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29 pages, 4560 KB  
Article
Neuroimaging and Genetic Markers of Cerebral Small Vessel Disease and Cognitive Outcomes: A Systematic Review and Meta-Analysis (NEUROGEN-SVD Study)
by Chelsea Jin, Roy G. Beran and Sonu M. M. Bhaskar
Diagnostics 2025, 15(20), 2585; https://doi.org/10.3390/diagnostics15202585 - 13 Oct 2025
Viewed by 434
Abstract
Background/Objectives: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and dementia. The comparative prognostic value of MRI-based neuroimaging markers and genetic risk factors such as the APOE ε4 allele for cognitive outcomes remains uncertain. The objectives of this study [...] Read more.
Background/Objectives: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and dementia. The comparative prognostic value of MRI-based neuroimaging markers and genetic risk factors such as the APOE ε4 allele for cognitive outcomes remains uncertain. The objectives of this study were to estimate the pooled prevalence of cognitive impairment in CSVD, evaluate the associations of key neuroimaging markers (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes) and APOE ε4 with cognitive outcomes, and assess their diagnostic performance. Methods: This study included a systematic review and meta-analysis in accordance with PRISMA and MOOSE guidelines, searching five databases (2005–2025). Eligible studies included adults with CSVD and MRI-visible markers reporting cognitive outcomes (mild cognitive impairment [MCI], global cognitive impairment [GCI], all-cause dementia [ACD], vascular dementia [VaD], and Alzheimer’s disease [AD]). Thirty-nine studies comprising 18,425 participants were included. Pooled prevalence and associations were estimated using random-effects models, and diagnostic accuracy was evaluated. Certainty of evidence was assessed using the GRADE framework. Results: The pooled prevalence of GCI in CSVD was 57% (95% CI: 51–62%), while MCI prevalence was 46% (95% CI: 42–51%). WMHs were strongly associated with VaD (OR 10.35, 95% CI: 7.32–14.64), lacunes with ACD (OR 3.18, 95% CI: 1.24–8.20), and CMBs with AD (OR 1.52, 95% CI: 1.04–2.24). APOE ε4 carriage increased the risk of GCI (OR 1.80, 95% CI: 1.41–2.29). Across markers, diagnostic sensitivity was low, specificity was moderate-to-high, and AUROC values were modest. GRADE certainty ranged from low to moderate, with the highest confidence for WMHs and VaD. Conclusions: CSVD-related MRI markers and APOE ε4 are significantly associated with both early and late cognitive outcomes, supporting the integrated vascular–neurodegenerative continuum. The limited diagnostic sensitivity and variable certainty of evidence highlight the need for harmonized definitions, lesion quantification, and multimodal imaging–genetic approaches to improve early detection and risk stratification of CSVD-related cognitive impairment. Full article
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23 pages, 7111 KB  
Article
Pulmonary Embolism After Acute Ischaemic Stroke (PEARL-AIS): Global Prevalence, Risk Factors, Outcomes, and Evidence Grading from a Meta-Analysis
by Darryl Chen, Yuxiang Yang and Sonu M. M. Bhaskar
Neurol. Int. 2025, 17(10), 168; https://doi.org/10.3390/neurolint17100168 - 12 Oct 2025
Viewed by 253
Abstract
Objectives: Pulmonary embolism (PE) is an uncommon but potentially fatal complication of acute ischaemic stroke (AIS). Its global burden and prevention remain incompletely defined. We performed a systematic review and meta-analysis (PEARL-AIS) to estimate prevalence, risk factors, outcomes, and prophylactic efficacy, with GRADE [...] Read more.
