Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “species‐specific environmental filtering”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,028 records · Page 8Linked to original sources
PubMed2025

Double-Axis Maxillary Skeletal Expander Suggests Higher Expansion Efficiency in Early Activation: A Finite Element Analysis.

INTRODUCTION: Conventional single-axis maxillary skeletal expanders (MSE) have some drawbacks, such as limited control over maxillary expansion and possible asymmetric expansion between the anterior nasal spine (ANS) and posterior nasal spine (PNS). This report introduces a double-axis maxillary skeletal expander (DAMSE) concept to overcome these drawbacks and enhance the efficiency of maxillary skeletal expansion. MATERIALS AND METHODS: Five different DAMSE designs were compared with a conventional single-axis MSE. Finite element analysis was performed to analyse their expansion efficiency, stress magnitude and distribution occurring in a simplified bone model. RESULTS: DAMSE outperformed the single-axis MSE and provided better control over ANS and PNS expansion. During early activation, the highest expansion efficiency (31.7%) was achieved by DAMSE Model V, 13% more efficient than the single-axis MSE. This efficiency was increased to 100.8% by combining the DAMSE Model V with midpalatal suture surgery. However, with the simplified bone model, the current study could not demonstrate that DAMSE can resolve the issue of asymmetric expansion between ANS and PNS. CONCLUSIONS: An appropriately designed DAMSE can be a promising tool for maxillary expansion treatment. DAMSE offers more efficient treatment than the conventional single-axis MSE while maintaining similar levels of patient comfort and invasiveness.

Finite Element Analysis↗
PubMed2026

Navigating Social Media: Balancing Connectivity With Media Literacy to Combat Misinformation and Protect Mental Well-Being.

BACKGROUND: The pervasive use of social media has created a complex digital ecosystem where high connectivity coexists with significant challenges, including the rapid spread of misinformation, particularly regarding mental health, and documented negative impacts on psychological well-being. Platform architectures designed for engagement maximization have been identified as central factors in both issues. OBJECTIVE: This paper critically analyzes the interconnected relationships between social media use, misinformation dissemination, and mental health impacts, with particular attention to psychiatric misinformation across diagnostic categories (e.g., depression, anxiety, ADHD). A primary objective is to evaluate the potential of advanced critical digital literacy frameworks to serve as protective mechanisms against these dual threats. METHODS: A systematic search was conducted following PRISMA 2020 guidelines across APA PsycInfo, PubMed, JSTOR, and Google Scholar for literature published between January 2018 and March 2026 (updated from the original 2023 search). The search yielded 2672 records. After removing 624 duplicates, 2048 records underwent title and abstract screening, with 1802 excluded. The remaining 246 full-text articles were assessed for eligibility, resulting in 86 studies included in the final qualitative synthesis. Inter-rater reliability was established (Cohen's κ = 0.82). Quality assessment was conducted using the Joanna Briggs Institute Checklist, AXIS, and CASP tools, with findings weighted by methodological quality. A thematic analysis was undertaken to synthesize findings. RESULTS: The analysis reveals that core architectural features of social media platforms, algorithmic curation and engagement-based metrics, simultaneously foster environments ripe for misinformation spread and contribute to psychological distress, including anxiety, depression, and harmful social comparison. Psychiatric misinformation specifically (e.g., inaccurate claims about treatment effectiveness, diagnostic criteria, and medication side effects) represents a growing concern, particularly on image- and video-based platforms. The findings indicate that conventional media literacy approaches focused solely on fact-checking are insufficient. Instead, a critical digital literacy framework encompassing algorithmic awareness, data literacy, and emotional awareness is essential for building user resilience, with evidence from high-quality systematic reviews supporting this approach. CONCLUSIONS: Navigating the complexities of modern social media requires an integrated approach combining "pedagogies of play" for experiential skill development with advocacy for structural change (e.g., algorithmic transparency, well being by design principles). This dual strategy empowers individual users to critically engage with digital content while advocating for ethical platform design, thereby safeguarding both mental well-being and democratic discourse. Implications for educators, mental health professionals (including competencies for addressing patient encounters with psychiatric misinformation), policymakers, and platform designers are discussed.

