bluuebunny/crossref_metadata_2025 huggingface dataset:
Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in acute myeloid leukemia
Authors: Mannelli Francesco , Gianfaldoni Giacomo , Bencini Sara , Piccini Matteo , Cutini Ilaria , Bonetti Maria Ida , Scappini Barbara , Pancani Fabiana , Ponziani Vanessa , Chiarini Marco , Borlenghi Erika , Bassan Renato , Rossi Giuseppe , Bosi Alberto
Published: July 2020

Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) is increasingly used in risk stratification. However, several issues around this use are unresolved, including, among others, the most suitable time‐point(s) for its application. Overall, late assessments appear more effective at distinguishing outcome but, in some studies, the early evaluations were already highly informative, anticipating the value of later ones. Our work integrated MRD with peripheral blast clearance (PBC), a treatment‐related biomarker previously demonstrated to be a powerful predictor of response. From 2007 to 2014, we have studied 120 patients treated according to the NILG 02‐06 trial and who achieved CR after induction. Patients in PBC‐defined categories (separated by a 1.5‐log threshold) showed significantly different probabilities of attaining MRD negativity, after either induction (MRD1) or consolidation (MRD2). Peripheral blast clearance combined with MRD1 largely anticipated MRD2‐related information: when both biomarkers predicted chemosensitive disease (PBChigh/MRD1neg), the rate of MRD2‐negativity was 90%, and DFS and OS estimates were 68% and 76% at 3 years, respectively. When both markers were unfavorable (PBClow/MRD1pos), rates of MRD2 negativity, DFS, and OS were 20%, 34%, and 24%, respectively, at 3 years. In fact, MRD2 added prognostic value only in cases with discordant PBC/MRD1 data. Our data support a reasoned timing for MRD‐based therapeutic decisions, modulated on individual chemosensitivity, an approach we have implemented in a forthcoming prospective multi‐center trial by Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA).
Polymersomes as Nanoreactors Enabling the Application of Solvent‐Sensitive Enzymes in Different Biphasic Reaction Setups
Authors: Golombek Florian , Castiglione Kathrin
Published: July 2020

There is an increasing interest in biocatalysis to perform chemical reactions in biphasic systems, consisting of an aqueous phase and a water‐immiscible organic solvent or ionic liquid. In most cases, the hydrophobic phase is used as reservoir for poorly water‐soluble substrates or for in situ product removal. However, many enzymes are solvent‐sensitive and cannot be used in such systems. In this study, the solvent‐sensitive enzyme mandelate racemase is exemplarily protected from the organic phase by its entrapment in (crosslinked) polymersomes. The covalent crosslinking of the individual chains of the block copolymer poly(2‐methyloxazoline)15‐poly(dimethylsiloxane)68‐poly(2‐methyloxazoline)15 via terminal methacrylates leads to enhanced membrane stability. This effect is especially pronounced for long‐time incubation in the presence of organic solvents and ionic liquids. By using a gentle polymerization initiator at its minimal necessary concentration, the prior encapsulated enzymes remain intact during crosslinking. Although the insertion of natural channel proteins into the membrane improves the mass transport into the vesicles, it is non‐essential. Mandelate racemase in (crosslinked) polymersomes remains active in different highly dispersed biphasic systems for more than 24 h. The free enzyme, on the other hand, gets completely inactivated within 1 h, thus illustrating the potential of polymersomes as nanoreactors in biphasic reaction setups.
Exon 11 homozygous mutations and intron 10/exon 11 junction deletions in the KIT gene are associated with poor prognosis of patients with gastrointestinal stromal tumors
Authors: Shen Yan‐Ying , Ma Xin‐Li , Wang Ming , Zhuang Chun , Ni Bo , Tu Lin , Liu Qiang , Zhao Wen‐Yi , Cao Hui
Published: July 2020

Background

Gastrointestinal stromal tumors (GISTs) with different types of mutations exhibit different clinical characteristics and prognosis. This study aimed to evaluate the prognostic value of mutations in KIT and PDGFRA in a large‐scale cohort of GIST patients with current therapy including surgery and imatinib.

Methods

A total of 1163 patients diagnosed with GISTs between January 2006 and December 2018 were enrolled in this study. Mutation analysis was performed for exons 9, 11, 13, and 17 of KIT and exons 12 and 18 of PDGFRA. Mutations were grouped into 12 categories according to the gene, exon, and involved codons; they were analyzed considering the clinical characteristics, disease‐free survival (DFS), and overall survival (OS) of patients with GISTs.

Results

In low‐risk GISTs, we identified two predictors of worse DFS: tumor origin in the rectum and KIT exon 11 deletion involving two or more codons. In high‐risk GISTs treated with R0 resection and imatinib, patients with KIT exon 11 homozygous mutations and KIT intron 10/exon 11 junction deletions demonstrated the highest recurrence rate, indicating that these mutations can be independent prognostic factors of DFS. The presence of KIT exon 11 homozygous mutations also independently influenced OS.

