bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenecteplase versus alteplase for large vessel occlusion recanalization (T-FLAVOR): Trial protocol
Authors: Kawano Hiroyuki , Hirano Teruyuki , Inoue Manabu , Fukuda-Doi Mayumi , Iwasaki Koji , Omae Katsuhiro , Tanaka Kanta , Yamamoto Haruko , Koga Masatoshi , Sakai Nobuyuki , Nagao Takehiko , Sasaki Makoto , Hayakawa Naoki , Toyoda Kazunori 
Published: January 2022

Background Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients. Hypothesis Tenecteplase is superior to alteplase in achieving recanalization on the initial angiogram when administered ≤4.5-hour of stroke onset in patients planned for mechanical thrombectomy (MT) in Japan where alteplase at the unique dose of 0.6mg/kg is officially used. Methods The Tenecteplase versus alteplase For LArge Vessel Occlusion Recanalization (T-FLAVOR) trial is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, masked-endpoint, superiority study. Eligibility criteria include acute ischemic stroke with pre-stroke modified Rankin Scale score ≤3 and large vessel occlusion (internal carotid artery, middle cerebral artery, or basilar artery) eligible for intravenous thrombolysis ≤4.5-hour and MT ≤6-hour of stroke onset. After completing the safety confirmation phase involving three patients who received non-masked tenecteplase (0.25 mg/kg), 220 patients will be randomized to two groups (1:1), intravenous alteplase (0.6mg/kg, n = 110) or tenecteplase (0.25mg/kg, n = 110), prior to MT. Outcomes In the safety confirmation phase, the primary outcome is symptomatic intracranial hemorrhage (sICH) ≤24-36-hour. In the randomized, comparative phase, the primary efficacy outcome is substantial angiographic reperfusion (mTICI grade 2b/2c/3) or absence of retrievable thrombus on the initial angiogram. The primary safety outcome is sICH ≤24-36-hour and 90-day mortality. Discussion T-FLAVOR may help determine if tenecteplase should be recommended as a routine clinical strategy before MT for Japanese stroke patients. Trial registration jRCTs051210055
Provenance analysis of sediments in the south-east Aegean during the Upper Quaternary: a composite approach based on bulk and clay mineralogy and geochemistry
Authors: Leontopoulou Georgia , Christidis Georgios E. , Rousakis Grigorios , Müller Noémi S. , Papatheodorou George , Geraga Maria 
Published: January 2022

AbstractSediments from the ST5 deep-sea bottom core collected from the south-east Aegean Sea between Symi and Tilos islands, Greece, were examined by quantitative mineralogical analysis and geochemical analysis to infer provenance and palaeoenvironmental control over sediment deposition. The mineralogical composition comprises carbonates (mainly calcite and Mg-calcite), quartz, feldspars, serpentine, amphibole and clay minerals. Chlorite is the most abundant clay mineral, whereas smectite and illite are less abundant than in the sediments in the south-west Aegean and the Cretan Sea. Semi-quantitative analysis of clay minerals from oriented clay fractions overestimates significantly the smectite content and underestimates the abundances of illite, chlorite and kaolinite. The studied sediments are enriched in MgO, Ni and Cr, which decrease in abundance with decreasing depth, following the distribution of serpentine. By contrast, the abundances of SiO2, Al2O3, Fe2O3, Na2O and K2O increase upcore. The regional S1 sapropel horizon is enriched in V and Co and has considerably greater Ba/Al ratios than the remaining sequence. The mineralogical and geochemical relationships indicate a strong ultrabasic influence, probably from the Marmaris ophiolite in the Lycian nappes. The clay mineral distribution suggests that the smectite was mainly of volcanogenic origin, the illite was supplied by the nearby landmasses of west Anatolia and the islands of Rhodes, Tilos and Symi and the contribution from the south-east Mediterranean was limited or totally lacking. The combined use of the mineralogical and geochemical analysis of bulk sediments rather than the clay fractions is not only extremely useful in tracing sediment provenance in relatively closed basins, but it also enables a more realistic assessment of the importance of water circulation patterns on sedimentation processes in such environments.
Hydrogen diffusion mechanisms in quartz: insights from H–Li,2H–H and2H–H–Li exchange experiments
Authors: Jollands Michael C. , Tollan Peter M. E. , Baumgartner Lukas P. , Müntener Othmar 
Published: January 2022

