UNASSIGNED: A significant proportion of patients with chronic pain exhibit mixed pain and thus do not display symptoms exclusively associated with either nociceptive or neuropathic pain syndromes. We aimed to explore whether Fast-Acting Sub-Perception Therapy, FAST - a new Spinal Cord Stimulation (SCS)-based approach capable of inducing a rapid-onset of analgesia using electrical neurostimulation applied below patient-perception threshold - could potentially be useful as a treatment for chronic mixed pain.
UNASSIGNED: Fourteen consecutively-enrolled patients diagnosed with chronic mixed pain and implanted with an SCS device were enrolled in this single-center case-series. All patients completed a validated, self-administered painDETECT questionnaire prior to SCS-device implantation (baseline). The painDETECT questionnaire was used to characterize each patient\'s chronic pain as likely neuropathic only, uncertain (but potential for presence of a non-neuropathic component), or likely presence of a non-neuropathic component. Overall pain scores (Numeric Rating Scale, NRS), Oswestry Disability Index (ODI) and Quality-of-life (EQ-5D-5L) were collected (per standard-of-care) at baseline, 3-months, and 6-months post-implantation.
UNASSIGNED: The average age of those assessed in this study was 64.7 ​± ​11.5 (SD) years and 43% (6/14) were female. Fifty-percent (7/14) of patients were classified with non-neuropathic pain (painDETECT), while the remainder exhibited chronic pain that could not be characterized as either neuropathic or non-neuropathic (uncertain). Mean overall pain (NRS) among all patients was 8.3 ​± ​0.3 (SE) at baseline. At 6-months post-implant, a mean 6.9-points NRS score reduction was observed (1.4 ​± ​0.3 (SE); p ​< ​0.0001). Notable improvements in disability (ODI) and Quality of Life (EQ-5D-5L) were also observed at 6-month follow-up.
UNASSIGNED: The data from this observational case-series indicate that FAST-SCS can improve outcomes in patients reporting complex symptoms of mixed pain with a likely non-neuropathic component. These results suggest that neurostimulation modalities such as FAST may be a suitable treatment approach for non-neuropathic pain indications.

UNASSIGNED: Low back pain (LBP) is a highly prevalent, disabling condition affecting millions of people. Patients with an identifiable anatomic pain generator and resulting neuropathic lower extremity symptoms often undergo spine surgery, but many patients lack identifiable and/or surgically corrective pathology. Nonoperative treatment options often fail to provide sustained relief. Spinal cord stimulation (SCS) is sometimes used to treat these patients, but the lack of level 1 evidence limits its widespread use and insurance coverage. The DISTINCT RCT study evaluates the efficacy of passive recharge burst SCS compared to conventional medical treatment (CMM) in alleviating chronic, refractory axial low back pain.
UNASSIGNED: This prospective, multicenter, randomized, study with an optional 6-month crossover involved patients who were not candidates for lumbar spine surgery. The primary and secondary endpoints evaluated improvements in low back pain intensity (NRS), back pain-related disability (ODI), pain catastrophizing (PCS), and healthcare utilization. Patients were randomized to SCS therapy or CMM at 30 US study sites.
UNASSIGNED: The SCS arm reported an 85.3% NRS responder rate (≥ 50% reduction) compared to 6.2% (5/81) in the CMM arm. After the 6M primary endpoint, SCS patients elected to remain on assigned therapy and 66.2% (49/74) of CMM patients chose to trial SCS (crossover). At the 12M follow-up, SCS and crossover patients reported 78.6% and 71.4% NRS responder rates. Secondary outcomes indicated significant improvements in ODI, PCS, and reduced healthcare utilization. Six serious adverse events were reported and resolved without sequelae.
UNASSIGNED: DISTINCT chronic low back pain patients with no indication for corrective surgery experienced a significant and sustained response to burst SCS therapy for up to 12 months. CMM patients who crossed over to the SCS arm reported profound improvements after 6 months. This data advocates for a timely consideration of SCS therapy in patients unresponsive to conservative therapy.

