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Safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in USA and Puerto Rico: Results from a Phase III, randomized, active-controlled study.

MenACYW-TT, a quadrivalent meningococcal tetanus toxoid-conjugate vaccine, is approved for prevention of invasive meningococcal disease in infants ≥ 6 weeks of age in the USA. This Phase III study (NCT03673462; September 17, 2018 - March 16, 2023) evaluated the safety of MenACYW-TT compared with a licensed quadrivalent meningococcal oligosaccharide diphtheria CRM197-conjugate vaccine (MenACWY-CRM) when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in a four-dose series (3+1 schedule). Participants were randomized 3:1 to receive MenACYW-TT (Group 1; n = 2080) or MenACWY-CRM (Group 2; n = 697) at 2, 4, 6, and 12 months of age, with concomitant administration of routine pediatric vaccines (DTaP5-IPV/Hib, PCV13, rotavirus, hepatitis B, MMR, and varicella vaccines). Safety assessments included immediate unsolicited adverse events within 30 minutes post-vaccination, solicited injection site and systemic reactions within 7d, unsolicited AEs within 30d, serious adverse events (SAEs) including adverse events of special interest (AESIs), and medically attended adverse events (MAAEs) throughout the study. MenACYW-TT and MenACWY-CRM were overall well tolerated, and safety profiles were comparable. Solicited injection site reactions occurred in 84.9% and 84.6% of participants in Groups 1 and 2, respectively; solicited systemic reactions in 87.1% and 88.2%, respectively. During the entire study, 5.2% in Group 1 and 3.0% in Group 2 experienced at least one SAE; 0.9% and 0.1%, respectively, reported at least one AESI. Three deaths occurred in Group 1. All SAEs, AESIs, and deaths were unrelated to study vaccines. This study supports the safety profile of MenACYW-TT in infants and toddlers aged ≥ 6 weeks.Study registration: Clinicaltrials.gov: NCT03673462; EudraCT: 2019-004459-35.

Child, Preschool

Simultaneous Administration of Human Papillomavirus (HPV) Vaccine With Other Recommended Vaccines Among Adolescents Aged 13-17 years, National Immunization Survey-Teen (NIS-Teen), United States, 2023.

PURPOSE: To investigate the percent of adolescents who receive human papillomavirus (HPV) vaccine with one or more other vaccines recommended for adolescents in a single medical visit. METHODS: Data from the 2023 National Immunization Survey-Teen were analyzed. Timing of receipt of HPV vaccine, tetanus, diphtheria, and acellular pertussis vaccine (Tdap), quadrivalent meningococcal conjugate vaccine (MenACWY), and influenza vaccine was assessed using provider-reported vaccination histories. RESULTS: In 2023, among adolescents aged 13-17 years, 69.5% received HPV vaccine with one or more other vaccines recommended for adolescents in a single medical visit. In addition, 47.8% received specifically HPV vaccine, Tdap, and MenACWY together in a single medical visit. DISCUSSION: The HPV vaccine is commonly given with other vaccines recommended for adolescents in a single medical visit. These findings demonstrate variation in simultaneous vaccination patterns, suggesting that flexibility in the recommended adolescent vaccination schedule allows for different approaches to vaccination across clinical settings and family preferences while maintaining adherence to the recommended schedule.

Humans

Efficacy of dapagliflozin on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: a pre-specified single-arm analysis from a randomized controlled trial.

AIM: To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12&#xa0;months. METHODS: This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10&#xa0;mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12&#xa0;months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS: Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7&#xa0;dB/m; mean change&#xa0;-&#xa0;71.02&#xa0;dB/m, 95% CI: -63.4 to&#xa0;-&#xa0;78.6; p&#xa0;<&#xa0;0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28&#xa0;kPa; mean change&#xa0;-&#xa0;1.31&#xa0;kPa, 95% CI: -0.92 to&#xa0;-&#xa0;1.70; p&#xa0;<&#xa0;0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS: Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12&#xa0;months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Humans

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans

Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.

