bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review and meta-analysis
Authors: Ssentongo Paddy , Heilbrunn Emily S. , Ssentongo Anna E. , Advani Shailesh , Chinchilli Vernon M. , Nunez Jonathan J. , Du Ping
Published: March 2021

Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05–1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21–2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.
Transport property of multi-band topological material PtBi$$_2$$ studied by maximum entropy mobility spectrum analysis (MEMSA)
Authors: Zhao Haijun , Li Wenchong , Chen Yue , Xu Chunqiang , Li Bin , Luo Weidong , Qian Dong , Shi Zhixiang
Published: March 2021

Electrical transport of both longitudinal and transverse directions carries rich information. Mobility spectrum analysis (MSA) is capable of extracting charge information from conductivity tensor, including charge types, concentration and mobilities. Using a numerical method based on maximum entropy principle, i.e., maximum entropy mobility spectrum analysis (MEMSA), mobility spectrum for $$\beta $$
β
-type PtBi$$_2$$

2

is studied. Three hole-pockets and two electron-pockets were found, including a small hole pocket with very high mobility, which is very likely corresponding to Dirac Fermions. Benefiting from our high resolution result, we studied temperature dependence of carrier properties and explained the sign change phenomenon of Hall conductivity. We further compared the results with band structure obtained by our first principle calculation. The present results prove MEMSA is a useful tool of extracting carries’ information in recently discovered Iron-based superconductors, and topological materials.
A new image encryption algorithm based on the OF-LSTMS and chaotic sequences
Authors: He Yi , Zhang Ying-Qian , He Xin , Wang Xing-Yuan
Published: March 2021

In this paper, a novel image encryption algorithm based on the Once Forward Long Short Term Memory Structure (OF-LSTMS) and the Two-Dimensional Coupled Map Lattice (2DCML) fractional-order chaotic system is proposed. The original image is divided into several image blocks, each of which is input into the OF-LSTMS as a pixel sub-sequence. According to the chaotic sequences generated by the 2DCML fractional-order chaotic system, the parameters of the input gate, output gate and memory unit of the OF-LSTMS are initialized, and the pixel positions are changed at the same time of changing the pixel values, achieving the synchronization of permutation and diffusion operations, which greatly improves the efficiency of image encryption and reduces the time consumption. In addition the 2DCML fractional-order chaotic system has better chaotic ergodicity and the values of chaotic sequences are larger than the traditional chaotic system. Therefore, it is very suitable to image encryption. Many simulation results show that the proposed scheme has higher security and efficiency comparing with previous schemes.
Longitudinal birth cohort study finds that life-course frailty associates with later-life heart size and function
Authors: Topriceanu Constantin-Cristian , Moon James C. , Hardy Rebecca , Chaturvedi Nishi , Hughes Alun D. , Captur Gabriella
Published: March 2021

A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is unknown whether the health deficit burden is related to the appearance of cardiovascular disease. In order to answer this question, the same multidimensional FI looking at 45-health deficits was serially calculated per participant at 4 time periods (0–16, 19–44, 45–54 and 60–64 years) using data from the 1946 Medical Research Council (MRC) British National Survey of Health and Development (NSHD)—the world’s longest running longitudinal birth cohort with continuous follow-up. From these the mean and total FI for the life-course, and the step change in deficit accumulation from one time period to another was derived. Echocardiographic data at 60–64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCFi) and E/e′. Generalized linear models assessed the association between FIs and echocardiographic parameters after adjustment for relevant covariates. 1375 participants were included. For each single new deficit accumulated at any one of the 4 time periods, LVmassi increased by 0.91–1.44% (p < 0.013), while MCFi decreased by 0.6–1.02% (p < 0.05). A unit increase in FI at age 45–54 and 60–64, decreased EF by 11–12% (p < 0.013). A single health deficit step change occurring between 60 and 64 years and one of the earlier time periods, translated into higher odds (2.1–78.5, p < 0.020) of elevated LV filling pressure. Thus, the accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function.
Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
Authors: Lee Sophie N. , Kraska Jenna , Papargiris Melissa , Teng Linda , Niranjan Birunthi , Hammar Johanna , Ryan Andrew , Frydenberg Mark , Lawrentschuk Nathan , Middendorff Ralf , Ellem Stuart J. , Whittaker Michael , Risbridger Gail P. , Exintaris Betty
Published: March 2021

