bluuebunny/crossref_metadata_2025 huggingface dataset:
COPB2: a transport protein with multifaceted roles in cancer development and progression
Authors: Feng Y. , Lei X. , Zhang L. , Wan H. , Pan H. , Wu J. , Zou M. , Zhu L. , Mi Y.
Published: June 2021

The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer.
Physio-pathological effects of m6A modification and its potential contribution to melanoma
Authors: Liao Y. , Han P. , Zhang Y. , Ni B.
Published: June 2021

Methylation of N6-adenosine (m6A) is the most prevalent internal RNA modification and is especially common among the messenger RNAs. These m6A modifications regulate splicing, translocation, stability and translation of RNA through dynamic and reversible interactions with m6A-binding proteins, namely the writers, erasers and readers. RNA methyltransferases catalyze the m6A modifications, while demethylases reverse this methylation. Deregulation of the m6A modification process has been implicated in human carcinogenesis, including melanoma—which carries one of the highest mutant rates. In this review, we provide an up-to-date summary of m6A regulation and its biological impacts on normal and cancer cells, with emphasis on the deregulation of m6A modification and m6A regulators in melanoma. In addition, we highlight the prospective potential of exploiting m6A modification in the treatment of melanoma and non-cancer diseases.
Lonely in Lockdown: Predictors of Emotional and Mental Health Difficulties Among Jewish Young Adults during the COVID-19 Pandemic
Authors: Wright Graham , Volodarsky Sasha , Hecht Shahar , Saxe Leonard
Published: June 2021

As individuals undergoing a developmental process characterized by identity exploration, Jewish young adults are particularly vulnerable to the disruption of social connections related to the COVID-19 pandemic. Recent research has demonstrated that young adults, including young Jews, have experienced higher rates of mental health difficulties than older individuals during the pandemic. Using data from a survey of Jewish young adults who applied to participate in Birthright Israel summer 2020 trips but were unable to participate due to the pandemic, we examined the factors contributing to young adults’ mental health difficulties. We found that loneliness, rather than financial worries or concerns about the health impacts of COVID-19, was the single most important driver of reported emotional or mental health difficulties. Results also suggested that simply increasing the frequency of contacts between individuals is unlikely to reduce loneliness, unless these are positive, substantial connections, such as those among members of a “social support network.” Building and rebuilding deep, meaningful social connections between Jewish young adults should be a top priority for Jewish organizations going forward.
Planning and governing nature-based solutions in river landscapes: Concepts, cases, and insights
Authors: Albert Christian , Hack Jochen , Schmidt Stefan , Schröter Barbara
Published: June 2021

Nature-based solutions (NBS), understood as actions that use ecosystem processes to address societal needs, can play important roles to future-proof river landscape development for people and nature. However, knowledge gaps exist how NBS can be planned and implemented at landscape scales. This Special Issue brings together insights and experiences from studies of assessing, planning, and implementing NBS in river landscapes in Europe and beyond. It addresses three research fields: (i) NBS effects, looking at the effectiveness of NBS to achieve ecological, social, and/or economic outcomes, (ii) NBS planning, focusing on approaches for planning and designing NBS, and (iii) NBS governance, relating to governance and business models for implementation. The twelve contributions deliver evidence on how NBS outperform conventional, rather technical solutions, provide guidance and tools to operationalize the NBS concept into practice, and showcase successful governance models of NBS in different contexts. The editorial ends with an outlook on further research needs.
Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals
Authors: Thiyagarajan Durairaj , Huck Benedikt , Nothdurft Birgit , Koch Marcus , Rudolph David , Rutschmann Mark , Feldmann Claus , Hozsa Constantin , Furch Marcus , Besecke Karen F. W. , Gieseler Robert K. , Loretz Brigitta , Lehr Claus-Michael
Published: June 2021

Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers’ characteristics influenced the MPs’ sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying.

Graphical abstract
Boron Nanosheet-Supported Rh Catalysts for Hydrogen Evolution: A New Territory for the Strong Metal-Support Interaction Effect
Authors: Chen Keng , Wang Zeming , Wang Liang , Wu Xiuzhen , Hu Bingjie , Liu Zheng , Wu Minghong
Published: June 2021

