Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice.

Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic medial preoptic area (MPOA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the MPOA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our MPOA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

Cerebral Vascular Toxicity after Developmental Exposure to Arsenic (As) and Lead (Pb) Mixtures.

Arsenic (As) and lead (Pb) are environmental pollutants found in common sites linked to similar adverse health effects. This study determined driving factors of neurotoxicity on the developing cerebral vasculature with As and Pb mixture exposures. Cerebral vascular toxicity was evaluated at mixture concentrations of As and Pb representing human exposures levels (10 or 100 parts per billion; ppb; µg/L) in developing zebrafish by assessing behavior, morphology, and gene expression. In the visual motor response assay, hyperactivity was observed in all three outcomes in dark phases in larvae with exposure (1-120 h post fertilization, hpf) to 10 ppb As, 10 ppb Pb, or 10 ppb mix treatment. Time spent moving exhibited hyperactivity in dark phases for 100 ppb As and 100 ppb mix treatment groups only. A decreased brain length and ratio of brain length to total length in the 10 ppb mix group was measured with no alterations in other treatment groups or other endpoints (i.e., total larval length, head length, or head width). Alternatively, measurements of cerebral vasculature in the midbrain and cerebellum uncovered decreased total vascularization at 72 hpf in all treatment groups in the mesencephalon and in all treatment groups, except the 100 ppb Pb and 10 ppb As groups, in the cerebellum. In addition, decreased sprouting and branching occurred in the mesencephalon, while only decreased branching was measured in the cerebellum. The 10 ppb Pb group showed several cerebral vasculature modifications that were aligned with a specific gene expression alteration pattern different from other treatment groups. Additionally, the 100 ppb As group drove gene alterations, along with several other endpoints, for changes observed in the 100 ppb mix treatment group. Perturbations assessed in this study displayed non-linear concentration-responses, which are important to consider in environmental health outcomes for As and Pb neurotoxicity.

Astragaloside I from Astragalus Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF-ß1 Loop.

Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from Astragalus membranaceus (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using db/db mice in vivo and high glucose (HG)-induced SV40-MES-13 cells in vitro. The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues of db/db mice. Moreover, ASI was found to reduce the levels of renal fibrosis makers and suppress the activation of TGF-[Formula: see text]1/Smad2/3 pathway in both db/db mice and HG-induced SV40-MES-13 cells. Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF-[Formula: see text]1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF-[Formula: see text]1, thereby regulating HDAC3-mediciated Klotho/TGF-[Formula: see text]1/Smad2/3 pathway.

A Scoping Review on Complications in Modern Hair Transplantation: More than Just Splitting Hairs.

BACKGROUND: Hair restoration surgery (HRS) is a commonly performed elective procedure but to date lacks a review of the full scope of complications. OBJECTIVES: To provide a comprehensive overview of observed complications associated with follicular unit extraction (FUE) and follicular unit transplantation (FUT). ELIGIBILITY CRITERIA: Randomized control trials, cohort studies, case series, and case reports published in 1985 or later on adults (age>18). Nontraumatic or autoimmune etiologies of alopecia were excluded as procedure indications. SOURCES OF EVIDENCE: PubMed, EMBASE, Cochrane databases (last search December 31, 2022). CHARTING METHODS: Data-charting and extraction were independently performed with two reviewers using Covidence. RESULTS: Forty-three publications were included. Two large series reported the overall complication rate to be 1.2 and 4.7%. Common complications included bleeding requiring intervention (up to 8%), persistent numbness (up to 11%), infection (up to 11% with two reports of Kaposi varicelliform eruptions and one of mucormycosis), effluvium at donor and recipient sites (up to 4.1% and 6.5%, respectively). The most common donor-site complication was hypertrophic scarring/keloid formation after FUT (up to 15.1%). Complications at the recipient site, including crusting (up to 54.8%), frontal edema (up to 50%), and sterile folliculitis (up to 53.3%), tended to be poorly defined with a broad range of incidences. CONCLUSION: Serious complications associated with HRS are rare in the hands of experienced providers. However, comprehensive discussions of risk must be had with prospective patients as any complication in the context of an elective procedure may be significant and psychologically devastating for the individual patient. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Peripherally Restricted CB1 Receptor Inverse Agonist JD5037 Treatment Exacerbates Liver Injury in MDR2-Deficient Mice.