Pharmacotherapies for the treatment of Benign Prostatic Hyperplasia (BPH) are targeted at reducing cellular proliferation (static component) or reducing smooth muscle tone (dynamic component), but response is unpredictable and many patients fail to respond. An impediment to identifying novel pharmacotherapies is the incomplete understanding of paracrine signalling. Oxytocin has been highlighted as a potential paracrine mediator of BPH. To better understand oxytocin signalling, we investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue. We show that the Oxytocin Receptor (OXTR) is widely expressed in the human prostate, and co-localises to contractile cells within the prostate stroma. Exogenous oxytocin did not modulate prostatic fibroblast proliferation, but did significantly (p < 0.05) upregulate the frequency of spontaneous contractions in prostate tissue, indicating a role in generating smooth muscle tone. Application of atosiban, an OXTR antagonist, significantly (p < 0.05) reduced spontaneous contractions. Individual tissue responsiveness to both exogenous oxytocin (R2 = 0.697, p < 0.01) and atosiban (R2 = 0.472, p < 0.05) was greater in tissue collected from older men. Overall, our data suggest that oxytocin is a key regulator of inherent spontaneous prostate contractions, and targeting of the OXTR and associated downstream signalling is an attractive prospect in the development of novel BPH pharmacotherapies.
Streptococcus pneumoniae endophthalmitis: clinical settings, antibiotic susceptibility, and visual outcomes
Authors: Chen Kuan-Jen , Chong Ying-Jiun , Sun Ming-Hui , Chen Hung-Chi , Liu Laura , Chen Yen-Po , Wu Wei-Chi , Kang Eugene Yu-Chuan , Lai Chi-Chun
Published: March 2021

Streptococcus pneumoniae endophthalmitis is clinically more severe, more difficult to treat, and carry a higher risk of vision loss, evisceration, or enucleation. This study is to investigate the clinical settings, antibiotic susceptibility, and visual outcomes of S. pneumoniae endophthalmitis at a tertiary referral center in Taiwan. S. pneumoniae endophthalmitis was diagnosed in 38 eyes of 38 patients. The main clinical features were postcataract endophthalmitis (n = 13, 34%) and endophthalmitis associated with corneal ulcer (n = 12, 32%), trauma (n = 6, 16%), endogenous etiology (n = 4, 11%), trabeculectomy (n = 2, 5%), and pterygium excision-related scleral ulcer (n = 1, 3%). Presenting visual acuity ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics was performed in 17 eyes (39%) in primary or secondary treatments. S. pneumoniae isolates were susceptible to vancomycin (38/38, 100%), penicillin (37/38, 97%), ceftriaxone (37/38, 97%), cefuroxime (12/15, 80%), levofloxacin (13/15 ,87%), and moxifloxacin (15/17, 88%). Final visual acuity was better than 20/400 in 3 of 38 eyes (8%), 5/200 to hand motions in 3 eyes (8%), and light perception to no light perception in 32 eyes (84%). Ten eyes (26%) underwent evisceration or enucleation. Although S. pneumoniae isolates were susceptible to vancomycin, S. pneumoniae endophthalmitis had a very poor visual prognosis.
Serial lung ultrasounds in pediatric pneumonia in Mozambique and Pakistan
Authors: Ginsburg Amy Sarah , Nisar Imran , Madrid Lola , Lenahan Jennifer L. , Balouch Benazir , Vitorino Pio , Hwang Jun , Lamorte Alessandro , Kanth Neel , Bila Rubao , Valente Marta , Varo Rosauro , May Susanne , Bassat Quique , Jehan Fyezah , Volpicelli Giovanni
Published: March 2021

Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing and managing pneumonia. We sought to explore serial LUS examinations in children with chest-indrawing pneumonia in resource-constrained settings and compare their clinical and LUS imaging courses longitudinally. We conducted a prospective, observational study among children aged 2 through 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at 2 district hospitals in Mozambique and Pakistan. We assessed serial LUS at enrollment, 2, 6, and 14 days, and performed a secondary analysis of enrolled children’s longitudinal clinical and imaging courses. By Day 14, the majority of children with chest-indrawing pneumonia and consolidation on enrollment LUS showed improvement on follow-up LUS (100% in Mozambique, 85.4% in Pakistan) and were clinically cured (100% in Mozambique, 78.0% in Pakistan). In our cohort of children with chest-indrawing pneumonia, LUS imaging often reflected the clinical course; however, it is unclear how serial LUS would inform the routine management of non-severe chest-indrawing pneumonia.
Novel magnetically retrievable In2O3/MoS2/Fe3O4 nanocomposite materials for enhanced photocatalytic performance
Authors: Raha Sauvik , Ahmaruzzaman Md.
Published: March 2021

