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Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard&#xae;) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n&#x202f;=&#x202f;53) or an untreated control group (n&#x202f;=&#x202f;51). Clinical evaluations were performed on Days 0, 15 (&#xb1;2), 30 (&#xb1;2), and 45 (&#xb1;2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p&#x202f;<&#x202f;.001), with large effect sizes at the final visit for all outcomes (r&#x202f;=&#x202f;0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals

Identification and functional characterization of a novel antiviral chicken interferon-&#x3c5;.

Interferons are critical mediators of antiviral immunity in vertebrates. While type IV interferon (IFN-&#x3c5;) has been identified in fish and amphibians, its existence and function in chickens remained unknown. Through systematic genomic screening, we identified and cloned a novel chicken interferon gene, designated ChIFN-&#x3c5;. Phylogenetic analysis placed ChIFN-&#x3c5; within a distinct clade alongside zebrafish and clawed frog IFN-&#x3c5;, confirming its identity as a type IV interferon, with minimal homology to classical type I, II, or III IFNs. Expression profiling revealed constitutive ChIFN-&#x3c5; expression in mucosal and immune tissues of healthy chickens, exhibiting a distinct developmental shift: highest in trachea and small intestine in 1-day-old chicks, shifting to spleen and lung in 4-week-old chickens. ChIFN-&#x3c5; expression was strongly upregulated following H9N2 AIV infection. Functionally, recombinant ChIFN-&#x3c5; protein activated the interferon-stimulated response element (ISRE) and Mx promoter in a dose-dependent manner and significantly inhibited the replication of both vesicular stomatitis virus (VSV) and H9N2 AIV in DF-1 cells. In vivo, early treatment with exogenous ChIFN-&#x3c5; significantly reduced pulmonary and tracheal viral loads and decreased oropharyngeal and cloacal virus shedding in H9N2-infected chickens. In conclusion, this study identifies and functionally characterizes the type IV interferon in chickens, elucidating the evolutionary status, regulated expression, and antiviral efficacy of ChIFN-&#x3c5;. These findings highlight its potential as a candidate for developing interferon-based therapies against avian viral diseases.

Animals

Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5&#xa0;mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5&#xa0;mg or Val/Aml 80/5&#xa0;mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25&#xa0;mg or Val/Aml 160/5&#xa0;mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean &#xb1; SE change in MSSBP was -19.70 &#xb1; 1.31&#xa0;mmHg in the Val/Aml/CTD group versus -8.71 &#xb1; 1.26&#xa0;mmHg in the control group, yielding a statistically significant between-group difference of -10.99 &#xb1; 1.81&#xa0;mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

Humans

Examining early-phase symptom trajectories in interpersonal psychotherapy versus antidepressant medication for adults with depression: A dynamic time warp network analysis.

BACKGROUND: Depression is characterized by substantial symptom heterogeneity, which is often concealed when examining total severity scores. Analyzing symptom-level change can improve our understanding of treatment effects and recovery processes. This study, therefore, examined dynamic symptom networks during early-phase interpersonal psychotherapy (IPT) and selective serotonin reuptake inhibitor (SSRI) antidepressant treatment, assessing patterns of symptom change across as well as differences between treatments. METHODS: Using weekly item-level Hamilton Depression Rating Scale (HAM-D) data from a randomized clinical trial comparing IPT and SSRIs for adults with depression, this preregistered study examined symptom trajectories in the first six weeks of treatment with Dynamic Time Warping (DTW). RESULTS: Depressive symptom trajectories and DTW-based symptom networks were largely similar for IPT and SSRI. In both conditions, changes in somatic symptoms of anxiety and middle insomnia tended to precede improvements in depressed mood. CONCLUSIONS: Early symptom change may occur outside the core affective domain, underscoring the importance of monitoring symptoms broadly. Symptom-level patterns may reflect patients' stage of recovery and provide clinically relevant information beyond total severity scores. The absence of differences in improvement patterns between IPT and SSRI suggest few indications for treatment selection based on baseline symptom profiles. Future research should replicate and extend these findings to subsequent treatment phases using more frequent assessments and a broader range of interventions.

