Category: Statistics

Phys Eng Sci Med. 2023 Nov 29. doi: 10.1007/s13246-023-01344-2. Online ahead of print.

ABSTRACT

OBJECTIVE: The consistency of bladder volume is very important in pelvic tumor radiotherapy, and portable bladder scanner is a promising device to measure bladder volume. The purpose of this study was to investigate whether the bladder volume of patients with pelvic tumor treated with radiotherapy can be accurately measured using the Meike Palm Bladder Scanner PBSV3.2 manufactured in China and the accuracy of its measurement under different influencing factors.

METHODS: A total of 165 patients with pelvic tumor undergoing radiotherapy were prospectively collected. The bladder volume was measured with PBSV3.2 before simulated localization. CT simulated localization was performed when the bladder volume was 200-400ml. The bladder volume was measured with PBSV3.2 immediately after localization and recorded. The bladder volume was then delineated on CT simulation images and recorded. To compare the consistency of CT simulation bladder volume and bladder volume measured by PBSV3.2. To investigate the accuracy of PBSV3.2 in different sex, age, treatment purpose, and bladder volume.

RESULTS: There was a significant positive correlation with bladder volume on CT and PBSV3.2 (r = 0.874; p < 0.001). The mean difference between CT measured values and PBSV3.2 was (-0.14 ± 50.17) ml. The results of the different variables showed that the overall mean of PBSV3.2 and CT measurements were statistically different in the age ≥ 65 years, bladder volumes > 400ml and ≤ 400ml groups (p = 0.028, 0.002, 0.001). There was no statistical significance between the remaining variables. The volume difference between PBSV3.2 measurement and CT was 12.87ml in male patients, which was larger than that in female patients 3.27ml. Pearson correlation analysis showed that the correlation coefficient was 0.473 for bladder volume greater than 400ml and 0.868 for bladder volume less than 400ml; the correlation coefficient of the other variables ranged from 0.802 to 0.893.

CONCLUSION: This is the first large-sample study to evaluate the accuracy of PBSV3.2 in a pelvic tumor radiotherapy population using the convenient bladder scanner PBSV3.2 made in China. PBSV3.2 provides an acceptable indicator for monitoring bladder volume in patients with pelvic radiotherapy. It is recommended to monitor bladder volume with PBSV3.2 when the planned bladder volume is 200-400ml. For male and patients ≥ 65 years old, at least two repeat measurements are required when using a bladder scanner and the volume should be corrected by using a modified feature to improve bladder volume consistency.

PMID:38019446 | DOI:10.1007/s13246-023-01344-2

Cerebellum. 2023 Nov 29. doi: 10.1007/s12311-023-01638-x. Online ahead of print.

ABSTRACT

Numerous studies have demonstrated the potential of non-invasive brain stimulation (NIBS) techniques as a viable treatment option for cerebellar ataxia. However, there is a notable dearth of research investigating the efficacy of NIBS specifically for hereditary ataxia (HA), a distinct subgroup within the broader category of cerebellar ataxia. This study aims to conduct a comprehensive systematic review and meta-analysis in order to assess the efficacy of various NIBS methods for the treatment of HA. A thorough review of the literature was conducted, encompassing both English and Chinese articles, across eight electrical databases. The focus was on original articles investigating the therapeutic effectiveness of non-invasive brain stimulation for hereditary ataxia, with a publication date prior to March 2023. Subsequently, a meta-analysis was performed specifically on randomized controlled trials (RCTs) that fulfilled the eligibility criteria, taking into account the various modalities of non-invasive brain stimulation. A meta-analysis was conducted, comprising five RCTs, which utilized the Scale for the Assessment and Rating of Ataxia (SARA) as the outcome measure to evaluate the effects of transcranial magnetic stimulation (TMS). The findings revealed a statistically significant mean decrease of 1.77 in the total SARA score following repetitive TMS (rTMS) (p=0.006). Subgroup analysis based on frequency demonstrated a mean decrease of 1.61 in the total SARA score after high-frequency rTMS (p=0.05), while no improvement effects were observed after low-frequency rTMS (p=0.48). Another meta-analysis was performed on three studies, utilizing ICARS scores, to assess the impact of rTMS. The results indicated that there were no statistically significant differences in pooled ICARS scores between the rTMS group and the sham group (MD=0.51, 95%CI: -5.38 to 6.39; p=0.87). These findings align with the pooled results of two studies that evaluated alterations in post-intervention BBS scores (MD=0.74, 95%CI: -5.48 to 6.95; p=0.82). Despite the limited number of studies available, this systematic review and meta-analysis have revealed promising potential benefits of rTMS for hereditary ataxia. However, it is strongly recommended that further high-quality investigations be conducted in this area. Furthermore, the significance of standardized protocols for NIBS in future studies was also emphasized.

