Miracle-dz/UniFAR-FTUs huggingface dataset:
The post‐inspiratory complex (PiCo), what is the evidence?

Breathing is a vital behaviour that ensures a constant oxygen supply to the body and the removal of CO2. The underlying repetitive activity of the diaphragm, the coordinated activity of intercostal and even laryngeal muscles is controlled by a neuronal network that is located in the medulla and the pons (Richter & Smith, 2014; Del Negro et al. 2018). While the preBötzinger complex (preBötC) has been identified as an indispensable element of rhythm generation and inspiratory activity (Smith et al. 1991), neurons in the Bötzinger complex (BötC) and the pontine respiratory group, e.g. the Kölliker–Fuse nucleus (KF), have been shown to provide a negative control of the preBötC and mediate the off switch of inspiratory activity (Smith et al. 2013; Bautista et al. 2014; Richter & Smith, 2014; Molkov et al. 2016; Ausborn et al. 2018). Now, in a very elegant study, recently published in The Journal of Physiology, Dhingra and colleagues showed how neuronal activity of the respiratory network is spatially distributed during the different phases of the respiratory rhythm
Reduced Expression of Cerebral Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome

Glutamatergic receptor expression is mostly unknown in adults with fragile X syndrome (FXS). Favorable behavioral effects of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5) in fmr1 knockout (KO) mouse models have not been confirmed in humans with FXS. Measurement of cerebral mGluR5 expression in humans with FXS exposed to NAMs might help in that effort. We used positron emission tomography (PET) to measure the mGluR5 density as a proxy of mGluR5 expression in cortical and subcortical brain regions to confirm target engagement of NAMs for mGluR5s. The density and the distribution of mGluR5 were measured in two independent samples of men with FXS (N = 9) and typical development (TD) (N = 8). We showed the feasibility of this complex study including MRI and PET, meaning that this challenging protocol can be accomplished in men with FXS with an adequate preparation. Analysis of variance of estimated mGluR5 expression showed that mGluR5 expression was significantly reduced in cortical and subcortical regions of men with FXS in contrast to age-matched men with TD.
In Dialogue: How Writing to the Dead and the Living Can Increase Self-Awareness in Those Bereaved by Addiction

This article examines how writing can increase the self-awareness of a socially isolated and often stigmatized population: those bereaved by addiction. Writing about a traumatic event has been shown to increase self-awareness which can improve health and regulate negative behaviors. Using narrative analysis on the writing of individuals bereaved by addiction, this study found that participants were able to increase their self-awareness through writing to the dead, the living and themselves. Participants’ writing also demonstrated their attempts to make sense and make meaning out of their loss which are both strong predictors of positive health outcomes. All participants in this study demonstrated increased self-awareness as well as sense-making and/or meaning-making which can lead to improvements in behavior regulation, psychological health and physical heath. This suggests that writing may be a uniquely beneficial therapeutic intervention for those experiencing disenfranchised grief as a result of bereavement by addiction.
Oral Antioxidant Vitamins and Magnesium Limit Noise-Induced Hearing Loss by Promoting Sensory Hair Cell Survival: Role of Antioxidant Enzymes and Apoptosis Genes

Noise induces oxidative stress in the cochlea followed by sensory cell death and hearing loss. The proof of principle that injections of antioxidant vitamins and Mg2+ prevent noise-induced hearing loss (NIHL) has been established. However, effectiveness of oral administration remains controversial and otoprotection mechanisms are unclear. Using auditory evoked potentials, quantitative PCR, and immunocytochemistry, we explored effects of oral administration of vitamins A, C, E, and Mg2+ (ACEMg) on auditory function and sensory cell survival following NIHL in rats. Oral ACEMg reduced auditory thresholds shifts after NIHL. Improved auditory function correlated with increased survival of sensory outer hair cells. In parallel, oral ACEMg modulated the expression timeline of antioxidant enzymes in the cochlea after NIHL. There was increased expression of glutathione peroxidase-1 and catalase at 1 and 10 days, respectively. Also, pro-apoptotic caspase-3 and Bax levels were diminished in ACEMg-treated rats, at 10 and 30 days, respectively, following noise overstimulation, whereas, at day 10 after noise exposure, the levels of anti-apoptotic Bcl-2, were significantly increased. Therefore, oral ACEMg improves auditory function by limiting sensory hair cell death in the auditory receptor following NIHL. Regulation of the expression of antioxidant enzymes and apoptosis-related proteins in cochlear structures is involved in such an otoprotective mechanism.
Johnston's organ and its central projections in Cataglyphis desert ants

