bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic Consumption Patterns in European Countries Might Be Associated with the Prevalence of Type 1 and 2 Diabetes
Authors: Ternák Gábor , Németh Márton , Rozanovic Martin , Bogár Lajos 
Published: May 2022

Several publications have raised the issue that the development of diabetes precedes the alteration of the microbiome (dysbiosis) and the role of environmental factors. Antibiotic use induces dysbiosis, and we wanted to estimate the associations between the consumption of antibiotics and the prevalence of diabetes (both types 1 and 2; T1D and T2D, respectively) in European countries. If such an association exists, the dominant use antibiotic classes might be reflected in the prevalence rates of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes estimated for 2019 and featured in the Diabetes Atlas and the average yearly consumption of antibiotic classes between 2010 and 2109, calculated from the European Centre for Disease Prevention and Control (ECDC) yearly reports on antibiotic consumption in Europe. Pearson’s correlation and variance analyses were used to estimate the possible relationship. Strong positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A: p = 0.001) and the narrow-spectrum penicillin (J01CE: p = 0.006; CF: p = 0.018). A strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase-resistant penicillin (J01CR: p = 0.003), macrolide (J01F: p = 0.008), and quinolone (J01M: p = 0.001). T2D showed significant positive associations with cephalosporin (J01D: p = 0.048) and quinolone (J01M: p = 0.025), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA: p = 0.067). Countries showing the highest prevalence rates of diabetes (top 10) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (top 10), as indicated by variance analysis. Countries with high prevalence rates of T1D showed high consumption of tetracycline (p = 0.015) and narrow-spectrum, beta-lactamase sensitive penicillin (p = 0.008) and low consumption of “inhibitor” antibiotics [broad-spectrum, beta-lactamase-resistant, combination penicillin (p = 0.005); cephalosporin (p = 0.036); and quinolone (p = 0.003)]. Countries with high prevalence rates of T2D consumed more cephalosporin (p = 0.084) and quinolone (p = 0.054) and less broad-spectrum, beta-lactamase-sensitive penicillin (p = 0.012) than did other countries. The development of diabetes-related dysbiosis might be related to the higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics, those showing negative (inhibitory) associations. These groups of antibiotics are different in T1D and T2D.
Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis
Authors: Ebihara Takeshi , Matsumoto Hisatake , Matsubara Tsunehiro , Togami Yuki , Nakao Shunichiro , Matsuura Hiroshi , Kojima Takashi , Sugihara Fuminori , Okuzaki Daisuke , Hirata Haruhiko , Yamamura Hitoshi , Ogura Hiroshi 
Published: May 2022

IntroductionCoronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called “cytokine storm” is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 1463 plasma proteins, validate these cytokines, and compare them with sepsis.Materials and MethodsIn a derivation cohort of 306 patients with COVID-19, 1463 unique plasma proteins were measured on days 1, 4, and 8. Cytokines associated with disease severity and prognosis were derived. In a validation cohort of 62 COVID-19 patients and 38 sepsis patients treated in the intensive care unit [ICU], these derived cytokines were measured on days 1 (day of ICU admission), 2-3, and 6-8 (maximum: 3 time points/patient). Derived cytokines were compared with healthy controls and between COVID-19 and sepsis patients, and the associations with prognosis were evaluated. The time to wean off mechanical ventilation (MV) was evaluated only for COVID-19.ResultsIL-6, amphiregulin, and growth differentiation factor (GDF)-15 were associated with disease severity and prognosis in the derivation cohort. In the validation cohort, IL-6 and GDF-15 were elevated in COVID-19 and sepsis on day 1, and the levels of these cytokines were higher in sepsis than in COVID-19. IL-6 and GDF-15 were associated with prognosis in sepsis. Cox proportional hazards model with time as a dependent covariate showed a significant relationship between plasma GDF-15 level and time to wean off MV (hazard ratio, 0.549 [95% confidence level, 0.382–0.789]). The GDF-15 level at ICU admission predicted late recovery.ConclusionGDF-15 and IL-6 derived from proteomics analysis were related with disease severity of COVID-19. Their values were higher in sepsis than in COVID-19 and were associated with prognosis in sepsis. In COVID-19 patients treated in the ICU, GDF-15 was associated with the time to wean off MV and better predicted late recovery.
Interstitial Lung Disease in Dermatomyositis Without Myositis-Specific and Myositis-Associated Autoantibodies: Study of a Series of 72 Patients From a Single Cohort
Authors: Chen Fang , Wang Jinping , Zhang Puli , Zuo Yu , Ye Lifang , Wang Guochun , Shu Xiaoming 
Published: May 2022

