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The Global State of Contemporary Andrology Practice: A Comprehensive Analysis of Clinical Practice, Training Pathways, and Emerging Challenges.
No full textPURPOSE: This study evaluates the current state of andrology practice worldwide, identifies challenges faced by clinicians, and explores training, certification, and research opportunities. It also seeks to redefine the qualifications necessary to be recognized as an andrologist and to propose areas for standardization and improvement.
MATERIALS AND METHODS: A global, cross-sectional survey was conducted using a 48-question online questionnaire designed by international experts. The survey, distributed in English, covered various domains of modern andrology practice. Responses from 405 participants across 59 countries were analyzed using R version 4.1.2, with categorical variables reported as frequencies and percentages.
RESULTS: Among respondents, 47.3% held medical doctor (MD) degrees, with urologists (31.1%) and clinical andrologists (25.3%) being the most represented specialties. Formal, board-certified andrological training was reported as available in only 48.1% of countries. While half of the respondents identified as andrologists based on experience, only one-third did so through certification, obtained from diverse, nationally recognized organizations. The primary areas of practice included male infertility (36.7%), male sexual dysfunction (27.2%), and sexually transmitted infections (14.5%). Many participants were actively engaged in assisted reproductive technologies, imaging, and andrological surgical emergencies. Despite strong interest in clinical, basic, and translational research, respondents highlighted significant challenges, including inconsistent training pathways, insufficient certification standards, and the complexity of managing diverse andrological conditions.
CONCLUSIONS: Andrology is an evolving multidisciplinary specialty where board-certified urologists, clinical andrologists, and reproductive medicine specialists collaborate to address male reproductive and sexual health challenges. Despite their advanced competencies in medical, surgical, and laboratory interventions, specialists face significant global disparities in training and certification. This survey highlights the urgent need for standardized training, evidence-based guidelines, and unified certification to ensure consistency, enhance patient care, and advance andrology's academic and clinical excellence worldwide
Hyper-resolution in X-ray emission spectroscopy: integrating extended-range high energy resolution fluorescence detection and multiple-crystal spectrometry with advanced binary data splicing
No full textThis study of manganese (Mn, Z = 25) introduces a novel combination of extended-range high energy resolution fluorescence detection (XR-HERFD), multiple-crystal spectrometers and advanced binary data splicing techniques to address challenges in X-ray emission spectroscopy. XR-HERFD enhances spectral precision by utilizing high-resolution crystal analysers and optimized detector configurations. The systematic application of these methods using multiple Bragg crystal analysers at Diamond Light Source has led to substantial improvements in data quality. Simultaneously, advanced binary data splicing integrates multiple datasets to correct distortions and improve resolution, resulting in sharper spectral features. Our results show a significant increase in peak counts and a notable reduction in full width at half-maximum (FWHM), with peak amplitudes increasing by 83% and resolution improving by 46%. These developments provide greater detail for X-ray absorption or emission spectra, offering valuable insights into complex materials, and permitting advances and breakthroughs in atomic relativistic quantum mechanics, chemical sensitivity of atomic transitions and modelling of solid-state effects
Deep Intronic SVA_E Insertion Identified as the Most Common Pathogenic Variant Associated With Canavan Disease: A Diagnostic Blind Spot.
No full textBACKGROUND AND OBJECTIVES: Canavan disease (CD) is a neurodegenerative disorder in which biallelic pathogenic variants in ASPA result in spongiform degeneration of the cerebral white matter, leading to progressive and irreversible motor and cognitive decline. Despite comprehensive genetic testing, many individuals with clinical and biochemical diagnoses of CD remain without a definitive molecular diagnosis. This gap hinders access to emerging gene-targeted therapies and limits participation in clinical trials. Our objective was to understand the genetic etiology of 8 unsolved cases of CD. METHODS: We used long-read sequencing (LRS) to investigate 8 individuals clinically and biochemically diagnosed with CD but who had negative genetic testing results. We performed targeted LRS using the Oxford Nanopore Technologies platform for 3 unrelated individuals and PacBio HiFi for an additional individual from our cohort. We performed targeted LRS on barcoded and pooled samples from the remaining affected individuals. To investigate functional impact on gene function, we performed RNA sequencing (RNA-seq) with and without cycloheximide on fibroblasts. We then evaluated the allele frequency in the population using gnomAD. RESULTS: We identified an ∼2,600-bp SVA_E retrotransposon intronic insertion in ASPA in all 8 individuals. The insertion was found to be either homozygous or compound heterozygous trans with a known pathogenic variant in all individuals. RNA-seq indicated that the SVA_E insertion creates a novel splice acceptor site within intron 4 of ASPA that causes aberrant splicing and transcript degradation. Surprisingly, the frequency of this variant in population databases suggests that it is the most common pathogenic variant in ASPA and that it is present across ancestry groups. DISCUSSION: Our study identified the most common pathogenic variant in ASPA, which has been overlooked in 25 years of CD research. Considering this, it is important to ensure that all testing laboratories can detect this variant through diagnostic testing and carrier screening. Our study highlights a substantial blind spot in standard short-read diagnostic pipelines, which historically have missed or overlooked these types of insertions. It also shows the power of emerging technologies, such as LRS and RNA-seq, to identify new classes of variants for genetic disorders, including CD