Conclusion

Low‐incidence mutations such as KIT exon 11 homozygous mutations or intron 10/exon 11 junction deletions in GISTs should be carefully evaluated to explore novel treatment strategies, as tumors with these mutations have a high recurrence rate and a very poor prognosis after surgery followed by imatinib adjuvant treatment.
A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non–small cell lung cancer: Hoosier Cancer Research Network LUN 14‐179
Authors: Durm Greg A. , Jabbour Salma K. , Althouse Sandra K. , Liu Ziyue , Sadiq Ahad A. , Zon Robin T. , Jalal Shadia I. , Kloecker Goetz H. , Williamson Michael J. , Reckamp Karen L. , Langdon Robert M. , Kio Ebenezer A. , Gentzler Ryan D. , Adesunloye Bamidele A. , Harb Wael A. , Walling Radhika V. , Titzer Michael L. , Hanna Nasser H.
Published: July 2020

Background

Five‐year overall survival (OS) for patients with unresectable stage III non–small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti–programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease.

Methods

Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression‐free survival (PFS) and OS.

Results

The median follow‐up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2‐46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4‐33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1‐, 2‐, and 3‐year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%).

Conclusions

Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.
Prognostic value of blasts in peripheral blood in myelofibrosis in the ruxolitinib era
Authors: Masarova Lucia , Bose Prithviraj , Pemmaraju Naveen , Daver Naval G. , Zhou Lingsha , Pierce Sherry , Sasaki Koji , Kantarjian Hagop M. , Estrov Zeev , Verstovsek Srdan
Published: July 2020

Background

Circulating blasts (peripheral blood [PB] blasts) ≥1% have long been considered an unfavorable feature for patients with primary myelofibrosis. Whether further quantification of PB blasts and their correlation with bone marrow (BM) blasts have incremental value with regard to patient prognostication is unclear. Similarly, the role of the JAK1/JAK2 inhibitor ruxolitinib (RUX) is not well defined in patients who have increased blasts.

Methods

The authors retrospectively studied 1316 patients with myelofibrosis who presented at their institution between 1984 and 2018 and had available PB and BM blasts.

Results

The PB blast percentage influenced overall survival (OS) only among patients who had BM blasts <5%, with a median OS of 64 months for patients with 0% PB blasts, 48 months for those with 1% to 3% PB blasts, and 22 months for those with 4% PB blasts (P < .01). Patients who had 4% PB blasts and 5% to 9% BM/PB blasts had clinical features similar to those of patients who had 10% to 19% blasts. Although the OS of the former patients was longer than in patients who had 10% to 19% blasts, it was not statistically different (median OS: 22, 26, and 13 months, respectively; P > .05). Forty‐four percent of patients received RUX throughout their disease course. All patients who had <10% blasts (PB or BM) and received treatment with RUX had superior OS compared with those who did not receive RUX within the same group. PB blasts ≥4% and BM blasts ≥5% were significant for predicting inferior survival in multivariate analysis.

Conclusions

The current results provide comprehensive insight into the role of peripheral blasts in patients with myelofibrosis and indicates that patients who have PB blasts ≥4% have an unfavorable prognosis. RUX provides a survival benefit to patients who have PB blasts <10%.
A2Cloud‐RF: A random forest based statistical framework to guide resource selection forhigh‐performancescientific computing on the cloud
Authors: Samuel David , Khan Syeduzzaman , Balos Cody J. , Abuelhaj Zachariah , Dutoi Anthony D. , Kari Chadi , Mueller David , Pallipuram Vivek K.
Published: July 2020

This article proposes a random‐forest based A2Cloud framework to match scientific applications with Cloud providers and their instances for high performance. The framework leverages four engines for this task: PERF engine, Cloud trace engine, A2Cloud‐ext engine, and the random forest classifier (RFC) engine. The PERF engine profiles the application to obtain performance characteristics, including the number of single‐precision (SP) floating‐point operations (FLOPs), double‐precision (DP) FLOPs, x87 operations, memory accesses, and disk accesses. The Cloud trace engine obtains the corresponding performance characteristics of the selected Cloud instances including: SP floating point operations per second (FLOPS), DP FLOPS, x87 operations per second, memory bandwidth, and disk bandwidth. The A2Cloud‐ext engine uses the application and Cloud instance characteristics to generate objective scores that represent the application‐to‐Cloud match. The RFC engine uses these objective scores to generate two types of random forests to assist users with rapid analysis: application‐specific random forests (ARF) and application‐class based random forests. The ARF consider only the input application's characteristics to generate a random forest and provide numerical ratings to the selected Cloud instances. To generate the application‐class based random forests, the RFC engine downloads the application profiles and scores of previously tested applications that perform similar to the input application. Using these data, the RFC engine creates a random forest for instance recommendation. We exhaustively test this framework using eight real‐world applications across 12 instances from different Cloud providers. Our tests show significant statistical agreement between the instance ratings given by the framework and the ratings obtained via actual Cloud executions.
Creatinine‐Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally Eliminated Drugs
Authors: Zhang Yifei , Sherwin Catherine M. , Gonzalez Daniel , Zhang Qunshu , Khurana Mona , Fisher Jeffrey , Burckart Gilbert J. , Wang Yaning , Yao Lynne P. , Ganley Charles J. , Wang Jian
Published: July 2020