The Johnston's organ (JO) in the insect antenna is a multisensory organ involved in several navigational tasks including wind‐compass orientation, flight control, graviception, and, possibly, magnetoreception. Here we investigate the three dimensional anatomy of the JO and its neuronal projections into the brain of the desert ant Cataglyphis, a marvelous long‐distance navigator. The JO of C. nodus workers consists of 40 scolopidia comprising three sensory neurons each. The numbers of scolopidia slightly vary between different sexes (female/male) and castes (worker/queen). Individual scolopidia attach to the intersegmental membrane between pedicel and flagellum of the antenna and line up in a ring‐like organization. Three JO nerves project along the two antennal nerve branches into the brain. Anterograde double staining of the antennal afferents revealed that JO receptor neurons project to several distinct neuropils in the central brain. The T5 tract projects into the antennal mechanosensory and motor center (AMMC), while the T6 tract bypasses the AMMC via the saddle and forms collaterals terminating in the posterior slope (PS) (T6I), the ventral complex (T6II), and the ventrolateral protocerebrum (T6III). Double labeling of JO and ocellar afferents revealed that input from the JO and visual information from the ocelli converge in tight apposition in the PS. The general JO anatomy and its central projection patterns resemble situations in honeybees and Drosophila. The multisensory nature of the JO together with its projections to multisensory neuropils in the ant brain likely serves synchronization and calibration of different sensory modalities during the ontogeny of navigation in Cataglyphis.
Effect of active resisted 30 m sprints upon step and joint kinematics and muscle activity in experienced male and female sprinters

ABSTRACT This study compared the kinematics (step and joint) and muscle activity of unresisted and active resisted 30 m sprints with different loads (10–40% body mass) in experienced male and female sprinters. Step kinematics were measured using a laser gun and contact mat in 28 male and female participants during unresisted 30 m sprint, and sprints with 10–40% of body mass (BM) active resistance, while peak angular velocities of lower limb was measured, together with muscle activation of nine muscles. Increased resisted loads resulted in slower 30 m times, as a result of lower step velocity mainly caused by shorter step lengths and frequencies, flight times and longer contact times, with a greater effect on women than on men. These step kinematic differences, due to increasing load were accompanied with lower peak joint movements. However, gender differences were only found for peak plantar flexion with unresisted and 10% BM resisted sprints. Furthermore, increasing load decreased calf and hamstring muscles activity, while medial vastus activity increased. Based upon these findings, it was concluded that when introducing active resisted sprints, women should sprint with approximately 10% less active loads than men to have equal step and joint kinematics development over the sprint distance.
Mobile-Assisted Cognitive Behavioral Therapy for Negative Symptoms: Open Single-Arm Trial With Schizophrenia Patients

