bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing role of EMS –analyses of non-conveyed and conveyed patients in Finland
Authors: Paulin Jani , Kurola Jouni , Salanterä Sanna , Moen Hans , Guragain Nischal , Koivisto Mari , Käyhkö Niina , Aaltonen Venla , Iirola Timo
Published: May 2020

Background

Emergency Medical Services (EMS) and Emergency Departments (ED) have seen increasing attendance rates in the last decades. Currently, EMS are increasingly assessing and treating patients without the need to convey patients to health care facility. The aim of this study was to describe and compare the patient case-mix between conveyed and non-conveyed patients and to analyze factors related to non-conveyance decision making.

Methods

This was a prospective study design of EMS patients in Finland, and data was collected between 1st June and 30th November 2018. Adjusted ICPC2-classification was used as the reason for care. NEWS2-points were collected and analyzed both statistically and with a semi-supervised information extraction method. EMS patients’ geographic location and distance to health care facilities were analyzed by urban–rural classification.

Results

Of the EMS patients (40,263), 59.8% were over 65 years of age and 46.0% of the patients had zero NEWS2 points. The most common ICPC2 code was weakness/tiredness, general (A04), as seen in 13.5% of all patients. When comparing patients between the non-conveyance and conveyance group, a total of 35,454 EMS patients met the inclusion criteria and 14,874 patients (42.0%) were not conveyed to health care facilities. According the multivariable logistic regression model, the non-conveyance decision was more likely made by ALS units, when the EMS arrival time was in the evening or night and when the distance to the health care facility was 21-40 km. Furthermore, younger patients, female gender, whether the patient had used alcohol and a rural area were also related to the non-conveyance decision. If the patient’s NEWS2 score increased by one or two points, the likelihood of conveyance increased. When there was less than 1 h to complete a shift, this did not associate with either non-conveyance or conveyance decisions.

Conclusions

The role of EMS might be changing. This warrants to redesign the chain-of-survival in EMS to include not only high-risk patient groups but also non-critical and general acute patients with non-specific reasons for care. Assessment and on-scene treatment without conveyance can be called the “stretched arm of the emergency department”, but should be planned carefully to ensure patient safety.
A novel biocatalyst, Enterobacter aerogenes LU2, for efficient production of succinic acid using whey permeate as a cost-effective carbon source
Authors: Szczerba Hubert , Komoń-Janczara Elwira , Dudziak Karolina , Waśko Adam , Targoński Zdzisław
Published: May 2020

Background

Succinic acid (SA), a valuable chemical compound with a broad range of industrial uses, has become a subject of global interest in recent years. The bio-based production of SA by highly efficient microbial producers from renewable feedstock is significantly important, regarding the current trend of sustainable development.

Results

In this study, a novel bacterial strain, LU2, was isolated from cow rumen and recognized as an efficient producer of SA from lactose. Proteomic and genetic identifications as well as phylogenetic analysis were performed, and strain LU2 was classified as anEnterobacter aerogenesspecies. The optimal conditions for SA production were 100 g/L lactose, 10 g/L yeast extract, and 20% inoculum at pH 7.0 and 34 °C. Under these conditions, approximately 51.35 g/L SA with a yield of 53% was produced when batch fermentation was conducted in a 3-L stirred bioreactor. When lactose was replaced with whey permeate, the highest SA concentration of 57.7 g/L was achieved with a yield and total productivity of 62% and 0.34 g/(L*h), respectively. The highest productivity of 0.67 g/(L*h) was observed from 48 to 72 h of batch fermentation, whenE.aerogenesLU2 produced 16.23 g/L SA.

Conclusions

This study shows that the newly isolated strainE.aerogenesLU2 has great potential as a new biocatalyst for producing SA from whey permeate.
Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression
Authors: Larsson Chatarina , Cordeddu Lina , Siggens Lee , Pandzic Tatjana , Kundu Snehangshu , He Liqun , Ali Muhammad Akhtar , Pristovšek Nuša , Hartman Karin , Ekwall Karl , Sjöblom Tobias
Published: May 2020

Background

The histone 3 lysine 4 (H3K4) monomethylase KMT2C is mutated across several cancer types; however, the effects of mutations on epigenome organization, gene expression, and cell growth are not clear. A frequently recurring mutation in colorectal cancer (CRC) with microsatellite instability is a single nucleotide deletion within the exon 38 poly-A(9) repeat (c.8390delA) which results in frameshift preceding the functional carboxy-terminal SET domain. To study effects of KMT2C expression in CRC cells, we restored one allele to wild type KMT2C in the two CRC cell lines RKO and HCT116, which both are homozygous c.8390delA mutant.

