Cardiometabolic outcomes in Kronos Early Estrogen Prevention Study continuation: 14-year follow-up of a hormone therapy trial.

OBJECTIVE: This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS). METHODS: KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17ß-estradiol (Climara, 50 µg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years. KEEPS continuation recontacted KEEPS participants 14 years after randomization and 10 years after the completion of the 4-year clinical trial to attend in-person clinic visits. RESULTS: Participants of KEEPS continuation (n = 299 of the 727 KEEPS participants; 41%) had an average age of 67 years (range, 58-73 y). Measurements of systolic and diastolic blood pressures, waist-to-hip ratio, fasting levels of glucose, insulin, lipid profiles, and homeostasis model assessment of insulin resistance were not different among the treatment groups at either KEEPS baseline or at KEEPS continuation visits, or for change between these two visits. The frequency of self-reported diabetes ( P = 0.007) and use of diabetes medications was higher in the placebo than the oral conjugated equine estrogens ( P = 0.045) or transdermal 17ß-estradiol ( P = 0.02) groups, but these differences were not supported by the laboratory measurements of glycemia or insulin resistance. CONCLUSIONS: There was no evidence of cardiovascular and/or metabolic benefits or adverse effects associated with 4 years use of oral or transdermal forms of hormone therapy by recently menopausal women with good cardiovascular health after 10 years.

[Assessment of the efficacy and safety of alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis in Russian population]. / Otsenka effektivnosti i bezopasnosti alemtuzumaba u patsientov s vysokoaktivnym techeniem rasseyannogo skleroza v rossiiskoi populyatsii.

OBJECTIVE: To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy. MATERIAL AND METHODS: In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022. RESULTS: Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs. CONCLUSION: All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.

Shortcut barcoding and early pooling for scalable multiplex single-cell reduced-representation CpG methylation sequencing at single nucleotide resolution.

DNA methylation is essential for a wide variety of biological processes, yet the development of a highly efficient and robust technology remains a challenge for routine single-cell analysis. We developed a multiplex scalable single-cell reduced representation bisulfite sequencing (msRRBS) technology. It allows cell-specific barcoded DNA fragments of individual cells to be pooled before bisulfite conversion, free of enzymatic modification or physical capture of the DNA ends, and achieves read mapping rates of 62.5 ± 3.9%, covering 60.0 ± 1.4% of CpG islands and 71.6 ± 1.6% of promoters in K562 cells. Its reproducibility is shown in duplicates of bulk cells with close to perfect correlation (R = 0.97-0.99). At a low 1 Mb of clean reads, msRRBS provides highly consistent coverage of CpG islands and promoters, outperforming the conventional methods with orders of magnitude reduction in cost. Here, we use this method to characterize the distinct methylation patterns and cellular heterogeneity of six cell lines, plus leukemia and hepatocellular carcinoma models. Taking 4 h of hands-on time, msRRBS offers a unique, highly efficient approach for dissecting methylation heterogeneity in a variety of multicellular systems.

Integrating Single-Cell Transcriptome and Network Analysis to Characterize the Therapeutic Response of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by a unique BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) were developed to target the BCR-ABL oncoprotein, inhibiting its abnormal kinase activity. TKI treatments have significantly improved CML patient outcomes. However, the patients can develop drug resistance and relapse after therapy discontinues largely due to intratumor heterogeneity. It is critical to understand the differences in therapeutic responses among subpopulations of cells. Single-cell RNA sequencing measures the transcriptome of individual cells, allowing us to differentiate and analyze individual cell populations. Here, we integrated a single-cell RNA sequencing profile of CML stem cells and network analysis to decipher the mechanisms of distinct TKI responses. Compared to normal hematopoietic stem cells, a set of genes that were concordantly differentially expressed in various types of stem cells of CML patients was revealed. Further transcription regulatory network analysis found that most of these genes were directly controlled by one or more transcript factors and the genes have more regulators in the cells of the patients who responded to the treatment. The molecular markers including a known drug-resistance gene and novel gene signatures for treatment response were also identified. Moreover, we combined protein-protein interaction network construction with a cancer drug database and uncovered the drugs that target the marker genes directly or indirectly via the protein interactions. The gene signatures and their interacted proteins identified by this work can be used for treatment response prediction and lead to new strategies for drug resistance monitoring and prevention. Our single-cell-based findings offered novel insights into the mechanisms underlying the therapeutic response of CML.