The current work involves synthesis of hybrid nanomaterial of In2O3/MoS2/Fe3O4 and their applications as photocatalysts for disintegration of esomeprazole under visible light illumination. The data emerged from various analyses testified to the successful construction of the desired nano-scaled hybrid photocatalyst. Tauc plot gave the band gap of In2O3/MoS2/Fe3O4 to be ~ 2.15 eV. Synergistic effects of the integrant components enabled efficacious photocatalytic performances of the nanocomposite. The nanohybrid photocatalyst In2O3/MoS2/Fe3O4 showed photodecomposition up to ~ 92.92% within 50 min. The current work realizes its objective of constructing metal oxide based hybrid nano-photocatalyst supported on MoS2 sheets for activity in the visible spectrum, which displayed remarkable capacity of disintegrating emerging persistent organic contaminants and are magnetically recoverable.
Germline masculinization by Phf7 in D. melanogaster requires its evolutionarily novel C-terminus and the HP1-family protein HP1D3csd
Authors: Yang Shu Yuan
Published: March 2021

Germ cells in Drosophila melanogaster need intrinsic factors along with somatic signals to activate proper sexual programs. A key factor for male germline sex determination is PHD finger protein 7 (Phf7), a histone reader expressed in the male germline that can trigger sex reversal in female germ cells and is also important for efficient spermatogenesis. Here we find that the evolutionarily novel C-terminus in Phf7 is necessary to turn on the complete male program in the early germline of D. melanogaster, suggesting that this domain may have been uniquely acquired to regulate sexual differentiation. We further looked for genes regulated by Phf7 related to sex determination in the embryonic germline by transcriptome profiling of FACS-purified embryonic gonads. One of the genes positively-regulated by Phf7 in the embryonic germline was an HP1family member, Heterochromatin Protein 1D3 chromoshadow domain (HP1D3csd). We find that this gene is needed for Phf7 to induce male-like development in the female germline, indicating that HP1D3csd is an important factor acting downstream of Phf7 to regulate germline masculinization.
Studies on the deposition of copper in lithium-ion batteries during the deep discharge process
Authors: Langner Thomas , Sieber Tim , Acker Jörg
Published: March 2021

End-of-life lithium-ion batteries represent an important secondary raw material source for nickel, cobalt, manganese and lithium compounds in order to obtain starting materials for the production of new cathode material. Each process step in recycling must be performed in such a way contamination products on the cathode material are avoided or reduced. This paper is dedicated to the first step of each recycling process, the deep discharge of lithium-ion batteries, as a prerequisite for the safe opening and disassembling. If pouch cells with different states of charge are connected in series and deep-discharged together, copper deposition occurs preferably in the cell with the lower charge capacity. The current forced through the cell with a low charge capacity leads, after lithium depletion in the anode and the collapse of the solid-electrolyte-interphase (SEI) to a polarity reversal in which the copper collector of the anode is dissolved and copper is deposited on the cathode surface. Based on measurements of the temperature, voltage drop and copper concentration in the electrolyte at the cell with the originally lower charge capacity, the point of dissolution and incipient deposition of copper could be identified and a model of the processes during deep discharge could be developed.
Enhanced interactions of Kuroshio Extension with tropical Pacific in a changing climate
Authors: Joh Youngji , Di Lorenzo Emanuele , Siqueira Leo , Kirtman Benjamin P.
Published: March 2021

Quasi-decadal climate of the Kuroshio Extension (KE) is pivotal to understanding the North Pacific coupled ocean–atmosphere dynamics and their predictability. Recent observational studies suggest that extratropical-tropical coupling between the KE and the central tropical Pacific El Niño Southern Oscillation (CP-ENSO) leads to the observed preferred decadal time-scale of Pacific climate variability. By combining reanalysis data with numerical simulations from a high-resolution climate model and a linear inverse model (LIM), we confirm that KE and CP-ENSO dynamics are linked through extratropical-tropical teleconnections. Specifically, the atmospheric response to the KE excites Meridional Modes that energize the CP-ENSO (extratropicstropics), and in turn, CP-ENSO teleconnections energize the extratropical atmospheric forcing of the KE (tropicsextratropics). However, both observations and the model show that the KE/CP-ENSO coupling is non-stationary and has intensified in recent decades after the mid-1980. Given the short length of the observational and climate model record, it is difficult to attribute this shift to anthropogenic forcing. However, using a large-ensemble of the LIM we show that the intensification in the KE/CP-ENSO coupling after the mid-1980 is significant and linked to changes in the KE atmospheric downstream response, which exhibit a stronger imprint on the subtropical winds that excite the Pacific Meridional modes and CP-ENSO.
Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas
Authors: Lee Sun Mi , Sung Chang Ohk
Published: March 2021