High-efficiency electrochemical hydrogen evolution reaction (HER) offers a promising strategy to address energy and environmental crisis. Platinum is the most effective electrocatalyst for the HER. However, challenging scarcity, valuableness, and poor electrochemical stability still hinder its wide application. Here, we designed an outstanding HER electrocatalyst, highly dispersed rhodium (Rh) nanoparticles with an average diameter of only 3 nm supported on boron (B) nanosheets. The HER catalytic activity is even comparable to that of commercial platinum catalysts, with an overpotential of only 66 mV in 0.5 M H2SO4 and 101 mV in 1 M KOH to reach the current density of 10 mA cm−2. Meanwhile, the catalyst exhibited impressive electrochemical durability during long-term electrochemical processes in acidic and alkaline media, even the simulated seawater environment. Theoretical calculations unraveled that the structure–activity relationship between B(104) crystal plane and Rh(111) crystal plane is beneficial to the release of hydrogen, and surface O plays a vital role in the catalysis process. Our work may gain insights into the development of supported metal catalysts with robust catalytic performance through precise engineering of the strong metal-supported interaction effect.
Evaluation of Concurrent Variation in Rain Specific Attenuation and Tropospheric Amplitude Scintillation Over Akure, Southwest Nigeria
Authors: Ashidi Ayodeji Gabriel , Ojo Joseph Sunday , Ajayi Oluwaseyi Julius , Akinmoladun Toluwalope Mary
Published: June 2021

Rain constitutes a major limitation to the performance and use of terrestrial and satellite communication systems with operational frequencies greater than 10 GHz. The situation gets further complicated by fast fluctuations in the received signal amplitude due to in homogeneities in atmospheric weather conditions; a phenomenon known as amplitude scintillation. The concurrent evaluation of the two phenomena guarantees a better fade margin determination for the planning of radio communication over any location. This work employs 3 years of in-situ measurement of temperature, humidity, rainfall rate and rainfall amount for the estimation of tropospheric amplitude scintillation and rain specific attenuation over Akure (7.17° N, 5.18° E, 358 m) South West Nigeria. Davis vantage pro weather station at 1-min integration time was used for the measurement and the ITU models for rain specific attenuation (ITU-R P.838-3) and amplitude scintillation (ITU–R 618-13) were employed for the estimation. Time series and statistical analyses of the phenomena show that rain attenuation is the more prominent cause of signal degradation at Ku-band frequencies. Nevertheless, the need to make an extra fade margin allowance of about 0.25 dB due to amplitude scintillation fade subsists to forestall any loss of synchronization on the link. Also, a 3-parameter power-law expression developed for estimating amplitude scintillation fade from rain attenuation performed excellently well, as indicated by average root mean square error (RMSE) and coefficient of determination (R2) values of 0.002151 and 0.8747, respectively.
Users roles identification on online crowdsourced Q&A platforms and encyclopedias: a survey
Authors: Saxena Akrati , Reddy Harita
Published: June 2021

Online informal learning and knowledge-sharing platforms, such as Stack Exchange, Reddit, and Wikipedia have been a great source of learning. Millions of people access these websites to ask questions, answer the questions, view answers, or check facts. However, one interesting question that has always attracted the researchers is if all the users share equally on these portals, and if not then how the contribution varies across users, and how it is distributed? Do different users focus on different kinds of activities and play specific roles? In this work, we present a survey of users’ social roles that have been identified on online discussion and Q&A platforms including Usenet newsgroups, Reddit, Stack Exchange, and MOOC forums, as well as on crowdsourced encyclopedias, such as Wikipedia, and Baidu Baike, where users interact with each other through talk pages. We discuss the state of the art on capturing the variety of users roles through different methods including the construction of user network, analysis of content posted by users, temporal analysis of user activity, posting frequency, and so on. We also discuss the available datasets and APIs to collect the data from these platforms for further research. The survey is concluded with open research questions.
A Probabilistic Approach for Three-Dimensional Variation Analysis in Aero-engine Rotors Assembly
Authors: Ding Siyi , He Yuhang , Zheng Xiaohu
Published: June 2021

Rotor assembly is a core tache in the whole process of aero-engine manufacturing. Preventing out-of-tolerance of concentricity is one of the primary tasks. Conventional assembly approaches are based on a manual test with the dial indicator, depending on experience appraises, which lack systematic and quantitative precision design theory. As a result, two issues need to be solved: the modeling problem of complicated geometric variations in three-dimensions, as well as the abnormal distribution of ubiquitous actual deviations. This work attempts to propose a novel probabilistic approach for three-dimensional variation analysis in rotor assembly. Based on rotor’s revolving characteristics and multistage stacking process, Jacobian–Torsor model is adopted to establish the variation propagation, and Pearson distribution family is used to derive the probability density function, which can quickly determine the variation distribution pattern and efficiently perform statistical variation analysis. A real case of mechanical assemblies consisting of revolving axisymmetric components is concerned. The results show that the suggested method has a similar accuracy, but much higher efficiency than conventional methods. Calculations agree with the experimentations, and the probability distribution type of the part’s variation has an appreciable impact on the final assembly precision.
Completely order bounded maps on non-commutative $${\varvec{L_p}}$$-spaces
Authors: Neuhardt Erwin
Published: June 2021

