BACKGROUND AND OBJECTIVES: The jugular foramen (JF) is rather a complex anatomical structure with internal configuration. Its osteomorphology was assessed to redefine this rather long bony passage as a jugular canal (JC) based on its morphometric data. METHODS: The JF was endocranially and exocranially observed and measured by a digital Vernier caliper bilaterally in 402 dry skulls with opened cranial cavity. The following parameters were measured and analyzed statistically: (1) external and internal widths in the mediolateral dimension, (2) external and internal lengths in the anteroposterior dimension, and (3) depth between the external and internal planes of the foramen. The JF/canal was classified based on its appearance and its morphometric features. RESULTS: The mean length of the JC was approximately 12 mm (12.25 mm-right, 11.76 mm-left) and was longer on the right side (P = .05, 95% CI). Its external opening was found to be slightly larger than the internal opening (P = .07-right, P = .06-left). The JC took 3 distinctive course patterns of straight (47.6%), curved (45.5%), and angulated (6.9%). Its openings exhibited 3 types based on their morphometric analysis: 14.4% Type-I (width = length ±1 mm), 9.8% Type-II (width > length), and 75.9% Type-III (width < length). The size of the external opening into the JC was larger than its internal opening (straight: P = .08-right and P = .07-left), (curved: P = .03-right and P = .03-left), (angulated: P = .03-right and P = .04-left). CONCLUSION: The JF should be regarded clinically as a canal. It is composed of internal and external openings where the jugular fossa resides in between. The provided osteomorphological variations of the JC would enhance the diagnostics and surgical planning in JF syndromes radioimaging and surgical interventions.
- Klíčová slova
- Jugular canal, Jugular foramen, Jugular foramen syndrome, Skull base,
- Publikační typ
- časopisecké články MeSH
Sarcopenia, characterized by skeletal muscle atrophy, was previously considered age-related; however, it is also associated with other diseases. Nonalcoholic fatty liver disease (NAFLD) is known to cause sarcopenia, and its complications have been reported to affect prognosis. The intestinal microbiota of patients with NAFLD or sarcopenia has been found to be altered compared to that of healthy individuals. However, the alterations that occur when both diseases coexist in humans or experimental animals remain unclear. Therefore, this study aimed to determine the intestinal microbiota changes associated with NAFLD with sarcopenia in SHRSP5/Dmcr rats at the time of concomitant disease. Fecal samples were collected from the rectum of SHRSP5/Dmcr rats fed a normal diet (non-NAFLD and non-Sarcopenia, n = 5) or a high-fat and high-cholesterol diet (NAFLD and Sarcopenia, n = 5) for 20 weeks, and subjected to 16S rRNA analysis. In the NAFLD and sarcopenia group, the diversity of the intestinal microbiota was reduced; further, the bacterial species reported in patients with NAFLD or sarcopenia were also changed. At the family level, the abundances of Akkermansiaceae, Bacteroidaceae, and Tannerellaceae were significantly higher whereas Ruminococcaceae and Lactobacillaceae were decreased in the NAFLD and sarcopenia group. At the genus level, the abundances of Akkermansia, Bacteroides, Ruminococcus, and Parabacteroides were significantly higher whereas the abundance of Lactobacillus was significantly decreased in the NAFLD and sarcopenia group. Overall, these findings help improve the existing understanding regarding the intestinal microbiota changes observed in conditions where NASH and sarcopenia co-occur.
- Klíčová slova
- Bacteroides, Ruminococcus, Intestinal microbiota, Nonalcoholic steatohepatitis, Sarcopenia,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: For many years, syphilis treatment was considered straightforward due to the universal susceptibility of Treponema pallidum subsp. pallidum (TPA) to penicillin antibiotics. METHODS: Penicillin-binding protein genes from a ceftriaxone treatment failure T. pallidum isolate were assessed, and the introduction of identified mutations into two laboratory strains via natural competence was aimed for, followed by in vitro analysis of antibiotic susceptibility of the recombinants. RESULTS: TPA from the ceftriaxone treatment failure case contained A1873G and G2122A mutations in the TP0705 gene. Introduction of the A1873G mutation into laboratory strains DAL-1 and SS14 resulted in partial resistance to ceftriaxone and penicillin G in vitro. Furthermore, in silico analyses revealed that the majority of contemporary TPA SS14-like strains harbors this mutation and are thus partially resistant to ceftriaxone and penicillin G. CONCLUSIONS: This finding indicates that TPA strains accumulate mutations that increase their resistance to β-lactam antibiotics. Alternative approaches for controlling syphilis will be needed, including the development of the syphilis vaccine.