Results

Gene editing resulted in increased KMT2C expression, increased H3K4me1 levels, altered gene expression profiles, and subtle negative effects on cell growth, where higher dependence and stronger effects of KMT2C expression were observed in RKO compared to HCT116 cells. Surprisingly, we found that the two RKO and HCT116 CRC cell lines have distinct baseline H3K4me1 epigenomic profiles. In RKO cells, a flatter genome-wide H3K4me1 profile was associated with more increased H3K4me1 deposition at enhancers, reduced cell growth, and more differential gene expression relative to HCT116 cells when KMT2C was restored. Profiling of H3K4me1 did not indicate a highly specific regulation of gene expression as KMT2C-induced H3K4me1 deposition was found globally and not at a specific enhancer sub-set in the engineered cells. Although we observed variation in differentially regulated gene sets between cell lines and individual clones, differentially expressed genes in both cell lines included genes linked to known cancer signaling pathways, estrogen response, hypoxia response, and aspects of immune system regulation.

Conclusions

Here, KMT2C restoration reduced CRC cell growth and reinforced genome-wide H3K4me1 deposition at enhancers; however, the effects varied depending upon the H3K4me1 status of KMT2C deficient cells. Results indicate that KMT2C inactivation may promote colorectal cancer development through transcriptional dysregulation in several pathways with known cancer relevance.
SMILES-based deep generative scaffold decorator for de-novo drug design
Authors: Arús-Pous Josep , Patronov Atanas , Bjerrum Esben Jannik , Tyrchan Christian , Reymond Jean-Louis , Chen Hongming , Engkvist Ola
Published: May 2020

Molecular generative models trained with small sets of molecules represented as SMILES strings can generate large regions of the chemical space. Unfortunately, due to the sequential nature of SMILES strings, these models are not able to generate molecules given a scaffold (i.e., partially-built molecules with explicit attachment points). Herein we report a new SMILES-based molecular generative architecture that generates molecules from scaffolds and can be trained from any arbitrary molecular set. This approach is possible thanks to a new molecular set pre-processing algorithm that exhaustively slices all possible combinations of acyclic bonds of every molecule, combinatorically obtaining a large number of scaffolds with their respective decorations. Moreover, it serves as a data augmentation technique and can be readily coupled with randomized SMILES to obtain even better results with small sets. Two examples showcasing the potential of the architecture in medicinal and synthetic chemistry are described: First, models were trained with a training set obtained from a small set of Dopamine Receptor D2 (DRD2) active modulators and were able to meaningfully decorate a wide range of scaffolds and obtain molecular series predicted active on DRD2. Second, a larger set of drug-like molecules from ChEMBL was selectively sliced using synthetic chemistry constraints (RECAP rules). In this case, the resulting scaffolds with decorations were filtered only to allow those that included fragment-like decorations. This filtering process allowed models trained with this dataset to selectively decorate diverse scaffolds with fragments that were generally predicted to be synthesizable and attachable to the scaffold using known synthetic approaches. In both cases, the models were already able to decorate molecules using specific knowledge without the need to add it with other techniques, such as reinforcement learning. We envision that this architecture will become a useful addition to the already existent architectures for de novo molecular generation.
Use of static and dynamic [18F]-F-DOPA PET parameters for detecting patients with glioma recurrence or progression
Authors: Zaragori Timothée , Ginet Merwan , Marie Pierre-Yves , Roch Véronique , Grignon Rachel , Gauchotte Guillaume , Rech Fabien , Blonski Marie , Lamiral Zohra , Taillandier Luc , Imbert Laëtitia , Verger Antoine
Published: May 2020

Background

Static [18F]-F-DOPA PET images are currently used for identifying patients with glioma recurrence/progression after treatment, although the additional diagnostic value of dynamic parameters remains unknown in this setting. The aim of this study was to evaluate the performances of static and dynamic [18F]-F-DOPA PET parameters for detecting patients with glioma recurrence/progression as well as assess further relationships with patient outcome.

Methods

Fifty-one consecutive patients who underwent an [18F]-F-DOPA PET for a suspected glioma recurrence/progression at post-resection MRI, were retrospectively included. Static parameters, including mean and maximum tumor-to-normal-brain (TBR) ratios, tumor-to-striatum (TSR) ratios, and metabolic tumor volume (MTV), as well as dynamic parameters with time-to-peak (TTP) values and curve slope, were tested for predicting the following: (1) glioma recurrence/progression at 6 months after the PET exam and (2) survival on longer follow-up.

Results

All static parameters were significant predictors of glioma recurrence/progression (accuracy ≥ 94%) with all parameters also associated with mean progression-free survival (PFS) in the overall population (allp< 0.001, 29.7 vs. 0.4 months for TBRmax, TSRmax, and MTV). The curve slope was the sole dynamic PET predictor of glioma recurrence/progression (accuracy = 76.5%) and was also associated with mean PFS (p< 0.001, 18.0 vs. 0.4 months). However, no additional information was provided relative to static parameters in multivariate analysis.

