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Abstract The study of flow and particle dynamics in microfluidic cross-slot channels is of high relevance for lab-on-a-chip applications. In this work, we investigate the dynamics of a rigid spherical particle in a cross-slot junction for a channel height-to-width ratio of 0.6 and at a Reynolds number of 120 for which a steady vortex exists in the junction area. Using an in-house immersed-boundary-lattice-Boltzmann code, we analyse the effect of the entry position of the particle in the junction and the particle size on the dynamics and trajectory shape of the particle. We find that the dynamics of the particle depend strongly on its lateral entry position in the junction and weakly on its vertical entry position; particles that enter close to the centre show trajectory oscillations. Larger particles have longer residence times in the junction and tend to oscillate less due to their confinement. Our work contributes to the understanding of particle dynamics in intersecting flows and enables the design of optimised geometries for cytometry and particle manipulation.

ABSTRACTInertial particle microfluidics (IPMF) is an emerging technology for the manipulation and separation of microparticles and biological cells. Since the flow physics of IPMF is complex and experimental studies are often time-consuming or costly, computer simulations can offer complementary insights. In this tutorial review, we provide a guide for researchers who are exploring the potential of the lattice-Boltzmann (LB) method for simulating IPMF applications. We first review the existing literature to establish the state of the art of LB-based IPMF modelling. After summarising the physics of IPMF, we then present related methods used in LB models for IPMF and show several case studies of LB simulations for a range of IPMF scenarios. Finally, we conclude with an outlook and several proposed research directions.

TGF-β plays a critical role in maintaining immune cells in a resting state by inhibiting cell activation and proliferation. Resting HIV-1 target cells represent the main cellular reservoir after long-term antiretroviral therapy (ART). We hypothesized that releasing cells from TGF-β–driven signaling would promote latency reversal. To test our hypothesis, we compared HIV-1 latency models with and without TGF-β and a TGF-β type 1 receptor inhibitor, galunisertib. We tested the effect of galunisertib in SIV-infected, ART-treated macaques by monitoring SIV-env expression via PET/CT using the 64Cu-DOTA-F(ab′)2 p7D3 probe, along with plasma and tissue viral loads (VLs). Exogenous TGF-β reduced HIV-1 reactivation in U1 and ACH-2 models. Galunisertib increased HIV-1 latency reversal ex vivo and in PBMCs from HIV-1–infected, ART-treated, aviremic donors. In vivo, oral galunisertib promoted increased total standardized uptake values in PET/CT images in gut and lymph nodes of 5 out of 7 aviremic, long-term ART-treated, SIV-infected macaques. This increase correlated with an increase in SIV RNA in the gut. Two of the 7 animals also exhibited increases in plasma VLs. Higher anti-SIV T cell responses and antibody titers were detected after galunisertib treatment. In summary, our data suggest that blocking TGF-β signaling simultaneously increases retroviral reactivation events and enhances anti-SIV immune responses.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Accumulating evidence from recent human studies and animal models suggests that seizure-related respiratory arrest may be important for initiating cardiorespiratory arrest and death. Prior evidence suggests that apnea onset can coincide with seizure spread to the amygdala and that stimulation of the amygdala can reliably induce apneas in epilepsy patients, potentially implicating amygdalar regions in seizure-related respiratory arrest and subsequent postictal hypoventilation and cardiorespiratory death. This study aimed to determine if an extended amygdalar structure, the dorsal bed nucleus of the stria terminalis (dBNST), is involved in seizure-induced respiratory arrest (S-IRA) and death using DBA/1 mice, a mouse strain which has audiogenic seizures (AGS) and a high incidence of postictal respiratory arrest and death. The presence of S-IRA significantly increased c-Fos expression in the dBNST of DBA/1 mice. Furthermore, disruption of synaptic output from the dBNST via viral-induced tetanus neurotoxin (TeNT) significantly improved survival following S-IRA in DBA/1 mice without affecting baseline breathing or hypercapnic (HCVR) and hypoxic ventilatory response (HVR). This disruption in the dBNST resulted in changes to the balance of excitatory/inhibitory (E/I) synaptic events in the downstream brainstem regions of the lateral parabrachial nucleus (PBN) and the periaqueductal gray (PAG). These findings suggest that the dBNST is a potential subcortical forebrain site necessary for the mediation of S-IRA, potentially through its outputs to brainstem respiratory regions.