Objectives: Pulmonary embolism (PE) is an uncommon but potentially fatal complication of acute ischaemic stroke (AIS). Its global burden and prevention remain incompletely defined. We performed a systematic review and meta-analysis (PEARL-AIS) to estimate prevalence, risk factors, outcomes, and prophylactic efficacy, with GRADE evidence appraisal. Methods: Following PRISMA 2020 and MOOSE guidelines, five databases (PubMed, Embase, Cochrane, Scopus, Web of Science) were searched (1995–2024). The protocol was prospectively registered (OSF s25ny). Random-effects models (DerSimonian–Laird; REML sensitivity) were used to pool prevalence and odds ratios; heterogeneity was evaluated with I2, Cochran’s Q, and τ2. Influence (leave-one-out) and subgroup analyses for prevalence and mortality of PE in AIS were explored. Bias was assessed using the Modified Jadad Scale; overall certainty was graded with the GRADE framework. Results: Twenty-four studies met the inclusion criteria (n = 25,666,067), of which seventeen studies (n = 23,637,708) contributed to pooled prevalence analyses. The pooled prevalence of PE after AIS was 0.40% (95% CI 0.33–0.49), approximately six-fold higher than in the general population, with considerable heterogeneity (I2 > 90%, Cochrane classification). The pooled mortality among AIS patients with PE was 12.9% (95% CI 1.6–31.7). Mortality risk was significantly higher in AIS patients with PE (OR 4.96, 95% CI 2.98–8.24). Atrial fibrillation (29%), cancer (19%), and smoking (23%) were common; hypertension (54%) and diabetes (23%) were prevalent but not predictive, with diabetes showing a paradoxical protective association (OR 0.88, 95% CI 0.84–0.92). Pharmacological prophylaxis was associated with a reduced risk of PE (OR 0.64, 95% CI 0.46–0.90; I2 = 0%), supported by moderate-certainty evidence. Conclusions: PE is an uncommon but often fatal complication of AIS. Traditional venous thromboembolism predictors underperform in this context, suggesting a stroke-specific thromboinflammatory mechanism linking the brain and lung axis. Despite considerable heterogeneity and low-to-moderate certainty of evidence, pharmacological prophylaxis demonstrates a consistent protective effect. Systematic PE surveillance and tailored prophylactic strategies should be integral to contemporary stroke care, while future studies should refine risk stratification and elucidate the mechanistic underpinnings of this brain–lung thromboinflammatory continuum. Full article
(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)
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20 pages, 1456 KB  
Article
DirectFS: An RDMA-Accelerated Distributed File System with CPU-Oblivious Metadata Indexing
by Lingjun Jiang, Zhaoyao Zhang, Ruixuan Ni and Miao Cai
Electronics 2025, 14(19), 3778; https://doi.org/10.3390/electronics14193778 - 24 Sep 2025
Viewed by 513
Abstract
The rapid growth of data-intensive applications has imposed significant demands on the performance of distributed file systems, particularly in metadata operations. Traditional systems rely heavily on metadata servers to handle indexing tasks, leading to Central Processing Unit (CPU) bottlenecks and increased latency. To [...] Read more.
The rapid growth of data-intensive applications has imposed significant demands on the performance of distributed file systems, particularly in metadata operations. Traditional systems rely heavily on metadata servers to handle indexing tasks, leading to Central Processing Unit (CPU) bottlenecks and increased latency. To address these challenges, we propose Direct File System (DirectFS), an Remote Direct Memory Access (RDMA)-accelerated distributed file system that offloads metadata indexing to clients by leveraging one-sided RDMA operations. Further, we propose a range of techniques, including hash-based namespace indexing and hotness-aware metadata prefetching, to fully unleash the performance potential of RDMA hardware. We implement DirectFS on top of Moose File System (MooseFS) and compare DirectFS with state-of-the-art distributed file systems using a variety of Filebench v1.4.9.1 and MDTest from the IOR suite v4.0.0 workloads. Evaluation results demonstrate that DirectFS achieves significant performance improvements for metadata-intensive benchmarks compared to other file systems. Full article
(This article belongs to the Section Computer Science & Engineering)
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16 pages, 1011 KB  
Article
Molecular Identification of Cryptic Cysticercosis: Taenia spp. in Wild and Domestic Intermediate Hosts in Kazakhstan
by Vladimir Kiyan, Ainura Smagulova, Rabiga Uakhit, Carlos Hermosilla, Lyudmila Lider, Karina Jazina and Nurassyl Manapov
Diversity 2025, 17(9), 655; https://doi.org/10.3390/d17090655 - 18 Sep 2025
Viewed by 412
Abstract
Cysticercosis in wild and domestic ungulates, caused by the larval metacestode stages of Taenia hydatigena and Taenia multiceps (formerly known as Cysticercus tenuicollis and Coenurus cerebralis, respectively), is a widespread parasitic disease and poses a significant concern worldwide, particularly in endemic regions. [...] Read more.
