bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein A‐1 protected hepatic ischaemia–reperfusion injury through suppressing macrophage pyroptosis via TLR4–NF‐κB pathway
Authors: Chen Rui‐Xiang , Jiang Wang‐Jie , Liu Shuo‐Chen , Wang Zi‐Yi , Wang Zhi‐Bo , Zhou Tao , Chen Yan‐An‐Lan , Wang Ji‐Fei , Chang Jiang , Wang Yi‐Rui , Zhang Yao‐Dong , Wang Xue‐Hao , Li Xiang‐Cheng , Li Chang‐Xian
Published: October 2022

Background and Aims

Apolipoprotein A‐1 (ApoA‐1), the major apolipoprotein of high‐density lipoprotein, plays anti‐atherogenic role in cardiovascular diseases and exerts anti‐inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA‐1 in hepatic ischaemia–reperfusion (I/R) injury is unknown.

Methods

In this study, we measured ApoA‐1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA‐1 knockout mice, ApoA‐1 mimetic peptide D‐4F treatment mice and corresponding control mice to examine the effect of ApoA‐1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study.

Results

The results showed that ApoA‐1 expression was down‐regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA‐1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA‐1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA‐1 deficiency. Furthermore, the up‐regulated pyroptosis process was testified to be mediated by ApoA‐1 through TLR4–NF‐κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D‐4F ameliorated hepatic I/R injury.

Conclusions

Our study has identified the protective role of ApoA‐1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4–NF‐κB pathway. The effect of ApoA‐1 may provide a novel therapeutic approach for hepatic I/R injury.
Hypochloremia as a novel adverse prognostic factor in acute liver failure
Authors: Wang Jiexin , Liu Po‐Hong , Xu Pin , Sumarsono Andrew , Rule Jody A. , Hedayati S. Susan , Lee William M. ,   for the Acute Liver Failure Study Group
Published: October 2022

Background and Aims

Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America.

Methods

The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21‐day all‐cause mortality or requirement for liver transplantation (death/LT).

Results

Patients with hypochloremia (<98 mEq/L) had a significantly higher 21‐day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant‐free cumulative survival in the hypochloremic group than in the normo‐ or hyper‐chloremic groups (log‐rank, χ2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21‐day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969–0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13–0.25) but underestimated the probability of transplant‐free survival in 34% of patients (NRI = −0.34, 95% CI: −0.39 to −0.28).

Conclusions

Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG‐Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.
SPINDLY interacts with EIN2 to facilitate ethylene signalling‐mediated fruit ripening in tomato
Authors: Xu Jin , Liu Sidi , Cai Licong , Wang Lingyu , Dong Yufei , Qi Zhenyu , Yu Jingquan , Zhou Yanhong
Published: October 2022

The post‐translational modification of proteins enables cells to respond promptly to dynamic stimuli by controlling protein functions. In higher plants, SPINDLY (SPY) and SECRET AGENT (SEC) are two prominent O‐glycosylation enzymes that have both unique and overlapping roles; however, the effects of their O‐glycosylation on fruit ripening and the underlying mechanisms remain largely unknown. Here we report that SlSPY affects tomato fruit ripening. Using slspy mutants and two SlSPY‐OE lines, we provide biological evidence for the positive role of SlSPY in fruit ripening. We demonstrate that SlSPY regulates fruit ripening by changing the ethylene response in tomato. To further investigate the underlying mechanism, we identify a central regulator of ethylene signalling ETHYLENE INSENSITIVE 2 (EIN2) as a SlSPY interacting protein. SlSPY promotes the stability and nuclear accumulation of SlEIN2. Mass spectrometry analysis further identified that SlEIN2 has two potential sites Ser771 and Thr821 of O‐glycans modifications. Further study shows that SlEIN2 is essential for SlSPY in regulating fruit ripening in tomatoes. Collectively, our findings reveal a novel regulatory function of SlSPY in fruit and provide novel insights into the role of the SlSPY‐SlEIN2 module in tomato fruit ripening.
Measuring Risk of Re-Identification in Microdata: State-of-the Art and New Directions
Authors: Shlomo Natalie , Skinner Chris
Published: October 2022

We review the influential research carried out by Chris Skinner in the area of statistical disclosure control, and in particular quantifying the risk of re-identification in sample microdata from a random survey drawn from a finite population. We use the sample microdata to infer population parameters when the population is unknown, and estimate the risk of re-identification based on the notion of population uniqueness using probabilistic modelling. We also introduce a new approach to measure the risk of re-identification for a subpopulation in a register that is not representative of the general population, for example a register of cancer patients. In addition, we can use the additional information from the register to measure the risk of re-identification for the sample microdata. This new approach was developed by the two authors and is published here for the first time. We demonstrate this approach in an application study based on UK census data where we can compare the estimated risk measures to the known truth.
Stromatolite‐rimmed thrombolite columns and domes constructed by microstromatolites, calcimicrobes and sponges in late Cambrian biostromes, Texas, USA
Authors: Lee Jeong‐Hyun , Riding Robert
Published: October 2022