Conclusion

Although patients with glioma recurrence/progression can be detected by both static and dynamic [18F]-F-DOPA PET parameters, most of this diagnostic information can be achieved by conventional static parameters.
The flow-metabolism ratio might predict treatment response and survival in patients with locally advanced esophageal squamous cell carcinoma
Authors: Zhao Kewei , Wang Chunsheng , Mao Qingfeng , Shang Dongping , Huang Yong , Ma Li , Yu Jinming , Li Minghuan
Published: May 2020

Background

Perfusion CT can offer functional information about tumor angiogenesis, and 18F-FDG PET/CT quantifies the glucose metabolic activity of tumors. This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC).

Methods

Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and 18F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman’s rank correlation, Mann–Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan–Meier method, and Cox proportional hazards models.

Results

The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (r = 0.886, p < 0.001) and negatively correlated with SUVmax (r = − 0.547, p = 0.003) and TTP (r = − 0.462, p = 0.015) in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders (42.05 ± 16.47 vs 27.48 ± 8.55, p = 0.007; 3.18 ± 1.15 vs 1.84 ± 0.65, p = 0.001). The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014).

Conclusions

The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC.
Identification of a species-specific aminotransferase in Pediococcus acidilactici capable of forming α-aminobutyrate
Authors: Wenger Alexander , Schmidt Remo S. , Portmann Reto , Roetschi Alexandra , Eugster Elisabeth , Weisskopf Laure , Irmler Stefan
Published: May 2020

During cheese ripening, the bacterial strain Pediococcus acidilactici FAM18098 produces the non-proteinogenic amino acid, α-aminobutyrate (AABA). The metabolic processes that lead to the biosynthesis of this compound are unknown. In this study, 10 P. acidilactici, including FAM18098 and nine Pediococcus pentosaceus strains, were screened for their ability to produce AABA. All P. acidilactici strains produced AABA, whereas the P. pentosaceus strains did not. The genomes of the pediococcal strains were sequenced and searched for genes encoding aminotransferases to test the hypothesis that AABA could result from the transamination of α-ketobutyrate. A GenBank and KEGG database search revealed the presence of a species-specific aminotransferase in P. acidilactici. The gene was cloned and its gene product was produced as a His-tagged fusion protein in Escherichia coli to determine the substrate specificity of this enzyme. The purified recombinant protein showed aminotransferase activity at pH 5.5. It catalyzed the transfer of the amino group from leucine, methionine, AABA, alanine, cysteine, and phenylalanine to the amino group acceptor α-ketoglutarate. Αlpha-ketobutyrate could replace α-ketoglutarate as an amino group acceptor. In this case, AABA was produced at significantly higher levels than glutamate. The results of this study show that P. acidilactici possesses a novel aminotransferase that might play a role in cheese biochemistry and has the potential to be used in biotechnological processes for the production of AABA.
Probiotic Bifidobacterium lactis V9 attenuates hepatic steatosis and inflammation in rats with non-alcoholic fatty liver disease
Authors: Yan Yan , Liu Chunyan , Zhao Shimin , Wang Xinxu , Wang Jinling , Zhang Heping , Wang Yuzhen , Zhao Guofen
Published: May 2020

Both steatosis and inflammation are key pathological events in the progression of non-alcoholic fatty liver disease (NAFLD). Probiotics are beneficial for the prevention and treatment of NAFLD. Bifidobacterium animalis subsp. lactis V9 (V9) is a newly isolated strain with favorable probiotic properties. The study aims to evaluate the effects and mechanisms of V9 on the hepatic steatosis and inflammatory responses in a rat model of NAFLD induced by high-fat diets (HFD). Our results showed that administration of V9 significantly attenuated the HFD-induced increases in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, resulting in alleviated hepatic steatosis. V9 supplementation reduced the accumulation of hepatic triglyceride and free fatty acid,while increasing the levels of glycogen. Serum levels of glucose were also decreased in HFD rats administrated with V9. Meanwhile, the transcription of SREBP-1c and FAS was reduced, and the hepatic expression of phosphorylated-AMPK and PPAR-α was restored after V9 administration. V9 suppressed the production of inflammatory cytokines (e.g. IL-6, IL-1β, and TNF-α) in HFD-fed rats. The anti-inflammatory effects of V9 was found to be associated with the inhibition of hepatic expression of TLR4, TLR9, NLRP3, and ASC mRNA. Furthermore, the activation of ERK, JNK, AKT and NF-κB were suppressed by V9 treatment. These results indicate that Bifidobacterium lactis V9 improves NAFLD by regulating de novo lipid synthesis and suppressing inflammation through AMPK and TLR-NF-κB pathways, respectively.
Recruitment pattern of the diaphragm and extradiaphragmatic inspiratory muscles in response to different levels of pressure support
Authors: Roesthuis L. H. , van der Hoeven J. G. , van Hees H. W. H. , Schellekens W.-J. M. , Doorduin J. , Heunks L. M. A.
Published: May 2020

Background

Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm.