Background Negative symptoms are an important unmet treatment need for schizophrenia. This study is a preliminary, open, single-arm trial of a novel hybrid intervention called mobile-assisted cognitive behavioral therapy for negative symptoms (mCBTn). Objective The primary aim was to test whether mCBTn was feasible and could reduce severity of the target mechanism, defeatist performance attitudes, which are associated with experiential negative symptoms and poor functioning in schizophrenia. Methods Participants with schizophrenia or schizoaffective disorder (N=31) who met prospective criteria for persistent negative symptoms were enrolled. The blended intervention combines weekly in-person group therapy with a smartphone app called CBT2go. The app extended therapy group skills, including recovery goal setting, thought challenging, scheduling of pleasurable activities and social interactions, and pleasure-savoring interventions to modify defeatist attitudes and improve experiential negative symptoms. Results Retention was excellent (87% at 18 weeks), and severity of defeatist attitudes and experiential negative symptoms declined significantly in the mCBTn intervention with large effect sizes. Conclusions The findings suggest that mCBTn is a feasible and potentially effective treatment for experiential negative symptoms, if confirmed in a larger randomized controlled trial. The findings also provide support for the defeatist attitude model of experiential negative symptoms and suggest that blended technology-supported interventions such as mCBTn can strengthen and shorten intensive psychosocial interventions for schizophrenia. Trial Registration ClinicalTrials.gov NCT03179696; https://clinicaltrials.gov/ct2/show/NCT03179696
Chemical Composition of Sour Beer Resulting from Supplementation the Fermentation Medium with Magnesium and Zinc Ions

The bioavailability of minerals, such as zinc and magnesium, has a significant impact on the fermentation process. These metal ions are known to influence the growth and metabolic activity of yeast, but there are few reports on their effects on lactic acid bacteria (LAB) metabolism during sour brewing. This study aimed to evaluate the influence of magnesium and zinc ions on the metabolism of Lactobacillus brevis WLP672 during the fermentation of brewers’ wort. We carried out lactic acid fermentations using wort with different mineral compositions: without supplementation; supplemented with magnesium at 60 mg/L and 120 mg/L; and supplemented with zinc at 0.4 mg/L and 2 mg/L. The concentration of organic acids, pH of the wort and carbohydrate use was determined during fermentation, while aroma compounds, real extract and ethanol were measured after the mixed fermentation. The addition of magnesium ions resulted in the pH of the fermenting wort decreasing more quickly, an increase in the level of L-lactic acid (after 48 h of fermentation) and increased concentrations of some volatile compounds. While zinc supplementation had a negative impact on the L. brevis strain, resulting in a decrease in the L-lactic acid content and a higher pH in the beer. We conclude that zinc supplementation is not recommended in sour beer production using L. brevis WLP672.
Sex Differences in Time-Series Changes in Pseudo-R2 Values Regarding Hyperuricemia in Relation to the Kidney Prognosis

Studies on sex differences in time-series changes in pseudo-R2 values regarding hyperuricemia (HU) in relation to the kidney prognosis among patients with chronic kidney disease (CKD) are scant. The kidney prognosis was evaluated in 200 patients with CKD (median follow-up, 12.3 years). Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. We used four definitions of HU according to serum uric acid (SUA) levels (HU6, SUA ≥ 6.0 mg/dL; HU7, SUA ≥ 7.0 mg/dL; HU8, SUA ≥ 8.0 mg/dL) and antihyperuricemic agent use to calculate the mean and percentage of the change in pseudo-R2 values from the 6th year until the end of the study (6Y–End Mean and 6Y–End Change, respectively). The multivariable Cox regression analysis showed that HU7 was significantly associated with kidney outcomes. When stratified by sex, the 6Y–End Mean was clearly higher in women than in men for all HU definitions, with the highest value (0.1755) obtained for HU7 in women. The pseudo-R2 values for HU6 in women showed an increasing pattern, with a 6Y–End Change of 11.4%/year. Thus, it may be clinically meaningful to consider sex differences in the time-series pseudo-R2 values regarding HU and kidney outcomes.
Multi-Omics and Informatics Analysis of FFPE Tissues Derived from Melanoma Patients with Long/Short Responses to Anti-PD1 Therapy Reveals Pathways of Response