Previous research highlighted the involvement of the cannabinoid CB1 receptor in regulating the physiology of hepatocytes and hepatic stellate cells. The inhibition of the CB1 receptor via peripherally restricted CB1 receptor inverse agonist JD5037 has shown promise in inhibiting liver fibrosis in mice treated with CCl4. However, its efficacy in phospholipid transporter-deficiency-induced liver fibrosis remains uncertain. In this study, we investigated the effectiveness of JD5037 in Mdr2-/- mice. Mdr2 (Abcb4) is a mouse ortholog of the human MDR3 (ABCB4) gene encoding for the canalicular phospholipid transporter. Genetic disruption of the Mdr2 gene in mice causes a complete absence of phosphatidylcholine from bile, leading to liver injury and fibrosis. Mdr2-/- mice develop spontaneous fibrosis during growth. JD5037 was orally administered to the mice for four weeks starting at eight weeks of age. Liver fibrosis, bile acid levels, inflammation, and injury were assessed. Additionally, JD5037 was administered to three-week-old mice to evaluate its preventive effects on fibrosis development. Our findings corroborate previous observations regarding global CB1 receptor inverse agonists. Four weeks of JD5037 treatment in eight-week-old Mdr2-/- mice with established fibrosis led to reduced body weight gains. However, contrary to expectations, JD5037 significantly exacerbated liver injury, evidenced by elevated serum ALT and ALP levels and exacerbated liver histology. Notably, JD5037-treated Mdr2-/- mice exhibited significantly heightened serum bile acid levels. Furthermore, JD5037 treatment intensified liver fibrosis, increased fibrogenic gene expression, stimulated ductular reaction, and upregulated hepatic proinflammatory cytokines. Importantly, JD5037 failed to prevent liver fibrosis formation in three-week-old Mdr2-/- mice. In summary, our study reveals the exacerbating effect of JD5037 on liver fibrosis in genetically MDR2-deficient mice. These findings underscore the need for caution in the use of peripherally restricted CB1R inverse agonists for liver fibrosis treatment, particularly in cases of dysfunctional hepatic phospholipid transporter.

Traumatic Brain Injury as an Independent Predictor of Futility in the Early Resuscitation of Patients in Hemorrhagic Shock.

This review explores the concept of futility timeouts and the use of traumatic brain injury (TBI) as an independent predictor of the futility of resuscitation efforts in severely bleeding trauma patients. The national blood supply shortage has been exacerbated by the lingering influence of the COVID-19 pandemic on the number of blood donors available, as well as by the adoption of balanced hemostatic resuscitation protocols (such as the increasing use of 1:1:1 packed red blood cells, plasma, and platelets) with and without early whole blood resuscitation. This has underscored the urgent need for reliable predictors of futile resuscitation (FR). As a result, clinical, radiologic, and laboratory bedside markers have emerged which can accurately predict FR in patients with severe trauma-induced hemorrhage, such as the Suspension of Transfusion and Other Procedures (STOP) criteria. However, the STOP criteria do not include markers for TBI severity or transfusion cut points despite these patients requiring large quantities of blood components in the STOP criteria validation cohort. Yet, guidelines for neuroprognosticating patients with TBI can require up to 72 h, which makes them less useful in the minutes and hours following initial presentation. We examine the impact of TBI on bleeding trauma patients, with a focus on those with coagulopathies associated with TBI. This review categorizes TBI into isolated TBI (iTBI), hemorrhagic isolated TBI (hiTBI), and polytraumatic TBI (ptTBI). Through an analysis of bedside parameters (such as the proposed STOP criteria), coagulation assays, markers for TBI severity, and transfusion cut points as markers of futilty, we suggest amendments to current guidelines and the development of more precise algorithms that incorporate prognostic indicators of severe TBI as an independent parameter for the early prediction of FR so as to optimize blood product allocation.

