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Purpose The present study aimed to analyze the endometrial and vaginal microbiome among a Japanese infertile population by sequencing and the impact of the endometrial and vaginal environment on implantation. Methods In total, 102 infertile (79 in vitro fertilization [IVF] and 23 non‐IVF) patients and seven healthy volunteers were recruited from August to December, 2017. Endometrial fluid and vaginal discharge samples for sequencing were collected by using an intrauterine insemination catheter. The bacterial status of the endometrium and vagina were analyzed. Results The Lactobacillus‐dominated microbiota (>90% Lactobacillus spp.) in the endometrium vs vagina was 38% (30/79) vs 44.3% (44/79) in the IVF patients, 73.9% (17/23) vs 73.9% (17/23) in the non‐IVF patients, and 85.7% (6/7) vs 85.7% (6/7) in the healthy volunteers. The percentage of endometrial Lactobacillus in the healthy volunteers was highly stable within the same menstrual cycle and even in the following cycle. The major taxonomies were Gardnerella, Streptococcus, Atopobium, Bifidobacterium, Sneathia, Prevotella, and Staphylococcus. Fifteen patients achieved pregnancy by a single vitrified‐warmed blastocyst transfer during this study; the median percentage of Lactobacillus in the pregnant women was 96.45 ± 33.61%. Conclusion A considerable percentage of non‐Lactobacillus‐dominated (NLD) microbiota was found in the endometrium of Japanese infertile women. Increasing the endometrial level of the Lactobacilli to >90% might favor the implantation outcome of NLD infertile patients. We analyzed the endometrial and vaginal microbiome among a Japanese infertile population by sequencing, and found a considerable percentage of non‐Lactobacillus dominated microbiota in the endometrium of Japanese infertile women.

Autobiographical memory deficits are well-documented in aphantasia, yet the underlying mechanisms remain unclear. Emerging models suggest that interoception plays a crucial role in mental imagery, a key component of memory retrieval. In this study, we investigate the relationship between self-reported interoception, mental imagery, and autobiographical memory, with a specific focus on aphantasia. First, we examined whether interoceptive awareness and autobiographical memory differ between individuals with core aphantasia ( n  = 69), hypophantasia ( n  = 266) and typical imagers ( n  = 133). Our findings reveal that aphantasics report significantly lower autobiographical memory as well as subjective interoceptive awareness across key subscales, including emotional awareness and noticing. Secondly, a mediation analysis reveals that mental imagery mediates the relationship between the emotional awareness subscale of the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire and autobiographical memory, suggesting that subjective interoception may contribute to memory recall indirectly through its influence on imagery. These findings provide novel empirical support for the idea that interoception is linked to both mental imagery and memory retrieval. The reduced interoceptive awareness observed in aphantasia may contribute to their known deficits in autobiographical memory, positioning aphantasia as a condition that extends beyond a lack of mental imagery to include altered interoceptive processing.

Studies suggest that persisting intrauterine bacterial infectious conditions such as chronic endometritis potentially impair the embryo implantation process. The microbial environment in the female reproductive tract, however, remains largely undetermined in infertile patients with a history of repeated implantation failure (RIF). Using next-generation sequencing, we aimed to characterize the microbiota in the endometrial fluid (EF) and vaginal secretions (VS) in women with RIF. Twenty-eight infertile women with a history of RIF and eighteen infertile women undergoing the first in vitro fertilization-embryo transfer attempt (the control group) were enrolled in the study. On days 6-8 in the luteal phase of the natural, oocyte-pickup, or hormone replacement cycle, the paired EF and VS samples were obtained separately. Extracted genomic DNA was pyrosequenced for the V4 region of 16S ribosomal RNA using a next-generation sequencer. The EF microbiota had higher α-diversity and broader bacterial species than the VS microbiota both in the RIF and control groups. The analysis of the UniFrac distance matrices between EF and VS also revealed significantly different clustering. Additionally, the EF microbiota, but not the VS microbiota, showed significant variation in community composition between the RIF group and the control group. Burkholderia species were not detected in the EF microbiota of any samples in the control group but were detectable in a quarter of the RIF group. To our best knowledge, this is the first study investigating the microbiota in the paired EF and VS samples in infertile women with RIF.