Methods

Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH2O every 5 min with steps of 3 cmH2O. The magnitude and timing of respiratory muscle activity were assessed.

Results

We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r2 = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles.

Conclusions

Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm.
Positive periodic solution for Nicholson’s blowfies systems with patch structure
Authors: Duan Feng , Du Bo
Published: May 2020

A generalized Nicholson blowfies system with patch structure is studied. Some existence and asymptotic stability results of the positive periodic solution to the considered system are obtained by coincidence degree theory and some analysis techniques. Finally, two examples are given to show the effectiveness of the results in the present paper.
Population vulnerability to COVID-19 in Europe: a burden of disease analysis
Authors: Wyper Grant M. A. , Assunção Ricardo , Cuschieri Sarah , Devleesschauwer Brecht , Fletcher Eilidh , Haagsma Juanita A. , Hilderink Henk B. M. , Idavain Jane , Lesnik Tina , Von der Lippe Elena , Majdan Marek , Milicevic Milena S. , Pallari Elena , Peñalvo José L. , Pires Sara M. , Plaß Dietrich , Santos João V. , Stockton Diane L. , Thomsen Sofie Theresa , Grant Ian
Published: May 2020

Background

Evidence has emerged showing that elderly people and those with pre-existing chronic health conditions may be at higher risk of developing severe health consequences from COVID-19. In Europe, this is of particular relevance with ageing populations living with non-communicable diseases, multi-morbidity and frailty. Published estimates of Years Lived with Disability (YLD) from the Global Burden of Disease (GBD) study help to characterise the extent of these effects. Our aim was to identify the countries across Europe that have populations at highest risk from COVID-19 by using estimates of population age structure and YLD for health conditions linked to severe illness from COVID-19.

Methods

Population and YLD estimates from GBD 2017 were extracted for 45 countries in Europe. YLD was restricted to a list of specific health conditions associated with being at risk of developing severe consequences from COVID-19 based on guidance from the United Kingdom Government. This guidance also identified individuals aged 70 years and above as being at higher risk of developing severe health consequences. Study outcomes were defined as: (i) proportion of population aged 70 years and above; and (ii) rate of YLD for COVID-19 vulnerable health conditions across all ages. Bivariate groupings were established for each outcome and combined to establish overall population-level vulnerability.

Results

Countries with the highest proportions of elderly residents were Italy, Greece, Germany, Portugal and Finland. When assessments of population-level YLD rates for COVID-19 vulnerable health conditions were made, the highest rates were observed for Bulgaria, Czechia, Croatia, Hungary and Bosnia and Herzegovina. A bivariate analysis indicated that the countries at high-risk across both measures of vulnerability were: Bulgaria; Portugal; Latvia; Lithuania; Greece; Germany; Estonia; and Sweden.

Conclusion

Routine estimates of population structures and non-fatal burden of disease measures can be usefully combined to create composite indicators of vulnerability for rapid assessments, in this case to severe health consequences from COVID-19. Countries with available results for sub-national regions within their country, or national burden of disease studies that also use sub-national levels for burden quantifications, should consider using non-fatal burden of disease estimates to estimate geographical vulnerability to COVID-19.
Beyond neutrality: adding habitat filtering to neutral models
Authors: Abeysinghe Wasana , Punchi-Manage Ruwan
Published: May 2020

Background

Understanding the processes that structure species is one of the primary focuses in community ecology. Hubbell’s neutral model shows stochastic processes alone can describe the two macro-ecological patterns, species richness and species-area relationship, of the community. Although Hubbell’s neutral model can explain the macro-ecological patterns of the species at large scales, it paid less attention to construct the spatial structure of the community. Previous studies suggest that such spatial structures are mostly due to habitat filtering processes work at the intermediate spatial scales. Therefore, Hubbell’s neutral model does not explain the full picture of the community structuring due to its fully stochastic nature.

Results

In this study, we proposed a two-schema model that has the habitat filtering component and the stochastic component to construct the species assemblages seen in the community level. The proposed model uses one additional parameter (i.e. number of individuals in habitat) in addition to Hubbell’s three-parameter neutral model (i.e. fundamental bio-diversity number (θ), dispersal limitation (m) and speciation (v)). The proposed model works at two spatial scales: habitat filtering at the intermediate scales and stochastic processes at the large and very small spatial scales. The model coupled the local community dynamics with the meta-community dynamics. The local community has a fixed area with carrying capacity that is proportional to the local community size. The number of habitats in the proposed model can vary. Individuals are placed into habitats with probabilities according to the habitat suitability. Species richness and species composition in each habitat were calculated. The model is fitted for differentθvalues,mvalues, and a different number of habitats.

