bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing early erythrolysis and the relationship to perihematomal iron overload and white matter survival in human intracerebral hemorrhage
Authors: Novakovic Nemanja , Wilseck Zachary M. , Chenevert Thomas L. , Xi Guohua , Keep Richard F. , Pandey Aditya S. , Chaudhary Neeraj 
Published: June 2021

AbstractAimsIron released from lysed red blood cells within the hematoma plays a role in intracerebral hemorrhage (ICH)‐related neurotoxicity. This study utilizes magnetic resonance imaging (MRI) to examine the time course, extent of erythrolysis, and its correlation with perihematomal iron accumulation and white matter loss.MethodsThe feasibility of assessing proportional erythrolysis using T2* MRI was examined using pig blood phantoms with specified degrees of erythrolysis. Fifteen prospectively enrolled ICH patients had MRIs (3‐Tesla) at days 1–3, 14, and 30 (termed early, subacute, and late periods, respectively). Measurement was performed on T2*, 1/T2*, and fractional anisotropy (FA) maps.ResultsPig blood phantoms showed a linear relationship between 1/T2* signal and percent erythrolysis. MRI on patients showed an increase in erythrolysis within the hematoma between the early and subacute phases after ICH, almost completing by day 14. Although perihematomal iron overload (IO) correlated with the erythrolysis extent and hematoma volume at days 14 and 30, perihematomal white matter (WM) loss significantly correlated with both, only at day 14.ConclusionMRI may reliably assess the portion of the hematoma that lyses over time after ICH. Perihematomal IO and WM loss correlate with both the erythrolysis extent and hematoma volume in the early and subacute periods following ICH.
Gaps in DNA sequence libraries for Macaronesian marine macroinvertebrates imply decades till completion and robust monitoring
Authors: Vieira Pedro E. , Lavrador Ana S. , Parente Manuela I. , Parretti Paola , Costa Ana C. , Costa Filipe O. , Duarte Sofia 
Published: June 2021

AbstractAimDNA metabarcoding has great potential to improve biomonitoring in island's marine ecosystems, which are highly vulnerable to global change and non‐indigenous species (NIS) introductions. However, the depth and accuracy of the taxonomic identifications are mainly dependent on reference libraries containing representative and reliable sequences for the targeted species. In this study, we evaluated the gaps in the availability of DNA sequences and their accuracy for macroinvertebrates inhabiting Macaronesia's shallow marine habitats.LocationMacaronesia (Azores, Madeira, Selvagens, Canaries).MethodsChecklists of marine invertebrates occurring above 50 m depth were compiled using public databases and published checklists. The availability of cytochrome c oxidase subunit I (COI) and 18S rRNA (18S) gene sequences was verified in BOLD and GenBank. Finally, COI data were audited to check the congruence between morphospecies and Barcode Index Numbers (BINs).ResultsThe taxonomic coverage of different phyla was greater for COI but unbalanced and variable among archipelagos. NIS were better represented in genetic databases (up to 73% and 59%, for COI and 18S, respectively) than native species (up to 47% and 31%, for COI and 18S, respectively). NIS displayed a higher number of discordant records, and native species, a higher quantity of cases of multiple BINs. Notably, DNA sequences generated from specimens collected from Macaronesia were found in less than 10% of the species. Projection of the rates of accretion of DNA sequences suggests that decades will be needed to complete these reference libraries.Main conclusionsThe level of completion of reference libraries for Macaronesia's marine macroinvertebrates is generally poor. Without a solid effort to speed up the production of sequence data (i.e. generate more DNA barcodes), the ability to employ DNA‐based biomonitoring of such vulnerable fauna is compromised. The high levels of suspected hidden diversity further deepen the expected gaps and reinforce the vulnerability of this endemism‐rich fauna.
Digitizing Taxation and Premature Formalization in Developing Countries
Authors: Roy Pallavi , Khan Mushtaq H. 
Published: June 2021

ABSTRACTThe digitization of taxation systems can assist inclusion. However, it can also inadvertently lead to adverse outcomes for the poor in developing countries where many firms in the informal sector have low capabilities. Moreover, larger formal sector firms are often politically networked and in a position to engage in extractive informal transactions that digitization alone cannot restrict. Thus, while digitization creates tools for the enforcement of formal regulations, formalization can be unequal. This contribution focuses on digitized taxation as an application of a more general problem with digitization as a tool for formalization, referring to evidence from the rollout of the Goods and Services Tax (GST) in India. Using the analysis of political settlements, the authors distinguish between types of rule violations in developing economies. Networked higher‐capability firms engage in ‘informal’ transactions when they violate rules to extract rents. This is different from the informality of unregistered micro and small enterprises in the informal sector who often violate rules they cannot adhere to, and make informal payments to enforcers to continue operating. When digital technologies are used in these contexts, adverse outcomes for welfare and inclusion can follow from ‘premature formalization’. A more cautious and inclusive path to formalization is necessary to protect vulnerable groups.
Predictors of diabetes‐related distress before and after FreeStyle Libre‐1 use: Lessons from the Association of British Clinical Diabetologists nationwide study
Authors: Deshmukh Harshal , Wilmot Emma G. , Gregory Robert , Barnes Dennis , Narendran Parth , Saunders Simon , Furlong Niall , Kamaruddin Shafie , Banatwalla Rumaisa , Herring Roselle , Kilvert Anne , Patmore Jane , Walton Chris , Ryder Robert E. J. , Sathyapalan Thozhukat 
Published: June 2021