Humans

Cardiovascular Drug Access in Australia and New Zealand: New PBS and PHARMAC Listings, 2023-2025.

BACKGROUND: Cardiovascular disease is a leading cause of death in Australia and New Zealand. Publicly subsidised access to new cardiovascular medications is governed by the PBS (Pharmaceutical Benefits Scheme) in Australia and PHARMAC (Pharmaceutical Management Agency) in New Zealand, yet no consolidated resource catalogues recent listings across both jurisdictions. METHODS: We reviewed all new cardiovascular drug listings and indications on the PBS and PHARMAC schedules from 1 January 2023 to 31 December 2025. PBS data were obtained from the PBS Pricing and Policy Branch through the Cardiac Society for Australia and New Zealand. PHARMAC data were obtained via direct communication with PHARMAC and cross-referenced with public schedule information. Pivotal trial evidence, restriction criteria, and prescribing considerations were extracted from published literature and regulatory documents. RESULTS: Five new cardiovascular drugs were PBS-listed (inclisiran, mavacamten, tafamidis, icosapent ethyl and migalastat), two existing drugs received new cardiovascular indications (empagliflozin and dapagliflozin for heart failure with preserved ejection fraction) and prasugrel was relisted for acute coronary syndrome. One major change occurred on the PHARMAC schedule (empagliflozin for heart failure with reduced ejection fraction). CONCLUSIONS: The 2023-2025 period has seen notable additions to cardiovascular pharmacotherapy in Australia, including the first cardiac myosin inhibitor, the first transthyretin stabiliser, expanded lipid lowering therapy options, and extension of SGLT2 inhibitor coverage across the heart failure ejection fraction spectrum. A pronounced access disparity persists between Australia and New Zealand.

New Zealand

Efficacy of the NMIC-150 system in identifying extended-spectrum beta-lactamases in clinical isolates.

Extended-spectrum beta-lactamases (ESBLs) are significant contributors to the growing global crisis of antimicrobial resistance. This study evaluated the performance of the NMIC-150 System for susceptibility testing of third-generation cephalosporins (3GCs) and assessed whether ceftazidime-avibactam and aztreonam-avibactam could identify ESBL-producing carbapenem-resistant Enterobacterales (CREs). A total of 278 non-duplicate clinical isolates (Klebsiella pneumoniae, E. coli, and Proteus mirabilis) were analyzed. Antimicrobial susceptibility was determined using reference broth microdilution (BMD) and the NMIC-150 System. ESBL production was defined as an &#x2265;eight-fold reduction in the minimum inhibitory concentration (MIC) of 3GCs in the presence of clavulanic acid, according to CLSI criteria. Whole-genome sequencing was performed to characterize ESBL and carbapenemase genes among 3GC-resistant isolates. A Random Forest model was used to predict ESBL-producing isolates based on MIC values. The NMIC-150 System demonstrated over 90% categorical and essential agreement with BMD for ceftazidime and ceftriaxone, along with robust predictive performance via Random Forest analysis. These findings suggest that the NMIC-150 System is a reliable platform for 3GC susceptibility testing and that an &#x2265;eight-fold MIC reduction with ceftazidime-avibactam or aztreonam-avibactam may serve as a phenotypic indicator of ESBL production in CRE isolates. In conclusion, the NMIC-150 System shows potential for routine antimicrobial resistance surveillance and may facilitate the rapid identification of ESBL-producing CREs in clinical settings.

Microbial Sensitivity Tests

Influence of Immediate Post-Bleaching Polishing on Enamel Color, Morphology, and Sensitivity: A Randomized Clinical Trial.