BACKGROUND: Triazole resistance in Aspergillus fumigatus is a global public health concern associated with treatment failure, notably in invasive aspergillosis. However, population-level data on triazole resistance from India remain limited, with most reports originating from single-center studies. METHODS: We conducted a multicenter surveillance study to assess the prevalence of triazole resistance among clinical A. fumigatus isolates across India. Antifungal susceptibility testing was performed using the CLSI broth microdilution method (M38-Ed3), and molecular characterization was conducted on resistant isolates. A total of 518 isolates were analyzed: 115 prospectively collected from 13 tertiary-care hospitals from 2015-2020, and 403 archived isolates obtained from the National Culture Collection of Pathogenic Fungi (1994-2020). RESULTS: The overall pooled prevalence of non-wildtype isolates was 4.1% for itraconazole (95% CI: 2.54-6.17%), 3.9% for posaconazole (95% CI: 2.39-5.94%), while 1.4% were resistant to voriconazole (95% CI: 0.55-2.77%). One multi-azole-resistant isolate from an immunocompromised, mold-active triazole-na&#xef;ve patient carried the TR34/L98H mutation, suggesting environmental acquisition. Prevalence of resistance did not differ significantly across geographic regions or between public and private sector hospitals. Linear regression analysis revealed a significant temporal increase in median MICs of all three licensed triazoles between 1994 and 2020. Approximately 29% of isolates exhibited amphotericin B MICs exceeding the epidemiological cutoff value; however, the clinical significance of this finding remains uncertain. CONCLUSIONS: Azole resistance among clinical A. fumigatus isolates in India remains uncommon (<5%), supporting the continued use of triazoles as first-line therapy. However, the observed temporal increase in triazole MICs underscores the need for sustained national surveillance to detect emerging resistance trends.

Aspergillus fumigatus

Comparative efficacy of percutaneous vertebroplasty combined with minimally invasive pedicle screw fixation versus percutaneous vertebroplasty alone in the treatment of elderly osteoporotic vertebral compression fractures.

The study aimed to assess the comparative efficacy of percutaneous vertebroplasty (PVP) combined with minimally invasive pedicle screw fixation versus PVP alone in elderly patients with osteoporotic vertebral compression fractures (OVCF). Ninety-four elderly patients with OVCF were randomly classified into the control (47 patients) and combined (47 patients) groups. The control group received PVP, while the combined group received PVP combined with minimally invasive pedicle screw fixation. Perioperative indicators such as intraoperative blood lose, operative time, and hospitalization time were recorded. Pain was assessed using the VAS before and at baseline and 1, 3, and 7 days postoperatively. At 1 and 3 days postoperatively, Serum CRP levels, WBC, and neutrophil counts were measured postoperatively. Radiographic outcomes (vertebral height ratio and Cobb angle), ADL scores, JOA scores, and ODI were evaluated preoperatively and at 3 months post-operation. Postoperative complications were documented. Baseline characteristics were comparable. The combined group showed superior pain relief, vertebral height restoration, Cobb angle correction, functional recovery, and reduced inflammatory markers (CRP, WBC, neutrophils) postoperatively (all P&#x2009;<&#x2009;0.05). Blood loss and hospital stay were shorter in the combined group, though operative time was longer (P&#x2009;<&#x2009;0.05). Complication rates did not differ significantly (P&#x2009;>&#x2009;0.05). PVP combined with minimally invasive pedicle screw fixation yields better outcomes in elderly OVCF patients by enhancing pain control, vertebral height, and functional recovery without increasing perioperative risk.

Humans

Efficacy of current approaches to non-invasive diagnosis of skin cancer and the potential impact of artificial intelligence: A systematic review and meta-analysis.