We define norms on $$L_p({\mathcal {M}}) \otimes M_n$$

L
p

(
M
)

⊗

M
n

where $${\mathcal {M}}$$
M
is a von Neumann algebra and $$M_n$$

M
n

is the space of complex $$n \times n$$

n
×
n

matrices. We show that a linear map $$T: L_p({\mathcal {M}}) \rightarrow L_q({\mathcal {N}})$$

T
:

L
p

(
M
)

→

L
q

(
N
)

is decomposable if $${\mathcal {N}}$$
N
is an injective von Neumann algebra, the maps $$T \otimes Id_{M_n}$$

T
⊗
I

d

M
n

have a common upper bound with respect to our defined norms, and $$p = \infty $$

p
=
∞

or $$q = 1$$

q
=
1

. For $$2p< q < \infty $$

2
p
<
q
<
∞

we give an example of a map $$T$$
T
with uniformly bounded maps $$T \otimes Id_{M_n}$$

T
⊗
I

d

M
n

which is not decomposable.
Bibliometric Analysis of COVID-19 and the Association With the Number of Total Cases
Authors: Pasin Ozge , Pasin Tugce
Published: June 2021

Objectives:

Coronavirus disease 2019 (COVID-19) has spread quickly all over the world. The number of studies in this field being performed and published is increasing day by day. The aim of this study is to analyze the publications in the field of COVID-19 with the help of bibliometric methods. After bibliometric analysis, the second aim is to investigate the relationship between the number of publications in countries and the number of total cases.

Methods:

The data in the study were taken from the Web of Science (WOS) site. Analyses and mapping processes were performed using VOSviewer and SPSS package program. The words “COVID-19”, “Novel Coronavirus”, “2019-nCoV”, “SARS-CoV-2” were used as key words for analysis. The data include publications from 2019 to 2021 (January 10).

Results:

As a result of the study, a total of 38,080 publications were evaluated. It was determined that the countries with the highest number of publications on COVID-19 were China and the United States, and the country with the highest number of citations was China. Most of the studies in the field of COVID-19 have been conducted on General Internal Medicine and Public Enviromental Occupational Health. In addition, statistically significant relationships were observed between the number of publications and the number of total cases in terms of countries (r = 0.806; P < 0.001).

Conclusions:

As a result, bibliometric analysis about COVID-19 can be useful for the future studies. It gives a general perspective of the studies.
MODELS OF MARTIN-LÖF TYPE THEORY FROM ALGEBRAIC WEAK FACTORISATION SYSTEMS
Authors: GAMBINO NICOLA , LARREA MARCO FEDERICO
Published: June 2021

We introduce type-theoretic algebraic weak factorisation systems and show how they give rise to homotopy-theoretic models of Martin-Löf type theory. This is done by showing that the comprehension category associated with a type-theoretic algebraic weak factorisation system satisfies the assumptions necessary to apply a right adjoint method for splitting comprehension categories. We then provide methods for constructing several examples of type-theoretic algebraic weak factorisation systems, encompassing the existing groupoid and cubical sets models, as well as new models based on normal fibrations.
Assessment of dietary intake of bioactive food compounds according to income level in the Brazilian population
Authors: Carnauba Renata A. , Sarti Flavia M. , Hassimotto Neuza M.A. , Lajolo Franco M.
Published: June 2021

There is an inverse association between bioactive compounds intake and disease risk. The knowledge of its consumption according to socio-economic strata is important, which allows identification of potential intervention targets. Thus, we aimed to investigate bioactive compounds intake according to income level in Brazilian population. Data were obtained from the Brazilian Household Budget Survey, a cross-sectional survey which included data on individual food intake of 34,003 subjects aged 10 years and over collected using two 24-h dietary records. Polyphenol and carotenoid content of foods was identified using published databases. Total polyphenol and carotenoid intake were determined according to per capita income, as well as main food sources. Total polyphenols and flavonoids intake increased with income level, and subjects with lower income showed higher phenolic acids intake than individuals in highest income (p = 0.0001). Total carotenoids and classes intake (with exception to β-cryptoxanthin and zeaxanthin) were higher among subjects in highest income quartile, compared to the lowest quartile (p = 0.0001). Coffee was major source to total polyphenols and phenolic acids intake, and orange juice was main flavonoid provider in individuals from all income levels. In the upper income quartile, total carotenoid was supplied mainly by tomato and kale, and fruits had important contribution to carotenoid intake in the lowest income quartile. There is important influence of income level on diet quality regarding intake of foods with bioactive compounds, and individuals with lower income may experience lower quality diets due to less availability of foods with bioactive compounds.
Effects of olives and their constituents on the expression of ulcerative colitis: a systematic review of randomised controlled trials
Authors: Daniel Kenneth , Vitetta Luis , Fiatarone Singh Maria A.
Published: June 2021

