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Effect of a Combined Antidepressant Drug Flupentixol-Melitracen on Glucose Level and Expression of Insulin-Like Peptide Genes DILP5 and DILP6 in Drosophila melanogaster

Biomed Res Int. 2026;2026(1):e6698526. doi: 10.1155/bmri/6698526.

ABSTRACT

The number of depression sufferers is increasing at an alarming rate around the world. As a result, the usage of antidepressant drugs is growing day by day. However, the effect of this medication on glucose homeostasis is not clear. We investigated the impact of a combined antidepressant drug flupentixol-melitracen on glucose levels and the expression of associated genes in Drosophila melanogaster. The flies were reared in control and treatment vials having standard and drug-treated food. The glucose oxidase method showed significantly reduced glucose levels in the treated Drosophila. The Ct values obtained from qPCR for the relative quantification of Drosophila insulin-like peptide (DILP) genes, DILP5 and DILP6, were analyzed using the 2-ΔΔCT method. The DILP5 gene was expressed slightly higher in the antidepressant-treated group, though the expressions of the DILP genes appeared statistically insignificant. The current study suggests that anxiolytics and antidepressant drugs might be associated with the insulin signaling pathway, which is crucial for growth, glucose regulation, and other fundamental metabolic processes. Further study is required to determine the expression pattern of all DILP and other genes that might affect glucose homeostasis.

PMID:42060265 | DOI:10.1155/bmri/6698526

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Nevin Manimala Statistics

Periportal and Puncture Capsulotomy Techniques Have Similar Outcomes to Traditional Capsulotomies With Closure in Hip Arthroscopy: A Systematic Review and Meta-analysis of 2-Year Outcomes

Arthroscopy. 2026 Apr 30. doi: 10.1002/arj.70207. Online ahead of print.

ABSTRACT

PURPOSE: To systematically evaluate capsulotomy techniques through patient-reported outcome measures, rates of revision arthroscopy, conversion to total hip arthroplasty, and achievement of clinically meaningful outcomes.

METHODS: PubMed, Scopus, and Embase databases were queried in June 2024 for studies that could be used to compare capsular management strategies primarily via patient-reported outcome measures at a minimum 2-year follow-up. Inclusion criteria consisted of patients who underwent primary hip arthroscopy for the treatment of femoroacetabular impingement, minimum 2-year follow-up, and reported capsulotomy type. Based on the capsular management technique performed, groups were defined as interportal capsulotomy with closure, T-capsulotomy with complete closure, periportal capsulotomy, or puncture capsulotomy. Heterogeneity was adjusted for using metaregression models.

RESULTS: Of the 1322 unique studies identified in our search, 8 studies (1961 hips) were included. The combined puncture capsulotomy and periportal capsulotomy group (mean difference range, 21.30-32.56) performed similarly to interportal capsulotomy with closure (mean difference range, 18.33-32.00) and T-capsulotomy with complete closure (mean difference range, 20.70-23.30) groups in modified Harris Hip Score (P = .274). This continued when evaluating revision and total hip arthroplasty rates (proportion range, 0.0-0.05 and 0.0-0.01, respectively). Metaregression adjustments found baseline modified Harris Hip Score significantly influences mean differences (adjusted mean difference, -0.53 [-0.83, -0.23], P = .0006). When considering the achievement rates of minimal clinically important difference, all capsulotomy methods were similar for modified Harris Hip Score; however, minimal clinically important difference thresholds had a significant influence of -0.46 (95% confidence interval, [-0.54, -0.39], P < .0001) based on a metaregression model.

CONCLUSIONS: Periportal and puncture capsulotomy techniques did not yield statistically different outcomes compared with traditional capsulotomy techniques that use capsular closure at 2-year follow-up.

LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

PMID:42060264 | DOI:10.1002/arj.70207

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Effectiveness of clear aligners for maxillary expansion in growing patients: a systematic review and meta-analysis

Prog Orthod. 2026 Apr 30;27(1):19. doi: 10.1186/s40510-026-00620-7.

ABSTRACT

BACKGROUND: Maxillary transverse deficiency is one of the most common issues encountered in orthodontic practice. Ideally, intervention should take place before the midpalatal suture has completely ossified, in order to take advantage of the patient’s active growth. In recent years, treatment with clear aligners has emerged as an alternative to fixed appliances, offering a new way to achieve expansion in paediatric patients.

