bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
Authors: Moloney Eoin , Mashayekhi Atefeh , Sharma Sakshi , Kontogiannis Vasileios , Ansaripour Amir , Brownlee Wallace , Paling David , Javanbakht Mehdi 
Published: December 2024

BackgroundRelapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).MethodsThe SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA).ResultsWe included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64–1.62)), natalizumab (RR 0.99 (0.59–1.65)), alemtuzumab (RR 0.86 (0.51–1.46)), and ocrelizumab (RR 0.75 (0.44–1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49–1.92)), natalizumab (HR 1.13 (0.53–2.40)), alemtuzumab (HR 1.25 (0.56–2.81)), and ocrelizumab (HR 1.29 (0.57–2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab.ConclusionsResults of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.
Development and validation of a two-dimensional pseudorandom balance perturbation test
Authors: Wagner Andrew R. , Chirumbole Sophia G. , Caccese Jaclyn B. , Chaudhari Ajit M. W. , Merfeld Daniel M. 
Published: December 2024

IntroductionPseudorandom balance perturbations use unpredictable disturbances of the support surface to quantify reactive postural control. The ability to quantify postural responses to a continuous multidirectional perturbation in two orthogonal dimensions of sway (e.g., AP and ML) has yet to be investigated.MethodsWe developed a balance perturbation paradigm that used two spectrally independent sum of sinusoids signals (SoS1, SoS2), one for each orthogonal dimension of tilt (roll and pitch), to deliver a two-dimensional (2D) balance perturbation. In a group of 10 healthy adults we measured postural sway during 2D perturbations, as well as for each of the two individual 1D perturbation components.ResultsWe found that during 2D perturbations, spectral peaks in the sway response were larger at the perturbed frequencies when compared to (1) the adjacent non-perturbed frequencies and (2) the frequencies contained within the orthogonal, spectrally independent perturbation signal. We also found that for each of the two spectra (SoS1, SoS2), the magnitude and timing of the sway response relative to the platform disturbance was similar when measured during 1D and 2D conditions.DiscussionThese data support that our novel 2D SoS perturbation test was able to evoke ML and AP postural responses that were (1) specific to the roll and pitch perturbations, respectively, and (2) similar to the responses provoked by individual 1D perturbations.
Mediterranean diet and brain functional connectivity in a population without dementia
Authors: Karavasilis Efstratios , Balomenos Vasileios , Christidi Foteini , Velonakis Georgios , Angelopoulou Georgia , Yannakoulia Mary , Mamalaki Eirini , Drouka Archontoula , Brikou Dora , Tsapanou Angeliki , Gu Yian , Scarmeas Nikolaos 
Published: December 2024

IntroductionAdjustable lifestyle factors, such as diet, are associated with cognitive functions, structural and functional brain measures, but the association between the functional connectivity (FC) and the Mediterranean Diet (Medicine) in population without dementia is yet to be explored.MethodsThe association between MeDi and brain FC in 105 individuals without dementia aged 63 (SD ± 8.72) years old who underwent brain MRI including resting-state (rs) functional MRI (fMRI) was examined. Dietary intake was evaluated through four 24-h recalls using the multiple-pass method and adherence to the MeDi was estimated using the MedDietScore, with higher values indicating greater adherence to MeDi. Multivariable linear regression models were used to investigate the associations between FC (both positive and negative associations) and MedDietScore.ResultsRs-fMRI analysis revealed significant associations between FC and MedDietScore. The FC between the medial prefrontal cortex and a cluster located in left postcentral gyrus and in the left supramarginal gyrus was positively associated with MedDietScore. On the other hand, the FC between medial visual and right posterior division of both middle and superior temporal gyrus was negatively associated with MedDietScore. Of note, a temporal negative correlation was detected between above-mentioned FC networks. The FC between superior temporal gyrus and occipital regions was associated with participants' attention, executive functions, and memory scores. Furthermore, the associations for attention and executive functions were pronounced in participants with high adherence to MeDi compared to those with low adherence to MeDi.DiscussionIn conclusion, our study documented an association between higher adherence to MeDi and rs-FC in fronto-parietal and temporo-occipital regions, particularly in areas that are involved in cognitive processes altered across normal and pathological aging. From a clinical point of view, our findings support a favorable role of MeDi on FC which may have significant clinical implications in the rapidly aging population. Rs-fMRI is also proposed as a useful tool in the emerging field of nutritional neuroscience and a candidate non-invasive biomarker of brain aging.
The cerebellum is involved in implicit motor sequence learning
Authors: Firouzi Mahyar , Baetens Kris , Duta Catalina , Baeken Chris , Van Overwalle Frank , Swinnen Eva , Deroost Natacha 
Published: December 2024