Microbial carbonates formed stromatolitic, thrombolitic, dendrolitic and maceriate (mazelike) fabrics in shallow marine Cambrian–Early Ordovician carbonates encircling Laurentia. However, poor preservation often hinders recognition of their specific components. Well‐preserved examples of normal shallow marine limestones in the ca 490 Ma upper Cambrian Point Peak Member, Wilberns Formation, central Texas, include stromatolitic cones, steep‐sided laminated rimmed columns with grainy interiors, and laminated and maceriate domes. Together these form decimetre to metre‐thick biostromes. In these examples, a single component, microstromatolite, on its own or with minor calcimicrobes, creates macroscopic stromatolitic, dendrolitic, thrombolitic and maceriate fabrics. Microstromatolites constructed upward widening stromatolitic cones that developed into columns with laminated rims surrounding slightly depressed interiors. These columns accumulated allochthonous sediment by a ‘bucket effect’. Their interiors contain either clusters of dendrolitic microstromatolite or ragged columns of laminated stromatolite–sponge biolithite, and are often characterized by a ‘mottled’ fabric that superficially resembles thrombolite. This mottling was formed by localized dolomitization around millimetric burrows that otherwise do not appear to have significantly influenced the biolithite fabric. Calcimicrobes, including cyanobacteria (Razumovskia) and microproblematica (Renalcis and Tarthinia), impart a mesoscopic clotted appearance to maceriate fabric, and locally to column rims, both of which are dominated by microstromatolite. Similar component‐fabric relationships should be recognizable in rimmed columns and domes that were locally abundant elsewhere in Cambrian–Early Ordovician shallow carbonate seas.
Identification of the novel HLA allele, HLA‐A*11:01:01:86, in an individual from north India
Authors: Tambe Manisha , D'Silva Selma Z. , Pinto Andrea S. , Singh Meenakshi
Published: October 2022

The novel allele HLA‐A*11:01:01:86 differs from HLA‐A*11:01:01:86 by one nucleotide change at position; gDNA‐32 (A– > C).
Synthesis of Porous g-C₃N₄ and Its Application as Photocatalyst for Methylene Blue Degradation
Authors: Yuhaneka Grace , Rozafia Ade Irma , Utomo Wahyu Prasetyo , Iryani Ani , Hartanto Djoko
Published: October 2022

Graphitic carbon nitride (g-C3N4) is a photocatalyst possessing a unique layered structure, remarkable thermal and chemical stability, and tunable bandgap. However, the bulk g-C3N4 has limited active sites and fast electron-holes recombination. In this work, we prepared porous g-C3N4 with an enhanced photoactivity toward methylene blue (MB) degradation. The porous g-C3N4 were prepared from melamine with addition of various amount of citric acid as a pore-forming agent (0.0 mmole, 0.1 mmole, 0.2 mmole, and 0.3 mmole; assigned as g-C3N4-0, g-C3N4-1, g-C3N4-2, and g-C3N4-3, respectively).  The structural and morphologycal properties of the samples were analyzed using XRD, SEM, FTIR, and N2 sorption. The optical property was analyzed using UV-vis diffuse reflectance and photoluminesence spectroscopy. While the electronic conductivity was analyzed using Mott-Schottky analysis and electron impedance spectroscopy (EIS). The photocatalytic test revealed that g-C3N4-2 exhibited the highest MB degradation rate (k=0.0090 min-1), while the bulk g-C3N4-0 showed the lowest rate (k=0.0068 min-1). The g-C3N4-2 possesed relatively smaller crystallite size (~43.5 nm) and a larger surface area (13.975 m2 g-1) compared to the bulk g-C3N4-0 (crystallite size: 46.9 nm; surface area: 9.163 m2 g-1). The optical property and charge carrier transfer analysis also revealed that the g-C3N4-2 possessed more efficient charge carrier transfer, which suppress the charge recombination. The combination between a larger surface area and more efficient charge carrier transfer contributes to the enhanced photocatalytic activity of porous g-C3N4 toward MB degradation.
Impact of Climate Change on Cassava Yield in Guapimirim, State of Rio de Janeiro, Southeast Brazil
Authors: Maciel Santos Carlos Alberto , Lyra Gustavo Bastos , Rodriguez Daniel Andrés
Published: October 2022

