bluuebunny/crossref_metadata_2025_split huggingface dataset:
AlphaBet: Combination of Radium-223 and [177Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol)
Authors: Kostos Louise , Buteau James P. , Yeung Theresa , Iulio Juliana Di , Xie Jing , Cardin Anthony , Chin Kwang Y. , Emmerson Brittany , Owen Katie L. , Parker Belinda S. , Fettke Heidi , Furic Luc , Azad Arun A. , Hofman Michael S. 
Published: November 2022

Background[177Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [177Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression. Micrometastases in this area likely receive an inadequate dose of radiation, as the emitted beta-particles from 177Lu travel an average range of 0.7 mm in soft tissue, well beyond the diameter of micrometastases. Radium-223 (223Ra) is a calcium-mimetic and alpha-emitting radionuclide approved for use in men with mCRPC with bone metastases. The range of emitted alpha particles in soft tissue is much shorter (≤100 μm) with high linear energy transfer, likely more lethal for osseous micrometastases. We anticipate that combining a bone-specific alpha-emitter with [177Lu]Lu-PSMA will improve eradication of micrometastatic osseous disease, and thereby lead to higher and longer responses.MethodsThis is a single-center, single-arm phase I/II trial evaluating the combination of 223Ra and [177Lu]Lu-PSMA-I&amp;T in men with mCRPC. Thirty-six patients will receive 7.4 GBq of [177Lu]Lu-PSMA-I&amp;T, concurrently with 223Ra in escalating doses (28 kBq/kg – 55kBq/kg), both given intravenously every six weeks for up to six cycles. Eligible patients will have at least two untreated bone metastases visible on bone scintigraphy, and PSMA-positive disease on PSMA PET scan. Patients must have adequate bone marrow and organ function and be willing to undergo tumor biopsies. Patients with discordant disease visible on FDG PET scan (defined as FDG positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other key exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than one prior line of chemotherapy for prostate cancer. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with [177Lu]Lu-PSMA-I&amp;T and the 50% PSA response rate.ConclusionThe AlphaBet trial is a phase I/II study combining 223Ra with [177Lu]Lu-PSMA-I&amp;T in patients with mCRPC. We aim to enroll the first patient in Q3 2022, and recruitment is anticipated to continue for 24 months.Study registrationNCT05383079.
Antarctic Sphingomonas sp. So64.6b showed evolutive divergence within its genus, including new biosynthetic gene clusters
Authors: Núñez-Montero Kattia , Rojas-Villalta Dorian , Barrientos Leticia 
Published: November 2022

IntroductionThe antibiotic crisis is a major human health problem. Bioprospecting screenings suggest that proteobacteria and other extremophile microorganisms have biosynthetic potential for the production novel antimicrobial compounds. An Antarctic Sphingomonas strain (So64.6b) previously showed interesting antibiotic activity and elicitation response, then a relationship between environmental adaptations and its biosynthetic potential was hypothesized. We aimed to determine the genomic characteristics in So64.6b strain related to evolutive traits for the adaptation to the Antarctic environment that could lead to its diversity of potentially novel antibiotic metabolites.MethodsThe complete genome sequence of the Antarctic strain was obtained and mined for Biosynthetic Gene Clusters (BGCs) and other unique genes related to adaptation to extreme environments. Comparative genome analysis based on multi-locus phylogenomics, BGC phylogeny, and pangenomics were conducted within the closest genus, aiming to determine the taxonomic affiliation and differential characteristics of the Antarctic strain.Results and discussionThe Antarctic strain So64.6b showed a closest identity with Sphingomonas alpina, however containing a significant genomic difference of ortholog cluster related to degradation multiple pollutants. Strain So64.6b had a total of six BGC, which were predicted with low to no similarity with other reported clusters; three were associated with potential novel antibiotic compounds using ARTS tool. Phylogenetic and synteny analysis of a common BGC showed great diversity between Sphingomonas genus but grouping in clades according to similar isolation environments, suggesting an evolution of BGCs that could be linked to the specific ecosystems. Comparative genomic analysis also showed that Sphingomonas species isolated from extreme environments had the greatest number of predicted BGCs and a higher percentage of genetic content devoted to BGCs than the isolates from mesophilic environments. In addition, some extreme-exclusive clusters were found related to oxidative and thermal stress adaptations, while pangenome analysis showed unique resistance genes on the Antarctic strain included in genetic islands. Altogether, our results showed the unique genetic content on Antarctic strain Sphingomonas sp. So64.6, −a probable new species of this genetically divergent genus–, which could have potentially novel antibiotic compounds acquired to cope with Antarctic poly-extreme conditions.
Gait variability predicts cognitive impairment in older adults with subclinical cerebral small vessel disease
Authors: Mukli Peter , Detwiler Sam , Owens Cameron D. , Csipo Tamas , Lipecz Agnes , Pinto Camila Bonin , Tarantini Stefano , Nyul-Toth Adam , Balasubramanian Priya , Hoffmeister Jordan R. , Csiszar Anna , Ungvari Zoltan , Kirkpatrick Angelia C. , Prodan Calin I. , Yabluchanskiy Andriy 
Published: November 2022