Cysticercosis in wild and domestic ungulates, caused by the larval metacestode stages of Taenia hydatigena and Taenia multiceps (formerly known as Cysticercus tenuicollis and Coenurus cerebralis, respectively), is a widespread parasitic disease and poses a significant concern worldwide, particularly in endemic regions. Although Taenia species have been extensively studied globally, their epidemiology and genetic diversity in Kazakhstan remain poorly understood. In this study, wild (roe deer, red deer, moose) and domestic (cattle, sheep) ungulates, serving as intermediate hosts for Taenia spp., were examined for cysticerci in muscle tissues and internal organs. Phylogenetic analysis and pairwise nucleotide variation assessments of the cox1 and nad1 genes were conducted. An overall prevalence of 5.2% was recorded among 1370 ruminant carcasses (cattle = 773, sheep = 563, roe deer = 25, moose = 9), with infection rates of 0.6% in cattle, 1.1% in sheep, 8.0% in roe deer, and 11.1% in moose. Cattle, sheep, and moose were infected with T. hydatigena, while roe deer were infected with T. multiceps. DNA sequence analysis of all isolates revealed four nad1 gene haplotypes for T. hydatigena, with Hap_3 being the most common (10 isolates). Phylogenetic analysis showed that T. multiceps isolates from roe deer clustered within the clade defined by the reference sequences for this species. This study provides important baseline data on the prevalence and genetic variation in T. hydatigena and T. multiceps in Kazakhstan and lays the groundwork for future research on the epidemiology and population genetics of Taenia species in the region. Full article
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39 pages, 1706 KB  
Systematic Review
Improving Vaccine Coverage Among Older Adults and High-Risk Patients: A Systematic Review and Meta-Analysis of Hospital-Based Strategies
by Flavia Pennisi, Stefania Borlini, Rita Cuciniello, Anna Carole D’Amelio, Rosaria Calabretta, Antonio Pinto and Carlo Signorelli
Healthcare 2025, 13(14), 1667; https://doi.org/10.3390/healthcare13141667 - 10 Jul 2025
Viewed by 1972
Abstract
Background/Objectives: Adult vaccination remains suboptimal, particularly among older adults and individuals with chronic conditions. Hospitals represent a strategic setting for improving vaccination coverage among these high-risk populations. This systematic review and meta-analysis evaluated hospital-based interventions aimed at enhancing vaccine uptake in adults aged [...] Read more.
Background/Objectives: Adult vaccination remains suboptimal, particularly among older adults and individuals with chronic conditions. Hospitals represent a strategic setting for improving vaccination coverage among these high-risk populations. This systematic review and meta-analysis evaluated hospital-based interventions aimed at enhancing vaccine uptake in adults aged ≥60 years or 18–64 years with at-risk medical conditions. Methods: We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. Searches in PubMed, EMBASE, and Scopus identified studies published in the last 10 years evaluating hospital-based interventions reporting vaccination uptake. The risk of bias was assessed using validated tools (NOS, RoB 2, ROBINS-I, QI-MQCS). A meta-analysis was conducted for categories with ≥3 eligible studies reporting pre- and post-intervention vaccination coverage in the same population. Results: We included 44 studies. Multi-component strategies (n = 21) showed the most consistent results (e.g., pneumococcal uptake from 2.2% to 43.4%, p < 0.001). Reminder-based interventions (n = 4) achieved influenza coverage increases from 31.0% to 68.0% and a COVID-19 booster uptake boost of +38% after SMS reminders. Educational strategies (n = 11) varied in effectiveness, with one study reporting influenza coverage rising from 1.6% to 12.2% (+662.5%, OR 8.86, p < 0.01). Standing order protocols increased pneumococcal vaccination from 10% to 60% in high-risk adults. Hospital-based catch-up programs improved DTaP-IPV uptake from 56.2% to 80.8% (p < 0.001). For patient education, the pooled OR was 2.11 (95% CI: 1.96–2.27; p < 0.001, I2 = 97.2%) under a fixed-effects model, and 2.47 (95% CI: 1.53–3.98; p < 0.001) under a random-effects model. For multi-component strategies, the OR was 2.39 (95% CI: 2.33–2.44; p < 0.001, I2 = 98.0%) with fixed effects, and 3.12 (95% CI: 2.49–3.92; p < 0.001) with random effects. No publication bias was detected. Conclusions: Hospital-based interventions, particularly those using multi-component approaches, effectively improve vaccine coverage in older and high-risk adults. Embedding vaccination into routine hospital care offers a scalable opportunity to reduce disparities and enhance population-level protection. Future policies should prioritize the institutional integration of such strategies to support healthy aging and vaccine equity. Full article
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13 pages, 702 KB  
Review
Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis
by Manuela Chiavarini, Jacopo Dolcini, Giorgio Firmani, Kasey J. M. Brennan, Andrès Cardenas, Andrea A. Baccarelli and Pamela Barbadoro
Int. J. Mol. Sci. 2025, 26(14), 6610; https://doi.org/10.3390/ijms26146610 - 10 Jul 2025
Viewed by 986
Abstract
LC continues to be the leading cause of cancer mortality globally, among both males and females, representing a major public health challenge. The impact of mitochondria on human health and disease is a rapidly growing focus in scientific research, due to their critical [...] Read more.
