Notes

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Parkinson's disease is a neurodegenerative disorder caused by neuronal cell loss in the substantia nigra pars compacta (SNpc). We aimed to perform atlas-based relaxometry using an anatomical SNpc atlas and obtain baseline values of SNpc regions in healthy volunteers.

Neuromelanin (NM)-sensitive imaging of the midbrain and whole-brain 3D

weighted images of 27 healthy volunteers (20 males; aged 36.3 ± 11.5 years) were obtained. An anatomical SNpc atlas was created using NM-sensitive images in standard space, and divided into medial (MG), dorsal (DG), and ventrolateral (VG) groups. Proton density (PD), T
, and T
values in these regions were obtained using quantitative MRI. The relationships between PD, T
, and T
values in each SNpc region and age were evaluated.

The VG PD value was significantly higher than the MG and DG values. MG, DG, and VG T
values were significantly different, whereas the T
value of the MG was significantly lower than the DG and VG values. Moreover, a significant negative correlation between PD and T
values of the MG and age was observed.

The PD, T
, and T
values of the SNpc regions measured in standard space using an anatomical atlas can be used as baseline values. PD and T
values of the SNpc regions may be associated with NM concentrations.

An anatomical SNpc atlas was created using NM-sensitive MRI and can be used for the quantitative evaluation of subsegments of the SNpc in standard space.
An anatomical SNpc atlas was created using NM-sensitive MRI and can be used for the quantitative evaluation of subsegments of the SNpc in standard space.Respiration is a core biological energy-converting process whose last steps are carried out by a chain of multisubunit complexes in the inner mitochondrial membrane. To probe the functional and structural diversity of eukaryotic respiration, we examined the respiratory chain of the ciliate Tetrahymena thermophila (Tt). Using cryo-electron microscopy on a mixed sample, we solved structures of a supercomplex between Tt complex I (Tt-CI) and Tt-CIII2 (Tt-SC I+III2) and a structure of Tt-CIV2. Tt-SC I+III2 (~2.3 megadaltons) is a curved assembly with structural and functional symmetry breaking. Tt-CIV2 is a ~2.7-megadalton dimer with more than 50 subunits per protomer, including mitochondrial carriers and a TIM83-TIM133-like domain. Our structural and functional study of the T. thermophila respiratory chain reveals divergence in key components of eukaryotic respiration, thereby expanding our understanding of core metabolism.It is without question that the Internet has democratized access to medical information, with estimates that 70% of the American population use it as a resource, particularly for cancer-related information. Such unfettered access to information has led to an increase in health misinformation. Fortunately, the data indicate that health care professionals remain among the most trusted information resources. Therefore, understanding how the Internet has changed engagement with health information and facilitated the spread of misinformation is an important task and challenge for cancer clinicians. In this review, we perform a meta-synthesis of qualitative data and point toward empirical evidence that characterizes misinformation in medicine, specifically in oncology. We present this as a call to action for all clinicians to become more active in ongoing efforts to combat misinformation in oncology.SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. After vaccination of mice, the MVA/SdFCS vaccine induced eightfold higher neutralizing antibodies compared with MVA/S, which expressed spike without FCS inactivation, and protected against the Beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, and rectum) that neutralized the homologous (WA-1/2020) and heterologous VOCs, including Delta, with minimal loss ( less then 2-fold) of activity. IM vaccination also induced both spike- and nucleocapsid-specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared with IM vaccination. After challenge with the SARS-CoV-2 Delta variant, the IM route induced robust protection, the BU route induced moderate protection, and the SL route induced no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination.
Primary plasma cell leukemia (pPCL) is an aggressive subtype of multiple myeloma, which is distinguished from newly diagnosed multiple myeloma (NDMM) on the basis of the presence of ≥ 20% circulating tumor cells (CTCs). A molecular marker for pPCL is currently lacking, which could help identify NDMM patients with high-risk PCL-like disease, despite not having been recognized as such clinically.

A transcriptomic classifier for PCL-like disease was bioinformatically constructed and validated by leveraging information on baseline CTC levels, tumor burden, and tumor transcriptomics from 154 patients with NDMM included in the Cassiopeia or HO143 trials and 29 patients with pPCL from the EMN12/HO129 trial. Its prognostic value was assessed in an independent cohort of 2,139 patients with NDMM from the HOVON-65/GMMG-HD4, HOVON-87/NMSG-18, EMN02/HO95, MRC-IX, Total Therapy 2, Total Therapy 3, and MMRF CoMMpass studies.