UNASSIGNED: Visceral pain, characterized by pain that is diffuse and challenging to localize, occurs frequently and is difficult to treat. In cases where the pain becomes intractable despite optimal medical management, it can affect patients\' Quality of Life (QoL). Spinal Cord Stimulation (SCS) has emerged as a potential solution for intractable visceral pain.
UNASSIGNED: In this narrative review, we collected all evidence regarding the efficacy of SCS for visceral pain across various underlying conditions.
UNASSIGNED: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science in which articles published from October 1st, 1963 up to March 7th, 2023 were identified.
UNASSIGNED: Seventy articles were included in this review of which most were retrospective cohort studies, case series and case reports. The studies, often with a small number of participants, reported on SCS for chronic pancreatitis, anorectal pain and bowel disorders, gynaecological diagnoses, visceral pelvic pain, urological disorders and finally general visceral pain. They found positive effects on pain and/or symptom relief, opioid consumption, anxiety and depression and QoL. Complications occurred frequently but were often minor and reversible.
UNASSIGNED: Better screening and selection criteria need to be established to optimally evaluate eligible patients who might benefit from SCS. A positive outcome of a sympathetic nerve block appears to be a potential indicator of SCS effectiveness. Additionally, women receiving SCS for endometriosis had a better outcome compared to other indications. Finally, SCS could also relief functional symptoms such as voiding problems and gastroparesis. Complications could often be resolved with revision surgery. Since SCS is expensive and not always covered by standard health insurance, the incorporation of cost-analyses is recommended. In order to establish a comprehensive treatment plan, including selection criteria for SCS, rigorous prospective, possibly randomized and controlled studies that are diagnosis-oriented, with substantial follow-up and adequate sample sizes, are needed.

Development is regulated by various factors, including protein methylation status. While PRMT5 is well known for its roles in oncogenesis by mediating symmetric di-methylation of arginine, its role in normal development remains elusive. Using Myod1Cre to drive Prmt5 knockout in embryonic myoblasts (Prmt5MKO), we dissected the role of PRMT5 in myogenesis. The Prmt5MKO mice are born normally but exhibit progressive muscle atrophy and premature death. Prmt5MKO inhibits proliferation and promotes premature differentiation of embryonic myoblasts, reducing the number and regenerative function of satellite cells in postnatal mice. Mechanistically, PRMT5 methylates and destabilizes FoxO1. Prmt5MKO increases the total FoxO1 level and promotes its cytoplasmic accumulation, leading to activation of autophagy and depletion of lipid droplets (LDs). Systemic inhibition of autophagy in Prmt5MKO mice restores LDs in myoblasts and moderately improves muscle regeneration. Together, PRMT5 is essential for muscle development and regeneration at least partially through mediating FoxO1 methylation and LD turnover.

In higher eukaryotes, distance enhancer-promoter interactions are organized by topologically associated domains, tethering elements, and chromatin insulators/boundaries. While insulators/boundaries play a central role in chromosome organization, the mechanisms regulating their functions are largely unknown. In the studies reported here, we have taken advantage of the well-characterized Drosophila bithorax complex (BX-C) to study one potential mechanism for controlling boundary function. The regulatory domains of BX-C are flanked by boundaries, which block crosstalk with their neighboring domains and also support long-distance interactions between the regulatory domains and their target gene. As many lncRNAs have been found in BX-C, we asked whether readthrough transcription (RT) can impact boundary function. For this purpose, we took advantage of two BX-C boundary replacement platforms, Fab-7attP50 and F2attP, in which the Fab-7 and Fub boundaries, respectively, are deleted and replaced with an attP site. We introduced boundary elements, promoters, and polyadenylation signals arranged in different combinations and then assayed for boundary function. Our results show that RT can interfere with boundary activity. Since lncRNAs represent a significant fraction of Pol II transcripts in multicellular eukaryotes, it is therefore possible that RT may be a widely used mechanism to alter boundary function and regulation of gene expression.

UNASSIGNED: To revise Sport Courage Scale (SCS) suitable for Chinese athletes.
UNASSIGNED: Six hundred and eighty three athletes were selected for verification factor analysis, correlation analysis, reliability analysis, and independent sample t-test using the method of random sampling of the entire group.
UNASSIGNED: Confirmatory factor analysis model showed that model 1 (25 items) failed to fit the data; while model 2 (20 items) was finally accepted with its five-factor model. The factor structure consists of 5 dimensions (χ2/df = 2.262;CFI = 0.969;TLI = 0.963; RMSEA = 0.043; SRMR = 0.044). Cronbach\'s α of the final version of SCS was 0.845, and the corrected correlation coefficient between the items and the total score of the scale was between 0.352 and 0.788.
UNASSIGNED: Revised SCS has good reliability and validity and can be used as a measurement tool for the sports courage of athletes in China.