Identifying implementation science research and policy priorities to advance universal health coverage: A multi-country modified Delphi study
No full textDespite efforts to advance universal health coverage (UHC) in different contexts, evidence gaps remain, and implementation science has been underused to address these gaps and determine 'what works'. The study aimed to establish a research agenda that could guide future research by identifying implementation science research priorities to advance UHC. A three-round modified Delphi study design with a multi-country panel was employed. Initial implementation science research gaps were identified from two scoping reviews conducted by our team, supplemented by 10 papers that we identified through a search of Medline and CINAHL databases. We generated 64 research gaps that were shared with 272 participants in Round I. Round I responses were analysed using descriptive statistics and a cut-off of 75% to move to Round II. Round I qualitative analysis resulted in an additional 15 research gaps and one new topic area. Based on Round I findings, an improved set of research gaps was shared in Round II. Quantitative data in Round II were analysed using the same approach as Round I, using an 85% cut-off point. Open-ended responses were analysed thematically. Round II research gaps were then presented in a virtual workshop. Results from the workshop were analysed using weighted ranking analysis. Round I response rate was 34.9% with 43 research gaps across 12 topic areas. Round II response rate was 77.9% with 42 gaps across 13 topic areas that passed to the virtual workshop. The workshop response rate was 39%. Through this process, the top 10 ranked implementation science research gaps were identified. Identified research gaps are focused on assessing equity in the delivery of health services and financial risk protection interventions. Future research will further contextualise this research agenda with country-level actors
Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes
No full textUbiquitination is the key eukaryotic post-translational modification that governs protein degradation, localisation, and activity which is mediated by a concerted enzyme cascade. The largest superfamily of these enzymes include the Cullin-RING-Ligase (CRL) complexes. Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, encodes the critical proteins required for ubiquitination, but we do not yet understand the function of this pathway. Here the P. falciparum CRL complexes were characterised to reveal an essential but minimal repertoire controlled by two Cullin scaffolds. A PfCullin1-linked CRL complex, recruiting a single substrate receptor, was identified as being required for parasite inner-membrane biogenesis and DNA replication. A second CRL complex functioning through a PfCullin4 scaffold was identified that utilised a previously unidentified adaptor protein and receptors to support DNA replication. These results show that the P. falciparum CRL complexes are essential in both nuclear maintenance and membrane integrity.10.1038/s41598-025-05342-
Is the pay-for-performance program associated with better quality of life among type 2 diabetes patients, including those with gastrointestinal conditions, in Taiwan? A cross-sectional survey
No full textBACKGROUND: Many studies have shown that Taiwan's diabetes pay-for-performance (P4P) program can improve several patients' clinical outcomes; however, it remains unclear whether P4P initiatives yield effects on health-related quality of life (HRQoL) for all diabetes patients as well as those with comorbidities, especially comorbid gastrointestinal conditions. PURPOSE: In this study, we evaluated the effects of the diabetes P4P program on QoL among all patients as well as the effects of this program on QoL among patients with comorbid gastrointestinal conditions. METHODS: Data were collected across 6 hospitals. We used the five-level version of the EuroQol-5 Dimension (EQ-5D-5L) to obtain scores for health disutility. The scores for these measures were subsequently predicted via a generalized linear model (GLM) with a gamma distribution. We also applied propensity score weighting (PSW) to adjust for potential selection bias. RESULTS: After PSW, P4P program participation was found to be significantly correlated with lower EQ-5D disutility scores among all patients (parameter = -0.169, [-0.325, -0.012], P = 0.034). Additionally, P4P program participation was significantly correlated with a lower EQ-5D disutility score among patients with comorbid gastrointestinal conditions (parameter = -0.604, [-0.891, -0.317], P < 0.001). CONCLUSION: Our findings suggest that participation in the diabetes P4P program is associated with improved HRQoL among all patients with type 2 diabetes, including those with gastrointestinal comorbidities. A P4P model incorporating continuing education, coordinated care, and regular follow-up may be particularly beneficial in enhancing HRQoL for patients with gastrointestinal complications
Prevalence of depression and cognitive impairment and their inter-relationship and association with quality of life among older stroke survivors: the findings of a national survey in China