AbstractAimTo identify the baseline demographic and clinical characteristics associated with diabetes‐related distress (DRD) and factors associated with improvement in DRD after initiating use of the FreeStyle Libre (FSL) in people living with type 1 diabetes (T1D).MethodsThe study was performed using baseline and follow‐up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes who initiated use of the FSL in the United Kingdom. DRD was assessed using the two‐item diabetes‐related distress scale (DDS; defined as the average of the two‐item score ≥3). People living with T1D were categorized into two groups: those with high DRD, defined as an average DDS score ≥3 and those with lower DRD, defined as a DDS score <3. We used a gradient‐boosting machine‐learning (GBM) model to identify the relative influence (RI) of baseline variables on average DDS score.ResultsThe study population consisted of 9159 patients, 96.6% of whom had T1D. The median (interquartile range [IQR]) age was 45.1 (32‐56) years, 50.1% were women, the median (IQR) baseline body mass index was 26.1 (23.2‐29.6) kg/m2 and the median (IQR) duration of diabetes was 20 (11‐32) years. The two components of the DDS were significantly correlated (r2 = 0.73; P < 0.0001). Higher DRD was prevalent in 53% (4879/9159) of people living with T1D at baseline. In the GBM model, the top baseline variables associated with average DDS score were baseline glycated haemoglobin (HbA1c; RI = 51.1), baseline Gold score (RI = 23.3), gender (RI = 7.05) and fear of hypoglycaemia (RI = 4.96). Follow‐up data were available for 3312 participants. The top factors associated with improvement in DDS score following use of the FSL were change in Gold score (RI = 28.2) and change in baseline HbA1c (RI = 19.3).ConclusionsIn this large UK cohort of people living with T1D, diabetes distress was prevalent and associated with higher HbA1c, impaired awareness of hypoglycaemia and female gender. Improvement in glycaemic control and hypoglycaemia unawareness with the use of the FSL was associated with improvement in DRD in people living with T1D.
Use of once‐weekly semaglutide in patients with type 2 diabetes in routine clinical practice: Results from the SURE Canada multicentre, prospective, observational study
Authors: Yale Jean‐François , Catarig Andrei‐Mircea , Grau Katrine , Harris Stewart , Klimek‐Abercrombie Agnieszka , Rabasa‐Lhoret Rémi , Reardon Laura , Woo Vincent , Liutkus Joanne 
Published: June 2021

AbstractAimTo investigate once‐weekly (OW) semaglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in patients with type 2 diabetes (T2D) in routine clinical practice.MethodsThe SURE Canada study was a multicenter, prospective, observational study. Adults with T2D and one or more documented HbA1c values 12 weeks or less before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change in body weight (BW), waist circumference and patient‐reported outcomes (PROs) and the proportion of patients achieving HbA1c of less than 7.0%, weight loss (WL) of 5% or higher, and a composite of HbA1c reduction of 1% or higher and WL of 3% or higher at EOS. Data were analysed and presented for patients on semaglutide at EOS overall and for the following baseline medication subgroups: oral antihyperglycaemic drugs (OADs) only; GLP‐1RA experienced; insulin ± OADs without GLP‐1RA.ResultsIn total, 452 patients initiated semaglutide and 356 completed the study on treatment. For the 452 patients, mean baseline HbA1c was 8.1%; 86 (19.0%) patients had HbA1c of less than 7.0%. Mean dose of semaglutide at EOS was 0.76 ± 0.31 mg. Mean HbA1c was reduced by 0.9%‐point (95% confidence interval [CI]: 0.97; 0.78). Mean BW was reduced by 4.3 kg (95% CI: 4.79; 3.76). At EOS, 46.9% of patients achieved HbA1c of less than 7.0%, 40.9% achieved WL of 5% or higher and 24.1% achieved the composite endpoint. PROs improved from baseline to EOS. No new safety concerns were reported.ConclusionsIn SURE Canada, patients treated with OW semaglutide in routine clinical practice experienced clinically significant improvements in HbA1c, BW and other outcomes, supporting semaglutide use in routine clinical practice.
Sodium‐glucose cotransporter‐2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews
Authors: Augusto Gustavo A. , Cassola Nicolle , Dualib Patrícia M. , Saconato Humberto , Melnik Tamara 
Published: June 2021