Poorly differentiated neuroendocrine carcinoma (NEC) is a rare subtype of colorectal cancer (CRC). This study aimed to investigate clinicopathologic characteristics of colorectal NECs and elucidate genomic differences and similarities between colorectal NECs and colorectal adenocarcinomas (ACs). A total of 30 colorectal NECs were screened for frequently identified CRC oncogenic driver genes by targeted next-generation sequencing of 382 genes. The median age of the patients was 67 years (range, 44 to 88 years). NECs occurred predominantly in the rectum (47%) and exhibited multiple adverse prognostic pathologic factors, including frequent lymphatic and vascular invasions, high rates of lymph node metastasis and distant metastasis and advanced TNM stage. The 1-, 3-, and 5-year overall survival rates of NEC patients were 46.7%, 36.4%, and 32.7%, respectively, with a median overall survival period of 11.5 months. In a molecular analysis, NECs showed high rates of BRAF mutation (23%), predominantly p.V600E (71%), and alterations in RB1 (47%), particularly deletion (57%). The frequencies and distributions of other genes, such as KRAS, APC, SMAD4, and PIK3CA, and microsatellite instability status were similar to those of ACs. These findings provide beneficial information for selecting therapeutic options, including targeted therapy, and a better understanding of the histogenesis of this tumour.
Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma
Authors: Oksvold Morten P. , Berglund Ulrika Warpman , Gad Helge , Bai Baoyan , Stokke Trond , Rein Idun Dale , Pham Therese , Sanjiv Kumar , Øy Geir Frode , Norum Jens Henrik , Smeland Erlend B. , Myklebust June H. , Helleday Thomas , Våtsveen Thea Kristin
Published: March 2021

Chemo-immunotherapy has improved survival in B-cell lymphoma patients, but refractory/relapsed diseases still represent a major challenge, urging for development of new therapeutics. Karonudib (TH1579) was developed to inhibit MTH1, an enzyme preventing oxidized dNTP-incorporation in DNA. MTH1 is highly upregulated in tumor biopsies from patients with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, hence confirming a rationale for targeting MTH1. Here, we tested the efficacy of karonudib in vitro and in preclinical B-cell lymphoma models. Using a range of B-cell lymphoma cell lines, karonudib strongly reduced viability at concentrations well tolerated by activated normal B cells. In B-cell lymphoma cells, karonudib increased incorporation of 8-oxo-dGTP into DNA, and prominently induced prometaphase arrest and apoptosis due to failure in spindle assembly. MTH1 knockout cell lines were less sensitive to karonudib-induced apoptosis, but were displaying cell cycle arrest phenotype similar to the wild type cells, indicating a dual inhibitory role of the drug. Karonudib was highly potent as single agent in two different lymphoma xenograft models, including an ABC DLBCL patient derived xenograft, leading to prolonged survival and fully controlled tumor growth. Together, our preclinical findings provide a rationale for further clinical testing of karonudib in B-cell lymphoma.
Prediction of anemia at delivery
Authors: Yefet Enav , Yossef Avishag , Nachum Zohar
Published: March 2021

We aimed to assess risk factors for anemia at delivery by conducting a secondary analysis of a prospective cohort study database including 1527 women who delivered vaginally ≥ 36 gestational weeks. Anemia (Hemoglobin (Hb) < 10.5 g/dL) was assessed at delivery. A complete blood count results during pregnancy as well as maternal and obstetrical characteristics were collected. The primary endpoint was to determine the Hb cutoff between 24 and 30 gestational weeks that is predictive of anemia at delivery by using the area under the curve (AUC) of the receiver operating characteristic curve. Independent risk factors for anemia at delivery were assessed using stepwise multivariable logistic regression. Hb and infrequent iron supplement treatment were independent risk factors for anemia at delivery (OR 0.3 95%CI [0.2–0.4] and OR 2.4 95%CI [1.2–4.8], respectively; C statistics 83%). Hb 10.6 g/dL was an accurate cutoff to predict anemia at delivery (AUC 80% 95%CI 75–84%; sensitivity 75% and specificity 74%). Iron supplement was beneficial to prevent anemia regardless of Hb value. Altogether, Hb should be routinely tested between 24 and 30 gestational weeks to screen for anemia. A flow chart for anemia screening and treatment during pregnancy is proposed in the manuscript.

Trial registration: ClinicalTrials.gov Identifier: NCT02434653.
Xeno-free cryopreservation of adherent retinal pigmented epithelium yields viable and functional cells in vitro and in vivo
Authors: Pennington Britney O. , Bailey Jeffrey K. , Faynus Mohamed A. , Hinman Cassidy , Hee Mitchell N. , Ritts Rory , Nadar Vignesh , Zhu Danhong , Mitra Debbie , Martinez-Camarillo Juan Carlos , Lin Tai-Chi , Thomas Biju B. , Hinton David R. , Humayun Mark S. , Lebkowski Jane , Johnson Lincoln V. , Clegg Dennis O.
Published: March 2021

Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit ≥ 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN2) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.
Optimum protein requirement of juvenile orange-spotted grouper (Epinephelus coioides)
Authors: Yan Xiaobo , Yang Junjiang , Dong Xiaohui , Tan Beiping , Zhang Shuang , Chi Shuyan , QihuiYang  , Liu Hongyu , Yang Yuanzhi
Published: March 2021

The purpose of subject was to explore the optimum protein requirement of juvenile grouper (Epinephelus coioides). In the test, 450 juveniles with an average weight (10.02 ± 0.22) g were randomly divided into six groups with triplicate, and were fed with 350, 400, 450, 500, 550 and 600 g/kg iso-lipid test diet twice 1 day for 8 weeks, respectively. The results showed that: (1) With the increase of protein level, the body weight gain rate and specific growth rate first increased and then reduced, while the feed coefficient rate first decreased and then increased, while the protein efficiency significantly decreased (P < 0.05). (2) With the increase of protein level, the condition factor, hepaticsomatic index and visceralsomatic index significantly reduced (P < 0.05). (3) With the increase of protein level, the crude protein content of whole fish and muscle gradually increased, while the crude lipid content gradually decreased. (4) High-protein diet (550–600 g/kg) significantly increased the plasma total protein content and decreased the triglyceride content of orange-spotted grouper (P < 0.05). (5) Compared with the 350 g/kg group, 500, 550, 600 g/kg groups significantly increased the activities of glutamic-pyruvic transaminase and glutamic oxaloacetic transaminase in liver (P < 0.05). (6) With the increase of protein level, the protease activity of intestine first increased and then decreased, and reached the maximum at the protein level of 500 g/kg, while lipase and amylase decreased significantly (P < 0.05). (7) The activities of acid phosphatase, superoxide dismutase and lysozyme in liver increased first and then decreased with the increase of protein level, and reached the maximum in the 400 g/kg protein group. According to the analysis specific growth rate, the optimum protein level of juvenile orange-spotted grouper is 521.84 g/kg.
Enhanced catalytic ozonation of ibuprofen using a 3D structured catalyst with MnO2 nanosheets on carbon microfibers
Authors: Ponnusamy Guhankumar , Farzaneh Hajar , Tong Yongfeng , Lawler Jenny , Liu Zhaoyang , Saththasivam Jayaprakash
Published: March 2021

Heterogeneous catalytic ozonation is an effective approach to degrade refractory organic pollutants in water. However, ozonation catalysts with combined merits of high activity, good reusability and low cost for practical industrial applications are still rare. This study aims to develop an efficient, stable and economic ozonation catalyst for the degradation of Ibuprofen, a pharmaceutical compound frequently detected as a refractory pollutant in treated wastewaters. The novel three-dimensional network-structured catalyst, comprising of δ-MnO2 nanosheets grown on woven carbon microfibers (MnO2 nanosheets/carbon microfiber), was synthesized via a facile hydrothermal approach. Catalytic ozonation performance of Ibuprofen removal in water using the new catalyst proves a significant enhancement, where Ibuprofen removal efficiency of close to 90% was achieved with a catalyst loading of 1% (w/v). In contrast, conventional ozonation was only able to achieve 65% removal efficiency under the same operating condition. The enhanced performance with the new catalyst could be attributed to its significantly increased available surface active sites and improved mass transfer of reaction media, as a result of the special surface and structure properties of this new three-dimensional network-structured catalyst. Moreover, the new catalyst displays excellent stability and reusability for ibuprofen degradation over successive reaction cycles. The facile synthesis method and low-cost materials render the new catalyst high potential for industrial scaling up. With the combined advantages of high efficiency, high stability, and low cost, this study sheds new light for industrial applications of ozonation catalysts.
Radical pairs may play a role in xenon-induced general anesthesia
Authors: Smith Jordan , Zadeh Haghighi Hadi , Salahub Dennis , Simon Christoph
Published: March 2021

Understanding the mechanisms underlying general anesthesia would be a key step towards understanding consciousness. The process of xenon-induced general anesthesia has been shown to involve electron transfer, and the potency of xenon as a general anesthetic exhibits isotopic dependence. We propose that these observations can be explained by a mechanism in which the xenon nuclear spin influences the recombination dynamics of a naturally occurring radical pair of electrons. We develop a simple model inspired by the body of work on the radical-pair mechanism in cryptochrome in the context of avian magnetoreception, and we show that our model can reproduce the observed isotopic dependence of the general anesthetic potency of xenon in mice. Our results are consistent with the idea that radical pairs of electrons with entangled spins could be important for consciousness.
Introduction, adaptation and characterization of monk fruit (Siraitia grosvenorii): a non-caloric new natural sweetener
Authors: Shivani  , Thakur Babit Kumar , Mallikarjun C. P. , Mahajan Mitali , Kapoor Priya , Malhotra Jigyasa , Dhiman Rimpy , Kumar Dinesh , Pal Probir Kumar , Kumar Sanjay
Published: March 2021