Extra virgin olive oil is often associated with anti-inflammatory and antioxidant properties. Its effects on inflammatory conditions such as ulcerative colitis (UC), however, have yet to be defined. As such, we aimed to conduct a systematic review and meta-analysis of studies investigating olive-based interventions in UC. A comprehensive database search for randomised controlled trials was performed between 9 July 2018 and 16 August 2018. Studies identified from search alerts were included up to 22 June 2020. Both individuals living with UC at any disease stage and murine models of UC were included in this review. No human trials meeting the eligibility criteria were identified, while nineteen animal studies comprised 849 murine models of UC were included in this review. Pooling of the data could not be performed due to heterogeneous outcomes; however, general trends favouring olive-based interventions were identified. Milder disease expression including weight maintenance, reduced rectal bleeding and well-formed stools favouring olive-based interventions was statistically significant in 16/19 studies, with moderate-to-large effect sizes (−0·66 (95 % CI −1·56, 0·24) to −12·70 (95 % CI −16·8, −8·7)). Olive-based interventions did not prevent the development of colitis-like pathologies in any study. In conclusion, effects of olive-based interventions on murine models of UC appear promising, with milder disease outcomes favouring the intervention in most trials and effect sizes suggesting potential clinical relevance. However, the lack of published randomised controlled human trials warrants further investigation to determine if these effects would translate to individuals living with UC.
Who benefits most from an evidence-based program to reduce anxiety and depression in children? A latent profile analysis
Authors: Melero Silvia , Morales Alexandra , Tomczyk Samuel , Espada José Pedro , Orgilés Mireia
Published: June 2021

Comorbidity between anxiety and depression symptoms is often high in children. Person-oriented statistical approaches are useful to detect heterogeneity of individuals and diverse patterns of response to treatment. This study aimed to explore the different profiles in a sample of Spanish children who received the Super Skills for Life (SSL) transdiagnostic program, to identify which profile of individuals benefited most from the intervention and the likelihood of transition of symptom patterns over time. Participants were 119 children (42.9% were female) aged 8–12 years old (M = 9.39; SD = 1.26). Children completed anxiety and depression measures at the baseline, postintervention, and 12-months follow-up. Results from latent transition analysis (LTA) revealed two groups depending on the severity of the anxiety and depression symptoms: low symptoms (LS) and high symptoms (HS). LS group remained stable and HS decreased by 25%, switching to the LS group. Children with greater social anxiety benefited most from the program over time. Furthermore, older children were more likely to improve rapidly one year after the intervention compared to younger children. This study provides information to consider when implementing preventive interventions for schoolchildren and to tailor them according to the target population characteristics to increase their effectiveness.
Miniaturized CPW-fed UWB-MIMO antennas with decoupling stub and enhanced isolation
Authors: Khattak Muhammad Irfan , Khan Muhammad Irshad , Anab Muhammad , Ullah Amjad , Al-Hasan Muath , Nebhen Jamel
Published: June 2021

In this paper, a coplanar waveguide-fed ultra-wideband-multiple-input and multiple-output (UWB-MIMO) antenna with a novel stub for isolation has been presented. The dimensions of the proposed antenna are 18 × 22 × 1.6 mm3. The proposed antenna is design on an FR4 substrate and simulated in CST studio. The |S11| of the presented MIMO antenna is less than −10 dB between 2.8 and 13 GHz with an impedance bandwidth of 10.2 GHz. The envelope correlation coefficient (ECC) is less than 0.007 and diversity gain (DG) is greater than 9.97 dB. The proposed UWB-MIMO antenna is analyzed in terms of isolation, reflection coefficient, current distribution, ECC, DG, peak gain, multiplexing efficiency, and radiation pattern.
Low vitamin B12 level in relation to trace element, total sialic acid and antioxidant enzymes in children with vitamin B12 deficiency anemia
Authors: Kiran Isa , Ekin Suat , Vural Özge
Published: June 2021