OBJECTIVE: This study evaluated the influence of polishing on enamel color change after in-office bleaching treatment on tooth morphology and sensitivity. MATERIALS AND METHODS: A total of 50 volunteers were randomized into two groups (n&#x2009;=&#x2009;25): in-office bleaching with 35% hydrogen peroxide gel for 45&#x2009;min without polishing (GSEM) or with polishing (GP). Color analysis was performed four times, at the beginning of the starting line and immediately after the first, second, and third bleaching sessions with a spectrophotometer. A qualitative analysis of enamel morphology was performed under a scanning electron microscope. Tooth sensitivity was assessed daily using the Visual Analog Scale (&#x3b1;&#x2009;=&#x2009;0.05). RESULTS: There was no statistically significant difference (p&#x2009;>&#x2009;0.05) in tooth color change when comparing &#x394;E, &#x394;E00, and &#x394;WID between the groups. The enamel surface showed larger areas of irregularities and depressions in the GP group than in the GSEM group. There was no difference in tooth sensitivity (p&#x2009;>&#x2009;0.05) between the groups. CONCLUSIONS: Polishing after whitening in the office does not change the color and sensitivity of the tooth but promotes greater changes in the morphology of the enamel, such as increased surface roughness. CLINICAL RELEVANCE: Polishing immediately after teeth whitening causes greater changes in enamel surface morphology.

Humans

Characterization and application potential of two newly isolated phages targeting the prevalent multidrug resistant Salmonella serovars in China.

The escalating global threat of multidrug resistant (MDR) Salmonella, a foodborne pathogen with animal-derived foods serving as the primary transmission vehicle, underscores the urgent need for effective lytic phages for biocontrol. From 142 environmental and farm samples in Shandong Province, we isolated 103 phages active against MDR S. Enteritidis and S. Typhimurium, which were the most prevalent Salmonella serovars in China. Two Siphoviridae phages vB-SenS-S1 and vB-SenS-SEC2 were selected for further study. With optimal multiplicities of infection (MOIs) of 10-2 (vB-SenS-S1) and 10-5 (vB-SenS-SEC2), both phages exhibited a 20&#xa0;min latent period, yielding burst sizes of 52 and 37 PFU/cell, respectively. They also demonstrated stability across a range of temperatures (50-60&#xa0;&#xb0;C), pH levels (5-11), and after 1&#xa0;h of UV exposure. Genomic analysis identified vB-SenS-S1 (43,002&#xa0;bp, 47.04% GC) and vB-SenS-SEC2 (42,948&#xa0;bp, 47.65% GC) as novel double-stranded DNA phages. Functional annotation confirmed the presence of genes essential for structural assembly, host lysis, and DNA replication/metabolism, and also verified the absence of resistance, virulence, and lysogeny-associated genes. Both phages vB-SenS-S1 and vB-SenS-SEC2 exhibited synergy with colistin and tetracycline. The synergy with colistin was particularly potent, leading to complete bacterial eradication in vitro. The in vivo therapeutic efficacy was further validated in both Galleria mellonella larvae and murine models of MDR Salmonella infection. Combination therapy with vB-SenS-SEC2 and colistin not only dramatically increased survival but also achieved a significant reduction in bacterial burden across multiple visceral organs of infected mice. Moreover, vB-SenS-S1 (108 PFU/mL) completely inhibited MDR Salmonella on chicken meat at 4&#xa0;&#xb0;C and -20&#xa0;&#xb0;C when initial contamination was &#x2264;103&#xa0;CFU/mL. This study not only expands the diversity of Salmonella phages but also highlights their potential as biocontrol agents in both clinical veterinary use and food decontamination, thereby enhancing food quality and safety at both the meat production source and the terminal product.

Animals

[Complex therapy of chronic bacterial prostatitis using the immunomodulatory drug sodium aminodihydrophthalazinedione].