IntroductionAdvanced methods of gait research, including approaches to quantify variability, and orderliness/regularity/predictability, are increasingly used to identify patients at risk for the development of cognitive impairment. Cerebral small vessel disease (CSVD) is highly prevalent in older adults and is known to contribute to the development of vascular cognitive impairment and dementia (VCID). Studies in preclinical models demonstrate that subclinical alterations precede CSVD-related cognitive impairment in gait coordination. In humans, CSVD also associates with gait abnormalities. The present study was designed to test the hypothesis that increased gait variability and gait asymmetry predict a decline in cognitive performance in older adults with CSVD.MethodsTo test this hypothesis, we compared cognitive performance and gait function in patients with CSVD (age: 69.8 ± 5.3 years; n = 11) and age- and sex-matched control participants (age: 70.7 ± 5.8 years; n = 11). Based on imaging findings, patients with CSVD were identified [presence of white matter hyperintensities plus silent brain infarcts and/or microhemorrhages on magnetic resonance imaging (MRI) assessment]. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Gait parameters were measured during the single and dual tasks, during which participants, in addition to the motor task, completed a series of mental arithmetic calculations. Spatial and temporal parameters of gait variability, symmetry, and permutation entropy were determined using a pressure-sensitive gait mat during single and dual cognitive task conditions.ResultsPatients with CSVD exhibited lower performance in a visual learning test (p = 0.030) and in a sustained attention test (p = 0.007). CSVD also affected step time variability (p = 0.009) and step length variability (p = 0.017). Step lengths of CSVD participants were more asymmetric (p = 0.043) than that of controls, while the two groups were statistically similar regarding step time symmetry and entropy of step time and length. Gait variability was inversely associated with sustained attention, especially among CSVD patients, and this relationship was significantly different between the two groups. The association of sustained attention with gait symmetry was also significantly different between the two groups.DiscussionOur findings provide additional evidence in support of the concept that increased gait variability and asymmetry may predict cognitive impairment in older adults with CSVD.
Effectiveness of COVID-19 vaccines in a large European hemodialysis cohort
Authors: Bernardo Ana Paula , Carioni Paola , Stuard Stefano , Kotanko Peter , Usvyat Len A. , Kovarova Vratislava , Arkossy Otto , Bellocchio Francesco , Tupputi Antonio , Gervasoni Federica , Winter Anke , Zhang Yan , Zhang Hanjie , Ponce Pedro , Neri Luca 
Published: November 2022