OBJECTIVES: This systematic review aimed to analyse the predictability of movements induced by clear aligners in maxillary expansion, and to compare the effectiveness of the Invisalign First® system with conventional expansion appliances.

SEARCH METHODS: A systematic review was conducted by searching PubMed-Medline, Scopus, Embase, Web of Science and Cochrane databases.

ELIGIBILITY CRITERIA: Retrospective and prospective studies, as well as one randomised clinical trial, published between January 2021 and October 2025, which answered the PICO question, were included.

DATA EXTRACTION AND SYNTHESIS: The quality of the included studies and the risk of bias were assessed using ROBINS-I (Risk of Bias in Non-randomised Studies) and ROB2 (Risk of Bias 2). For the quantitative analysis, heterogeneity among the included studies was quantified using the I2 statistic, and the results were presented in a forest plot. The Trim and Fill method was used to assess publication bias.

RESULTS: Following a review of 267 publications, 15 studies were ultimately included in the review, and seven in the meta-analysis. Statistically significant differences were reported for the following variables: intermolar distance (6-6) ( – 1.77 mm; -2.57; – 0.97 95%CI; – 4.35 Z-test, p < 0.0001); total palatal volume ( – 460.63 mm3; – 738.32; – 182.94 95%CI; – 3.25 Z-test, p = 0.0011); and arch perimeter ( – 1.75 mm; – 2.71; – 0.80 95%CI; – 3.59 Z-test, p = 0.0003). These results indicate that aligners produce significantly less skeletal transverse expansion than conventional expanders.

CONCLUSIONS: Clear aligners appear to be capable of producing maxillary expansion, mainly through dentoalveolar changes that are more evident in the anterior region and at the level of deciduous teeth. In patients presenting with more pronounced transverse deficiencies, conventional expanders seem to achieve greater skeletal and posterior transverse changes. However, given that most of the current evidence derives from retrospective studies with moderate risk of bias, these conclusions should be interpreted cautiously and confirmed by well-designed prospective research.

REGISTRATION NUMBER: CRD420250608558.

PMID:42060239 | DOI:10.1186/s40510-026-00620-7

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A patient-derived organoid model identifies TP53-dependent gemcitabine sensitivity in spinal chordoma

Discov Oncol. 2026 Apr 30. doi: 10.1007/s12672-026-05086-x. Online ahead of print.

ABSTRACT

BACKGROUND: Chordoma is a rare malignant bone tumor with limited effective systemic treatment options. Conventional chemotherapy generally shows minimal benefit, highlighting the need for predictive preclinical models to explore therapeutic vulnerabilities. Patient-derived organoids (PDOs) have emerged as a promising three-dimensional culture system that preserves tumor architecture and molecular features while enabling functional testing. However, mechanistic studies linking pathway activity to drug response in chordoma PDOs remain limited.

METHODS: Fresh surgical specimens from five patients with primary spinal chordoma were used to attempt generation of three-dimensional PDO cultures, of which primary three-dimensional cultures were successfully established. Organoids were characterized by histology, immunohistochemistry, and quantitative PCR analysis of chordoma-associated markers. Functional drug screening was performed using a panel of clinically relevant agents in a representative PDO model, followed by dose-response testing of gemcitabine. The role of TP53 in drug response was examined using small interfering RNA-mediated knockdown, with assessment of cell viability, Ki-67 expression, and DNA-damage response-related proteins. Statistical analyses were performed using one-way analysis of variance, with p < 0.05 considered statistically significant.

RESULTS: The established PDOs recapitulated the histopathological and molecular characteristics of their matched primary tumors and maintained stable growth across six passages. Among the screened agents, gemcitabine showed the strongest growth-inhibitory effect in PDO-based functional assays. Dose-response experiments confirmed significant gemcitabine-induced growth suppression. Importantly, TP53 knockdown markedly attenuated gemcitabine-induced cytotoxicity, increased proliferative activity, and reduced activation of DNA-damage response signaling, indicating a TP53-dependent vulnerability.

CONCLUSIONS: This study establishes a spinal chordoma PDO platform for functional precision oncology. Our findings identify a TP53-dependent DNA-damage vulnerability engaged by gemcitabine in patient-derived three-dimensional models, supporting biomarker-informed hypothesis generation rather than routine chemotherapy in unselected patients. This PDO-based approach provides a translational framework for exploring pathway-defined therapeutic susceptibilities in rare tumors such as chordoma.

PMID:42060212 | DOI:10.1007/s12672-026-05086-x

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Recent advances in miRNAs mediated agronomical advantageous traits improvement in rice

Mol Biol Rep. 2026 Apr 30;53(1):702. doi: 10.1007/s11033-026-11884-x.

ABSTRACT

A central enigma in crop improvement lies in introducing beneficial traits without fitness trade-offs. Rice, the cornerstone of global food security, demands multifaceted genetic innovation to sustain yield, quality, and resilience in the face of mounting climatic constraints. With the global population projected to surpass ten billion, functional master regulators such as miRNAs stand out as transformative molecular tools, capable of orchestrating complex trait networks and offering a tangible path toward the next green revolution. These are robust fine-tuners that orchestrate a myriad of functional processes and provide a value addition in emerging technologies such as assisted breeding, genome editing, and genomic selection to make rice production feasible. Herein, we have provided a comprehensive synthesis and updates on functional miRNA-mediated agronomically advantageous trait improvement exclusively for rice. It represents the latest functional understanding of miRNAs and their involvement as signatures of domestication and divergence processes, in support of the previously established notion and recent updates on emerging miRNA-assisted resources and technologies, such as their application as artificial solutions for improving genotypes, coding, and dietary potentialities for environmental safeguards and innovative biotherapeutics. Recent updates signify their robust cross-kingdom communicators’ potential for multifaceted non-host dialoguing, and their integrative action relies on the coordination with other non-coding regulatory elements for various downstream trait regulation. Moreover, specific highlights refer to the application of miRNAs for rice agronomical trait improvements, broadly classified into three functional domains, viz., biotic and abiotic stresses and yield and quality traits. Such updated functional aspects of different miRNA modules would strengthen rice improvement by facilitating a foundation and future roadmap for miRNA-mediated trait discovery and improvement.

PMID:42060211 | DOI:10.1007/s11033-026-11884-x

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Factors influencing accelerated progression in behavioral variant frontotemporal dementia

J Neurol. 2026 Apr 30;273(5):297. doi: 10.1007/s00415-026-13839-5.

ABSTRACT

INTRODUCTION: This study aimed to identify neuropsychiatric, motor, and cognitive features associated with accelerated disease progression in behavioral variant frontotemporal dementia (bvFTD).

METHODS: 192 participants were classified as having mild or moderate disease severity based on CDR + NACC FTLD global scores, with scores of 0.5 or 1.0 defined as mild (n = 106) and 2.0 as moderate (n = 86). Participants were further categorized as having accelerated (mild: n = 35; moderate: n = 32) or non-accelerated (mild: n = 71; moderate: n = 54) progression rates based on change in CDR + NACC FTLD-SB sum of boxes (SB) scores (≥ 3.5 points) between Visit 1 and 2. Random forest modeling and logistic regression identified features most predictive of accelerated progression within each group.

RESULTS: In mild bvFTD, episodic memory impairment and presence of frontal-behavioral neuropsychiatric symptoms were predictive of accelerated progression, whereas in moderate bvFTD, language impairments and motor signs were the strongest predictors. Identified features improved prediction of accelerated progression beyond demographic and clinical factors in mild (∆R2 = .22, p < 0.001) and moderate bvFTD (∆R2 = 0.11, p = 0.08) but did not achieve statistical significance in the moderate group.

DISCUSSION: Distinct clinical profiles predict accelerated progression in mild versus moderate bvFTD, underscoring the importance of stage-specific clinical markers for prognosis and care.

PMID:42060164 | DOI:10.1007/s00415-026-13839-5

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Evaluation of Patients with Hyperthermia According to the Thermoregulation Nursing Outcomes Classification

Int J Nurs Knowl. 2026 Apr 30:20473087261443269. doi: 10.1177/20473087261443269. Online ahead of print.

