bluuebunny/crossref_metadata_2025 huggingface dataset:
Deactivation Kinetics of ZSM‐5 by Coke in Ethanol‐to‐Hydrocarbons Process
Authors: Seifert Markus , Jonscher Clemens , Haufe Liane A. , Weigand Jan J.
Published: March 2021

Conversion of ethanol to hydrocarbons by porous zeolite ZSM‐5 is a sustainable alternative compared to crude oil, gas or coal conversion. A quantification and description of micro‐ and macroscopic deactivation kinetics with basic transport and reactor models reveals deeper insight into the dynamics of coking and product formation at varying contact time. A new first order deactivation model helps to separate linear deactivation and autocatalytic acceleration of catalyst decay. A deeper look into product formation reveals a change in selectivity during initiation and deactivation phase from bigger build‐up C5+ to smaller cracking products C3 after formation of coke precursors, which does not coincide with site‐loss and reduction of contact time alone. Thereby, deactivation and switching selectivity in the hydrocarbon pool concept become more deterministic, which paves the way to more selective ethanol conversion processes.
Sensing gastric cancer via point‐of‐care sensor breath analyzer
Authors: Leja Marcis , Kortelainen Juha M. , Polaka Inese , Turppa Emmi , Mitrovics Jan , Padilla Marta , Mochalski Pawel , Shuster Gregory , Pohle Roland , Kashanin Dmitry , Klemm Richard , Ikonen Veikko , Mezmale Linda , Broza Yoav Y. , Shani Gidi , Haick Hossam ,   the SniffPhone Project Research Group
Published: March 2021

Background

Detection of disease by means of volatile organic compounds from breath samples using sensors is an attractive approach to fast, noninvasive and inexpensive diagnostics. However, these techniques are still limited to applications within the laboratory settings. Here, we report on the development and use of a fast, portable, and IoT–connected point‐of‐care device (so‐called, SniffPhone) to detect and classify gastric cancer to potentially provide new qualitative solutions for cancer screening.

Methods

A validation study of patients with gastric cancer, patients with high‐risk precancerous gastric lesions, and controls was conducted with 2 SniffPhone devices. Linear discriminant analysis (LDA) was used as a classifying model of the sensing signals obatined from the examined groups. For the testing step, an additional device was added. The study group included 274 patients: 94 with gastric cancer, 67 who were in the high‐risk group, and 113 controls.

Results

The results of the test set showed a clear discrimination between patients with gastric cancer and controls using the 2‐device LDA model (area under the curve, 93.8%; sensitivity, 100%; specificity, 87.5%; overall accuracy, 91.1%), and acceptable results were also achieved for patients with high‐risk lesions (the corresponding values for dysplasia were 84.9%, 45.2%, 87.5%, and 65.9%, respectively). The test‐phase analysis showed lower accuracies, though still clinically useful.

Conclusion

Our results demonstrate that a portable breath sensor device could be useful in point‐of‐care settings. It shows a promise for detection of gastric cancer as well as for other types of disease.

Lay Summary

A portable sensor‐based breath analyzer for detection of gastric cancer can be used in point‐of‐care settings.

The results are transferrable between devices via advanced IoT technology.

Both the hardware and software of the reported breath analyzer could be easily modified to enable detection and monitirng of other disease states.
Early radiotherapy preserves vision in sporadic optic pathway glioma
Authors: Hanania Alexander N. , Paulino Arnold C. , Ludmir Ethan B. , Shah Veeral S. , Su Jack M. , McGovern Susan L. , Baxter Patricia A. , McAleer Mary Frances , Grosshans David R. , Okcu M. Fatih , Chintagumpala Murali M.
Published: March 2021

BACKGROUND

Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low‐grade glioma. Despite favorable survival, location makes treatment difficult and local progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades.

METHODS

Clinical characteristics were abstracted for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3‐ to 6‐month intervals were examined with age‐appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan‐Meier blindness‐free survival (BFS) curves, calculated as time‐to‐bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first‐line salvage treatment) or chemotherapy (CT) and evaluated using the log‐rank test.

RESULTS

Thirty‐eight patients with a median follow‐up of 8.5 years (range, 2‐17 years) were identified. Median age at diagnosis was 3 years (interquartile range, <1‐6 years). Early RT was administered in 11 patients (29%). Twenty‐seven patients (71%) were treated primarily with CT, initiated at a median age of 3.5 years (range, <1‐11 years). Eight patients in the CT group did eventually require RT secondary to VA loss and following multiple lines of CT. Median age at RT for all patients was 11 years (range, 3‐17 years). BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017).

CONCLUSIONS

In a contemporary cohort, early RT, defined as initial or first‐line salvage therapy, was found to have superior BFS for appropriately selected patients with sporadic optic pathway/hypothalamic gliomas.

LAY SUMMARY

Children with low‐grade brain tumors of the optic pathway generally have excellent long‐term survival; however, given the location of these tumors, there can commonly be threatened vision if the tumor grows.