AbstractThe diffusivity and diffusion mechanisms of hydrogen together with with deuterium and lithium, parallel to thecaxis of quartz, were investigated experimentally at 800°C, 0.1 GPa with the activity of H2O or2H2O ≈ 1 [2H is used throughout this work to describe deuterium rather than D, to avoid confusion with the diffusion coefficient,D]. The pH was set using mixtures of H2O (or2H2O) and HCl. Three types of experiment were conducted: (1) H-in/Li-out; (2)2H-in/H-out; and (3)2H-in/H + Li out, using three different natural quartz crystals as starting materials. Profiles of H,2H and Li were measured using Fourier-transform infrared (FTIR) spectroscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). H,2H and Li are charge-compensated by Al3+replacing Si4+, or by excess O2–. The total atomic concentration of monovalent cations appears to remain constant over the duration of the experiments. The resulting diffusion profiles are different for the three experimental designs and three starting materials, and some show complex shapes inconsistent with simple diffusion. A multi-site diffusion–reaction model is developed, with the theory based on previous models that have been derived mainly on the basis of conductivity measurements. In these models, the monovalent cations move away from their charge-balancing ion then diffuse rapidly to another site. The mobility of the monovalent cations is described by both a diffusion coefficient and an equilibrium constant that enables dissociation of the immobile charge-balanced defects. This model can describe complex step-shaped profiles formed in H-in/Li-out experiments, profiles with local maxima ('humped’ profiles) in2H-in/H + Li out experiments, and error function-shaped profiles in2H-in/H-out and previously published Li-in/H-out experiments. Our data provide support for models previously proposed for quartz. Studies of the lengths and forms of diffusion profiles from such experiments provide a useful complement to assertions from conductivity experiments.
Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status
Authors: Roboz Gail J. , Ravandi Farhad , Wei Andrew H. , Dombret Hervé , Thol Felicitas , Voso Maria Teresa , Schuh Andre C. , Porkka Kimmo , La Torre Ignazia , Skikne Barry , Zhong Jianhua , Beach C. L. , Risueño Alberto , Menezes Daniel L. , Ossenkoppele Gert , Döhner Hartmut 
Published: January 2022

AbstractMeasurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD− status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD− during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity &gt;6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients’ MRD status at baseline. Registered at clinicaltrials.gov as #NCT01757535.
Echocardiographic probability of pulmonary hypertension: a validation study
Authors: D'Alto Michele , Di Maio Marco , Romeo Emanuele , Argiento Paola , Blasi Ettore , Di Vilio Alessandro , Rea Gaetano , D'Andrea Antonello , Golino Paolo , Naeije Robert 
Published: January 2022

BackgroundAccording to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterisation (RHC). How echocardiography predicts PH recently redefined by mean pulmonary arterial pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by pulmonary vascular resistance (PVR) ≥3 or >2 WU has not been established.MethodsA total of 278 patients referred for PH underwent comprehensive echocardiography followed by RHC. 15 patients (5.4%) were excluded because of insufficient quality echocardiography.ResultsWith PH defined by mPAP >20 mmHg, 23 patients had no PH, 146 had pre-capillary PH and 94 had post-capillary PH. At univariate analysis, maximum tricuspid regurgitation velocity (TRV) 2.9–3.4 m·s−1, left ventricle (LV) eccentricity index >1.1, right ventricle outflow tract acceleration time (RVOT-AT) <105 ms or notching, RV/LV basal diameter >1 and pulmonary artery diameter predicted PH, whereas inferior vena cava diameter and right atrial area did not. At multivariable analysis, only TRV ≥2.9 m·s−1independently predicted PH. Additional independent prediction of PVR ≥3 WU was offered by LV eccentricity index >1.1, and RVOT-AT <105 ms and/or notching, but with no improvement of optimal combination of specificity and sensitivity or positive prediction.ConclusionsEchocardiography as recommended in current guidelines can be used to assess the probability of redefined PH in a referral centre. However, the added value of indirect signs is modest and sufficient quality echocardiographic signals may not be recovered in some patients.
Relationships between male secondary sexual traits, physiological state and offspring viability in the three-spined stickleback
Authors: Chiara Violette , Velando Alberto , Kim Sin-Yeon 
Published: January 2022