BackgroundHemodialysis patients have high-risk of severe SARS-CoV-2 infection but were unrepresented in randomized controlled trials evaluating the safety and efficacy of COVID-19 vaccines. We estimated the real-world effectiveness of COVID-19 vaccines in a large international cohort of hemodialysis patients.MethodsIn this historical, 1:1 matched cohort study, we included adult hemodialysis patients receiving treatment from December 1, 2020, to May 31, 2021. For each vaccinated patient, an unvaccinated control was selected among patients registered in the same country and attending a dialysis session around the first vaccination date. Matching was based on demographics, clinical characteristics, past COVID-19 infections and a risk score representing the local background risk of infection at vaccination dates. We estimated the effectiveness of mRNA and viral-carrier COVID-19 vaccines in preventing infection and mortality rates from a time-dependent Cox regression stratified by country.ResultsIn the effectiveness analysis concerning mRNA vaccines, we observed 850 SARS-CoV-2 infections and 201 COVID-19 related deaths among the 28110 patients during a mean follow up of 44 ± 40 days. In the effectiveness analysis concerning viral-carrier vaccines, we observed 297 SARS-CoV-2 infections and 64 COVID-19 related deaths among 12888 patients during a mean follow up of 48 ± 32 days. We observed 18.5/100-patient-year and 8.5/100-patient-year fewer infections and 5.4/100-patient-year and 5.2/100-patient-year fewer COVID-19 related deaths among patients vaccinated with mRNA and viral-carrier vaccines respectively, compared to matched unvaccinated controls. Estimated vaccine effectiveness at days 15, 30, 60 and 90 after the first dose of a mRNA vaccine was: for infection, 41.3%, 54.5%, 72.6% and 83.5% and, for death, 33.1%, 55.4%, 80.1% and 91.2%. Estimated vaccine effectiveness after the first dose of a viral-carrier vaccine was: for infection, 38.3% without increasing over time and, for death, 56.6%, 75.3%, 92.0% and 97.4%.ConclusionIn this large, real-world cohort of hemodialyzed patients, mRNA and viral-carrier COVID-19 vaccines were associated with reduced COVID-19 related mortality. Additionally, we observed a strong reduction of SARS-CoV-2 infection in hemodialysis patients receiving mRNA vaccines.
A comparative analysis of body composition assessment by BIA and DXA in children with type II and III spinal muscular atrophy
Authors: Wang Wenqiao , Feng Yijie , Long Qi , Chen Fei , Chen Yuzhi , Ma Ming , Mao Shanshan 
Published: November 2022

BackgroundBody composition analysis is a valuable tool for assessing and monitoring the nutritional status of children with spinal muscular atrophy (SMA). This study was designed to compare the consistency of bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), as the gold standard method for assessing body composition in clinical practice when treating children with type II and III SMA.MethodsFrom 2019 to 2021, we performed a retrospective analysis of body composition by DXA and BIA measurement methods in patients with type II and III SMA treated at a Chinese tertiary children's hospital. Fat mass (FM), muscle mass (MM), bone mineral content (BMC), and visceral fat area (VFA) were compared using paired sample t-tests. We calculated Lin's concordance correlation coefficient (CCC) and Spearman correlation coefficient to verify the correlation between DXA and BIA measurements. Bland–Altman analysis was used to assess the consistency of the two methods.ResultsFifty-seven children with type II and III SMA were recruited. Compared with body composition measured by DXA, the average FM measured by BIA is significantly lower (P &lt;0.001), whereas the average MM, BMC, and VFA measured by BIA are significantly higher (P &lt; 0.001) in children with SMA. Overall, the difference between MM (Delta [BIA-DAX] = 1.6 kg) and FM (Delta [BIA-DAX] = −1.6 kg) measured by DXA and BIA was minor, whereas the difference of VFA (Delta [BIA-DAX] = −43.5 cm) was significantly large. Correlation analysis indicated a substantial correlation of MM (CCC = 0.96 [95% confidence interval (CI) = 0.93–0.98], r = 0.967 [P &lt; 0.0001]) and FM (CCC = 0.95 [95% CI = 0.92–0.97], r = 0.953 [P &lt; 0.0001]), and poor correlation of BMC (CCC = 0.61 [95% CI = 0.42–0.75], r = 0.612 [P &lt; 0.0001]) and VFA (CCC = 0.54 [95% CI = 0.33–0.70], r = 0.689 [P &lt; 0.0001]) measurements between the two methods. The Bland–Altman analysis suggests that the majority of participants were within LOA. In addition, differences in MM and VFA measurements between BIA and DAX increased according to patients' increasing height, whereas differences in FM and BMC did not differ with height.ConclusionBIA overestimates MM and underestimates the FM, BMC, and VFA in children with SMA compared with DXA measurements. Overall, the non-invasive, easy-to-use, and repeatable BIA measurements were found to be in good agreement with DXA measurements, especially for FM and MM, which are essential parameters for the nutritional evaluation of children with SMA.
Affective Theory of Mind as a residual ability to preserve mentalizing in amnestic Mild Cognitive Impairment: A 12-months longitudinal study
Authors: Rossetto Federica , Isernia Sara , Cabinio Monia , Pirastru Alice , Blasi Valeria , Baglio Francesca 
Published: November 2022