BACKGROUND: Skin cancer is one of the most prevalent malignancies worldwide, particularly within Caucasian populations. This systematic review and meta-analysis aimed to quantitatively review the current literature on non-invasive diagnosis of skin cancer and evaluate the current evidence to support the use of tools in addition to, or in replacement of clinician face-to-face assessment. METHODS: A literature search was conducted for publications in PubMed, Medline and Embase databases. Articles describing accuracy, sensitivity, specificity and outcomes of their mode of assessment were included. A total of 208 articles met the inclusion criteria. RESULTS AND CONCLUSION: This systematic review and meta-analysis showed that the diagnostic performance of artificial intelligence (AI) in the interpretation of dermatoscopic images was high for melanoma diagnosis, basal cell carcinoma or malignancy, in comparison to dermatoscopic assessment alone by clinicians and experts. Although AI interpretation of images demonstrated higher sensitivity for melanoma diagnosis in comparison to clinical assessment combined with dermatoscopic assessment, it is unclear if this is also the case for basal cell carcinoma and squamous cell carcinoma diagnosis. Reflectance confocal microscopy, a non-invasive high resolution imaging technique, is known to have a high sensitivity for diagnosing cutaneous malignancy, and this may have applications within secondary care. Therefore, AI could help reduce resource burden and aid in clinical assessment, particularly within primary care settings.

Humans

Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study.

BACKGROUND: Patients undergoing minimally invasive esophagectomy (MIE) frequently experience moderate-to-severe postoperative pain and anxiety-depressive symptoms, compromising postoperative quality of recovery (QoR). Esketamine is a promising adjunct for analgesia and anxiolysis; however, the effect of low-dose esketamine on patient-centered recovery outcomes in MIE remains unclear. METHODS: In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25&#x2009;mg/kg loading dose and 0.125&#x2009;mg/kg/h continuous infusion during surgery) or placebo (equivalent volume and rate of saline). The primary outcome was the QoR-15 score on postoperative day (POD) 2. Secondary outcomes included QoR-15 scores on POD 1, 3, 7 and 30. Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) and Depression Subscale (HADS-D) scores, numeric rating scale (NRS) pain scores, and the Brief Pain Inventory (BPI) scores on POD 1 to 3, and safety evaluations. RESULTS: A total of 198 patients were analyzed (esketamine, n&#x2009;=&#x2009;98; placebo, n&#x2009;=&#x2009;100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9&#x2009;&#xb1;&#x2009;9.4 vs. 110.2&#x2009;&#xb1;&#x2009;9.8, p&#x2009;<&#x2009;0.001) and POD 3 (123.6&#x2009;&#xb1;&#x2009;7.2 vs. 116.8&#x2009;&#xb1;&#x2009;8.4, p&#x2009;<&#x2009;0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p&#x2009;<&#x2009;0.001). Additionally, esketamine recipients reported significantly lower NRS scores at rest and during movement and BPI scores for pain severity and pain interference items (all p&#x2009;<&#x2009;0.001). There were no significant between-group differences in safety outcomes. CONCLUSIONS: Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Register (identifier: ChiCTR2400088916).

Humans

The efficacy of non-invasive brain stimulation interventions in obsessive-compulsive disorder management: A network meta-analysis of randomized controlled trials.