BackgroundImplicit motor sequence learning (IMSL) is a cognitive function that allows us to execute multiple movements in a specific sequential order and plays a crucial role in our daily functional activities. Although the role of the basal ganglia network in IMSL is well-established, the exact involvement of the cerebellar network is less clear.AimHere, we aimed to address this issue by investigating the effects of cerebellar transcranial direct-current stimulation (tDCS) on IMSL.MethodsIn this sham-controlled, crossover study in 45 healthy young adults, we used mixed-effects models to analyze sequence-specific (primary outcome) and general learning effects (secondary outcome) in the acquisition (during tDCS), short- (five minutes post-tDCS) and long-term consolidation (one week post-tDCS) phases of IMSL, as measured by the serial reaction time (SRT) task.ResultsAnalyses based on response times (RTs) revealed that anodal tDCS over the cerebellum significantly increased sequence-specific learning during acquisition, compared to sham (anodal: M = 38.24 ms, sham: M = 26.78 ms, p = 0.032); did not affect general learning; and significantly slowed overall RTs (anodal: M = 362.03 ms, sham: M = 356.37 ms, p = 0.049). Accuracy-based analyses revealed that anodal tDCS reduced the probability of correct responses occurring in random trials versus sequential trials by 1.17%, p = 0.009, whereas sham tDCS had no effect, p = 0.999.ConclusionOur finding of enhanced sequence-specific learning, but not general learning, suggests that the cerebellar network not only plays a role in error correction processes, but also serves a sequence-specific function within the integrated motor learning network that connects the basal ganglia and cerebellum.
Determination of weight loss methods and effects among wrestlers before an official championship
Authors: Seker Ramazan , Isik Ozkan , Durukan Erdil , Eraslan Meric , Talaghir Laurentiu-Gabriel , Dorgan Viorel 
Published: December 2024

IntroductionIt is known that combat athletes frequently lose weight before a competition. This study aimed to determine the weight loss methods before an official championship and the effects of these weight loss methods on the performance of wrestlers.MethodThe sample of the study consisted of 350 competitive wrestlers. The “Athlete Weight Loss Methodology and Effects Scale” and personal information form were used as data collection tools in the study. In the data analysis, independent samples T-test, One-way ANOVA, and Pearson correlation analysis were used in addition to descriptive statistics.ResultsWrestlers generally reported dieting by restricting fatty (89.1%) and carbohydrate (83.4%) foods. It was observed that they preferred jogging with a raincoat (89.1%) and/or using the sauna (79.7%) as a weight loss method. Wrestlers also reported that they performed weight loss, although at a low level, by using ergogenic aids such as laxatives (31.7%) and/or diuretic pills (28.0%). They were observed to experience physiological effects such as muscle cramps (72.9%), injury (71.1%), and/or difficulty breathing (60.9%), as well as psychological effects such as feeling extremely tired (81.7%), stress (79.7%), decreased performance (78.6%) and/or extremely irritability (71.4%). It was determined that there was no difference between the weight loss methods and effects of the wrestlers according to their gender and wrestling style (p &gt; 0.05). On the other hand, it was determined that the diet level of U20 wrestlers was higher than U17 (p &lt; 0.05) and Senior wrestlers and that U17 and U20 wrestlers were exposed to higher levels of physiological and psychological effects than Senior wrestlers (p &lt; 0.05).ConclusionIt was determined that wrestlers preferred methods such as restricting food and fluids, using a sauna, and jogging with a raincoat to lose weight. It is necessary to prevent young wrestlers from losing weight before the competition. Thus, it is possible to prevent wrestlers in their development period (U17 and U20) from being exposed to physiological and psychological effects caused by losing weight.
Direct comparison of an ultrasensitive real-time PCR assay with droplet digital PCR for the detection of PIK3CA hotspot mutations in primary tumors, plasma cell-free DNA and paired CTC-derived gDNAs
Authors: Smilkou Stavroula , Kaklamanis Loukas , Balgouranidou Ioanna , Linardou Helena , Papatheodoridi Alkistis Maria , Zagouri Flora , Razis Evangelia , Kakolyris Stylianos , Psyrri Amanda , Papadimitriou Christos , Markou Athina , Lianidou Evi 
Published: December 2024

