AML. In this review, we summarize the results of the landmark clinical trials associated with the newly approved agents as well as the current ongoing clinical trials for the treatment of AML. A literature search was performed to retrieve data on agents currently being studied for use. Although the overall prognosis for patients with AML remains poor, the addition of the newly FDA-approved medications is a step in the right direction for a disease state that has proved difficult to treat.

Registered Replication Report: Dijksterhuis and van Knippenberg (1998).

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the "professor" category and those primed with the "hooligan" category (0.14%) and no moderation by gender.

Does Upper Extremity Training Influence Body Composition after Spinal Cord Injury?

Spinal cord injury (SCI) leads to serious body composition adaptations characterized by increasing whole body fat mass and decreased soft tissue lean mass (LM). These adaptations in body composition may lead to several cardio-metabolic disorders that reduce the quality of life, increase patients' and caregivers' burden and eventually leads to mortality. Exercise, an appropriate dietary regimen, and an active lifestyle may alleviate several of the negative effects on body composition after a SCI. Today however, there is no established consensus on the recommended dose, frequency or type of exercise to ameliorate several of the body composition sequelae after an acute SCI. Resistance training has been previously recommended as an effective strategy to restore soft tissue LM and decrease fat mass (FM). The strategy can be simply implemented as a routine home-based training program using free weights or resistance bands after a SCI. Additionally, upper extremity (UE) circuit resistance training has been previously used to improve cardiovascular and metabolic parameters after a SCI; however compared to the vast knowledge regarding the able-bodied (AB) population, the effects of UE circuit resistance training on body composition after a SCI is not well established. In summary, the available evidence does not support the rationale that UE circuit resistance training can lead to positive adaptations in body composition after a SCI. Further studies are suggested to examine the effects of UE circuit resistance training on body composition.

Parties heed (with caution): Public knowledge of and attitudes towards party finance in Britain.

Despite comprehensive reform (Political Parties, Elections and Referendums Act) and recent review (Phillips Review in 2007) of party finance in Britain, public opinion of party finance remains plagued by perceptions of corruption, undue influence from wealthy donors, carefree and wasteful spending and, more generally, from the perception that there is just 'too much money' in politics. In this article we argue that knowledge of and attitudes to party finance matter, not least because advocates of reform have cited public opinion as evidence for reform. However, because attitudes to party finance are part of a broader attitudinal structure, opinion-led reforms are unlikely to succeed in increasing public confidence. Using data generated from YouGov's online panel (N=2,008), we demonstrate that the public know little of the key provisions regulating party finance and attitudes to party finance can be explained along two underlying dimensions - Anti-Party Finance and Reformers. As such, we consider whether parties and politicians should be freed from the constraints of public opinion in reforming party finance.

A case of hereditary inclusion body myopathy: 1 patient, 2 novel mutations.

Hereditary inclusion body myopathy is an autosomal recessive disorder that presents in early adulthood with slowly progressive weakness sparing the quadriceps. Muscle histopathology reveals rimmed vacuoles without inflammation. The disorder is caused by a mutation in the gene for UDP-N-acetylglucosamine 2-epimerase-N-acetylmannosamine kinase (GNE), a bifunctional enzyme involved in protein glycosylation. Over 40 mutations have been described to date. We present a case of a young woman with progressive lower extremity weakness. Clinical presentation, laboratory evaluation, electrodiagnostic testing, muscle pathology, and genetic sequencing are described. The patient was found to have heterozygous mutations in the GNE gene, confirming the diagnosis of hereditary inclusion body myopathy. The mutations she carried have not been described previously. We briefly review the clinical, histopathologic, and molecular genetic findings of this disorder.

Frequency of anxiety in myasthenia gravis.

Symptoms of anxiety are common in many chronic medical conditions. Myasthenia gravis (MG) is a chronic neuromuscular condition characterized by fatigable weakness; few studies to date have examined the occurrence of anxiety in patients with MG and related it to anxiety in other chronic conditions. Sixty-nine patients were given a set of self-administered questionnaires, which included the Beck Anxiety Inventory (BAI). The BAI was scored and showed that 55% of the patients had scores suggestive of anxiety. Forty percent was mildly anxious, 12% were moderately anxious, and 3% were severely anxious. This study suggests that anxiety is at least as common in patients with MG as in patients with other chronic medical conditions. It also suggests that the BAI is a clinically useful tool for assessing anxiety in such a population.

Self-reported Depressive Symptoms in Myasthenia Gravis.

It is well known that patients with a chronic medical illness experience major depression at a higher rate than the general population. The purpose of this study was to determine the frequency of depression among patients with myasthenia gravis (MG) who were referred to a Muscular Dystrophy Association clinic. Forty-five patients with a diagnosis of MG were evaluated with a self-administered survey regarding various typical somatic and psychologic symptoms of depression (the Beck Depression Inventory [BDI]) and then scored according to the BDI guidelines. Thirty-three percent of these patients generated scores suggestive of depression (24% were categorized as mildly depressed, 7% as moderately depressed, and 2% as severely depressed). These results suggest that patients with MG patients experience depression at a higher rate than the general population and at a similar rate as patients with other chronic illnesses.