Non-invasive brain stimulation (NIBS) has been widely used as an alternative treatment for obsessive compulsive disorder (OCD). However, the most effective NIBS parameters are unclear. To compare the efficacy of NIBS in OCD. We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of NIBS.Systematic searches were conducted in Cochrane CENTRAL, EMBASE, PubMed, and Web of Science from inception to June 20, 2025. Forty-two randomized sham-controlled trials (n = 1456) were included. All statistical analyses were conducted with R statistical software. Bayesian NMAs mainly using the BUGSnet package and gemtc package. Five NIBS protocols produced statistically significant reductions in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores compared with sham stimulation: high-frequency rTMS over the FzFCz (Hf-rTMS-FzFCz; MD -11.77, 95% CrI -20.62 to -3.09), low-frequency rTMS over F3F4 (Lf-rTMS-F3F4; MD -9.93, 95% CrI -18.07 to -1.65), low-frequency rTMS over FCz (Lf-rTMS-FCz; MD -3.25, 95% CrI -6.06 to -0.40), high-frequency deep TMS over FzFC (Hf-dTMS-FzFC; MD -6.48, 95% CrI -12.32 to -0.50), and 2 mA anodal tDCS over F3 with cathodal over Fp2 (MD -9.34, 95% CrI -16.01 to -3.03).For secondary outcomes, high-frequency deep rTMS over FzFCz produced the largest reduction both in depressive symptoms (SMD -1.24, 95% CrI -1.92 to -0.55) and anxiety scores (SMD -1.88, 95% CrI -2.62 to -1.11), but had no effect on Clinical Global Impression-Severity (CGI-S) scores.Specific NIBS protocols are safe and effective adjunctive treatments for OCD, with promising yet inconclusive improvements in comorbid depressive symptoms. Further high-quality, head-to-head trials are needed.

Humans

High-Flow Nasal Oxygen Versus Conventional Oxygen Therapy and Non-Invasive Ventilation for Acute Respiratory Failure in the Emergency Department: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis compares the use of high-flow nasal oxygen (HFNO) with conventional oxygen therapy (COT) and non-invasive ventilation (NIV) in the management of acute respiratory failure (ARF) in the emergency department (ED). A comprehensive search of relevant sources was undertaken. Randomised controlled trials (RCTs) assessing adult patients (&#x2265;&#x2009;18&#x2009;years) treated in the ED for ARF and comparing HFNO to COT/NIV were included. The primary outcome was the need for endotracheal intubation and mechanical ventilation (IMV). Secondary outcomes included physiological and biochemical parameters, ICU admission, hospital length of stay, dyspnoea scores and mortality. A total of 17 RCTs (1955 patients) were included. There was a significant reduction in IMV favouring the HFNO group compared to COT and NIV (RR 0.64, 95% CI 0.47-0.88). HFNO showed significant improvements in RR, SpO2, PaO2 and Modified Borg Dyspnoea Scale. Subgroup analysis showed reduced rates of IMV with HFNO compared to COT (RR 0.61, 95% CI 0.41-0.91), but not compared to NIV (RR 0.69, 95% CI 0.42-1.14). HFNO additionally showed a reduction of IMV compared to NIV and COT in undifferentiated patients (RR 0.61, 95% CI 0.41-0.93), but not in exacerbations of COPD or acute heart failure. Ten of the 17 studies had at least some concern for risk of bias, with several analyses having notable heterogeneity. HFNO showed a significant reduction in rates of IMV, improvement in peripheral oxygen saturations, PaO2, respiratory rate and patient dyspnoea scores compared to COT and NIV.

Humans

Frequent mutations in the BIRC3 gene promote metastatic potential of nasopharyngeal carcinoma cells through the TRAF2-NF-&#x3ba;B pathway.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer characterized by highly locoregionally invasive behavior attributable to the latent infection with Epstein-Barr virus (EBV) and genomic instability. It is well established that EBV-encoded oncogenic molecules actively contribute to the malignant behavior of NPC cells. However, the mechanism by which aberrant genomic alterations enable NPC cells to become aggressive remains largely unknown. In the present study, whole-exome sequencing (WES) revealed that the gene encoding the baculoviral IAP repeat-containing 3 (BIRC3) protein was frequently mutated in circulating tumor cells (CTCs) but not in paired primary tumor cells from patients with metastatic NPC. A minigene assay indicated that the c.637&#xa0;A&#xa0;>&#xa0;G mutation disrupted normal mRNA splicing, resulting in the partial deletion of Exons 2 and 3 and altered stability of BIRC3 mRNA. In vitro experiments demonstrated that ectopic expression of the BIRC3c.637A>G mutant enhanced NPC cell invasive properties, including proliferation, resistance to apoptosis, migration, and invasion. Furthermore, overexpression of wild-type BIRC3 promoted invasive characteristics in NPC cells through the TRAF2-NF-&#x3ba;B signaling axis. In summary, BIRC3 acts as a regulator of the malignant features of NPC cells. Frequent BIRC3 mutations in CTCs, such as the c.637&#xa0;A&#xa0;>&#xa0;G mutation, further enhance the metastatic potential of disseminated NPC cells by inducing aberrant alternative splicing. These findings suggest the therapeutic feasibility of targeting the BIRC3/TRAF2/NF-&#x3ba;B axis in the treatment of NPC.