LC continues to be the leading cause of cancer mortality globally, among both males and females, representing a major public health challenge. The impact of mitochondria on human health and disease is a rapidly growing focus in scientific research, due to their critical roles in cellular survival and death. Mitochondria play an important role in controlling imperative cellular parameters, and alterations in mtDNAcn might be crucial for LC development. MtDNAcn has been studied as a possible marker for LC risk, but its role in prevention is still unclear. This review and meta-analysis aims to summarize the current evidence and provide an overall estimate of the relationship between the mtDNA copy number in human samples like blood and sputum. PubMed, Web of Science, and Scopus databases were used for studies published up to February 2024, following PRISMA and MOOSE guidelines. Studies were combined using a random-effects model, and we assessed the heterogeneity between studies with the chi-square-based Cochran’s Q statistic and the I2 statistic. Publication bias was checked using Begg’s and Egger’s tests. Five studies, including a total of 3.748 participants, met the eligibility criteria. The MtDNA copy number was measured in blood or sputum samples and compared across different quantiles. The pooled analysis did not find a significant association between the mtDNA copy number and LC risk (OR = 0.94; 95% CI: 0.49–1.78). Moreover, when looking at different study designs, no significant results were found, due to the small number of studies available. No significant publication bias was detected. Further studies are needed to better understand the connection between the mtDNA copy number and LC risk and to better understand the role of potential confounders. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Lung Health and Disease)
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32 pages, 1820 KB  
Systematic Review
Association and Prevalence of Lower Urinary Tract Symptoms in Individuals with Sarcopenia: A Systematic Review and Meta-Analysis
by Lek-Hong Tan and Eric Chieh-Lung Chou
Medicina 2025, 61(7), 1214; https://doi.org/10.3390/medicina61071214 - 3 Jul 2025
Viewed by 1055
Abstract
Background and Objectives: Sarcopenia and lower urinary tract symptoms (LUTSs) are both prevalent among older adults and may share underlying pathophysiological mechanisms. However, their association has not been systematically quantified. This systematic review and meta-analysis aimed to evaluate the association between sarcopenia [...] Read more.
Background and Objectives: Sarcopenia and lower urinary tract symptoms (LUTSs) are both prevalent among older adults and may share underlying pathophysiological mechanisms. However, their association has not been systematically quantified. This systematic review and meta-analysis aimed to evaluate the association between sarcopenia and LUTSs, including the pooled estimates of prevalence and odds ratios (ORs), and to explore the influence of diagnostic definitions and study-level factors. Materials and Methods: A comprehensive literature search was conducted using PubMed and Embase for studies published between 1 January 2000 and 26 April 2025. This study adhered to PRISMA and MOOSE guidelines and was registered in PROSPERO (CRD420251037459). Eligible observational studies reported LUTS prevalence or ORs in individuals with sarcopenia, low muscle strength (LMS), low lean mass (LLM), low gait speed (LGS), or sarcopenia risk identified by SARC-F (score ≥4). Pooled ORs and prevalence rates were calculated using a random-effects model. Subgroup analyses were performed based on sarcopenia definitions—Asian Working Group for Sarcopenia (AWGS) and European Working Group on Sarcopenia in Older People (EWGSOP)—as well as LUTS subtypes and diagnostic components. Univariate meta-regression assessed associations with age, BMI, sex distribution, WHO region, and risk of bias. Results: Twenty-five studies comprising 84,484 participants were included. Sarcopenia was significantly associated with LUTSs (pooled OR = 1.78; 95% CI: 1.29–2.45; p < 0.001), with a pooled LUTS prevalence of 43.2% (95% CI: 26.9–61.0%). Stronger associations were observed in studies using AWGS diagnostic criteria (OR = 2.24; 95% CI: 1.41–3.56; p = 0.001), in those evaluating severe sarcopenia (OR = 1.66; 95% CI: 1.03–2.68; p = 0.038), and in institutionalized populations (OR = 3.68; 95% CI: 2.18–6.24; p < 0.001) compared to community-dwelling populations (OR = 1.43; 95% CI: 1.06–1.92; p = 0.018). Sarcopenia risk identified by SARC-F (score ≥4) showed the strongest association with LUTSs (OR = 3.20; 95% CI: 1.92–5.33; p < 0.001). Significant associations were also found for LLM (OR = 1.52; 95% CI: 1.19–1.95; p = 0.001) and LGS (OR = 1.37; 95% CI: 1.06–1.76; p = 0.015), but not for LMS (OR = 0.94; 95% CI: 0.47–1.89; p = 0.871). Exploratory analyses comparing LLM diagnostic modalities—including standardized criteria (ASMI, ASM/BMI), imaging-based methods (SMI, PMA), and surrogate measures (calf circumference)—revealed no significant differences (all p > 0.05). Heterogeneity was high (I2 > 90%). Egger’s test indicated no evidence of publication bias (p = 0.838), and trim-and-fill analysis did not affect the pooled estimates. Conclusions: Sarcopenia—particularly in its severe forms—is significantly associated with LUTSs. Additionally, individuals who screened positive for sarcopenia using the SARC-F tool demonstrated a heightened risk of LUTSs. Subgroup analyses revealed a stronger association in institutionalized populations, suggesting that care setting may modify risk. These findings underscore the importance of assessing muscle health in older adults with urinary symptoms. Standardization of diagnostic criteria and longitudinal studies are needed to clarify causality and guide targeted interventions. Full article
(This article belongs to the Section Urology & Nephrology)
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24 pages, 2803 KB  
Review
Mammal Fauna Changes in Baltic Countries During Last Three Decades
by Linas Balčiauskas, Valdis Pilāts and Uudo Timm
Diversity 2025, 17(7), 464; https://doi.org/10.3390/d17070464 - 1 Jul 2025
Viewed by 1584
Abstract
We examined three decades of changes in the mammal fauna of Estonia, Latvia, and Lithuania in the context of climate variability, land use transformation, and anthropogenic pressures. We compiled distributional, abundance, and status data from publications, atlases, official game statistics, and long-term monitoring [...] Read more.