The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. This study evaluated the performance of those equations in estimating individual clearance of drugs that are predominantly eliminated by glomerular filtration, using clinical data from the renally eliminated drugs gadobutrol, gadoterate, amikacin, and vancomycin. The eGFR was compared with the observed drug clearance (CL) in 352 pediatric patients from birth to 12 years of age. Multiple eGFR equations overestimated the drug CL on average, including the original and bedside Schwartz equations, which showed an average eGFR/CL ratio between 1 and 3. Further analysis with bedside Schwartz equation showed a higher eGFR/CL ratio in the subjects with a lower SCR or CL. Supraphysiological eGFR as high as 380 mL/min/1.73 m2 was obtained using the bedside Schwartz equation for some of the subjects, most of whom are children < 2 years of age with SCR < 0.2 mg/dL. Excluding the subjects with supraphysiological eGFR from the analysis did not change the overall trend of overestimation. In conclusion, Schwartz equations led to an overestimation of drug clearance for the drugs evaluated. When greater precision is required in predicting eGFR for pediatric patients, such as in drug dosing, revised k constants for the Schwartz equation or new methods of glomerular filtration rate estimation may be necessary.
TiO2 Mesocrystals Processed at Low Temperature as the Electron‐Transport Material in Perovskite Solar Cells
Authors: Guo Minghuang , Shen Deli , Li Yafeng , Akram Muhammad Aftab , Wei Mingdeng
Published: July 2020

TiO2 is the most widely used material for preparing the electron‐transporting layer (ETL) in perovskite solar cells (PSCs). However, it requires a high‐temperature sintering process. Moreover, the intrinsic defects and low electron mobility of TiO2 ETLs cause instability and hysteresis effects in PSCs. In this study, a mesoporous film composed of anatase TiO2 mesocrystals was facilely fabricated by a low‐temperature route and then used as an ETL in PSCs for the first time. A satisfactory efficiency of 20.26 % can be achieved through delicate control of the entire device fabrication procedure. The optimal device, with an area of 1 cm2, achieves an efficiency of 17.07 %. In comparison to the common TiO2 ETLs, those composed of TiO2 mesocrystals show the enhanced electron extraction and suppression of charge accumulation at the perovskite/ETL interface, resulting in improved photovoltaic performance and reduced hysteresis.
Prevention of heart failure events with intensive versus standard blood pressure lowering across the spectrum of kidney function and albuminuria: a SPRINT substudy
Authors: Vaduganathan Muthiah , Pareek Manan , Kristensen Anna M.D. , Biering‐Sørensen Tor , Byrne Christina , Almarzooq Zaid , Olesen Thomas Bastholm , Olsen Michael H. , Bhatt Deepak L.
Published: July 2020

Aims

To determine whether a strategy of intensive blood pressure control reduces the risk of heart failure (HF) events consistently across the spectrum of kidney function and albuminuria.

Methods and results

SPRINT was a randomized clinical trial in which 9361 individuals ≥50 years, at high risk for or with cardiovascular disease, a systolic blood pressure of 130–180 mmHg, but without diabetes, were randomized to intensive (target <120 mmHg) vs. standard (target <140 mmHg) blood pressure control. We assessed whether estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio (UACR) modified the effects of the blood pressure control strategy in reducing HF events (either hospitalization or emergency department visits) and the composite of HF events or cardiovascular death, using Cox proportional hazards regression and restricted cubic splines. Of the 9361 individuals included in SPRINT, eGFR and UACR were available for 9324 (99.6%) and 8913 (95.2%) subjects, respectively, including 2650 (28.4%) with eGFR <60 mL/min/1.73 m2 and 248 (2.8%) with UACR >300 mg/g. During a median follow‐up of 3.2 years (range 0–4.8 years), 160 (1.8%) participants had HF events and 233 (2.6%) had HF events or cardiovascular death. Risks of HF events or cardiovascular death increased from 0.42 (0.34–0.53) per 100 patient‐years in patients with eGFR ≥60 mL/min/1.73 m2 and UACR <30 mg/g to 4.55 (3.00–6.91) per 100 patient‐years in patients with eGFR <60 mL/min/1.73 m2 and UACR >300 mg/g. A similar gradient was observed for HF events alone. Both eGFR and UACR were independently, non‐linearly associated with HF hospitalization and HF hospitalization or cardiovascular death (test for overall trend, P < 0.001). While the effects of intensive blood pressure control on HF event risk appeared to attenuate at lower eGFR and higher UACR, there was no significant interaction between eGFR or UACR and blood pressure control strategy (continuous and categorical interaction P > 0.05).

Conclusion

In SPRINT, eGFR and albuminuria were strong and additive determinants in forecasting HF risk. The effect of intensive blood pressure control in decreasing HF risk did not significantly vary across the spectrum of kidney function or albuminuria. Multidisciplinary pathways, incorporating blood pressure control, are needed for at‐risk patients with chronic kidney disease to attenuate HF risk.