[Dance therapy in the rehabilitation of neurological diseases]. / Tantseval'no-dvigatel'naya terapiya v reabilitatsii nevrologicheskikh zabolevanii.

A literature review of clinical trials on the effectiveness of the use of dance movement therapy in patients with neurological diseases is presented. A systematic review and meta-analysis of the effectiveness of dance movement therapy on non-motor manifestations of Parkinson's disease is presented. Dance movement therapy was found to have a significant positive effect on cognitive impairment, but no effect on depression, fatigue, and apathy. The effectiveness of dance movement therapy in post-stroke rehabilitation is shown. The data of a systematic review are presented, which found that dance movement therapy is effective not only in the rehabilitation of Parkinson's disease and stroke, but also in the rehabilitation of patients with multiple sclerosis, Huntington's disease and the consequences of spinal cord injury.

Sample-multiplexing approaches for single-cell sequencing.

Single-cell sequencing is widely used in biological and medical studies. However, its application with multiple samples is hindered by inefficient sample processing, high experimental costs, ambiguous identification of true single cells, and technical batch effects. Here, we introduce sample-multiplexing approaches for single-cell sequencing in transcriptomics, epigenomics, genomics, and multiomics. In single-cell transcriptomics, sample multiplexing uses variants of native or artificial features as sample markers, enabling sample pooling and decoding. Such features include: (1) natural genetic variation, (2) nucleotide-barcode anchoring on cellular or nuclear membranes, (3) nucleotide-barcode internalization to the cytoplasm or nucleus, (4) vector-based barcode expression in cells, and (5) nucleotide-barcode incorporation during library construction. Other single-cell omics methods are based on similar concepts, particularly single-cell combinatorial indexing. These methods overcome current challenges, while enabling super-loading of single cells. Finally, selection guidelines are presented that can accelerate technological application.

Energetics, but not development, is impacted in coral embryos exposed to ocean acidification.

In light of the chronic stress and mass mortality reef-building corals face under climate change, it is critical to understand the processes driving reef persistence and replenishment, including coral reproduction and development. Here, we quantified gene expression and sensitivity to ocean acidification across a set of developmental stages in the rice coral, Montipora capitata. Embryos and swimming larvae were exposed to pH treatments of 7.8 (ambient), 7.6 (low) and 7.3 (extreme low) from fertilization to 9 days post-fertilization. Embryo and larval volume, and stage-specific gene expression were compared between treatments to determine the effects of acidified seawater on early development. Although there was no measurable size differentiation between pH treatments at the fertilized egg and prawn chip (9 h post-fertilization) stages, early gastrulae and larvae raised in reduced pH treatments were significantly smaller than those raised in ambient seawater, suggesting an energetic cost to developing under low pH. However, no differentially expressed genes were found until the swimming larval stage. Notably, gene expression patterns of larvae developing at pH 7.8 and pH 7.3 were more similar than those of larvae developing at pH 7.6. Larvae from pH 7.6 showed upregulation of genes involved in cell division, regulation of transcription, lipid metabolism and response to oxidative stress in comparison to the other two treatments. Although low pH appears to increase energetic demands and trigger oxidative stress in larvae, the developmental process is robust to this at a molecular level, with the swimming larval stage reached in all pH treatments.

Pilot study of women's perspectives when abnormal uterine bleeding occurs during perimenopause.