ABSTRACT

PurposeThis study was designed to evaluate the process of controlling body temperature in patients who were diagnosed with infection and followed up with the diagnosis of “hyperthermia” according to the NANDA-I nursing diagnosis classification according to the outcome criterion “NOC (0800) Thermoregulation Assessment.”MethodThis methodological and descriptive study was conducted with 102 inpatients followed up with the nursing diagnosis of “hyperthermia” in the Department of Infectious Diseases and Clinical Microbiology of a training and research hospital between June 2024 and June 2025. The data were collected using the “Patient Information Form” and the “NOC (0800) Thermoregulation Assessment Scale.” Statistical analyses specific to groups that were normally distributed (t-test) or not (Mann-Whitney U, Kruskal-Wallis, and Spearman correlation analysis) were done to analyze the data. For validity and reliability, the Davis Technique, Cronbach’s α coefficient, Standardized Root Mean Square Residual fit indices, and item-total correlation statistical analyses were done.FindingsThe content validity index of the NOC scale was calculated as 0.97. When the mean scores of the patients on the NOC (0800) Thermoregulation Assessment Scale were analyzed, a statistically significant difference was observed for repeated assessments (p < 0.01). The indicators “dropped skin temperature”, “hypothermia”, “heat cramps”, “heat stroke”, and “cold-related tissue damage” were “not applicable” in the study population. No statistically significant difference was found between the NOC scale mean scores of the patients according to their gender, marital status, educational level, occupation, and presence of chronic diseases (p > 0.05).ConclusionsThe Turkish version of the NOC (0800) Thermoregulation Assessment Scale was a valid tool that could be used during the process of controlling body temperature in patients with infection.Implications of nursing practiceThe use of the NOC (0800) Thermoregulation Assessment Scale would create a common language for delivering nursing care while assessing the process of controlling body temperature.

PMID:42060139 | DOI:10.1177/20473087261443269

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Circulating α-Klotho and Multidimensional Aging and Frailty Outcomes: A Systematic Review and Meta-Analysis from the European Renal Association CKD-MBD Working Group

Calcif Tissue Int. 2026 Apr 30;117(1):72. doi: 10.1007/s00223-026-01537-3.

ABSTRACT

Although α-Klotho has gained attention as a promising biomarker of aging, its association with frailty and broader aging-related outcomes beyond chronic kidney disease-mineral and bone disorder remains incompletely characterized. This systematic review and meta-analysis aimed to investigate the association between circulating α-Klotho levels and aging-related outcomes, including frailty, effects of physical activity and exercise interventions, body composition, cognitive and neuropsychiatric status, sarcopenia, and bone mineral density (BMD). A comprehensive literature search was performed across multiple electronic databases, including Ovid MEDLINE, Web of Science, Scopus, PubMed, and the Cochrane Library, to identify relevant studies published up to April 30, 2025. Pooled analyses were conducted using random-effects models, with effect estimates synthesized as mean differences, odds ratios, or correlation coefficients, and heterogeneity assessed using the I2 statistic. Risk of bias was assessed using design-specific tools, including the Newcastle-Ottawa Scale, the Risk of Bias 2 tool (RoB2) of the Cochrane collaboration, and the Joanna Briggs Institute (JBI) checklists. A total of 109 studies met the inclusion criteria and were included. In our meta-analysis, higher circulating α-Klotho levels were significantly associated with lower odds of frailty (OR = 0.61, 95% CI: 0.49, 0.77; p < 0.0001, I2 = 0%). Exercise interventions increased circulating α-Klotho (95% CI: 93.93, 261.73, p < 0.0001; I2 = 89%), but habitual physical activity showed no significant effect on α-Klotho compared to inactive controls (p = 0.25; I2 = 100%). Lower circulating α-Klotho levels were observed in individuals with osteoporosis compared with those with normal BMD (95% CI: – 114.98, – 25.49; p = 0.002) and in individuals with osteopenia compared with those with normal BMD (95% CI: – 123.22, – 0.74; p = 0.05), and were associated with fractures. Based on qualitative synthesis, circulating α-Klotho levels were positively associated with multiple physical function outcomes, including grip strength, short physical performance battery scores, and sit-to-stand performance, with mixed findings for gait speed and the 6-min walk test. Circulating α-Klotho appears to be a promising biomarker for frailty, physical function, and bone health in aging; however, evidence for cognitive outcomes remains limited and inconsistent. Substantial heterogeneity and the observational nature of most studies highlight the need for more standardized and longitudinal research.

PMID:42060134 | DOI:10.1007/s00223-026-01537-3

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Surgical treatment of coronal shear fractures: short- to mid-term results and risk factor analysis

Eur J Trauma Emerg Surg. 2026 Apr 30;52(1):154. doi: 10.1007/s00068-026-03192-7.