INTRODUCTION: Chronic bacterial prostatitis (CBP) is characterized by a recurrent course caused by pathogen persistence and impaired local immunity of the prostate. AIM: To assess the effectiveness of the use of sodium aminodihydrophthalazinedione in the complex therapy of chronic bacterial prostatitis. MATERIALS AND METHODS: The prospective comparative study included 60 men aged 21-50 years with CBP (NIH category II). Patients were randomized into two groups of 30: the comparison group received levofloxacin 500 mg/day for 28 days; the main group additionally received rectal sodium aminodihydrophthalazinedione. NIH-CPSI, IPSS, QoL, uroflowmetry, leukocyte and lecithin body counts in prostatic secretion, and bacteriological examination were assessed at baseline and on day 28, and the recurrence rate over 3 months. RESULTS: By day 28, the main group showed a more pronounced decrease in the total NIH-CPSI score (8.1+/-2.1 vs 13.4+/-2.6; p<0.001), restoration of lecithin bodies (+65.1% vs +24.5%; p<0.05), normalization of uroflowmetry, and pathogen eradication in 86.7% vs 66.7% of patients (p<0.05). The 3-month recurrence rate decreased from 26.7 to 10.0% (p<0.05). No adverse events were registered. DISCUSSION: The advantage of combinationtherapy is due to the combination of anti-inflammatory,immunomodulatory,antioxidantandregenerativeeffects of the drug,which is confirmed by the restoration of the secretoryfunction of the prostateepitheliumaccording to the dynamics of lecithingrains. CONCLUSION: The inclusion of sodium aminodihydrophthalazinedione in the combination therapy of CBP increases the clinical and microbiological efficacy of treatment and reduces the recurrence rate.

Humans

Nimodipine in animal models of demyelination relevant to multiple sclerosis: a systematic review.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease in which axonal injury, neuronal death, and demyelination occur. Treatment for MS relapses remains limited, which alleviates acute loss of function but has no impact on long-term disability. This study aimed to perform a systematic review of the effects of nimodipine on experimental demyelination models, including experimental autoimmune encephalomyelitis (EAE) and Cuprizone models in rodents. METHODS: This study was conducted following the PRISMA statement. A systematic search was performed in PubMed, Scopus, the Cochrane Library, and Google Scholar. The primary outcome was EAE clinical disease severity (peak clinical score and/or cumulative disease burden). Secondary outcomes included relapse activity (when reported), histological myelin outcomes, oligodendrocyte lineage markers, neuroaxonal injury markers, and inflammatory readouts. Risk of bias was assessed using the SYRCLE tool. RESULTS: Out of 4660 results, 5 studies were included in the systematic review (four EAE studies and one cuprizone model). Nimodipine was administered using heterogeneous regimens (oral, intravenous, intraperitoneal, subcutaneous, or osmotic pump delivery; 1-30&#xa0;mg/kg/day). The included studies reported the variable effects of nimodipine on relapse-related outcomes, myelination, inflammatory processes, and neuroprotection in the EAE model of MS. Across EAE studies, nimodipine generally reduced clinical disease severity or cumulative burden, although relapse-related outcomes were inconsistent. CONCLUSIONS: Preclinical evidence suggests that nimodipine may attenuate disease severity and demyelination and may promote repair-related processes in rodent models relevant to MS. However, to evaluate the clinical applicability of nimodipine in MS patients, well-powered, transparently reported preclinical replication and early-phase clinical studies are required before clinical translation.

Animals

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70&#xa0;mg/dL]: 40-42.5 vs 40&#xa0;min; Level 2 [<54&#xa0;mg/dL]: 35-39.9 vs 35&#xa0;min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult

New insights into soil amendment: Impact of humic acid on typical antibiotic resistance in agricultural soil.