OBJECTIVE: We gained insights into women's experiences and knowledge about the occurrence of vaginal bleeding during perimenopause requiring evaluation. METHODS: Qualitative inquiry was chosen to explore topics in greater depth to understand individuals' experiences. Interviews with individuals were chosen due to the sensitive nature of gynecologic symptoms and management. Interviews were completed following gynecologic care to explore individuals' experiences with the evaluation and management of vaginal bleeding during perimenopause. RESULTS: Twelve individuals were interviewed between December 2019 and March 2020. Patient uncertainty about the medical significance of developing vaginal bleeding during perimenopause was associated with self-appraisal and gathering information from multiple sources. This experience of seeking evaluation and treatment resulted in varying degrees of trust concerning information received within or outside the clinic. Regarding new technologies that could replace the current invasive tests performed for diagnosis (i.e. ultrasound, hysteroscopy and biopsy), most women preferred the smartphone app and tampon home collection option. CONCLUSIONS: The experience of irregular or heavy vaginal bleeding during perimenopause is fraught with ambiguity, feelings of uncertainty about how to make sense of symptoms and inevitably begins with a period of self-appraisal.

[Dynamics of psychovegetative syndrome in patients during the period of rehabilitation after coronary bypass]. / Dinamika psikhovegetativnogo sindroma u patsientov v period reabilitatsii posle koronarnogo shuntirovaniya.

OBJECTIVE: The study was to investigate the role of moderate and severe anxiety in development of psychovegetative syndrome after coronary artery bypass graft (CABG), to describe the nature and direction of resulting autonomic dysfunction and to study possibilities of anti-ancient therapy. MATERIAL AND METHODS: We studied 33 patients (19 - in the main group, 14 - in the comparison group) on average 13 days after CABG and in dynamics in the process of early postoperative rehabilitation. A point assessment of the psychological and autonomic spheres, and sleep quality was made. Indicators of vegetative tone and vegetative regulation were studied, in particular, temporal and spectral indicators of heart rate variability. In addition to basic therapy for ischemic heart disease (IHD), the patients in main group were received therapy with alimemazine. RESULTS: In most cases, after CABG, moderate situational and personal anxiety and sleep disturbances were recorded in combination with autonomic dysregulation with a predominance of sympathetic influences from the autonomic nervous system (ANS). Adding to the basic therapy of IHD among patients of the main group of the drug with a mild anti-anxiety effect, allowed for 2 weeks to significantly reduce the level of anxiety and correct the existing autonomic disorders. CONCLUSION: This study found that patients with an increased level of anxiety after CABG are characterized by the formation of a psychovegetative syndrome with a predominance of sympathetic activity. The using anti-anxiety drugs can reduce the severity of anxiety and autonomic dysfunction, which can probably become a factor contributing to the successful rehabilitation of patients after CABG in the early and late postoperative periods, and the prevention of progression of IHD.

[Epidemiology of neuromyelitis optica spectrum disorder]. / Epidemiologiya zabolevanii spektra optikoneiromielita.

Neuromyelitis optica spectrum disorder (NMOSD) is a group of rare and mostly severe autoimmune demyelinating central nervous system disorders which prevalence is 0.7-1 per 100.000 population and incidence is 0.037-0.73 per 100.000 person-years. NMOSD may present as a combination of uni- or bilateral optic neuritis, transverse myelitis or lesions of brain stem and other brain regions. The symptoms are mostly relapsing (up to 97.5%) and progressive. Occurrence of relapses is associated with seropositivity for aquaporin-4 (up to 80% of NMOSD patients) and bears a less favorable prognosis (mortality up to 32%). Women seropositive for aquaporin 4 constitute 90% of NMOSD patients. Compared to other demyelinating disorders, NMOSD is characterized by late onset (mean age is about 39 years) and association with other autoimmune disorders, including systemic lupus erythematosus, myasthenia gravis and Sjogren's syndrome. A genetic predisposition was found among Blacks and Asians, with HLA-DRB1*03:01 gene associated with higher risk of NMOSD in Asians. The course of the disease tends to be more severe in Blacks. There are clusters of an increased incidence of NMOSD in the Carribeans and in the Far East. Continued increase of prevalence and incidence of NMOSD worldwide compels continued epidemiological research in order to provide early diagnosis and treatment for this disorder.