AbstractBackgroundSexual signals produced by males play a central role in sexual selection, but the relationship between these traits and the quality of the bearer are often ambiguous. Secondary sexual traits may represent genetic quality of the bearer, resulting in positive relationships with physiological state, or may be costly to produce, showing trade-off with physiological state. A number of studies have explored the relationships between secondary sexual traits and other functional traits, but few have studied their fitness consequences. We studied the link between diverse physiological traits and both morphological and behavioural sexual traits and examined how their interplay influences offspring viability in the three-spined stickleback.ResultsMale sticklebacks showing nest building and courtship behaviour were smaller than those not investing in reproductive activities. There was no evidence that the expression of red nuptial colouration and the quality of courtship behaviour of males are positively related to their metabolic rates, swim ability, oxidative damage and mtDNA copy number. However, individuals showing larger red nuptial colour areas had higher levels of oxidative DNA damage in their sperm. Male courtship behaviour and aggressiveness, but not red colour area, were good predictors of offspring hatching and survival.ConclusionsOur results suggest that, in our study population at the southern edge of the species’ distribution, sexual colouration of male sticklebacks was not a good indicator of their body state, but both courtship quality and aggressiveness during the courtship are reliable cues of their gamete quality, influencing the viability of their offspring. Thus, females that choose mates based on their courtship behaviour will have high fitness. In the study population, which represents a fast pace-of-life with high reproductive rate and short lifespan, sexual ornaments of males may not honestly signal their physiological and physical state because they invest at maximum in a single reproductive season despite high costs.
HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed abstracts
Authors: Dholakia Dhwani , Kalra Ankit , Misir Bishnu Raman , Kanga Uma , Mukerji Mitali 
Published: January 2022

AbstractExtreme complexity in the Human Leukocyte Antigens (HLA) system and its nomenclature makes it difficult to interpret and integrate relevant information for HLA associations with diseases, Adverse Drug Reactions (ADR) and Transplantation. PubMed search displays ~ 146,000 studies on HLA reported from diverse locations. Currently, IPD-IMGT/HLA (Robinson et al., Nucleic Acids Research 48:D948–D955, 2019) database houses data on 28,320 HLA alleles. We developed an automated pipeline with a unified graphical user interface HLA-SPREAD that provides a structured information on SNPs, Populations, REsources, ADRs and Diseases information. Information on HLA was extracted from ~ 28 million PubMed abstracts extracted using Natural Language Processing (NLP). Python scripts were used to mine and curate information on diseases, filter false positives and categorize to 24 tree hierarchical groups and named Entity Recognition (NER) algorithms followed by semantic analysis to infer HLA association(s). This resource from 109 countries and 40 ethnic groups provides interesting insights on: markers associated with allelic/haplotypic association in autoimmune, cancer, viral and skin diseases, transplantation outcome and ADRs for hypersensitivity. Summary information on clinically relevant biomarkers related to HLA disease associations with mapped susceptible/risk alleles are readily retrievable from HLASPREAD. The resource is available at URL http://hla-spread.igib.res.in/. This resource is first of its kind that can help uncover novel patterns in HLA gene-disease associations.
Combined assembly of long and short sequencing reads improve the efficiency of exploring the soil metagenome
Authors: Xu Guoshun , Zhang Liwen , Liu Xiaoqing , Guan Feifei , Xu Yuquan , Yue Haitao , Huang Jin-Qun , Chen Jieyin , Wu Ningfeng , Tian Jian 
Published: January 2022

Abstract
Background
Advances in DNA sequencing technologies have transformed our capacity to perform life science research, decipher the dynamics of complex soil microbial communities and exploit them for plant disease management. However, soil is a complex conglomerate, which makes functional metagenomics studies very challenging.