Humic acid (HA) addition can improve agricultural soil, but little is known about how it affects the soil resistome. In this study, we used selective agar plate combined with quantitative PCR (qPCR) and 16S rRNA gene sequencing to investigate how HA influences antibiotic resistant bacteria (ARB) and antibiotic resistant genes (ARGs) in soil contaminated with erythromycin and kanamycin. 0.1 % HA reduced the abundance of culturable erythromycin-resistant bacteria (ERB), while promoting the growth of kanamycin-resistant bacteria (KRB). Lysinibacillus and Paenibacillus were the dominant genera in ERB and KRB, respectively, governing the changes in their abundances. At this concentration, the Lysinibacillus abundance in ERB decreased from 96.74 % to 70.57 %. Meanwhile, that of Paenibacillus in KRB increased from 33.40 % to 77.44 %. The copy number of ermF decreased after HA addition, while that of ermB increased. Furthermore, 0.1 % HA significantly reduced the copy number and relative abundance of aadA1 and aac(6')-Ib (aka aacA4)-03 in the soil. Changes in these two types of ARB and ARGs were primarily driven by shifts in the microbial community structure. Soil physicochemical properties, particularly increased organic matter (OM), altered the absolute abundance of ermB. Meanwhile, changes in intI1 abundance determined the risk associated with aadA1 and aac(6')-Ib (aka aacA4)-03. These findings emphasize the dual role of HA in the dissemination of antibiotic resistance in agricultural soils and highlight the necessity of considering dose-dependent effects when applying HA as a soil amendment.

Soil Microbiology

Acetate- Versus Lactate-Buffered Crystalloids for Prevention of Post-ERCP Pancreatitis in Patients Without Access to Rectal NSAIDs: A Multicentre Double-Blind Randomized Trial.

BACKGROUND: Aggressive peri-procedural intravenous fluid (IVF) therapy with lactated Ringer's solution (LR) reduces the risk of post-ERCP pancreatitis (PEP), but the standard 8-h protocol is impractical in outpatient settings and the optimal fluid type remains uncertain. We compared LR with an acetate-buffered balanced crystalloid (AC) using a symptom-guided 4-h aggressive IVF protocol. METHODS: This multicentre, double-blind, randomized superiority trial was conducted at three academic hospitals in Korea where rectal NSAIDs are unavailable. Adults with native papillae and moderate-to-high PEP risk were randomized to receive LR or AC. The IVF protocol comprised 10&#xa0;mL/kg boluses before and after ERCP, followed by 3&#xa0;mL/kg/h for 4&#xa0;hours and extended to 8&#xa0;hours if abdominal pain developed or worsened. The primary outcome was PEP incidence; secondary outcomes included early post-ERCP pain and adverse events. RESULTS: Of 813 patients (404 LR, 409 AC), PEP occurred in 12.4% of the LR group and 11.5% of the AC group (relative risk [RR] 0.93; 95% CI, 0.64-1.35; P&#xa0;=&#xa0;0.70). Rates of mild (7.9% vs. 7.1%) and moderate (4.5% vs. 4.4%) PEP were similar, and no severe PEP or fluid overload occurred. Among the 68.3% of patients who remained asymptomatic at 4&#xa0;hours and required only 4-h IVF, PEP occurred in 7.4%, with no cases of severe PEP. CONCLUSION: In this superiority trial, acetate-buffered crystalloid did not reduce PEP compared with lactated Ringer's solution, and no significant safety differences were observed between the two agents. Lactated Ringer's remains the recommended first-line crystalloid for aggressive hydration when rectal NSAIDs are unavailable. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05832047).

Humans

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12&#x202f;cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B)&#x202f;&#x2248;&#x202f;9, coefficient of variance (CV)&#x202f;<&#x202f;10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus

Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.

Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.

Humans

Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science through March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or active comparators. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was GI neoplasms reported in publications, supplementary materials, or trial registries, usually as adverse events rather than centrally adjudicated cancer endpoints. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0. In 48 RCTs (n&#x2009;=&#x2009;48,765), SGLT2 inhibitor therapy was not associated with overall GI neoplasm risk (OR&#x2009;=&#x2009;1.10, 95% CI: 0.84-1.44; p&#x2009;=&#x2009;0.46; I&#xb2; = 0%). Site-specific analyses showed no statistically significant association for esophageal (OR&#x2009;=&#x2009;1.12, 95% CI 0.37-3.45), gastric (1.20, 0.65-2.23), hepatic (0.62, 0.31-1.22), pancreatic (0.91, 0.51-1.64), colonic (1.28, 0.78-2.08), colorectal (0.76, 0.27-2.17), and rectal neoplasms (0.98, 0.49-1.97), with all p-values&#x2009;>&#x2009;0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, body mass index (BMI), HbA1c, treatment duration, and dose were also non-significant (all p&#x2009;>&#x2009;0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Available RCT evidence does not show a clear increase in GI neoplasm risk with SGLT2 inhibitors in T2DM. However, limited follow-up, low event counts, and non-cancer-specific outcome ascertainment, the findings should be interpreted as reassuring but not definitive evidence of long-term oncologic safety.Systematic review registration: PROSPERO No. CRD42024619019.