ObjectiveThe clinical features of interstitial lung disease (ILD) in patients with dermatomyositis (DM) and negative myositis autoantibodies had not been exactly demonstrated previously. This study aimed to describe and expand the phenotype of interstitial lung disease (ILD) in this cohort of patients.MethodsA total of 1125 consecutive Chinese patients with idiopathic inflammatory myopathies (IIM) between 2006 and 2020 were screened retrospectively. All proven cases of isolated ILD with both negative myositis-specific autoantibodies (MSA) and negative myositis-associated autoantibodies (MAA) were selected for inclusion. The clinical features and outcome among this group, MDA5+DM (DM patients with positive anti-MDA5 antibody) and ASS (patients with positive anti-aminoacyl tRNA synthetases antibodies were recorded and compared.ResultsOf 1125 IIM patients with an average follow-up of 6 years, 154 DM patients with negative MSA and MAA (MSA/MAA) were identified, with an ILD incidence of 46.8%. DM-ILD Patients with negative MSA/MAA presented younger age at onset (p&lt;0.001), lower incidence of elevated CA153 (p=0.03) and fever (p=0.04)than those ILD patients with MDA5+DM and ASS.The estimated high-resolution computed tomography patterns of ILD showed non-specific interstitial pneumonia (66.6%), followed by organizing pneumonia in patients with negative MSA/MAA. OP pattern was more common in patients with MDA5+DM (69.7%), and the ratios of the OP (48.7%) and NSIP (51.3%) patterns were almost equal in patients with ASS. Of these DM-ILD patients with negative MSA/MAA, 25% developed rapidly progressive interstitial lung disease (RP-ILD). Patients with RP-ILD had a shorter disease duration (p=0.002), higher percentage of positive ANA(p=0.01) and organizing pneumonia patterns (p=0.04), elevated CYFRA211(p=0.04) and decreased FiO2/PaO2 (p&lt;0.001) than those with chronic progressive ILD. The incidence of OP pattern in RP-ILD patients with negative MSA/MAA was lower than in those RPILD patients with MDA5+ DM (75%) and ASS (89%) (p=0.006). The cumulative 5- and 10-year survival rates in the DM-ILD patients with negative MSA/MAA were 91% and 88%, respectively, during the long-term follow-up study. And they had more favorable survival rate compared with ILD patients with MDA5+DM and ASS (p&lt;0.001). An independent prognostic factor was identified as decreased PaO2/FiO2 (hazard ratio, 0.97; p=0.004].ConclusionsThis study indicates DM-ILD patients with negative MSA/MAA had favorable long-term outcomes. Decreased baseline PaO2/FiO2 acted as an independent prognostic factor for this group of patients.
Salivary Xanthine Oxidase as a Potential Biomarker in Stroke Diagnostics
Authors: Maciejczyk Mateusz , Nesterowicz Miłosz , Zalewska Anna , Biedrzycki Grzegorz , Gerreth Piotr , Hojan Katarzyna , Gerreth Karolina 
Published: May 2022