AbstractAimsTo summarize the evidence from systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the efficacy and safety of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors versus placebo or active comparators for type 2 diabetes mellitus.Materials and MethodsWe searched six databases between 2014 and 2021. We assessed the quality of evidence using Assessment of Multiple Systematic Reviews (AMSTAR 2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and summarized the main outcome results according to their evidence of benefit (PROSPERO ID: CRD42019132431).ResultsWe included 46 SRs, comprising 175 RCTs and 136 096 participants. The results showed “clear evidence of benefit” in relation to: myocardial infarction (odds ratio [OR]/hazard ratio [HR] 0.85 to 0.91); cardiovascular mortality (OR/HR 0.67 to 0.86); heart failure (OR/HR 0.64 to 0.69); albuminuria progression and composite renal outcome (relative risk [RR]/HR 0.55 to 0.63); glycated haemoglobin (HbA1c) versus placebo (mean difference [MD] −0.49% to −0.77% [5.4 to 8.4 mmol/mol]); and weight versus placebo (MD −1.09 kg to −2.99 kg). “Possible benefit” was observed in relation to major adverse cardiovascular events (OR/HR 0.80 to 0.89), all‐cause mortality and nonalcoholic fatty liver disease. SGLT2 inhibitors showed “clear evidence of no effect or equivalence” in relation to stroke and fractures. “Clear evidence of harm” was observed in relation to genital infections (RR/OR 2.06 to 5.25) and ketoacidosis (HR/OR 1.36 to 2.20). Regarding amputation risk and urinary tract infections, we found “no conclusions possible due to lack of evidence”.ConclusionsOur results showed that SGLT2 inhibitors have beneficial effects in relation to renal and cardiovascular outcomes (except for stroke), HbA1c and weight. Further studies are needed to assess urinary infections and amputation risk.
Performance of early risk assessment tools to predict the later development of gestational diabetes
Authors: Kotzaeridi Grammata , Blätter Julia , Eppel Daniel , Rosicky Ingo , Mittlböck Martina , Yerlikaya‐Schatten Gülen , Schatten Christian , Husslein Peter , Eppel Wolfgang , Huhn Evelyn A. , Tura Andrea , Göbl Christian S. 
Published: June 2021

AbstractBackgroundSeveral prognostic models for gestational diabetes mellitus (GDM) are provided in the literature; however, their clinical significance has not been thoroughly evaluated, especially with regard to application at early gestation and in accordance with the most recent diagnostic criteria. This external validation study aimed to assess the predictive accuracy of published risk estimation models for the later development of GDM at early pregnancy.MethodsIn this cohort study, we prospectively included 1132 pregnant women. Risk evaluation was performed before 16 + 0 weeks of gestation including a routine laboratory examination. Study participants were followed‐up until delivery to assess GDM status according to the IADPSG 2010 diagnostic criteria. Fifteen clinical prediction models were calculated according to the published literature.ResultsGestational diabetes mellitus was diagnosed in 239 women, that is 21.1% of the study participants. Discrimination was assessed by the area under the ROC curve and ranged between 60.7% and 76.9%, corresponding to an acceptable accuracy. With some exceptions, calibration performance was poor as most models were developed based on older diagnostic criteria with lower prevalence and therefore tended to underestimate the risk of GDM. The highest variable importance scores were observed for history of GDM and routine laboratory parameters.ConclusionsMost prediction models showed acceptable accuracy in terms of discrimination but lacked in calibration, which was strongly dependent on study settings. Simple biochemical variables such as fasting glucose, HbA1c and triglycerides can improve risk prediction. One model consisting of clinical and laboratory parameters showed satisfactory accuracy and could be used for further investigations.
Development of Hymenoscyphus fraxineus on seedlings from different half‐sib lines of Fraxinus angustifolia in Serbia
Authors: Vemić Aleksandar , Kerkez Janković Ivona , Kudláček Tomáš , Jung Thomas , Šijačić‐Nikolić Mirjana , Nonić Marina , Milenković Ivan 
Published: June 2021