Humans↗
PubMed2026

Clinical Outcomes and Patient Experiences With Celiprolol Therapy in Vascular Ehlers-Danlos Syndrome: The First Non-European Cohort.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder caused by heterozygous pathogenic variants in COL3A1. European studies have shown that celiprolol may reduce the risk of life-threatening vascular events, but outcomes in non-European populations and the therapy's psychological impact remain unclear. We conducted a retrospective cohort study of individuals aged ≥ 20 years with genetically confirmed vEDS in a single referral center in Japan between 2000 and 2024. Clinical, molecular, and treatment data were obtained from medical records, and semi-structured interviews were conducted with a subset of participants to assess patient experiences. Twenty-six patients were included. The mean age at celiprolol initiation was 36.9 years, with a mean follow-up of 96.6 months. All patients received celiprolol, and 61.5% reached the target dose (400 mg/day). One patient died of hepatic artery rupture; vascular events occurred in 11, while 14 remained event-free. No significant associations were observed between vascular event occurrence and genotype or celiprolol dose. Interviews with 11 patients revealed that celiprolol use provided emotional reassurance and promoted a more proactive approach to disease management. Celiprolol therapy may reduce fatal vascular events in vEDS and have a positive psychological impact, though nonfatal vascular complications remain frequent.

Humans↗
PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART↗
PubMed2026

Second Primary Malignancies in Patients With B-Cell Lymphomas Treated With Bruton's Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the overall second primary malignancy (SPM) burden in patients with B-cell lymphomas treated with Bruton's tyrosine kinase (BTK) inhibitors and compare SPM risk versus non-BTK inhibitor or placebo controls. METHODS: We searched major databases from inception to September 30, 2025. The primary outcome was SPM incidence. Consistent treatment backgrounds were defined as comparable baseline clinical and treatment characteristics, with BTK inhibitor exposure as the main between-arm difference. RESULTS: Fifty-two studies involving 9337 patients were included, mainly CLL/SLL; MCL was the largest non-CLL/SLL subtype. Pooled SPM incidence was 8% (95% CI: 6%-11%) with a median follow-up of 31.5 months. Multivariable meta-regression identified follow-up duration as the only independent predictor, whereas disease subtype, inhibitor generation, prior therapy lines, study design, and age were not significant. Furthermore, SPM patterns were comparable between CLL/SLL and non-CLL/SLL cohorts. Compared with controls, BTK inhibitors did not significantly increase SPM risk (RR = 1.30, 95% CI: 0.95-1.78), a finding confirmed in analyses with consistent treatment backgrounds (RR = 1.03, 95% CI: 0.85-1.25). CONCLUSIONS: SPMs occur across disease backgrounds and are mainly influenced by follow-up duration. Current evidence does not establish a direct carcinogenic effect of BTK inhibitors.

Humans↗
PubMed2026

Unraveling a Diagnostic Enigma: A TECPR2 Case Solved Through Multi-Omic Genomics.

TECPR2 is a key regulator of autophagy, encoded by the TECPR2 gene. Pathogenic variants in this gene have been linked to a rare hereditary sensory and autonomic neuropathy with intellectual disability (HSAN9). We report a teenage female with a syndromic intellectual disability disorder associated with neuromuscular abnormalities. Multi-omics analysis including genomics, transcriptomics, and proteomics, together with muscle biopsy from the affected individual, were used in this clinical case. Through trio exome sequencing we identified two heterozygous variants in the TECPR2 gene, NM_014844.4: c.480G>A; p.(Gln160=) and c.2846C>A; p.(Ala949Glu). Both were classified as variants of uncertain significance due to the lack of supporting evidence for pathogenicity. Subsequent long-read sequencing phased the variants and confirmed they were in trans. Additional functional studies using RNAseq and proteomics analyses verified the pathogenicity of the variants. This case study demonstrated the value of a multi-omics assisted analysis, which complemented the traditional phenotype-first approach in reaching a definitive clinical diagnosis.