Global warming has changed the climate in many parts of the world and affected ecosystems due to anthropogenic greenhouse gas (GHG) emissions that contribute to the rise in the surface temperature of the planet. Rising temperatures have important effects on agriculture, which accounts for one- third of Brazil's economy. This study assesses the impact of climate change over agriculture on cassava yield in Guapimirim city, State of Rio de Janeiro, Southeast Brazil. Bias corrected climate simulation performed from the nested model Eta-HadGEM2-ES was used to reproduce the climate data observed in the region and for climate projections under Representative Concentration Pathways (RCPs) 4.5 and 8.5 scenarios. Simulated rainfall and evapotranspiration for the period between 1961 and 1990 was compared to the observation period and, showed a correlation with R² = 0.99 and the Average Absolute Percentage Error was less than 5.0%. The effect of climate projections on water stress during crop development was estimated using the Thornthwaite-Mather (TM) soil water balance adapted for crops. Rainfall and actual evapotranspiration projections for the three thirty-year periods 2011-2040, 2041-2070, 2071-2100 served as the basis for the assessment of the Water Requirement Satisfaction Index (WRSI) and Yield Reduction (YR) for cassava crop. Projections show significant cassava yield losses around 8.6 and 9.7 ton ha-1, respectively, under RCPs 4.5 and 8.5. This approach allows exploratory analysis applied to support crop management decision-making and irrigation strategies for sustainable agriculture and to increase crop yield in the face of impacts of climate change.
A Comparative Study of Entropy Generation Analysis Through Cartesian and Cylindrical Annulus Geometries
Authors: Sakly Abir , Mahjoub Said Nejla
Published: October 2022

This research paper presents a comparative study dealing with entropy generation analysis in Cartesian and cylindrical annulus geometries. This numerical investigation involves heat and mass transfer coupled with forced convection and gas radiation in a semitransparent medium during the evaporation of a thin liquid film. The systems of equations are solved with interfacial and boundary conditions using an implicit finite volume method by the tridiagonal matrix algorithm method. The radiative transfer equation (RTE) was solved by the Ray tracing model. The statistical narrow band correlated-K model with the updated model parameters was applied to calculate the gas transmissivity. The main intent of this paper is to compare the entropy generation components in two different configurations. The result shows that the entropy generation related to heat and mass transfer in the channel is higher than that estimated for the cylindrical annulus. Regarding optimal design selection, the entropy generation analysis, detailed in this paper, suggests a preference for the cylindrical annulus geometry. Our results may guide designers to select from the studied configuration.
A Simple Correlation for Horizontal Microfin Tube Convective Boiling
Authors: Kedzierski M. A. , Lin L.
Published: October 2022

This paper presents a simple correlation containing nine dimensionless parameters to predict the local convective boiling heat transfer within a microfin tube that was developed from a dataset that included a wide range of refrigerants, flow conditions, and hydraulic diameters. Flow boiling measurements from 36 studies were gathered to produce a dataset containing 29 refrigerants and 15 different hydraulic diameters ranging from 1.8 mm to 6.7 mm. The database was adjusted so that the definition of the Nusselt number, the Reynolds number, the heat flux, and heat transfer coefficient were all defined in the same way for each study. In addition, values for the most recent fluid properties were used for the calculation of dimensionless parameters that were used in the new correlation. The new correlation for microfin convective boiling predicted the measurements from the database to within ±10.3% for pure-refrigerants and azeotropic mixtures and ±12.3% for zeotropic mixtures.
Detection of the Onset of Trip Symptoms Embedded in Gas Turbine Operating Data
Authors: Losi Enzo , Venturini Mauro , Manservigi Lucrezia , Bechini Giovanni
Published: October 2022

One of the most disrupting events that affect gas turbine (GT) operation is trip, since its occurrence reduces machine life span and also causes business interruption. Thus, early detection of incipient symptoms of GT trip is crucial to ensure efficient operation and save costs. This paper presents a data-driven methodology of which the goal is the disclosure of the onset of trip symptoms by exploring multiple trigger scenarios. For each scenario, a time window of the same length is considered before and after the trigger time point: the former is supposed to be representative of normal operation and is labeled “no trip,” whereas the latter is labeled “trip.” A long short-term memory (LSTM) neural network is first trained for each scenario and subsequently tested on new trips over a timeframe of 3 days of operation before trip occurrence. Finally, trips are clustered into homogeneous groups according to their most likely trigger position, which identifies the time point of onset of trip symptoms. The methodology is applied to two real-world case studies composed of a collection of trips, of which the causes are different, taken from various fleets of GTs in operation. Data collected from multiple sensors are employed and analyzed. The methodology provides the most likely trigger position for four clusters of trips and both case studies with a confidence in the range 66–97%.
Effects of Preheating on Microstructural and Mechanical Properties of Friction Stir Welded Thin Low Carbon Steel Joints
Authors: Yamani Seyed Mehrdad , Raja Sufian , bin Ariffin Mohammad Ashraf , Mohd Isa Mohammad Syahid , Muhamad Mohd Ridha , Jamaludin Mohd Fadzil , Yusof Farazila , bin Ahmad Hairuddin Muhammad Khairi Faiz
Published: October 2022

Friction stir welding of a low carbon thin steel plate was performed with preheating the base material to increase the joining performance. The rotational speed of the tool was set from 1500 to 2000 rpm with a constant travel speed of 15 mm/min and preheating temperature of 50 to 150 °C. The tensile strength of 340 MPa was achieved for the preheated specimen compared with 310 MPa for the non-preheating specimen at the welding speed of 15 mm/min. Electron microscopic images of the preheated joint revealed a remarkable plasticized material flow and dynamic recrystallization, which resulted in the grain refinement that had increased the joining strength. The weld thinning issue was almost eliminated in the preheated welded specimen. However, by increasing the preheat temperature further, the tensile strength decreases due to the formation of defects from excessive heat. The preheated sample fractured at the base metal, revealing a ductile fracture mode.
Oblique Wave Diffraction by a Bottom-Standing Thick Barrier and a Pair of Partially Immersed Barriers
Authors: Sarkar Biman , De Soumen
Published: October 2022