Results
Metagenomes were assembled by long-read (PacBio, PB), short-read (Illumina, IL), and mixture of PB and IL (PI) sequencing of soil DNA samples were compared. Ortholog analyses and functional annotation revealed that the PI approach significantly increased the contig length of the metagenomic sequences compared to IL and enlarged the gene pool compared to PB. The PI approach also offered comparable or higher species abundance than either PB or IL alone, and showed significant advantages for studying natural product biosynthetic genes in the soil microbiomes.

Conclusion
Our results provide an effective strategy for combining long and short-read DNA sequencing data to explore and distill the maximum information out of soil metagenomics.
The lolB gene in Xanthomonas campestris pv. campestris is required for bacterial attachment, stress tolerance, and virulence
Authors: Liao Chao-Tsai , Li Chih-En , Chang Hsiao-Ching , Hsu Chien-Hui , Chiang Ying-Chuan , Hsiao Yi-Min 
Published: January 2022

Abstract
Background
Xanthomonas campestris pv. campestris (Xcc) is a Gram-negative bacterium that can cause black rot disease in crucifers. The lipoprotein outer membrane localization (Lol) system is involved in the lipoprotein sorting to the outer membrane. Although Xcc has a set of annotated lol genes, there is still little known about the physiological role in this phytopathogen. In this study, we aimed to characterize the role of LolB of Xcc in bacterial attachment, stress tolerance, and virulence.

Results
To characterize the role of LolB, lolB mutant was constructed and phenotypic evaluation was performed. The lolB mutant revealed reductions in bacterial attachment, extracellular enzyme production, and virulence. Mutation of lolB also resulted in reduced tolerance to a myriad of stresses, including heat and a range of membrane-perturbing agents. Trans-complementation of lolB mutant with intact lolB gene reverted these altered phenotypes to the wild-type levels. From subsequent reporter assay and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis, the expression of genes that encode the major extracellular enzymes and the stress-related proteins was reduced after lolB mutation.

Conclusions
The results in this work contribute to the functional understanding of lolB in Xanthomonas for the first time, and provide new insights into the function of lolB in bacteria.
In vitro activities of thiazolidione derivatives combined with daptomycin against clinical Enterococcus faecium strains
Authors: Chen Zhong , Xiong Yanpeng , Tang Yuanyuan , Zhao Yuxi , Chen Junwen , Zheng Jinxin , Wu Yang , Deng Qiwen , Qu Di , Yu Zhijian 
Published: January 2022

AbstractBackgroundPrevious reports have demonstrated two thiazolidione derivatives (H2-60 and H2-81) can robustly inhibit the planktonic growth and biofilm formation ofS. epidermidisandS. aureusby targeting the histidine kinase YycG.Whereas the antibacterial and anti-biofilm activity of these two thiazolidione derivatives (H2-60 and H2-81) againstEnterococcus faeciumremains elusive. Here, the pET28a-YycG recombinant plasmid were in vitro expressed inE. colicompetent cell BL21 (DE3) and induced to express YycG’ protein (conding HisKA and HATPase_c domain) by 0.5 mM IPTG and was purified by Ni – NTA agarose and then for the autophosphorylation test. Antimicrobial testing and time-killing assay were also be determined. Anti-biofilm activity of two derivatives with sub-MIC concentration towards positive biofilm producers of clinicalE. faeciumwere detected using polystyrene microtiter plate and CLSM.ResultsThe MICs of H2-60 and H2-81 in the clinical isolates ofE. faeciumwere in the range from 3.125 mg/L to 25 mg/L. Moreover, either H2-60 or H2-81 showed the excellent bactericidal activity againstE. faeciumwith monotherapy or its combination with daptomycin by time-killing assay.E. faeciumplanktonic cells can be decreased by H2-60 or H2-81 for more than 3 × log10 CFU/mL after 24 h treatment when combined with daptomycin. Furthermore, over 90% ofE. faeciumbiofilm formation could markedly be inhibited by H2-60 and H2-81 at 1/4 × MIC value. In addition, the frequency of the eradicated viable cells embedded in mature biofilm were evaluated by the confocal laser microscopy, suggesting that of H2-60 combined with ampicillin or daptomycin was significantly high when compared with single treatment (78.17 and 74.48% vs. 41.59%, respectively,P < 0.01).ConclusionThese two thiazolidione derivatives (H2-60 and H2-81) could directly impact the kinase phosphoration activity of YycG ofE. faecium. H2-60 combined with daptomycin exhibit the excellent antibacterial and anti-biofilm activity againstE. faeciumby targeting YycG.
Geo–economic variations in epidemiology, ventilation management and outcome of patients receiving intraoperative ventilation during general anesthesia– posthoc analysis of an observational study in 29 countries
Authors: Hol Liselotte , Nijbroek Sunny G. L. H. , Neto Ary Serpa , Hemmes Sabrine N. T. , Hedenstierna Goran , Hiesmayr Michael , Hollmann Markus W. , Mills Gary H. , Vidal Melo Marcos F. , Putensen Christian , Schmid Werner , Severgnini Paolo , Wrigge Hermann , de Abreu Marcelo Gama , Pelosi Paolo , Schultz Marcus J. ,   for the LAS VEGAS study–investigators
Published: January 2022