PMID:38019418 | DOI:10.1007/s12311-023-01638-x

CNS Drugs. 2023 Nov 29. doi: 10.1007/s40263-023-01042-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Depression, anxiety, and/or panic disorder are often comorbid and have a complex etiology mediated through the same neuronal network. Cholecystokinin-tetrapeptide (CCK-4), a synthetic analog of the endogenous neuropeptide cholecystokinin (CCK), is thought to be implicated in this network. The CCK-4 challenge model is an accepted method of investigating the pathophysiology of panic and has been shown to mediate neuronal activation via the transient receptor potential canonical (TRPC) ion channels.

OBJECTIVES: This study aimed to assess the pharmacodynamic effects of BI 1358894, a small-molecule inhibitor of TRPC ion channel members 4 and 5 (TRPC4/5), on CCK-4-induced anxiety/panic-like symptoms and evaluate circuit engagement.

METHODS: Twenty healthy male CCK-4-sensitive volunteers entered a Phase I, double blind, randomized, two-way cross-over, single dose, placebo-controlled trial. Randomization was to oral BI 1358894 100 mg in the fed state followed by oral placebo in the fed state, or vice versa. Treatments were administered 5 h prior to intravenous CCK-4 50 µg. The primary endpoint was maximum change from baseline of the Panic Symptom Scale (PSS) sum intensity score after CCK-4 injection. Further endpoints included the emotional faces visual analog score (EVAS), the Spielberger State-Trait Anxiety Inventory (STAI), plasma adrenocorticotropic hormone (ACTH), and serum cortisol values. The safety and tolerability of BI 1358894 was assessed based on a number of parameters including occurrence of adverse events (AEs). All pharmacodynamic, pharmacokinetic, and safety endpoints were analyzed using descriptive statistics.

RESULTS: Single oral doses of BI 1358894 were generally well tolerated by the healthy male volunteers included in this study. Adjusted mean maximum change from baseline in PSS sum intensity score was 24.4 % lower in volunteers treated with BI 1358894 versus placebo, while adjusted mean maximum change from baseline of EVAS was reduced by 19.2 % (BI 1358894 vs placebo). The STAI total score before CCK-4 injection was similar in both groups (placebo: 25.1; BI 1358894: 24.3). Relative to placebo, BI 1358894 reduced CCK-4-induced mean maximum plasma ACTH and serum cortisol values by 58.6 % and 27.3 %, respectively. Investigator-assessed drug-related AEs were reported for 13/20 participants (65.0 %). There were no serious or severe AEs, AEs of special interest, AEs leading to discontinuation of trial medication, or deaths.

CONCLUSIONS: Overall, BI 1358894 reduced psychological and physiological responses to CCK-4 compared with placebo, as measured by PSS, subjective EVAS and objectively measured stress biomarkers. BI 1358894 had a positive safety profile, and single oral doses were well tolerated by the healthy volunteers. This trial (NCT03904576/1402-0005) was registered on Clinicaltrials.gov on 05.04.19.

PMID:38019356 | DOI:10.1007/s40263-023-01042-3

Eur Radiol Exp. 2023 Nov 29;7(1):74. doi: 10.1186/s41747-023-00382-5.

ABSTRACT

BACKGROUND: We tested the hypothesis that radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) promotes tumor cell release and explored a method for reducing these effects.

METHODS: A green fluorescent protein-transfected orthotopic HCC model was established in 99 nude mice. In vivo flow cytometry was used to monitor circulating tumor cell (CTC) dynamics. Pulmonary fluorescence imaging and pathology were performed to investigate lung metastases. First, the kinetics of CTCs during the periablation period and the survival rate of CTCs released during RFA were investigated. Next, mice were allocated to controls, sham ablation, or RFA with/without hepatic vessel blocking (ligation of the portal triads) for evaluating the postablation CTC level, lung metastases, and survival over time. Moreover, the kinetics of CTCs, lung metastases, and mice survival were evaluated for RFA with/without ethanol injection. Pathological changes in tumors and surrounding parenchyma after ethanol injection were noted. Statistical analysis included t-test, ANOVA, and Kaplan-Meier survival curves.

RESULTS: CTC counts were 12.3-fold increased during RFA, and 73.7% of RFA-induced CTCs were viable. Pre-RFA hepatic vessel blocking prevented the increase of peripheral CTCs, reduced the number of lung metastases, and prolonged survival (all p ≤ 0.05). Similarly, pre-RFA ethanol injection remarkably decreased CTC release during RFA and further decreased lung metastases with extended survival (all p ≤ 0.05). Histopathology revealed thrombus formation in blood vessels after ethanol injection, which may clog tumor cell dissemination during RFA.

CONCLUSION: RFA induces viable tumor cell dissemination, and pre-RFA ethanol injection may provide a prophylactic strategy to reduce this underestimated effect.