We examined three decades of changes in the mammal fauna of Estonia, Latvia, and Lithuania in the context of climate variability, land use transformation, and anthropogenic pressures. We compiled distributional, abundance, and status data from publications, atlases, official game statistics, and long-term monitoring programs, and we evaluated trends using compound annual growth rates or temporal indices. Our review identified losses such as regional extinctions of garden dormice and European mink, declines in small insectivores (e.g., pond bats and shrews) and herbivores (e.g., Microtus voles), and the contraction of boreal specialists (e.g., Siberian flying squirrels). However, we also identified gains, including increases in ungulate numbers (e.g., roe deer, red deer, fallow deer, moose, and wild boars before African swine fewer outbreak) and the recovery of large carnivores (e.g., wolves and lynxes). Invasions by non-native species (e.g., American mink, raccoon dog, and raccoon) and episodic disturbances, such as African swine fever and the “anthropause” caused by the SARS-CoV-2 pandemic, have further reshaped community composition. The drivers encompass climatic warming, post-socialist forest succession, intensified hunting management, and rewilding policies, with dispersal capacity mediating the responses of species. Our results underscore the dual legacy of historical land use and contemporary climate forcing in structuring the fauna dynamics of Baltic mammal communities in the face of declining specialists and invasive taxa. Full article
(This article belongs to the Special Issue Diversity in 2025)
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18 pages, 1311 KB  
Review
Bite by Bite: How Ungulate Browsing Shapes North America’s Forest Future
by Darius Hardalau, Vladut Stefanescu, Mindaugas Bakševičius, Michael Manton, Charles Ruffner, Gediminas Brazaitis, Georgeta Ionescu and Ovidiu Ionescu
Forests 2025, 16(7), 1079; https://doi.org/10.3390/f16071079 - 28 Jun 2025
Viewed by 723
Abstract
Ungulate browsing represents a contemporary issue for forest development, influencing forest regeneration, composition, and management practices across the world, especially in North America. This review synthesizes findings from 101 studies conducted between 1980 and 2025 to examine patterns of herbivory damage through browsing [...] Read more.
Ungulate browsing represents a contemporary issue for forest development, influencing forest regeneration, composition, and management practices across the world, especially in North America. This review synthesizes findings from 101 studies conducted between 1980 and 2025 to examine patterns of herbivory damage through browsing by moose, elk, white-tailed deer, black-tailed deer, and bison. Despite regional variation, high ungulate density consistently emerges as the primary factor driving browsing intensity and ecological and economic impact, leading to decreased social acceptance of coexistence with ungulates. This review highlights the selective suppression of palatable species such as balsam fir, red oak, and white cedar, leading to shifts toward less-preferred conifers. Preventive and control measures, ranging from fencing and repellents to regulated hunting, are widely implemented but vary in effectiveness and social acceptability. Although predator presence is an evident controlling factor, it was not statistically associated in this review with reduced browsing, nor with behavioral or trophic cascade effects. Ultimately, this study underscores the importance of integrated management strategies that combine silvicultural adaptation, population control, and, where feasible, predator reintroduction to ensure forest resilience and sustainability in the face of increasing pressure from climate change. Full article
(This article belongs to the Special Issue Biodiversity and Ecosystem Functions in Forests)
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18 pages, 1456 KB  
Systematic Review
Prevalence of Sexual Dysfunction with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): An Updated Systematic Review and Meta-Analysis
by Saad Alshahrani, Basem A. Fathi, Tamer A. Abouelgreed and Ashraf El-Metwally
Medicina 2025, 61(6), 1110; https://doi.org/10.3390/medicina61061110 - 19 Jun 2025
Cited by 1 | Viewed by 3520
Abstract
Background and Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition linked to substantial urogenital symptoms, notably sexual dysfunction. This meta-analysis sought to determine the overall prevalence of sexual dysfunction in men with CP/CPPS, considering the four primary categories: desire, [...] Read more.
