bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photophobia and migraine outcome during treatment with galcanezumab
Authors: Schiano di Cola Francesca , Ceccardi Giulia , Bolchini Marco , Caratozzolo Salvatore , Liberini Paolo , Padovani Alessandro , Rao Renata 
Published: January 2023

BackgroundCalcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in reducing ictal photophobia.Material and methodsThis is a retrospective observational study, conducted at the Headache Center–ASST Spedali Civili Brescia. All patients in monthly treatment with galcanezumab with at least a 6-month follow-up in September 2022 with reported severe photophobia during migraine attacks were included. Data regarding headache frequency, analgesics consumption, and migraine disability were collected quarterly. Moreover, patients were asked the following information regarding photophobia: (1) whether they noticed an improvement in photophobia during migraine attacks since galcanezumab introduction; (2) the degree of photophobia improvement (low, moderate, and high); and (3) timing photophobia improvement.ResultsForty-seven patients were enrolled in the present study as they met the inclusion criteria. Seventeen patients had a diagnosis of high-frequency episodic migraine and 30 of chronic migraine. From baseline to T3 and T6, a significant improvement in terms of headache days (19.2 ± 7.6 vs. 8.6 ± 6.8 vs. 7.7 ± 5.7; p &lt; 0.0001), migraine days (10.4 ± 6.7 vs. 2.9 ± 4.3 vs. 3.6 ± 2.8; p &lt; 0.0001), analgesics consumption (25.1 ± 28.2 vs. 7.6 ± 7.5 vs. 7.6 ± 8.1; p &lt; 0.0001), MIDAS score (82.1 ± 48.4 vs. 21.6 ± 17.6 vs. 18.1 ± 20.5; p &lt; 0.0001), and HIT-6 score (66.2 ± 6.2 vs. 57.2 ± 8.6 vs. 56.6 ± 7.6; p &lt; 0.0001) was found. Thirty-two patients (68.1%) reported a significant improvement in ictal photophobia, with over half of the patients reporting it within the first month of treatment. Photophobia improvement was more frequent in patients with episodic migraine (p = 0.02) and triptans responders (p = 0.03).ConclusionsThe present study confirms previous reports regarding galcanezumab efficacy beyond migraine frequency. In particular, over 60% of patients, in our cohort, documented a significant improvement also in reducing ictal photophobia. This improvement was, in most patients, moderate to high, and within the first 6 months of treatment, regardless of the clinical response on migraine frequency.
Study of brain network alternations in non-lesional epilepsy patients by BOLD-fMRI
Authors: Li Zhisen , Hou Xiaoxia , Lu Yanli , Zhao Huimin , Wang Meixia , Xu Bo , Shi Qianru , Gui Qian , Wu Guanhui , Shen Mingqiang , Zhu Wei , Xu Qinrong , Dong Xiaofeng , Cheng Qingzhang , Zhang Jibin , Feng Hongxuan 
Published: January 2023

ObjectiveTo investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.MethodsTwenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.ResultsThe area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.ConclusionThe topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease.
Proof of lung muscarinic receptor occupancy by tiotropium: Translational Positron Emission Tomography studies in non-human primates and humans
Authors: Cselényi Zsolt , Jucaite Aurelija , Ewing Pär , Stenkrona Per , Kristensson Cecilia , Johnström Peter , Schou Magnus , Bolin Martin , Halldin Christer , Larsson Bengt , Grime Ken , Eriksson Ulf G , Farde Lars 
Published: January 2023

IntroductionMolecular imaging has not been used to support the development of drugs for the treatment of pulmonary disorders. The aim of the present translational study was to advance quantitative pulmonary PET imaging by demonstrating occupancy of the reference asthma drug tiotropium at muscarinic acetylcholine receptors (mAChR).MethodsPET imaging was performed using the muscarinic radioligand [11C]VC-002. The key methodological step involved estimating muscarinic receptor binding while disentangling it from the background of non-specific binding. The relationship between tiotropium exposure and receptor occupancy (RO) was assessed in non-human primates (NHPs) after intravenous injection of tiotropium doses at a broad dose interval (0.03–1 µg/kg). The feasibility of measuring RO in the human lung was then confirmed in seven healthy human subjects after inhalation of a single therapeutic dose of tiotropium (18 µg).ResultsThere was an evident effect of tiotropium on [11C]VC-002 binding to mAChRs in lungs in both NHPs and humans. In NHPs, RO was 11 to 78% and increased in a dose dependent manner. Non-displaceable binding in NHPs was about 10% of total binding. In humans, RO was 6%–65%, and non-displaceable binding was about 20% of total binding at baseline.DiscussionThe results demonstrate that [11C]VC-002 binds specifically to mAChRs in the lungs enabling the assessment of RO following administration of muscarinic antagonist drugs. Furthermore, the methodology has potential not only for dose finding and comparison of drug formulations in future applied studies, but also for evaluating changes in lung receptor distribution during disease or in response to therapy.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03097380.
Comparative genomic analysis of esophageal squamous cell carcinoma among different geographic regions
Authors: Zhang Ruixiang , Li Canjun , Wan Zhiyi , Qin Jianjun , Li Yong , Wang Zhen , Zheng Qingfeng , Kang Xiaozheng , Chen Xiankai , Li Yun , He Jie , Li Yin 
Published: January 2023

IntroductionEsophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the genomic differences between different geographic regions remain unclear.MethodsIn this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China [XJC], Japan [JP], Vietnam [VN], and Europe &amp; America [EA]) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively.ResultsPatients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including KMT2D, FAT1, and NOTCH1 were more frequently identified in patients with ESCC from NC. Furthermore, some genes (TDG and DNAH8) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions.ConclusionsOur study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival.
Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model
Authors: Milot Marie-Christine , Bélissant-Benesty Ophélie , Dumulon-Perreault Véronique , Ait-Mohand Samia , Geha Sameh , Richard Patrick O. , Rousseau Étienne , Guérin Brigitte 
Published: January 2023

IntroductionWe have previously shown that copper-64 (64Cu)-DOTHA2-PSMA can be used for positron emission tomography (PET) imaging of prostate cancer. Owing to the long-lasting, high tumoral uptake of 64Cu-DOTHA2-PSMA, the objective of the current study was to evaluate the therapeutic potential of 64Cu-DOTHA2-PSMA in vivo.MethodsLNCaP tumor-bearing NOD-Rag1nullIL2rgnull (NRG) mice were treated with an intraveinous single-dose of 64Cu-DOTHA2-PSMA at maximal tolerated injected activity, natCu-DOTHA2-PSMA at equimolar amount (control) or lutetium-177 (177Lu)-PSMA-617 at 120 MBq to assess their impact on survival. Weight, well-being and tumor size were followed until mice reached 62 days post-injection or ethical limits. Toxicity was assessed through weight, red blood cells (RBCs) counts, pathology and dosimetry calculations.ResultsSurvival was longer with 64Cu-DOTHA2-PSMA than with natCu-DOTHA2-PSMA (p &lt; 0.001). Likewise, survival was also longer when compared to 177Lu-PSMA-617, although it did not reach statistical significance (p = 0.09). RBCs counts remained within normal range for the 64Cu-DOTHA2-PSMA group. 64Cu-DOTHA2-PSMA treated mice showed non-pathological fibrosis and no other signs of radiation injury. Human extrapolation of dosimetry yielded an effective dose of 3.14 × 10-2 mSv/MBq, with highest organs doses to gastrointestinal tract and liver.DiscussionCollectively, our data showed that 64Cu-DOTHA2-PSMA-directed radioligand therapy was effective for the treatment of LNCaP tumor-bearing NRG mice with acceptable toxicity and dosimetry. The main potential challenge is the hepatic and gastrointestinal irradiation.
Associations between CES1 variants and dosing and adverse effects in children taking methylphenidate
Authors: Brown Jacob T. , Beery Nancy , Taran Allise , Stevens Tyler , Henzler Christine , Badalamenti Jonathan , Regal Ron , McCarty Catherine A. 
Published: January 2023