Abstract: In this study, children with vitamin B12 deficiency anemia (V-B12DA) and control subjects were evaluated for erythrocyte glutathione peroxidase, catalase and superoxide dismutase enzyme activities, glutathione, malondialdehyde, serum total sialic acid, total antioxidant status, cobalt, chromium, copper, selenium, vanadium, zinc, iron, lead, magnesium, calcium, sodium, potassium, chloride, phosphorus levels, and the associations of these variables were assessed. The study included 50 children with V-B12DA and 50 control subjects. It was found that the V-B12DA group was significantly lower than the control group, with regard to the mean±the standard error of the mean levels of cobalt (0.089±0.009; 0.058±0.0063 μmol/L, p<0.01), selenium (2.19±0.087; 1.88±0.057 μmol/L, p<0.01), vanadium (1.31±0.053; 1.18±0.035 μmol/L, p<0.05), magnesium (3.02±0.15; 2.73±0.068 μmol/L, p<0.05), zinc (50.76±1.96; 42.23± 1.53 μmol/L, p<0.001), and vitamin B12 (427.20±21.45; 157.08±3.96 pg/mL, p<0.001). Moreover, a significant elevation in total sialic acid (1.44±0.050; 1.61±0.043 mmol/L, p<0.01), and mean corpuscular volume (MCV) (75.37±0.95; 79.91±1.14 fL, p<0.01). It was observed that in the V-B12DA, significantly linear correlations were observed between cobalt – vitamin B12 (r=0.334; p=0.025), vanadium – MCV (r=0.315; p=0.017), vitamin B12 – MCV (r=−0.297; p=0.026). The findings of the study indicated that the levels of cobalt, vanadium significantly associated with traditional vitamin B12-deficiency parameters. Vitamin B12 and MCV should be measured together with cobalt, vanadium for monitoring the vitamin B12 deficiency anemia.
DCA-Transparency
Authors: Hossiep C. Richard , Märtins Julian , Schewe Gerhard
Published: June 2021

Abstract. Even though there is strong theoretical support that transparency in organizations leads to trust between employees and managers as well as increasing job satisfaction (e. g., Albu & Flyverbom, 2019 ; Giri & Kumar, 2010 ), such research lacks consistent empirical evidence. This inconsistency might be explained by the use of specific nongeneralizable scales ( Schnackenberg & Tomlinson, 2016 ). Therefore, Schnackenberg et al. (2020) developed a multidimensional transparency scale consisting of three dimensions: disclosure, clarity, and accuracy (so-called DCA-transparency). This paper validates a German version of the scale as well as conceptually and empirically extends its utility by adding the two dimensions of timeliness and relevance. We conducted three quantitative studies to examine the factorial structure ( N = 325), content validity ( N1 = 133 , N2 = 120), and usefulness ( N = 376, with a representative longitudinal sample). The results support the accuracy and utility of the extended German DCA scale in organizational settings and its multidimensionality.
A Baldwin interpretation of adult hippocampal neurogenesis: from functional relevance to physiopathology
Authors: Abrous Djoher Nora , Koehl Muriel , Lemoine Maël
Published: June 2021

Hippocampal adult neurogenesis has been associated to many cognitive, emotional, and behavioral functions and dysfunctions, and its status as a selected effect or an “appendix of the brain” has been debated. In this review, we propose to understand hippocampal neurogenesis as the process underlying the “Baldwin effect”, a particular situation in evolution where fitness does not rely on the natural selection of genetic traits, but on “ontogenetic adaptation” to a changing environment. This supports the view that a strong distinction between developmental and adult hippocampal neurogenesis is made. We propose that their functions are the constitution and the lifelong adaptation, respectively, of a basic repertoire of cognitive and emotional behaviors. This lifelong adaptation occurs through new forms of binding, i.e., association or dissociation of more basic elements. This distinction further suggests that a difference is made between developmental vulnerability (or resilience), stemming from dysfunctional (or highly functional) developmental hippocampal neurogenesis, and adult vulnerability (or resilience), stemming from dysfunctional (or highly functional) adult hippocampal neurogenesis. According to this hypothesis, developmental and adult vulnerability are distinct risk factors for various mental disorders in adults. This framework suggests new avenues for research on hippocampal neurogenesis and its implication in mental disorders.
How artificial intelligence might disrupt diagnostics in hematology in the near future
Authors: Walter Wencke , Haferlach Claudia , Nadarajah Niroshan , Schmidts Ines , Kühn Constanze , Kern Wolfgang , Haferlach Torsten
Published: June 2021