Trial Registration: ClinicalTrials.gov Identifier NCT01206062.
Geographic patterns of implicit age bias and associations with state‐level health outcomes across the United States
Authors: Giasson Hannah L. , Chopik William J.
Published: July 2020

Negative attitudes toward aging are pervasive in society and may be detrimental to people's health as they become older. Older people tend to report feeling significantly younger than their chronological age, often as a way of psychologically distancing themselves from the stigma of old age. However, attitudes and behaviors toward aging may differ across regional contexts. We examined associations among state‐level patterns of bias against older adults and state‐level health outcomes across the United States. Data from 803,009 respondents (ages: 15–94) across 50 U.S. states (and the District of Columbia) revealed geographic variation in implicit age bias. Higher state‐level implicit age bias was associated with poorer state‐level health outcomes among adults ages 65+. Older adults living in states high in implicit age bias showed greater age‐group dissociation compared to older adults living in states low in implicit age bias. Findings highlight potential consequences of implicit age bias and invite further research on the long‐term health implications of individual age‐group dissociation in response to regional age bias.
Diesel and gasoline like fuel production with minimum styrene content from catalytic pyrolysis of polystyrene
Authors: Amjad Um‐e‐Salma , Ishaq Manzar , Rehman Hamood ur , Ahmad Nabeel , Sherin Lubna , Hussain Murid , Mustafa Maria
Published: July 2020

Pyrolysis of waste polystyrene to generate fuel was carried out to yield pyrolysis oil. For the first time, NiO deposited over ZrO2 carrier as catalyst, was deployed and evaluated in the catalytic pyrolysis. Catalysts based on different loading (2, 5, 10, and 15%) of NiO deposited over ZrO2 carrier were prepared by solution combustion synthesis and tested toward screening of catalytic pyrolysis of PS in semi batch reactor. Based on conversion, yield of oil and low styrene monomer content, the catalytic performance with different loadings was evaluated and optimized. Furthermore, the oil obtained from the best catalysts were analyzed using GC–MS for carbon number distribution, depolymerization reactions, and diesel fuel generation. These catalysts were also characterized using X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), pyridine FTIR, and scanning electron microscopy (SEM) techniques. As compared to thermal pyrolysis, the catalytic pyrolysis process was found to be highly selective toward diesel like fuel generation with minimum styrene monomer formation. Also, 2 and 10% NiO catalyst showed the best catalytic performance in pyrolysis process that could be ascribed to the presence of Lewis and Brönsted acid sites resulting in selectivity for C16 carbon number, diesel fuel generation, and depolymerization reactions.
Enhancement in rice seed germination via improved respiratory metabolism under chilling stress
Authors: Nie Lixiao , Liu Hongyan , Zhang Li , Wang Weiqin
Published: July 2020

Chilling stress is one of the abiotic stresses that severely limited the production of many field crops. The chilling stress during emergence stages of rice severely hampered the process of seed germination and seedling growth and resulted in yield losses. Meanwhile, the development of seed priming has been proved to effectively enhance the seedling establishment of rice under chilling stress. However, the regulating effects of seed priming on the respiratory metabolism during rice seed germination under chilling stress have rarely been explored. In the present study, the effects of two pre‐optimized seed priming treatments, selenium priming (Se) and salicylic priming (SA), were examined under chilling stress. The results revealed that chilling stress significantly reduced the rice seed germination and seedling growth, as well as the respiration rate and ATP contents in rice seeds and seedlings. While seed priming was effective to significantly enhance the respiration rate and ATP levels in rice seeds and seedlings, such positive effects might be induced by the enhanced glycolysis metabolism, as well as the repair and biogenesis of mitochondria. However, the molecular mechanisms in association with the enhanced respiration in primed rice seeds and seedlings under chilling stress still needed to be addressed in future studies.
Common HTR2A variants and 5‐HTTLPR are not associated with human in vivo serotonin 2A receptor levels
Authors: Spies Marie , Nasser Arafat , Ozenne Brice , Jensen Peter S. , Knudsen Gitte M. , Fisher Patrick M.
Published: July 2020

The serotonin 2A receptor (5‐HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18F]altanserin and [11C]Cimbi‐36 positron emission tomography (PET) allow for high‐resolution imaging of 5‐HT2AR in the living human brain. Cerebral 5‐HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5‐HT2AR or other serotonin (5‐HT) proteins, their effect on human in vivo brain 5‐HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5‐HTTLPR predict neocortex in vivo 5‐HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18F]altanserin or [11C]Cimbi‐36 PET. Although we observed genotype group differences in 5‐HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5‐HT2AR binding in what is the largest human in vivo 5‐HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5‐HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5‐HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5‐HT2AR binding.
Boardroom gender diversity and dividend payout strategies: Effects of mergers deals
Authors: Trinh Vu Quang , Cao Ngan Duong , Dinh Linh Hai , Nguyen Hong Ngoc
Published: July 2020

Our study examines the effects of mergers and acquisitions deals on the relationship between female leadership and dividend strategies for 90 UK listed firms during the period 2006–2016. Results indicate that firms with a larger proportion of female directors serving on the board are more likely to pay higher dividends, but this positive finding is weaker when the firms experienced a higher number of mergers and acquisitions deals. Interestingly, extended analyses on female directors' positions show the opposing effects of female Chairmen and female CEOs on a firm's payout strategies. Although a female Chairman is associated with higher dividend payout levels, a female CEO shows an adverse impact. Yet these results tend to be reversed for firms with more merger and acquisition transactions. Our findings make a significant contribution to a trendy but relatively limited and inconclusive topic that links gender diversity to scrutiny intensity.
Quantile causality and dependence between crude oil and precious metal prices
Authors: Shafiullah Muhammad , Chaudhry Sajid M. , Shahbaz Muhammad , Reboredo Juan C.
Published: July 2020