Background and Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition linked to substantial urogenital symptoms, notably sexual dysfunction. This meta-analysis sought to determine the overall prevalence of sexual dysfunction in men with CP/CPPS, considering the four primary categories: desire, arousal, orgasm, and pain disorders. Materials and Methods: A systematic literature review, following MOOSE guidelines, was performed across four electronic databases (PubMed, Embase, Web of Science, and Google Scholar) for the period from January 2000 to 2025. The review included observational studies reporting the prevalence of sexual dysfunction in men with CP/CPPS. Data extraction and quality assessment were conducted independently by two reviewers. A random-effects model was used to calculate the pooled prevalence estimates and 95% confidence intervals. Heterogeneity was evaluated using I2, τ2, and Chi-squared tests, while publication bias was assessed via funnel plot asymmetry and Egger’s test. Results: The meta-analysis incorporated data from 26 studies, representing a total of 20,127 participants. The pooled prevalence of overall sexual dysfunction was 59% (95% CI: 34–81%; I2 = 98%) across six studies and 5333 participants. Pooled erectile dysfunction (ED) prevalence was 34% (95% CI: 26–42%; I2 = 99%) across 24 studies with 20,127 participants, whereas pooled prevalence for premature ejaculation (PE) was 35% (95% CI: 22–49%; I2 = 98%) across 10 studies with 13,686 participants. Significant heterogeneity was observed across all analyses (I2 > 98%). Funnel plot analysis suggested potential asymmetry, but Egger’s test was non-significant (p = 0.7034). Conclusions: This meta-analysis confirms the high prevalence of sexual dysfunction, including ED and PE, in men with CP/CPPS, providing a comprehensive estimate of its burden. The substantial heterogeneity observed underscores the need for further research to identify contributing factors and develop targeted interventions. Full article
(This article belongs to the Section Urology & Nephrology)
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17 pages, 990 KB  
Systematic Review
Combination of Drugs in the Treatment of Alcohol Use Disorder: A Meta-Analysis and Meta-Regression Study
by João Vitor Guimarães Mandaji, Maria Olivia Pozzolo Pedro, Kae Leopoldo, João Pini Alemar, Julio Torales, Antonio Ventriglio and João Mauricio Castaldelli-Maia
Brain Sci. 2025, 15(6), 542; https://doi.org/10.3390/brainsci15060542 - 22 May 2025
Viewed by 6064
Abstract
Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely [...] Read more.
Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely available. Methods: We searched for randomized clinical trials through PubMed, ClinicalTrials.gov, Cochrane Library, SciELO, Biblioteca Virtual em Saúde, and Google Scholar databases. Original clinical trials published in English and Portuguese were selected. Data collection followed the PRISMA and MOOSE guidelines and was assessed using the Risk of Bias Tool (RoB 2). Heterogeneity was assessed using the Q test. Meta-regression was conducted using Egger’s regression method. Twelve articles were finally included in the analysis, and random-effects models were applied on aggregate trial results. Results: The meta-analysis found that combination therapies led to an average 4.045% increase in abstinence rates (95% CI: 0.415% to 7.675%) compared to monotherapies. Meta-regression showed a strong positive association between the use of naltrexone, acamprosate, and sertraline—either alone or in combination—and treatment success in AUD. The meta-regression also highlighted the impact of patients’ variables, such as gender, age, country, and psychiatric comorbidities, on their treatment outcomes. These findings may identify a potential therapeutic pathway promoting alcohol abstinence, further supported by a Number Needed to Treat (NNT) of 25, as an acceptable value for substance use disorder treatments. Conclusions: Combined pharmacotherapies are more effective than monotherapy in enhancing abstinence rates in AUD treatment, with naltrexone, acamprosate, and sertraline emerging as key adjunctive agents promoting these outcomes. These findings underscore the complexity of AUD as a multifactorial psychiatric condition and highlight the potential of combined pharmacotherapy as a promising strategy for achieving better treatment outcomes, particularly in terms of abstinence rates. Full article
(This article belongs to the Section Neuropsychiatry)
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16 pages, 1847 KB  
Systematic Review
Lower Urinary Tract Symptoms in Uterine Myoma: A Systematic Review and Meta-Analysis
by Lek-Hong Tan and Li-Hsien Tsai
Medicina 2025, 61(5), 890; https://doi.org/10.3390/medicina61050890 - 14 May 2025
Viewed by 1382
Abstract
Background and Objectives: Lower urinary tract symptoms (LUTSs) are prevalent among patients with uterine myoma (UM); however, these health issues have not been systematically evaluated. To address this research gap, this systematic review and meta-analysis synthesizes existing findings on the prevalence estimates [...] Read more.