No full textBACKGROUND: Post-stroke depression (PSD) and post-stroke cognitive impairment (PSCI) are prevalent neuropsychiatric problems that are associated with high disability burden and low quality of life (QoL). This study explored the PSD-PSCI network, along with the interaction and association with QoL among Chinese older stroke survivors. METHODS: Data from the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey were obtained to investigate the inter-relationship between PSD and PSCI among older stroke survivors. Central and bridge symptoms within the PSD-PSCI network and their association with QoL were explored. Depressive symptoms, cognitive impairment and QoL were measured using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10), Mini-Mental State Examination and the WHO QoL-brief version, respectively. RESULTS: The prevalence of PSD and PSCI among older stroke survivors was 31.5% and 22.1%, respectively. In the PSD-PSCI network, 'feeling blue/depressed' (CESD3, strength: 1.117) and 'Attention and calculation' (At_C, strength: 0.972) were the most influential symptoms, while 'Naming' (Nam, bridge strength: 0.175) was the most significant bridge symptom. Notably, 'Sleep disturbances' (CESD10) had the strongest association with lower QoL. CONCLUSION: This study revealed that both PSD and PSCI were prevalent among older stroke survivors. The key central and bridge symptoms in the PSD-PSCI network, along with those symptoms that negatively impact on QoL, should be prioritised in targeted interventions to enhance treatment outcomes in this population
The effect of antimicrobial stewardship interventions upon antimicrobial consumption and appropriateness in Vietnamese district hospitals: a cluster randomised trial
No full textBACKGROUND: Inappropriate antimicrobial use is a key driver of antimicrobial resistance. Antimicrobial stewardship (AMS) promotes the judicious use of antimicrobials to address this problem. This study evaluated the effect of an AMS program on antimicrobial prescribing practices in district hospitals in Vietnam. METHODS: A cluster randomised controlled trial was conducted in 16 district hospitals in northern and southern Vietnam over four months. Hospitals were randomly assigned to intervention or control groups. Interventions included establishing AMS committees and teams, distributing antimicrobial guidelines, training healthcare workers, providing patient educational material, and conducting periodic audits with feedback on antimicrobial prescribing. Co-primary outcomes were the "difference in differences" in (i) total antimicrobial consumption and (ii) inappropriate prescribing according to standardised guidelines, before and after the intervention, between intervention and control groups. Secondary outcomes included antimicrobial costs and all-cause mortality. After the intervention period, control sites also received the AMS program. Trial registry: Australia and New Zealand Clinical Trials Registry (ANZCTR) number 12622000715774. FINDINGS: A total of 877 and 1220 antimicrobial prescriptions were reviewed in intervention hospitals, and 1277 and 1454 prescriptions in control hospitals at baseline and post-intervention. Inappropriate antimicrobial prescribing exceeded 60% in each hospital at baseline. After the intervention, inappropriate prescribing in the intervention group reduced by 6.3% (95% CI -10.9%, -1.7%) relative to the control group. Total antimicrobial consumption did not differ between groups, but antimicrobial costs reduced in the intervention group. No difference in all-cause mortality was observed. INTERPRETATION: AMS interventions modestly reduced inappropriate antimicrobial prescribing in district hospitals in Vietnam, underscoring the importance of AMS in resource-limited settings. FUNDING: The Australian Department of Foreign Affairs and Trade
Water Balance and Evaporation for Two Intermittent Estuarine Lakes
No full textThe management of small intermittently open or closed estuaries (ICOLLs) requires the prediction of lake water levels and the probability of breaching of the entrance barrier in real time, seasonally, and long term. The water balance is a key tool that in turn requires prediction of the open water evaporation. The drivers of the water balance of two ICOLLs on the south-east coast of Australia were studied: The two ICOLLs, Durras Lake and Lake Wollumboola, have very different morphologies: Durras Lake is a drowned stream valley with a largely steep, forested catchment, while Lake Wollumboola is a back-dune lagoon ICOLL with a wider, shallow water body. For these small estuaries, hydrologic and geomorphic data are generally limited or unavailable; hence, methods were developed to use data routinely available, primarily from government agencies, without using regionally averaged or “text book” parameter values. For both lakes, evaporation was shown to be on average larger than either of the inflows from the catchment or from the direct rainfall on the lakes; thus, evaporation must be reliably predicted for use in the water balance. The calculated evaporation agreed with widely used but data-intensive formulas. For each ICOLL a robust linear correlation of lake evaporation with the incident solar radiation accounted for 94% of the variance in the evaporation. The seasonal variation of evaporation fitted a cosine curve, again accounting for 94% of the variance of the evaporation. Validation of the water balances using the evaporation-solar correlation and a derived runoff coefficient provided a close match with the historical record. On most days, the water loss from the lakes by evaporation was larger than the sum of the inflows from catchment runoff and direct rainfall on the lakes. Storms of duration 1–3 days rapidly increased the water storages and the lake levels, potentially leading to breaching of the entrance barrier. This fluctuating balance drives the intermittent behaviour of these ICOLLs and emphasises the importance of accurately assessing the lake evaporation
Generation of an iPSC line (with isogenic control) from the PBMCs of a COL6A1 (c.1056 + 2T > A) Bethlem myopathy patient
No full textTo produce an in vitro model of Bethlem myopathy, we reprogrammed the peripheral blood mononuclear cells (PBMCs) of a patient with a heterozygous COL6A1 c.1056 + 2T > A mutation at the exon/intron 14 boundary of the COL6A1 gene to induced pluripotent stem cells (iPSCs). Using CRISPR/Cas9 gene editing, we corrected the mutation to generate an isogenic control line. Both the patient and isogenic control iPSCs show a normal karyotype, express pluripotency markers and can differentiate into cell states that represent the three embryonic germ layers (endoderm, mesoderm and ectoderm). These cell lines will be differentiated and used to explore disease mechanisms and evaluate novel therapeutics for Bethlem myopathy