On the basis of the linearized theory of water waves, the present study has demonstrated a semi-analytical method to assess the hydrodynamic performance of a pair of partially immersed barriers just above a thick bottom-standing barrier. By means of the eigenfunction expansion method, a system of the first kind Fredholm-type integral equation involving a horizontal component of velocity as unknown functions is developed for the interaction of water waves with both types of barriers. The multiterm Galerkin approximation is adopted to determine these unknown functions having square root singularities at the submerged edge of the thin barriers and one-third singularities at the corners of the thick barrier. In order to overcome such types of singularities, Chebychev polynomials for half-singularities and ultra-spherical Gegenbauer polynomials for one-third singularities with suitable weight functions have been taken into consideration. The numerical examples of both reflection and transmission coefficients are presented to examine the hydrodynamic performance of breakwater. Some fascinating results like resonant frequencies are obtained for practical engineering. At the same time, reflection coefficients for the present breakwater agree reasonably for the limiting cases with the previously available results.
Predicting Vertical Daylight Illuminance Data From Measured Solar Irradiance: A Machine Learning-Based Luminous Efficacy Approach
Authors: Li Danny Hin Wa , Aghimien Emmanuel Imuetinyan
Published: October 2022

Daylight data are required for energy-efficient building designs. However, daylight is scarcely measured, making the luminous efficacy model an alternative. This paper presents a method for modeling vertical luminous efficacy (Kvg) using measured data from measuring stations in Hong Kong. The artificial neural network (ANN), support vector machines (SVM), and empirical correlations were proposed for modeling Kvg. Machine learning (ML) models like ANN and SVM were used because they offer more accurate daylight predictions and ease in explaining complex relationships between atmospheric variables. Also, ML was explored since it has not been used in earlier vertical luminous efficacy studies. Sensitivity analysis was also carried out to determine the relative importance of input variables used for developing the proposed models. Findings show that scattering angle and diffuse fraction are crucial variables in vertical luminous efficacy modeling. Furthermore, when all proposed models were used to predict vertical daylight, it was observed that the peak relative root mean square error (%RMSE) was less than 18.6%. The obtained %RMSE showed that all models provided acceptable performance when evaluated against the measured daylight data. Finally, the findings also showed that the ANN models outperformed the SVM and empirical models.
The Finite Segment Method—A Numerical Rolling Contact Fatigue Life Model for Bearings Subjected to Stochastic Operating Conditions
Authors: Menck Oliver
Published: October 2022

Fatigue life calculation in bearings is an issue that has been the focus of decades of research culminating in national and international standards that are easily applicable to a wide variety of applications. However, almost all research has focused on simple, repetitive operating conditions. This paper explains why these approaches are not completely applicable to bearings under certain conditions, particularly not to those with a change in the load position over time undergoing inconstant movement. Based on existing standards, namely ISO 281, the paper then proposes a numerical approach to calculate the life of a bearing under stochastic operating conditions. The bearing life for any arbitrary load history and movement patterns can be calculated using the presented approach. The approach is presented and some example applications are given, notably including the life calculation of a rotor blade bearing in a wind turbine.
Severe COVID-19 induces autoantibodies against angiotensin II that correlate with blood pressure dysregulation and disease severity
Authors: Briquez Priscilla S. , Rouhani Sherin J. , Yu Jovian , Pyzer Athalia R. , Trujillo Jonathan , Dugan Haley L. , Stamper Christopher T. , Changrob Siriruk , Sperling Anne I. , Wilson Patrick C. , Gajewski Thomas F. , Hubbell Jeffrey A. , Swartz Melody A.
Published: October 2022

Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can experience life-threatening respiratory distress, blood pressure dysregulation, and thrombosis. This is thought to be associated with an impaired activity of angiotensin-converting enzyme 2 (ACE2), which is the main entry receptor of SARS-CoV-2 and which also tightly regulates blood pressure by converting the vasoconstrictive peptide angiotensin II (AngII) to a vasopressor peptide. Here, we show that a significant proportion of hospitalized patients with COVID-19 developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity. Anti-AngII antibodies can develop upon specific immune reaction to the SARS-CoV-2 proteins Spike or receptor-binding domain (RBD), to which they can cross-bind, suggesting some epitope mimicry between AngII and Spike/RBD. These results provide important insights on how an immune reaction against SARS-CoV-2 can impair blood pressure regulation.
Distinct roles of ORAI1 in T cell–mediated allergic airway inflammation and immunity to influenza A virus infection
Authors: Wang Yin-Hu , Noyer Lucile , Kahlfuss Sascha , Raphael Dimitrius , Tao Anthony Y. , Kaufmann Ulrike , Zhu Jingjie , Mitchell-Flack Marisa , Sidhu Ikjot , Zhou Fang , Vaeth Martin , Thomas Paul G. , Saunders Sean P. , Stauderman Kenneth , Curotto de Lafaille Maria A. , Feske Stefan
Published: October 2022