High CTC levels were associated with the expression of 1,700 genes, independent of tumor burde.
pPCL was identified on the basis of a specific tumor transcriptome, which was also present in patients with high-risk NDMM, despite not being clinically leukemic. Incorporating PCL-like status into current risk models in NDMM may improve prognostic accuracy.Persistent, interpersonal difficulties are a core feature of borderline personality disorder (BPD). Theories propose that these may result from an insufficient object constancy, for example, the insufficient capacity to maintain feelings of closeness (FC) toward a person when he or she is absent. Based on this assumption, this study examined whether FC toward the mother or the best friend were more dependent on previous contact in adolescents with BPD pathology compared with healthy controls. In addition, the influence of different contact modes was explored. N = 52 female adolescents aged 14 to 18 years (n = 24 with ≥ 5 BPD symptoms [full-threshold BPD], n = 10 with 1-4 BPD symptoms [subthreshold BPD], n = 18 healthy controls) completed up to 12 e-diaries a day on 2 consecutive weekends. Using multilevel mixed-effect regression analyses, we found that the more BPD symptoms a patient fulfilled, the more dependent were FC toward the best friend on actual contact. In contrast, BPD pathology did not influence the dependency of the FC toward the mother on actual contact. Finally, the mode of contact seems to matter The more BPD symptoms a patient met, the more was the FC toward the best friend dependent on personal compared with written or no contact, whereas phone or written contact was no different from no contact. The present findings partially support the theory of an insufficient object constancy in BPD that seems to become apparent in adolescence mainly in relationships with peers. Replication of the findings, particularly with regard to the impact of mode of contact, in larger samples is required. (PsycInfo Database Record (c) 2022 APA, all rights reserved).Despite research indicating that exerting dominance and control is characteristic of psychopathy, no research has examined the role that feelings of and desire for power plays in psychopathy-related aggression. Borrowing from various literatures and novel conceptualizations, we investigated the contributions of feeling powerful and/or desiring power and distinct psychopathy facets in explaining aggression manifested in different forms (i.e., physical, verbal, indirect) across 4 samples. Results from regression analyses within each sample and a meta-analysis across the samples indicated that the impulsive facet of psychopathy was generally related to multiple forms of aggression, and the unique variance in the affective facet was primarily related to physical aggression across samples. In contrast, the unique variance of the interpersonal facet showed a primary relationship with indirect aggression (e.g., relational, passive). Desiring power made unique contributions in relation to multiple forms of aggression, whereas feeling powerful was generally unrelated and/or negatively related to aggression. In sum, the unique variance in the psychopathy facets showed fairly specialized relationships with forms of aggression, and desire for power may be an independent explanatory construct for multiple forms of aggression proneness. check details (PsycInfo Database Record (c) 2022 APA, all rights reserved).Moral psychology has long debated whether moral judgment is rooted in harm versus affect. We reconcile this debate with the affective harm account (AHA) of moral judgment. The AHA understands harm as an intuitive perception (i.e., perceived harm), and divides "affect" into two embodied visceral arousal (i.e., gut feelings) and stimulus-directed affective appraisals (e.g., ratings of disgustingness). The AHA was tested in a randomized, double-blind pharmacological experiment with healthy young adults judging the immorality, harmfulness, and disgustingness of everyday moral scenarios (e.g., lying) and unusual purity scenarios (e.g., sex with a corpse) after receiving either a placebo or the β-blocker propranolol (a drug that dampens visceral arousal). Results confirmed the three key hypotheses of the AHA. First, perceived harm and affective appraisals are neither competing nor independent but intertwined. Second, although both perceived harm and affective appraisals predict moral judgment, perceived harm is consistently relevant across all scenarios (in line with the theory of dyadic morality), whereas affective appraisals are especially relevant in unusual purity scenarios (in line with affect-as-information theory). Third, the "gut feelings" of visceral arousal are not as important to morality as often believed. Dampening visceral arousal (via propranolol) did not directly impact moral judgment, but instead changed the relative contribution of affective appraisals to moral judgment-and only in unusual purity scenarios. By embracing a constructionist view of the mind that blurs traditional dichotomies, the AHA reconciles historic harm-centric and current affect-centric theories, parsimoniously explaining judgment differences across various moral scenarios without requiring any "moral foundations." (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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