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Pain-related discussions on social media provide valuable insights into how people naturally express and communicate their pain experiences. However, the network structure of these discussions remains poorly understood. This study analyzed 57,000 Reddit comments from the GoEmotions dataset (2005–2019) using natural language processing and network analysis techniques grounded in discrete mathematical principles. The constructed network, comprising 5,630 nodes and 86,972 edges, revealed complex patterns of pain-related language use. The network exhibited a sparse overall density (0.0055) but a high clustering coefficient (0.7700), indicating the presence of distinct thematic communities. At the center of the network was the term pain , which showed the highest degree centrality (0.821429), reflecting its semantic anchoring function in pain discourse. Other terms, such as headache , served as context-sensitive bridge nodes that connected different semantic subdomains. In contrast, terms like burning , despite moderate centrality values, were found to co-occur predominantly with metaphorical or decorative expressions rather than emotion- or symptom-related descriptors. Community detection revealed 12 distinct clusters, with the largest containing 1,021 nodes, capturing diverse aspects of pain communication. Stability analysis demonstrated that core pain-related terms maintained consistent centrality, while peripheral or metaphorical terms showed greater variability. These findings offer novel insights into the semantic structure of pain discourse and suggest that network analysis of social media discussions can inform improved clinical communication and symptom assessment.

The vasopressin inhibitor tolvaptan is clinically effective in slowing growth of renal cysts and reduction in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD), but these effects are mitigated by the associated polyuria. Changes of total kidney volume, eGFR, and symptoms will guide physicians and patients in tolvaptan treatment. Guidance about when to initiate treatment in the course of ADPKD may be forthcoming. Ongoing long-term observations will inform future recommendations about tolvaptan use in ADPKD.

Autosomal recessive polycystic kidney disease (ARPKD) is a severe genetic disorder characterized by renal cystogenesis and hepatic fibrosis, primarily associated with PKHD1 mutations. While differential expression analysis (DEG) has identified key genes involved in ARPKD, their network-level interactions remain unclear. Recent studies have implicated WNT signaling in ARPKD pathogenesis, but a topological framework may provide additional insights into gene community structures. This study applied a network-based approach integrating single-sample gene set enrichment analysis (ssGSEA) and topological centrality analysis to investigate gene communities in ARPKD. We identified three key communities: Community 2, centered on IFT22 , exhibited stable activation in both ARPKD and healthy samples, suggesting its role in ciliary function. Community 5, predominantly activated in ARPKD, included genes linked to tissue repair and immune regulation. In contrast, Community 3 was suppressed in ARPKD, indicating potential structural instability. Notably, PKHD1 was mathematically isolated, suggesting limited direct involvement in ARPKD-specific transcriptional networks, while the absence of WNT5A , CDH1 , and FZD10 from defined communities in ARPKD may indicate potential alterations in their network associations compared to healthy individuals. These findings highlight the advantages of network topology over conventional DEG analysis in elucidating ARPKD pathophysiology. By identifying gene communities and regulatory hubs, this approach offers novel insights into disease mechanisms and potential therapeutic targets.

Cystic kidneys are common causes of end-stage renal disease, both in children and in adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are cilia-related disorders and the two main forms of monogenic cystic kidney diseases. ADPKD is a common disease that mostly presents in adults, whereas ARPKD is a rarer and often more severe form of polycystic kidney disease (PKD) that usually presents perinatally or in early childhood. Cell biological and clinical research approaches have expanded our knowledge of the pathogenesis of ADPKD and ARPKD and revealed some mechanistic overlap between them. A reduced ‘dosage’ of PKD proteins is thought to disturb cell homeostasis and converging signalling pathways, such as Ca 2+ , cAMP, mechanistic target of rapamycin, WNT, vascular endothelial growth factor and Hippo signalling, and could explain the more severe clinical course in some patients with PKD. Genetic diagnosis might benefit families and improve the clinical management of patients, which might be enhanced even further with emerging therapeutic options. However, many important questions about the pathogenesis of PKD remain. In this Primer, we provide an overview of the current knowledge of PKD and its treatment. Autosomal dominant polycystic kidney disease (PKD) and autosomal recessive PKD are progressive cilia-related disorders that often lead to chronic kidney disease and end-stage renal disease. This Primer provides an overview of the current knowledge of PKD pathogenesis and its treatment.