Although radiation is generally deferred in children on the basis of legitimate concerns regarding the effects on the developing brain, it may represent a vision‐preserving therapy for well‐selected older patients.
Outcome of T‐cell–replete haploidentical stem cell transplantation improves with time in adults with acute lymphoblastic leukemia: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Nagler Arnon , Labopin Myriam , Koc Yener , Angelucci Emanuele , Tischer Johanna , Arat Mutlu , Pioltelli Pietro , Bernasconi Paolo , Chiusolo Patrizia , Diez‐Martin J. L. , Sanz Jamie , Ciceri Fabio , Peric Zinaida , Giebel Sebastian , Canaani Jonathan , Mohty Mohamad
Published: March 2021

BACKGROUND

The use of haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL).

METHODS

The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo‐HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018.

RESULTS

The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2‐year leukemia‐free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100‐day incidence of grade 2 through 4 acute graft‐vs‐host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia‐free survival (64.9% vs 47.3%; P = .019) and OS (75.5% vs 53.5%; P = .006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P = .047). The incidence of relapse, GVHD‐free/relapse‐free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22‐0.89; P = .022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26‐0.86; P = .014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes.

CONCLUSIONS

The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2‐year OS of 75% and, most recently, an NRM rate of only 17%.
Types of cancer and outcomes in patients with cancer requiring admission from the emergency department: A nationwide, population‐based study, 2016‐2017
Authors: Kim Youn‐Jung , Seo Dong‐Woo , Kim Won Young
Published: March 2021

BACKGROUND

Emergency department (ED) utilization and emergency admissions by patients with cancer have increased. The authors aimed to evaluate the characteristics of patients with cancer admitted through the ED and determine whether cancer types are related to in‐hospital mortality.

METHODS

The National Emergency Department Information System database of patients visiting EDs in South Korea between 2016 and 2017 was analyzed. Among 6,179,088 adult patients who presented to an ED with nontraumatic medical illness, patients with cancer were identified. The primary outcome was in‐hospital mortality.

RESULTS

Patients with cancer accounted for 6.8% of ED visits, and 239,630 patients (57.0%) were admitted to the hospital (intensive care unit [ICU], 9.5%; others, 90.5%). The prevalent cancers requiring hospitalization were lung cancer (15.7%), liver cancer (14.2%), and colon cancer (11.6%). The commonest reasons for admission other than cancer‐related medical problems (41.4%) were pneumonia (4.8%) and hepatobiliary infection (2.8%). Overall in‐hospital mortality was 16.1% (ICU, 28.3%; general wards, 14.8%); lung cancer (22.9%), liver cancer (19.7%), and leukemia/multiple myeloma (17.8%) showed the highest mortality rates. The highest odds for mortality were for lung cancer (adjusted odds ratio [OR], 2.227; 95% confidence interval [CI], 2.124‐2.335; P < .001) and liver cancer (adjusted OR, 1.839; 95% CI, 1.751‐1.930; P < .001), which were referenced to genitourinary cancer by multivariable logistic regression analysis.

CONCLUSIONS

More than half of the patients with cancer visiting EDs were admitted to the hospital with a mortality rate of 16.1%. Physicians treating patients with cancer and policymakers and planners designing health systems should understand the different prevalences and outcomes of oncological emergencies by cancer type to improve patient care.
The application of corporate social responsibility (CSR) actions for mitigation of environmental, social, corporate governance (ESG) and reputational risk in integrated reports
Authors: Karwowski Mariusz , Raulinajtys‐Grzybek Monika
Published: March 2021

Many studies stress the importance of understanding actions within sustainable development to prevent risks brought by companies. Environment, social factors, corporate governance (ESG) as well as reputation are even more important risk factors. In turn, companies can take corporate social responsibility (CSR) actions to avoid ESG and reputational risk. The aim of the article is to analyze the role of CSR in risk mitigation. The study includes content analysis of integrated reports in terms of reporting information on both risk and CSR activities such as stakeholder engagement or environmental policy. The companies most often indicate governmental risk, followed by social risk. The most common CSR actions are those related to social impact. Despite the fact that the analyzed database of over 120 integrated reports is not fully homogeneous, the conducted research shows a statistically important correlation in categorization of risks and CSR actions. Both statistical analysis and analysis of the content of reports confirms that companies identify their ESG and reputational risks and use CSR actions to mitigate them.
Degradation of Carbon Electrodes in the All‐Vanadium Redox Flow Battery
Authors: Singh Ashutosh K. , Pahlevaninezhad Maedeh , Yasri Nael , Roberts Edward P. L.
Published: March 2021

The charge−discharge operation of the vanadium redox flow battery degrades the electrodes over time and results in a performance and efficiency decay. The impact of extended charge−discharge cycling operation on carbon electrodes is investigated using carbon paper as a model electrode. Electrode degradation along with 70 % degradation of charge−discharge capacity was observed after 100 charge−discharge cycles of a single cell vanadium redox flow battery operating at a current density of 80 mA cm−2 at room temperature (23 °C). Raman mapping of the electrodes shows a decrease in structural defects in the negative electrode, and an increase in defects in the positive electrode, indicating differences in the degradation mechanism at each electrode. Electrochemical investigation reveals an increase in the activation overpotential at both the positive and negative electrodes. However, the negative electrode showed a higher activation overpotential indicating a higher impact of electrode degradation on the negative side. X‐ray photoelectron spectroscopy shows around an eightfold increase in surface oxygen functional groups after degradation in both positive and negative electrodes. The composition of oxygen functional groups was also observed to change significantly after degradation from dominantly carbonyl‐based to a combination of carbonyl‐ and carboxyl‐based groups. This study provides insight into the electrode degradation mechanism and highlights the differences in the mechanism for the positive and negative electrodes.
A fast settling frequency synthesizer with switched‐bandwidth loop filter
Authors: Beiraghdar Farhad , Ghobadi Rad Alireza , Sheikhaei Samad , Tohidian Massoud
Published: March 2021