Interpretable featurisation allows Quantitative Structure-Property Relationships (QSPR) between chiral diene ligand structures and product stereoselectivities in rhodium-catalysed asymmetric Michael additions (RhCASA). The machine learning approach developed herein is simple to implement yet provides instructive insights and useful predictions (q2/R2 0.7–0.8). These simple interpretable features are found to give comparable predictive ability to both commercial (Dragon) and molecular signature descriptor library approaches. Strong insights into the specific areas of the chiral diene ligand that engender improved RhCASA process enantioselectivity are achieved. These were more interpretable, to synthetic chemists, than existing ML approaches, greatly facilitating design of new chiral diene-ligands.

This study examines changes in synaptic transmission with progression of the chronic epileptic state. Male Sprague-Dawley rats (P40–45) were injected with either saline or pilocarpine. In rats injected with pilocarpine, status epilepticus ensued. Hippocampal slices were cut 20–60 days or 80–110 days post-treatment. Evoked and miniature EPSCs (mEPSCs) were recorded from CA1 pyramidal neurons using whole-cell voltage-clamp. Fiber volleys were also recorded from stratum radiatum. Evoked EPSCs from the pilocarpine-treated cohort showed enhanced amplitudes 20–60 days post-treatment compared to the saline-treated cohort, whereas mEPSCs recorded from the same age group showed no change in event frequency and a slight but significant decrease in mEPSC amplitude distribution. In contrast, comparing evoked EPSCs and mEPSCs recorded 80–110 days after treatment indicated reduced amplitudes from pilocarpine-treated animals compared to controls. mEPSC inter-event interval decreased. This could be explained by a partial depletion of the ready releasable pool of neurotransmitter vesicles in Schaffer collateral presynaptic terminals of the pilocarpine-treated rats. In both saline- and pilocarpine-treated cohorts, concomitant decreases in mEPSC amplitudes as time after treatment progressed suggest that age-related changes in CA1 circuitry may be partially responsible for changes in synaptic transmission that may influence the chronic epileptic state.

Congenital heart disease (CHD) is the most common birth defect globally and coarctation of the aorta (CoA) is one of the commoner CHD conditions, affecting around 1/1800 live births. CoA is considered a CHD of critical severity. Unfortunately, the prognosis for a child born in a low and lower-middle income country (LLMICs) with CoA is far worse than in a high-income country. Reduced diagnostic and interventional capacities of specialists in these regions lead to delayed diagnosis and treatment, which in turn lead to more cases presenting at an advanced stage. Computational fluid dynamics (CFD) is an important tool in this context since it can provide additional diagnostic data in the form of hemodynamic parameters. It also provides an in silico framework, both to test potential procedures and to assess the risk of further complications arising post-repair. Although this concept is already in practice in high income countries, the clinical infrastructure in LLMICs can be sparse, and access to advanced imaging modalities such as phase contrast magnetic resonance imaging (PC-MRI) is limited, if not impossible. In this study, a pipeline was developed in conjunction with clinicians at the Red Cross War Memorial Children’s Hospital, Cape Town and was applied to perform a patient-specific CFD study of CoA. The pipeline uses data acquired from CT angiography and Doppler transthoracic echocardiography (both much more clinically available than MRI in LLMICs), while segmentation is conducted via SimVascular and simulation is realized using OpenFOAM. The reduction in cost through use of open-source software and the use of broadly available imaging modalities makes the methodology clinically feasible and repeatable within resource-constrained environments. The project identifies the key role of Doppler echocardiography, despite its disadvantages, as an intrinsic component of the pipeline if it is to be used routinely in LLMICs.