Penicillin antibiotics have been used to treat syphilis since the 1950s. Resistance to antibiotics is a growing concern. We investigated cases where antibiotics had failed to treat infection and found two mutations in a specific gene that could be responsible. Introduction of one of these mutations into two laboratory T. pallidum strains (the bacteria that cause syphilis) resulted in partial resistance to both ceftriaxone and penicillin antibiotics. Moreover, analysis of existing data revealed the presence of this mutation in numerous circulating T. pallidum strains, suggesting widespread partial resistance may already exist and increasing concerns about the future emergence of fully resistant syphilis strains.
- Publikační typ
- časopisecké články MeSH
Monoclonal antibodies targeting CD38 are a therapeutic mainstay in multiple myeloma (MM). While they have contributed to improved outcomes, most patients still experience disease relapse, and little is known about tumor-intrinsic mechanisms of resistance to these drugs. Antigen escape has been implicated as a mechanism of tumor cell evasion in immunotherapy. Yet, it is unknown whether MM cells can develop permanent resistance to anti-CD38 antibodies by acquiring genomic events leading to biallelic disruption of the CD38 gene locus. Here, we analyzed whole genome and whole exome sequencing data from 701 newly diagnosed patients, 67 patients at relapse with naivety to anti-CD38 antibodies, and 50 patients collected at relapse following anti-CD38 antibodies. We report a loss of CD38 in 20% (10/50) of patients post-CD38 therapy, three of which exhibited a loss of both copies. Two of these cases showed convergent evolution where distinct subclones independently acquired similar advantageous variants. Functional studies on missense mutations involved in biallelic CD38 events revealed that two variants, L153H and C275Y, decreased binding affinity and antibody-dependent cellular cytotoxicity of the commercial antibodies Daratumumab and Isatuximab. However, a third mutation, R140G, conferred selective resistance to Daratumumab, while retaining sensitivity to Isatuximab. Clinically, patients with MM are often rechallenged with CD38 antibodies following disease progression and these data suggest that next generation sequencing may play a role in subsequent treatment selection for a subset of patients.
- Publikační typ
- časopisecké články MeSH
Allodiploid hybrid species, Aspergillus latus, belonging to section Nidulantes, is a hybrid of A. spinulosporus and unknown species closely related to A. quadrilineatus and A. sublatus. This hybrid has often been misidentified as the species in section Nidulantes, such as A. nidulans, A. spinulosporus, A. sublatus, or other cryptic species. A. latus has not been reported in Japan as well as Asia so far. In this study, we screened 23 clinical strains identified as A. spinulosporus isolated in Japan from 2012 to 2023 and found seven A. latus strains. To characterize the A. latus strains, we conducted comprehensive phenotyping including morphological observation, whole genome sequences and phylogenetic analysis based on calmodulin (CaM) gene. In addition, we conducted antifungal susceptibility testing for A. latus strains. As a result, the morphological characters of A. latus were more similar to those of A. spinulosporus compared to A. sublatus. However, the ascospore of A. latus differed from that of A. spinulosporus. A. latus phylogenetically clustered with A. spinulosporus and A. sublatus. Furthermore, A. latus strains showed reduced susceptibility to caspofungin and amphotericin B compared to A. spinulosporus, while they were susceptible to azoles. Our results suggest that A. latus has been a causative pathogen of aspergillosis in Japan since 2013.
Aspergillus species are the causal agents for aspergillosis. We present the first report of allodiploid hybrid species A. latus being isolated in Japan through screening of A. spinulosporus strains. A. latus has been the causative agent of aspergillosis in Japan since 2013.
- Klíčová slova
- Aspergillus latus, Aspergillus spinulosporus, Aspergillus sublatus, aspergillosis, section Nidulantes,
- Publikační typ
- časopisecké články MeSH
Previous scholarship has analysed decisions to remain childfree in terms of individual agency. This study reorients attention towards the collective dimensions of childfree-based advocacy by analysing the actions of groups that directly or indirectly advocate for childfree-based decision making. Qualitative thematic analysis was carried out on eight case study groups. Each case captures an advocacy group which is treated as an organisational unit of analysis, and whose public-facing content, manifestos and digital communications are comparatively analysed. By analysing organisations rather than individual testimonies, this study seeks to capture the collective dimensions of activism. Findings point to different discourses and trajectories through which groups have challenged traditional reproductive norms. These include climate change concerns and digital identity-centred activism. Each trajectory has offered a distinctive framing of the issues and has articulated being childfree as a legitimate and empowering lifestyle choice. Advocacy groups and online communities have influenced public perceptions of reproductive autonomy by challenging societal narratives that equate parenthood with personal fulfilment and social legitimacy. Conceptually, the analysis presents an empirical foundation for understanding how childfree-based decision making is constructed and mobilised both offline through traditional activism, and online through networking across digital spaces.