T cell activation and function depend on Ca
2+
signals mediated by store-operated Ca
2+
entry (SOCE) through Ca
2+
release–activated Ca
2+
(CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T
H
1) cell–mediated response to influenza A virus (IAV) infection and T
H
2 cell–mediated allergic airway inflammation. T cell–specific deletion of
Orai1
did not exacerbate pulmonary inflammation and viral burdens following IAV infection but protected mice from house dust mite–induced allergic airway inflammation. ORAI1 controlled the expression of genes including p53 and E2F transcription factors that regulate the cell cycle in T
H
2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T
H
2 cell function. Systemic application of a CRAC channel blocker suppressed allergic airway inflammation without compromising immunity to IAV infection, suggesting that inhibition of SOCE is a potential treatment for allergic airway disease.
An artificial intelligence enabled chemical synthesis robot for exploration and optimization of nanomaterials
Authors: Jiang Yibin , Salley Daniel , Sharma Abhishek , Keenan Graham , Mullin Margaret , Cronin Leroy
Published: October 2022

We present an autonomous chemical synthesis robot for the exploration, discovery, and optimization of nanostructures driven by real-time spectroscopic feedback, theory, and machine learning algorithms that control the reaction conditions and allow the selective templating of reactions. This approach allows the transfer of materials as seeds between cycles of exploration, opening the search space like gene transfer in biology. The open-ended exploration of the seed-mediated multistep synthesis of gold nanoparticles (AuNPs) via in-line ultraviolet-visible characterization led to the discovery of five categories of nanoparticles by only performing ca. 1000 experiments in three hierarchically linked chemical spaces. The platform optimized nanostructures with desired optical properties by combining experiments and extinction spectrum simulations to achieve a yield of up to 95%. The synthetic procedure is outputted in a universal format using the chemical description language (χDL) with analytical data to produce a unique digital signature to enable the reproducibility of the synthesis.
Oncogenic role of a developmentally regulated
NTRK2
splice variant
Authors: Pattwell Siobhan S. , Arora Sonali , Nuechterlein Nicholas , Zager Michael , Loeb Keith R. , Cimino Patrick J. , Holland Nikolas C. , Reche-Ley Noemi , Bolouri Hamid , Almiron Bonnin Damian A. , Szulzewsky Frank , Phadnis Vaishnavi V. , Ozawa Tatsuya , Wagner Michael J. , Haffner Michael C. , Cao Junyue , Shendure Jay , Holland Eric C.
Published: October 2022

Temporally regulated alternative splicing choices are vital for proper development, yet the wrong splice choice may be detrimental. Here, we highlight a previously unidentified role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis across multiple tumor types in humans and mice. TrkB.T1 is the predominant
NTRK2
isoform across embryonic organogenesis, and forced overexpression of this embryonic pattern causes multiple solid and nonsolid tumors in mice in the context of tumor suppressor loss. TrkB.T1 also emerges as the predominant
NTRK
isoform expressed in a wide range of adult and pediatric tumors, including those harboring tropomyosin receptor kinase fusions. Affinity purification–mass spectrometry proteomic analysis reveals distinct interactors with known developmental and oncogenic signaling pathways such as Wnt, transforming growth factor–β, Sonic Hedgehog, and Ras. From alterations in splicing factors to changes in gene expression, the discovery of isoform specific oncogenes with embryonic ancestry has the potential to shape the way we think about developmental systems and oncology.
An enzyme-mimic single Fe-N
3
atom catalyst for the oxidative synthesis of nitriles via C─C bond cleavage strategy
Authors: Qin Jingzhong , Han Bo , Liu Xixi , Dai Wen , Wang Yanxin , Luo Huihui , Lu Xiaomei , Nie Jiabao , Xian Chensheng , Zhang Zehui
Published: October 2022

The cleavage and functionalization of recalcitrant carbon─carbon bonds is highly challenging but represents a very powerful tool for value-added transformation of feedstock chemicals. Here, an enzyme-mimic iron single-atom catalyst (SAC) bearing iron (III) nitride (FeN
3
) motifs was prepared and found to be robust for cleavage and cyanation of carbon–carbon bonds in secondary alcohols and ketones. High nitrile yields are obtained with a wide variety of functional groups. The prepared FeN
3
-SAC exhibits high enzyme-like activity and is capable of generating a dioxygen-to-superoxide radical at room temperature, while the commonly reported FeN
4
-SAC bearing FeN
4
motifs was inactive. Density functional theory (DFT) calculation reveals that the activation energy of dioxygen activation and the activation energy of the rate-determining step of nitrile formation are lower over FeN
3
-SAC than FeN
4
-SAC. In addition, DFT calculation also explains the catalyst’s high selectivity for nitriles.
Creating enzyme-mimicking nanopockets in metal-organic frameworks for catalysis
Authors: Zhang Xiaofei , Yang Caoyu , An Pengfei , Cui Chengqian , Ma Yumiao , Liu Haitao , Wang Hui , Yan Xiaoying , Li Guodong , Tang Zhiyong
Published: October 2022

