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Abstract Disorders of consciousness (DoC) represent a challenging and complex group of neurological conditions characterised by profound disturbances in consciousness. The current range of treatments for DoC is limited. This has sparked growing interest in developing new treatments, including the use of psychedelic drugs. Nevertheless, clinical investigations and the mechanisms behind them are methodologically and ethically constrained. To tackle these limitations, we combined biologically plausible whole-brain models with deep learning techniques to characterise the low-dimensional space of DoC patients. We investigated the effects of model pharmacological interventions by including the whole-brain dynamical consequences of the enhanced neuromodulatory level of different neurotransmitters, and providing geometrical interpretation in the low-dimensional space. Our findings show that serotonergic and opioid receptors effectively shifted the DoC models towards a dynamical behaviour associated with a healthier state, and that these improvements correlated with the mean density of the activated receptors throughout the brain. These findings mark an important step towards the development of treatments not only for DoC but also for a broader spectrum of brain diseases. Our method offers a promising avenue for exploring the therapeutic potential of pharmacological interventions within the ethical and methodological confines of clinical research.

Abstract The neuroscience of consciousness aims to identify neural markers that distinguish brain dynamics in healthy individuals from those in unconscious conditions. Recent research has revealed that specific brain connectivity patterns correlate with conscious states and diminish with loss of consciousness. However, the contribution of these patterns to shaping conscious processing remains unclear. Our study investigates the functional significance of these neural dynamics by examining their impact on participants’ ability to process external information during wakefulness. Using fMRI recordings during an auditory detection task and rest, we show that ongoing dynamics are underpinned by brain patterns consistent with those identified in previous research. Detection of auditory stimuli at threshold is specifically improved when the connectivity pattern at stimulus presentation corresponds to patterns characteristic of conscious states. Conversely, the occurrence of these conscious state-associated patterns increases after detection, indicating a mutual influence between ongoing brain dynamics and conscious perception. Our findings suggest that certain brain configurations are more favorable to the conscious processing of external stimuli. Targeting these favorable patterns in patients with consciousness disorders may help identify windows of greater receptivity to the external world, guiding personalized treatments.

Recent research suggests that brain-heart interactions are associated with perceptual and self-consciousness. In this line, the neural responses to visceral inputs have been hypothesized to play a leading role in shaping our subjective experience. This study aims to investigate whether the contextual processing of auditory irregularities modulates both direct neuronal responses to the auditory stimuli (ERPs) and the neural responses to heartbeats, as measured with heartbeat-evoked responses (HERs). HERs were computed in patients with disorders of consciousness, diagnosed with a minimally conscious state or unresponsive wakefulness syndrome. We tested whether HERs reflect conscious auditory perception, which can potentially provide additional information for the consciousness diagnosis. EEG recordings were taken during the local-global paradigm, which evaluates the capacity of a patient to detect the appearance of auditory irregularities at local (short-term) and global (long-term) levels. The results show that local and global effects produce distinct ERPs and HERs, which can help distinguish between the minimally conscious state and unresponsive wakefulness syndrome patients. Furthermore, we found that ERP and HER responses were not correlated suggesting that independent neuronal mechanisms are behind them. These findings suggest that HER modulations in response to auditory irregularities, especially local irregularities, may be used as a novel neural marker of consciousness and may aid in the bedside diagnosis of disorders of consciousness with a more cost-effective option than neuroimaging methods.

A unifying turbulent dynamics framework using both model-free and modelbased measures of whole-brain information provides insights into brain states.

A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used for the early detection, staging, treatment monitoring, and prognosis of PCa. A novel approach called liquid biopsy has emerged in recent years, which is a less- or non-invasive procedure since it focuses on plasmatic biomarkers such as DNA and RNA. In the blood of patients with cancer, circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) have been identified such as DNA, mRNA, and non-coding RNA (miRNA and lncRNA). The presence of these molecules encouraged researchers to investigate their potential as biomarkers. In this article, we focused on circulating cfNAs as plasmatic biomarkers of PCa and analyzed their advantages compared to traditional biopsy methods.

Summary: Heart rate has natural fluctuations that are typically ascribed to autonomic function. Recent evidence suggests that conscious processing can affect the timing of the heartbeat. We hypothesized that heart rate is modulated by conscious processing and therefore dependent on attentional focus. To test this, we leverage the observation that neural processes synchronize between subjects by presenting an identical narrative stimulus. As predicted, we find significant inter-subject correlation of heart rate (ISC-HR) when subjects are presented with an auditory or audiovisual narrative. Consistent with our hypothesis, we find that ISC-HR is reduced when subjects are distracted from the narrative, and higher ISC-HR predicts better recall of the narrative. Finally, patients with disorders of consciousness have lower ISC-HR, as compared to healthy individuals. We conclude that heart rate fluctuations are partially driven by conscious processing, depend on attentional state, and may represent a simple metric to assess conscious state in unresponsive patients.