RELEVANCE STATEMENT: RFA for HCC promotes viable tumor cell release during ablation, while ethanol injection can prevent RFA induced tumor cell release.

KEY POINTS: • RFA induced the release of viable tumor cells during the ablation procedure in an animal model. • Hepatic vessel blocking can suppress tumor cells dissemination during RFA. • Ethanol injection can prevent RFA-induced tumor cell release, presumably because of the formation of thrombosis.

PMID:38019353 | DOI:10.1186/s41747-023-00382-5

Support Care Cancer. 2023 Nov 29;31(12):730. doi: 10.1007/s00520-023-08193-5.

ABSTRACT

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients’ quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin-angiotensin-aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN).

METHODS: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine-Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding.

RESULTS: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762-0.929). The result was consistent in various sensitivity analyses and important subgroup analyses.

CONCLUSIONS: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer.

PMID:38019339 | DOI:10.1007/s00520-023-08193-5

Eur J Appl Physiol. 2023 Nov 29. doi: 10.1007/s00421-023-05364-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Newly developed wearable fabric sensors (WFS) can increase the ease and accuracy of sweat sodium measurements by performing simultaneous sampling and analysis on the body during exercise.

PURPOSE: Determine the accuracy of a WFS for measurement of sodium concentration in sweat.

METHODS: Subjects wore a WFS prototype and sweat collectors on their forearm during cycle ergometry. Subjects exercised at a moderate intensity (~ 65% heart rate reserve) for 30-60 min. Sweat samples were collected and analyzed using a commercial sweat sodium analyzer (SSA) every 10-15 min. WFS were adhered with an armband and connected to custom built electronics. Accuracy was determined by comparing predicted WFS concentration to the actual concentration from the commercial SSA and analyzed statistically using ANOVA and Bland-Altman plots.

RESULTS: A total of 19 subjects completed the study. The average sweat sodium concentration was 59 mM ± 22 mM from a SSA compared with 54 mM ± 22 mM from the WFS. Overall, the average accuracy of the WFS was 88% in comparison to the SSA with p = 0.45. A line of best fit comparing predicted versus actual sweat sodium concentration had a slope of 0.99, intercept of – 4.46, and an r² of 0.90. Bland-Altman analysis showed the average concentration difference between the WFS and the SSA was 5.35 mM, with 99% of data points between ± 1.96 times the standard deviation.

CONCLUSION: The WFS accurately predicted sweat sodium concentration during moderate intensity cycle ergometry. With the need for precise assessment of sodium loss, especially during long duration exercise, this novel analysis method can benefit athletes and coaches. Further research involving longer duration and more intense exercise is warranted.

PMID:38019318 | DOI:10.1007/s00421-023-05364-4

Eur J Appl Physiol. 2023 Nov 29. doi: 10.1007/s00421-023-05356-4. Online ahead of print.

ABSTRACT

Physical activity (PA) has positive effects on various health aspects and neuronal functions, including neuronal plasticity. Exceeding a certain exercise frequency and duration has been associated with negative effects. Our study investigated the effects of excessive PA with a marathon run (MA) and regular PA (training and recovery phases) on electrocortical activity, as measured by electroencephalography (EEG). Thirty healthy marathon runners (26 male, 45 ± 9 yrs) were enrolled in the study. Four resting-state 32 channel EEG recordings were conducted: 12-8 weeks before MA (T-1), 14-4 days prior to MA (T0), 1-6 days after (T2), and 13-15 weeks after MA (T3). Power spectrum analyses were conducted using standardized Low-Resolution Electromagnetic Tomography (sLORETA) and included the following frequency bands: delta (1.5-6 Hz), theta (6.5-8.0 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-12.0 Hz), beta1 (12.5-18.0 Hz), beta2 (18.5-21.0 Hz), beta3 (21.5-30.0 Hz), and total power (1.5-30 Hz). Statistical nonparametric mapping showed reduced power both in the alpha-2 (log-F ratio = – 0.705, threshold log-F ratio = ± 0.685, p < 0.05) and in the delta frequency band (log-F ratio = -0.699, threshold log-F ratio = ± 0.685, p < 0.05) in frontal cortical areas after MA (T2 vs. T0). These effects diminished at long-term follow-up (T3). The results can be interpreted as correlates for subacute neuroplasticity induced by strenuous and prolonged PA. Although previous studies reported an increase in alpha frequency during and directly postexercise, the adverse observation a few days after exercise cessation suggests counterregulatory mechanisms, whose complex origin can be suspected in subcortical circuits, changes in neurotransmitter systems and modulation of affectivity.

PMID:38019317 | DOI:10.1007/s00421-023-05356-4

Phys Chem Chem Phys. 2023 Nov 29. doi: 10.1039/d3cp04576e. Online ahead of print.