Siraitia grosvenorii, an herbaceous perennial plant, native to the southern parts of China, is commonly used as a low-calorie natural sweetener. It contains cucurbitane-type triterpene glycosides known as mogrosides. The extract from monk fruit is about 300 times sweeter than sucrose. In spite of its immense importance and International demand, Siraitia grosvenorii (Swingle) is not commercially cultivated outside China since scientific information for cultivation of this species is lacking. Planting material of monk fruit plant was not available in India. Thus, the seeds of monk fruit were introduced in India from China after following International norms. Then the experiments were conducted on different aspects such as seed germination, morphological and anatomical characterization, phenology, flowering and pollination behaviors, and dynamic of mogroside-V accumulation in fruit. The hydropriming at 40 °C for 24 h was found effective to reduce the germination time and to increase the germination rate (77.33%). The multicellular uniseriate trichomes were observed in both the leaf surfaces, however, higher trichomes density was observed in the ventral surface of males compared to females. The microscopic view revealed that the ovary was trilocular (ovary consists three chambers) having two ovules in each chamber or locule. Most of the fruits were globose or oblong type with 5–7 cm in length and 4–7 cm diameter. Mogroside-V content in fruit at 80 days after pollination was 0.69% on dry weight basis. The rate of increase of mogroside-V accumulation from 50 to 70 days was very slow, whereas a sharp increase was observed from 70 to 80 days. The higher receptivity of stigma was observed with fully open flowers. The floral diagram and formula have also been developed for both male and female flowers. Our results highlighted that monk fruit can be grown in Indian conditions.
Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands
Authors: Cramer-van der Welle Christine M. , Verschueren Marjon V. , Tonn Merel , Peters Bas J. M. , Schramel Franz M. N. H. , Klungel Olaf H. , Groen Harry J. M. , van de Garde Ewoudt M. W. ,   The Santeon NSCLC Study Group, Kastelijn E. A. , Vermeer L. C. , van den Borne B. E. E. M. , van Putten J. W. G. , Schouwink J. H. , Smit A. A. J.
Published: March 2021

This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015–2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75–1.55), and HR 0.91 (95% CI 0.74–1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07–2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.
Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia
Authors: Średniawa Władysław , Wróbel Jacek , Kublik Ewa , Wójcik Daniel Krzysztof , Whittington Miles Adrian , Hunt Mark Jeremy
Published: March 2021

Wake-related ketamine-dependent high frequency oscillations (HFO) can be recorded in local field potentials (LFP) from cortical and subcortical regions in rodents. The mechanisms underlying their generation and occurrence in higher mammals are unclear. Unfortunately, anesthetic doses of pure ketamine attenuate HFO, which has precluded their investigation under anesthesia. Here, we show ketamine-xylazine (KX) anesthesia is associated with a prominent 80–130 Hz rhythm in the olfactory bulb (OB) of rats, whereas 30–65 Hz gamma power is diminished. Simultaneous LFP and thermocouple recordings revealed the 80–130 Hz rhythm was dependent on nasal respiration. This rhythm persisted despite surgical excision of the piriform cortex. Silicon probes spanning the dorsoventral aspect of the OB revealed this rhythm was strongest in ventral areas and associated with microcurrent sources about the mitral layer. Pharmacological microinfusion studies revealed dependency on excitatory-inhibitory synaptic activity, but not gap junctions. Finally, a similar rhythm occurred in the OB of KX-anesthetized cats, which shared key features with our rodent studies. We conclude that the activity we report here is driven by nasal airflow, local excitatory-inhibitory interactions, and conserved in higher mammals. Additionally, KX anesthesia is a convenient model to investigate further the mechanisms underlying wake-related ketamine-dependent HFO.
Performance of preclinical models in predicting drug-induced liver injury in humans: a systematic review
Authors: Dirven Hubert , Vist Gunn E. , Bandhakavi Sricharan , Mehta Jyotsna , Fitch Seneca E. , Pound Pandora , Ram Rebecca , Kincaid Breanne , Leenaars Cathalijn H. C. , Chen Minjun , Wright Robert A. , Tsaioun Katya
Published: March 2021

Drug-induced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidence-based methods to investigate the role of preclinical studies in predicting human DILI using two anti-diabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazone- and rosiglitazone-related DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidence-based methodologies and performed according to pre-registered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in “low” or “very low” certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more off-target effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liver-related adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazone’s potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugs’ off-target activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions.
Distribution and altitudinal patterns of carbon and nitrogen storage in various forest ecosystems in the central Yunnan Plateau, China
Authors: Li Jianqiang , Chen Qibo , Li Zhuang , Peng Bangxiao , Zhang Jianlong , Xing Xuexia , Zhao Binyang , Song Denghui
Published: March 2021