Simple Summary Immune based therapies have benefited many melanoma patients, but many patients still do not respond. This study analyzes biospecimens obtained from patients undergoing a type of immune based therapy called anti-PD-1 to understand mechanisms of response and resistance to this treatment. The operational definition of good response utilized in this investigation permitted us to examine the biochemical pathways that are facilitating anti-PD-1 responses independent of prior therapies received by patients. Currently, there are no clinically available tests to reliably test for the outcome of patients treated with anti-PD-1 therapy. The purpose of this study was to facilitate the development of prospective biomarker-directed trials to guide therapy, as even though the side effect profile is favorable for anti-PD-1 therapy, some patients do not respond to therapy with significant toxicity. Each patient may require testing for the pathways upregulated in the tumor to predict optimal benefit to anti-PD-1 treatment. Abstract Anti-PD-1 based immune therapies are thought to be dependent on antigen processing and presentation mechanisms. To characterize the immune-dependent mechanisms that predispose stage III/IV melanoma patients to respond to anti-PD-1 therapies, we performed a multi-omics study consisting of expression proteomics and targeted immune-oncology-based mRNA sequencing. Formalin-fixed paraffin-embedded tissue samples were obtained from stage III/IV patients with melanoma prior to anti-PD-1 therapy. The patients were first stratified into poor and good responders based on whether their tumors had or had not progressed while on anti-PD-1 therapy for 1 year. We identified 263 protein/gene candidates that displayed differential expression, of which 223 were identified via proteomics and 40 via targeted-mRNA analyses. The downstream analyses of expression profiles using MetaCore software demonstrated an enrichment of immune system pathways involved in antigen processing/presentation and cytokine production/signaling. Pathway analyses showed interferon (IFN)-γ-mediated signaling via NF-κB and JAK/STAT pathways to affect immune processes in a cell-specific manner and to interact with the inducible nitric oxide synthase. We review these findings within the context of available literature on the efficacy of anti-PD-1 therapy. The comparison of good and poor responders, using efficacy of PD-1-based therapy at 1 year, elucidated the role of antigen presentation in mediating response or resistance to anti-PD-1 blockade.
Empiric Antibiotic Therapy for Staphylococcus aureus Septic Shock: Is Vancomycin Indicated?

association of positive respiratory culture and PRM across both follow-up points warrants thoughtful evaluation. Cultures were considered positive if growth of a single bacteria was detected, with mixed flora considered negative. We did not collect data related to indication or timing of culture obtainment. It is possible that some of the cultures were obtained at presentation while others due to clinical worsening or concern for development of ventilator-associated pneumonia. Radiologic or inflammatory data that could have been used to better delineate colonization from acute infection were not collected. Despite these limitations, after controlling for confounders, positive bacterial culture was associated with 6-month (odds ratio [OR], 3.72; 95% CI, 1.39– 9.95) and 12-month (OR, 3.54; 95% CI, 1.24–10.08) PRM. We agree that drawing conclusions about the role of bacterial respiratory infections in respiratory morbidity after ARF is premature, but strongly urge that future investigation into morbidity after pediatric ARF should examine bacterial respiratory infections in a standardized fashion to adequately address this potential association. Our data also support investigation into the respiratory microbiome after an episode of intubated ARF in children. Dr. Yehya’s institution received funding from the National Institutes of Health (NIH). Dr. Thomas’s institution received funding from the National Institute of Child Health and Human Development R21HD47463-2. All authors received support for article research from the NIH.
A Cyp51B Mutation Contributes to Azole Resistance in Aspergillus fumigatus

The emergence and spread of Aspergillus fumigatus azole resistance has been acknowledged worldwide. The main problem of azole resistance is the limited therapeutic options for patients suffering aspergillosis. Azole resistance mechanisms have been mostly linked to the enzyme Cyp51A, a target of azole drugs, with a wide variety of modifications responsible for the different resistance mechanisms described to date. However, there are increasing reports of A. fumigatus strains showing azole resistance without Cyp51A modifications, and thus, novel resistance mechanisms are being explored. Here, we characterized two isogenic A. fumigatus clinical strains isolated two years apart from the same patient. Both strains were resistant to clinical azoles but showed different azole resistance mechanisms. One strain (CM8940) harbored a previously described G54A mutation in Cyp51A while the other strain (CM9640) had a novel G457S mutation in Cyp51B, the other target of azoles. In addition, this second strain had a F390L mutation in Hmg1. CM9640 showed higher levels of gene expression of cyp51A, cyp51B and hmg1 than the CM8940 strain. The role of the novel mutation found in Cyp51B together with the contribution of a mutation in Hmg1 in azole resistance is discussed.
Deconvolution of heterogeneous tumor samples using partial reference signals