Humans

Ultrasound-Guided Microwave Ablation Versus Open Surgery for Benign Breast Disease: Impact on Postoperative Lactation.

BACKGROUND: Benign breast disease (BBD) is common in adult women. While ultrasound-guided microwave ablation (MWA) is an established minimally invasive treatment, its comparative impact on postoperative lactation, particularly mastitis, remains understudied. This study aimed to evaluate mastitis outcomes following MWA versus open surgery for BBD. METHODS: In this retrospective study, 79 patients (105 nodules) treated between January 2018 and August 2023 were included 41 patients (62 nodules) underwent MWA and 38 patients (43 nodules) underwent open surgery. All patients lactated within 5 years post-procedure. The primary outcome was the incidence of lactational mastitis without systemic symptoms (MWoSS) and mastitis with systemic symptoms (MSS). Patient satisfaction was also assessed. RESULTS: The incidence of MWoSS was significantly lower in the MWA group (19.5%) than in the open surgery group (50.0%). Similarly, MSS occurred in 4.9% of the MWA group versus 34.2% of the open surgery group. Multivariate analysis identified open surgery as an independent risk factor, associated with a 4.13-fold increased risk of MWoSS (OR = 4.125, 95% CI: 1.517-11.218) and a 10.14-fold increased risk of MSS (OR = 10.140, 95% CI: 2.107-48.793). Patient satisfaction was significantly higher in the MWA group (9.29 &#xb1; 0.72 vs. 8.15 &#xb1; 1.13, p < 0.001). CONCLUSION: Compared to open surgery, ultrasound-guided MWA for BBD is associated with a significantly lower risk of postoperative mastitis and higher patient satisfaction, supporting its use for women of reproductive age, particularly when future breastfeeding is planned.

Humans

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (&#x3c7;), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA&#xa0;=&#xa0;5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated &#x3c7; in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific &#x3c7; alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples&#xa0;were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.&#xa0; Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans

Population-level impact of HPV vaccination: a global systematic review of ecological, cross-sectional, and cohort studies.

BACKGROUND: Human papillomavirus (HPV) causes approximately 4.5% of cancers globally, with the highest burden in low- and middle-income countries (LMICs). Since their introduction in 2006, HPV vaccination programs have led to substantial declines in HPV-related outcomes, although impact varies across settings. RESEARCH DESIGN AND METHODS: We conducted a systematic review to evaluate the population-level impact of HPV vaccination on HPV infection, cervical intraepithelial neoplasia grade 2 or higher (CIN2+), genital warts, invasive cervical cancer (ICC), and oropharyngeal cancer (OPC), and examined the influence of coverage, age at initiation, and vaccine type. The review followed PRISMA 2020. RESULTS: Of 13,549 records screened, 63 were included: 9 assessed HPV infection, 24 on CIN2+, 25 on genital warts, and 7 on ICC. Greatest reductions were observed in settings with at least 70% coverage and early vaccination prior to sexual debut, typically achieved through school-based programs. Reported declines ranged from 58-100% for HPV infection, 30-88% for CIN2+, 60-90% for genital warts, and 70-88% for ICC. CONCLUSIONS: HPV vaccination offers strong protection, especially when delivered early and at high coverage within schools. Expanding access and prioritizing underserved populations are essential to achieving global cancer prevention goals. Limitations include heterogeneity across designs, outcome definitions, and follow-up.

Humans

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 &#xd7; 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans