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The contemporary management of prostate cancer

Abstract Prostate cancer is the most common cancer in two thirds of the world, with an expected doubling in both incidence and mortality in the next two decades. No strong environmental associations exist for the development of prostate cancer; therefore, lifestyle measures are unlikely to mitigate this increasing burden. The last three decades have seen rapid developments in the diagnostic and therapeutic landscape of prostate cancer, including multiparametric magnetic resonance imaging, positron emission tomography, robotic surgery, image‐guided hypofractionated and stereotactic radiotherapy, novel anti‐androgens and radioligand therapies. Prostate cancer is unique in that not everyone with a diagnosis needs treatment, and active surveillance is the preferred option for some. This review discusses the contemporary management of all stages of prostate cancer in the light of these modern developments, enabling holistic individualization of treatment, and describes the promise of future research to further improve outcomes.

Simple in vitro single-stranded linear and circular DNA preparation, functional selection, and validation using phosphor-derived modifications

Association between the atherogenic index of plasma and the occurrence of acute kidney injury in critically ill patients with sepsis: A retrospective study

Background The atherogenic index of plasma (AIP) is a recognized marker of atherosclerosis and cardiovascular disease (CVD). However, the association between AIP and the risk of acute kidney injury (AKI) in critically ill patients with sepsis has not yet been investigated. Methods The data used in this study were derived from the Medical Information Mart for Intensive Care (MIMIC-IV) database. The clinical outcome was the occurrence of AKI. Logistic regression was used to assess the association between AIP and the risk of AKI in sepsis patients. Restricted cubic spline (RCS) analysis was applied to explore potential non-linear relationships. Threshold analysis confirmed a turning point at this value. Subgroup analyses evaluated the consistency of the association across different strata. Mediation analysis was performed to explore potential intermediate variables. Results Among 1,874 sepsis patients, higher AIP levels were associated with increased AKI incidence. Logistic regression showed a significant association between AIP and AKI in unadjusted and partially adjusted models, but the association was no longer significant after full adjustment. RCS analysis revealed a nonlinear relationship with a peak AKI risk at AIP = 1.333. Threshold analysis confirmed a turning point at this value. Subgroup analyses showed consistent associations, while nonlinear effects were more evident in specific groups. Mediation analysis suggested that SOFA score, creatinine, WBC count, and respiratory rate partially mediated the AIP-AKI relationship. Conclusion AIP was nonlinearly associated with AKI in sepsis, with a clear threshold effect. This relationship was partially mediated by SOFA score, creatinine, WBC, and respiratory rate. AIP may serve as a useful marker for AKI risk assessment.

Cyanophycinase is required for heterotrophy in cyanobacteria

A data-driven analysis of patient selection for xenotransplant human clinical trials

The demand for transplant organs far exceeds the available supply. In the United States alone, more than 90,000 patients are currently on the kidney transplant waitlist, yet only about one third of them will ever receive a transplant. Xenotransplantation, organ transplants from gene edited pigs, offers a potential solution to this shortage. Successful investigational transplants of pig kidneys into brain-dead recipients and expanded access cases involving living human recipients have resulted in the green-lighting of the first human clinical trials. Using the benchmark of 2-year survival of non-human primates in pre-clinical studies, we developed a tool that can identify individual wait-listed patients predicted to have a shorter life expectancy than with a xenotransplant, utilizing Random Survival Forest, DeepSurv and Cox Proportional-Hazards models. We found that it is hard to identify patients that reach clinical equipoise unless the expected xenograft survival exceeds two years, with the Random Survival Forest model identifying less than 5% of such patients. Few patients would benefit based on survival alone and potential beneficiaries are spread across more than 200 transplant centers. Several incentives could allow more patients to reach equipoise. At the same benchmark of 2-year xenograft survival, keeping patients inactive on the waitlist while they have a functioning xeno-kidney increases the percentage achieving equipoise by up to 1.7% across cohorts. Granting patients with failed xenografts the same priority as prior living donors increases this by up to 17.9%, while assigning them the highest priority raises it by up to 28.5%. We are able, however, to identify phenotypes that have a high mortality and low transplant rates in the current allocation system that could serve as acceptable candidates; while not achieving equipoise, they would enjoy the benefits of being dialysis free.

Urothelial carcinoma: Perioperative considerations from top to bottom

Abstract Urothelial carcinoma is an aggressive entity that is associated with significant morbidity, but there have been major advances in both our understanding of and treatment options for patients with this disease. In this review, the authors focus on novel therapeutic and diagnostic approaches in the perioperative setting, with an emphasis on patient‐centered and individualized care. For urothelial carcinoma of the bladder (UCB), advances in nonplatinum‐based therapies, specifically immunotherapy and antibody–drug conjugates, have expanded the therapeutic arsenal for patients with muscle‐invasive UCB in both the neoadjuvant and adjuvant settings to improve survival outcomes. Given the significant morbidity of extirpative surgery (radical cystectomy and urinary diversion), there have also been greater efforts to evaluate bladder‐sparing protocols and improve the selection of patients for surgery and their postoperative recovery. The authors review special considerations for organ‐sparing surgery in females, geriatric co‐management, and enhanced recovery after surgery protocols. For upper tract urothelial carcinoma, there has been increasing recognition of its unique diagnostic and therapeutic challenges, including risks of renal functional loss. There have been advances in molecular profiling that have demonstrated various genomic differences between upper tract urothelial carcinoma and UCB, with treatment implications. This article reviews studies evaluating perioperative care that focused on optimizing therapeutic approaches, including neoadjuvant/adjuvant chemotherapy and immunotherapy, as well as nephron‐sparing strategies in carefully selected cases.

The Pseudomonas aeruginosa membrane histidine kinase BqsS/CarS directly senses environmental ferrous iron (Fe2+)

Precarious employment and gender-based violence against migrant women: A scoping review mapping the intersections

The risk of gender-based violence (GBV) against migrant women is largely exacerbated by precarious employment opportunities available to them as they go through the resettlement process. Despite the risk that the connection of precarious employment and GBV pose to migrant women’s health and wellbeing, critical gaps exist in literature. Our scoping review sought to identify and synthesize evidence on the interconnectedness of GBV and precarious employment among migrant women. Six electronic databases were searched for empirical literature and two reviewers independently conducted title/abstract and full text screening of studies that met the inclusion criteria. Data synthesis was guided by the intersectionality theory and the Feminist Political Economy framework. 50 articles met the criteria for inclusion in this review. Our findings reveal that precarious employment plays both a catalytic and consequential role in GBV. Findings highlighted how post-migration shifts in gender roles, schedule unpredictability leading to work-life imbalance, and debt bondage trap migrant women in cycles of exploitation and abuse. Few studies highlighted how human trafficking is intertwined with precarious labor markets, where the exploitation and abuse of migrant women mirror the characteristics of human trafficking. This review underscores the urgent need for integrated policy responses that are not only focused on individual supports but also address the structural drivers or labor precarity and protect migrant women from GBV and human trafficking. By applying an intersectional lens, policies and intervention programs can tackle systemic oppression across economic, and social systems essential in reducing exploitation and abuse to advance migrant women’s wellbeing.

Sertad1 is elevated and plays a necessary role in neuron loss and cognitive impairment in a mouse model of Alzheimer's disease

Evolution of talent policies in Guangdong-Hong Kong-Macao greater bay area: An LDA thematic model approach

As construction of the Guangdong-Hong Kong-Macao Greater Bay Area advances, talent has become the core driving force for its development. This study quantitatively analyzes 94 talent policies from Guangdong, Hong Kong, and Macao, revealing the strategic focuses and thematic evolution of these policies across different stages from a time-series perspective. It also distills relevant experiences to propose optimization strategies and a development blueprint for talent policies in the region. By combining historical review and thematic modeling, this study categorizes talent policies from the three regions over the past five years (2019–2024) into three phases: initial phase, developmental phase, and deep plowing phase. Theme heat analysis and similarity analysis are then applied to clarify the strategic focus and evolutionary trajectory of each phase, while the implementation effects of the talent policies are evaluated based on four dimensions: talent inflow volume, talent satisfaction, economic impact, and social influence. The Latent Dirichlet Allocation (LDA) model uncovers seven strategic talent themes and their heat distribution across the three phases. The study reveals that “Hong Kong and Macao tax incentives” have consistently served as the cornerstone of talent policy throughout the development process, while also fostering the rapid emergence of related themes. Looking ahead, efforts will be dedicated to building a comprehensive talent ecosystem integrating education, science and technology, and social security, thereby positioning the Guangdong-Hong Kong-Macao Greater Bay Area as an international first-class bay area. Finally, this paper draws on the successful experiences of the Yangtze River Delta, Beijing-Tianjin-Hebei region, and other international bay areas to formulate targeted strategies for the development of the Guangdong-Hong Kong-Macao Greater Bay Area.