Abstract
Background
The aim of this analysis is to determine geo–economic variations in epidemiology, ventilator settings and outcome in patients receiving general anesthesia for surgery.

Methods
Posthoc analysis of a worldwide study in 29 countries. Lower and upper middle–income countries (LMIC and UMIC), and high–income countries (HIC) were compared. The coprimary endpoint was the risk for and incidence of postoperative pulmonary complications (PPC); secondary endpoints were intraoperative ventilator settings, intraoperative complications, hospital stay and mortality.

Results
Of 9864 patients, 4% originated from LMIC, 11% from UMIC and 85% from HIC. The ARISCAT score was 17.5 [15.0–26.0] in LMIC, 16.0 [3.0–27.0] in UMIC and 15.0 [3.0–26.0] in HIC (P = .003). The incidence of PPC was 9.0% in LMIC, 3.2% in UMIC and 2.5% in HIC (P < .001). Median tidal volume in ml kg− 1 predicted bodyweight (PBW) was 8.6 [7.7–9.7] in LMIC, 8.4 [7.6–9.5] in UMIC and 8.1 [7.2–9.1] in HIC (P < .001). Median positive end–expiratory pressure in cmH2O was 3.3 [2.0–5.0]) in LMIC, 4.0 [3.0–5.0] in UMIC and 5.0 [3.0–5.0] in HIC (P < .001). Median driving pressure in cmH2O was 14.0 [11.5–18.0] in LMIC, 13.5 [11.0–16.0] in UMIC and 12.0 [10.0–15.0] in HIC (P < .001). Median fraction of inspired oxygen in % was 75 [50–80] in LMIC, 50 [50–63] in UMIC and 53 [45–70] in HIC (P < .001). Intraoperative complications occurred in 25.9% in LMIC, in 18.7% in UMIC and in 37.1% in HIC (P < .001). Hospital mortality was 0.0% in LMIC, 1.3% in UMIC and 0.6% in HIC (P = .009).

Conclusion
The risk for and incidence of PPC is higher in LMIC than in UMIC and HIC. Ventilation management could be improved in LMIC and UMIC.

Trial registration
Clinicaltrials.gov, identifier: NCT01601223.
Identification of causal effects in case-control studies
Authors: L. Penning de Vries Bas B. , Groenwold Rolf H. H. 
Published: January 2022

Abstract
Background
Case-control designs are an important yet commonly misunderstood tool in the epidemiologist’s arsenal for causal inference. We reconsider classical concepts, assumptions and principles and explore when the results of case-control studies can be endowed a causal interpretation.

Results
We establish how, and under which conditions, various causal estimands relating to intention-to-treat or per-protocol effects can be identified based on the data that are collected under popular sampling schemes (case-base, survivor, and risk-set sampling, with or without matching). We present a concise summary of our identification results that link the estimands to the (distribution of the) available data and articulate under which conditions these links hold.

Conclusion
The modern epidemiologist’s arsenal for causal inference is well-suited to make transparent for case-control designs what assumptions are necessary or sufficient to endow the respective study results with a causal interpretation and, in turn, help resolve or prevent misunderstanding. Our approach may inform future research on different estimands, other variations of the case-control design or settings with additional complexities.