This paper presents a new method to substantially decrease the settling time of analog phase‐locked loops (PLLs) while keeping its phase noise unaffected. This is achieved by switching the loop filter capacitors and resistor in such a way that output frequency is kept seamless. This method only affects the loop filter architecture and does not need any other changes to other blocks of the PLL. A frequency synthesizer circuit is implemented to validate the proposed method. The reference synthesizer has a 342‐μs settling time for a 1‐GHz frequency step (1.5 to 2.5 GHz), while if the proposed technique is enabled, the settling time is reduced to 48 μs (worst case). The measured phase noise of the synthesizer at 10‐kHz offset from a 2‐GHz carrier is −110 dBc/Hz.
Immature reticulocytes are sensitive and specific to low‐dose erythropoietin treatment at sea level and altitude
Authors: Jeppesen Jan Sommer , Breenfeldt Andersen Andreas , Bonne Thomas Christian , Thomassen Martin , Sørensen Helle , Nordsborg Nikolai Baastrup , Olsen Niels Vidiendal , Huertas Jesús Rodríguez , Bejder Jacob
Published: March 2021

We investigated whether immature reticulocyte fraction (IRF) and immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive biomarkers for low‐dose recombinant human erythropoietin (rhEpo) treatment at sea level (SL) and moderate altitude (AL) and whether multi (FACS) or single (Sysmex‐XN) fluorescence flow cytometry is superior for IRF and IR/RBC determination. Thirty‐nine participants completed two interventions, each containing a 4‐week baseline, a 4‐week SL or AL (2,230 m) exposure, and a 4‐week follow‐up. During exposure, rhEpo (20 IU kg−1) or placebo (PLA) was injected at SL (SLrhEpo, n = 25, SLPLA n = 9) and AL (ALrhEpo, n = 12, ALPLA n = 27) every second day for 3 weeks. Venous blood was collected weekly. Sysmex measurements revealed that IRF and IR/RBC were up to ~70% (P < 0.01) and ~190% (P < 0.001) higher in SLrhEpo than SLPLA during treatment and up to ~45% (P < 0.001) and ~55% (P < 0.01) lower post‐treatment, respectively. Compared with ALPLA, IRF and IR/RBC were up to ~20% (P < 0.05) and ~45% (P < 0.001) lower post‐treatment in SLrhEpo, respectively. In ALrhEpo, IRF and IR/RBC were up to ~40% (P < 0.05) and ~110% (P < 0.001) higher during treatment and up to ~25% (P < 0.05) and ~40% (P < 0.05) lower post‐treatment, respectively, compared with ALPLA. Calculated thresholds provided ~90% sensitivity for both biomarkers at SL and 33% (IRF) and 66% (IR/RBC) at AL. Specificity was >99%. Single‐fluorescence flow cytometry coefficient of variation was >twofold higher at baseline (P < 0.001) and provided larger or similar changes compared to multi‐fluorescence, albeit with smaller precision. In conclusion, IRF and IR/RBC were sensitive and specific biomarkers for low‐dose rhEpo misuse at SL and AL.
Impact of Phytophthora agathidicida infection on canopy and forest floor plant nutrient concentrations and fluxes in a kauri‐dominated forest
Authors: Schwendenmann Luitgard , Michalzik Beate
Published: March 2021

Kauri dieback, caused by Phytophthora agathidicida, is a biotic disturbance that poses a recent threat to the survival of kauri (Agathis australis) forests in New Zealand. Previous studies have shown that throughfall and stemflow play an important role in the kauri forests’ internal nutrient cycle. However, the effects of P. agathidicida infection on canopy and forest floor nutrient fluxes in kauri forests remain unknown. Here, we measured throughfall, stemflow and forest floor water yield, nutrient (potassium, calcium, magnesium, manganese, silicon, sulfur, sodium, iron) concentrations and fluxes of ten kauri trees differing in soil P. agathidicida DNA concentration, and health status. We did not observe an effect of soil P. agathidicida DNA concentration on throughfall, stemflow, and forest floor water yield. Throughfall and forest floor nutrient concentrations and fluxes decreased (up to 50%) with increasing soil P. agathidicida DNA concentration. We found significant effects on potassium and manganese fluxes in throughfall; calcium and silicon fluxes in forest floor leachate. A decline in canopy and forest floor nutrient fluxes may result in soil nutrient imbalances, which in turn may negatively impact forest productivity and may increase the susceptibility of trees to future pathogen infection in these ecologically unique kauri forests. Given our findings and the increasing spread of Phytophthora species worldwide, research on the underlying physiological mechanisms linking dieback and plant–soil nutrient fluxes is critical.
Cyclometallated 2‐Phenylpyrimidine Derived Platinum Complexes: Synthesis and Photophysical Properties
Authors: Fecková Michaela , Kahlal Samia , Roisnel Thierry , Saillard Jean‐Yves , Boixel Julien , Hruzd Mariia , le Poul Pascal , Gauthier Sébastien , Robin‐le Guen Françoise , Bureš Filip , Achelle Sylvain
Published: March 2021