Purpose The present study aimed to analyze the pregnancy outcomes of IVF patients presenting Lactobacillus‐dominated microbiota (LDM) or non‐Lactobacillus‐dominated microbiota (NLDM) of their endometrium and to report cases who were treated for NLDM concurrently with antibiotics and prebiotic/probiotic supplements in a Japanese infertile population. Methods Ninety‐two IVF patients were recruited from August 2017 to March 2018. Endometrial fluid samples for sequencing were collected using an IUI catheter. The bacterial status of the endometrium and the pregnancy outcomes were analyzed. For cases with NLDM, antibiotics and prebiotics/probiotics were administered according to their individual microbial conditions. Results Forty‐seven cases (51.1%) presented LDM and 45 cases (48.9%) presented NLDM at initial analysis. Nine Patients with NLDM were treated by antibiotics and prebiotics/probiotics, and successfully became Lactobacillus‐dominant. Pregnancy rates by single vitrified‐warmed blastocyst transfers were higher in the LDM group (58.9% per patient and 36.3% per FBT) than in the NLDM group (47.2% per patient and 34.7% per FBT) but not significantly different. Conclusion The results of this study could not necessarily prove the clear benefit of establishing Lactobacillus‐dominated endometrium in terms of pregnancy outcome, but there is significance in searching for endometrial microbial status of infertile patients and recovering Lactobacillus‐dominated endometrium might benefit implantation. This is a follow‐up to the previous study, analyzing the endometrial microbiome of IVF patients and assessing the pregnancy outcome of patients with Lactobacillus‐dominant or non‐Lactobacillus‐dominant endometrium, and we found that Lactobacillus dominancy may be beneficial for the pregnancy outcome of IVF patients. Also, we tried to establish a treatment strategy for recovering Lactobacillus‐dominant endometrium, and this may be the first study reporting on a treatment for dysbiotic endometrium. We found that concurrent administration of antibiotics and prebiotics and/or probiotics was successful in recovering endometrium to a Lactobacillus‐dominant condition.

With ageing, normal human tissues experience an expansion of somatic clones that carry cancer mutations 1 – 7 . However, whether such clonal expansion exists in the non-neoplastic intestine remains unknown. Here, using whole-exome sequencing data from 76 clonal human colon organoids, we identify a unique pattern of somatic mutagenesis in the inflamed epithelium of patients with ulcerative colitis. The affected epithelium accumulates somatic mutations in multiple genes that are related to IL-17 signalling—including NFKBIZ , ZC3H12A and PIGR , which are genes that are rarely affected in colon cancer. Targeted sequencing validates the pervasive spread of mutations that are related to IL-17 signalling. Unbiased CRISPR-based knockout screening in colon organoids reveals that the mutations confer resistance to the pro-apoptotic response that is induced by IL-17A. Some of these genetic mutations are known to exacerbate experimental colitis in mice 8 – 11 , and somatic mutagenesis in human colon epithelium may be causally linked to the inflammatory process. Our findings highlight a genetic landscape that adapts to a hostile microenvironment, and demonstrate its potential contribution to the pathogenesis of ulcerative colitis. Whole-exome sequencing of colon organoids derived from patients with ulcerative colitis identifies somatic mutations in components of the IL-17 signalling pathway, which may confer a growth advantage to cells under inflammatory conditions.