This paper examines long‐run dependence and causality between oil and precious metal (gold, silver, platinum, palladium, steel, and titanium) prices across quantiles by exploiting their time series properties with the help of novel econometric techniques. The empirical results for the period 1990–2019 indicate that oil and metal prices are nonstationary across different quantiles and that cointegration patterns differ widely across quantiles. Causality running from oil to metal prices is quantile‐dependent and differs according to the metal, whereas upward and downward movements in metal prices have no causal effect on oil prices. These results have implications for investors and policymakers in terms of portfolio and risk management decisions.
COVID‐19 and obstetric practice: A critical review of the Nigerian situation
Authors: Ijarotimi Omotade A. , Ubom Akaninyene E. , Olofinbiyi Babatunde A. , Kuye‐Kuku Taiwo , Orji Ernest O. , Ikimalo John I.
Published: July 2020

Objective

To review what is known about COVID‐19 and highlight gaps in the context of Nigerian obstetric practice. Research data on COVID‐19 are understandably sparse in Africa. Nigeria, like most African countries, is battling a disease she is poorly equipped to fight.

Methods

The current available literature on COVID‐19 was reviewed in relation to obstetric practice in the Nigerian context, gaps were identified, and recommendations were made to improve the handling of the COVID‐19 pandemic in Nigerian obstetric practice.

Results

In and out of hospital, both the obstetrician and the obstetric patient are constantly being put at risk of exposure to the coronavirus because testing and preventive measures are either ineffective or non‐existent.

Conclusion

The pandemic has exposed the gross inadequacies in Nigeria’s healthcare system and is therefore a wake‐up call to the need for a complete overhaul of infrastructure and services. The government will do well to increase the budget allocation for health from the current paltry 4.14% to the recommended 15% of the total budget.

The Nigerian obstetrician stands a high risk of exposure due to inadequate preventive measures, and testing and diagnostic challenges.
A rapid white blood cell classification system based on multimode imaging technology
Authors: Lv Meng , Zhao Xi , Chen Feng , Yu Ming , Li Chao , Sun Jinggong
Published: July 2020

In order to simplify the complexity of white blood cell classification in existing point‐of‐care testing (POCT) testing equipment, a white blood cell classification detection system based on microfluidic and multimode imaging was constructed. Microfluidic chip was used in the system. A multimodal optical imaging system based on the characteristics of blood samples was designed to obtain eigenvalue extraction of cells. Afterward, a BP neural network model was constructed to realize automatic classification of white blood cells. Finally, 80 human blood samples were classified and detected by this system and compared with the results of Sysmex XE‐5000. The consistency correlation coefficients of white blood cells, lymphocytes, monocytes, neutrophils and eosinophils are 1.038, 0.907, 0.549, 0.922 and 1.028, respectively, and the CV values of the four types of white blood cells in the stability test were all below 10%. In this study, a white blood cell classification and detection system with small size, simple operation, fast single‐sample detection, high accuracy, and no maintenance is required. It will provide a solid technical support for the further development of POCT blood cell analysis equipment.
Deep learning protocol for improved photoacoustic brain imaging
Authors: Manwar Rayyan , Li Xin , Mahmoodkalayeh Sadreddin , Asano Eishi , Zhu Dongxiao , Avanaki Kamran
Published: July 2020

One of the key limitations for the clinical translation of photoacoustic imaging is penetration depth that is linked to the tissue maximum permissible exposures (MPE) recommended by the American National Standards Institute (ANSI). Here, we propose a method based on deep learning to virtually increase the MPE in order to enhance the signal‐to‐noise ratio of deep structures in the brain tissue. The proposed method is evaluated in an in vivo sheep brain imaging experiment. We believe this method can facilitate clinical translation of photoacoustic technique in brain imaging, especially in transfontanelle brain imaging in neonates.
Unveiling dose‐ and time‐dependent osteosarcoma cell responses to the γ‐secretase inhibitor, DAPT, by confocal Raman microscopy
Authors: Li Jie , Qin Jie , Zeng Haishan , Li Jing , Wang Kaige , Wang Shuang
Published: July 2020

Using confocal Raman micro‐spectroscopy, this study aims to elucidate the cellular responses of the γ‐secretase inhibitor, N‐[N‐(3,5‐difluorophenacetyl)‐L‐alanyl]‐S‐phenylglycine t‐butyl ester (DAPT), in osteosarcoma (OS) cells in a dose‐ and time‐dependent manner. The K7M2 murine OS cell line was treated with different DAPT doses (0, 10, 20, and 40 μM) for 24 and 48 hours before investigations. Significant compositional changes (nucleic acids, protein and lipid) after DAPT treatment were addressed, which testified inhibitory effect of DAPT on the growth of OS cells. Moreover, both partial least squares‐discriminant analysis (PLS‐DA) and principal component analysis‐linear discriminant analysis (PCA‐LDA) analyses revealed governing composition variations among groups by distinguishing their spectral characteristics. Furthermore, by adopting leave‐one‐out cross validation method, it is shown that PLS‐DA exhibited more classification capacity than PCA‐LDA algorithm. Hence, by understanding the DAPT‐based cellular variations, the achieved results provided an experimental foundation to establish new DAPT‐based anticancer therapeutic strategies, and preclinical Raman analytical methodologies on drug‐cell interactions.
Delayed Union of a Diaphyseal Forearm Fracture Associated With Impaired Osteogenic Differentiation of Prospectively Isolated Human Skeletal Stem Cells
Authors: Goodnough L Henry , Ambrosi Thomas H , Steininger Holly , DeBaun Malcolm R , Abrams Geoffrey D , McAdams Timothy R , Gardner Michael J , Chan Charles KF , Bishop Julius A
Published: July 2020

