Episode 42: Biolore: India’s most aggressive botanical invaders
Related Articles
A Bayesian analysis of heart rate variability changes over acute episodes of bipolar disorder
Bipolar disorder (BD) involves autonomic nervous system dysfunction, detectable through heart rate variability (HRV). HRV is a promising biomarker, but its dynamics during acute mania or depression episodes are poorly understood. Using a Bayesian approach, we developed a probabilistic model of HRV changes in BD, measured by the natural logarithm of the Root Mean Square of Successive RR interval Differences (lnRMSSD). Patients were assessed three to four times from episode onset to euthymia. Unlike previous studies, which used only two assessments, our model allowed for more accurate tracking of changes. Results showed strong evidence for a positive lnRMSSD change during symptom resolution (95.175% probability of positive direction), though the sample size limited the precision of this effect (95% Highest Density Interval [−0.0366, 0.4706], with a Region of Practical Equivalence: [-0.05; 0.05]). Episode polarity did not significantly influence lnRMSSD changes.
Molecular principles underlying aggressive cancers
Aggressive tumors pose ultra-challenges to drug resistance. Anti-cancer treatments are often unsuccessful, and single-cell technologies to rein drug resistance mechanisms are still fruitless. The National Cancer Institute defines aggressive cancers at the tissue level, describing them as those that spread rapidly, despite severe treatment. At the molecular, foundational level, the quantitative biophysics discipline defines aggressive cancers as harboring a large number of (overexpressed, or mutated) crucial signaling proteins in major proliferation pathways populating their active conformations, primed for their signal transduction roles. This comprehensive review explores highly aggressive cancers on the foundational and cell signaling levels, focusing on the differences between highly aggressive cancers and the more treatable ones. It showcases aggressive tumors as harboring massive, cancer-promoting, catalysis-primed oncogenic proteins, especially through certain overexpression scenarios, as predisposed aggressive tumor candidates. Our examples narrate strong activation of ERK1/2, and other oncogenic proteins, through malfunctioning chromatin and crosslinked signaling, and how they activate multiple proliferation pathways. They show the increased cancer heterogeneity, plasticity, and drug resistance. Our review formulates the principles underlying cancer aggressiveness on the molecular level, discusses scenarios, and describes drug regimen (single drugs and drug combinations) for PDAC, NSCLC, CRC, HCC, breast and prostate cancers, glioblastoma, neuroblastoma, and leukemia as examples. All show overexpression scenarios of master transcription factors, transcription factors with gene fusions, copy number alterations, dysregulation of the epigenetic codes and epithelial-to-mesenchymal transitions in aggressive tumors, as well as high mutation loads of vital upstream signaling regulators, such as EGFR, c-MET, and K-Ras, befitting these principles.
BREATHLEssness in INDIA (BREATHE-INDIA): realist review to develop explanatory programme theory about breathlessness self-management in India
Breathlessness is highly prevalent in low and middle-income countries (LMICs). Low-cost, non-drug, breathlessness self-management interventions are effective in high-income countries. However, health beliefs influence acceptability and have not been explored in LMIC settings. Review with stakeholder engagement to co-develop explanatory programme theories for whom, if, and how breathlessness self-management might work in community settings in India. Iterative and systematic searches identified peer-reviewed articles, policy and media, and expert-identified sources. Data were extracted in terms of contribution to theory (high, medium, low), and theories developed with stakeholder groups (doctors, nurses and allied professionals, people with lived experiences, lay health workers) and an International Steering Group (RAMESES guidelines (PROSPERO42022375768)). One hundred and four data sources and 11 stakeholder workshops produced 8 initial programme theories and 3 consolidated programme theories. (1) Context: breathlessness is common due to illness, environment, and lifestyle. Cultural beliefs shape misunderstandings about breathlessness; hereditary, part of aging, linked to asthma. It is stigmatised and poorly understood as a treatable issue. People often use rest, incense, or tea, while avoiding physical activity due to fear of worsening breathlessness. Trusted voices, such as healthcare workers and community members, can help address misconceptions with clear, simple messages. (2) Breathlessness intervention applicability: nonpharmacological interventions can work across different contexts when they address unhelpful beliefs and behaviours. Introducing concepts like “too much rest leads to deconditioning” aligns with cultural norms while promoting beneficial behavioural changes, such as gradual physical activity. Acknowledging breathlessness as a medical issue is key to improving patient and family well-being. (3) Implementation: community-based healthcare workers are trusted but need simple, low-cost resources/skills integrated into existing training. Education should focus on managing acute episodes and daily breathlessness, reducing fear, and encouraging behavioural change. Evidence-based tools are vital to gain support from policymakers and expand implementation. Breathlessness management in India must integrate symptom management alongside public health and disease treatment strategies. Self-management interventions can be implemented in an LMIC setting. However, our novel methods indicate that understanding the context for implementation is essential so that unhelpful health beliefs can be addressed at the point of intervention delivery.
Brain structural correlates of an impending initial major depressive episode
Neuroimaging research has yet to elucidate whether reported gray matter volume (GMV) alterations in major depressive disorder (MDD) exist already before the onset of the first episode. Recruitment of presently healthy individuals with a subsequent transition to MDD (converters) is extremely challenging but crucial to gain insights into neurobiological vulnerability. Hence, we compared converters to patients with MDD and sustained healthy controls (HC) to distinguish pre-existing neurobiological markers from those emerging later in the course of depression. Combining two clinical cohorts (n = 1709), voxel-based morphometry was utilized to analyze GMV of n = 45 converters, n = 748 patients with MDD, and n = 916 HC in a region-of-interest approach and exploratory whole-brain. By contrasting the subgroups and considering both remission state and reported recurrence at a 2-year clinical follow-up, we stepwise disentangled effects of (1) vulnerability, (2) the acute depressive state, and (3) an initial vs. a recurrent episode. Analyses revealed higher amygdala GMV in converters relative to HC (ptfce-FWE = 0.037, d = 0.447) and patients (ptfce-FWE = 0.005, d = 0.508), remaining significant when compared to remitted patients with imminent recurrence. Lower GMV in the dorsolateral prefrontal cortex (ptfce-FWE < 0.001, d = 0.188) and insula (ptfce-FWE = 0.010, d = 0.186) emerged in patients relative to HC but not to converters, driven by patients with acute MDD. By examining one of the largest available converter samples in psychiatric neuroimaging, this study allowed a first determination of neural markers for an impending initial depressive episode. Our findings suggest a temporary vulnerability, which in combination with other common risk factors might facilitate prediction and in turn improve prevention of depression.
Insights from a century of data reveal global trends in ex situ living plant collections
Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.2 million records, from a meta-collection currently holding ~500,000 accessions and 41% of global ex situ species diversity. Our study provides critical insights into the historical evolution, current state and future trajectory of global living collections. We reveal sigmoidal growth of a meta-collection that has reached capacity in both total accessions and total diversity, and identify intrinsic constraints on biodiversity management, including a median survival probability of 15 years. We explore the impact of external constraints and quantify the influence of the Convention on Biological Diversity, which we link to reduced acquisition of wild-origin and internationally sourced material by 44% and 38%, respectively. We further define the impact of these constraints on ex situ conservation but highlight targeted initiatives that successfully mitigate these challenges. Ultimately, our study underscores the urgent need for strategic prioritization and the re-evaluation of ex situ biodiversity management to achieve both scientific and conservation goals.
Responses