Conclusions

We assume that habitat filtering plays an important role together with stochastic processes to structure species in forests. Therefore, the proposed model with only four parameters can explain a large proportion of the species structuring of the communities. We found that more species can be maintained in a heterogeneous environment than a uniform environment. Therefore, habitat conservation is highly important for maintaining species diversity in forest communities.
A simplified LC−MS/MS approach for simultaneous quantification and pharmacokinetics of five compounds in rats following oral administration of Gastrodia elata extract
Authors: Dong Jiajia , Ji De , Su Lianlin , Zhang Fengyang , Tong Huangjin , Mao Chunqin , Lu Tulin
Published: May 2020

Background

To support the multicomponent pharmacokinetics ofGastrodia elata, a rapid, simple, and sensitive ultra-performance liquid chromatography tandem with mass spectrometry (LC–MS/MS) approach was established for simultaneous quantification of gastrodin, parishin A, parishin B, parishin C, and parishin E.

Methods

Five compounds were extracted from plasma by using one-step protein precipitation. The chromatographic separation was achieved on a C18column with gradient mobile phase comprising acetonitrile and 0.05% formic acid. The detection was performed using negative electrospray ionization in multiple reaction monitoring mode.

Results

This new method maximizes assay throughput by using minimal sample clean-up procedures and a shorter analytical run time. The approach exhibited good linearity for the five compounds (r2> 0.995) in the concentration ranges. The lower limits of quantification (LLOQ) were determined as 1.37 ng/mL for parishin A, parishin B, parishin C, and parishin E and 10 ng/mL for gastrodin. Then the method was fully validated with intra- and inter-day precision, accuracy, matrix effects, extraction recovery, and stability.

Conclusion

This validated approach was successfully applied to the pharmacokinetic study following oral administration ofGastrodia elataextract to rats. This investigation may provide some guidance for the clinical application and explanation of the pharmacological mechanism ofGastrodia elata.
First record of ostracods from the Upper Ordovician red-coloured marine sandstones of the Tierekeawati Formation in Tarim Basin, NW China: implications on palaeoenvironment and palaeobiogeography
Authors: Song Jun-Jun , Shen Yi-Xin , Tang Peng , Zhang Xiao-Le , Li Qi-Jian , Luo Zheng-Jiang
Published: May 2020

Ostracods are described for the first time from the red-coloured marine sandstones of Arisu section (Arisu red beds) of the Upper Ordovician Tierekeawati Formation in Kalpin area of northwestern Tarim Basin, Xinjiang Uygur Autonomous Region (Xinjiang), Northwest China. Twenty-two species belonging to thirteen genera are described and figured. The ostracod fauna suggests a probable Sandbian–Katian age for these beds. The palaeoecological assemblage of ostracod fauna implies the deposition in a nearshore-offshore environment during a regression when the Arisu red beds of the Tierekeawati Formation were laid down in the Tarim Basin. Many cosmopolitan and provincial genera were present in diversified ostracod fauna of the Arisu red beds, suggesting the possible biogeographic relationships among the Tarim, Tibet, and South China plates, as well as Europe and North America continents during the Late Ordovician. Ostracods experienced faunal exchanges between Laurentia and the Tarim Plate during the Late Ordovician Period.
Azimuthal anisotropy analysis applied to naturally fractured unconventional reservoirs: A Barnett Shale example
Authors: Zhang Jing , Qi Jie , Zeng Yijin , Marfurt Kurt , Slatt Roger
Published: May 2020

Studying the seismic responses of velocity and amplitude on wide-/full-azimuth seismic data is now common for unconventional reservoir characterization. Velocity variation with azimuth (VVAz) and amplitude variation with azimuth (AVAz) are two of the most popular tools to map not only the relative intensity and orientation of natural fractures but also the strength and orientation of the maximum horizontal stress SH. We prestack time migrated a wide-azimuth Barnett Shale survey in North Texas into eight azimuths and reduced noise on the gathers using prestack structure-oriented filtering. We then computed the envelope, spectral peak frequency, and prestack P-wave impedance attributes for each azimuthally limited seismic volume. We compensated the VVAz effects by flattening each sector along the Barnett Shale key horizons, thereby registering the gathers for subsequent AVAz analysis. The results indicate the intensity, orientation, and confidence of azimuthal anisotropy effects on seismic velocity and amplitude, which can be referred to smaller scale vertical cracks or natural fractures. Our analysis reveals four zones of high anisotropy intensity that can be tied to either the regional structures or paleo stress field. Analysis of production data indicate from the anisotropy interpretation results that vertical, sealed fractures are the dominant cause of anisotropy and those specific fractures inhibit production. This observation and results indicate that horizon-based azimuthal anisotropy analysis avoids the VVAz effect and can be applied to fractures and regional stress field prediction.
Transdiagnostic and disease-specific abnormalities in the default-mode network hubs in psychiatric disorders: A meta-analysis of resting-state functional imaging studies
Authors: Doucet Gaelle E. , Janiri Delfina , Howard Rebecca , O’Brien Madeline , Andrews-Hanna Jessica R. , Frangou Sophia
Published: May 2020

Background.