Background Serum total testosterone (TT) interacts with multiple physiological systems and is implicated in heterogeneous aging processes in men. However, aging-related phenotypes associated with TT are unlikely to be captured by single biomarkers or conventional clinical categories. This study aims to identify data-driven aging phenotypes based on TT and related clinical biomarkers using an unsupervised analytical framework. Methods Clinical laboratory data from 5,877 Japanese male patients undergoing routine health evaluations are analyzed. After restricting the cohort to individuals with complete age and body mass index data, missing values in other variables are imputed using column-wise mean imputation. Unsupervised clustering is performed using K-means on standardized biomarkers related to endocrine, metabolic, inflammatory, and renal function. Principal component analysis and correlation network analysis are used for visualization. External validation uses cancer prevalence data from the NHANES dataset. Results Four physiological clusters are identified. One cluster shows low TT levels, elevated inflammatory markers, impaired renal function, and higher cancer prevalence in external validation, indicating a high-risk aging profile. Other clusters show preserved hormonal and metabolic profiles. Network analysis reveals cluster-specific differences in the centrality of TT within physiological networks. Principal component analysis shows overlapping cluster distributions, reflecting continuous aging-related variation. Conclusions Unsupervised clustering of TT-related biomarkers reveals aging phenotypes beyond conventional clinical classifications. TT functions as part of an integrated physiological network rather than as an isolated marker. These findings support a systems-level perspective on male aging and demonstrate utility of data-driven phenotyping, while acknowledging the descriptive and cross-sectional nature of the analysis. Plain language summary Testosterone is commonly measured in adult men, but its clinical meaning is often unclear when considered in isolation. Similar testosterone levels can reflect very different physiological states depending on inflammation, kidney function, and other biological factors. In this study, routine blood test data from more than 5,800 Japanese men were analyzed to examine how testosterone relates to other clinical biomarkers. Using an unsupervised machine learning approach, individuals were grouped based on combined patterns of testosterone, inflammatory markers, renal function, and metabolic measures, rather than on testosterone levels alone. Several distinct physiological contexts of testosterone were identified. In one group, low testosterone was accompanied by elevated inflammation and impaired kidney function, suggesting a coordinated biological state rather than an isolated hormone abnormality. When similar biomarker profiles were examined in an independent U.S. population dataset, individuals with this profile showed higher cancer prevalence, supporting consistency across populations. These findings indicate that measuring testosterone is most informative when interpreted alongside other routinely available biomarkers, rather than as a standalone test. Okui et al. applied unsupervised clustering and network analyses to testosterone related clinical biomarkers from 5,877 men to identify data driven aging phenotypes. The resulting four physiological clusters revealed a high risk group marked by low testosterone, inflammation, and renal dysfunction, suggesting that testosterone functions within an integrated physiological network and that such phenotyping may better capture aging related risk than conventional markers.

Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic–pituitary–gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.

Intratumoral androgen biosynthesis has been recognized as an essential factor of castration‐resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1‐month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC‐MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose‐dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1‐month oral administration of curcumin, Aldo‐Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. The present study demonstrates significant effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer.

Interstitial cystitis/bladder pain syndrome is a chronic condition involving pelvic pain and urinary symptoms. A three-stage analytical framework examined the correspondence between vocabulary from validated clinical questionnaires and language used in patient discussions on social media. Stage 1 identified 19 symptom-related terms from three questionnaires, all consistent with international diagnostic criteria. Stage 2 analyzed over 500,000 words from online discussions, detecting 73.7% of these terms and revealing a central “pain–urgency–voiding” triad in patient discourse. Stage 3 mapped strong symptom–site links, including burning–urethra and pain–abdomen, which may indicate underrecognized comorbidities. Clinical terms occupied central positions in the discourse network and showed greater structural importance than general vocabulary. Findings highlight differences between clinical terminology and patient-preferred language, suggesting strategies to improve assessment tools, address terminology gaps, and enhance patient-centered care. The approach is adaptable to other chronic conditions, supporting integration of real-world patient expression into clinical practice.

Androgen deprivation therapy and aromatase inhibitors are known to cause a decrease in bone mineral density and an increase in fractures. Patients receiving these treatments have been shown to have a fracture risk equal to or greater than that of patients with osteoporosis with prevalent fractures. This manual was created to prevent fractures in patients with cancer treatment-induced bone loss with high fracture risks who cannot be treated under the current Japanese guideline for the prevention and treatment of osteoporosis. This manual recommends drug treatment for patients with BMD − 2.0 ≤ T score < − 1.5 with the family history of hip fracture or 15% or more 10-year probability of major osteoporotic fractures by FRAX®; or in patients with BMD T score < − 2.0. It is important to verify whether the use of this manual can reduce fractures and improve the quality of life of patients with cancer treatment-induced bone loss by prospective studies.

ObjectiveThe objective of this study was to evaluate the early surgical outcomes of robot-assisted partial nephrectomy (RAPN) for small renal masses in a large Japanese multicenter series.MethodsA total of 804 consecutive cases of RAPN were examined at 42 institutes between 2011 and 2016. Medical records for clinical, pathological characteristics and perioperative outcomes were retrospectively reviewed. Univariable and multivariable analyses were performed to determine factors predicting Trifecta achievement.ResultsThe median tumor size was 2.6 cm. The median RENAL score was 7. The median warm ischemia time was 21 min. The median estimated blood loss was 30 mL. Eight patients (1.0%) were converted to radical nephrectomy. The overall and Clavien–Dindo grade ≥ 3 complication rates were 13.0% and 5.8%, respectively. Pathologically, 91.4% of tumors were malignant and the positive surgical margin (PSM) rate was 1.1%. During the median 27.1-month observation period, the recurrence rate was 1.6%. Postoperative preservation rates of eGFR at 1, 6, 12 and 24 months were 90.3, 89.8, 89.4 and 89.2%, respectively. Trifecta was achieved in 62.1%. Multivariable analysis demonstrated that tumor diameter, estimated blood loss and hilar location of the tumor were significant negative factors predicting Trifecta achievement. The rate of Trifecta achievement for T1b tumors and hilar tumors was significantly lower (48.4% and 50.0%, respectively).ConclusionsRAPN was safely performed with acceptable oncological and functional outcomes, but the rate of Trifecta accomplishment for T1b or hilar tumors was significantly lower than that for T1a or non-hilar tumors, respectively.