Delayed union or nonunion are relatively rare complications after fracture surgery, but when they do occur, they can result in substantial morbidity for the patient. In many cases, the etiology of impaired fracture healing is uncertain and attempts to determine the molecular basis for delayed union and nonunion formation have been limited. Prospectively isolating skeletal stem cells (SSCs) from fracture tissue samples at the time of surgical intervention represent a feasible methodology to determine a patient's biologic risk for compromised fracture healing. This report details a case in which functional in vitro readouts of SSCs derived from human fracture tissue at time of injury predicted a poor fracture healing outcome. This case suggests that it may be feasible to stratify a patient's fracture healing capacity and predict compromised fracture healing by prospectively isolating and analyzing SSCs during the index fracture surgery. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Genetic analysis of methicillin‐susceptible Staphylococcus aureus clinical isolates: High prevalence of multidrug‐resistant ST239 with strong biofilm‐production ability
Authors: Goudarzi Hossein , Goudarzi Mehdi , Sabzehali Fattaneh , Fazeli Maryam , Salimi Chirani Alireza
Published: July 2020

Background

The distributions of methicillin‐susceptible Staphylococcus aureus (MSSA) are divers geographically with different genetic backgrounds. Data related to molecular characteristics of MSSA compare to methicillin‐resistant Staphylococcus aureus (MRSA) is sparse.

Methods

In this cross‐sectional study, antimicrobial susceptibility testing, virulence genes analysis, biofilm formation, accessory gene regulator (agr) typing, and multilocus sequence typing (MLST) characterized on 75 MSSA isolates.

Results

Multidrug‐resistance MSSA was found to be 84%. Forty‐eight (64%) isolates were toxinogenic with 34 and 14 isolates carrying pvl and tst representing 45.3% and 18.7%. The most common SE genes were sed (20%), sec (16%), and sea (16%). Fifty‐five (73.3%) isolates were confirmed as biofilm producer with a markedly high prevalence of fnbA (93.3%), fnbB (86.7%), icaA (65.3%), icaD (53.3%), can (24%), ebp (10.7%), and bap (1.3%). A total of 3 agr types (I, 73.3%; III, 16%; II, 10.7%) and 4 clonal complexes (CCs) and sequence types (STs), namely CC8/ST293 (45.3%), CC/ST22 (28%), CC/ST30 (16%), and CC/ST5 (10.7%) were detected in this study. All the high and low‐level mupirocin resistance strains belonged to ST239 and ST22 strains, respectively. All the fusidic acid‐resistant isolates carried fusC and belonged to ST30.

Conclusions

These findings indicated that ST239 with strong biofilm production ability is the most common type in MSSA strains isolated from patients. It seems that the antimicrobial resistance profiles, toxin, and biofilm formation were closely associated with specific STs. Further studies are required to identify and control of these clonal lineages in our area.
The control of routine fish maneuvers: Connecting midline kinematics to turn outcomes
Authors: Howe Stephen P. , Astley Henry C.
Published: July 2020

Maneuverability is an important factor in determining an animal's ability to navigate its environment and succeed in predator–prey interactions. Although fish are capable of a wide range of maneuvers, most of the literature has focused on escape maneuvers while less attention has been paid to routine maneuvers, such as those used for habitat navigation. The quantitative relationships between body deformations and maneuver outcomes (displacement of the center of mass and change in trajectory) are fundamental to understanding how fish control their maneuvers, yet remain unknown in routine maneuvers. We recorded high‐speed video of eight giant danios (Devario aquepinnatus) performing routine and escape maneuvers and quantified the deformation of the midline, the heading of the anterior body, and the kinematics of the centroid (a proxy for center of mass). We found that both routine and escape behaviors used qualitatively similar independent body bending events, which we curvature pulses, that propagate from head to tail but show quantitative differences in midline kinematics and turn outcomes. In routine maneuvers, the direction change and acceleration of the fish are influenced by both the magnitude of the bending pulse and by the duration of the pulse, whereas in escape maneuvers, only pulse duration influenced direction change and turn acceleration. The bending pulse appears to be the smallest functional unit of a turn, and can function independently or in combination, enabling a fish to achieve a wide range of complex maneuvers.
Aggravated MRSA pneumonia secondary to influenza A virus infection is derived from decreased expression of IL‐1β
Authors: Shi Yunfeng , Shi Xiaohan , Liang Jingjing , Luo Jinmei , Ba Junhui , Chen Jianning , Wu Benquan
Published: July 2020