PurposeResearch has shown that youth experiencing homelessness (YEH) face barriers to social inclusion and are at risk for poor mental health. With the COVID-19 pandemic threatening the health, wellbeing, and economic circumstances of people around the world, this study aims to assess the impacts of the pandemic on YEH in Toronto, Ontario, as well as to identify recommendations for future waves of COVID-19.MethodsSemi-structured interviews were conducted with YEH (ages 16-24, n = 45) and staff who work in one of four downtown emergency shelters for youth (n = 31) in Toronto, Ontario.ResultsYEH experienced both structural changes and psychosocial impacts resulting from the pandemic. Structural changes included a reduction in services, barriers to employment and housing, and changes to routines. Psychosocial outcomes included isolation, worsened mental health, and increased substance use. Impacts were magnified and distinct for subpopulations of youth, including for youth that identified as Black, 2SLGBTQ+, or those new to Canada.ConclusionsThe COVID-19 pandemic increased distress among YEH while also limiting access to services. There is therefore a need to balance health and safety with continued access to in-person services, and to shift the response to youth homelessness to focus on prevention, housing, and equitable supports for subpopulations of youth.

PurposeLesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals experience high rates of adverse mental health outcomes due to the stressors they experience in families, communities, and society more broadly. Work and workplaces have the potential to influence these outcomes given their ability to amplify minority stress, and their ability to influence social and economic wellbeing in this already marginalized population. This study aims to identify how sociodemographic characteristics and characteristics of work, including degree of precarity, industry and perceived workplace support for LGBTQ people, influence self-reported mental health among LGBTQ people in two Canadian cities.MethodsSelf-identified LGBTQ workers ≥16 years of age (n = 531) in Sudbury and Windsor, Ontario, Canada were given an online survey between July 6 and December 2, 2018. Multivariate ordinal logistic regression was used to calculate odds ratios (OR) to evaluate differences in gender identity, age, income, industry, social precarity, work environment, and substance use among workers who self-reported very poor, poor, or neutral mental health, compared with a referent group that self-reported good or very good mental health on a five-point Likert scale about general mental health.ResultsLGBTQ workers with poor or neutral mental health had greater odds of: being cisgender women or trans compared with being cisgender men; being aged ConclusionsBoth precarious work and unsupportive work environments contribute to poor mental health among LGBTQ people. These factors are compounded for trans workers who face poorer mental health than cis-LGBQ workers in similar environments.

The purpose of this article on the marketing of cassava chips brought by the cyclists to Kisangani is to analyze the marketing of cassava chips by the producers them - selves as well as the retailers in Kisangani. The starting question is to know if the producers of cassava come to sell them - selves their product on the market of Kisangani. Thus, we can ask these questions: - This movement would it be beneficial for them? - Would they gain by selling their cassava in Kisangani to supply themselves with various products of first need? - Would their factors of production be well remunerated? The assumptions hereafter were formulated, in regard to the interrogations raised above. From our opinion, we consider that this operation would not be economically advantageous for the "Tolekistes" or cyclists salesmen because they often ignore the elements concerned in the calculation of sell price (their deprivations and sacrifices). In order to check these assumptions, a survey questionnaire and a direct observation near the producers and retailers enabled us to achieve the goals of the departure. After examination and processing the data collected, the principal results which come out from this study are as follows: - This operation is not financially advantageous to the cyclist's retailers. This is due to the fact that they often ignore the elements to be considered in the calculation of the cost price (their deprivations and sacrifices). Thus their profit margin is really a loss as a whole i.e. less than 52 000 FC (see table n°V). - While for the farmers, this movement can be regarded as relatively beneficial because if a peasant intends to buy an English Wax part on the level of his surveyed village, he must engage 2,3 baskets of cassava chips whereas on the level of Kisangani, he loses only 1,3 baskets of cassava chips that is practically half (see table VII). In the light of the results obtained, it arises that the starting assumption was confirmed; this operation is thus not advantageous the "Tolékistes" or to cyclists salesmen in terms of income.