Tag: statistics

Clin Pharmacol Drug Dev. 2025 May 22. doi: 10.1002/cpdd.1522. Online ahead of print.

ABSTRACT

Dazukibart is a humanized monoclonal antibody selectively targeting interferon-β. The pharmacokinetics (PK), safety, tolerability, and immunogenicity of dazukibart were evaluated in 2 double-blind, randomized, placebo-controlled, single-dose, Phase 1 studies in healthy adults in China (Study 1: N = 18; dazukibart 900 mg = 15; placebo = 3) and Japan (Study 2: N = 12; Cohort 1: dazukibart 300 mg = 5, placebo = 1; and Cohort 2: dazukibart 900 mg = 5, placebo = 1). PK parameters were assessed after dosing in Study 1 and Study 2, and no significant differences were observed between PK findings among participants in both studies. A biphasic decline in dazukibart serum concentrations was observed in both studies. Exposures increased dose proportionally in Study 2. Body weight, but not race, was identified as an independent covariate of exposure using population PK modeling (including data from a Phase 1 US study [NCT02766621]). No deaths/discontinuations or serious/severe adverse events were observed, mostly mild adverse events were reported. No participants in Study 1 were antidrug antibody positive; 20.0% in Study 2 were positive for treatment-induced antidrug antibodies and neutralizing antibodies. PK parameters and immunogenicity rates were consistent with the US study, and no new safety signals were identified.

PMID:40401504 | DOI:10.1002/cpdd.1522

Nanoscale. 2025 May 22. doi: 10.1039/d4nr04820b. Online ahead of print.

ABSTRACT

Metal-organic nanotubes (MONTs) are porous, tunable 1D nanomaterials akin to metal-organic frameworks (MOFs). MONTs are synthesized via metal salts and coordinating ligands akin to MOFs, but crucially they are anisotropic, unlike most MOFs. Recently, MONTs have been shown to form statistically random copolymers; however, their mechanism of growth remains largely unexplored. Full realization of the potential of MONTs necessitates a thorough understanding of the mechanism of MONT growth. Herein, small-angle neutron scattering (SANS) was employed to investigate the copolymerization mechanism of two 1,2,4-ditriazole ligands and to quantify the inclusion of a solvent within the MONT pores. The results show parallelepiped-shaped structures are initially formed, which then aggregate to form larger lamellar structures. Additional experimentation with a deuterated ligand showed that the reactivities of all ligands are approximately equal, causing random ligand distribution within the resulting MONT. Finally, the results quantify the amount of solvent incorporated within the nanostructure pores at different stages of the formation process. These results show that early in the reaction the MONTs contain ca. 45% solvent, and they contain ca. 55% solvent late in the reaction when the MONTs are nearly fully formed.

PMID:40401467 | DOI:10.1039/d4nr04820b

Hematol Oncol. 2025 May;43(3):e70105. doi: 10.1002/hon.70105.

ABSTRACT

When describing relationships between variables and an outcome, dichotomization of continuous variables remains a widely used approach in medical research despite many drawbacks: the loss of information which reduces the statistical power to detect an association, the risk of misclassification and the problem of comparability of the results. Alternative approaches based on flexible functions are available and would allow to use all the information contained in the data and thus to model the possible non-linear relation between the continuous variable and the outcome. But these alternative approaches are rarely used probably because of a lack of clear guidance. This article aimed to illustrate the use of splines through an example based on hematological study. We showed the information provided by the plot of survival probabilities at a pre-specified time and according to the level of a continuous variable, thus displaying the trends of the studied phenomenon, as compared to a simple cut-off approach. In view of the major issues surrounding the patients’ health, it is more than necessary to use the most powerful statistical approaches for greater precision in the understanding of health phenomena so that we may make more informed decisions. We hope this article will encourage the use of these approaches.

PMID:40401449 | DOI:10.1002/hon.70105

Vector Borne Zoonotic Dis. 2025 May 22. doi: 10.1089/vbz.2025.0019. Online ahead of print.