Secondary methicillin‐resistant Staphylococcus aureus (MRSA) infection is a cause of severe pneumonia with high mortality during influenza A virus (IAV) pandemics. Alveolar macrophages (AMs) mount cellular defenses against IAV and MRSA infection, which occurs via the nucleotide‐binding domain‐like receptor protein 3 (NLRP3) inflammasome. However, the activity and function of the NLRP3 inflammasome in MRSA pneumonia secondary to IAV infection remain unclear. To clarify this, we studied MRSA infection secondary to IAV both in vitro and in mouse model. The expression of the NLRP3 inflammasome was evaluated by quantitative reverse transcription polymerase chain reaction, immunofluorescence, Western blot, and enzyme‐linked immunosorbent assay. The lung pathology and the rate of weight change were observed. We found that IAV infection for 1 week activated NLRP3 inflammasome. The enhanced expression of NLRP3, caspase‐1, and cleaved caspase‐1 was associated with MRSA infection secondary to IAV, but the expression of interleukin (IL)‐1β decreased in superinfection with MRSA both in vitro and in vivo. The aggravated inflammatory pathology in MRSA pneumonia secondary to IAV infection was associated with decreased expression of IL‐1β. And increased weight loss in MRSA pneumonia secondary to IAV infection was related to decreased concentration of IL‐1β in serum. It infers that superinfection with MRSA reduces expression of IL‐1β someway, and decreased expression of IL‐1β impairs the host immunity and leads to aggravated pneumonia. These results contributed to our understanding of the detailed activity of the NLRP3 inflammasome, IL‐1β, and their relationship with aggravation of MRSA pneumonia secondary to IAV infection. Immunotherapy targeting the IL‐1β signaling pathway could be possible therapeutic strategy for secondary MRSA pneumonia.
Characterization of the volatile organic compounds produced from avocado during ripening by gas chromatography ion mobility spectrometry
Authors: Liu Yijun , Bu Mengting , Gong Xiao , He Jinna , Zhan Yu
Published: July 2020

BACKGROUND

The volatile organic compounds (VOCs) produced from avocados during storage may be distinct at different periods, and this difference may be related to their degree of maturity, for which no relevant research has been conducted yet.

RESULTS

A total of 30 typical target compounds were identified by gas chromatography–ion mobility spectrometry (GC–IMS) combined with principal component analysis (PCA) for the VOCs produced during the post‐harvesting process of avocado. With an increase in storage time, the VOCs content produced by avocado due to ripening continued to increase, and the uptrend was particularly obvious on day 13. The storage time of avocado could be distinguished according to the PC1 and PC2 values in the PCA chart.

Conclusion

GC–IMS detection combined with PCA was used to establish the fingerprints of VOCs in avocado for the first time. The maturity of avocados was determined by identifying the signal strength of characteristic VOCs, and this method could be of great potential to predict the maturity of fruits in the future. © 2020 Society of Chemical Industry
Contrast‐Enhanced Ultrasound Imaging Features of Focal Chemotherapy‐Induced Sinusoidal Injury in Patients With Colorectal Cancer
Authors: Qin Si , Cui Rui , Wang Yimin , Chen Yao , Huang Yan , Liu Guang Jian
Published: July 2020

Objectives

Increasing studies have reported focal chemotherapy‐induced sinusoidal injury (CSI) mimicking colorectal liver metastasis (CRLM) on imaging studies, resulting in unnecessary lobectomy. This study aimed to investigate the contrast‐enhanced ultrasound (CEUS) imaging features of focal CSI.

Methods

We retrospectively evaluated 16 patients who had a pathologic diagnosis of focal CSI and underwent CEUS between January 2013 and January 2019. The images were compared with those obtained from 27 patients with CRLM.

Results

On CEUS, 14 (87.5%) focal CSIs showed heterogeneous isoenhancement, 1 (6.3%) peripheral hyperenhancement, and 1 (6.3%) homogeneous hyperenhancement during the arterial phase. Compared with the adjacent liver parenchyma, the initial enhancement time of focal CSI was earlier in 2 (12.5%), simultaneous in 9 (56.3%), and later in 5 (31.3%) patients. In the portal and late phases, all of the focal CSI cases showed hypoenhancement compared with the adjacent liver parenchyma. Focal CSI had the following CEUS findings, which were different from those of CRLM: (1) heterogeneous isoenhancement in the arterial phase (87.5% versus 0%; P < .001); (2) an initial enhancement time later than that of the liver parenchyma (mean ± SD, 0.5 ± 1.5 versus −1.5 ± 1.9; P < .001); (3) a longer time to peak (30.5 ± 5.6 versus 22.5 ± 4.4 seconds; P < .001); and (4) a later time to wash‐out (51.0 ± 12.5 versus 35.0 ± 6.2 seconds; P = .002).