The default mode network (DMN) dysfunction has emerged as a consistent biological correlate of multiple psychiatric disorders. Specifically, there is evidence of alterations in DMN cohesiveness in schizophrenia, mood and anxiety disorders. The aim of this study was to synthesize at a fine spatial resolution the intra-network functional connectivity of the DMN in adults diagnosed with schizophrenia, mood and anxiety disorders, capitalizing on powerful meta-analytic tools provided by activation likelihood estimation.

Methods.

Results from 70 whole-brain resting-state functional magnetic resonance imaging articles published during the last 15 years were included comprising observations from 2,789 patients and 3,002 healthy controls.

Results.

Specific regional changes in DMN cohesiveness located in the anteromedial and posteromedial cortex emerged as shared and trans-diagnostic brain phenotypes. Disease-specific dysconnectivity was also identified. Unmedicated patients showed more DMN functional alterations, highlighting the importance of interventions targeting the functional integration of the DMN.

Conclusion.

This study highlights functional alteration in the major hubs of the DMN, suggesting common abnormalities in self-referential mental activity across psychiatric disorders.
The impact of the COVID-19 outbreak on the medico-legal and human rights of psychiatric patients
Authors: Thome Johannes , Coogan Andrew N. , Simon Frederick , Fischer Matthias , Tucha Oliver , Faltraco Frank , Marazziti Donatella , Butzer Hermann
Published: May 2020

The COVID-19 pandemic has raised significant concerns for population mental health and the effective provision of mental health services in the light of increased demands and barriers to service delivery [1]. Particular attention is being directed toward the possible neuropsychiatric sequelae of both COVID-19 and of the stringent societal mitigation steps deployed by national governments, concerns that are informed by historical increases in the incidence of psychotic disorders following influenza pandemics [2]. However, so far there has been scant attention paid to other important areas of psychiatry during COVID-19, including medico-legal aspects and human rights. In this paper, we discuss the legal implications for psychiatry of the COVID-19 pandemic and report a novel situation in which psychiatric patients may experience diminution of their statutory protections. We believe that this represents a paradigm shift in psychiatric care and that the consideration of the fundamental rights of psychiatric patients as “less important” than infection control measures compel mental health professionals to “advocate for … patients and their caregivers” in this time of crisis [1].
Mortality and Advanced Support Requirement for Patients With Cancer With COVID-19: A Mathematical Dynamic Model for Latin America
Authors: Ruiz-Patiño Alejandro , Arrieta Oscar , Pino Luis E. , Rolfo Christian , Ricaurte Luisa , Recondo Gonzalo , Zatarain-Barron Zyanya-Lucia , Corrales Luis , Martín Claudio , Barrón Feliciano , Vargas Carlos , Carranza Hernán , Otero Jorge , Rodriguez July , Sotelo Carolina , Viola Lucia , Russo Alessandro , Rosell Rafael , Cardona Andrés F.
Published: May 2020

PURPOSE

In the midst of a global pandemic, evidence suggests that similar to other severe respiratory viral infections, patients with cancer are at higher risk of becoming infected by COVID-19 and have a poorer prognosis.

METHODS

We have modeled the mortality and the intensive care unit (ICU) requirement for the care of patients with cancer infected with COVID-19 in Latin America. A dynamic multistate Markov model was constructed. Transition probabilities were estimated on the basis of published reports for cumulative probability of complications. Basic reproductive number (R0) values were modeled with R using the EpiEstim package. Estimations of days of ICU requirement and absolute mortality were calculated by imputing number of cumulative cases in the Markov model.

RESULTS

Estimated median time of ICU requirement was 12.7 days, median time to mortality was 16.3 days after infection, and median time to severe event was 8.1 days. Peak ICU occupancy for patients with cancer was calculated at 16 days after infection. Deterministic sensitivity analysis revealed an interval for mortality between 18.5% and 30.4%. With the actual incidence tendency, Latin America would be expected to lose approximately 111,725 patients with cancer to SARS-CoV-2 (range, 87,116-143,154 patients) by the 60th day since the start of the outbreak. Losses calculated vary between < 1% to 17.6% of all patients with cancer in the region.

CONCLUSION

Cancer-related cases and deaths attributable to SARS-CoV-2 will put a great strain on health care systems in Latin America. Early implementation of interventions on the basis of data given by disease modeling could mitigate both infections and deaths among patients with cancer.
Variability in Cytogenetic Testing for Multiple Myeloma: A Comprehensive Analysis From Across the United States
Authors: Yu Yang , Brown Wade Niquelle , Hwang Amie E. , Nooka Ajay K. , Fiala Mark A. , Mohrbacher Ann , Peters Edward S. , Pawlish Karen , Bock Cathryn , Van Den Berg David J. , Rand Kristin A. , Stram Daniel , Conti David V. , Auclair Daniel , Colditz Graham A. , Mehta Jayesh , Haiman Christopher A. , Terebelo Howard , Janakiraman Nalini , Singhal Seema , Chiu Brian , Vij Ravi , Bernal-Mizrachi Leon , Zonder Jeffrey A. , Huff Carol A. , Lonial Sagar , Orlowski Robert Z. , Cozen Wendy , Ailawadhi Sikander
Published: May 2020

Purpose:

Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized.