BackgroundMethylphenidate is the most prescribed stimulant to treat attention deficit-hyperactivity disorder (ADHD). Despite its widespread usage, a fair proportion of children are classified as non-responders to the medication. Variability in response and occurrence of adverse events with methylphenidate use may be due to several factors, including drug-drug interactions as well as pharmacogenetic differences resulting in pharmacokinetic and/or pharmacodynamic variances within the general population. The objective of this study was to analyze the effect of carboxylesterase 1 (CES1) variants on the frequency of adverse effects and dosing requirements of methylphenidate in children with ADHD.MethodsThis was a retrospective cohort study of children and adolescents who met the inclusion criteria and had a routine visit during the enrollment period were invited to participate. Inclusion criteria included: ADHD diagnosis by a healthcare provider, between 6 and 16 years of age at the time of permission/assent, had not previously been prescribed methylphenidate, and treatment with any methylphenidate formulation for at least three consecutive months. Three months of records were reviewed in order to assess changes in dose and frequency of discontinuing methylphenidate. Participants’ ADHD symptoms, medication response, adverse effects, select vitals, and dose were extracted from the electronic health record. Saliva samples were collected by trained study coordinators. Haplotypes were assigned based on copy number in different portions of the CES1 gene. Due to limited numbers, diplotypes (combinations of two haplotypes) were grouped for analysis as CES1A1/CES1A1, CES1A1/CES1A1c and CES1A1c/CES1A1c.ResultsA total of 99 participants (n = 30 female; n = 69 male) had both clinical data and CES1 sequencing data, with an average age of 7.7 years old (range 3–15 years). The final weight-based dose in all individuals was 0.79 mg/kg/day. The most common adverse effects reported were decreased appetite (n = 47), weight loss (n = 24), and sleep problems (n = 19). The mean final weight-based dose by haplotype was 0.92 mg/kg for CES1A2/CES1A2, 0.81 mg/kg for CES1A2/CES1P1, and 0.78 mg/kg for CES1P1/CES1P1. After correction for multiple hypothesis testing, only one SNV, rs114119971, was significantly associated with weight-based dosing in two individuals. The individuals with the rs114119971 SNV had a significantly lower weight-based dose (0.42 mg/kg) as compared to those without (0.88 mg/kg; p &lt; 0.001).DiscussionVariation in CES1 activity may impact dose requirements in children who are prescribed methylphenidate, as well as other CES1 substrates. Although intriguing, this study is limited by the retrospective nature and relatively small sample size.
Effectiveness of plyometric training vs. complex training on the explosive power of lower limbs: A Systematic review
Authors: Wang Xiaolin , Lv Changhai , Qin Xinmin , Ji Shuyu , Dong Delong 
Published: January 2023

Introduction: Explosive power is considered an important factor in competitive events. Thus, strategies such as complex training (CT) and plyometric training (PLT) are effective at improving explosive power. However, it is still not clear which of the two strategies can enable greater improvements on the explosive power. Thus, the aim of this systematic review was to compare the effects of PLT and CT on the explosive power of the lower limbs.Methods: The Review Manager and GraphPad Prism programs were used to analyze the synthetic and time effects (effects over training time) on explosive power (i.e., jump ability, sprint ability) and maximum strength. Our research identified 87 studies comprising 1,355 subjects aged 10–26.4 years.Results: The results suggested the following: 1) Synthetic effects on jump ability (Hedges’ g): .79 (p &lt; .001) for unloaded PLT, 1.35 (p &lt; .001) for loaded PLT and .85 (p &lt; .001) for CT; 2) Synthetic effects on sprint ability: .83 (p &lt; .001) for unloaded PLT, −2.11 (p &lt; .001) for loaded PLT and −.78 (p &lt; .001) for CT; 3) Synthetic effects on maximum strength: .84 (p &lt; .001) for loaded PLT and 1.53 (p &lt; .001) for CT; 4) The time effects of unloaded PLT and CT on explosive power were similar, but the time effects of CT on maximum strength were obviously above that of PLT.Discussion: In conclusion, unloaded PLT and CT have a similar effect on explosive performance in the short term but loaded PLT has a better effect. The improvement of the maximum strength caused by CT was greater than that induced by PLT. In addition, more than 10 weeks of training may be more beneficial for the improvement of power. Therefore, for explosive power training, we suggest adopting unloaded or light-loaded PLT during a short season and applying CT during an annual or long training cycle.
Comparison of body composition components and anaerobic performance parameters of elite male motorcycle speedway riders between pre- and post-competitive season
Authors: Michalik Kamil , Szczepan Stefan , Markowski Maciej , Zatoń Marek 
Published: January 2023