Conclusions

Focal CSI usually shows heterogeneous isoenhancement in arterial phase and hypoenhancement in portal and late phases on CEUS, with slow contrast wash‐in and wash‐out, which can be helpful in the differential diagnosis with CRLM.
Long term natural restoration creates soil‐like microbial communities in bauxite residue: A 50‐year filed study
Authors: Wu Hao , Tang Tian , Zhu Feng , Wei Xiaomeng , Hartley William , Xue Shengguo
Published: July 2020

Ecological reconstruction on bauxite residue (tailings) disposal areas is regarded as an effective approach to eliminate potential environmental risks. Establishment of microbial communities and associated functions may improve physical and chemical properties, and may stimulate soil formation in bauxite residue. Spontaneous colonization at a disposal area in Shandong Province, China, over 50 years, indicated that natural weathering can ameliorate residues, and in turn, support the establishment of vegetation communities. Residue samples were collected from unrestored, poorly restored and well restored areas to investigate the development of microbial communities and associated functions. Microbiota significantly developed after long term natural restoration. Microbial biomass, respiration and enzyme activities significantly increased in restored bauxite residue, whereas the metabolic quotient significantly decreased. In addition, the long‐term natural restoration significantly shaped the microbial structure from alkalophilic and halophilic assemblages (Firmicutes and Actinobacteria) to neutrophilic assemblages (Acidobacteria and Planctomycetes). Both microbial communities and associated functions in well restored residue had high similarity with that in natural soil, indicating that long term restoration created diverse soil‐like microbial communities and functions. Redundancy analysis (RDA) revealed that TN, followed by Na+, ESP, SOC, AP and pH were the major influence factors in the development of microbial communities in bauxite residue. These findings provide us a biogeochemical perspective to reveal soil formation in bauxite residue and suggest that nutrient supplement and regulation of salinity‐alkalinity may benefit for the establishment of microbial communities and functions in bauxite residue.
Linking weather patterns to regional extreme precipitation for highlighting potential flood events in medium‐ to long‐range forecasts
Authors: Richardson Doug , Neal Robert , Dankers Rutger , Mylne Ken , Cowling Robert , Clements Holly , Millard Jonathan
Published: July 2020

Medium‐ to long‐range precipitation forecasts are a crucial component in mitigating the impacts of fluvial flood events. Although precipitation is difficult to predict at these lead times, the forecast skill of atmospheric circulation tends to be greater. The study explores using weather patterns (WPs) as a preliminary step in producing forecasts of upper‐tail precipitation threshold exceedance probabilities for the UK. The WPs are predefined, discrete states representing daily mean sea‐level pressure (MSLP) over a European–North Atlantic domain. The WPs most likely to be associated with flooding are highlighted by calculating upper‐tail exceedance probabilities derived from the conditional distributions of regional precipitation given each WP. WPs associated with higher probabilities of extreme precipitation are shown to have occurred during two well‐known flood events: the 2014 Somerset Levels floods in southwest England; and Storm Desmond over the northern UK in December 2015. To illustrate the potential of this WP‐based prediction framework, a forecast guidance tool called Fluvial Decider is introduced. It is intended for use by hydro‐meteorologists in the England and Wales Flood Forecasting Centre (FFC). Forecasts of the MSLP from ensemble prediction systems (EPSs) are assigned to the closest‐matching WP, providing daily probabilistic forecasts of WPs out to the chosen lead time. Combining these probabilities with observed precipitation threshold exceedance probabilities provides a parsimonious tool for highlighting potential periods with increased risk of flooding. Model forecasts using the European Centre for Medium‐range Weather Forecasts (ECMWF) EPS highlighted both flood events as being at a higher than average risk of heavy extreme precipitation at lead times of over five days.
Survival of a male patient harboring CASK Arg27Ter mutation to adolescence
Authors: Mukherjee Konark , Patel Paras A. , Rajan Deepa S. , LaConte Leslie E. W. , Srivastava Sarika
Published: July 2020

Background

CASK is an X‐linked gene in mammals and its deletion in males is incompatible with life. CASK heterozygous mutations in female patients associate with intellectual disability, microcephaly, pontocerebellar hypoplasia, and optic nerve hypoplasia, whereas CASK hemizygous mutations in males manifest as early infantile epileptic encephalopathy with a grim prognosis. Here, we report a rare case of survival of a male patient harboring a CASK null mutation to adolescent age.

Methods

Trio whole exome sequencing analysis was performed from blood genomic DNA. Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electroencephalogram (EEG) analyses were performed to determine anomalies in brain development, metabolite concentrations, and electrical activity, respectively.

Results

Trio‐WES analysis identified a de novo c.79C>T (p.Arginine27Ter) mutation in CASK causing a premature translation termination at the very N‐terminus of the protein. The 17‐years, and 11‐month‐old male patient displayed profound intellectual disability, microcephaly, dysmorphism, ponto‐cerebellar hypoplasia, and intractable epilepsy. His systemic symptoms included overall reduced somatic growth, dysautonomia, ventilator and G tube dependence, and severe osteopenia. Brain MRI revealed a severe cerebellar and brain stem hypoplasia with progressive cerebral atrophy. EEG spectral analysis revealed a global functional defect with generalized background slowing and delta waves dominating even in the awake state.

Conclusion

This case study is the first to report survival of a male patient carrying a CASK loss‐of‐function mutation to adolescence and highlights that improved palliative care could extend survival. Moreover, the genomic position encoding Arg27 in CASK may possess an increased susceptibility to mutations.