Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia.

Background: Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach.

Trauma-Based Sexually Dimorphic Changes in the Connectome and Its Association with Central Sensitization Syndromes-A Systematic Review.

Background/objectives: Chronic pain syndromes pose a significant global health challenge to patients and physicians with a complex relationship of biological and psychosocial factors that are only partly understood. Emerging research suggests an association between prenatal and childhood adversity and the development of somatic syndromes, particularly in females. This study aims to explore the relationship between sexual dimorphic epigenetic changes in the connectome and prenatal and early life adversity (ELA).

A Rare Intracortical Schwannoma of the Distal Tibia: A Case Report.

Case: A 28-year-old man presented for a painful lower extremity mass. Imaging revealed a nonspecific, poorly defined lucent lesion in the left distal tibial cortex with scalloping. The diagnosis of intracortical schwannoma was made after open biopsy revealed positive S-100 immunohistochemical staining and characteristic spindled cells.

Proteome-wide copy-number estimation from transcriptomics.

Protein copy numbers constrain systems-level properties of regulatory networks, but proportional proteomic data remain scarce compared to RNA-seq. We related mRNA to protein statistically using best-available data from quantitative proteomics and transcriptomics for 4366 genes in 369 cell lines. The approach starts with a protein's median copy number and hierarchically appends mRNA-protein and mRNA-mRNA dependencies to define an optimal gene-specific model linking mRNAs to protein.

Identifying targetable metabolic dependencies across colorectal cancer progression.

Colorectal cancer (CRC) is a multi-stage process initiated through the formation of a benign adenoma, progressing to an invasive carcinoma and finally metastatic spread. Tumour cells must adapt their metabolism to support the energetic and biosynthetic demands associated with disease progression. As such, targeting cancer cell metabolism is a promising therapeutic avenue in CRC.

Cognitive predictors of response to interpersonal and social rhythm therapy in mood disorders.

Background: There has been increasing interest in examining the potential moderating effects that cognitive functioning has on treatment outcome in bipolar disorder (BD) and major depressive disorder (MDD). Therefore, the aim of this exploratory study was to examine the relationship between baseline cognitive function and treatment outcome in individuals with mood disorders who completed 12 months of interpersonal and social rhythm therapy (IPSRT), and were randomised to receive adjunctive cognitive remediation (CR) or no additional intervention.

Methods: Fifty-eight patients with mood disorders (BD, n = 36, MDD, n = 22), who were randomised to IPSRT-CR or IPSRT, underwent cognitive testing at baseline and completed follow-up mood measures after 12 months.

Effects of Cervical Spinal Manipulation on Saccadic Eye Movements.

Quantifying saccadic eye movements can assist in identifying dysfunctional brain networks in both healthy and diseased people. Infrared Oculography is a simple and non-invasive approach to capturing and quantifying saccades, providing information that might aid in diagnosis and outcome assessments. The effect of spinal manipulation on quantified saccadic performance parameters has not been fully studied despite known post-manipulative effects on the brain and brainstem regions controlling them.

A polygenic risk score added to a QRISK®2 cardiovascular disease risk calculator demonstrated robust clinical acceptance and clinical utility in the primary care setting.

Aims: The aim of the study was to assess the real-world feasibility, acceptability, and impact of an integrated risk tool for cardiovascular disease (CVD IRT, combining the standard QRISK®2 risk algorithm with a polygenic risk score), implemented within routine primary practice in the UK National Health Service.

Methods And Results: The Healthcare Evaluation of Absolute Risk Testing Study (NCT05294419) evaluated participants undergoing primary care health checks. Both QRISK2 and CVD IRT scores were returned to the healthcare providers (HCPs), who then communicated the results to participants.

Phosphodiesterase 4 activity uniquely regulates ciliary cAMP-dependent 3T3-L1 adipogenesis.

Recent evidence indicates that the presence of a primary cilium (PC), and of selective cAMP signaling within this smallest of organelles, promotes adipogenic differentiation of 3T3-L1 preadipocytes incubated in media supplemented with either a natural (docosahexaenoic acid, DHA), or a synthetic (TUG-891), free fatty acid receptor 4 (FFAR4) agonist. Indeed, in this earlier work, activation of ciliary FFAR4 in 3T3-L1 cells was correlated with selective increases in PC cAMP and adipogenesis in these cells. However, this study was silent on the role of local PC cAMP phosphodiesterases (PDEs)-mediated events in regulating these adipogenic responses and on the identity of cAMP PDEs that could regulate the "pool" of ciliary cAMP accessed by FFAR4 agonists.

Exploring disease-causing traits for drug repurposing in critically ill COVID-19 patients: A causal inference approach.

Despite recent development of vaccines to prevent SARS-CoV-2 infection, treatment of critically ill COVID-19 patients remains an important goal. In principle, genome-wide association studies (GWASs) provide a shortcut to the clinical evidence needed to repurpose existing drugs; however, genes identified frequently lack a causal disease link. We report an alternative method for finding drug repurposing targets, focusing on disease-causing traits beyond immediate disease genetics.

Quantifying cancer cell plasticity with gene regulatory networks and single-cell dynamics.

Phenotypic plasticity of cancer cells can lead to complex cell state dynamics during tumor progression and acquired resistance. Highly plastic stem-like states may be inherently drug-resistant. Moreover, cell state dynamics in response to therapy allow a tumor to evade treatment.

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.

Background: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established.

Methods: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven Braf/Pten/Cxcr2 and NRas/INK4a/Cxcr2 melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in Braf/Pten and NRas/INK4a mice and in melanoma cell lines.

Exercise improves depression through positive modulation of brain-derived neurotrophic factor (BDNF). A review based on 100 manuscripts over 20 years.

The aim of this review was to explore the relevant neurobiology and the association between peripheral levels of brain-derived neurotrophic factor (BDNF) and acute and short to long-term exercise regimes, as well as its relation to depression and antidepressant treatment. A 20-year literature search was conducted. The screening process resulted in 100 manuscripts.

Involvement of Epithelial-Mesenchymal Transition Genes in Small Cell Lung Cancer Phenotypic Plasticity.

Small cell lung cancer (SCLC) is an aggressive cancer recalcitrant to treatment, arising predominantly from epithelial pulmonary neuroendocrine (NE) cells. Intratumor heterogeneity plays critical roles in SCLC disease progression, metastasis, and treatment resistance. At least five transcriptional SCLC NE and non-NE cell subtypes were recently defined by gene expression signatures.

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial.

Background: There is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial.

Methods: A decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUCT trial to estimate relative cost-effectiveness of two competing drugs from the United Kingdom (UK) National Health Services (NHS) perspective.