A series of five platinum (II) complexes based on 2‐phenylpyrimidine ligands have been designed. Pyridine and chloride were used as auxiliary ligands. These complexes exhibit a slightly distorted square‐planar geometry. The nature and position of substituent on the phenyl ring was thoroughly studied. The presence of an electron‐donating substituent on the phenyl ring in the para position of the platinum atom leads to a red shift of the lowest‐energy absorption band, which corresponds to the HOMO→LUMO transition and permits to obtain phosphorescence in deoxygenated CH2Cl2 solution. All compounds are emissive in the solid state with a significant redshift for complexes bearing electron‐donating substituent on the phenyl ring of phenylpyrimidine ligand.
Maleic Acid/Thiourea‐Catalyzed Dearomative ipso‐Friedel–Crafts Reaction of Indoles to Produce Functionalized Spiroindolenines
Authors: Ueda Jun , Harada Shingo , Kobayashi Mayu , Yanagawa Mai , Nemoto Tetsuhiro
Published: March 2021

A dearomative spirocyclization of diazo‐functionalized indoles was developed under metal‐free conditions. Although the spiroindolenine architecture with a tertiary alkyl substituent at the 2‐position is a privileged scaffold of bioactive molecules, a general synthetic strategy has remained elusive. In this study, a dual catalyst system comprising maleic acid and Schreiner's thiourea was used to construct a spiroindolenine core that was inaccessible by rhodium or silver catalysis. Computational studies revealed a unique macrocyclic transition state consisting of the substrate, maleic acid, and thiourea cocatalyst, which lowered the activation energy of spirocyclization through multipoint mutual interactions.
Abnormal sensory thresholds of dystonic patients are not affected by deep brain stimulation
Authors: Listik Clarice , Cury Rubens Gisbert , da Silva Valquiria Aparecida , Casagrande Sara Carvalho Barbosa , Listik Eduardo , Link Naira , Galhardoni Ricardo , Barbosa Egberto Reis , Teixeira Manoel Jacobsen , Ciampi de Andrade Daniel
Published: March 2021

Background

Unlike motor symptoms, the effects of deep brain stimulation (DBS) on non‐motor symptoms associated with dystonia remain unknown.

Methods

The objective of this study was to assess the effects of DBS on evoked experimental pain and cutaneous sensory thresholds in a crossover, double‐blind on/off study and compare these results with those of healthy volunteers (HV).

Results

Sixteen patients with idiopathic dystonia (39.9 ± 13 years old, n = 14 generalized) with DBS of the globus pallidus internus underwent a battery of quantitative sensory testing and assessment using a pain top‐down modulation system (conditioned pain modulation, CPM). Results for the more and less dystonic body regions were compared in on and off stimulation. The patients' results were compared to age‐ and sex‐matched HV. Descending pain modulation CPM responses in dystonic patients (on‐DBS, 11.8 ± 40.7; off‐DBS, 1.8 ± 22.1) was abnormally low (defective) compared to HV (−15.6 ± 23.5, respectively p = .006 and p = .042). Cold pain threshold and cold hyperalgesia were 54.8% and 95.7% higher in dystonic patients compared to HV. On‐DBS CPM correlated with higher Burke‐Fahn‐Marsden disability score (r = 0.598; p = .014). While sensory and pain thresholds were not affected by DBS on/off condition, pain modulation was abnormal in dystonic patients and tended to be aggravated by DBS.

Conclusion

The analgesic effects after DBS do not seem to depend on short‐duration changes in cutaneous sensory thresholds in dystonic patients and may be related to changes in the central processing of nociceptive inputs.
ProBDNF induces sustained elevation of intracellular Ca2+ possibly mediated by TRPM7 channels in rodent microglial cells
Authors: Mizoguchi Yoshito , Ohgidani Masahiro , Haraguchi Yoshinori , Murakawa‐Hirachi Toru , Kato Takahiro A. , Monji Akira
Published: March 2021