Methods:

We address variability in the testing and reporting methodology for MM cytogenetics in the United States using the ongoing African American Multiple Myeloma Study (AAMMS). We evaluated clinical and cytogenetic data from 1,221 patients (1,161 with conventional karyotyping and 976 with FISH) tested between 1998 and 2016 across 58 laboratories nationwide.

Results:

Interlab and intralab variability was noted for the number of cells analyzed for karyotyping, with a significantly higher number of cells analyzed in patients in whom cytogenetics were normal (P 5.0025). For FISH testing, CD138-positive cell enrichment was used in 29.7% of patients and no enrichment in 50% of patients, whereas the remainder had unknown status. A significantly smaller number of cells was analyzed for patients in which CD138 cell enrichment was used compared with those without such enrichment (median, 50 v 200; P, .0001). A median of 7 loci probes (range, 1-16) were used for FISH testing across all laboratories, with variability in the loci probed even within a given laboratory. Chromosome 13–related abnormalities were the most frequently tested abnormality (n5956; 97.9%), and t(14;16) was the least frequently tested abnormality (n 5 119; 12.2%).

Conclusions:

We report significant variability in cytogenetic testing across the United States for MM, potentially leading to variability in risk stratification, with possible clinical implications and personalized treatment approaches.
InSight Care Pilot Program: Redefining Seeing a Patient
Authors: Daly Bobby , Kuperman Gilad , Zervoudakis Alice , Baldwin Medsker Abigail , Roy Ankita , Ro Alice S. , Arenas Javiera , Yanamandala Hrudaya Veena , Kottamasu Raj , Salvaggio Rori , Holland Jessie , Hirsch Stephanie , Walters Chasity B , Lauria Tara , Chow Kim , Begue Aaron , Rozenshteyn Margarita , Zablocki Melissa , Dhami Amandeep K. , Silva Nicholas , Brown Emily , Katzen Lauren L. , Chiu Yeneat O. , Perry Claire , Sokolowski Stefania , Wagner Isaac , Veach Stephen R. , Grisham Rachel N. , Dang Chau T. , Reidy-Lagunes Diane L. , Simon Brett A. , Perchick Wendy
Published: May 2020

PURPOSE:

Early detection and management of symptoms in patients with cancer improves outcomes. However, the optimal approach to symptom monitoring and management is unknown. InSight Care is a mobile health intervention that captures symptom data and facilitates patient-provider communication to mitigate symptom escalation.

PATIENTS AND METHODS:

Patients initiating antineoplastic treatment at a Memorial Sloan Kettering regional location were eligible. Technology supporting the program included the following: a predictive model that identified patient risk for a potentially preventable acute care visit; a secure patient portal enabling communication, televisits, and daily delivery of patient symptom assessments; alerts for concerning symptoms; and a symptom-trending application. The main outcomes of the pilot were feasibility and acceptability evaluated through enrollment and response rates and symptom alerts, and perceived value evaluated on the basis of qualitative patient and provider interviews.

RESULTS:

The pilot program enrolled 100 high-risk patients with solid tumors and lymphoma (29% of new treatment starts v goal of 25%). Over 6 months of follow-up, the daily symptom assessment response rate was 56% (the goal was 50%), and 93% of patients generated a severe symptom alert. Patients and providers perceived value in the program, and archetypes were developed for program improvement. Enrolled patients were less likely to use acute care than were other high-risk patients.

CONCLUSION:

InSight Care was feasible and holds the potential to improve patient care and decrease facility-based care. Future work should focus on optimizing the cadence of patient assessments, the workforce supporting remote symptom management, and the return of symptom data to patients and clinical teams.
Mixed Response to Immunotherapy in Patients with Metastatic Melanoma
Authors: Rauwerdink Daan Jan Willem , Molina George , Frederick Dennie Tompers , Sharova Tanya , van der Hage Jos , Cohen Sonia , Boland Genevieve Marie
Published: May 2020

Background

Immunotherapy has improved overall survival in metastatic melanoma. Response to therapy can be difficult to evaluate as the traditionally used RECIST 1.1 criteria do not capture heterogeneous responses. Here we describe the clinical characterization of melanoma patients with a clinically defined mixed response to immunotherapy.

Methods

This was a single institution, retrospective analysis of stage IV melanoma patients who received first-line anti-CTLA-4, anti-PD1, or combination anti-CTLA-4/anti-PD1. Therapy response was assessed via clinical definitions, which consisted of cross-sectional imaging combined with clinical exam. Course of disease, clinicopathological characteristics, and management in patients with a mixed clinical response were analyzed.