Humans↗
PubMed2026

Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11βHSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11βHSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11βHSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11βHSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11βHSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female↗
PubMed2026

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans↗
PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗
PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗
PubMed2026

Diagnostic Value and Limitations of Dermoscopy in Humans and Animals: A Critical Comparative Analysis.

BACKGROUND: Dermoscopy is a noninvasive imaging technique that is well-established in human dermatology, where it enhances the diagnosis of neoplastic, inflammatory, infectious, and alopecic skin disorders. In veterinary dermatology, its use is expanding yet remains heterogeneous and largely descriptive, despite growing evidence of conserved dermoscopic patterns across species. HYPOTHESIS/OBJECTIVES: To review the applications of dermoscopy in veterinary dermatology, and to provide a comparative analysis of dermoscopic features observed in dogs, cats, and horses in relation to corresponding findings in human dermatology. MATERIALS AND METHODS: A systematic review of the literature reporting dermoscopic findings in veterinary dermatology was conducted in accordance with PRISMA guidelines. PubMed, Scopus and Google Scholar were searched for studies published up to 30 July 2025. Eligible studies included original articles describing dermoscopic features in dogs, cats, or horses. Extracted data included species, dermatological condition, dermoscopic findings, device type and histopathological correlation, when available. Levels of evidence were assessed using the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: Thirty studies met the inclusion criteria. Most were descriptive case reports or case series. Dermoscopy was applied to a wide range of conditions, including alopecias, parasitic infestations, dermatophytosis, neoplastic and sebaceous lesions, inflammatory dermatoses, and congenital vascular anomalies. Recurrent dermoscopic features showed strong similarities to those described in human dermatology, although species-specific anatomical differences influenced interpretation. CONCLUSIONS: Dermoscopy represents a valuable adjunct diagnostic tool in veterinary dermatology, with clear translational relevance. Standardisation of terminology and further prospective studies are required to support its broader clinical integration.

Animals↗
PubMed2026

Dynamics and virulence of Enterobacteriaceae reservoirs harboring blaCTX-M group 1 in community wastewater.

UNLABELLED: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are ubiquitous and can cause serious infections. Here, we examined untreated community wastewater influent as a reservoir for blaCTX-M group 1 organisms and their virulence potential. Raw influent samples (n = 268) were collected from four wastewater treatment plants (WWTPs) representing dense urban populations. We observed that blaCTX-M group 1 levels were high at all WWTPs and only ~1-2 log10 lower and not correlated to common human-specific microbiome fecal markers, Lachno3 and HF183, indicating a lack of connection to human fecal inputs. Concentrations of blaCTX-M group 1 genes and markers for presumptive host organisms Escherichia coli and Klebsiella pneumoniae were influenced by travel time and season. Amplicon sequencing revealed high diversity of blaCTX-M group 1-9 genes, with 63% belonging to group 1. Selective culture and 16S rRNA gene sequencing showed blaCTX-M group 1 isolates were 26% E. coli, 26% K. pneumoniae, 40% other Enterobacteriaceae, and 8% Aeromonas. Overall, E. coli averaged 3.6E7 cells/L, with 3% of all E. coli found to contain blaCTX-M group 1. Whole-genome sequencing of blaCTX-M group 1 E. coli from wastewater revealed resistance and virulence gene profiles similar to clinical isolates and distinct from other wastewater ESBL-resistant and non-resistant E. coli. Interpretation of wastewater data needs to consider both the existence of environmental reservoirs that contain potentially pathogenic organisms and the strong influence the dynamics of the conveyance system can have on final concentrations measured at the WWTP. IMPORTANCE: The CTX-M enzyme family is highly abundant in nosocomial, community, and environmental settings and is leading to treatment of infections with carbapenem antibiotics, a last-line therapeutic option. The progressive increase of the clinically relevant blaCTX-M group 1 resistance genes in the human population warrants investigation, particularly to understand the establishment and dynamics of environmental reservoirs. This study utilized molecular and culture methods to gain insight into the possible origin, abundance, and dynamics of blaCTX-M group 1 genes in untreated wastewater influent samples. We found extremely high levels of these genes, with Escherichia coli as a major host organism that closely resembled clinical strains, suggesting they are seeded and propagate in sewer pipe systems. The significance of our research is in developing approaches to monitor antimicrobial resistance reservoirs in community wastewater, which could shed light on global burdens and potential transmission cycles and indicate increasing inputs of clinically relevant strains originating from human populations.