Quality of Popular Online Resources About Vestibular Migraine.

Objective: To evaluate the readability, understandability, actionability, and accuracy of online resources covering vestibular migraine (VM). Study Design: Cross-sectional descriptive study design. Setting: Digital collection of websites appearing on Google search. Methods: Google searches were conducted to identify common online resources for VM. We examined readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level scores, understandability and actionability using the Patient Education Materials Assessment Tool (PEMAT), and accuracy by comparing the website contents to the consensus definition of "probable vestibular migraine." Results: Eleven of the most popular websites were analyzed. Flesch-Kincaid Grade Level averaged at a 13th-grade level (range: 9th-18th). FRE scores averaged 35.5 (range: 9.1-54.4). No website had a readability grade level at the US Agency for Healthcare Research and Quality recommended 5th-grade level or an equivalent FRE score of 90 or greater. Understandability scores varied ranging from 49% to 88% (mean 70%). Actionability scores varied more, ranging from 12% to 87% (mean 44%). There was substantial inter-rater agreement for both PEMAT understandability scoring (mean κ = 0.76, SD = 0.08) and actionability scoring (mean κ = 0.65, SD = 0.08). Three sites included all 3 "probable vestibular migraine" diagnostic criteria as worded in the consensus statement. Conclusion: The quality of online resources for VM is poor overall in terms of readability, actionability, and agreement with diagnostic criteria.

Hereditary chronic neutrophilic leukemia in a four-generation family without transformation to acute leukemia.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by peripheral blood neutrophilia, marrow granulocyte hyperplasia, hepatosplenomegaly, and driver mutations in the colony-stimulating factor 3 receptor (CSF3R). Designation of activating CSF3R mutations as a defining genomic abnormality for CNL has led to increased recognition of the disease. However, the natural history of CNL remains poorly understood with most patients reported being of older age, lacking germline data, and having poor survival, in part due to transformation to acute leukemia. CSF3R driver mutations in most patients with CNL have been reported to be acquired, although rare cases of germline mutations have been described. Here, we report the largest pedigree to date with familial CNL, spanning four generations with affected family members ranging in age from 4 to 53 years, none of whom have transformed to acute leukemia. A heterozygous T618I CSF3R mutation was identified in peripheral blood and mesenchymal stromal cells from the proband and in all affected living family members, while the unaffected family members tested were homozygous wild type. We show that the T618I mutation also confers a survival advantage to neutrophils in an MCL1-dependent manner. Collectively, these data provide additional insights into the natural history of familial CNL arising from T618I CSF3R mutations and suggest that enhanced neutrophil survival also contributes to the high neutrophil count observed in patients with CNL.

Uptake and Outcomes of Peritoneal Dialysis among Aboriginal and Torres Strait Islander People: Analysis of Registry Data.

Introduction: Peritoneal dialysis (PD) enables people to use kidney replacement therapy (KRT) outside of healthcare-dependent settings, a strong priority of Aboriginal and Torres Strait Islander people. Methods: We undertook an observational study analyzing registry data to describe access to PD and its outcome as the first KRT among Aboriginal and Torres Strait Islander people between January 1, 2004 and December 31 2020. Results: Out of 4604 Aboriginal and Torres Strait Islander people, reflecting 10.4% of all Australians commencing KRT, PD was the first KRT modality among 665 (14.4%). PD utilization was 17.2% in 2004 to 2009 and 12.7% in 2016 to 2020 (P = 0.002); 1105 episodes of peritonitis were observed in 413 individuals, median of 3 (interquartile range [IQR], 2-5) episodes/patient. The crude peritonitis rate was 0.53 (95% confidence interval [CI], 0.50-0.56) episodes/patient-years without any significant changes over time. The median time to first peritonitis was 1.1 years. A decrease in the peritonitis incidence rate ratio (IRR) was observed in 2016 to 2020 (IRR, 0.63 [95% CI, 0.52-0.77], P < 0.001) compared to earlier eras (2010-2015: IRR, 0.90 [95% CI, 0.76-1.07], P = 0.23; Ref: 2004-2009). The cure rates decreased from 80.0% (n = 435) in 2004 to 2009, to 70.8% (n = 131) in 2016 to 2020 (P < 0.001). Conclusion: Aboriginal and Torres Strait Islander people who utilized PD as their first KRT during 2004 to 2020 recorded a higher peritonitis rate than the current benchmark of 0.4 episodes/patient-years. The cure rates have worsened recently, which should be a big concern. There is an exigent need to address these gaps in kidney care for Aboriginal and Torres Strait Islander people.