Artificial intelligence (AI) is about to make itself indispensable in the health care sector. Examples of successful applications or promising approaches range from the application of pattern recognition software to pre-process and analyze digital medical images, to deep learning algorithms for subtype or disease classification, and digital twin technology and in silico clinical trials. Moreover, machine-learning techniques are used to identify patterns and anomalies in electronic health records and to perform ad-hoc evaluations of gathered data from wearable health tracking devices for deep longitudinal phenotyping. In the last years, substantial progress has been made in automated image classification, reaching even superhuman level in some instances. Despite the increasing awareness of the importance of the genetic context, the diagnosis in hematology is still mainly based on the evaluation of the phenotype. Either by the analysis of microscopic images of cells in cytomorphology or by the analysis of cell populations in bidimensional plots obtained by flow cytometry. Here, AI algorithms not only spot details that might escape the human eye, but might also identify entirely new ways of interpreting these images. With the introduction of high-throughput next-generation sequencing in molecular genetics, the amount of available information is increasing exponentially, priming the field for the application of machine learning approaches. The goal of all the approaches is to allow personalized and informed interventions, to enhance treatment success, to improve the timeliness and accuracy of diagnoses, and to minimize technically induced misclassifications. The potential of AI-based applications is virtually endless but where do we stand in hematology and how far can we go?
Role of noncoding RNA in drug resistance of prostate cancer
Authors: Ding Lifeng , Wang Ruyue , Shen Danyang , Cheng Sheng , Wang Huan , Lu Zeyi , Zheng Qiming , Wang Liya , Xia Liqun , Li Gonghui
Published: June 2021

Prostate cancer is one of the most prevalent forms of cancer around the world. Androgen-deprivation treatment and chemotherapy are the curative approaches used to suppress prostate cancer progression. However, drug resistance is extensively and hard to overcome even though remarkable progress has been made in recent decades. Noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, are a group of cellular RNAs which participate in various cellular processes and diseases. Recently, accumulating evidence has highlighted the vital role of non-coding RNA in the development of drug resistance in prostate cancer. In this review, we summarize the important roles of these three classes of noncoding RNA in drug resistance and the potential therapeutic applications in this disease.
Persistent inequality in economically optimal climate policies
Authors: Gazzotti Paolo , Emmerling Johannes , Marangoni Giacomo , Castelletti Andrea , Wijst Kaj-Ivar van der , Hof Andries , Tavoni Massimo
Published: June 2021

Benefit-cost analyses of climate policies by integrated assessment models have generated conflicting assessments. Two critical issues affecting social welfare are regional heterogeneity and inequality. These have only partly been accounted for in existing frameworks. Here, we present a benefit-cost model with more than 50 regions, calibrated upon emissions and mitigation cost data from detailed-process IAMs, and featuring country-level economic damages. We compare countries’ self-interested and cooperative behaviour under a range of assumptions about socioeconomic development, climate impacts, and preferences over time and inequality. Results indicate that without international cooperation, global temperature rises, though less than in commonly-used reference scenarios. Cooperation stabilizes temperature within the Paris goals (1.80∘C [1.53∘C–2.31∘C] in 2100). Nevertheless, economic inequality persists: the ratio between top and bottom income deciles is 117% higher than without climate change impacts, even for economically optimal pathways.
Maternal iron deficiency perturbs embryonic cardiovascular development in mice
Authors: Kalisch-Smith Jacinta I. , Ved Nikita , Szumska Dorota , Munro Jacob , Troup Michael , Harris Shelley E. , Rodriguez-Caro Helena , Jacquemot Aimée , Miller Jack J. , Stuart Eleanor M. , Wolna Magda , Hardman Emily , Prin Fabrice , Lana-Elola Eva , Aoidi Rifdat , Fisher Elizabeth M. C. , Tybulewicz Victor L. J. , Mohun Timothy J. , Lakhal-Littleton Samira , De Val Sarah , Giannoulatou Eleni , Sparrow Duncan B.
Published: June 2021

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene–environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.
Lipophilic nanocrystal prodrug-release defines the extended pharmacokinetic profiles of a year-long cabotegravir
Authors: Gautam Nagsen , McMillan JoEllyn M. , Kumar Devendra , Bade Aditya N. , Pan Qiaoyu , Kulkarni Tanmay A. , Li Wenkuan , Sillman Brady , Smith Nathan A. , Shetty Bhagya L. Dyavar , Szlachetka Adam , Edagwa Benson J. , Gendelman Howard E. , Alnouti Yazen
Published: June 2021