Humans

Mitomycin C in the Endoscopic Treatment of Airway Stenosis: A Systematic Review and a Meta-Analysis.

OBJECTIVE: To assess the efficacy of adjuvant MMC in the endoscopic treatment of airway stenoses. DATA SOURCES: PubMed/MEDLINE, Cochrane Library, Scopus, Embase, and Google Scholar databases. REVIEW METHODS: A literature search was conducted following PRISMA guidelines. The PICOS tool was used to determine the eligibility criteria for this study. A single arm meta-analysis was performed for stenosis resolution, the rate of patients requiring multiple endoscopic procedures, and the rate of patients requiring other surgical treatments. RESULTS: A total number of 358 patients (median age: 48.0&#x2009;years; 95% CI 44.8-50.8) were included. The median follow-up was 25.2&#x2009;months (n&#x2009;=&#x2009;244/358; 95% CI 15.4-38.3). Overall, the cumulative stenosis resolution rate was 76.37% (n&#x2009;=&#x2009;187/254; 95% CI 59.72-89.64), the rate of patients requiring multiple endoscopic procedures was 52.33% (n&#x2009;=&#x2009;131/260; 95% CI 32.03-72.25), and the rate of patients requiring other surgical treatments was 4.08% (n&#x2009;=&#x2009;26/310; 95% CI 0.37-11.48). The median intervention-free interval was 366&#x2009;days (n&#x2009;=&#x2009;155/358; 95% CI 270-696). CONCLUSIONS: Current evidence does not allow definitive conclusions regarding the efficacy of adjuvant MMC in reducing recurrence or prolonging intervention-free intervals in airway stenosis. Further well-designed prospective studies are needed to clarify the role of MMC and to inform evidence-based guidelines for patient selection and treatment use. LEVEL OF EVIDENCE: NA.

Humans

Pharmacogenomics of antipsychotic-induced weight gain: A systematic review.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a major clinical concern, affecting approximately 30% of patients. Clinical predictors explain only part of AIWG risk. Genetic and molecular variations are hypothesized to contribute to susceptibility. The purpose of this review is to summarize recent results to identify replicated and novel findings. STUDY DESIGN: Applying PRISMA guidelines, we searched MEDLINE, Embase, and PsycINFO (May 2018-May 2026) for studies on genetic and molecular associations with AIWG, extending our prior review. Reviews, editorials, and conference abstracts were excluded. We extracted study characteristics (design, diagnosis, antipsychotic exposure, sample size, ancestry, genetic variants, and AIWG outcomes) (e.g., &#x2265;7% weight gain, BMI change). RESULTS: Fifty-three studies met inclusion criteria. In candidate gene studies, the most consistently replicated genes associated with AIWG were observed for DRD2, HTR2C, and MC4R. Multiple novel associations were identified by genome-wide association studies (GWAS) (e.g., MAP2K1, ZDBF2, PEPD), polygenic risk scores (PRS) (e.g., body mass index PRS), gene expression (e.g., CYP3A4, EP300), and epigenetic analyses (e.g., cg12034943 at CRTC1). CONCLUSIONS: Polymorphisms in candidate genes related to neurotransmission and appetite regulation continue to be investigated for associations with AIWG, while novel findings have emerged from GWAS, gene expression, and epigenetic studies. Evidence remains inconsistent due to limited replication, methodological variability, sparse ancestry data, and geographical underrepresentation. No single genetic variant is ready for clinical use, and multi-omic and multi-ancestry models are needed to improve prediction and clinical utility.

Humans