Microglia are intrinsic immune cells that release factors including pro‐ and anti‐inflammatory cytokines, nitric oxide (NO) and neurotrophins following activation in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines or NO from activated microglia. Brain‐derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia. Interestingly, proBDNF, the precursor form of mature BDNF, and mature BDNF elicit opposing neuronal responses in the brain. Mature BDNF induces sustained intracellular Ca2+ elevation through the upregulation of the surface expression of TRPC3 channels in rodent microglial cells. In addition, TRPC3 channels are important for the BDNF‐induced suppression of NO production in activated microglia. In this study, we observed that proBDNF and mature BDNF have opposite effects on the relative expression of surface p75 neurotrophin receptor (p75NTR) in rodent microglial cells. ProBDNF induces a sustained elevation of [Ca2+]i through binding to the p75NTR, which is possibly mediated by Rac 1 activation and TRPM7 channels in rodent microglial cells. Flow cytometry showed that proBDNF increased the relative surface expression of TRPM7. Although proBDNF did not affect either mRNA expression of pro‐ and anti‐inflammatory cytokines or the phagocytic activity, proBDNF potentiates the generation of NO induced by IFN‐γ and TRPM7 channels could be involved in the proBDNF‐induced potentiation of IFN‐γ‐mediated production of NO. We show direct evidence that rodent microglial cells are able to respond to proBDNF, which might be important for the regulation of inflammatory responses in the brain.
Spatial correlation maps of the hippocampus with cerebrospinal fluid biomarkers and cognition in Alzheimer's disease: A longitudinal study
Authors: Liu Guodong , Liu Chaoqiang , Qiu Anqi ,   the Alzheimer's Disease Neuroimaging Initiative
Published: March 2021

This study is an observational study that takes the existing longitudinal data from Alzheimer's disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s‐MCI), 304 Alzheimer's Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c‐MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s‐MCI, and AD groups and corresponded to a greater decline of memory and attention in the s‐MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s‐MCI group. Interestingly, patients with c‐MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c‐MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.
Analysis and Validation of Human Targets and Treatments Using a Hepatocellular Carcinoma–Immune Humanized Mouse Model
Authors: Zhao Yue , Wang Jiaxu , Liu Wai Nam , Fong Shin Yie , Shuen Timothy Wai Ho , Liu Min , Harden Sarah , Tan Sue Yee , Cheng Jia Ying , Tan Wilson Wei Sheng , Chan Jerry Kok Yen , Chee Cheng Ean , Lee Guan Huei , Toh Han Chong , Lim Seng Gee , Wan Yue , Chen Qingfeng
Published: March 2021

Background and Aims

Recent development of multiple treatments for human hepatocellular carcinoma (HCC) has allowed for the selection of combination therapy to enhance the effectiveness of monotherapy. Optimal selection of therapies is based on both HCC and its microenvironment. Therefore, it is critical to develop and validate preclinical animal models for testing clinical therapeutic solutions.

Approach and Results

We established cell line–based or patient‐derived xenograft–based humanized‐immune‐system mouse models with subcutaneous and orthotopic HCC. Mice were injected with human‐specific antibodies (Abs) to deplete human immune cells. We analyzed the transcription profiles of HCC cells and human immune cells by using real‐time PCR and RNA sequencing. The protein level of HCC tumor cells/tissues or human immune cells was determined by using flow cytometry, western blotting, and immunohistochemistry. The HCC tumor size was measured after single, dual‐combination, and triple‐combination treatment using N‐(1ʹ,2‐Dihydroxy‐1,2ʹ‐binaphthalen‐4ʹ‐yl)‐4‐methoxybenzenesulfonamide (C188‐9), bevacizumab, and pembrolizumab. In this study, human immune cells in the tumor microenvironment were strongly selected and modulated by HCC, which promoted the activation of the IL‐6/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in tumor cells and led to augmented HCC proliferation and angiogenesis by releasing angiogenic cytokines in humanized‐immune‐system mice with HCC. In particular, intratumor human cluster of differentiation–positive (hCD14+) cells could produce IL‐33 through damage‐associated molecular pattern/Toll‐like receptor 4/activator protein 1, which up‐regulated IL‐6 in other intratumor immune cells and activated the JAK2/STAT3 pathway in HCC. Specific knockdown of the CD14 gene in human monocytes could impair IL‐33 production induced by cell lysates. Subsequently, we evaluated the in vivo anti‐HCC effect of C188‐9, bevacizumab, and pembrolizumab. The results showed that the anti‐HCC effect of triple‐combination therapy was superior to that of single or dual treatments.

Conclusions

Humanized‐immune‐system HCC mouse models are suitable for identifying targets from cancer and immune components and for testing combinational therapies.
Synthesis of Highly Substituted Cyclobutanones by a One‐Pot Keteniminium‐Enamine Process
Authors: Dagoneau Dylan , Kolleth Amandine , Quinodoz Pierre , Horoz Beyza , Catak Saron , Lumbroso Alexandre , Sulzer‐Mossé Sarah , De Mesmaeker Alain
Published: March 2021

Herein, we describe an effective one‐pot sequence for the regio‐ and stereoselective synthesis of highly substituted cyclobutanones. This process relies on first a [2+2] cycloaddition involving a keteniminium salt intermediate with an alkene followed by isomerization of the resulting cyclobutaniminium salt into its cyclic enamine form and then reaction of the latter with an electrophile. The adduct can be either hydrolyzed or reduced to give the corresponding cyclobutanone or cyclobutanamine, respectively, with excellent diastereocontrol. A variety of electrophiles was tolerated allowing the incorporation of diverse substituents and functionalities onto the cyclobutyl ring. Additionally, the coplanarity of diverse cyclic enamines was investigated through a DFT study.
Outcomes of patients with intermediate‐risk or poor‐risk metastatic renal cell carcinoma who received their first cycle of nivolumab and ipilimumab in the hospital because of symptomatic disease: The MD Anderson Cancer Center experience
Authors: Alhalabi Omar , Hasanov Elshad , Wilson Nathaniel R. , Araujo John , Wang Jianbo , Campbell Matthew T. , Goswami Sangeeta , Shah Amishi Y. , Gao Jianjun , Msaouel Pavlos , Tannir Nizar M.
Published: March 2021