Clinical Variables and Radiomics Features for Predicting Pneumothorax in Patients Undergoing CT-guided Transthoracic Core Needle Biopsy.

Purpose To develop a prediction model combining both clinical and CT texture analysis radiomics features for predicting pneumothorax complications in patients undergoing CT-guided core needle biopsy. Materials and Methods A total of 424 patients (mean age, 65.6 years ± 12.7 [SD]; 232 male, 192 female) who underwent CT-guided core needle biopsy between January 2021 and October 2022 were retrospectively included as the training data set. Clinical and procedure-related characteristics were documented. Texture analysis radiomics features were extracted from the subpleural lung parenchyma traversed by needle. Moderate pneumothorax was defined as a postprocedure air rim of 2 cm or greater. The prediction model was developed using logistic regression with backward elimination, presented by linear fusion of the selected features weighted by their coefficients. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Validation was conducted in an external cohort (n = 45; mean age, 58.2 years ± 12.7; 19 male, 26 female) from a different hospital. Results Moderate pneumothorax occurred in 12.0% (51 of 424) of the training cohort and 8.9% (four of 45) of the external test cohort. Patients with emphysema (P < .001) or a longer needle path length (P = .01) exhibited a higher incidence of moderate pneumothorax in the training cohort. Texture analysis features, including gray-level co-occurrence matrix cluster shade (P < .001), gray-level run-length matrix low gray-level run emphasis (P = .049), gray-level run-length matrix run entropy (P = .003), gray-level size-zone matrix gray-level variance (P < .001), and neighboring gray-tone difference matrix complexity (P < .001), showed higher values in patients with moderate pneumothorax. The combined clinical-radiomics model demonstrated satisfactory performance in both the training (AUC 0.78, accuracy = 71.9%) and external test cohorts (AUC 0.86, accuracy 73.3%). Conclusion The model integrating both clinical and radiomics features offered practical diagnostic performance and accuracy for predicting moderate pneumothorax in patients undergoing CT-guided core needle biopsy. Keywords: Biopsy/Needle Aspiration, Thorax, CT, Pneumothorax, Core Needle Biopsy, Texture Analysis, Radiomics, CT Supplemental material is available for this article. © RSNA, 2024.

Conceptualizing Fit in Surgical Residency Selection: The Experience in Otolaryngology-Head and Neck Surgery.

OBJECTIVE: Fit is a crucial factor in surgical residency selection, but how this abstract concept is applied in practice is poorly understood. Person-environment (PE) fit theory suggests that there are multiple fit domains that can clarify usage: person-job, person-organization, and person-workgroup fit. We used PE fit theory to explore how otolaryngology residency selection committee (RSC) members operationalize the concept of fit. DESIGN: One-hour focus groups were conducted in November 2022. Interview questions explored participants' definitions and uses of fit in the resident selection process. Transcripts were analyzed using directed qualitative content analysis to generate themes and evaluate how these align with PE fit domains. SETTING: Society of University Otolaryngologists Annual Meeting breakout session in November 2022. PARTICIPANTS: 21 RSC members from 20 different otolaryngology-head and neck surgery departments participated in three seven-person focus groups. RESULTS: Participants described aspects of fit that aligned with PE fit domains. Person-job included how applicants fit as both surgeons and residents. Person-organization included how applicants fit with the program's characteristics, program's mission, and the local community. Person-workgroup emphasized how applicants fit with current residents. Various challenges in the selection process limited the extent to which PE fit was operationalized, including 1) ambiguous uses of fit, 2) unique features of the match process, 3) lack of outcomes data for selection decisions, and 4) interactions with diversity, equity, and inclusion goals. CONCLUSIONS: Fit manifests in various ways during the surgical residency selection process that parallel domains of PE fit theory. Recommendations are made to assist programs in using fit in resident selection, including clearly articulating definitions of fit to increase transparency in conversations. Further work on selection challenges is needed to maximize the utility of fit in practice.