A variant of the MenB strain of Synechocystis sp. PCC 6803 disrupts a stress response pathway allowing DMPBQ to occupy the A1 sites of photosystem I

Anion‐Induced Bridged Electrolyte Design Strategy Mitigates Capacity Decay in Lithium–Sulfurized Polyacrylonitrile Batteries

Abstract Previous strategies have improved the compatibility of sulfurized polyacrylonitrile (SPAN) in ether‐based electrolytes by constructing a relatively stable interphase, but the electrode degradation caused by sluggish kinetics has limited the practical implementation of SPAN cathodes. Here, we propose an anion‐induced bridged electrolyte (AIBE) design strategy to simultaneously achieve anode/cathode compatibility, anion‐derived interphase formation, and fast Li + transfer kinetics in Li||SPAN batteries through utilizing small‐sized nitrate (NO 3 − ) anions with multidentate coordination propensity. One NO 3 − could coordinate with multiple Li + ions to promote the formation of bridged complexes ([Li + –NO 3 − –Li + ]) with reduced Li + –Li + distances. These densely packed ion pairs create an anion‐dominated solvation structure and fast Li + interfacial reaction kinetics. Simultaneously, the optimized AIBE facilitates the formation of a robust inorganic‐rich interphase to suppress electrode degradation. This electrolyte mitigates SPAN cathode decay, enabling a Li||SPAN full cell to retain 80.5% capacity after 500 cycles. An Ah‐level pouch cell (50 µm Li, 4.0 mA h cm −2 SPAN, lean 1.52 g Ah −1 electrolyte) achieves 99.7% capacity retention after 95 cycles. This work elucidates the fundamental role of NO 3 − anions in modifying the solvation structure and interphase composition/structure, offering novel perspectives for advanced electrolytes for Li||SPAN batteries.

Development of a low-cost culture medium from industrial and environmental by-products for sustainable cultivation of Lactic Acid Bacteria

Conventional culture media such as de Man, Rogosa and Sharpe are essential for the growth of lactic acid bacteria and the production of metabolites used in the food and pharmaceutical industries. However, their high cost limits their application, particularly in low and middle-income countries. This study aimed to develop a cost-effective and efficient culture medium based on agro-industrial and environmental by-products, pineapple peels, sugarcane molasses, and black soldier fly larvae cake. After physico-chemical analysis of the by-products, excluding sugarcane molasses, a statistical mixture design was used to determine the optimal proportions for supporting lactic acid bacteria growth and bacteriocin production. Growth and metabolite production were monitored via plate count and agar well diffusion assays respectively. The strains tested belonged to the genera Lactobacillus , Bifidobacterium , Streptococcus , Lactococcus, and Bacillus as an out taxa group. The larvae cake showed high protein (48.47 ± 0.14%) and amino acid (17 types) content, while pineapple peels and molasses were rich in carbohydrates (89.52 ± 0.16% and 86.86 ± 0.07%). Based on regression models, the compromise formulation was defined as 55.15% larvae cake hydrolysate, 19.85% pineapple peel hydrolysate, and 25.00% sugarcane molasses. This medium highly supported lactic acid bacteria growth (9.43–9.86 log CFU/mL) compared to MRS and M17 (9.20–9.69 log CFU/mL), with Lactobacillus strains performing better. It also supported bacteriocin activity (11.0–14.5 mm inhibition zones), higher or similar to MRS and M17, with Lactococcus lactis subsp. lactis MA2 exhibiting the strongest effect. These results highlight the potential of this formulation as a sustainable, low-cost alternative for microbiology and biotechnology, particularly in resource-limited settings. The determination of its formula will allow its manufacture once the proximate compositions of the ingredients are known, regardless their origin. Future investigations will focus on optimisation of culture conditions, powder form formulation, and cost evaluation.

Reirradiation: Standards, challenges, and patient‐focused strategies across tumor types

Abstract Reirradiation (reRT), defined as administering a course of radiation therapy to a specific area previously irradiated, is an evolving treatment strategy for locoregionally recurrent cancer that offers significant potential and poses inherent challenges. Advances in such techniques as intensity‐modulated and stereotactic body radiation therapy have improved precision, making reRT a viable option for complex scenarios previously deemed high‐risk. Nevertheless, reRT remains associated with substantial risks—including life‐threatening side effects, functional impairments, and psychosocial effects—which must be carefully balanced against the patient's overall health and the likelihood of achieving cancer control or palliation. Patient selection is essential to optimize outcomes while mitigating risks. Decisions should account for tumor characteristics at the time of primary diagnosis and recurrence, elapsed time since prior treatment, the possibility of delivering meaningful doses to the tumor, and the cumulative irradiation tolerance of normal tissues. Advanced imaging modalities, such as functional magnetic resonance imaging and fluorine‐18–labeled fluorodeoxyglucose–positron emission tomography, are important for distinguishing recurrences from treatment‐induced changes, refining treatment targets, and minimizing exposure to healthy tissue. Combined treatment with systemic regimens—targeted therapies and immunotherapy in particular—offers promising opportunities but requires coordination to manage side effects. Standardized guidelines, such as those from the European Society of Therapeutic Radiology and Oncology‐European Society for Research and Treatment of Cancer, are essential for improving the consistency of reporting, guiding clinical decision making, and fostering patient‐centered care. Multidisciplinary collaboration and ongoing research, particularly through clinical trials, are central to fully exploiting reRT strategies. In addition, the development of innovative techniques, such as proton therapy, would likely enable safer treatments. These efforts aim to improve the therapeutic balance of reRT, enhancing outcomes and quality of life.

Enhanced anti-tumor activity by the combination of the natural compounds (−)-epigallocatechin-3-gallate and luteolin

Symmetry‐Engineered Ultralong Phosphorescence in Double π‐Helical Nanographenes

Abstract The development of long‐lived organic phosphorescent materials faces significant challenges in achieving precise control over triplet exciton emission processes. Herein, we present an innovative design strategy toward a novel class of double π‐helical nanographenes ( 8 – 10 ) by integrating a chiral cyclooctahexaphenylene (COTh) core with diverse polycyclic aromatic hydrocarbons (PAHs). The process underwent sequential Knoevenagel condensation, Diels–Alder [4 + 2] cycloaddition, and final Scholl dehydrocyclization, using phenanthraquinone dimer 3 as the key chiral building block. By systematically varying the symmetry of PAH subunits from C 2 to C 2v to D 6h , we achieved remarkable orange‐red phosphorescence with lifetimes ( τ p ) reaching 5.5 s and afterglow durations up to 45 s at 77 K for 10 featuring highly D 6h ‐symmetric hexabenzocoronene (HBC) moieties. This exceptional performance stems from three synergistic effects in high‐symmetry, rigid PAHs: (1) significantly suppressed S 1 →S 0 radiative rates ( k f ) due to symmetry‐forbidden transitions governed by Clar's π‐sextet rule, (2) extremely low triplet radiative decay ( k p ), and (3) minimized nonradiative dissipation ( k nr ). These double π‐helical nanographenes further demonstrate tunable chiroptical properties, with absorption dissymmetry factor (| g abs |) of 0.011 for 9 and exceptional Cotton effects (Δ ε = 457 M −1 cm −1 ) for 10 . This research offers a valuable insight into the molecular design of chiral afterglow materials.