IntroductionDetection of PIK3CA mutations in primary tumors and liquid biopsy samples is of increasing importance for treatment decisions and therapy resistance in many types of cancer. The aim of the present study was to directly compare the efficacy of a relatively inexpensive ultrasensitive real-time PCR with the well-established and highly sensitive technology of ddPCR for the detection of the three most common hotspot mutations of PIK3CA, in exons 9 and 20, that are all of clinical importance in various types of cancer.Patients and methodsWe analyzed 42 gDNAs from primary tumors (FFPEs), 29 plasma-cfDNA samples, and 29 paired CTC-derived gDNAs, all from patients with ER+ metastatic breast cancer, and plasma from 10 healthy donors. The same blood draws were used for CTC isolation using EpCAM beads for positive immunomagnetic enrichment. All FFPEs and plasma-cfDNA samples were analyzed in parallel for PIK3CA mutations by ultrasensitive real-time PCR assay and droplet digital PCR.ResultsIn gDNAs from FFPEs, using ultrasensitive real-time PCR, the p.E545K mutation was detected in 22/42(52.4%), and the p.E542K and p.H1047R mutations were detected in 14/42(33.3%) and 16/42(38.1%), respectively. Using ddPCR, the p.E545K mutation was detected in 22/42(52.4%), p.E542K in 17/42(40.5%), and p.H1047R in 19/42(45.2%) samples, revealing a concordance between the two methodologies of 81%, 78.6% and 78.6% for each mutation respectively. In plasma-cfDNA, using ultrasensitive real-time PCR, the p.E545K mutation was detected in 11/29(38%) and both p.E542K and p.H1047R mutations in 2/29(6.9%).In the same plasma-cfDNA samples using ddPCR, p.E545K was detected in 1/29(3.5%), p.E542K in 2/29(6.9%), and p.H1047R in 3/29(10.5%) samples, revealing a concordance of 65.5%,100% and 93.1% for each mutation respectively. In paired CTC-derived gDNAs p.E545K was detected in 11/29(38%), p.E542K in 3/29(10.3%), and p.H1047R in 7/29(24.1%) samples.ConclusionsThis low-cost, high-throughput and ultrasensitive real-time PCR assay provides accurate and specific detection of PIK3CA hotspot mutations in liquid biopsy samples and gives similar results to ddPCR. This assay can be performed in labs where digital PCR instrumentation is not available. In CTC-derived gDNA and paired plasma-cfDNA, PIK3CA mutations detected were not identical, revealing that CTC and plasma-cfDNA give complementary information.
Cost-effectiveness of camrelizumab plus rivoceranib for advanced hepatocellular carcinoma in the context of regional disparities in China
Authors: Zhao Zhonghua , Jiang Xiongying , Wen Shiping , Hao Yanzhang 
Published: December 2024