Summary: Emphysema results in destruction of alveolar walls and enlargement of lung airspaces and has been shown to develop during helminth infections through IL-4R-independent mechanisms. We examined whether interleukin 17A (IL-17A) may instead modulate development of emphysematous pathology in mice infected with the helminth parasite Nippostrongylus brasiliensis. We found that transient elevations in IL-17A shortly after helminth infection triggered subsequent emphysema that destroyed alveolar structures. Furthermore, lung B cells, activated through IL-4R signaling, inhibited early onset of emphysematous pathology. IL-10 and other regulatory cytokines typically associated with B regulatory cell function did not play a major role in this response. Instead, at early stages of the response, B cells produced high levels of the tissue-protective protein, Resistin-like molecule α (RELMα), which then downregulated IL-17A expression. These studies show that transient elevations in IL-17A trigger emphysema and reveal a helminth-induced immune regulatory mechanism that controls IL-17A and the severity of emphysema. : Emphysema causes pathology that can compromise lung function, and mechanisms for reducing disease severity remain unclear. Using a helminth model, Chen et al. show that type 2 immune response triggers lung B cells to produce RELMα, which then downregulates IL-17 production in the lung to limit emphysema. Keywords: emphysema, IL-17, B lymphocytes, RELMα, helminth

Studies have suggested that Epithelial-Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas.

Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares

La hibridación in situ por fluorescencia (FISH) se puede utilizar para diagnosticar prenatalmente las aneuploidías más frecuentes. Se utilizan núcleos interfásicos de células fetales no cultivadas. Este es un avance importante en el diagnóstico prenatal. Se describe la aplicación de la FISH en 15 muestras de líquido amniótico no cultivado extraído entre la 12 ± 7.5 y 14 6/7 semanas de gestación (m ± 1 sd = 13,63 ± 0,52). El volumen de líquido amniótico recolectado oscilo entre de 2 y 4ml (3,16 ± 0,58). Todas las pacientes presentaban como principal indicación para la realización del procedimiento la edad materna avanzada. El tiempo para obtener los resultados varió de 1 a 5 días (2,13 ± 1,55 días). El tiempo de entrega de los resultados citogenéticos osciló entre 13 y 22 días (18,4 ± 3,2). En total, 14 casos (93,33%) fueron informativos. Las cinco aneuploidías diagnosticadas por FISH fueron confirmadas por citogenética tradicional, sin embargo, el análisis citogenético tradicional identificó un caso de rearreglo cromosómico equilibrado: [46, XY, t (16; 17) (q24; q12) pat] y un caso de mosaicismo: 46,XX/47,XX,+mar. La realización de FISH requiere muchos pasos que pueden impedir que los resultados sean obtenidos, es importante obtener un número suficiente de núcleos para la hibridación. El estudio de aneuploidías en amniocitos no cultivados debe ser introducido en el protocolo de diagnóstico prenatal en mujeres embarazadas con riesgo aumentado de concebir un feto con aneuploidias.

El diagnóstico citogenético en líquido amniótico obtenido por amniocentesis precoz (AP) es una alternativa a la embarazada de primer trimestre. El objetivo de este trabajo fue investigar el tipo y la frecuencia de anormalidades cromosómicas encontradas en muestras de líquido amniótico obtenido por medio de esa técnica de colecta. En un periodo de 5 años, 531 AP fueron realizadas en 505 pacientes (479 gestaciones únicas y 26 gemelares), con edad gestacional variando de 12 0/7 a 14 6/7 semanas. La principal indicación para la realización del procedimiento fue edad materna avanzada (66,3% de los casos). Los cultivos fueron establecidos en medio Chang y Amniomax (cultivo en frasco). El tiempo de colecta para la obtención de las preparaciones citogenéticas varió de 7 a 22 días (15,5 ± 2,8). Por lo menos 25 células fueron analizadas por paciente. El tiempo de entrega de resultados varió de 12 a 25 días (18,7±2,8 días). La frecuencia de éxito de cultivo fue del 98,7%. Cariotipos anormales fueron identificados en 22 casos (4,2%), siendo tres (0,6%) re arreglos cromosómicos equilibrados y 19 (3,6%) anomalías cromosómicas no equilibradas. De estas, la anormalidad cromosómica más frecuente fue la trisomía del cromosoma 21 (27,3%). Fueron identificados cinco casos de cromosomas marcadores, tres en forma de mosaico. Fueron confirmados seis (18,2%) resultados anormales detectados en Vellosidad Corial (VC). La frecuencia de pseudomosaicismo encontrada fue del 2,3%. Nuestros datos confirman la precisión del estudio citogenético en líquido amniótico obtenido por AP. Con procedimientos de rutina bien establecidos y protocolos adecuadamente estandarizados en el laboratorio de diagnóstico prenatal, se aumenta el éxito de los cultivos de células de líquido amniótico obtenido por AP y se reduce el tiempo medio de entrega de resultados.

We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (