bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forecasting the potential impact of cell and gene therapies in France: projecting product launches and patients treated
Authors: Lee Ming Kei , Seyedmousavi Sama , Auvity Sylvain , Pourroy Bertrand , Elleboode Vincent , Kachaner Isabelle , Jansen Christel , Lilliu Herve 
Published: February 2024

ObjectiveTo evaluate the potential impact of cell and gene therapies (CGTs) in France by forecasting the number of patients that will be treated with CGTs over the period 2023–2030 by therapeutic area and region.MethodsA review of CGTs in clinical development and related disease epidemiology was conducted to forecast the number of CGT launches and patient population between 2023 and 2030. The number of expected launches was identified by filtering the clinical development pipeline with estimated time to launch and probability of success values from Project ALPHA. Disease prevalence and incidence in France were combined with projected adoption rates derived from historical data to forecast the patient population to be treated.ResultsUp to 44 new CGTs are forecasted to launch in France in the period 2023–2030, which translates into more than 69,400 newly treated patients in 2030. Leading indications in terms of newly treated patients per year include cardiovascular disease, hematological cancers and solid tumors with 27,300, 15,200 and 13,000 newly treated patients in 2030, respectively.DiscussionThe forecast suggests that the future landscape of CGTs will undergo a shift, moving from CGTs targeting (ultra) rare diseases to more prevalent diseases. In France, this will likely pose organizational challenges hindering patient access to these transformative therapies. Further research and planning around network organization and patient distribution are needed to assess and improve the readiness of the French healthcare system for ensuring access for this growing number of patients to be treated with CGTs.
Iliopsoas fibrosis after revision of total hip arthroplasty revealed by 68Ga-FAPI PET/CT: a case report
Authors: Wang Yiqun , Sun Yabing , Song Junlei , Zhang Xiaojun , Li La , Shen Zhihui , Tian Jiahe , Ao Yingfang 
Published: February 2024

BackgroundTotal hip arthroplasty (THA) is a well-established surgical procedure that has been extensively validated to alleviate pain, enhance joint function, improve the ability to perform daily activities, and enhance overall quality of life. However, this procedure is associated with certain complications, among which skeletal muscle fibrosis is a frequently overlooked but significant complication that can lead to persistent pain. Currently, there is no effective method for diagnosing skeletal muscle fibrosis following total hip arthroplasty.Case reportWe report a 75-year-old male patient who complained of left groin pain after revision total hip arthroplasty. Serological examinations, X-rays, and bone scan results were all normal. However, during the 68Ga-FAPI PET/CT examination, we observed significant radiotracer uptake along the iliopsoas muscle. This abnormal uptake pattern suggested potential biological activity in this specific area. Combined with physical examination, the patient was diagnosed with iliopsoas fibrosis.ConclusionsThe presented images indicated that the uptake pattern was an important indicator for diagnosis, and the prospect of fibroblast activation protein in the diagnosis of skeletal muscle fibrosis has shown certain application value.
Christensenella minuta interacts with multiple gut bacteria
Authors: Xu Chang , Jiang He , Feng Li-Juan , Jiang Min-Zhi , Wang Yu-Lin , Liu Shuang-Jiang 
Published: February 2024

IntroductionGut microbes form complex networks that significantly influence host health and disease treatment. Interventions with the probiotic bacteria on the gut microbiota have been demonstrated to improve host well-being. As a representative of next-generation probiotics, Christensenella minuta (C. minuta) plays a critical role in regulating energy balance and metabolic homeostasis in human bodies, showing potential in treating metabolic disorders and reducing inflammation. However, interactions of C. minuta with the members of the networked gut microbiota have rarely been explored.MethodsIn this study, we investigated the impact of C. minuta on fecal microbiota via metagenomic sequencing, focusing on retrieving bacterial strains and coculture assays of C. minuta with associated microbial partners.ResultsOur results showed that C. minuta intervention significantly reduced the diversity of fecal microorganisms, but specifically enhanced some groups of bacteria, such as Lactobacillaceae. C. minuta selectively enriched bacterial pathways that compensated for its metabolic defects on vitamin B1, B12, serine, and glutamate synthesis. Meanwhile, C. minuta cross-feeds Faecalibacterium prausnitzii and other bacteria via the production of arginine, branched-chain amino acids, fumaric acids and short-chain fatty acids (SCFAs), such as acetic. Both metagenomic data analysis and culture experiments revealed that C. minuta negatively correlated with Klebsiella pneumoniae and 14 other bacterial taxa, while positively correlated with F. prausnitzii. Our results advance our comprehension of C. minuta’s in modulating the gut microbial network.ConclusionsC. minuta disrupts the composition of the fecal microbiota. This disturbance is manifested through cross-feeding, nutritional competition, and supplementation of its own metabolic deficiencies, resulting in the specific enrichment or inhibition of the growth of certain bacteria. This study will shed light on the application of C. minuta as a probiotic for effective interventions on gut microbiomes and improvement of host health.
Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease
Authors: Collu Roberto , Yin Zheng , Giunti Elisa , Daley Sarah , Chen Mei , Morin Peter , Killick Richard , Wong Stephen T. C. , Xia Weiming 
Published: February 2024

IntroductionThe goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD).MethodsWe used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice.ResultsProteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil.ConclusionsOur results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD.
Harmonizing multisite data with the ComBat method for enhanced Parkinson’s disease diagnosis via DAT-SPECT
Authors: Wakasugi Noritaka , Takano Harumasa , Abe Mitsunari , Sawamoto Nobukatsu , Murai Toshiya , Mizuno Toshiki , Matsuoka Teruyuki , Yamakuni Ryo , Yabe Hirooki , Matsuda Hiroshi , Hanakawa Takashi ,   Parkinson’s and Alzheimer’s disease Dimensional Neuroimaging Initiative (PADNI)
Published: February 2024

BackgroundDopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson’s disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as “combatting batch effects when combining batches of gene expression microarray data” (ComBat).MethodsWe analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC).ResultsThe original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges’s g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination.ConclusionAlthough we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.
Application of LightGBM hybrid model based on TPE algorithm optimization in sleep apnea detection
Authors: Xiong Xin , Wang Aikun , He Jianfeng , Wang Chunwu , Liu Ruixiang , Sun Zhiran , Zhang Jiancong , Zhang Jing 
Published: February 2024

IntroductionSleep apnoea syndrome (SAS) is a serious sleep disorder and early detection of sleep apnoea not only reduces treatment costs but also saves lives. Conventional polysomnography (PSG) is widely regarded as the gold standard diagnostic tool for sleep apnoea. However, this method is expensive, time-consuming and inherently disruptive to sleep. Recent studies have pointed out that ECG analysis is a simple and effective diagnostic method for sleep apnea, which can effectively provide physicians with an aid to diagnosis and reduce patients’ suffering.MethodsTo this end, in this paper proposes a LightGBM hybrid model based on ECG signals for efficient detection of sleep apnea. Firstly, the improved Isolated Forest algorithm is introduced to remove abnormal data and solve the data sample imbalance problem. Secondly, the parameters of LightGBM algorithm are optimised by the improved TPE (Tree-structured Parzen Estimator) algorithm to determine the best parameter configuration of the model. Finally, the fusion model TPE_OptGBM is used to detect sleep apnoea. In the experimental phase, we validated the model based on the sleep apnoea ECG database provided by Phillips-University of Marburg, Germany.ResultsThe experimental results show that the model proposed in this paper achieves an accuracy of 95.08%, a precision of 94.80%, a recall of 97.51%, and an F1 value of 96.14%.DiscussionAll of these evaluation indicators are better than the current mainstream models, which is expected to assist the doctor’s diagnostic process and provide a better medical experience for patients.
Investigating the potential causal association between consumption of green tea and risk of lung cancer: a study utilizing Mendelian randomization
Authors: Lu Jieming , Lin Ye , Jiang Junfei , Gao Lei , Shen Zhimin , Yang Changping , Lin Pinghua , Kang Mingqiang 
Published: February 2024

BackgroundLung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer.MethodsWe utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test.ResultsNo significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods.ConclusionGreen tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.
Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study
Authors: Mahajna Mahmood , Abu Fanne Rami , Odeh Mahmoud , Berkovitch Matitiahu , Tannous Elias , Eyal Sara , Vinker Shlomo , Green Ilan , Matok Ilan 
Published: February 2024

Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol’s adverse effects.Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects.Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects.Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18–11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84–9.28), and 3.25 (95% CI 1.78–5.93), respectively.Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes.
Embodied planning in climbing: how pre-planning informs motor execution
Authors: Luis-del Campo Vicente , Morenas Martín Jesús , Musculus Lisa , Raab Markus 
Published: February 2024

IntroductionThe aim of the study is to address embodied planning in climbing. Embodied planning was conceptualized as the interaction between perceptual-cognitive pre-planning and motor execution.MethodsIn an experimental study, 18 climbers were asked to pre-plan a climbing route and to perform the route afterward. During pre-planning, the visual search pattern of climbers was captured using a portable eye tracker. After previewing, they were invited to climb the wall.ResultsResults revealed that holds looked at during pre-planning were used twice as much during route execution than those not looked at. The duration of fixations was longer for holds used than those not used during route execution. The experience of climbers (training years) correlated with visual strategies and climbing performance, such that experienced participants climbed faster and fixated at the holds not used for a shorter time.DiscussionThe visual behaviors of climbers were influenced by their past sensorimotor experiences during route previewing, impacting subsequent climbing performance.
Individual and community-level factors associated with khat (Catha edulis) use among women of reproductive age in Halaba zone, South Ethiopia: a multilevel mixed effect analysis
Authors: Wogayehu Biruk , Demissie Tsegaye , Wolka Eskinder , Alemayehu Mekuriaw , Daka Kassa 
Published: February 2024

IntroductionThere is a paucity of data on factors associated with khat chewing among women of reproductive age using multilevel analysis. Furthermore, the effects of some potential factors like stressful life events, knowledge about and attitude toward the effects of khat have been given little attention and are not well understood. Therefore, this study aimed to examine the prevalence and multilevel factors associated with khat use among women of reproductive age in Halaba zone, South Ethiopia.MethodsA community-based cross sectional study was conducted in Halaba zone from February to July, 2023. Systematic random sampling technique was used to include 1573 study participants. The dependent variable was current khat use, which is operationalized as using khat within 30 days preceding the study. An interviewer administered questionnaire was used for the data collection.ResultsThe prevalence of current khat use among women of reproductive age was 65.9% [95%CI (63.5-68.2%)]. Factors significantly associated with khat use were; ages of women 35 and above years [Adjusted Odds Ratio (AOR) = 6.35, 95% CI: (3.62, 11.13)], ever married [AOR = 2.41, 95% CI: (1.10, 5.31)], secondary and above education [AOR = 0.28, 95% CI: (0.15, 0.49)], belong to richer household [AOR = 1.75, 95% CI: (1.12, 2.75)], mass media use [AOR = 3.12, 95% CI: (1.85, 4.81)], low knowledge about khat effects [AOR = 3.12, 95% CI: (1.85, 5.24)], positive attitude towards khat use [AOR = 11.55, 95% CI: (6.76, 19.71)], and strong social support [AOR = 0.43, 95% CI: (0.28, 0.64)] and non-user friend [AOR = 0.31, 95% CI: (0.20, 0.48)]. From the community level variables: rural residence [AOR = 5.06, 95% CI: (1.82, 14.09)] was significantly associated with khat use.ConclusionKhat use among women of reproductive age was found to be very high. From individual-level factors: advanced ages of women, secondary and above education, live in the richer wealth quintile, mass media exposure, low knowledge on khat effects, positive attitude towards khat use, strong social support, and from community-level variables: residing in rural area were significantly associated with khat use. Khat use screening for all women of childbearing age, as well as referral to substance use disorder centers for those women identified as having khat use disorder, should become a standard of care in all health facilities.
Nurse-led lifestyle counseling in Polish primary care: the effect of current health status and perceived barriers
Authors: Znyk Małgorzata , Kostrzewski Szymon , Kaleta Dorota 
Published: February 2024

IntroductionOur study included counseling on diet and physical activity, smoking, e-cigarette use, and alcohol consumption. The aim was to examine the correlates of counseling provided by primary care nurses with the health status/health behaviors of nurses and the barriers in the advice provided.Materials and methodsIn 2022, we conducted a cross-sectional survey among 331 nurses employed in the primary care sector in Lodz. The questionnaire consisted of three sections: characteristics of the patient population receiving treatment and provided with healthy lifestyle counseling by nurses, barriers to the process of assessing, controlling, and guiding patients, and health status/health behaviors of nurses.ResultsEighty percent of the nurses in our study provided advice on diet and physical activity to primary care patients. Over 70% of the survey participants performed minimal anti-smoking interventions forsmokers, 67.7% for alcohol drinkers, and 56.8% for e-cigarette users. The correlates of counseling in the field of diet and physical activity turned out to be the knowledge and skills, which enabled nurses to provide advice (OR = 2.57, p &lt; 0.01). The correlates of the conducted minimal anti-smoking interventions in smoking patients were: subjective assessment of overweight and obesity in nurses, knowledge and skills in conducting counseling (OR = 1.92, p &lt; 0.05), and measuring body weight, height and BMI (OR = 2.18, p &lt; 0.01). Among the three most common barriers identified by the nurses in the process of assessing, monitoring, and guiding patients were the opinion that patients are not interested in improving their diet, physical activity, and weight loss (60.7%), lack of time (51.4%), as well as the belief that patients find it too difficult to change their current habits (54.1%).ConclusionThe results of our survey indicate that nurses’ participation in healthy lifestyle counseling in adult patients is unsatisfactory. Interventions in primary care should be designed considering the specific obstacles nurses may face in leading healthy lifestyles. Further training of nursing staff is required to increase their knowledge on healthy lifestyles.