E. coli↗
PubMed2026

ReMeDy: A Flexible Statistical Framework for Region-Based Detection of DNA Methylation Dysregulation.

Region-based epigenome-wide association studies have demonstrated improved statistical power and biological interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily through changes in mean methylation levels associated with a phenotype of interest. Substantial evidence indicates that phenotype-associated methylation alterations may also manifest through changes in methylation variability or through joint shifts in mean and variability. Despite this, no existing statistical framework jointly models mean-variance methylation changes in a region-based manner. We propose ReMeDy, a flexible statistical framework that uses a hierarchical likelihood approach within a generalized linear model setting to identify differentially methylated regions, variably methylated regions, and regions exhibiting joint differential and variable methylation at a genome-wide scale. Unlike existing models, ReMeDy operates directly on biologically defined co-methylated regions, allowing it to naturally capture spatial correlation inherent in DNA methylation array data, while avoiding reliance on heuristic, user-defined tuning parameters such as smoothing spans and kernel bandwidths that can substantially influence results and introduce subjectivity. Through extensive simulation studies and comprehensive benchmarking against popular models, we demonstrate that ReMeDy maintains false discovery and Type-I error rates at nominal levels while achieving consistently higher statistical power across a wide range of realistic scenarios. Application to population-level DNA methylation data further shows that ReMeDy identifies biologically meaningful regions and pathways implicated in complex human diseases that are not captured by conventional mean-based analyses alone. ReMeDy is implemented as an open-source R package and is freely available at https://github.com/SChatLab/ReMeDy.

DNA Methylation↗
PubMed2026

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P&#x2009;<&#x2009;0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P&#x2009;<&#x2009;0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P&#x2009;=&#x2009;0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans↗
PubMed2026

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans↗
PubMed2026

Effectiveness of Platelet Rich Plasma in Reducing Oronasal Fistula and Scar Width in Primary Cleft Lip and Palate Repair-A Systematic Review and Meta-Analysis.

This review aimed to investigate platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) efficiency in reducing oronasal fistula during primary cleft lip and palate repair. An extensive search of PubMed, Google Scholar, Global Index Medics (WHO), PubMed Scopus, Cochrane Central, Proquest was performed up to march 2025. Eligible studies included prospective RCTs and non-randomized controlled trials in human subjects. Patients aged 6-24&#x2009;months undergoing primary cleft lip and palate repair were involved. Interventions involved intraoperative use of PRP/PRF compared with controls without PRP/PRF. The primary outcome was occurrence of oronasal fistula; secondary outcomes were scar width, wound infection and postoperative bleeding with wound dehiscence. Study selection followed PRISMA guidelines, and the risk of bias was determined with the ROB-2 and ROBINS-I method of assessment. Seven studies met the required criterion and were qualitatively synthesized. Evidence suggested that PRP/PRF application was associated with a lower incidence of oronasal fistula and reduced scar width compared with controls. Additional benefits included accelerated wound healing and faster recovery. The use of autologous PRP was also reported to decrease the need for further surgical interventions. However, the certainty of evidence was limited due to small sample sizes and methodological heterogeneity. PRP and PRF show promising benefits in cleft lip and palate repair, particularly decreased fistula formation and reduced scar width. Nevertheless, current evidence is of low to very low certainty. Larger, well-designed randomized trials are required to validate the results obtained. Trial Registration: PROSPERO registration no. CRD420251032421.

Humans↗
PubMed2026

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4&#x2009;days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15&#x2009;kcal kg FFM-1 day-1) and maintaining energy availability at 45&#x2009;kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and &#x3b2;-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, &#x3b2;-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40%&#x2009;&#xb1;&#x2009;14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male↗