Factors associated with phylogenetic clustering of hepatitis C virus, mainly among people who inject drugs who access HIV prevention services in South Africa, 2016–2017

People who inject drugs (PWID) are disproportionately burdened with hepatitis C virus (HCV) infection in South Africa (SA). Transmission dynamics can be inferred using phylogenetic clustering to inform prevention interventions. We utilized Core-E2 sequences and demographic data to investigate factors associated with HCV phylogenetic clustering among PWID and men who have sex with men (MSM) who inject drugs in SA. Previously genotyped samples (n = 285) that met the selection criteria were extracted, amplified, and Sanger sequenced. Phylogenetic trees were inferred using maximum likelihood implemented in RAxML (Cipres Gateway). Transmission clusters were determined in Clusterpicker using a 90% bootstrap threshold and a genetic distance cut-off on genetic similarity of ≤3.5%. Factors associated with clustering were assessed using logistic regression. Phylogenetic clustering of Core-E2 sequences was observed for 55% (78 of 141) of participant samples that were successfully sequenced, including 50 (64.1%) with genotype 1a and 28 (35.9%) with genotype 3a. Twelve clusters were identified, including six clusters each for genotypes 1a and 3a. Among genotype 1a, the cluster size ranged from 3 to 15 participants. Among genotype 3a, the cluster size ranged from 3 to 9 participants. Clustering among the mixed ancestry group in Cape Town was noted for ages 18–55. Factors independently associated with phylogenetic clustering included sharing a needle (adjusted odds ratio [aOR] 4.02, 95% confidence interval [CI] 1.08–14.87, p = 0.037), age ≥ 29 years (aOR 3.00, 95% CI 1.22–7.37, p = 0.016), and mixed ancestry race (aOR 6.11, 95% CI 1.87–19.95, p = 0.003). These data highlight the urgent need to reduce transmission by providing sufficient sterile needles and syringes and tailored education to prevent HCV transmission among older, experienced PWID.

Germ cell and other tumors in individuals with differences in sex development

Abstract Approximately one in 3500 to one in 5100 live‐born infants have atypical external genital development, known as differences in sex development (DSD). In 2005, an expert consensus conference thoroughly reviewed aspects of health care for individuals with DSD. The conference proposed a classification system to help provide individualized evaluations and management. Some types of DSD are associated with germ cell tumors, which comprise a heterogeneous group of neoplasms derived from germline cells. These neoplasms commonly occur in infants, children, adolescents, and young adults. Herein, an overview of DSDs and risks for germ cell tumors is provided.

A disintegrin and metalloproteinase with thrombospondin motifs 18 (ADAMTS18) cleaves fibronectin and negatively regulates its fibrillogenesis

Drivers and determinants of extreme humanitarian needs among Rohingya refugee households: Evidence from UNHCR’s multi-sectoral needs analysis

Background The Rohingya refugee crisis continues to deteriorate amid major funding cuts and a myriad of intensifying threats. Approximately one million Rohingya refugees are currently housed within 33 densely populated camps in Cox’s Bazar, Bangladesh. This study aimed to estimate the prevalence of households in extreme humanitarian need, identify sector-specific drivers, and elucidate household characteristics associated with extreme humanitarian needs to strategically inform humanitarian relief efforts. Methods Data were sourced from the 2023 Joint Multi-Sectoral Needs Assessment (J-MSNA) – a representative cross-sectional survey of Rohingya refugee households. Households were selected via stratified simple random sampling from UNHCR’s database of registered refugees. Data were collected from 3,400 households and 18,172 household members distributed across the 33 camps of Cox’s Bazar through face-to-face interviews using a pre-tested structured questionnaire between August and September 2023. Survey-adjusted logistic regression was used to elucidate household characteristics associated with extreme humanitarian needs. Results A total of 1,206 households (35.5%) were found to be in extreme humanitarian need, predominantly driven by sector-specific needs within the education (17.2%), food security (12.7%), and health sectors (7.2%). In adjusted analysis, household characteristics significantly associated with increased odds of extreme humanitarian needs included female head of households (aOR = 1.65, 95% CI = 1.29–2.12), head of household age between 30–49 years (aOR = 1.58, 95% CI = 1.27–1.96), or age 50 and older (aOR = 2.18, 95% CI = 1.74–2.72), increasing household size (aOR = 1.20, 95% CI = 1.15–1.25), and households with at least one member experiencing symptoms of psychosocial distress or trauma (aOR = 1.25, 95% CI = 1.06–1.46). Conclusion The findings attest to the deteriorating Rohingya refugee crisis in Cox’s Bazar. The household characteristics associated with extreme humanitarian needs highlight the repercussions of contemporary funding cuts among vulnerable cohorts that pay the heaviest price. The resurgence of targeted violence in Myanmar and intensity of the protracted crisis in Bangladesh demands a more compassionate and enduring humanitarian response from the international community.