Numerous efforts are being made toward constructing artificial nanopockets inside heterogeneous catalysts to implement challenging reactions that are difficult to occur on traditional heterogeneous catalysts. Here, the enzyme-mimetic nanopockets are fabricated inside the typical UiO-66 by coordinating zirconium nodes with terephthalate (BDC) ligands and monocarboxylate modulators including formic acid (FC), acetic acid (AC), or trifluoroacetic acid (TFA). When used in transfer hydrogenation of alkyl levulinates with isopropanol toward γ-valerolactone (GVL), these modulators endow zirconium sites with enhanced activity and selectivity and good stability. The catalytic activity of UiO-66FC is ~30 times that of UiO-66, also outperforming the state-of-the-art heterogeneous catalysts. Distinct from general consensus on electron-withdrawing or electron-donating effect on the altered activity of metal centers, this improvement mainly originates from the conformational change of modulators in the nanopocket to assist forming the rate-determining six-membered ring intermediate at zirconium sites, which are stabilized by van der Waals force interactions.
Transformation of eastern North America from compression to extension in the Permian–Triassic
Authors: Ma* Chong , Hames Willis E. , Foster David A. , Xiao Wenjiao , Mueller Paul A. , Steltenpohl Mark G.
Published: October 2022

The record of Permian–Triassic evolution in eastern North America indicates an important change in the tectonic regime from compression to extension as eastern Laurentia transitioned from the Alleghanian orogeny to continental rifting associated with the breakup of Pangea. The temporal pace (e.g., gradual vs. episodic, diachronous vs. synchronous), the accommodating structures, and the influential processes that characterized this transition provide critical insights into the late Paleozoic evolution of Laurentia and rifted continental margins in general. Connections between the formation of the South Georgia basin and regional cooling of the southernmost Appalachian crystalline rocks, along with the distribution of normal faults and discontinuities in metamorphic grade, indicate extensional collapse of the Alleghanian orogen along an extensive detachment system that was active from ca. 295 to 240 Ma. The 40Ar/39Ar cooling ages of biotites from low-angle normal shear zones cutting migmatitic gneisses of the southernmost Appalachians are interpreted to document extensional faulting ca. 280 Ma and to provide a snapshot of the prolonged orogenic collapse. The timing, orientation of structures, extent of reactivation, and character of late Alleghanian extension in the central and northern Appalachians provide an orogen-scale framework for this tectonic transition. This contribution focuses on correlations between the beginning of orogenic collapse and the initiation of continental rifting along with the tectonic processes that transformed eastern North America from a convergent to divergent plate boundary following the Alleghanian orogeny.
Bilateral adrenal haemorrhage in antiphospholipid syndrome and a short review of the literature
Authors: Cherico Adriani Samuel , White Richard J , Shah Deep , Bhagavatula Rama
Published: October 2022

Antiphospholipid syndrome (APS) is an uncommon autoantibody-mediated condition characterised by acquired thrombophilia resulting in recurrent arterial and venous thrombosis. An inciting factor allows for the exposure of endothelial phospholipids, causing antigen formation and subsequent creation of antibodies. A woman in her 70s presented after vehicular trauma, suffering broken ribs, pneumothorax and incidentally discovered left adrenal haemorrhage. Two weeks later she presented with acute-onset abdominal pain and was found to have a right adrenal gland haemorrhage on CT imaging without interval trauma occurring. The patient had antiphospholipid antibody laboratory studies drawn and was given intravenous heparin with a bridge to warfarin at discharge. Laboratory results returned positive for lupus anticoagulant, beta-2 glycoprotein and anticardiolipin antibodies indicating triple positivity, with repeated laboratory tests positive in 12 weeks’ time, confirming the diagnosis. Bilateral adrenal haemorrhage, rather than traditional venous thromboembolism, was the presenting pathology in this patient’s diagnosis of APS.
Factors influencing healthcare-seeking behaviour among Muslims from Southeast Asian countries (Indonesia and Malaysia) living in Japan: an exploratory qualitative study
Authors: Kohno Ayako , Dahlui Maznah , Koh David , Dhamanti Inge , Rahman Hanif , Nakayama Takeo
Published: October 2022

Objectives

To identify factors influencing healthcare-seeking behaviours and to explore issues with healthcare experiences of Muslims from Southeast Asian countries (Indonesia and Malaysia) living in Japan.

Design

Qualitative study.

Setting

Kansai area of Japan (Kyoto, Osaka, Hyogo and Nara prefectures).

Participants

Forty-five Muslims in Japan from Southeast Asian countries (Indonesia and Malaysia).