ObjectiveTo assess the cost-effectiveness of combining camrelizumab with rivoceranib versus sorafenib as initial treatment options for advanced hepatocellular carcinoma (HCC) across different developmental regions in China.MethodsUtilizing TreeAge Pro and data from the phase III randomized CARES-310 clinical trial, a model based on Markov state transitions was developed. Health state utility values were derived from the CARES-310 trial, and direct medical costs were obtained from relevant literature and local pricing data. The primary outcome measured was the incremental cost-effectiveness ratio (ICER), defined as the cost per additional quality-adjusted life year (QALY) gained per person. The ICERs were compared against the willingness-to-pay (WTP) thresholds of different regions in China, including low-income ($16,426.80), medium-income ($34,319.01), and high-income regions ($81,036.63). Sensitivity analyses were also conducted to assess the robustness and reliability of the model under various assumptions. A tornado diagram was used to illustrate the impact of parameter variations on the model’s cost-effectiveness.ResultsFor base case analysis, QALYs per person for the cohort receiving sorafenib were 0.91, with a corresponding cost of $8,860.97. For the cohort receiving camrelizumab plus rivoceranib, the QALYs per person were 1.71, with a corresponding cost of $16,190.72. The camrelizumab plus rivoceranib treatment group exhibited an increase of 0.80 QALYs and an additional expenditure of $7,329.75. The calculated ICER was $9,150.75 per QALY, which is below the WTP thresholds for all regions in China. The camrelizumab plus rivoceranib regimen is regarded as highly cost-effective in medium-income areas of China, with a probability of 99.9%. In high-income regions, the probability reaches 100.0%. Even in low-income regions, this regimen is considered 95.6% cost-effective. Sensitivity analysis further verified that these findings were robust across various assumptions.ConclusionThe combination of camrelizumab and rivoceranib as a treatment strategy not only improves health outcomes but also represents a cost-effective option across different developmental regions in China.
Pharmacological inhibition of receptor protein tyrosine phosphatase β/ζ decreases Aβ plaques and neuroinflammation in the hippocampus of APP/PS1 mice
Authors: Fontán-Baselga Teresa , Cañeque-Rufo Héctor , Rivera-Illades Elisa , Gramage Esther , Zapico José María , de Pascual-Teresa Beatriz , Ramos-Álvarez María Del Pilar , Herradón Gonzalo , Vicente-Rodríguez Marta 
Published: December 2024

Alzheimer’s disease (AD) is a major neurodegenerative disorder that courses with chronic neuroinflammation. Pleiotrophin (PTN) is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ which is upregulated in different neuroinflammatory disorders of diverse origin, including AD. To investigate the role of RPTPβ/ζ in neuroinflammation and neurodegeneration, we used eight-to ten-month-old APP/PS1 AD mouse model. They were administered intragastrically with MY10, an inhibitor of RPTPβ/ζ, at different doses (60 and 90 mg/kg) every day for 14 days. Treatment with 90 mg/kg MY10 significantly reduced the number and size of amyloid beta (Aβ) plaques in the dorsal subiculum of the hippocampus of APP/PS1 mice. In addition, we observed a significant decrease in the number and size of astrocytes in both sexes and in the number of microglial cells in a sex-dependent manner. This suggests that RPTPβ/ζ plays an important role in modulating Aβ plaque formation and influences glial responses, which may contribute to improved Aβ clearance. In addition, MY10 treatment decreased the interaction of glial cells with Aβ plaques in the hippocampus of APP/PS1 mice. Furthermore, the analysis of proinflammatory markers in the hippocampus revealed that MY10 treatment decreased the mRNA levels of Tnfa and Hmgb1. Notably, treatment with MY10 increased Bace1 mRNA expression, which could be involved in enhancing Aβ degradation, and it decreased Mmp9 levels, which might reflect changes in the neuroinflammatory environment and impact Aβ plaque dynamics. These results support the therapeutic potential of inhibition of RPTPβ/ζ in modulating Aβ pathology and neuroinflammation in AD.
Two detoxification enzyme genes, CYP6DA2 and CarFE4, mediate the susceptibility to afidopyropen in Semiaphis heraclei
Authors: Fu Xiaochen , Xue Chao , Wang Xin , Wang Aiyu , Zhu Yanwei , Yang Yuanxue , Zhang Yun , Zhou Yun , Zhao Ming , Shan Chenggang , Zhang Jianhua 
Published: December 2024