The carbon (C) pool in forest ecosystems plays a long-term and sustained role in mitigating the impacts of global warming, and the sequestration of C is closely linked to the nitrogen (N) cycle. Accurate estimates C and N storage (SC, SN) of forest can improve our understanding of C and N cycles and help develop sustainable forest management policies in the content of climate change. In this study, the SC and SN of various forest ecosystems dominated respectively by Castanopsis carlesii and Lithocarpus mairei (EB), Pinus yunnanensis (PY), Pinus armandii (PA), Keteleeria evelyniana (KE), and Quercus semecarpifolia (QS) in the central Yunnan Plateau of China, were estimated on the basis of a field inventory to determine the distribution and altitudinal patterns of SC and SN among various forest ecosystems. The results showed that (1) the forest SC ranged from 179.58 ± 20.57 t hm−1 in QS to 365.89 ± 35.03 t hm−1 in EB. Soil, living biomass and litter contributed an average of 64.73%, 31.72% and 2.86% to forest SC, respectively; (2) the forest SN ranged from 4.47 ± 0.94 t ha−1 in PY to 8.91 ± 1.83 t ha−1 in PA. Soil, plants and litter contributed an average of 86.88%, 10.27% and 2.85% to forest SN, respectively; (3) the forest SC and SN decreased apparently with increasing altitude. The result demonstrates that changes in forest types can strongly affect the forest SC and SN. This study provides baseline information for forestland managers regarding forest resource utilization and C management.
Determination of Dy substitution site in Nd2−xDyxFe14B by HAADF-STEM and illustration of magnetic anisotropy of “g” and “f” sites, before and after substitution
Authors: Haider Syed Kamran , Kang Min-Chul , Hong Jisang , Kang Young Soo , Yang Cheol-Woong , Kim Dongsoo
Published: March 2021

Nd2Fe14B and Nd2−xDyxFe14B (x = 0.25, 0.50) particles were prepared by the modified co-precipitation followed by reduction–diffusion process. Bright field scanning transmission electron microscope (BF-STEM) image revealed the formation of Nd–Fe–B trigonal prisms in [− 101] viewing zone axis, confirming the formation of Nd2Fe14B/Nd2−xDyxFe14B. Accurate site for the Dy substitution in Nd2Fe14B crystal structure was determined as “f” site by using high-angle annular dark field scanning transmission electron microscope (HAADF-STEM). It was found that all the “g” sites are occupied by the Nd, meanwhile Dy occupied only the “f” site. Anti-ferromagnetic coupling at “f” site decreased the magnetic moment values for Nd1.75Dy0.25Fe14B (23.48 μB) and Nd1.5Dy0.5Fe14B (21.03 μB) as compared to Nd2Fe14B (25.50 μB). Reduction of magnetic moment increased the squareness ratio, coercivity and energy product. Analysis of magnetic anisotropy at constant magnetic field confirmed that “f” site substitution did not change the patterns of the anisotropy. Furthermore, magnetic moment of Nd2Fe14B, Nd2−xDyxFe14B, Nd (“f” site), Nd (“g” site) and Dy (“f” site) was recorded for all angles between 0° and 180°.
Boundary condition and oceanic impacts on the atmospheric water balance in limited area climate model ensembles
Authors: Goergen Klaus , Kollet Stefan
Published: March 2021

Regional climate models (RCMs) are indispensable in climate research, albeit often characterized by biased terrestrial precipitation and water budgets. This study identifies excess oceanic evaporation, in conjunction with the RCMs’ boundary conditions, as drivers contributing to these biases in RCMs with forced sea surface temperatures in a CORDEX RCM ensemble over Europe. The RCMs are relaxed to the prescribed lateral boundary conditions originating from a global model, effectively matching the driving model's overall atmospheric moisture flux divergence. As a consequence, excess oceanic evaporation results in positive precipitation biases over land due to forced internal recycling of moisture to maintain the overall flux divergence prescribed by the boundary conditions. This systematic behaviour is shown through an analysis of long-term atmospheric water budgets and atmospheric moisture exchange between oceanic and continental areas in a multi-model ensemble.
The effects of direct current stimulation and random noise stimulation on attention networks
Authors: Lema Alberto , Carvalho Sandra , Fregni Felipe , Gonçalves Óscar F. , Leite Jorge
Published: March 2021