ABSTRACT

Rodents are associated with the spread of deadly zoonotic and emerging infectious diseases. Their widespread distribution is strongly linked to their ability to thrive in human-altered environments with access to food and shelter. Thus, humans are exposed to zoonotic agents that can spread and infect them directly and indirectly. We sourced published literature on ectoparasites associated with Rattus rattus, R. norvegicus, and Mus musculus from various academic databases such as Google Scholar, PubMed, Web of Science, and Scopus. The relevant literature was screened and selected in R statistical software using the packages ”metagear” and ”revtool.” We reviewed and analyzed a total of 53 articles published between 1994 and 2024. The literature review covered studies from 29 countries, represented by six continents, namely, Africa, Asia, Europe, North America, Oceania, and South America, with the majority of the studies from Asia. R. rattus had the most published studies. Our literature review identified 87 species of zoonotic ectoparasites, with Xenopsylla cheopis, Polyplax spinulosa, and Laelaps echidninus being the most reported across all host species. Mites were the most reported ectoparasites (40.83%), followed by fleas (25%), ticks (20%), and lice (14.17%). Most of these ectoparasites were reported from R. rattus, with the highest number of documented ectoparasites. Investigating the prevalence, distribution, and potential risks of alien invasive rodents and their ectoparasites is paramount for public health and improving integrated pest management control strategies.

PMID:40401442 | DOI:10.1089/vbz.2025.0019

Mov Disord Clin Pract. 2025 May 22. doi: 10.1002/mdc3.70140. Online ahead of print.

ABSTRACT

BACKGROUND: Abnormal posture occurs in about 30% of Parkinson’s disease (PD) patients. The neuromuscular taping (NMT) is a new treatment that induces micromovements that stimulate skin receptors. Application of NMT with a decompression and eccentric technique expands the interstitial spaces and therefore improves circulation and absorption of liquids by reducing the pressure under the skin favoring the muscular relaxation.

OBJECTIVES: We conducted a 4-week, randomized, observer-blind, trial of NMT on pharmacologically treated PD patients with postural abnormality according to the item 3.13 of Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).

METHODS: The primary endpoint of the study was the change in kinetic evaluation using movement analysis technique. Main secondary endpoint was change in scale UPDRS part III score from baseline to week 4, comparing NMT+Pharmacological therapy (NMT+PT) or only Pharmacological therapy (PT). 46 PD patients were enrolled and randomly assigned to two groups. Both groups remained on stable pharmacological treatment throughout the entire duration of the study. The NMT-PT group received 8 sessions of specific decompression with neuromuscular taping.

RESULTS: At the end of the study, the kinematic data showed statistically significant change in α1 (the parameter related to the sagittal trunk inclination), close to 12% of improvement in the NMT-PT group.

CONCLUSIONS: Results showed a significant improvement in some kinematic parameters along with an improvement in motor and nonmotor symptoms in NMT + PT group compared to PT. NMT can represent a valid therapeutic option in combination with neurorehabilitation to treat abnormal posture in PD patients.

PMID:40401435 | DOI:10.1002/mdc3.70140

Neurourol Urodyn. 2025 May 22. doi: 10.1002/nau.70080. Online ahead of print.

ABSTRACT

AIMS: We examined the role of subtypes of adenosine receptors in bladder dysfunction and changes in the adenosine receptor expression in the bladder using male rats with partial bladder outlet obstruction (BOO).

METHODS: In Sprague-Dawley rats (male 8-weeks old), BOO was produced by a partial ligation of the urethra along a metal rod of a 1.2 mm outer diameter. Control rats underwent sham operation. Awake cystometrograms (CMG) were first recorded during saline instillation, and then an adenosine A1 receptor agonist (CCPA, 4.1 μM), an adenosine A2A antagonist (ZM241385, 15 μM), or inosine (1 mM) were applied intravesically in sham and BOO rats. In addition, mRNA levels of adenosine receptor subtypes in the bladder wall were measured using RT-PCR. Histological studies of bladder specimen were also performed.

RESULTS: Weights of BOO bladders were significantly (p < 0.0001) larger compared with sham bladders. In CMG, a number of non-voiding contractions (NVCs), bladder contraction amplitudes during voiding, bladder capacity, and post-void residual (PVR) were significantly (p < 0.001) increased compared with sham rats. Voiding efficiency (VE) was significantly (p < 0.001) reduced in BOO versus sham rats. Intravesical application of CCPA or inosine did not induce statistically significant effects on CMG parameters in BOO rats. Yet, ZM241385 induced a significant (p = 0.040) reduction in NVCs of BOO rats. mRNA levels of adenosine A2A and A3 receptors were significantly (p < 0.0001 and p = 0.0145, respectively) upregulated in the BOO bladder mucosa, whereas adenosine A2B receptors showed a significant (p < 0.0001) reduction in the BOO bladder mucosa compared with sham bladders. Histologically, we found the thickened detrusor muscle layer in BOO versus sham rats.

CONCLUSIONS: The male rat model of BOO seems to be suitable for exploring urethral obstruction-related bladder dysfunction at the compensated phase. In addition, the adenosine A2A receptor subtype would be a potential target for the treatment of male BOO patients with bladder overactivity.

CLINICAL TRIAL REGISTRATION: A clinical trial registration is not required as this study reported the basic research data using animal models.

PMID:40401426 | DOI:10.1002/nau.70080

Environ Sci Technol. 2025 May 22. doi: 10.1021/acs.est.4c14013. Online ahead of print.

ABSTRACT

Marine pollution from potentially toxic elements (PTEs) threatens coastal ecosystems, making long-term assessments essential. This study analyzes trends in Al, Cr, Fe, Ni, Cu, Zn, As, Cd, and Hg using 446 samples of Fucus ceranoides, F. spiralis, and F. vesiculosus collected between 1990 and 2021 at 173 coastal sites in NW Spain. A consistent resampling approach revealed significant declines in most anthropogenic PTEs, including Cu (-84.7%), Cr (-84.6%), Hg (-49.6%), and Cd (-36.7%) over time. In contrast, arsenic increased by 36.1%, but the underlying causes remain unclear, with potential factors including changes in sediment inputs, bioavailability, or emerging sources such as groundwater discharges. Higher PTE levels were detected in inner estuarine areas, but no consistent latitudinal patterns emerged. Overall, the results suggest effective mitigation of coastal pollution, with reduced bioavailable PTEs entering the food web via Fucus spp. However, rising As levels and complex contamination dynamics underscore the need for continued monitoring. This study offers the most comprehensive standardized assessment of long-term PTE trends in brown algae to date, providing valuable insights for environmental policy and coastal management.

PMID:40401394 | DOI:10.1021/acs.est.4c14013

Brief Bioinform. 2025 May 1;26(3):bbaf223. doi: 10.1093/bib/bbaf223.

ABSTRACT

Network analysis has become an essential tool in biological and biomedical research, providing insights into complex biological mechanisms. Since biological systems are inherently time-dependent, incorporating time-varying methods is crucial for capturing temporal changes, adaptive interactions, and evolving dependencies within networks. Our study explores key time-varying methodologies for network structure estimation and network inference based on observed structures. We begin by discussing approaches for estimating network structures from data, focusing on the time-varying Gaussian graphical model, dynamic Bayesian network, and vector autoregression-based causal analysis. Next, we examine analytical techniques that leverage pre-specified or observed networks, including other autoregression-based methods and latent variable models. Furthermore, we explore practical applications and computational tools designed for these methods. By synthesizing these approaches, our study provides a comprehensive evaluation of their strengths and limitations in the context of biological data analysis.