Nivolumab plus ipilimumab (nivo/ipi) is an approved therapy for patients with intermediate‐risk or poor‐risk metastatic renal cell carcinoma (mRCC). Clinical factors that guide the selection of this regimen for patients with mRCC are urgently needed. We retrospectively analyzed medical records of patients with mRCC who were hospitalized at MD Anderson Cancer Center because of cancer‐related symptoms and received their first cycle of nivo/ipi in the inpatient setting. Clinical parameters, including demographics, histology, clinical history, response, and survival, were collected. The 4‐month survival probability, progression‐free survival (PFS), and overall survival (OS) were calculated using Kaplan‐Meier methods. Between November 2017 and 21 June 2020 patients were identified that fit the search: 19 patients (91%) had poor‐risk disease based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score; 17 patients (81%) had ≥4 risk factors; and 9 patients (43%) had sarcomatoid features on histology. Shortness of breath (28%) and abdominal pain (19%) were the two most common reasons for hospitalization. Partial response was achieved in 14% (3/21) of patients. Median PFS for all patients was 1.7 months (95% CI 0‐3.9); median OS for all patients was 1.7 months (95% CI 0‐4.2); and the 4‐month survival probability was 36% (95% CI 25%‐47%). In this retrospective study, patients with intermediate‐risk or poor‐risk mRCC who are hospitalized at a large tertiary referral center for cancer‐related symptoms derive limited clinical benefit from nivo/ipi when started in the inpatient setting. Alternative, more effective systemic therapies should be considered for these patients.
Fish cartilage: A promising source of biomaterial for biological scaffold fabrication in cartilage tissue engineering
Authors: Khajavi Maryam , Hajimoradloo Abdolmajid , Zandi Mojgan , Pezeshki‐Modaress Mohamad , Bonakdar Shahin , Zamani Abbas
Published: March 2021

Here, engineered cartilage‐like scaffold using an extracellular matrix (ECM) from sturgeon fish cartilage provided a chondroinductive environment to stimulate cartilaginous matrix synthesis in human adipose stem cells (hASCs). Three dimensional porous and degradable fish cartilage ECM‐derived scaffold (FCS) was produced using a protocol containing chemical decellularization, enzymatic solubilization, freeze‐drying and EDC‐crosslinking treatments and the effect of different ECM concentrations (10, 20, 30, and 40 mg/ml) on prepared scaffolds was investigated through physical, mechanical and biological analysis. The histological and scanning electron microscopy analysis revealed the elimination of the cell fragments and a 3‐D interconnected porous structure, respectively. Cell viability assay displayed no cytotoxic effects. The prepared porous constructs of fish cartilage ECM were seeded with hASCs for 21 days and compared to collagen (Col) and collagen‐10% hyaluronic acid (Col‐HA) scaffolds. Cell culture results evidenced that the fabricated scaffolds could provide a proper 3‐D structure to support the adhesion, proliferation and chondrogenic differentiation of hASCs considering the synthesis of specific proteins of cartilage, collagen type II (Col II) and aggrecan (ACAN). Based on the results of the present study, it can be concluded that the porous scaffold derived from fish cartilage ECM possesses an excellent potential for cartilage tissue engineering.
Automated radiosynthesis of [68Ga]Ga‐PSMA‐11 and [177Lu]Lu‐PSMA‐617 on the iPHASE MultiSyn module for clinical applications
Authors: Wichmann Christian W. , Ackermann Uwe , Poniger Stan , Young Kenneth , Nguyen Benjamin , Chan Gordon , Sachinidis John , Scott Andrew M.
Published: March 2021

Prostate‐specific membrane antigen (PSMA)‐targeted imaging and therapy of prostate cancer using theranostic pairs is rapidly changing clinical practice. To facilitate clinical trials, fully automated procedures for the radiosyntheses of [68Ga]Ga‐PSMA‐11 and [177Lu]Lu‐PSMA‐617 were developed from commercially available precursors using the cassette based iPHASE MultiSyn module. Formulated and sterile radiopharmaceuticals were obtained in 76 ± 3% (n = 20) and 91 ± 4% (n = 15) radiochemical yields after 17 and 20 min, respectively. Radiochemical purity was always >95% and molar activities exceeded 792 ± 100 and 88 ± 6 GBq/μmol, respectively. Quality control showed conformity with all relevant release criteria and radiopharmaceuticals were used in the clinic.
Use of radioiodine in nuclear medicine—A brief overview
Authors: Ferris Trevor , Carroll Laurence , Jenner Sarah , Aboagye Eric O.
Published: March 2021

Radioiodines have a long history in nuclear medicine. Herein, we discuss the production, properties and applications of these versatile iodine‐based imaging and theragnostic agents. There are 38 isotopes of iodine (I) including one stable form (127I). The most common radionuclides used in medical imaging and treatment, including Iodine‐123 (123I), Iodine‐124 (124I), Iodine‐125 (125I) and Iodine‐131 (131I), are discussed in this review.
Strong association of functional polymorphism in IL‐12B with susceptibility to chronic hepatitis B in Tunisia
Authors: Ben Dhifallah Imène , Ayouni Kaouther , Jmel Haifa , Kammoun Wafa , Hamzaoui Kamel , Sadraoui Amel , Triki Henda
Published: March 2021