ABSTRACT

BACKGROUND: Coronal shear fractures of the distal humerus are rare but severe injuries. Reconstruction is often challenging, especially in comminuted cases, which is why many surgeons opt for an elbow arthroplasty in those cases. However, total elbow arthroplasty is associated with a variety of potential problems itself. Therefore, the aim of this study was to present the functional and clinical outcome of coronal shear fractures treated by osteosynthetic reconstruction in a short- to mid-term follow-up, and to identify possible risk factors for an inferior outcome.

METHODS: We performed a retrospective follow-up assessment of 51 consecutive patients (30 women; median age 56 years, (IQR 39-62)) who underwent osteosynthetic reconstruction for coronal shear fractures between 2012 and 2022 after a minimum follow-up period of two years. The Mayo Elbow Performance Score, Oxford Elbow Score, and Disabilities of the Arm, Shoulder and Hand score were evaluated, and all available radiographs were analyzed. All complications and revision procedures were assessed. Univariable and multivariate regression analyses were performed to identify potential risk factors for a poor outcome following osteosynthetic reconstruction.

RESULTS: After a median follow-up period of 43 (IQR 28-78) months, the median Mayo Elbow Performance Score was 100 (IQR 85-100), the median Oxford Elbow Score was 42 (IQR 34-46), and median Disabilities of the Arm, Shoulder and Hand score was 6 (IQR 2-28). The median ROM was 148° (IQR 126-155) for flexion, 0° (IQR 0-0) for extension, 90° (IQR 85-90) for pronation, and 90° (IQR 85-90) for supination. There was no extension deficit on the injured site. The overall complication and reoperation rates were 35.3% and 27.4%, respectively, with severe elbow stiffness being the most common reason for revision. Increasing Dubberley classification and posterior comminution were significantly associated with a poor outcome and higher rates of complications and revision.

CONCLUSION: This short- to mid-term follow-up shows good functional results after osteosynthetic reconstruction in coronal shear fractures despite high complication and revision rates. However, increasing Dubberley classification, posterior comminution and the presence of complications show inferior outcome scores. This study shows that osteosynthetic reconstruction can be an option even in comminuted coronal shear fractures. Nevertheless, patient factors need to be considered and an individual decision concerning the surgical treatment is necessary. Patients should be counseled about the high complication rates and inferior outcome with increasing Dubberley classification.

LEVEL OF EVIDENCE: Level III.

PMID:42060120 | DOI:10.1007/s00068-026-03192-7

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Effects of a resistance training program on chemotherapy-induced peripheral neuropathy, cancer-related fatigue, muscle strength and physical activity in colorectal cancer patients undergoing chemotherapy: a pilot randomized controlled trial

Clin Transl Oncol. 2026 Apr 30. doi: 10.1007/s12094-026-04371-z. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent toxicity of neurotoxic agents commonly used in colorectal cancer (CRC) and has limited evidence-based management options. Exercise may help, but the optimal prescription during chemotherapy remains uncertain. To evaluate the effects of an eight-week exercise program on CIPN (primary outcome), cancer-related fatigue (CRF), handgrip strength, and physical activity in CRC patients receiving chemotherapy.

METHODS: This pilot parallel-group randomized controlled trial screened 44 CRC patients receiving chemotherapy; 40 were randomized (1:1) to an intervention group (supervised resistance training twice weekly plus home-based aerobic exercise) or a control group (home-based physical activity program only). Outcomes were assessed at baseline and after eight weeks. NCT06404359.

RESULTS: Twenty-seven participants completed follow-up (intervention n = 15; control n = 12). Baseline characteristics were comparable. No statistically significant between-group differences were observed for CIPN, CRF, or handgrip strength. Physical activity increased significantly in the intervention group compared with controls (p < 0.001). Adherence exceeded 80%, and no exercise-related adverse events were reported.

CONCLUSIONS: In this pilot trial, an eight-week program combining supervised resistance training with home-based aerobic exercise was feasible and safe and increased self-reported physical activity, but did not demonstrate statistically significant improvements in CIPN, fatigue, or strength compared with home-based aerobic exercise alone. Larger adequately powered trials are warranted.

PMID:42060079 | DOI:10.1007/s12094-026-04371-z