Gender Disparities in Mentorship and Career Outcomes in Ophthalmology.

Background: Gender disparities in the field of ophthalmology have been increasingly recognized. Although mentorship has been proposed as a contributing factor, there are limited data on the differences in mentorship experiences by gender among ophthalmologists. Objective: The purpose of this study was to evaluate gender disparities in mentorship experiences among ophthalmologists, and the impact of mentorship disparities on career outcomes. Design: Prospective, cross-sectional study. Setting: Web-based survey distributed through ophthalmology listservs. Participants: Ophthalmologists and ophthalmologists-in-training who completed the survey. Exposure: Training and practicing in the field of ophthalmology. Main Outcome Measures: Mentorship score based on 10 items from a previously published scale of mentorship quality and self-reported career outcomes (income, job satisfaction, achievement of career goals, and support to achieve future career goals). Results: We received survey responses from 202 male and 245 female ophthalmologists. Female ophthalmologists reported significantly lower mentorship satisfaction and worse quality of mentorship (p < 0.03). Female ophthalmologists also reported significantly lower income, worse job satisfaction, and lower rates of goal achievement and support to achieve future goals; all of these career outcomes, except income level, were partly mediated by mentorship score (mediation effect ranged from 29% to 68%, p < 0.014). Conclusions and Relevance: Gender-based inequities in achievement of career goals and job satisfaction are partly mediated by disparities in mentorship. Therefore, focused mentorship of women in ophthalmology at all career stages is imperative to reduce these inequities.

Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor.

INTRODUCTION: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) often require multiple lines of treatment and have a poor prognosis, particularly after failing covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. Newer treatments such as brexucabtagene autoleucel (brexu-cel, chimeric antigen receptor T cell therapy) and pirtobrutinib (non-covalent BTKi) show promise in improving outcomes. METHODS: Without direct comparative evidence, an unanchored matching-adjusted indirect comparison was conducted to estimate the relative treatment effects of brexu-cel and pirtobrutinib for post-cBTKi R/R MCL. Using logistic propensity score models, individual patient-level data from ZUMA-2 brexu-cel-infused population (N = 68) were weighted to match pre-specified clinically relevant prognostic factors based on study-level data from the BRUIN cBTKi pre-treated cohort (N = 90). The base-case model incorporated the five most pertinent factors reported in ≥ 50% of both trial populations: morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplant. A sensitivity analysis additionally incorporated TP53 mutation and Ki-67 proliferation. Relative treatment effects were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: In the base-case model, brexu-cel was associated with higher rates of objective response (OR 10.39 [95% CI 2.81-38.46]) and complete response (OR 10.11 [95% CI 4.26-24.00]), and improved progression-free survival (HR 0.44 [95% CI 0.25-0.75]), compared to pirtobrutinib. Overall survival and duration of response favored brexu-cel over pirtobrutinib but the differences crossed the bounds for statistical significance. Findings were consistent across the adjusted and unadjusted analyses. CONCLUSIONS: Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

Stakeholder perspectives on electronic prescribing in primary care: A scoping review.

