<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d6544947e83">Current bioinformatics does not adequately represent disease mechanisms. Protein–protein…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d389858e123">This article examines the role of Western celebrities as part of new networks in the incr...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d778167e70">Drug repurposing extends beyond conventional indication extension of an existing marketed medicine…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d1540329e135">This article examines how disabled people can achieve meaningful control over archival c...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d4408306e87"><b><b>Background</b></b></p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto"…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d4228752e61">In the absence of interest from big pharma companies in repurposed drugs, start-ups continue to be…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d34101e161">Research suggests that perimenopause can compound existing struggles for some Autistic peo...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d2970367e85">Reflecting on the revolutionary life and legacy of Frantz Fanon a century since his birth...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d1819e90">This briefing revisits Algerian debates on the writings of Frantz Fanon in the years following independenc...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d3417151e125">Every Cure's computational pharmacophenomics platform has spent two years identifying the highest…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d1374469e145">Introducing this special issue, this article gives an overview of recent debates around tech workers i...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d1567415e77">The Complex Portal (www.ebi.ac.uk/complexportal) [1] is a manually curated reference database of…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d612063e133"> <b>Objectives:</b> Long COVID (LC) is a disabling infection-associated chronic condition following SARS-CoV-2 infection that has been associated with cortisol dysregulation. Cortisol studies in LC to date have been limited to analyses at a single time point and do not account for known fluctuations in cortisol throughout the day. In this study we compare diurnal variations in cortisol patterns between individuals with LC and those who fully recovered from COVID-19 via nonlinear mixed effects modeling. </p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d612063e138"> <b>Methods:</b> Plasma cortisol was measured every 20 minutes from 0800 to 1600 hours in 16 individuals with confirmed history of SARS CoV 2 infection ≥ 3 months prior who either (1) met the National Academies of Sciences, Engineering, and Medicine (NASEM) case definition for LC including prominent fatigue and post-exertional symptoms (n = 7), or (2) had fully recovered from COVID-19 (“fully recovered,” n = 9). We excluded individuals who used any medication known to affect cortisol metabolism in the preceding 4 weeks, and those with sleep disorders or other conditions that could potentially alter their circadian rhythm. One participant who had a documented stressful occurrence on the day of study was also excluded from the model. To capture the hormone’s negative feedback regulation without suppressing circadian oscillation, we defined an inhibitory cortisol concentration (Cinh) driving release dynamics using a dual exponential function, one term representing production and one term representing feedback suppression. The irregular pulses across groups were defined using an exponential probability density function (PDF). Model parameters and inter individual variability were then estimated via nonlinear mixed effects modeling. Phenotype (LC versus recovered) was used as a covariate. Goodness-of-fit, visual predictive checks, and change in objective function value (OFV) were used to guide model selection. </p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d612063e143"> <b>Results:</b> The dataset comprised of 400 cortisol concentrations. A combined error structure (13.4 % proportional; 0.38 µg/dL additive) provided the optimal description of residual variability. Adding an exponential PDF for discrete cortisol pulses reduced OFV from 1151.8 to 600.5. The exponential PDF consisted of scaling parameter, rate parameter with a decay-shape modifier to describe the irregular cortisol secretion throughout the day. Introducing phenotype as an exponential covariate on the pulse decay rate (θ = –0.376) further improved fit (ΔOFV = -22.18), describing 25% of interindividual variability on pulse-decay rate. This covariate effect corresponds to approximately 31% slower decay in recovered versus LC participants. </p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d612063e148"> <b>Conclusions:</b> Our integrated circadian–pulsatile cortisol model accurately captures both the time of day pattern and discrete secretory events. The identified phenotype effect on pulse decay rate suggests altered HPA axis regulation in LC participants. </p>

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d8427091e77">The question of what causes disease has been a challenge since ancient times. Applying the…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d97363e111">Drug development is a complex process requiring crucial decisions, starting with selecting the right…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d3589036e100">The Indian Rebellion of 1857 seismically reconfigured the ways both religion and particular religions ...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d11194825e79">This piece reviews the ‘Talking back: African feminism in dialogue’ interview series I c...

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d18420126e94">Predicting the effect of a drug or drug combination is a highly relevant task in precision…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d18352047e69">Heart failure still represents one of the leading causes for hospitalizations and death in…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d18425570e83">The increasing availability of multi-omic data offers unprecedented opportunities to characterize…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d104077e61">Bringing a new drug to market now costs more than $3 billion. The cost per approval keeps rising…

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d18478674e103">Drug repurposing (DR) offers a cost-effective and expedited alternative to de novo drug discovery.…

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<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d123601e86">A critical aspect of Frantz Fanon’s thought is its rejection of transhistorical or ontolog...