IntroductionTheory of Mind (ToM) decline has been outlined in people with amnestic Mild Cognitive Impairment (aMCI), but evidence from longitudinal studies is lacking. This longitudinal study aims to investigate changes in cognitive and affective ToM performance in an aMCI sample (n = 28; 14 females, mean age = 76.54 ± 4.35).MethodParticipants underwent two steps of neurocognitive evaluation, at the baseline (T1) and 12-month follow-up (T2), to obtain their global cognitive level and both affective (Reading the Mind in the Eyes test, ET) and cognitive (Strange Stories, SS) ToM profile. Then, participants were categorized into two groups based on ToM changes: people who worsened (ETΔ &lt; 0; SSΔ &lt; 0) and people who did not (ETΔ≥0; SSΔ≥0) at follow-up. Differences between groups in cognitive functions and ToM profiles at baseline have been investigated.ResultsOur results showed that 46% of subjects worsened in affective (ET) and 28% in cognitive (SS) ToM at follow-up. People who worsened in ET reported a statistically significantly higher performance in ET at baseline (p = 0.002) but not at follow-up than people who did not worsen. In contrast, subjects who worsened in SS showed a lower Immediate Free Recall (IFR, p = 0.026) and Delayed Free Recall (DFR, p = 0.028) score of the Free and Cued Selective Reminding test at baseline and at follow-up, a lower ET (p = 0.020) baseline score, a lower SS and MMSE level at follow-up than people who not worsened. About 71% of MCI subjects showed the same trend of evolution of the Mini-Mental State Examination and SS. Variables that significantly differed between groups have been inserted in a stepwise logistic regression to pilot explore predictors of affective and cognitive ToM evolution. Logistic regression showed ET at baseline (p = 0.015) as the only significant predictor of affective ToM evolution (R2 = 0.450), while both ET (p = 0.044) and memory performance (p = 0.045) at baseline significantly predicted cognitive ToM evolution (R2 = 0.746).DiscussionIn conclusion, our results support the role of affective ToM as a residual mentalizing ability in preserving the mentalizing level in people with aMCI.
Association between plasma selenium and risk of ischemic stroke: A community-based, nested, and case-control study
Authors: Wang Zhuo , Hu Shiyu , Song Yun , Liu Lishun , Huang Zhengzheng , Zhou Ziyi , Wei Yaping , Lin Tengfei , Huang Meiqing , Zhang Hao , Guo Huiyuan , Sun Yong , Wang Binyan , Qin Xianhui , Xu Xiping , Chi Feng , Ren Bohua , Ren Lijie 
Published: November 2022

BackgroundThe prospective association between plasma Se and stroke risk remains inconclusive. The relationship between Se and ischemic stroke among a low circulating Se status population deserves more attention, especially for Chinese people who were a high-risk group for Se deficiency.ObjectiveThe relationship between plasma Se concentration and ischemic stroke risk in a large-scale Chinese community-based population and any potential effect modifiers were investigated.MethodsA nested, case-control study, using data from the “China H-type Hypertension Registry Study” were conducted. A total of 1,904 first ischemic stroke cases and 1,904 controls matched for age, sex, and village were included in this study. The association between plasma Se and first ischemic stroke was evaluated by conditional logistic regression analyses.ResultsThe median value of plasma Se was 65.8 μg/L among total participants. Overall, a significant inverse relationship between plasma Se and first ischemic stroke risk was found (per SD increment; adjusted OR: 0.87; 95% CI: 0.80 and 0.95). Accordingly, a significantly lower risk of first ischemic stroke was found in participants in quartile 3 (65.8−&lt;77.8 μg/L) (adjusted OR: 0.78; 95% CI: 0.63 and 0.96) and quartile 4 (≥77.8 μg/L) (adjusted OR: 0.76; 95% CI: 0.59 and 0.96), compared with those in quartile 1 (&lt;56.0 μg/L). Furthermore, a significantly lower ischemic stroke risk was found in those with lower low-density lipoprotein cholesterol (LDL-C) levels (&lt;3.4 vs. ≥3.4 mmol/L; P for interaction = 0.015) or those with lower homocysteine levels (&lt;12.1 (median) vs. ≥12.1 μmol/L; P for interaction = 0.027) at baseline.ConclusionPlasma Se was significantly inversely associated with the risk of first ischemic stroke among a large-scale Chinese community-based population (most adults with hypertension and elevated total homocysteine), especially among those with lower LDL-C and lower homocysteine levels.
Vitamin D insufficiency is high in Malaysia: A systematic review and meta-analysis of studies on vitamin D status in Malaysia
Authors: Mohd Saffian Shamin , Jamil Nor Aini , Mohd Tahir Nor Asyikin , Hatah Ernieda 
Published: November 2022