Bovine mastitis, the inflammation of the mammary gland, is a contagious disease characterized by chemical and physical changes in milk and pathological changes in udder tissues. Depressed immunity and higher expression of inflammatory cytokines with an elevated milk somatic cell count can be observed during mastitis in dairy cattle. The use of somatic cell count (SCC) and somatic cell score (SCS) as correlated traits in the indirect selection of animals against mastitis resistance is in progress globally. Traditional breeding for mastitis resistance seems difficult because of the low heritability (0.10-0.16) of SCC/SCS and clinical mastitis. Thus, genetic-marker-selective breeding to improve host genetics has attracted considerable attention worldwide. Moreover, genomic selection has been found to be an effective and fast method of screening for dairy cattle that are genetically resistant and susceptible to mastitis at a very early age. The current review discusses and summarizes the candidate gene approach using polymorphisms in immune- and inflammation-linked genes (CD4, CD14, CD46, TRAPPC9, JAK2, Tf, Lf, TLRs, CXCL8, CXCR1, CXCR2, C4A, C5, MASP2, MBL1, MBL2, LBP, NCF1, NCF4, MASP2, A2M, and CLU, etc.) and their related signaling pathways (Staphylococcus aureus infection signaling, Toll-like receptor signaling, NF-kappa B signaling pathway, Cytokine-cytokine receptor, and Complement and coagulation cascades, etc.) associated with mastitis resistance and susceptibility phenotypic traits (IL-6, interferon-gamma (IFN-γ), IL17, IL8, SCS, and SCC) in dairy cattle.

Mount Xianbei is one of the largest shallow seamounts located in the middle of the South China Sea (SCS), which might play a role in shaping the biodiversity of surrounding continental coastal waters, particularly the diversity of phytoplankton species causing frequent harmful algal blooms (HABs) in northern SCS. However, the diversity, composition, and distribution of phytoplankton species in the seamount regions of Xianbei remain largely unexplored. In this study, samples around and outside the seamount regions were collected during a late summer cruise of 2021 to test whether seamounts play a role in HAB species propagation. In total, we identified 19 HAB species across all samples using the ASV-based DNA metabarcoding approach, 6 of which had not been reported previously in the SCS, suggesting a diverse HAB species in the SCS. Specifically, 16 HAB species were found in the seamount region of Xianbei, and 5 of them were also found in the coastal waters, indicating a close connection between seamount and coastal waters. This study was the first attempt to explore HAB species\' spatial diversity and vertical distribution in the seamount region of Xianbei at single-nucleotide resolution, which provides a novel explanation for the coastal HAB occurrence in the northern SCS. IMPORTANCE There are a number of seamounts under the water of the South China Sea (SCS). The seamounts might play a role in shaping the biodiversity of surrounding continental coastal waters. However, there is no direct evidence revealing the relationship of the biodiversity of phytoplankton between seamounts and coastal waters in the SCS, especially those species having the potential to form harmful algal blooms (HABs). Some HAB species might proliferate in certain geographic locations, while others may be broadly distributed across oceanic provinces. In this study, we provided a detailed analysis of phytoplankton composition and molecular detection of HAB species from seamount to coastal waters in the SCS, which suggested a strong interaction in the HAB species between the two areas. This finding provides new insights into the diversity and distribution of HABs in seamounts and their role in shaping the composition and the occurrence of HABs in coastal water.

UNASSIGNED: Chronic pain is a common clinical condition and is frequently treated with a variety of medications, but pharmacotherapy is oftentimes not the optimal long-term treatment option. Safe and effective long-term pain relief for trunk and limb pain is available using high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS), which is delivered using a rechargeable implantable pulse generator (IPG). Although rechargeable devices have been shown to reduce patient risk and overall cost by eliminating the need for periodic surgeries to replace depleted non-rechargeable IPGs, there is little published evidence that rechargeable technology is practical and convenient for patients, especially in the context of 10 kHz SCS.
UNASSIGNED: This analysis of real-world patients implanted with 10 kHz SCS devices was undertaken using patient data from an industry-maintained database to investigate whether there was a substantial burden associated with rechargeable SCS and the degree of patient satisfaction or dissatisfaction with 10 kHz SCS.
UNASSIGNED: This study included 10,391 men and women who were implanted with 10 kHz SCS devices to treat chronic pain of the trunk and/or limbs. They received stimulation for a median of 361 days (180-1550 days), and 65.48% had previous spine surgery. In this patient sample, most patients were satisfied with the efficacy of 10 kHz SCS, including 77% who would repeat the procedure and 71% who would recommend it to other patients with similar pain. In regards to IPG recharging, 70% were satisfied or very satisfied and 19% were neutral, and a majority of patients recharged their device daily for 30 to 60 minutes.
UNASSIGNED: These results indicate most patients do not find IPG recharging inconvenient or burdensome. In addition, IPG recharging is not a barrier to the majority of patients benefitting from 10 kHz SCS for long-term pain relief.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and is mainly treated with chemotherapy-based combination therapy. In recent years, with the increasing development of global precision medicine, single-cell sequencing (SCS) has become one of the most promising technologies in the field of biotechnology. Moreover, the related application of this technology in TNBC has been applied and developed. By using SCS to study the heterogeneity of TNBC tumor cells, metastasis, drug resistance mechanisms, mutations, and cloning; it can further guide clinical chemotherapy, targeted therapy, and immunotherapy. To further reflect the importance of SCS in TNBC, this paper elaborated on and summarized the research and application progress of SCS in TNBC.