Stroke is one of the most common cerebrovascular diseases. Despite significant progress in understanding stroke pathogenesis, cases are still increasing. Thus, laboratory biomarkers of stroke are sought to allow rapid and non-invasive diagnostics. Ischemia-reperfusion injury is an inflammatory process with characteristic cellular changes leading to microvascular disruption. Several studies have shown that hyperactivation of xanthine oxidase (XO) is a major pathogenic factor contributing to brain dysfunction. Given the critical role of XO in stroke complications, this study aimed to evaluate the activity of the enzyme and its metabolic products in the saliva of stroke subjects. Thirty patients in the subacute phase of stroke were included in the study: 15 with hemorrhagic stroke and 15 with ischemic stroke. The control group consisted of 30 healthy subjects similar to the cerebral stroke patients regarding age, gender, and status of the periodontium, dentition, and oral hygiene. The number of individuals was determined a priori based on our previous experiment (power of the test = 0.8; α = 0.05). The study material was mixed non‐stimulated whole saliva (NWS) and stimulated saliva (SWS). We showed that activity, specific activity, and XO output were significantly higher in NWS of ischemic stroke patients than in hemorrhagic stroke and healthy controls. Hydrogen peroxide and uric acid levels were also considerably higher in NWS of ischemic stroke patients. Using receiver operating curve (ROC) analysis, we demonstrated that XO-specific activity in NWS distinguishes ischemic stroke from hemorrhagic stroke (AUC: 0.764) and controls (AUC: 0.973) with very high sensitivity and specificity. Saliva collection is stress-free, requires no specialized medical personnel, and allows continuous monitoring of the patient’s condition through non-invasive sampling multiple times per day. Salivary XO also differentiates with high accuracy (100%) and specificity (93.75%) between stroke patients with mild to moderate cognitive decline (AUC = 0.988). Thus, salivary XO assessment may be a potential screening tool for a comprehensive neuropsychological evaluation. To summarize, our study demonstrates the potential utility of salivary XO in the differential diagnosis of stroke.
Marine Heatwaves Offshore Central and South Chile: Understanding Forcing Mechanisms During the Years 2016-2017
Authors: Pujol Cécile , Pérez-Santos Iván , Barth Alexander , Alvera-Azcárate Aida 
Published: May 2022

Marine heatwaves (MHWs) are discrete warm-water anomalies events occurring in both open ocean and coastal areas. These phenomena have drawn researchers’ attention since the beginning of the 2010s, as their frequency and intensity are severely increasing due to global warming. Their impacts on the oceans are wide, affecting the ecosystems thus having repercussions on the economy by decreasing fisheries and aquaculture production. Chilean Patagonia (41° S-56° S) is characterised by fjord ecosystems already experiencing the global change effects in the form of large-scale and local modifications. This study aimed to realise a global assessment of the MHWs that have occurred along Central and South Chile between 1982 and 2020. We found that the frequency of MHWs was particularly high during the last decade offshore Northern Patagonia and that the duration of the events is increasing. During austral winter and spring 2016, combination of advected warm waters coming from the extratropical South Pacific Ocean and persisting high pressure inducing reduced winds have together diminished the heat transfer from the ocean to the atmosphere, creating optimal condition for a long-lasting MHW. That MHW hit Patagonia during 5 months, from May to October 2016, and was the longest MHW recorded over the 1982-2020 period. In addition, a global context of positive phases of El Niño Southern Oscillation and Southern Annular Mode contributed to the MHW formation.
Estimated Divergence Times of Lecanicillium in the Family Cordycipitaceae Provide Insights Into the Attribution of Lecanicillium
Authors: Zhou Ye-Ming , Zhi Jun-Rui , Qu Jiao-Jiao , Zou Xiao 
Published: May 2022