Background and Objectives: Lower urinary tract symptoms (LUTSs) are prevalent among patients with uterine myoma (UM); however, these health issues have not been systematically evaluated. To address this research gap, this systematic review and meta-analysis synthesizes existing findings on the prevalence estimates and odds ratios for LUTSs in patients with UM. Materials and Methods: A systematic literature search using PubMed and Embase was conducted for articles published between 1 January 2000 and 24 September 2023. The search and review processes followed the PRISMA and MOOSE guidelines. This study was registered in PROSPERO (CRD42023474156). Data on the prevalence and odds ratios of LUTSs—including storage symptoms (frequency, urgency, nocturia), voiding symptoms, and urinary incontinence (UI) subtypes such as stress incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI)—were extracted. Pooled prevalence estimates and odds ratios were calculated using random-effects meta-analysis. Subgroup analyses and univariate meta-regression were conducted to examine associations with age, BMI, parity, WHO region, and risk of bias. The impact of UM size was assessed using standardized mean differences. Results: Of the 572 articles screened, 20 met the inclusion criteria. The overall pooled prevalence of LUTSs in UM patients was 49% (95% CI, 26–72%), with substantial heterogeneity across studies (I2 = 99.8%). The pooled prevalence for urinary frequency, urgency, nocturia, voiding dysfunction, and overall UI, SUI, UUI, and MUI ranged from 15% to 54%. SUI and UUI were significantly associated with UM (OR = 2.0, 95% CI: 1.2–3.3; OR = 1.5, 95% CI: 1.1–2.0, respectively). Hysterectomy was not associated with an improvement in overactive bladder (OAB) symptoms (OR = 1.9, 95% CI: 0.6–5.7). A larger UM size was not linked to worsening LUTS. Fourteen studies (70%) had some concerns about the risk of bias, while six studies (30%) had a low risk of bias. Egger’s test showed no significant publication bias (p = 0.19). Conclusions: Approximately half of patients with UM experience LUTSs or UI. The findings emphasize the need to consider urinary symptoms in UM management. Further research is warranted to reduce heterogeneity and explore treatment-specific outcomes. Full article
(This article belongs to the Section Urology & Nephrology)
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18 pages, 2117 KB  
Systematic Review
Unraveling the Hidden Burden of Gastrointestinal and Nutritional Challenges in Children with Fabry Disease: A Systematic Review with Meta-Analysis
by Vanessa Nadia Dargenio, Maria Natale, Stefania Paola Castellaneta, Giovanni la Grasta, Leonardo Paulucci, Costantino Dargenio, Ruggiero Francavilla and Fernanda Cristofori
Nutrients 2025, 17(7), 1194; https://doi.org/10.3390/nu17071194 - 29 Mar 2025
Cited by 1 | Viewed by 1441
Abstract
Background/Objectives: Fabry Disease (FD) is a multisystem X-linked lysosomal storage disorder that often manifests with nonspecific gastrointestinal (GI) symptoms, such as abdominal pain, diarrhea, and constipation. These symptoms may appear early in childhood, severely impacting quality of life and delaying diagnosis, and may [...] Read more.
Background/Objectives: Fabry Disease (FD) is a multisystem X-linked lysosomal storage disorder that often manifests with nonspecific gastrointestinal (GI) symptoms, such as abdominal pain, diarrhea, and constipation. These symptoms may appear early in childhood, severely impacting quality of life and delaying diagnosis, and may be linked to nutritional challenges. This systematic review aims to evaluate the prevalence, characteristics, clinical relevance, and nutritional aspects of GI manifestations in pediatric FD patients to aid in early recognition and improve outcomes. Methods: A systematic literature search with meta-analysis adhering to PRISMA and MOOSE guidelines was conducted across PubMed, Web of Science, and Google Scholar from inception to November 2024 using fixed inclusion and exclusion criteria. Data were extracted by two reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, when necessary. Pooled analysis was performed by a random-effects model; heterogeneity was assessed using the I2 method. A quality assessment appraisal of the studies was carried out using the ROBINS-I tool. Results: The review encompassed 18 studies involving 736 pediatric patients. The evaluation of the pooled prevalence of GI symptoms in FD patients was 53% (95% CI 38–68%, I2 90%), with abdominal pain being the most frequent (pooled prevalence of 46% (95% CI 33–60%, I2 86%)). Symptoms often presented early, with a summarized standardized mean difference between the mean age of symptom onset and the mean age at FD diagnosis of 2.07 years (95% CI of 0.56–3.57, I2 42%, p < 0.01). Nutritional issues, including reduced food intake and potential malabsorption, were reported in cases with severe GI symptoms, contributing to growth impairments. Conclusions: GI symptoms frequently constitute the earliest clinical manifestation of FD in children. Their nonspecific nature underscores the importance of heightened clinical suspicion for timely diagnosis. Early intervention, including enzyme replacement therapy and tailored nutritional strategies, can alleviate symptoms, improve quality of life, and prevent disease progression. Multidisciplinary approaches are essential to optimize patient outcomes and further research into the pathophysiology and management of GI symptoms in FD is warranted. Full article
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17 pages, 5413 KB  
Systematic Review
Placental Location Site and Associated Intrapartum, Postpartum, and Neonatal Complications: A Comprehensive Review and Meta-Analysis
by Dayna D. Whitcombe, Zhuopei Hu, Songthip T. Ounpraseuth and Everett F. Magann
J. Clin. Med. 2025, 14(5), 1649; https://doi.org/10.3390/jcm14051649 - 28 Feb 2025
Viewed by 1204
Abstract
Background/Objectives: Adverse intrapartum, postpartum, and neonatal complications have been linked to placenta implantations sites. However, different reviews have led to contrasting conclusions about placental locations and pregnancy outcomes. We aim to determine if there is a relationship between the placental implantation site and [...] Read more.