A once every eight-week cabotegravir (CAB) long-acting parenteral is more effective than daily oral emtricitabine and tenofovir disoproxil fumarate in preventing human immunodeficiency virus type one (HIV-1) transmission. Extending CAB dosing to a yearly injectable advances efforts for the elimination of viral transmission. Here we report rigor, reproducibility and mechanistic insights for a year-long CAB injectable. Pharmacokinetic (PK) profiles of this nanoformulated CAB prodrug (NM2CAB) are affirmed at three independent research laboratories. PK profiles in mice and rats show plasma CAB levels at or above the protein-adjusted 90% inhibitory concentration for a year after a single dose. Sustained native and prodrug concentrations are at the muscle injection site and in lymphoid tissues. The results parallel NM2CAB uptake and retention in human macrophages. NM2CAB nanocrystals are stable in blood and tissue homogenates. The long apparent drug half-life follows pH-dependent prodrug hydrolysis upon slow prodrug nanocrystal dissolution and absorption. In contrast, solubilized prodrug is hydrolyzed in hours in plasma and tissues from multiple mammalian species. No toxicities are observed in animals. These results affirm the pharmacological properties and extended apparent half-life for a nanoformulated CAB prodrug. The report serves to support the mechanistic design for drug formulation safety, rigor and reproducibility.
Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis
Authors: Leach Joshua D. G. , Vlahov Nikola , Tsantoulis Petros , Ridgway Rachel A. , Flanagan Dustin J. , Gilroy Kathryn , Sphyris Nathalie , Vázquez Ester G. , Vincent David F. , Faller William J. , Hodder Michael C. , Raven Alexander , Fey Sigrid , Najumudeen Arafath K. , Strathdee Douglas , Nixon Colin , Hughes Mark , Clark William , Shaw Robin ,   S:CORT consortium, Maughan Tim , Salto-Tellez Manuel , Quirke Philip , Koelzer Viktor , Dunne Philip , Beggs Andrew , Campbell Peter , Buffa Francesca , Holmes Chris , Kaplan Rick , Brown Louise , Lawler Mark , Hordern Joshua , Tomlinson Ian , Leedham Simon , Morton Dion , van Hooff Sander R. , Huels David J. , Medema Jan Paul , Barry Simon T. , Frame Margaret C. , Unciti-Broceta Asier , Leedham Simon J. , Inman Gareth J. , Jackstadt Rene , Thompson Barry J. , Campbell Andrew D. , Tejpar Sabine , Sansom Owen J.
Published: June 2021

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells.
A first constraint on basal melt-water production of the Greenland ice sheet
Authors: Karlsson Nanna B. , Solgaard Anne M. , Mankoff Kenneth D. , Gillet-Chaulet Fabien , MacGregor Joseph A. , Box Jason E. , Citterio Michele , Colgan William T. , Larsen Signe H. , Kjeldsen Kristian K. , Korsgaard Niels J. , Benn Douglas I. , Hewitt Ian J. , Fausto Robert S.
Published: June 2021

The Greenland ice sheet has been one of the largest sources of sea-level rise since the early 2000s. However, basal melt has not been included explicitly in assessments of ice-sheet mass loss so far. Here, we present the first estimate of the total and regional basal melt produced by the ice sheet and the recent change in basal melt through time. We find that the ice sheet’s present basal melt production is 21.4 +4.4/−4.0 Gt per year, and that melt generated by basal friction is responsible for about half of this volume. We estimate that basal melting has increased by 2.9 ± 5.2 Gt during the first decade of the 2000s. As the Arctic warms, we anticipate that basal melt will continue to increase due to faster ice flow and more surface melting thus compounding current mass loss trends, enhancing solid ice discharge, and modifying fjord circulation.
Living fabrication of functional semi-interpenetrating polymeric materials
Authors: Dai Zhuojun , Yang Xiaoyu , Wu Feilun , Wang Lihua , Xiang Kun , Li Pengcheng , Lv Qingqing , Tang Jinhui , Dohlman Anders , Dai Lei , Shen Xiling , You Lingchong
Published: June 2021

Cell-mediated living fabrication has great promise for generating materials with versatile, programmable functions. Here, we demonstrate the engineering of living materials consisting of semi-interpenetrating polymer networks (sIPN). The fabrication process is driven by the engineered bacteria encapsulated in a polymeric microcapsule, which serves as the initial scaffold. The bacteria grow and undergo programmed lysis in a density-dependent manner, releasing protein monomers decorated with reactive tags. Those protein monomers polymerize with each other to form the second polymeric component that is interlaced with the initial crosslinked polymeric scaffold. The formation of sIPN serves the dual purposes of enhancing the mechanical property of the living materials and anchoring effector proteins for diverse applications. The material is resilient to perturbations because of the continual assembly of the protein mesh from the monomers released by the engineered bacteria. We demonstrate the adoption of the platform to protect gut microbiota in animals from antibiotic-mediated perturbations. Our work lays the foundation for programming functional living materials for diverse applications.
Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk
Authors: Wang Xiao-Hui , Xu Sha , Zhou Xiang-Yu , Zhao Rui , Lin Yan , Cao Jing , Zang Wei-Dong , Tao Hui , Xu Wei , Li Ming-Qing , Zhao Shi-Min , Jin Li-Ping , Zhao Jian-Yuan
Published: June 2021

Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.
An advance in transfer line chilldown heat transfer of cryogenic propellants in microgravity using microfilm coating for enabling deep space exploration
Authors: Chung J. N. , Dong Jun , Wang Hao , Darr S. R. , Hartwig J. W.
Published: June 2021

The extension of human space exploration from a low earth orbit to a high earth orbit, then to Moon, Mars, and possibly asteroids is NASA’s biggest challenge for the new millennium. Integral to this mission is the effective, sufficient, and reliable supply of cryogenic propellant fluids. Therefore, highly energy-efficient thermal-fluid management breakthrough concepts to conserve and minimize the cryogen consumption have become the focus of research and development, especially for the deep space mission to mars. Here we introduce such a concept and demonstrate its feasibility in parabolic flights under a simulated space microgravity condition. We show that by coating the inner surface of a cryogenic propellant transfer pipe with low-thermal conductivity microfilms, the quenching efficiency can be increased up to 176% over that of the traditional bare-surface pipe for the thermal management process of chilling down the transfer pipe. To put this into proper perspective, the much higher efficiency translates into a 65% savings in propellant consumption.
Evidence of haptoglobin in the porcine female genital tract during oestrous cycle and its effect on in vitro embryo production
Authors: García-Vázquez Francisco A. , Moros-Nicolás Carla , López-Úbeda Rebeca , Rodríguez-Tobón Ernesto , Guillén-Martínez Ascensión , Ross Jason W. , Luongo Chiara , Matás Carmen , Hernández-Caravaca Iván , Avilés Manuel , Izquierdo-Rico Mª José
Published: June 2021

Recent evidence supports involvement of the acute phase protein haptoglobin in numerous events during mammalian reproduction. The present study represents an in-depth investigation of haptoglobin expression and secretion in the porcine oviduct and uterus, and assesses its effect on porcine in vitro embryo production. A systematic study was made of sows in different oestrous stages: late follicular, early luteal and late luteal stages. Relative haptoglobin mRNA abundance was quantified by RT-qPCR. In addition, expression of the protein was analysed by immunohistochemistry and the results were complemented by Western-blot and proteomic analyses of the oviductal and uterine fluids. In vitro porcine fertilization and embryo culture were carried out in the presence of haptoglobin. The results indicate that haptoglobin mRNA expression in the porcine oviduct and uterus is most abundant during the late luteal stage of the oestrous cycle. By means of Western blot and proteomic analyses haptoglobin presence was demonstrated in the oviduct epithelium and in the oviductal and uterine fluids in different stages of the oestrous cycle. The addition of haptoglobin during gamete co-incubation had no effect on sperm penetration, monospermy or efficiency rates; however, compared with the control group, blastocyst development was significantly improved when haptoglobin was present (haptoglobin: 64.50%vs.control: 37.83%; p < 0.05). In conclusion, the presence of haptoglobin in the oviduct and uterus of sows at different stages of the oestrous cycle suggests that it plays an important role in the reproduction process. The addition of haptoglobin during in vitro embryo production improved the blastocyst rates.
Identifying and characterizing high-risk clusters in a heterogeneous ICU population with deep embedded clustering
Authors: Castela Forte José , Yeshmagambetova Galiya , van der Grinten Maureen L. , Hiemstra Bart , Kaufmann Thomas , Eck Ruben J. , Keus Frederik , Epema Anne H. , Wiering Marco A. , van der Horst Iwan C. C.
Published: June 2021

Critically ill patients constitute a highly heterogeneous population, with seemingly distinct patients having similar outcomes, and patients with the same admission diagnosis having opposite clinical trajectories. We aimed to develop a machine learning methodology that identifies and provides better characterization of patient clusters at high risk of mortality and kidney injury. We analysed prospectively collected data including co-morbidities, clinical examination, and laboratory parameters from a minimally-selected population of 743 patients admitted to the ICU of a Dutch hospital between 2015 and 2017. We compared four clustering methodologies and trained a classifier to predict and validate cluster membership. The contribution of different variables to the predicted cluster membership was assessed using SHapley Additive exPlanations values. We found that deep embedded clustering yielded better results compared to the traditional clustering algorithms. The best cluster configuration was achieved for 6 clusters. All clusters were clinically recognizable, and differed in in-ICU, 30-day, and 90-day mortality, as well as incidence of acute kidney injury. We identified two high mortality risk clusters with at least 60%, 40%, and 30% increased. ICU, 30-day and 90-day mortality, and a low risk cluster with 25–56% lower mortality risk. This machine learning methodology combining deep embedded clustering and variable importance analysis, which we made publicly available, is a possible solution to challenges previously encountered by clustering analyses in heterogeneous patient populations and may help improve the characterization of risk groups in critical care.