BackgroundThe genus Lecanicillium W.Gams &amp; Zare is a recognized insect pathogen but members of the genus have been found parasitizing various hosts including arthropods, nematodes, plants, and fungi. The new classification system for fungi proposed to reject Lecanicillium and transfer some of the species to the genus Akanthomyces. However, the attribution problem of most species in the original genus Lecanicillium remains unsolved. The current study aimed to improve understanding of the pivotal internal phylogeny in Lecanicillium by estimating the divergence times of Lecanicillium to provide additional insights into the status of this genus within the family Cordycipitaceae.ResultsDating analyses support the supposition that the ancestor of Lecanicillium was in the Cretaceous period (84.36 Mya, 95% HPD: 72.12–94.74 Mya). After originating from a common ancestor, eight clades of Lecanicillium were derived and evolved independently in parallel with other genera of Cordycipitaceae. Based on the clear divergence age estimates, Lecanicillium clade 8 originated earlier as an independent group in the Cretaceous period (75.61 Mya, 95% HPD: 63.31–87.54 Mya), while Lecanicillium clades 1–7 originated later as an independent group in the boundary of the Cretaceous and Paleogene periods (64.66 Mya, 95% HPD: 52.75–76.74 Mya). Lecanicillium huhutii formed an independent branch in a polytomy together with a clade containing Lecanicillium tenuipes (BI posterior probabilities 1, ML bootstrap 100%).ConclusionThe pivotal internal phylogeny, origin, and evolutionary history of Lecanicillium in the family Cordycipitaceae were investigated. Phylogenetic and morphological analyses indicated that there are eight representative clades (four representative branches of evolutionary history), including clade 1 (members have a relatively uniform sporulation structure comprising globose heads with a higher number of conidia), clade 8 (including all members of Gamszarea), clades 2–5 (the differences of the divergence time estimations were smaller compared with other clades), and clade 6–7 (members are close to Gibellula, Hevansia, and Ascopolyporus). Based on the above findings, a novel spider-pathogenic fungus, Lecanicillium huhutii, is described. All other species in Lecanicillium clade 1 (Lecanicillium araneogemum, L. nodulosum, L. pissodis, and L. uredinophilum) should be transferred to the genus Akanthomyces. Furthermore, the monotypic genus Parengyodontium should be merged with the genus Gamszarea. More novel species need to be discovered to thoroughly resolve the attribution problem of Lecanicillium. Finally, no major lineages of Lecanicillium were correlated with the nearby Cretaceous-Tertiary extinction event, indicating that the diversity of Lecanicillium is more likely to be caused by long-term environmental adaptation and coevolution with insects rather than by dramatic extinction events.
Altered Spontaneous Brain Activity in Patients With Diabetic Osteoporosis Using Regional Homogeneity: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Liu Min , Li Jiang , Li Juan , Yang Hui , Yao Qianqian , Zheng Xiuzhu , Zhang Zheng , Qin Jian 
Published: May 2022

BackgroundThe pathophysiological mechanism of cognitive impairment by osteoporosis in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to further investigate the regional spontaneous brain activity changes of patients with diabetic osteoporosis (DOP), and the correlation between abnormal brain regions and bone metabolites.MethodsA total of 29 subjects with T2DM were recruited, including fourteen patients with DOP and thirteen patients without osteoporosis (Control group). Based on the resting-state functional magnetic resonance imaging (rs-fMRI) datasets acquired from all the subjects, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Spearman correlation analysis was performed between the abnormal ReHo regions with the clinical parameters and Montreal Cognitive Assessment (MOCA) scores.ResultsIn the DOP group, we demonstrated the significantly increased ReHo values in the left middle temporal gyrus (MTG), right superior occipital gyrus (SOG), aright superior parietal lobule (SPL), right angular gyrus (AG), and left precuneus (PE). Additionally, we also found a significant positive correlation between increased ReHo values in the left MTG and the average bone mineral density (BMD AVG), and average T scores (T AVG). The ReHo values of the right SOG and right SPL showed a negative correlation with MOCA scores, as well as a negative correlation between increased ReHo values in the right SPL and osteocalcin (OC) level.ConclusionPatients with DOP showed increased spontaneous activity in multiple brain regions. The results indicated that osteoporosis exacerbated cognitive impairment and brain damage. Also, the OC might be considered as a bone marker to track the progression of cognitive impairment.
Dynamic Relationship Between Interhemispheric Functional Connectivity and Corticospinal Tract Changing Pattern After Subcortical Stroke
Authors: Liu Jingchun , Wang Caihong , Cheng Jingliang , Miao Peifang , Li Zhen 
Published: May 2022