AbstractFor the long‐term goal of improving planting success and reforestation of floodplain forests, an underbark inoculation test was performed using one‐year‐old seedlings from ten different half‐sib lines of narrow‐leaved ash (Fraxinus angustifolia) to examine the variability of host susceptibility to the ash dieback pathogen Hymenoscyphus fraxineus. Sizes of necrotic lesions, production of epicormic shoots and mortality was recorded in all inoculated seedlings 76 days after inoculation. Mortality of different half‐sib lines ranged between 13.3% and 80%. Only one of the tested half‐sib lines showed necrotic lesion sizes, production of epicormic sprouts and percentage of mortality substantially lower than all the other nine half‐sib‐lines of the respective symptom traits. About 20% of half‐sib lines had reduced only one of these three symptoms. The other 70% of tested half‐sib lines had large necrotic lesions, abundant occurrence of epicormic sprouts and high percentage of mortality. Mortality was also significantly influenced by seedling height at the time of inoculation with taller seedlings developing mortality more slowly than smaller seedlings. This study demonstrates significant differences in the susceptibility to H. fraxineus between different half‐sib lines of F. angustifolia and the influence of seedling height on the development of ash dieback.
Nilotinib‐induced bone marrow CD34+/lin‐Ph+ cells early clearance in newly diagnosed CP‐Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study
Authors: Pungolino Ester , D'adda Mariella , De Canal Gabriella , Trojani Alessandra , Perego Alessandra , Elena Chiara , Lunghi Francesca , Turrini Mauro , Borin Lorenza , Iurlo Alessandra , Latargia Maria Luisa , Carraro Maria Cristina , Spina Francesco , Artale Salvatore , Anghilieri Michela , Molteni Alfredo , Caramella Marianna , Baruzzo Giacomo , Nichelatti Michele , Di Camillo Barbara , Cairoli Roberto 
Published: June 2021

AbstractChronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph‐chromosome and the BCR‐ABL tyrosine‐kinase (TK). Target‐therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second‐generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in‐vivo activity and timecourse of first‐line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty‐seven CP‐CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per‐Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK‐STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.
Empirical abundance distributions are more uneven than expected given their statistical baseline
Authors: Diaz Renata M. , Ye Hao , Ernest S. K. Morgan 
Published: June 2021

AbstractExploring and accounting for the emergent properties of ecosystems as complex systems is a promising horizon in the search for general processes to explain common ecological patterns. For example the ubiquitous hollow‐curve form of the species abundance distribution is frequently assumed to reflect ecological processes structuring communities, but can also emerge as a statistical phenomenon from the mathematical definition of an abundance distribution. Although the hollow curve may be a statistical artefact, ecological processes may induce subtle deviations between empirical species abundance distributions and their statistically most probable forms. These deviations may reflect biological processes operating on top of mathematical constraints and provide new avenues for advancing ecological theory. Examining ~22,000 communities, we found that empirical SADs are highly uneven and dominated by rare species compared to their statistical baselines. Efforts to detect deviations may be less informative in small communities—those with few species or individuals—because these communities have poorly resolved statistical baselines. The uneven nature of many empirical SADs demonstrates a path forward for leveraging complexity to understand ecological processes governing the distribution of abundance, while the issues posed by small communities illustrate the limitations of using this approach to study ecological patterns in small samples.
Contribution of sleep disturbances to fatigue in multiple sclerosis: a prospective study using clinical and polysomnographic parameters
Authors: Riccitelli Gianna C. , Disanto Giulio , Sacco Rosaria , Sparasci Davide , Sacco Leonardo , Castelnovo Anna , Miano Silvia , Manconi Mauro , Gobbi Claudio , Zecca Chiara 
Published: June 2021

AbstractBackground and purposeFatigue is amongst the most frequent and disabling symptoms of multiple sclerosis and a close relation between fatigue and sleep quality has been hypothesized. In this study the contribution of sleep disturbances measured by clinical and polysomnographic parameters to fatigue in multiple sclerosis was investigated.MethodsThis was a prospective instrumental study performed at the Neurocenter of Southern Switzerland. Demographic data and clinical characteristics including fatigue (as measured by the modified fatigue impact scale [MFIS]), neurological disability, psychiatric symptoms, medications and sleep‐related variables were collected at baseline visit and by a home full‐night polysomnography. The associations between sleep‐related variables and the MFIS were tested using partial correlations adjusted by demographic and sleep‐unrelated clinical factors.ResultsSeventy‐six patients were included in the study, of whom 53 (69.7%) had an MFIS ≥38 points (median 49.5, interquartile range 31.0–62.0). MFIS scores were positively associated with age, neurological disability, symptoms of depression and anxiety, and use of benzodiazepines and selective serotonin reuptake inhibitors. When adjusting for these variables, the presence of restless legs syndrome (RLS) (r = 0.37, p = 0.005) and periodic leg movements index (r = −0.33, p = 0.014) were associated with MFIS. Excessive daytime sleepiness, total sleep time, sleep efficiency, respiratory disturbances, and percentage of time spent in the different sleep stages (N1, N2, N3 and rapid eye movement) were not associated with fatigue.ConclusionsMultiple sclerosis patients with a diagnosis of RLS had significantly higher global fatigue scores compared to those without RLS. Future studies should investigate whether medical treatment of RLS can ameliorate fatigue.