The purpose of this study was to compare body composition components and anaerobic capacity indices in elite motorcycle speedway riders before and after the competitive season. This study included 12 volunteer male motorcycle speedway riders from the highest speedway league in Poland (PGE Speedway Ekstraliga) (age: 22.7 ± 6.0 years, body height: 171.3 ± 4.0 cm, body weight: 62.5 ± 3.1 kg). Before and after the competitive season, an assessment of body composition and Wingate test (WAnT) on a cycle ergometer with analysis of acute cardiorespiratory and biochemical responses was conducted. Sport level for all riders was defined by the number of heats won (WS), the total number of points scored in all heats including bonus points (PTS + B), and the percentage of heats won (%W). The motorcycle speedway riders participated in an average of 75.3 ± 15.0 total heats (HS) and obtained PTS + B equal 136.8 ± 48.2. The anaerobic performance, body composition, cardiorespiratory and biochemical responses did not changed after the competitive season. The significant statistical correlations were noted between the differences in the Fatigue Index during WAnT and total number of heats (r = −0.61) and with PTS + B (r = −0.58). Positively correlations were observed also between HS and differences: fat mass (FM) (r = 0.60) and percentage of fat mass (r = 0.61) (all p &lt; 0.05). These findings reveal that the HS during the competitive season is related to the stabilization of anaerobic capacity in the WAnT. The HS is positively correlated with an increase in fat mass, and additional fat mass can adversely affect athletic performance in speedway.
Compulsory care of individuals with severe substance use disorders and alcohol- and drug-related mortality: A Swedish registry study
Authors: Scarpa Simone , Grahn Robert , Lundgren Lena M. 
Published: January 2023

AimThis study used 17 year of Swedish registry data (2003–2019) for 25,125 adults assessed for their severity of substance use to identify the baseline factors predicting the risk of being court-ordered into compulsory care and examine the association between admission to compulsory care and mortality risks due to alcohol- or drug-related causes.Methods and materialsAddiction Severity Index (ASI) assessment data were linked to register data on demographic characteristics, compulsory care, and alcohol- and drug-related mortality. Cox regression models were used to identify baseline factors predictive of post-assessment admission to compulsory care in the 5 years post-substance use assessment. Discrete-time random-effect logistic regression models were used to examine the association between compulsory care duration and alcohol or drug-related mortality risks. Propensity score matching was used for validation.ResultsThe first models identified that younger age, female gender, and ASI composite scores for drug use, mental health and employment were significantly associated with the risk of placement in compulsory care for drugs other than alcohol. Female gender and ASI composite scores for alcohol, drug use and employment were significantly associated with compulsory care treatment for alcohol use. The second models showed that older individuals and men were more likely to die due to alcohol-related causes, while younger individuals and men were more likely to die due to drug-related causes. Length of stay in compulsory care institutions significantly increased the likelihood of dying due to substance use-related causes. Propensity scores analyses confirmed the results.ConclusionIn Sweden, a significant concern is the higher likelihood of women and young individuals to be court-ordered to compulsory care. Although compulsory care is often advocated as a life-saving intervention, our findings do not provide strong support for this claim. On the contrary, our findings show that admission to compulsory care is associated with a higher risk of substance use-related mortality. Factors such as compulsory care often not including any medical or psychological therapy, together with relapse and overdose after discharge, may be possible contributing factors to these findings.
A feasibility study of a new instrument for detection of autism signs in preschool settings. Psychometric properties of the joint attention observation schedule preschool (JA-OBS preschool)
Authors: Linnsand Petra , Hermansson Jonas , Gillberg Christopher , Nygren Gudrun 
Published: January 2023

BackgroundIdentifying signs of autism is essential for enabling timely diagnosis and intervention. Children from multiethnic and socioeconomic disadvantaged settings are typically diagnosed with autism later than their general peers. This feasibility study explored the psychometric properties of a new instrument, Joint Attention Observation Schedule Preschool (JA-OBS Preschool), in children with suspected autism.MethodsData were collected from a prospective longitudinal study of 46 children aged 2–4 years who lived in a multiethnic, low resource area. The children had been referred from the Child Health Centre to a multiprofessional team for a neuropsychiatric assessment. In the diagnostic process, the instrument JA-OBS Preschool for observation of a child's capability of engaging in joint attention was included. Descriptive statistics and Cronbach's alfa were used to analyze the psychometric properties, including internal consistency reliability and inter-rater consistency.ResultsAll 46 children with suspected autism screened positive on the JA-OBS Preschool. The internal consistency reliability of the instrument was calculated at 0.8 (Cronbach's alfa). Percent agreement between two examiners in JA-OBS Preschool ranged from 77% to 100%.ConclusionJA-OBS Preschool was found to be a promising instrument for identifying signs of autism in children in this setting. However, further research is needed to determine the psychometric properties of the JA-OBS Preschool in a general child population as well as in a younger age group.