PMID:40401349 | DOI:10.1093/bib/bbaf223

Suicide Life Threat Behav. 2025 Jun;55(3):e70023. doi: 10.1111/sltb.70023.

ABSTRACT

BACKGROUND: Few studies investigate cause-specific mortality in individuals with tic disorders. We aimed to examine all-cause, natural-cause, and unnatural-cause mortality in individuals with tic disorders.

METHODS: Using the nationwide database of Taiwan from 2003 to 2017, we identified 50,018 patients with tic disorders and, using a ratio of 1:4, matched unaffected controls based on birth year and sex. Cause-specific mortality (i.e., natural cause, accident, and suicide mortality) and all-cause mortality were assessed between the two cohorts using time-dependent Cox regression models.

RESULTS: After adjusting for demographics, individuals with tic disorders had increased likelihoods (reported as adjusted hazard ratio [aHR] with 95% confidence interval [CI]) of all-cause (1.14, 1.03-1.26), unnatural-cause (including accidents and suicides; 1.78, 1.43-2.23), and suicide mortality (3.09, 2.07-4.59) compared to controls. With additional adjustments for psychiatric comorbidities, the likelihood of all-cause, unnatural-cause, and suicide mortality remained significant. However, we did not find a higher natural cause mortality in patients with tic disorders compared to controls (1.02, 0.91-1.15).

CONCLUSION: Individuals with tic disorders have a higher likelihood of unnatural causes and suicide mortality after adjusting for demographics, clinical characteristics, and psychiatric comorbidities. Our findings suggest that clinicians should routinely monitor both the physical and mental conditions of patients with tic disorders.

PMID:40401343 | DOI:10.1111/sltb.70023

Lupus. 2025 May 22:9612033251344192. doi: 10.1177/09612033251344192. Online ahead of print.

ABSTRACT

BackgroundTo summarize the clinical characteristics of pediatric lupus encephalopathy and to investigate the therapeutic efficacy of intrathecal methotrexate and dexamethasone in the treatment of pediatric lupus encephalopathy.MethodsA retrospective study was conducted on 83 children diagnosed with Neuropsychiatric systemic lupus erythematosus (NPSLE) at the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University from January 2002 to December 2023. The intrathecal injection and non-injection groups were divided based on whether they received intrathecal injections of methotrexate and dexamethasone. Clinical symptoms, laboratory tests, renal biopsy pathology, disease activity, and treatments were compared between the two groups, and the efficacy of intrathecal injection therapy for NPSLE was also assessed.ResultsOf the 83 children with NPSLE, 14 were male and 69 were female. NPSLE was the initial manifestation in 12 (14.46%) patients, while 71 (85.54%) developed it after systemic lupus erythematosus onset. The most frequently observed symptoms were headache and seizures. Imaging (CT/MRI) in 81 children showed abnormalities in 64 (79.01%), with cerebral atrophy being most common. The results of electroencephalography in 21 patients demonstrated abnormalities in 14 cases, and 7 of the 29 patients exhibited abnormal cerebrospinal fluid findings. A total of 68.67% of NPSLE patients were classified as chronic kidney disease (CKD) stage 1, while 31.33% were CKD stage 2 or higher. Renal biopsy in 60 children commonly indicated class IV or IV+V. The SLEDAI score at initial consultation was 20.93 ± 6.41. Among the 83 patients, 10 (12.05%) received intrathecal injections with an average of 5.2 per patient. Before treatment, the injection group had higher SLEDAI scores (p < 0.05). After treatment, the resolution times for NPSLE-related symptoms and imaging were shorter in the injection group, although the difference did not reach statistical significance. Notably, the injection group had a lower SLEDAI score and a more pronounced reduction (p < 0.05).ConclusionChildren with NPSLE in our center demonstrated more severe disease and higher disease activity index. Methotrexate and dexamethasone intrathecal therapy provided faster symptomatic relief and reduced disease activity in children with NPSLE.

PMID:40401342 | DOI:10.1177/09612033251344192