PurposeTo estimate the vitamin D status of participants residing in Malaysia.MethodsPubMed, Scopus, Web of Science, and MyJurnal were searched up to June 2022 without language restrictions. Studies that reported the 25-hydroxyvitamin D [25(OH)D] concentrations and defined their cut-off for deficiency or insufficiency from healthy participants residing in Malaysia were included. The random effects model was used to pool vitamin D status using established cut-offs of &lt;30, &lt;50, and &lt;75 nmol/L according to age group.ResultsFrom 299 studies screened, 32 studies were included in the meta-analysis. The pooled proportion for &lt;30 nmol/L was 21% (95% CI 9–36, n = 2,438 from 10 studies), while the pooled proportion &lt;50 nmol/L was 64% (95% CI 56–72, n = 13,977 from 30 studies), and &lt;75 nmol/L was 85% (95% CI 61–100, n = 1,376 from five studies). Heterogeneity was high (I2 ranged from 98–99%). Higher proportions of vitamin D insufficiency (defined as &lt;50 nmol/L) were found in participants living in the urban areas (compared to rural areas), in females (compared to males), and in Malays and Malaysian Indians (compared to Malaysian Chinese) ethnicities.ConclusionMore than half of Malaysians have insufficient vitamin D levels, despite being a country that is close to the equator. We strongly urge prompt public health measures to improve the vitamin D status in Malaysia.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021260259].
Association between maternal sugar-sweetened beverage consumption and the social-emotional development of child before 1 year old: A prospective cohort study
Authors: Gao Rui , Liu Xuemei , Li Xiuxiu , Zhang Yuanxing , Wei Min , Sun Peng , Zhang Jianan , Cai Li 
Published: November 2022

BackgroundExcessive consumption of sugar-sweetened beverages (SSBs) has become an international public health issue. Adverse effects of sugary beverage consumption on both mother and child during pregnancy continue to be found. However, evidence regarding maternal SSB consumption and social-emotional development of children is lacking.MethodsBased on the Shenzhen Birth Cohort Study (loss rate: 10.97%), we included 985 mother-infant pairs from 2018 to 2022. All mothers had a singleton live birth without hypertension, diabetes, tumor, or serious immune system disease before pregnancy. We used a chart of frequency distribution to show maternal SSB consumption, including non-diet soda, tea drinks (not 100% tea), fruit drinks, Sugar-sweetened coffee, bubble tea, or cocoa drinks, and total SSBs. A multivariate logistic regression model was used to estimate the odds ratios of the potential delay on social-emotional development of each child was monitored at both 6 months and 12 months of age based on maternal SSB consumption.ResultsAmong the mothers, 728 (73.91%) drank SSBs &lt;1 time per week, 194 (19.70%) drank SSBs 1–2 times per week, 43 (4.37%) drank SSBs 3–4 times per week, and 20 (2.03%) drank SSBs 5 or more times per week. Children aged 12 months with mothers who drank SSBs five or more times per week during pregnancy had an increased risk of potential delay on social-emotional development compared to those with mothers who drank SSBs less than once per week [odds ratio: 3.08 (1.13–8.39)]. Regarding the specific kinds of SSBs, we found that tea drinks (not 100% tea) were positively associated with potential delay on social-emotional development in children aged 6 months.ConclusionNearly three-quarters of mothers consumed almost no SSBs during pregnancy. High SSB intake during pregnancy was associated with an increased risk of the potential delay on social-emotional development of a child at 6 and 12 months of age.