Background and PurposeIncreased interhemispheric resting-state functional connectivity (rsFC) between the bilateral primary motor cortex (M1) compensates for corticospinal tract (CST) impairment, which facilitates motor recovery in chronic subcortical stroke. However, there is a lack of data on the evolution patterns and correlations between M1–M1 rsFC and diffusion indices of CSTs with different origins after subcortical stroke and their relations with long-term motor outcomes.MethodsA total of 44 patients with subcortical stroke underwent longitudinal structural and functional magnetic resonance imaging (MRI) examinations and clinical assessments at four time points. Diffusion tensor imaging was used to extract fractional anisotropy (FA) values of the affected CSTs with different origins. Resting-state functional MRI was used to calculate the M1–M1 rsFC. Longitudinal patterns of functional and anatomic changes in connections were explored using a linear mixed-effects model. Dynamic relationships between M1–M1 rsFC and FA values of the affected specific CSTs and the impact of these variations on the long-term motor outcomes were analyzed in patients with subcortical stroke.ResultsStroke patients showed a significantly decreased FA in the affected specific CSTs and a gradually increasing M1–M1 rsFC from the acute to the chronic stage. The FA of the affected M1 fiber was negatively correlated with the M1–M1 rsFC from the subacute to the chronic stage, FA of the affected supplementary motor area fiber was negatively correlated with the M1–M1 rsFC in the subacute stage, and FA of the affected M1 fiber in the acute stage was correlated with the long-term motor recovery after subcortical stroke.ConclusionOur findings show that the FA of the affected M1 fiber in the acute stage had the most significant correlation with long-term motor recovery and may be used as an imaging biomarker for predicting motor outcomes after stroke. The compensatory role of the M1–M1 rsFC enhancement may start from the subacute stage in stroke patients with CST impairment.
Association Between Specific Type 2 Diabetes Therapies and Risk of Alzheimer’s Disease and Related Dementias in Propensity-Score Matched Type 2 Diabetic Patients
Authors: Torrandell-Haro Georgina , Branigan Gregory L. , Brinton Roberta Diaz , Rodgers Kathleen E. 
Published: May 2022

ObjectiveWe sought to determine the impact of Type 2 Diabetes Mellitus (T2D) anti-hyperglycemic medications (A-HgM) on risk of Alzheimer’s disease (AD) and related dementias (ADRD) outcomes including vascular dementia, and non-AD dementia such as frontotemporal, Lewy body, and mixed etiology dementias.Research Design and MethodsThis retrospective cohort study used the US-based Mariner claims dataset. 1,815,032 T2D participants 45 years and older with records 6 months prior and at least 3 years after the diagnosis of T2D were included. Claims were surveyed for a diagnosis of AD and ADRD 12 months post T2D diagnosis. A propensity score approach was used to minimize selection bias. Analyses were conducted between January 1st and February 28th, 2021.ResultsIn this cohort study A-HgM exposure was associated with decreased diagnosis of AD (RR, 0.61; 95% CI, 0.59–0.62; p &lt; 0.001), vascular dementia (RR, 0.72; 95% CI, 0.69–0.74; p &lt; 0.001) and non-AD dementia (RR, 0.67; 95% CI, 0.66–0.68; p &lt; 0.001). Metformin was associated with the greatest risk reduction and insulin with the least reduction in risk compared to patients not receiving A-HgM for ADRD risk. Of interest, patients with a diagnosis of AD, while either on metformin or insulin, were older in age and predominately female, than individuals on these drugs that did not develop AD. Mean (SD) follow-up was 6.2 (1.8) years.ConclusionAfter controlling for age, sex, and comorbidities, A-HgM in patients with T2D was associated with a reduced risk of AD and ADRD. These findings provide evidence in support of T2D as a risk factor for AD and ADRD and the beneficial impact of early and effective control of hyperglycemia to mitigate risk.
Psychophysiological Effects of Biographical Interventions in People With Unresponsive Wakefulness Syndrome and Minimally Conscious State
Authors: Grimm Teresa , Groß Martin , Nater Urs M. , Summ Oliver , Kreutz Gunter 
Published: May 2022

BackgroundVarious music interventions can evoke favorable behavioral responses or physiological reactions in people with disorders of consciousness (DOC), such as coma, unresponsive wakefulness syndrome (UWS), and minimally conscious state (MCS). However, it appears that no study thus far has investigated the effects of music on the endocrine system of people with DOC.ObjectiveThis explorative study aimed to investigate the effects of biographical music and biographical language on the physiological and endocrine systems of people with UWS and MCS.MethodA cohort of 20 people with DOC (10 women, 10 men; age range 19–77) received 20 min of biographical music and biographical language. Before and afterward, they were exposed to silence. Physiological and hormonal measurements were conducted before, during, and after the interventions.ResultsPairedt-tests showed a significant decrease of salivary cortisol in the condition with biographical language interventions.ConclusionBiographical interventions can modulate reactions in the endocrine system in people with DOC. Further studies are needed to establish whether and how individuals living with DOC show psychoneuroendocrine responses to music and other arts-based interventions.