Background

The chronicity or clearance of hepatitis B virus (HBV) infection depends on viral and genetic variables. The immune response against HBV is thought to be responsible for viral persistence or clearance. Cytokines such as interleukin 1‐2B (IL1‐2B) involved in the T‐helper 1 system are key mediators in the defence mechanisms against viral infection and play a role in the regulation of HBV clearance during infection. We aimed to examine whether the polymorphic variant TaqI polymorphism in the 3′‐untranslated region (3′‐UTR; rs3212227) suspected to modulate interleukin‐levels of IL‐12B has an influence on the risk of development of chronicity after HBV exposure.

Methods

Genotyping was performed by the polymerase chain reaction‐restriction fragment length polymorphism method for 236 patients with chronic hepatitis B (CHB) and 240 controls from different cities of Tunisia recruited in the Pasteur Institute of Tunisia between January 2017 and December 2018.

Results

We found that the IL‐12B polymorphism was associated with a significantly increased risk of CHB in patients (p = 1 × 10−3; χ
2 = 10.31 and odds ratio [OR] = 2.14; 95% confidence interval [CI] = 1.30–3.52) when AC/CC variant genotypes were compared with the wild‐type AA homozygote. Statistical significance was found when CHB‐males were compared with CHB‐females (p = 2 × 10−7; χ
2 = 26.62 and p = 1 × 10−3; χ
2 = 10.36, for genotypic and allelic frequencies, respectively). Also, CHB‐patients carrying C‐allele less than 50‐years were at an increased risk of developing chronic HBV infection than patients more than 50‐years (p = 6.1 × 10−5; χ
2 = 16.07).

Conclusions

These results suggest that the C‐allele would affect susceptibility to chronicity after HBV exposure in Tunisian patients especially for males less than 50‐years. Age and sex have an influence on this polymorphism in CHB Tunisian patients.
Performances of the VitaPCR™ SARS‐CoV‐2 Assay during the second wave of the COVID‐19 epidemic in France
Authors: Fitoussi Frédéric , Dupont Raphaël , Tonen‐Wolyec Serge , Bélec Laurent
Published: March 2021

To assess the practicability (usability and satisfaction) and analytical performances of the VitaPCR™ SARS‐CoV‐2 Assay (Credo Diagnostics Biomedical Pte. Ltd.), a rapid point‐of‐care nucleic acid amplification test (NAAT), by reference to real‐time reverse‐transcription polymerase chain reaction (rRT‐PCR) for respiratory viruses. The practicability of the VitaPCR™ Assay and Instrument was assessed from usability evaluation and a satisfaction questionnaire. Nasopharyngeal swabs were collected from 239 patients with coronavirus disease 2019 (COVID‐19)‐like illness during the second epidemic wave, in Paris, France. Overall, the usability of the VitaPCR™ Instrument was high. The satisfaction questionnaire indicated a high appreciation of the VitaPCR™ NAAT mainly for the short duration of analysis in only 20 min. A total of 140 and 99 samples were positive and negative for SARS‐CoV‐2 RNA by rRT‐PCR, respectively. In the event of significant viral load (i.e., N gene Ct values  33), the platform's analytical performances dropped significantly, with lower sensitivity, concordance, and accuracy, while its specificity remained high. The VitaPCR™ SARS‐CoV‐2 Assay is an accurate rapid point‐of‐care NAAT, suitable for clinical practice for the rapid diagnosis of COVID‐19, especially in patients with COVID‐19‐suspected symptoms.
The inflammatory markers of multisystem inflammatory syndrome in children (MIS‐C) and adolescents associated with COVID‐19: A meta‐analysis
Authors: Zhao Yan , Yin Lijuan , Patel Jenil , Tang Lei , Huang Ying
Published: March 2021

To conduct a systematic review and meta‐analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS‐C) versus severe/non‐severe COVID‐19, severe MIS‐C versus non‐severe MIS‐C, and among age groups of MIS‐C. Nine databases were searched for studies on inflammatory markers of MIS‐C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C‐reactive protein (CRP), procalcitonin (PCT), ferritin, D‐dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty‐one studies with 1735 participants yielded 787 MIS‐C patients. Compared to non‐severe COVID‐19 patients, MIS‐C patients had lower ALC and higher ANC, CRP, and D‐dimer levels. Compared to severe COVID‐19 patients, MIS‐C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS‐C patients had higher levels of WBC, ANC, CRP, D‐dimer, and ferritin than non‐severe MIS‐C patients. For MIS‐C, younger children (0–5 years) had lower CRP and ferritin levels than middle‐aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS‐C and the associated disorders.
From Creative Environment to Administrative Innovation: Creation and Implementation in Top Management Teams
Authors: Chen Lu , Gong Yaping , Song Yifan , Wang Mo
Published: March 2021