Methods

Semistructured interviews were conducted by trained interviewers who are Muslims living in Japan. Interviews were conducted in Indonesian and Malaysian languages and transcribed and translated into English. The data were thematically analysed.

Results

Four themes were identified: (1) trying to comply with the recommendations of Islam, (2) confusion about healthcare system, (3) improvising an informal support system and (4) language barrier problems.

Conclusion

Muslims in Japan have some issues when obtaining healthcare services mainly because of communication issues besides the conflicts to meet their religious obligations. Education and awareness building for the Muslim patients in Japan as well as Japanese healthcare providers are needed to allow smooth communication between Japanese healthcare providers and Muslim patients in Japan.
Effectiveness of weight loss interventions in breast cancer survivors: a systematic review of reviews
Authors: Lake Blossom , Damery Sarah , Jolly Kate
Published: October 2022

Background

Elevated body mass index (BMI) in breast cancer survivors (BCS) is associated with cancer recurrence and poorer treatment response. Guidelines recommend 5%–10% weight loss for overweight or obese BCS.

Objectives

To assess effectiveness of lifestyle interventions for female BCS on weight loss, BMI, body composition, health-related quality of life (HRQoL), physical functioning, psychosocial measures, biomarkers.

Design

Systematic review of reviews and meta-analyses.

Setting

All clinical settings.

Participants

Adult female BCS (active treatment or post-treatment).

Methods

Medline, Embase, CINAHL, PsycINFO, Cochrane Library (including Database of Abstracts of Reviews of Effects) were searched for systematic reviews published in English between 1990 and 2022, with weight, BMI or body fat as primary outcome. Narrative reviews, editorials, letters, conference abstracts were excluded. Review quality was assessed using the Joanna Briggs Institute quality assessment tool.

Results

17 reviews were included. Twelve reported significant reductions in one or more anthropometric outcomes: weight −1.36 kg (95% CI:−2.51 to −0.21) to −3.8 kg (95% CI: −5.6 to −1.9); BMI −0.89 kg/m2(95% CI: −0.15 to −0.28) to −3.59 kg/m2(95% CI: −6.29 to 0.89) or body fat −1.6% (95% CI: −2.31 to −0.88) to −2.6% (95% CI not reported). Significant reductions in two or more anthropometric outcomes were reported in 7/12 reviews, with effective interventions comprising aerobic exercise/aerobic exercise plus resistance training (n=5), or diet and exercise with or without counselling (n=2). Significant improvements were also reported for HRQoL (8/11 reviews), mental health (4/7) and physical functioning (2/3). Group interventions comprising aerobic exercise or aerobic exercise plus resistance training were most likely to improve outcomes.

Conclusions

Lifestyle interventions can significantly improve outcomes for BCS. Multimodal interventions are likely to have the greatest impact in reducing weight, BMI and body fat. Further research must define the optimal combination, intensity and duration of effective interventions.

PROSPERO registration number

CRD42021283481.
Pharmacist direct dispensing of mifepristone for medication abortion in Canada: a survey of community pharmacists
Authors: Zusman Enav Z , Munro Sarah , Norman Wendy V , Soon Judith A
Published: October 2022

Introduction

Pharmacists were acknowledged as the most appropriate healthcare professional to dispense mifepristone for medication abortion shortly after the prescription therapy became available in January 2017 in Canada.

Objective

We aimed to identify the facilitators and barriers for successful initiation and ongoing dispensing of mifepristone among community pharmacists across Canada.

Study design

We surveyed community pharmacists from urban/rural practice settings across Canada by recruiting from January 2017 to January 2019 through pharmacist organisations, professional networks, at mifepristone training courses and at professional conferences. The Diffusion of Innovations theory informed the study design, thematic analysis and interpretation of findings. We summarised categorical data using counts and proportions, χ2 tests, Wilcoxon rank-sum and proportional odds logistic regression.

Results

Of the 433 responses from dispensing community pharmacists across 10/13 Canadian provinces and territories, 93.1% indicated they were willing and ready to dispense mifepristone. Key facilitators were access to a private consultation setting (91.4%), the motivation to increase accessibility for patients (87.5%) and to reduce pressure on the healthcare system (75.3%). The cost of the mifepristone/misoprostol product was an initial barrier, subsequently resolved by universal government subsidy. A few pharmacists mentioned liability, lack of prescribers or inadequate stock as barriers.

Conclusions

Pharmacist respondents from across Canada reported being able and willing to dispense mifepristone and rarely mentioned barriers to stocking/dispensing the medication in the community pharmacy setting. The removal of initial regulatory obstacles to directly dispense mifepristone to patients facilitated the provision of medication abortion in the primary care setting.
What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020)
Authors: Jenei Kristina , Haslam Alyson , Olivier Timothée , Miljkovíc Milos , Prasad Vinay
Published: October 2022

Objective

To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020.

Design, setting and participants

Retrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020.

Interventions

Clinical trials were analysed for the type of blinding, primary endpoint, whether crossover was specified in the publication, study phase, line of therapy, response rate, investigational sites, manufacturer and randomisation ratio.