- Klíčová slova
- Children, activism, climate change, reproductive rights, women,
- Publikační typ
- časopisecké články MeSH
The authors offer a model for curriculum for education and training in substance-assisted psychotherapy (SAP), that is, psychedelic, psycholytic, and entactogen/MDMA (3,4-methylenedioxymethamphetamine)-assisted psychotherapy, addressing both the detailed contents of training and the question of experiential training. All authors of this model have an abiding interest and extensive experience in both the theory and practical aspects of SAP and questions relating to training. The model curriculum has been written through an international consensus building process and represents a consensus statement about the topic. The model includes an enumeration of theoretical themes and topics, which we suggest for inclusion in an SAP curriculum. The practical part of the curriculum includes experiential training with the following components: (1) apprenticeship observation: learning from observing experienced therapists, (2) ongoing clinical supervision: conducting treatment under direct supervision of experienced SAP therapists, and (3) a proposal for the inclusion of self-experiences for the trainees. Other parts address the use of peer supervision and conventional supervision. The authors are aware of the abiding need for respect of intercultural differences. We are conscious that the proposed model is one largely adapted to western industrialized countries with established graduate level education and training procedures for psychotherapists. However, the model curriculum includes teachings about the use of related substances and treatment techniques in indigenous cultures and traditions. This curriculum model may be valuable to psychedelic researchers, those endeavoring to train therapists for research studies, and those preparing for the clinical work to follow, once SAP is conducted outside of research settings.
- Klíčová slova
- MDMA-assisted psychotherapy, Psychedelic therapy, education of therapists, psycholytic therapy, therapists self-experience, training curriculum,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND & AIMS: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on 2nd- and 3rd-line biologics are limited. We present the first direct comparison of 2nd - and 3rd -line biologics in pCD patients with active perianal disease previously treated with 1st-line anti-TNFs. METHODS: A multicenter retrospective cohort study included adult patients with pCD who failed 1st-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging [MRI] or transrectal ultrasound [TRUS]) and healing, and clinical remission. Propensity-score matching (PSM) was used to adjust for baseline differences. RESULTS: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the 2nd and 3rd -line treatment groups, respectively. In the 2nd -line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI 1.94-10.28, p<0.001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI 2.39-11.71, p<0.001). In the 3rd-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI 2.6-38.4, p<0.001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI 2.99-48.47, p<0.001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI 1.07-10.07, p=0.038). CONCLUSION: In pCD patients failing anti-TNFs as 1st-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNFs as 2nd or 3rd-line therapy.
- Klíčová slova
- Biologics, Crohn’s, Fistulas, Perianal, Second-line, Third-line,
- Publikační typ
- časopisecké články MeSH
In the present work, we examine how the recent quantum-computing algorithm known as the state-average orbital-optimized variational quantum eigensolver (SA-OO-VQE), viewed within the context of quantum chemistry as a type of multiconfiguration self-consistent field (MCSCF) electronic-structure approach, exhibits a propensity to produce an ab initio quasi-diabatic representation "for free" if considered as a least-transformed block-diagonalization procedure, as alluded to in our previous work (Yalouz, S. et al. J. Chem. Theory Comput. 2022, 18, 776-794) and thoroughly assessed herein. To this end, we introduce intrinsic and residual descriptors of diabaticity and re-explore the definition and linear-algebra properties, as well as their consequences on the vibronic nonadiabatic couplings, of an optimal diabatic representation within this context and how much one may deviate from it. Such considerations are illustrated numerically in the prototypical case of formaldimine, which presents a well-known conical intersection between its ground and first-excited singlet electronic states.
- Publikační typ
- časopisecké články MeSH
Preparative chromatography for purification of sugars has found numerous applications in food processing and biochemical industries. Parameter estimation leading to robust modelling and model-based design are essential for transferring this technology into industrial practice. This study examines the Equilibrium Dispersive model with a non-linear isotherm and the formulation of apparent dispersion based on the Bodenstein number. A parameter estimation workflow is proposed, incorporating chromatography-specific algorithmic data preprocessing and a curve uncertainty scoring system, enabling the simultaneous utilization of data from pulse-feed experiments conducted under varying conditions. A bilevel optimization scheme is introduced, leading to increased performance and robustness. The introduction of parameter bounding and initialization eliminates arbitrariness in the process. Experiments on the chromatographic separation of a d-glucose and sucrose mixture, performed under different flow rates and feed loads using an anion-exchange resin, were conducted. Lab-scale experiments were used for parameter estimation, supported by subsequent identifiability and sensitivity analyses. Scaling-up predictions of the calibrated model were evaluated by experimental data from a 2-meter-long pilot-scale column. The results demonstrate the benefits of the proposed modeling and parameter estimation framework, as well as the sufficient predictive accuracy of the calibrated model under the conditions of scaled-up flow rates and column dimensions.