Deconvolution of heterogeneous bulk tumor samples into distinct cellular populations is an important yet challenging problem, particularly when only partial references are available. A common approach to dealing with this problem is to deconvolve the mixed signals using available references and leverage the remaining signal as a new cell component. However, as indicated in our simulation, such an approach tends to over-estimate the proportions of known cell types and fails to detect novel cell types. Here, we propose PREDE, a partial reference-based deconvolution method using an iterative non-negative matrix factorization algorithm. Our method is verified to be effective in estimating cell proportions and expression profiles of unknown cell types based on simulated datasets at a variety of parameter settings. Applying our method to TCGA tumor samples, we found that proportions of pure cancer cells better indicate different subtypes of tumor samples. We also detected several cell types for each cancer type whose proportions successfully predicted patient survival. Our method makes a significant contribution to deconvolution of heterogeneous tumor samples and could be widely applied to varieties of high throughput bulk data. PREDE is implemented in R and is freely available from GitHub (https://xiaoqizheng.github.io/PREDE).
Fingerprint ridges allow primates to regulate grip

Significance Why have primates evolved epidermal ridges on the volar regions of the hands and feet and with a much greater density of sweat glands than flat skin, which respond to anxiety rather than act as a thermoregulation mechanism? During contact with solid objects, the ridges are important for grip and precision manipulation by regulating moisture levels from either external sources or the sweat pores so that the friction is maximized and catastrophic slip is inhibited. An understanding of the underlying mechanisms involved has become particularly important with the almost ubiquitous contact of the finger pads with flat screens and recent developments in haptic feedback using ultrasonic vibrations for which the performance is critically related to the friction. Fingerprints are unique to primates and koalas but what advantages do these features of our hands and feet provide us compared with the smooth pads of carnivorans, e.g., feline or ursine species? It has been argued that the epidermal ridges on finger pads decrease friction when in contact with smooth surfaces, promote interlocking with rough surfaces, channel excess water, prevent blistering, and enhance tactile sensitivity. Here, we found that they were at the origin of a moisture-regulating mechanism, which ensures an optimal hydration of the keratin layer of the skin for maximizing the friction and reducing the probability of catastrophic slip due to the hydrodynamic formation of a fluid layer. When in contact with impermeable surfaces, the occlusion of the sweat from the pores in the ridges promotes plasticization of the skin, dramatically increasing friction. Occlusion and external moisture could cause an excess of water that would defeat the natural hydration balance. However, we have demonstrated using femtosecond laser-based polarization-tunable terahertz wave spectroscopic imaging and infrared optical coherence tomography that the moisture regulation may be explained by a combination of a microfluidic capillary evaporation mechanism and a sweat pore blocking mechanism. This results in maintaining an optimal amount of moisture in the furrows that maximizes the friction irrespective of whether a finger pad is initially wet or dry. Thus, abundant low-flow sweat glands and epidermal furrows have provided primates with the evolutionary advantage in dry and wet conditions of manipulative and locomotive abilities not available to other animals.
Clinical Utility of the Child and Adolescent Memory Profile (ChAMP) After Pediatric Traumatic Brain Injury

Sixty-one children and adolescents with traumatic brain injury completed the Child and Adolescent Memory Profile (ChAMP; Sherman & Brooks, 2015) within 1 to 12 months post injury. Most of the ChAMP index scores demonstrated statistically significant negative correlations with time to follow commands following traumatic brain injury. Compared with demographically matched neurologically healthy controls, selected from the ChAMP standardization sample, participants with traumatic brain injury had statistically significantly lower scores on all ChAMP index scores but sensitivity and specificity were suboptimal. We conclude that the ChAMP has modest clinical utility as part of a more comprehensive evaluation of sequelae of traumatic brain injury in children and adolescents.