Drawing upon the stage model of innovation and the ability–motivation–opportunity (AMO) framework, we hypothesize the mediating role of top management team (TMT) creativity and the moderating roles of external social capital and environmental uncertainty in the relationship between TMT creative team environment and a firm’s administrative innovation. We collected multisource data from 136 TMTs and tested the hypotheses using bootstrap method with SPSS 23.0. As hypothesized, TMT creativity mediated the relationship between a creative team environment and administrative innovation. Moreover, external social capital amplified the effect of a creative team environment on TMT creativity and subsequently its indirect effect on administrative innovation via TMT creativity, whereas environmental uncertainty weakened the effect of a creative team environment on TMT creativity and subsequently its indirect effect on administrative innovation via TMT creativity. We advanced team creativity theory and research by showing how internal and external environment jointly shape creativity and innovation. We not only tested the stage model of innovation by showing TMT creativity as a mechanism linking creative team environment and administrative innovation, but also extended it by revealing external boundary conditions for this mechanism. Finally, we contribute to the upper echelon research by revealing the negative role of environmental uncertainty in the TMT creation stage.
Greening of the boreal peatland food web: Periphyton supports secondary production in northern peatlands
Authors: Ferguson Hannah M. , Slagle Elizabeth J. , McCann Ann Ashlea , Walls Jeremy T. , Wyatt Kevin H. , Rober Allison R.
Published: March 2021

Characterizing spatial and temporal variability of food web dynamics is necessary to predict how wetter and more nutrient‐rich conditions expected with climate change will influence the fate of organic matter within northern peatlands. The goals of this study were to (1) document spatial and temporal variability in the contribution of periphyton to peatland food webs using isotope analysis (13C and 15N), and (2) quantify the influence of increased nutrient availability on primary and secondary production across a gradient of rich, moderate, and poor fen peatlands common to the northern boreal biome. We established replicate m2 plots within each fen located in interior Alaska to quantify periphyton (algae and bacteria) and macroinvertebrate biomass with and without nutrient addition throughout a growing season (May–August). Stable isotope analysis showed that periphyton contributed = 65% of organic matter to the food web over time and across fens compared to = 7% from plants or detritus. The transfer of basal resources was reflected in an increase in herbivore biomass as algal biomass increased over time in all fens, followed by an increase in predatory macroinvertebrates during the latter part of the growing season. Furthermore, all measures of periphyton and macroinvertebrate biomass were enhanced by nutrient addition. These data provide insight into patterns of natural variation within the aquatic food web of boreal peatlands and show that basal resources within this ecosystem, which are generally considered to be “detritus‐based,” are actually driven by periphyton with minimal input from plant detrital pathways.
Review of Surface Modification Technologies for Mid‐Infrared Antireflection Microstructures Fabrication
Authors: Bushunov Andrey A. , Tarabrin Mikhail K. , Lazarev Vladimir A.
Published: March 2021

Mid‐infrared materials antireflection is in high demand for high‐powered or ultra‐broadband coherent light sources, where conventional antireflection coatings cannot be reliably applied. This work provides a critical review of the recent advances in microstructure fabrication technology for mid‐infrared antireflection applications. Several techniques are reviewed, including direct imprinting, wet and reactive ion etching using conventional photoresist masking, novel colloid crystal masks, and maskless etching, laser‐induced periodic structure formation, and multiple laser ablation method modifications, including femtosecond laser direct writing, direct laser interference ablation, and single pulse ablation. The advantages and drawbacks of the different approaches are discussed in detail to highlight the most promising techniques for the fabrication of antireflection microstructures capable of achieving 99% transmittance in the 2–16 m range.
Green InGaN Quantum Dots Breaking through Efficiency and Bandwidth Bottlenecks of Micro‐LEDs
Authors: Wang Lei , Wang Lai , Chen Chien‐Ju , Chen Kai‐Chia , Hao Zhibiao , Luo Yi , Sun Changzheng , Wu Meng‐Chyi , Yu Jiadong , Han Yanjun , Xiong Bing , Wang Jian , Li Hongtao
Published: March 2021

Micro‐LEDs are regarded as ideal light sources for next‐generation display and high‐speed visible‐light communication (VLC). However, the conventional micro‐LEDs based on InGaN quantum well (QW) active region suffer from a low efficiency under small injection (below 1 A cm−2) due to the size‐dependent effect and a limited 3 dB bandwidth (hundreds of MHz) due to quantum‐confined Stark effect. Here, InGaN quantum dots (QDs) are proposed as the active region of micro‐LEDs to address these challenges for their strong localization and low‐strain features. Green InGaN QDs are self‐assembled under Stranski–Krastanov (SK) and Volmer–Weber (VW) modes by using metal organic vapor phase epitaxy. The SK QDs can shift the peak efficiency of a micro‐LED to an extremely low current density of 0.5 A cm−2 (almost two orders of magnitude lower compared to QW ones) with an external quantum efficiency of 18.2% (nearly two times higher than present green micro‐LEDs). Besides, green micro‐LEDs based on VW QDs reach a 3 dB bandwidth of 1.3 GHz. These results indicate that InGaN QDs can provide an ultimate solution to micro‐LEDs for display and VLC applications, especially since they are fully compatible with current light‐emitting diode (LED) industrial technology.