Attention is a complex cognitive process that selects specific stimuli for further processing. Previous research suggested the existence of three attentional networks: alerting, orienting and executive. However, one important topic is how to enhance the efficiency of attentional networks. In this context, understanding how this system behaves under two different modulatory conditions, namely transcranial direct current stimulation (tDCS) and transcranial Random Noise Stimulation (tRNS), will provide important insights towards the understanding of the attention network system. Twenty-seven healthy students took part on a randomized single-blinded crossover study, testing the effects that involved three modalities of unilateral stimulation (tRNS, anodal tDCS, and sham) over the DLPFC, during the performance of the attention network test (ANT) in three different conditions: standard, speed and accuracy. Results showed that tRNS was able to increase attention during more complex situations, namely by increasing alerting and decreasing conflict effect in the executive network. Under the Speed condition, tRNS increased efficiency of the alerting network, as well as under the more demanding conflict network, tRNS overall increased the performance when comparing to sham. No statistical significant effects of tDCS were observed. These results are compatible with the attention requiring the synchronization of pre-existing networks, rather the reinforcement or creation of new pathways.
Disparities in access to health care system as determinant of survival for patients with pancreatic cancer in the State of São Paulo, Brazil
Authors: de Jesus Victor Hugo Fonseca , da Costa Wilson Luiz , Claro Laura Carolina Lopez , Coimbra Felipe José Fernandez , Dettino Aldo Lourenço Abbade , Riechelmann Rachel P. , Curado Maria Paula
Published: March 2021

Little is known about the features and outcomes of Brazilian patients with pancreatic cancer. We sought to describe the socio-economic characteristics, patterns of health care access, and survival of patients diagnosed with malignant pancreatic tumors from 2000 to 2014 in São Paulo, Brazil. We included patients with malignant exocrine and non-classified pancreatic tumors according to the International Classifications of Disease (ICD)-O-2 and -O-3, diagnosed from 2000 to 2014, who were registered in the FOSP database. Prognostic factors for overall survival (OS) in the subgroup of patients with ductal or non-specified (adeno)carcinoma were evaluated using Cox proportional hazard model. The study population consists of 6855 patients. Median time from the first visit to diagnosis and treatment were 13 (Interquartile range [IQR] 4–30) and 24 (IQR 8–55) days, respectively. Both intervals were longer for patients treated in the public setting. Median OS was 4.9 months (95% confidence interval [95% CI] 4.7–5.2). Increasing age, male gender, lower educational level, treatment in the public setting, absence of treatment, advanced stage, and treatment from 2000 to 2004 were associated with inferior OS. From 2000–2004 to 2010–2014, no improvement in OS was seen for patients treated in the public setting. Survival of patients with malignant pancreatic tumors remains dismal. Socioeconomical variables, especially health care funding, are major determinants of survival. Further work is necessary to decrease inequalities in access to medical care for patients with pancreatic cancer in Brazil.
Nutritional, phytochemical, and in vitro anticancer potential of sugar apple (Annona squamosa) fruits
Authors: Shehata Mohamed Gamal , Abu-Serie Marwa Muhammad , Abd El-Aziz Nourhan Mohammad , El-Sohaimy Sobhy Ahmed
Published: March 2021

In plants, Fruits and their wastes are the main sources of bioactive compounds. Currently, Annona fruits have attracted the attention of people interested in health-promoting foods due to their phytochemical content that their activities were not studied before. This study aimed to explore the potential antioxidant, antimicrobial, and in vitro anticancer activity of two cultivars Annona squamosa (Annona b. and Annona h.) seed, peel, and pulp. We also meausred phenolic, flavonoid, sulfated polysaccharide, tannins, and triterpenoids. Polyphenol identification was determined using RP-HPLC. Results of the antioxidant activity revealed that the highest activity was observed for Annona h. seed extract using DPPH and ABTS assays with IC50 6.07 ± 0.50 and 9.58 ± 0.53 µg/ml, respectively. The antimicrobial activity against various pathogenic strains revealed that the peel extracts of both Annona b. and Annona h. exhibited the best antimicrobial activity. We also assessed the IC50 values for anticancer activity in all six Annona b. and Annona h samples against four cancer cell lines colon (Caco-2), prostate (PC3), liver (HepG-2), and breast (MCF-7) using MTT assay. Annona b. and Annona h seed extracts had the lowest IC50 values for four cancer cell lines with 7.31 ± 0.03 and 15.99 ± 1.25 for PC-3 and MCF-7, respectively. Both seed extracts, Annona b. and Annona h., showed significantly down-regulated mRNA expression of Bcl-2 and up-regulated p53 in all treated cell lines. Apoptosis was evaluated using nuclear staining, flow cytometric analysis, and immunohistochemistry of the proliferation marker (Ki-67). Additional studies are required to characterize the bioactive compounds responsible for the observed activities of Annona seed and determine its mechanism as an anticancer drug.