Results

In 292 patients (anti-CTLA4 = 63; anti-PD1 = 148, anti-CTLA4/anti-PD1 = 81), 103 were responders (35%), 64 mixed responders (22%), and 125 patients had progressive disease (43%). Of patients with a mixed response, 56% eventually had response to therapy (mixed response followed by response, MR–R), while 31% progressed on therapy (MR–NR). MR–NR patients had higher median LDH (p < 0.01), 3 or more organ sites with metastases (p < 0.01), and more frequently had M1d disease (p < 0.01). Mixed responders who underwent surgery (n = 20) had a significantly longer mean OS compared to patients who did not undergo surgery (6.9 years, 95% CI 6.2–7.6 vs. 6.0 years, 95% CI 4.6–7.3,p = 0.02).

Discussion

Mixed response to immunotherapy in metastatic melanoma was not uncommon in our cohort (22%). Clinical characteristics associated with progression of disease after initial mixed response included higher LDH, brain metastases, and ≥ 3 organ sites with metastases. Surgical treatment for highly selected patients with a mixed response was associated with improved outcomes.
Long-Run Effects from Comprehensive Student Support: Evidence from Pathways to Education
Authors: Lavecchia Adam M. , Oreopoulos Philip , Brown Robert S.
Published: May 2020

Offering comprehensive education support services to disadvantaged students shows promise for improving academic attainment. We explore longer-term impacts of the Pathways to Education program, a set of coaching, tutoring, group activities, and financial incentives initially offered in 2001 to grade-nine students living in the largest public housing community in Toronto. Using a difference-in-difference methodology and matching school records to income tax data through age 28 for a sample of students living in public housing under similar circumstances, we find that Pathways eligibility increased adult annual earnings by 19 percent, employment by 14 percent, and reduced welfare receipt by more than 30 percent. (JEL I22, I23, I24, I26, I28, L31)
Métodos qualitativos nos estudos organizacionais e de gestão
Authors: Cunha Miguel Pina e , Rego Arménio
Published: May 2020

A investigação sobre gestão e organizações tem sido metodologicamente dominada pela lógica hipotético-dedutiva e pelos métodos quantitativos. Tal orientação tem possibilitado significativos desenvolvimentos do conhecimento. Todavia, essas disciplinas também se beneficiam da aplicação de métodos indutivos. Assim, os métodos indutivos são aqui apresentados como de especial relevância para um mundo organizacional em profunda mudança. Este artigo apresenta algumas das críticas recorrentes aos métodos qualitativos (MQ) de natureza indutiva, bem como possíveis remédios contra essas críticas. O texto procura ultrapassar a visão preconceituosa por vezes feita dos MQ. Mas estes métodos ajudam a explicar, a mostrar por quê, a retratar com rigor os fenômenos estudados –o objetivo último da investigação científica. Permitem, ainda, mitigar um problema atual dos estudos organizacionais, um campo no qual muitos estudos são rigorosos, mas oferecem conclusões triviais.
Optimization of bioremediation-cocktail for application in the eco-recovery of crude oil polluted soil
Authors: Agbaji Joseph E. , Nwaichi Eucharia O. , Abu Gideon O.
Published: May 2020

Background: Environmental sustainability is the driver for finding the optimal bioremediation cocktail with the combination of highly potent hydrocarbonoclastic strains and the nutrient additives that significantly enhance mineralization of crude oil in polluted soil in order to mitigate its deleterious effects on the environment. In this study, four hydrocarbon-degrading bacterial strains were pre-selected from mined rhizobacterial isolates in aged crude oil-contaminated soil.

 Method: Agrowaste residues of poultry-droppings, corn chaff, and plantain peel were selected among others for their ability to support high biomass of selected bacterial strains. Baseline proximate analysis was performed on the agrowaste residues. Simplified, one variable at a time (OVAT) was employed in the validation of the variables for optimization using the Multivariate analysis tool of Response Surface Methodology (RSM). To test the significant formulation variables, the Box-Behnken approach using 15 runs design was adopted.

Results:  The rate of contaminant removal was observed to fit into a quadratic function. For optimal rate or contaminant removal, the fitted model predicted the optimal formulation cocktail condition to be within 0.54 mg/kg (Corn steep liquor), phosphate 137.49 mg/kg (poultry droppings) and 6.4% inocula for initial TPH of 9744 mg kg-1 and THC of 9641 mg kg-1 contaminant level. The model for the application of the bioremediation product and the variables evaluated had a significant p-value < 0.005 for the attainment of 85 to 96 % of TPH and THC removal after 56 days of treatment.

Conclusions:  This study has shown the need to harness the abundant agrowaste nutrients in supporting high throughput rhizobacteria in the formulation of a bioremediation agent suitable for use in the reclamation of oil spill sites in the Niger Delta oil-producing region.