Factors associated with Noninvasive ventilation compliance in patients with ALS/MND.

Background: Although noninvasive ventilation (NIV) improves survival and quality of life (QOL) in ALS, use of NIV is suboptimal. Objective: To determine compliance with "early" NIV initiation, requisite for the feasibility of a large study of early NIV initiation, and examine factors impacting compliance. Methods: Seventy-three ALS participants with forced vital capacities (FVC) >50% were enrolled. Participants with FVC over 80% (Group 1) were initiated on NIV early (FVC between 80 and 85%). Participants with FVC between 50 and 80% (Group 2) started NIV at FVC between 50 and 55%. Symptom surveys, QOL scores, and NIV compliance (machine download documenting use ≥4 hours/night >60% of time) were collected following NIV initiation. Results: 53.6% of Group 1 and 50% of Group 2 were compliant 28 days following NIV initiation, with increased compliance over time. Participants who were unmarried, had lower income, lower educational attainment, or limited caregiver availability were less likely to be compliant. Bothersome symptoms in non-compliant participants included facial air pressure, frequent arousals with difficulty returning to sleep, and claustrophobia. Both compliant and noncompliant participants felt improved QOL with NIV; improvement was significantly greater in compliant participants. Conclusions: These data suggest ALS patients can comply with NIV early in their disease, and potentially benefit as evidenced by improved QOL scores, supporting both feasibility and need for a study comparing early versus late NIV initiation. Moreover, modifiable symptoms were identified that could be optimized to improve compliance. Further studies are needed to determine the impact of "early" intervention on survival and QOL.

An Engineered IL15 Cytokine Mutein Fused to an Anti-PD1 Improves Intratumoral T-cell Function and Antitumor Immunity.

The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused by excessive and systemic immune activation. Here, we set out to address these challenges by engineering a fusion protein of a single, potency-reduced, IL15 mutein and a PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed to deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation to PD1+ tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells. Treatment of tumor-bearing mice with a mouse cross-reactive fusion, anti-mPD1-IL15m, demonstrated potent antitumor efficacy without exacerbating body weight loss in B16 and MC38 syngeneic tumor models. Moreover, anti-mPD1-IL15m was more efficacious than an IL15 superagonist, an anti-mPD-1, or the combination thereof in the B16 melanoma model. Mechanistically, anti-PD1-IL15m preferentially targeted CD8+ TILs and single-cell RNA-sequencing analyses revealed that anti-mPD1-IL15m treatment induced the expansion of an exhausted CD8+ TIL cluster with high proliferative capacity and effector-like signatures. Antitumor efficacy of anti-mPD1-IL15m was dependent on CD8+ T cells, as depletion of CD8+ cells resulted in the loss of antitumor activity, whereas depletion of NK cells had little impact on efficacy. The impact of anti-hPD1-IL15m on primary human TILs from patients with cancer was also evaluated. Anti-hPD1-IL15m robustly enhanced the proliferation, activation, and cytotoxicity of CD8+ and CD4+ TILs from human primary cancers in vitro, whereas tumor-derived regulatory T cells were largely unaffected. Taken together, our findings showed that anti-PD1-IL15m exhibits a high translational promise with improved efficacy and safety of IL15 for cancer immunotherapy via targeting PD1+ TILs.See related Spotlight by Felices and Miller, p. 1110.

Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture.