Background/Objectives: Adverse intrapartum, postpartum, and neonatal complications have been linked to placenta implantations sites. However, different reviews have led to contrasting conclusions about placental locations and pregnancy outcomes. We aim to determine if there is a relationship between the placental implantation site and intrapartum, postpartum, and neonatal outcomes. Methods: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed during this review. The literature search used PubMed, CINAHL, and Embase. Years searched was not a study limitation. Only articles in English were included. Two authors reviewed the abstracts. Results: Of 40 articles identified as specific to intrapartum, postpartum, and/or neonatal complications (with some articles overlapping categories), 19 included intrapartum complications, 19 included postpartum complications, and 22 included neonatal complications. Pregnancies with a midline placenta (compared to a lateral placenta) had a greater likelihood of macrosomia/LGA infant (odds ratio (OR), 1.52 (95% CI: 1.22–1.90)) and lesser likelihood to have non-cephalic presentation (OR, 0.17 (95% CI: 0.06–0.51)), FGR/SGA infant (OR, 0.68 (CI: 0.55–0.85)), and retained placenta (OR, 0.33 (95% CI: 0.22–0.50)). Pregnancies with a low-lying placenta (compared to within uterine corpus) were more likely to have non-elective cesarean section (OR, 1.94 (95% CI: 1.06–3.55)) and postpartum hemorrhage (OR 1.49 (95% CI: 1.12–1.97)). Conclusions: Significant associations between placental location site and intrapartum complications (non-cephalic presentation, non-elective cesarean section), postpartum complications (postpartum hemorrhage, retained placenta), and neonatal complications (FGR/SGA, Macrosomia/LGA) were identified. There were no significant associations identified between the placental location site and several neonatal complications, including Apgar < 7 at 5 min, NICU admission, IUFD, and neonatal death. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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26 pages, 2875 KB  
Systematic Review
Modern Therapeutic Approaches in Anaplastic Thyroid Cancer: A Meta-Analytic Review of Randomised and Single Arm Studies on Efficacy and Survival
by Mutahar A. Tunio, Donna Hinder, Blaise Emery, Muhammad H. Riaz, Yusef A. Ibraheem, Krishnendu Kumar Nayak and Wael Mohamed
Cancers 2025, 17(5), 777; https://doi.org/10.3390/cancers17050777 - 24 Feb 2025
Viewed by 2693
Abstract
Background: Meta-analyses aimed to assess the effectiveness and safety of targeted and contemporary therapies utilised in locally advanced and metastatic anaplastic thyroid cancer (ATC). Methods: Employing PRISMA and MOOSE guidelines, PubMed, Scopus, Cochrane Library and Web of Science were explored from the inception [...] Read more.
Background: Meta-analyses aimed to assess the effectiveness and safety of targeted and contemporary therapies utilised in locally advanced and metastatic anaplastic thyroid cancer (ATC). Methods: Employing PRISMA and MOOSE guidelines, PubMed, Scopus, Cochrane Library and Web of Science were explored from the inception of targeted therapy until December 2024. A meta-analysis was performed to evaluate the effectiveness, toxicity and survival outcomes of various mutationally directed agents, chemotherapy and radiotherapy in locally advanced/metastatic ATC cases. Results: A total of 47 studies (26 prospective phase II trials and 21 retrospective studies) involving 980 patients met the inclusion criteria. The pooled results showed an overall response rate (ORR) of 29.7% (95% CI: 25.4–34.2%; I2 = 42.4%; p < 0.0001). A total of 49.9% deaths were reported, although a significant number remained alive compared to baseline (mean difference [MD]: 2.07, 95% CI: 1.90–2.24; I2 = 88.6%; p < 0.0001). The pooled median progression-free survival (PFS) was 5.4 months (95% CI: 4.0–6.7 months; I2 = 97.9%; p < 0.0001). Dabrafenib/trametinib (DT) with and without pembrolizumab and lenvatinib plus pembrolizumab (LP) were associated with higher ORR rates and improved OS and PFS. About 51.% of studies mentioned bio-marker analysis (BRAFV600 [14.7%], PDL1 [9.2%], RAS [1.1%], PIK3CA [1.0%] and NTRK1/3 [0.7%]). Toxicity was reported in 94.7% of patients. Conclusions: This meta-analysis found that DT could be a promising first-line treatment option for BRAFV600-mutated ATC, with or without immunotherapy. Alternatively, LP shows potential in BRAFV600 wild-type and PDL1-overexpressing cases. Routine biomarker analysis remains critical for optimising ATC management strategies. Full article
(This article belongs to the Section Cancer Therapy)
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