Main outcome measures

The main outcome was the rate of accrual, which is the number of patients accrued in the study per open month of enrolment.

Results

The study consisted of 133 randomised (68%) and 61 (32%) non-randomised clinical trials. In randomised studies, we found the accrual rate was higher in trials investigating first and second line drugs (adjusted rate ratios (aRR): 1.55, 95% CI 1.18 to 2.09), phase III trials (aRR: 2.13, 95% CI 1.48 to 2.99), and for studies sponsored by Merck (aRR: 1.47, 95% CI 1.18 to 2.37), adjusting for other covariates. In contrast, the primary endpoint of a study, presence of crossover, single agent response rate, the number of investigational sites, population disease burden and skewed randomisation ratios were not associated with the rate of accrual. In the non-randomised adjusted model, the accrual rate was 2.03 higher (95% CI 1.10 to 3.92) for clinical trials sponsored by manufacturer, specifically Merck. Primary endpoint, crossover, trial phase, response rate, the number of investigational sites, disease burden or line of therapy were not associated with the rate of accrual.

Conclusion

In this cross-sectional study, line of therapy, study phase and manufacturer were the only factors associated with accrual rate. These findings suggest many proffered factors for speedy trial accrual are not associated with greater enrolment rates.
Flow cytometry lyophilised-reagent tube for quantifying peripheral blood neutrophil myeloperoxidase expression in myelodysplastic syndromes (MPO-MDS-Develop): protocol for a diagnostic accuracy study
Authors: Raskovalova Tatiana , Scheffen Laura , Jacob Marie-Christine , Chevalier Simon , Tondeur Sylvie , Bulabois Bénédicte , Meunier Mathieu , Szymanski Gautier , Lefebvre Christine , Planta Charlotte , Dumestre-Perard Chantal , Gonnet Nicolas , Garban Frédéric , Merle Raymond , Park Sophie , Labarère José
Published: October 2022

Introduction

Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. Peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis might rule out MDS for up to 35% of patients referred for suspected disease, without requiring bone marrow aspiration. Yet laboratory-developed liquid antibody cocktails have practical limitations, because of lack of standardisation and poor stability. This research project aims to estimate the level of agreement and comparative accuracy between a single-use flow cytometry tube of lyophilised reagents (BD Lyotube Stain 468) and its laboratory-developed liquid reagent counterpart in quantifying peripheral blood neutrophil myeloperoxidase expression, among adult patients referred for suspected MDS.

Methods and analysis

The MPO-MDS-Develop project is a cross-sectional diagnostic accuracy study of two index tests by comparison with a reference standard in consecutive unselected adult patients conducted at a single university hospital. Flow cytometry analysis of peripheral blood samples will be performed by independent operators blinded to the reference diagnosis, using either Lyotube Stain 468 or laboratory-developed liquid reagent cocktail. The reference diagnosis of MDS will be established by cytomorphological evaluation of bone marrow aspirate by two independent haematopathologists blinded to the index test results. Morphologic assessment will be complemented by bone marrow flow cytometric score, karyotype and targeted next-generation sequencing panel of 43 genes, where relevant. The target sample size is 103 patients.

Ethics and dissemination

An institutional review board (Comité de Protection des Personnes Sud Est III, Lyon, France) approved the protocol prior to study initiation (reference number: 2020-028-B). Participants will be recruited using an opt-out approach. Efforts will be made to release the primary results within 6 months of study completion.

Trial registration number

NCT04399018.
Radioactive releases from the nuclear power sector and implications for child health
Authors: Folkers Cindy , Gunter Linda Pentz
Published: October 2022

Although radioactivity is released routinely at every stage of nuclear power generation, the regulation of these releases has never taken into account those potentially most sensitive—women, especially when pregnant, and children. From uranium mining and milling, to fuel manufacture, electricity generation and radioactive waste management, children in frontline and Indigenous communities can be disproportionately harmed due to often increased sensitivity of developing systems to toxic exposures, the lack of resources and racial and class discrimination. The reasons for the greater susceptibility of women and children to harm from radiation exposure is not fully understood. Regulatory practices, particularly in the establishment of protective exposure standards, have failed to take this difference into account. Anecdotal evidence within communities around nuclear facilities suggests an association between radiation exposure and increases in birth defects, miscarriages and childhood cancers. A significant number of academic studies tend to ascribe causality to other factors related to diet and lifestyle and dismiss these health indicators as statistically insignificant. In the case of a major release of radiation due to a serious nuclear accident, children are again on the frontlines, with a noted susceptibility to thyroid cancer, which has been found in significant numbers among children exposed both by the 1986 Chornobyl nuclear accident in Ukraine and the 2011 Fukushima-Daiichi nuclear disaster in Japan. The response among authorities in Japan is to blame increased testing or to reduce testing. More independent studies are needed focused on children, especially those in vulnerable frontline and Indigenous communities. In conducting such studies, greater consideration must be applied to culturally significant traditions and habits in these communities.