Biology subjects

Cioffi, I.

Publications and source records attributed to Cioffi, I..

4 recordsLinked to original sources

bioRxiv2026

LENS: a transferable neuromuscular signature of musculoskeletal pain intensity

Self-reported pain remains the clinical standard for assessing musculoskeletal pain severity, but its subjectivity limits objective diagnosis, monitoring, and therapeutic development. We present LENS (Latent sEMG Neuromuscular Signature), which decodes exertion-evoked musculoskeletal pain intensity from surface electromyography (sEMG) alone. LENS was pre-trained via a cross-modal self-supervised objective that reconstructs muscle oxygenation from sEMG in 183 adults. LENS was trained exclusively on healthy muscle physiology and generalized to an independent healthy cohort (Spearman's {rho}=0.52) and discriminated moderate-to-severe pain (AUROC=0.83). Using a label-free test-time adaptation, LENS generalized to an unseen chronic musculoskeletal pain cohort--myogenous temporomandibular disorder (mTMD)--with comparable performance ({rho}=0.61; AUROC=0.86). Reverse transfer, from mTMD to controls, was substantially weaker, an asymmetry attributable to elevated motor variability in chronic pain; excluding highly variable mTMD participants recovered performance, indicating a conserved pain signature masked by pathology-specific motor noise. LENS offers a scalable, physiological correlate of musculoskeletal pain from a single sEMG channel.

neuroscience↗

bioRxiv2025

Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high grade adenoid cystic carcinoma (ACC), yet exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, but HMSC lacks the MYB translocation typically seen in ACC. Transcriptional changes in HMSC tumors remain uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on a human HMSC tumor and compared expression profiles with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) scRNA-seq datasets. Primary malignant cells from HMSC (n=134) and ACC (n=980) clustered separately, and HMSC lacked bicellular differentiation into luminal and myoepithelial cells, distinguishing it from ACC. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83% vs. 62%, p=0.022) and MYB targets (p=6.4*10-6), suggesting an HPV-MYB association. This finding was validated in HPV-positive OPSCC, with 7/10 tumors showing MYB upregulation in HPVon versus HPVoff cells (p<0.05). A 264-gene signature from HPVon HMSC cells was also associated with worse prognosis in HPV+ OPSCC (p<0.003), suggesting an alternate role for HPV that has not been well characterized. Further validation of the HPV-MYB association and prognostically relevant HPV gene signature may improve patient stratification and therapeutic strategies in HPV-related malignancies.

cancer biology↗

bioRxiv2023

Delineation of the Trigeminal-Lateral Parabrachial-Central Amygdala Tract in Humans: An Ultra-High Field Diffusion MRI Study

Orofacial pain is thought to be more unpleasant than pain elsewhere in the body due to the importance of the face in social, feeding, and exploratory behaviors. Nociceptive information from the orofacial region is carried to the brain via the trigeminal nerve (CNV) via the trigeminal brainstem sensory nuclear complex (VBSNC). Pre-clinical evidence revealed a monosynaptic circuit from CNV to the lateral parabrachial nucleus (latPB), which underlies the greater unpleasantness elicited by orofacial pain. The latPB further projects to the central amygdala (CeA), which contributes to the affective component of pain in rodents. However, this circuit has yet to be delineated in humans. Here, we aimed to resolve this circuit using 7T diffusion-weighted imaging from the Human Connectome Project (HCP). We performed probabilistic tractography in 80 participants to resolve the CNV-latPB-CeA circuit. The basolateral amygdala (BLAT) was used as a negative control, given that we did not anticipate CNV-latPB-BLAT connectivity. Connectivity strengths were compared using a repeated-measures ANOVA with factors hemisphere (left; right), and target (CeA; BLAT), with sex included in the model for both pilot and validation samples. Only the target factor was significant in both samples (FPilot = 11.4804, p = 0.005; FValidation = 69.113, p < .001). Post hoc tests showed that the CeA had significantly stronger connectivity strength than the BLAT (pTukey-Pilot = 0.005; pTukey-Validation < 0.001). {square}This study delineates the human CNV-latPB-CeA circuit for the first time in vivo. This circuit may provide a neuroanatomical substrate for the affective dimensions of orofacial pain. SUMMARYThis study delineates the human trigeminal-parabrachio-amygdalar circuit in vivo. This circuit may provide a neuroanatomical substrate for the affective dimension of orofacial pain.

neuroscience↗

bioRxiv2020

Resting-State Functional Connectivity Predicts Individual Pain Ratings to a Tonic Orofacial Pain Stimulus

Pain is a subjective experience with significant individual differences. Laboratory studies investigating pain thresholds and experimental acute pain have identified structural and functional neural correlates. However, these types of pain stimuli have limited ecological validity to real-life pain experiences. Here, we use an orthodontic procedure--the insertion of an elastomeric separator between teeth--which typically induces mild to moderate pain that peaks within 2 days and lasts several days. We aimed to determine whether the baseline structure and resting-state functional connectivity (rsFC) of key regions along the trigeminal nociceptive and pain modulatory pathways correlate with subsequent peak pain ratings. Twenty-six healthy individuals underwent structural and resting-state functional (rs-fMRI) scanning prior to the placement of a separator between the first and second molars, which was kept in place for five days. Participants recorded pain ratings three times daily on a 100-mm visual analogue scale. Peak pain was not significantly correlated with diffusion metrics of the trigeminal nerve, or grey matter volume of any brain region. Peak pain did, however, positively correlate with baseline rsFC between the thalamus contralateral to the separator and bilateral insula, and negatively correlated with connectivity between the periaqueductal gray (PAG) and core nodes of the default mode network (medial prefrontal and posterior cingulate cortices). The ascending (thalamic) nociceptive and the descending (PAG) pain modulatory pathways at baseline each explained unique variation in peak pain intensity ratings. In sum, pre-interventional functional neural architecture of both systems determined the individual pain experience to a subsequent ecologically valid pain stimulus.

neuroscience↗