IntroductionSemiaphis heraclei is an important economic pest affecting Caprifoliaceae and Apiaceae plants, and chemical control is still the main effective control method in the field. Afidopyropen is a new type of pyridine cyclopropyl insecticide, which can effectively control piercing-sucking mouthparts pests and is suitable for pest resistance management. However, the detoxification mechanism of S. heraclei to afidopyropen is still poorly cleared.MethodsThe insecticidal activity of afidopyropen against S. heraclei and the enzyme activity assay and synergism bioassay were evaluated. The detoxification enzyme genes were obtained by transcriptome and validated by quantitative real-time PCR (RT-qPCR). Furthermore, RNA interference was used to study the functions of detoxification enzyme genes.ResultsThe activities of cytochrome P450 monooxygenases (P450s) and carboxylesterases (CarEs) were significantly increased under afidopyropen treatment. The toxicity of afidopyropen against S. heraclei was significantly increased after application the inhibitors of piperonyl butoxide and triphenyl phosphate. Sixteen P450 genes and three CarE genes were identified in the transcriptome of S. heraclei. The RT-qPCR results showed that eleven P450 genes and two CarE genes were significantly upregulated under afidopyropen treatment, and the expression of CYP6DA2 and CarFE4 was upregulated by more than 2.5 times. The expression pattern of CYP6DA2 and CarFE4 was further analyzed in different developmental stages of S. heraclei and knockdown of CYP6DA2 and CarFE4 significantly increased the susceptibility of S. heraclei to afidopyropen.ConclusionThe results of this study uncover the key functions of CYP6DA2 and CarFE4 in the detoxification mechanism of S. heraclei to afidopyropen, and provide a theoretical basis for the scientific use of afidopyropen in the field.
Predicting the potential distribution of Astragali Radix in China under climate change adopting the MaxEnt model
Authors: Wen Zixuan , Yan Ke , Zhang Man , Ma Ruiqing , Zhu Xiaoyan , Duan Qing , Jiang Xiaolin 
Published: December 2024

IntroductionAstragali Radix is the dried root of Astragalus mongoliae or Astragalus membranaceus, a leguminous plant. Since ancient times, Astragali Radix has been widely used in Chinese traditional Chinese medicine. As people become more health-conscious, the market demand for Astragali Radix grows and its popularity is increasing in the international market. As an important medicinal plant, the growth of Astragali Radix is strongly influenced by environmental conditions. In order to meet the market demand for high quality Astragali Radix herbs, it is necessary to search and find areas suitable for the growth of Astragali Radix.MethodsIn this study, we assessed the potential impacts of climate change on the distribution of the Chinese medicinal plant Astragali Radix using the maximum entropy (MaxEnt) model in combination with a geographic information system(GIS). Distribution data and environmental variables were analyzed to predict suitable areas for Astragali Radix under the SSP126, SSP245 and SSP585 scenario for current and future (2041-2060, 2061-2080, 2081-2100). Jackknife is used to assess the importance of environmental variables, and environmental variables with a model contribution greater than 5% were considered to be the main drivers.ResultsThe results showed that the current area of suitable area for Astragali Radix is 188.41 km2, and the three climate scenarios show an increasing trend in the future, with a maximum of 212.70 km2. North China has always been the main suitable area, while the area of suitable area in Southwest China is decreasing, and Xinjiang will be developed as a new suitable area in the future. Annual precipitation (41.6%), elevation (15.9%), topsoil calcium carbonate (14.8%), annual mean temperature (8.3%), precipitation seasonality (8%) and topsoil pH (6%) contributed more to the model and were the main environmental influences on the distribution of Astragali Radix. In addition, the centroids of the suitable areas shifted northward under all three climate scenarios, indicating a migratory response to global warming.DiscussionOur study found that suitable area of Astragali Radix has been expanding for most of the time in each period of the three climate scenarios compared with the current situation. In the future, humans can focus on enhancing the cultivation techniques of Astragali Radix in these suitable areas. This study provide a scientific basis for the development of planting strategies and spatial distribution management of Astragali Radix. It helps to optimize the selection of planting areas and resource conservation of Chinese herbs.