The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type (WT) and Tet2-/- fetal livers, by multiplexed error robust fluorescence in situ hybridization. We find that specific pairs of fetal liver cell types are preferentially positioned next to each other. Ligand-receptor signaling molecule pairs such as Kitl and Kit are enriched in neighboring cell types. The majority of HSCs are in direct contact with endothelial cells (ECs) in both WT and Tet2-/- fetal livers. Loss of Tet2 increases the number of HSCs, and upregulates Wnt and Notch signaling genes in the HSC niche. Two subtypes of ECs, arterial ECs and sinusoidal ECs, and other cell types contribute distinct signaling molecules to the HSC niche. Collectively, this study provides a comprehensive picture and bioinformatic foundation for HSC spatial regulation in fetal liver.

Colorectal Cancer Stem Cell States Uncovered by Simultaneous Single-Cell Analysis of Transcriptome and Telomeres.

Cancer stem cells (CSCs) presumably contribute to tumor progression and drug resistance, yet their definitive features have remained elusive. Here, simultaneous measurement of telomere length and transcriptome in the same cells enables systematic assessment of CSCs in primary colorectal cancer (CRC). The in-depth transcriptome profiled by SMART-seq2 is independently validated by high-throughput scRNA-seq using 10 × Genomics. It is found that rare CSCs exist in dormant state and display plasticity toward cancer epithelial cells (EPCs) that essentially are presumptive tumor-initiating cells (TICs), while both retaining the prominent signaling pathways including WNT, TGF-ß, and HIPPO/YAP. Moreover, CSCs exhibit chromosome copy number variation (CNV) pattern resembling cancer EPCs but distinct from normal stem cells, suggesting the phylogenetic relationship between CSCs and cancer EPCs. Notably, CSCs maintain shorter telomeres and possess minimal telomerase activity consistent with their nonproliferative nature, unlike cancer EPCs. Additionally, the specific signature of CSCs particularly NOTUM, SMOC2, BAMBI, PHLDA1, and TNFRSF19 correlates with the prognosis of CRC. These findings characterize the heterogeneity of CSCs and their linkage to cancer EPCs/TICs, some of which are conventionally regarded as CSCs.

Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody.

Development of antagonistic mAbs that specifically target the immune checkpoint receptor, programmed cell death protein-1 (PD-1), is of great interest for cancer immunotherapy. Here, we report the biophysical characteristics and nonclinical antagonistic activities of sasanlimab (PF-06801591), a humanized anti-PD-1 antibody of IgG4 isotype. We show that sasanlimab binds selectively and with similar high potency to human and cynomolgus monkey PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, with no detectable Fc-dependent effector function. The binding of sasanlimab to human and cynomolgus PD-1 is associated with the formation of a stable complex, which is likely to be the main driver of this high-affinity interaction. In vitro, sasanlimab significantly augmented T-cell proliferation and cytokine production in mixed lymphocyte reaction and superantigen stimulation assays. In vivo, sasanlimab accelerated the incidence of GvHD by enhancing T-cell proliferation and cytokine secretion in a xenogeneic model of acute GvHD and halted the growth of MC-38 colon adenocarcinoma tumors in human PD-1 knock-in mice. Pharmacokinetic and toxicokinetic findings from cynomolgus monkey showed that sasanlimab was active and well-tolerated. Taken together, the data presented here support the clinical development of sasanlimab for the treatment of patients with advanced cancers as a single agent or in combination with other immunotherapies.

Unmasked Testicular Seminoma During Use of Hormonal Transgender Woman Therapy: A Hidden hCG-Secreting Tumor.

Management of gender-affirming hormone therapy (HT) in transgender women includes surveillance of testosterone (T) levels. Failure of T to suppress, despite adherence to therapy, warrants additional investigations for unexpected sources of T or factors stimulating T secretion. Possible causes include T or gonadotropin production by an occult neoplasm. Testicular cancer is the most common malignancy affecting biological men aged between 15 and 35 years. Patients may be asymptomatic until tumor burden is high and/or metastatic. Hormone-producing tumors have rarely been reported in treated transgender women. Routine screening tests are recommended in a gender-incongruent person as per the 2017 Endocrine Society guidelines with measurement of T levels every 3 months initially to reach a goal of less than 50 ng/dL. Expectations should be discussed in detail with the transgender person since anticipated physical changes may not be notable for 6 to 18 months. We herein describe a case of a transgender woman who underwent standard HT including gonadotropin suppression with a gonadotropin-releasing hormone agonist, whose total T level failed to suppress. Testing revealed an elevated serum level of the beta subunit of human chorionic gonadotropin (ß-hCG), diagnostic of an hCG-secreting testicular seminoma, as the underlying cause of unexpected T production. This case illustrates how easily a testicular cancer can remain unnoticed because it can be asymptomatic and the necessity to be alert to, and act on, anomalous laboratory results during treatment of a transgender person.

Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons.

Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disorders without effective therapies. Here, we used 2D and 3D human brain cultures to investigate MeCP2 function. We found that MeCP2 mutations cause severe abnormalities in human interneurons (INs). Surprisingly, treatment with a BET inhibitor, JQ1, rescued the molecular and functional phenotypes of MeCP2 mutant INs. We uncovered that abnormal increases in chromatin binding of BRD4 and enhancer-promoter interactions underlie the abnormal transcription in MeCP2 mutant INs, which were recovered to normal levels by JQ1. We revealed cell-type-specific transcriptome impairment in MeCP2 mutant region-specific human brain organoids that were rescued by JQ1. Finally, JQ1 ameliorated RTT-like phenotypes in mice. These data demonstrate that BRD4 dysregulation is a critical driver for RTT etiology and suggest that targeting BRD4 could be a potential therapeutic opportunity for RTT.

Hippocampal Sclerosis Detection with NeuroQuant Compared with Neuroradiologists.

BACKGROUND AND PURPOSE: NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis. MATERIALS AND METHODS: We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology (n = 61) or not having hippocampal sclerosis on pathology (n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem. RESULTS: NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%). CONCLUSIONS: Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected.

Sex and psychiatric comorbidity correlates of the premonitory urge for tic scale in youth with persistent tic disorders.

The premonitory urge for tics scale (PUTS) is a common self-report measure of premonitory sensations preceding tics. The present study aimed to examine the internal consistency and concurrent validity of the PUTS by sex and psychiatric comorbidity status; and explored interactions between sex and psychiatric comorbidity in predicting premonitory urge and tic symptom severity. Seventy-four youth and young adults with persistent tic disorders completed the PUTS, while their parents completed the parent tic questionnaire (PTQ) and a demographic measure. Independent samples t-tests revealed no significant sex differences in PUTS items or total score. The PUTS total score also did not significantly differ between participants with and without attention-deficit hyperactivity disorder (ADHD) and/or obsessive-compulsive disorder (OCD) comorbidity. Internal consistency did not significantly differ between females (α = 0.85) and males (α = 0.75), and those with comorbid ADHD and/or OCD (α = 0.83) relative to those without (α = 0.69). With respect to concurrent validity, the PUTS total was significantly correlated with PTQ tic frequency, intensity, number, and severity for males but not for females. Among those with ADHD and/or OCD, the PUTS total score was correlated significantly and strongly with tic number and moderately with tic intensity. Interactions between sex and psychiatric comorbidity performed using 2 × 2 analysis of variance did not significantly predict the PUTS total or PTQ subscale scores. Findings suggest sex and comorbidity status may influence premonitory urge expression. Results have implications for understanding and measurement of the premonitory urge.

An Overview of Advances in Cell-Based Cancer Immunotherapies Based on the Multiple Immune-Cancer Cell Interactions.

Tumors have a complex ecosystem in which behavior and fate are determined by the interaction of diverse cancerous and noncancerous cells at local and systemic levels. A number of studies indicate that various immune cells participate in tumor development (Fig. 1). In this review, we will discuss interactions among T lymphocytes (T cells), B cells, natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), neutrophils, and myeloid-derived suppressor cells (MDSCs). In addition, we will touch upon attempts to either use or block subsets of immune cells to target cancer.