Interoception, the sense of the internal state of the body, plays a fundamental role in emotional awareness and self-referential processing. Recently, interoception has been linked to the experience of mental imagery. However, this association has not been empirically characterized. We therefore tested how task-based and self-reported measures of interoception predict individual differences in task-based and self-reported measures of mental imagery. Participants ( N  = 104) completed two heartbeat detection tasks (heartbeat tracking and heartbeat discrimination; assessing objective (behavioural) interoceptive performance accuracy), and the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire, assessing subjective (self-reported) dimensions of interoceptive experience. Behavioural and self-reported aspects of mental imagery were assessed respectively from performance of a mental rotation task and from scores on the Vividness of Visual Imagery Questionnaire (VVIQ). Results revealed that, across participants, interoceptive (heartbeat discrimination performance) accuracy predicted mental rotation ability. In contrast, both heartbeat tracking accuracy and self-reported interoceptive awareness (MAIA) predicted self-reported vividness of mental imagery (VVIQ). Interoceptive measures did not predict performance on a control task (2-back working memory task). Together, these findings suggest that distinct components of interoception underpin different aspects of mental imagery: Heightened (cardioceptive) physiological sensitivity facilitates the active deployment of imagery in mental rotation and enhances the vividness of imagery experience. Moreover, people reporting more subjective sensitivity to interoceptive state also perceive greater vividness of mental imagery. These new results underscore the influence of bodily representation in shaping conscious experience through both controlled and spontaneous expressions of mental simulation.

Purpose To identify specific bacterial communities in vaginal and endometrial microbiotas as biomarkers of implantation failure by comprehensively analyzing their microbiotas using next‐generation sequencing. Methods We investigated α‐ and β‐diversities of vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared their profiles between 145 women with repeated implantation failure (RIF) and 21 controls who lacked the factors responsible for implantation failure with a high probability of being healthy and fertile to identify specific bacteria that induce implantation failure. Results The endometrial microbiotas had higher α‐diversities than did the vaginal microbiotas (P < .001). The microbiota profiles showed that vaginal and endometrial samples in RIF patients had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in controls. Vaginal Lactobacillus rates in RIF patients were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% (P = .018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, P = .79). Conclusions Impaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The vaginal Lactobacillus rates, but not the endometrial, may be a biomarker for RIF. Vaginal and endometrial microbiotas might be independent. Endometrial microbiota has a richer alpha diversity than vaginal microbiota, and dysbiosis of vaginal or endometrial microbiota can cause implantation failure. Unlike previous reports, the Lactobacillus rate in the vagina, but not the endometrium, may be a biomarker for repeated implantation failure.

This article appraises cultural understanding and controversies regarding hikikomori (prolonged social withdrawal), with reference to research over the past 20 years. Initially viewed as a uniquely Japanese phenomenon, hikikomori is now recognised globally, prompting a re-evaluation of its cultural, psychological and socioeconomic demographics. A revision in lifestyle after the COVID-19 pandemic and ongoing technological advancements – particularly the rise of social media, gaming and the internet – have paradoxically both exacerbated isolation and provided new forms of social interaction for young adults who confine themselves at home. This phenomenon underlines the complex interplay between putative individual psychopathology, neurodiversity and broader societal shifts across the globe.

The popularity of breathwork as a therapeutic tool for psychological distress is rapidly expanding. Breathwork practices that increase ventilatory rate or depth, facilitated by music, can evoke subjective experiential states analogous to altered states of consciousness (ASCs) evoked by psychedelic substances. These states include components such as euphoria, bliss, and perceptual differences. However, the neurobiological mechanisms underlying the profound subjective effects of high ventilation breathwork (HVB) remain largely unknown and unexplored. In this study, we investigated the neurobiological substrates of ASCs induced by HVB in experienced practitioners. We demonstrate that the intensity of ASCs evoked by HVB was proportional to cardiovascular sympathetic activation and to haemodynamic alterations in cerebral perfusion within clusters spanning the left operculum/posterior insula and right amygdala/anterior hippocampus; regions implicated in respiratory interoceptive representation and the processing of emotional memories, respectively. These observed regional cerebral effects may underlie pivotal mental experiences that mediate positive therapeutic outcomes of HVB.

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.