ABSTRACT

Photoelectron imaging, electron action spectroscopy and electronic structure calculations are used to probe the structure and dynamics of MnO₄^–. Following excitation to the first bright absorption band of MnO₄^– (1¹T₂), photodetachment, via ground state electron loss, and photodissociation, to produce MnO₂^–, are both observed to occur simultaneously. MnO₂^– is produced in an excited electronic state, identified as a triplet state, which indicates that the dissociation proceeds on singlet potential energy surfaces via spin conservation. Furthermore, electronic structure calculations indicate that both photodetachment and photodissociation are multiple photon processes that are mediated by the same 1¹T₂ excited state. Taken together this data indicates that photodissociation of MnO₄^– occurs via a statistical dissociation on the MnO₄^– ground state at visible wavelengths.

PMID:38018508 | DOI:10.1039/d3cp04576e

Elife. 2023 Nov 29;12:e85012. doi: 10.7554/eLife.85012. Online ahead of print.

ABSTRACT

Even though human experience unfolds continuously in time, it is not strictly linear; instead, it entails cascading processes building hierarchical cognitive structures. For instance, during speech perception, humans transform a continuously varying acoustic signal into phonemes, words, and meaning, and these levels all have distinct but interdependent temporal structures. Time-lagged regression using temporal response functions (TRFs) has recently emerged as a promising tool for disentangling electrophysiological brain responses related to such complex models of perception. Here we introduce the Eelbrain Python toolkit, which makes this kind of analysis easy and accessible. We demonstrate its use, using continuous speech as a sample paradigm, with a freely available EEG dataset of audiobook listening. A companion GitHub repository provides the complete source code for the analysis, from raw data to group level statistics. More generally, we advocate a hypothesis-driven approach in which the experimenter specifies a hierarchy of time-continuous representations that are hypothesized to have contributed to brain responses, and uses those as predictor variables for the electrophysiological signal. This is analogous to a multiple regression problem, but with the addition of a time dimension. TRF analysis decomposes the brain signal into distinct responses associated with the different predictor variables by estimating a multivariate TRF (mTRF), quantifying the influence of each predictor on brain responses as a function of time(-lags). This allows asking two questions about the predictor variables: 1) Is there a significant neural representation corresponding to this predictor variable? And if so, 2) what are the temporal characteristics of the neural response associated with it? Thus, different predictor variables can be systematically combined and evaluated to jointly model neural processing at multiple hierarchical levels. We discuss applications of this approach, including the potential for linking algorithmic/representational theories at different cognitive levels to brain responses through computational models with appropriate linking hypotheses.

PMID:38018501 | DOI:10.7554/eLife.85012

Cell Transplant. 2023 Jan-Dec;32:9636897231213309. doi: 10.1177/09636897231213309.

ABSTRACT

This study was designed to provide evidence of the neuroprotective of human adipose-derived mesenchymal stem cells (hADSCs) in oxygen-induced retinopathy (OIR). In vivo, hADSCs were intravitreally injected into OIR mice. Various assessments, including HE (histological evaluation), TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, electroretinogram (ERG) analysis, and retinal flat-mount examination, were performed separately at postnatal days 15 (P15) and 17 (P17) to evaluate neurological damage and functional changes. Western blot analysis of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) was conducted at P17 to elucidate the neuroprotective mechanism. The P17 OIR group exhibited a significant increase in vascular endothelial cell nuclei and neovascularization that breached the ILM (inner limiting membrane) to the P17 control group. In addition, the retinal nonperfusion areas in the P17 OIR group and the number of apoptotic retinal cells in the P15 OIR group were significantly higher than in the corresponding hADSCs treatment group and control group. There was no significant thickness change in the inner nuclear layer (INL) but the outer nuclear layer (ONL) in the P17 OIR treatment group compared with the P17 OIR group. The cell density in the INL and ONL at P17 in the hADSCs treatment group was not significantly different from the OIR group. The amplitude of a-wave and b-wave in scotopic ERG analysis for the P17 OIR group was significantly lower than in the P17 hADSCs treatment group and the P17 control group. Furthermore, the latency of the a-wave and b-wave in the P17 OIR group was significantly longer than in the P17 hADSCs treatment group and the P17 control group. In addition, the expression levels of CNTF and BDNF in the P17 OIR group were statistically higher than those in the P17 control group, whereas the expression of GDNF was statistically lower in the P17 OIR group, compared with the P17 control group. The expression of CNTF and GDNF in the P17 hADSCs treatment group was statistically higher than in the P17 OIR group. However, the expression of BDNF in the P17 hADSCs treatment group was statistically lower than in the P17 OIR group. This study provides evidence for the neuroprotective effects of hADSCs in OIR.

PMID:38018498 | DOI:10.1177/09636897231213309