BACKGROUND: Electronic prescribing (e-prescribing) provides a convenient, efficient, paperless mechanism for the legal transfer of prescriptions between service users, prescribers, and dispensers. There have been advances in e-prescribing processes and increased uptake of e-prescribing globally, in recent years. OBJECTIVE: To explore stakeholder perspectives on e-prescribing in primary care settings. METHODS: A scoping review was conducted by systematically searching Medline, EMBASE, Scopus, and International Pharmaceutical Abstracts databases, using the key concepts "primary care", "e-prescribing", and "perspectives". Publications were selected by screening for eligibility against inclusion and exclusion criteria, whereby any publication written in English exploring e-prescribing in primary care settings from the perspective(s) of at least one type of stakeholder was eligible for inclusion. Following a systematic screening process, relevant data were extracted, collated, and synthesized. RESULTS: Two thousand publications were identified and systematically screened, rendering 44 publications (e.g., primary research articles, abstracts) eligible for inclusion in this review. Most publications reported on studies conducted in the USA, the UK, and Europe and explored the views of pharmacists, pharmacy technicians, and pharmacy staff. Barriers to e-prescribing included system design and technical issues, lack of adequate training and communication issues between stakeholders. Enablers for e-prescribing included time savings, convenience, and increased legibility of prescriptions. CONCLUSIONS: This review highlights many benefits of e-prescribing such as time efficiency, convenience, increased legibility, and less mishandling. Despite this, key barriers to e-prescribing within primary care settings were also recognized, including system design, technical issues, and lack of adequate training. As such, forcing functions, prescription tracking technologies, and better training have been identified as potential ways to address these barriers. While some negative experiences were reported, stakeholders were generally satisfied and had positive experiences with e-prescribing.

Evolution of gene expression across brain regions in behaviourally divergent deer mice.

The evolution of innate behaviours is ultimately due to genetic variation likely acting in the nervous system. Gene regulation may be particularly important because it can evolve in a modular brain-region specific fashion through the concerted action of cis- and trans-regulatory changes. Here, to investigate transcriptional variation and its regulatory basis across the brain, we perform RNA sequencing (RNA-Seq) on ten brain subregions in two sister species of deer mice (Peromyscus maniculatus and P. polionotus)-which differ in a range of innate behaviours, including their social system-and their F1 hybrids. We find that most of the variation in gene expression distinguishes subregions, followed by species. Interspecific differential expression (DE) is pervasive (52-59% of expressed genes), whereas the number of DE genes between sexes is modest overall (~3%). Interestingly, the identity of DE genes varies considerably across brain regions. Much of this modularity is due to cis-regulatory divergence, and while 43% of genes were consistently assigned to the same gene regulatory class across subregions (e.g. conserved, cis- or trans-regulatory divergence), a similar number were assigned to two or more different gene regulatory classes. Together, these results highlight the modularity of gene expression differences and divergence in the brain, which may be key to explain how the evolution of brain gene expression can contribute to the astonishing diversity of animal behaviours.

Research Progress on the Antitumor Molecular Mechanism of Ginsenoside Rh2.

Cancer has evolved into a substantial public health concern as the second-leading cause of mortality globally. Radiotherapy and chemotherapy have been the two most widely used cancer therapies in recent years; however, both have drawbacks. Therefore, the focus has shifted to the creation of herbal medicines, the extraction of active ingredients, replacement therapy, and the adverse effects of these medications. Ginsenoside Rh2, which is extracted from ginseng, has been identified in many cancer cells. The immune system of the body is strengthened by ginsenoside Rh2, which can also cause the proliferation, death, and differentiation of tumor cells through various pathways. For instance, it inhibits the expression of the NF-[Formula: see text]B signaling pathway and induces cell apoptosis, affects the expression levels of mitochondrial apoptosis proteins Bcl-2 and Bax, and cooperates with the PD-1 blockade to reactivate T cells to promote an antitumor immune response. Furthermore, ginsenosides Rh2 has the effect of reversing the toxic effect of chemotherapy drugs on normal cells, reducing myocardial damage, and relieving bone marrow function suppression. For clinical applications, it is mainly used as an adjuvant drug for preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and rescue treatment of advanced cancer. This paper summarizes the pharmacological action and mechanism of ginsenosides Rh2 in all kinds of cancer and looks forward to its future development and application.

PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.

RATIONALE AND OBJECTIVES: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer. MATERIALS AND METHODS: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [18F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival. RESULTS: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin, ADCmean, and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033). CONCLUSION: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS.