bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between welding fume exposure and neurological function in Japanese male welders and non-welders
Authors: Tsuji Mayumi , Koriyama Chihaya , Ishihara Yasuhiro , Isse Toyohi , Ishizuka Tsunetoshi , Hasegawa Wataru , Goto Motohide , Tanaka Rie , Kakiuchi Noriaki , Hori Hajime , Yatera Kazuhiro , Kunugita Naoki , Yamamoto Megumi , Sakuragi Toshihide , Yasumura Yoshiko , Kono Maori , Kuwamura Mami , Kitagawa Kyoko , Ueno Susumu
Published: February 2023

Objectives

There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan.

Methods

A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only.

Results

The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P = .013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P = .043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P = .227).

Conclusions

The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.
Crystal structure of the motor domain of centromere‐associated protein E in complex with a non‐hydrolysable ATP analogue
Authors: Shibuya Asuka , Suzuki Akira , Ogo Naohisa , Sawada Jun‐ichi , Asai Akira , Yokoyama Hideshi
Published: February 2023

Centromere‐associated protein E (CENP‐E) is a kinesin motor protein essential for mitosis and a new target for anticancer agents with less side effects. To rationally design anticancer drug candidates based on structure, it is important to determine the three‐dimensional structure of the CENP‐E motor domain bound to its inhibitor. Here, we report the first crystal structure of the CENP‐E motor domain in complex with a non‐hydrolysable ATP analogue, adenylyl‐imidodiphosphate (AMPPNP). Furthermore, the structure is compared with the ADP‐bound form of the CENP‐E motor domain as well as the AMPPNP‐bound forms of other kinesins. This study indicates that helix α4 of CENP‐E participates in the slow binding of CENP‐E to microtubules. These results will contribute to the development of anticancer drugs targeting CENP‐E.
Shaped Photothermal Conversion Phase‐Change Materials with Excellent Electromagnetic Shielding Performance and Flame Retardancy
Authors: Li Yi-Ran , Li Ying-Ming , Hu Wen-Juan , Wang De-Yi
Published: February 2023

Shaped photothermal conversion energy‐storage materials are urgently developed to deal with the energy crisis and environmental pollution, and widely applicated in the fields of solar‐thermal power, new energy vehicle power battery, and so on, in which the serious electromagnetic radiation affects its normal use. Meanwhile, frequently used organic phase‐change materials are easily flammable, which greatly threaten the safety of life and property. Therefore, it is urgent to design shaped photothermal conversion and energy‐storage materials with high electromagnetic interference (EMI) shielding efficiency and good flame retardancy. Herein, 2D graphene oxide sheets are simultaneously reduced and foamed by hydrazine, and a multifunctional F‐reduced graphene oxide (rGO)/paraffin composite is prepared by vacuum impregnation method. When incorporating 40 wt% of F‐rGO, the photothermal‐conversion efficiency reaches 81.6%, the latent heat rate only reduces by 22.4%, and the change of phase enthalpy for the composites only decreases by 9.5% and after 10 thermal cycles. In addition, its EMI shielding efficiency is as high as 74.6 dB. Compared with pure paraffin, its heat release capacity, peak heat release rate, and total heat release are reduced by 50.1%, 52.0%, and 43.0%, respectively, due to the tortuous path and catalytic carbonization of F‐rGO.
Morphology Associated Positive Correlation between Carrier Mobility and Carrier Density in Highly Doped Donor–Acceptor Conjugated Polymers
Authors: Min Jiwoo , Im Jaemin , Kim Seung Hyun , Choi Hyun Ho , Cho Kilwon
Published: February 2023

Molecular doping in conjugated polymers (CPs) has recently received intensive attention for its potential to achieve high electrical conductivity in organic thermoelectric materials. In particular, it affects not only the carrier density n but also the carrier mobility µ because high degree of molecular doping changes the morphological properties. Herein, the effect of molecular doping in CP thin films on the pathways and mechanisms of charge transport is investigated, which govern the µ‐n relationship. Two representative donor–acceptor type CPs with similar µ but different molecular assembly in an undoped state, that is poly[2,5‐(2‐octyldodecyl)‐3,6‐diketopyrrolopyrrole‐alt‐5,5‐(2,5‐di(thien‐2‐yl)thieno[3,2‐b]thiophene)] (DPPDTT) and indacenodithiophene‐co‐benzothiadiazole (IDTBT), are prepared. Heavy doping with iron chloride (FeCl3) induced DPPDTT with highly crystalline edge‐on orientation to increase its µ up to 19.6 cm2 V−1 s−1, whereas IDTBT with irregular intermolecular stacking showed little change in µ. It is revealed that this different µ‐n relationship is highly attributed to the initial molecular ordering of CP films. The charge transport mechanism also becomes significantly different: both coherent and incoherent transports are observed in the doped DPPDTT, whereas incoherent transport is only found in the doped IDTBT. This study suggests guidelines for enhancing charge transport of CPs under doping in terms of structural disorder.
The Impact of Lattice Distortions on the Magnetic Stability of Single Atoms: Dy and Ho on BaO(100)
Authors: Sorokin Boris V. , Pivetta Marina , Bellini Valerio , Merk Darius , Reynaud Sébastien , Barla Alessandro , Brune Harald , Rusponi Stefano
Published: February 2023

X‐ray magnetic circular dichroism, atomic multiplet simulations, and density functional theory calculations are employed to identify criteria for the optimum combination of supporting alkaline earth oxide and adsorption site maximizing the spin lifetimes of lanthanide single‐atom magnets. Dy and Ho atoms adsorbed on BaO(100) thin films on Pt(100) are characterized and compared with previous results for the same two elements on MgO/Ag(100). Dy shows hysteresis in magnetic fields up to ≈3.5 T and long spin lifetime, exceeding 300 s at 2.5 K and 0.5 T. Dy displays superior magnetic stability on the bridge site than on the top‐O site. Surprisingly, Ho shows paramagnetism, as opposed to its long spin lifetime on MgO. These differences originate from the local surface distortions induced by the adatoms. On MgO, minimal distortions involve only the closest O atoms, while, on BaO, they affect both the closest anions and cations. This trend reflects the decrease of the lattice energy along the series of the alkaline earth oxides, going from MgO to BaO. This study represents a step ahead in the understanding of the factors determining the spin dynamics of surface‐adsorbed single‐atom magnets in order to achieve their operation as qubits and memories.
Light‐Driven Conversion of Silicon Nitride Nanopore to Nanonet for Single‐Protein Trapping Analysis
Authors: Li Jing , Huang Bintong , Wang Yuanhao , Li Aijia , Wang Yong , Pan Yangyang , Chai Jia , Liu Ze , Zhai Yueming
Published: February 2023

The single‐molecule technique for investigation of an unlabeled protein in solution is very attractive but with great challenges. Nanopore sensing as a label‐free tool can be used for collecting the structural information of individual proteins, but currently offers only limited capabilities due to the fast translocation of the target. Here, a reliable and facile method is developed to convert the silicon nitride nanopore to a stable nanonet platform for single‐entity sensing by electrophoretic or electroosmotic trapping. A nanonet is fabricated based on a material reorganization process caused by electron‐beam and light‐irradiation treatment. Using protein molecules as a model, it is revealed that the solid‐state nanonet can produce collision and trapping flipping signals of the protein, which provides more structural information than traditional nanopore sensing. More importantly, thanks to the excellent stability of the solid‐state silicon nitride nanonet, it is demonstrated that the ultraviolet‐light‐irradiation‐induced structural‐change process of an individual protein can be captured. The developed nanonet supplies a robust platform for single‐entity studies but is not limited to proteins.
Printable Thermochromic Hydrogel‐Based Smart Window for All‐Weather Building Temperature Regulation in Diverse Climates
Authors: Chen Guoqi , Wang Kai , Yang Jiahui , Huang Jie , Chen Zhongfeng , Zheng Jingxia , Wang Jingquan , Yang Hailong , Li Shengnan , Miao Yueyue , Wang Wenquan , Zhu Nannan , Jiang Xiancai , Chen Yongming , Fu Jun
Published: February 2023

Thermochromic smart windows are widely developed to modulate building energy exchange to save building energy consumption. However, most smart windows have fixed working temperatures, moderate energy‐saving efficiency, and are not suitable for diverse (cold and hot) climates. Here smart windows with strong temperature modulation over a broad range of hydrogels with adjustable transition temperatures for all‐weather building temperature regulation in different climates are reported. Thermochromic poly(N‐isopropylacrylamide‐co‐N, N‐dimethylacrylamide) hydrogels, with lower critical transition temperatures ranging from 32.5 to 43.5 °C, are developed for smart windows with solar modulation up to 88.84% and intrinsic transmittance up to 91.30% over full spectrum without energy input. Simulated indoor investigations are performed in different cities from 23 °N to 39 °N from winter to summer. The results indicate that smart windows have a strong solar modulation in summer to reduce indoor temperature up to 7.3 °C and efficient heat conservation in winter to save energy up to 4.30 J m−3, in comparison to glass windows. Smart windows with grid patterns and Chinese kirigami are fabricated by using 3D printing of the hydrogels to achieve both solar modulation and light incidence. The strategy offers an innovative path for thermochromic smart windows for low carbon economy.
Activating Co(OH)2 Active Sites by Coupled with V2O5 to Boost Highly Efficient Oxygen Evolution Reaction
Authors: Tang Jing , Ruan Qingdong , Yu Hongmin , Huang Chao
Published: February 2023

Electrocatalytic water splitting generated oxygen (O2) and hydrogen (H2) is a promising way to solve the energy crisis. Oxygen evolution reaction (OER) compared to hydrogen evolution reaction (HER) has slow kinetics hindering overall process. Recently, cobalt hydroxide (Co(OH)2) with high activity and stability for OER has attracted more attention. During the OER process, the Co2+ in Co(OH)2 is further oxidized to Co3+ and CoOOH species are true active sites. However, the low conductivity of Co(OH)2 hinders its oxidization to CoOOH. In addition, spontaneous growth of Co(OH)2 agglomerates easily during hydrothermal treatment, leading to decreased active sites. Herein, an efficient strategy is developed to construct highly dispersive Co(OH)2 nanosheets vertically grown on V2O5 nanoflowers (Co(OH)2/V2O5) at room temperature. The V5+ of V2O5 can oxidize Co2+ of Co(OH)2 into Co3+, resulting in in situ formations of CoOOH species favorable to the OER process. In situ Raman also investigates that the OH‐ species are inserted more easily into the interlayer of Co(OH)2 of (Co(OH)2/V2O5) than that of pure Co(OH)2. Therefore, the hybrid Co(OH)2/V2O5 exhibits low overpotentials of 320 and 370 mV at a current density of 10 and 50 mV cm‐2, respectively, and a small Tafel slope of 68 mV dec‐1.
The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency
Authors: Lin Bruce , Hung Andrew , Singleton William , Darmawan Kevion K. , Moses Rachael , Yao Bicheng , Wu Hongkang , Barlow Anders , Sani Marc‐Antoine , Sloan Alastair J. , Hossain Mohammed Akhter , Wade John D. , Hong Yuning , O'Brien‐Simpson Neil M. , Li Wenyi
Published: February 2023

Antimicrobial peptides (AMPs) are potentially powerful alternatives to conventional antibiotics in combating multidrug resistance, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures, resulting in permeability and destruction of target microorganism membranes. Our earlier work showed that two leading AMPs, MSI‐78 (4–20) and pardaxin (1–22), had potent antimicrobial activity against a range of bacteria. It is known that the attachment of moderate‐length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer, inducing membrane curvature, destabilization, and potential leakage. Thus, in this work, we aimed to investigate the antimicrobial activity, oligomerization propensity, and lipid‐membrane binding interactions of a range of N‐terminal lipidated analogs of MSI‐78 (4–20) and pardaxin (1–22). Molecular modeling results suggest that aggregation of the N‐lipidated AMPs may impart greater structural stability to the peptides in solution and a greater depth of lipid bilayer insertion for the N‐lipidated AMPs over the parental peptide. Our experimental and computational findings provide insights into how N‐terminal lipidation of AMPs may alter their conformations, with subsequent effects on their functional properties in regard to their self‐aggregation behavior, membrane interactions, and antimicrobial activity.
Diagnosis of TBC1D32‐associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy
Authors: Harris Sarah C. , Chong Karen , Chitayat David , Gilmore Kelly L. , Jorge Alexander A. L. , Freire Bruna L. , Lerario Antonio , Shannon Patrick , Cope Heidi , Gallentine William B. , Le Guyader Gwenal , Bilan Frederic , Létard Pascaline , Davis Erica E. , Vora Neeta L.
Published: February 2023

Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher™). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life‐limiting congenital anomalies.
Protein disulfide isomerases as CSF biomarkers for the neuronal response to tau pathology
Authors: Wolzak Kimberly , Vermunt Lisa , Campo Marta del , Jorge‐Oliva Marta , van Ziel Anna Maria , Li Ka Wan , Smit August B. , Chen‐Ploktkin Alice , Irwin David J. , Lemstra Afina W. , Pijnenburg Yolande , van der Flier Wiesje , Zetterberg Henrik , Gobom Johan , Blennow Kaj , Visser Pieter Jelle , Teunissen Charlotte E. , Tijms Betty M. , Scheper Wiep
Published: February 2023

INTRODUCTION

Cerebrospinal fluid (CSF) biomarkers for specific cellular disease processes are lacking for tauopathies. In this translational study we aimed to identify CSF biomarkers reflecting early tau pathology‐associated unfolded protein response (UPR) activation.

METHODS

We employed mass spectrometry proteomics and targeted immunoanalysis in a combination of biomarker discovery in primary mouse neurons in vitro and validation in patient CSF from two independent large multicentre cohorts (EMIF‐AD MBD, n = 310; PRIDE, n = 771).

RESULTS

First, we identify members of the protein disulfide isomerase (PDI) family in the neuronal UPR‐activated secretome and validate secretion upon tau aggregation in vitro. Next, we demonstrate that PDIA1 and PDIA3 levels correlate with total‐ and phosphorylated‐tau levels in CSF. PDIA1 levels are increased in CSF from AD patients compared to controls and patients with tau‐unrelated frontotemporal and Lewy body dementia (LBD).

Highlights

Neuronal unfolded protein response (UPR) activation induces the secretion of protein disulfide isomerases (PDIs) in vitro.

PDIA1 is secreted upon tau aggregation in neurons in vitro.

PDIA1 and PDIA3 levels correlate with total and phosphorylated tau levels in CSF.

PDIA1 levels are increased in CSF from Alzheimer's disease (AD) patients compared to controls.

PDIA1 levels are not increased in CSF from tau‐unrelated frontotemporal dementia (FTD) and Lewy body dementia (LBD) patients.
Nickel‐Catalyzed Unsymmetrical Bis‐Allylation of Alkynes
Authors: Li Ying , Zhang Wei‐Song , Yang Sa‐Na , Wang Xiao‐Yu , Liu Yan , Ji Ding‐Wei , Chen Qing‐An
Published: February 2023

The catalytic bis‐allylation of alkynes is an important but challenging protocol to construct all‐carbon tetra‐substituted alkenes. Particularly, the catalytic unsymmetrical bis‐allylation of alkynes remains as an underexplored task to date. We herein report an unprecedented unsymmetrical bis‐allylation by simultaneously utilizing electrophilic trifluoromethyl alkene and nucleophilic allylboronate as the allylic reagents. With the aid of robust Ni0/NHC catalysis, valuable skipped trienes can be obtained in high regio‐ and stereo‐selectivities under mild conditions. Mechanistic studies indicate that the reaction may proceed through a β‐fluorine elimination of a nickelacycle followed by a transmetalation step with allylboronate. The present method exhibits a good tolerance of various functional groups. Besides, the skipped triene products can undergo an array of elaborate transformations, which highlights the potential applications of this strategy.
Fucose Migration Pathways Identified Using Infrared Spectroscopy**
Authors: Moge Baptiste , Schindler Baptiste , Yeni Oznur , Compagnon Isabelle
Published: February 2023

Fucose is a ubiquitous monosaccharide associated to major classes of glycans. A main obstacle to the sequencing of fucosylated glycans is the migration of fucose, which leads to misinterpretations in mass spectrometry analysis. Here, using ion vibrational spectroscopy, we resolve the structure of fucosylated fragments of Lewis and blood group H antigen trisaccharides and we unveil the position and linkage of the fucose after migration. Our findings demonstrate that the structure of fragment ions resulting from fucose migration can be characterized. Additionally, we report a new type of fucose migration, which does not feature any change of mass and therefore had not been previously reported: it consists of a local migration where the fucose changes its position remaining on the initial residue. Our approach allows the characterization of glycans, an essential step to interpret glycomics data, as well as to understand underlying processes at play in mass spectrometry.
Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy
Authors: Cho Wansang , Won Solchan , Choi Yoona , Yi Sihyeong , Park Jong Beom , Park Jun‐Gyu , Kim Caroline E. , Narayana Chintam , Kim Ju Hee , Yim Junhyeong , Choi Young Il , Lee Dong‐Sup , Park Seung Bum
Published: February 2023

Modulating target proteins via the ubiquitin‐proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein‐protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING‐TRIM29 E3 ligase interaction, thus blocking TRIM29‐induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti‐PD‐1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno‐oncology.
The Regioselective Solid‐State Photo‐Mechanochemical Synthesis of Nanographenes with UV light
Authors: Baier Daniel M. , Spula Carolina , Fanenstich Stephen , Grätz Sven , Borchardt Lars
Published: February 2023

Photochemical reactors inherently suffer from the low penetration depth of light and therefore rely on high dilutions to enable chemical reactions. Here we present the first method of UV (ultraviolet) photochemistry in the complete absence of bulk solvents in a ball mill. Triphenylene was synthesized by two routes, the Mallory reaction and the cyclodehydrochlorination (CDHC), resulting in yields of 81 and 92 %, respectively. The reaction was successfully scaled up to the gram scale and the robustness of the method was demonstrated for several different substrates. Finally, the regioselective assembly of nanographenes by mechanochemistry was demonstrated for larger systems. Thus, the mechanochemical approach presented here provides a powerful new tool for the atomically precise construction of nanographenes.
Laparoscopic Hiatal Hernia Repair With Concomitant Transoral Incisionless Fundoplication
Authors: Pype DeAnn L.
Published: February 2023

Patients with gastroesophageal reflux disease and a large hiatal hernia can have life‐disrupting symptoms, such as heartburn, regurgitation, cough, and hoarseness. Gastroesophageal reflux disease symptoms are often treated with proton pump inhibitors and occasionally treated with surgery. The last decade has seen the development of a new procedure—laparoscopic hiatal hernia repair with concomitant transoral incisionless fundoplication. When transoral incisionless fundoplication is performed immediately after a laparoscopic hiatal hernia repair, it may enable the discontinuation of proton pump inhibitors and improve a patient's quality of life. This article explores the development of the transoral incisionless fundoplication procedure as well as its concomitant use after hiatal hernia repair at all stages of perioperative care. Also included is a hypothetical case study that illustrates the perioperative nursing care of a patient undergoing this procedure.
Clinical Issues — March 2023
Authors: Wright Renae
Published: February 2023

THIS MONTH

Conversion to an open procedure

Key words: laparoscopic procedure, open procedure, emergent conversion, open procedure cart, preoperative briefing.

Excess absorption of fluid distension media

Key words: fluid distension media, arthroscopy, transurethral resection (TUR) syndrome, fluid extravasation, fluid intravasation.

Hysteroscopic fluid deficit thresholds

Key words: maximum fluid deficit, hysteroscopy, hypotonic solution, isotonic solution, distension media.

Alternative insufflation gases

Key words: carbon dioxide (CO2), nitrous oxide (N2O), insufflation, gas distension media, pneumoperitoneum.
Synergistic behavior of dual filler system (n‐Si3N4/COOH‐MWCNT) on the mechanical, tribological, curing, and corrosion characteristics of epoxy hybrid nanocomposites
Authors: Bhagavatula Sai Gopal Krishna , Painkal Sarath Kumar , Nanoth Rasana , Murugasamy Kannan , Karingamanna Jayanarayanan
Published: February 2023

Epoxy hybrid nanocomposites reinforced with silicon nitride nanoparticles (SiN) and carboxylic acid‐modified multiwalled carbon nanotubes (COOH‐MWCNT) were prepared by hand layup. These hybrid nanocomposites have not undergone thorough investigation in the fields of mechanical, tribological, and corrosion‐resistant characteristics. The 0.25/0.5 SiN/MWCNT hybrid nanocomposite displayed improvement in elongation by 190% and fracture toughness by 360%. The effect of dual filler system on the wear and friction properties of the composite was investigated. The influence of silicon nitride and hybrid fillers the curing characteristics of epoxy was examined using Fourier transform infrared spectroscopy (FTIR). From differential scanning calorimetry (DSC), it was found that the use of dual fillers in the epoxy system reduced the residual heat of reaction and curing time by 15%. In a highly corrosive environment (3.5% NaCl), TAFEL polarization showed that 0.5/0.5 SiN/MWCNT epoxy hybrid coating on mild steel (MS) increased protection against corrosion by 30%. The dispersion of nanofillers and their interactions were verified using high‐resolution transmission electron microscopy (HR‐TEM). The morphology of the fracture, wear, and corroded surfaces were examined by field emission scanning electron microscopy (FE‐SEM). SiN manifested a synergistic effect with MWCNTs making it a superior reinforcement at very low content.
Tumor‐derived insulin‐like growth factor‐binding protein‐1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors
Authors: Suzuki Hiroyuki , Iwamoto Hideki , Seki Takahiro , Nakamura Toru , Masuda Atsutaka , Sakaue Takahiko , Tanaka Toshimitsu , Imamura Yasuko , Niizeki Takashi , Nakano Masahito , Shimose Shigeo , Shirono Tomotake , Noda Yu , Kamachi Naoki , Sakai Miwa , Morita Kazutoyo , Nakayama Masamichi , Yoshizumi Tomoharu , Kuromatsu Ryoko , Yano Hirohisa , Cao Yihai , Koga Hironori , Torimura Takuji
Published: February 2023

Background

Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC.

Methods

We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients. We evaluated the prognosis, therapeutic response, and serum insulin‐like growth factor‐binding protein‐1 (IGFBP‐1) levels of 31 lenvatinib‐treated HCC patients. Based on the array of results, a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted. Additionally, in vivo genetic and pharmacological gain‐ and loss‐of‐function experiments were performed.

Results

In the patient cohort, IGFBP‐1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival. Mechanistically, antiangiogenic TKI treatment markedly elevated tumor IGFBP‐1 levels via the hypoxia‐hypoxia inducible factor signaling. IGFBP‐1 stimulated angiogenesis through activation of the integrin α5β1‐focal adhesion kinase pathway. Consequently, loss of IGFBP‐1 and integrin α5β1 by genetic and pharmacological approaches re‐sensitized HCC to lenvatinib treatment.

Conclusions

Together, our data shed light on mechanisms underlying acquired resistance of HCC to antiangiogenic TKIs. Antiangiogenic TKIs induced an increase of tumor IGFBP‐1, which promoted angiogenesis through activating the IGFBP‐1‐integrin α5β1 pathway. These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP‐1 inhibitors.
USQA: A User Story Quality Analyzer prototype for supporting software engineering students
Authors: Jiménez Samantha , Alanis Arnulfo , Beltrán Claudio , Juárez‐Ramírez Reyes , Ramírez‐Noriega Alan , Tona Claudia
Published: February 2023

The Standish Group Reports 83.9% of IT Projects fail, and one of the top factors in failed projects is the incomplete requirements or user stories. Therefore, it is essential to teach undergraduate students from computer science degree programs how to create complete user stories. Computer science programs include some subjects or topics involving requirements or user stories collection and writing, such as Requirements Engineering, Software Engineering, Project Management, or Quality Software Assurance. For that reason, we designed a web application called User Story Quality Analyzer (USQA) that uses Natural Language Processing modules to detect errors regarding aspects of usefulness, completeness, and polysemes in the user stories creation. The tool was proved from three perspectives: (1) a reliability test, where 35 user stories developed by experts were tested in the app to prove the prototype's reliability; (2) usability and utility analysis; 48 students interacted with the tool and responded a Satisfaction Usability Scale and an open‐ended question, the students reported a high usability score; (3) finally, error classification, we gathered 159 user stories processed by the system, and we classified the students' common errors considering incompleteness and polysemes. After the evaluations, we concluded that USQA could evaluate the user stories as an expert, which could help the professors/teachers/instructors in their courses by providing feedback to the students when they are writing user stories.
Recent advances in immunotherapy for lung cancer
Authors: Wang Qi , Su Chunxia , Zhou Caicun
Published: February 2023

Lung cancer is the malignant tumor with the highest morbidity and mortality in China, and nonsmall cell lung cancer is a common form of lung cancer. After undergoing chemotherapy and molecular targeted therapy, the treatment of lung cancer has now fully entered the era of immunotherapy. Immunotherapy‐based treatment has become one of the standard treatments for lung cancer. Immunotherapy has also gradually moved from the back line to the front line, from advanced to early patients. This article focuses on the latest developments in perioperative and advanced lung cancer immunotherapy, discusses the problems and challenges at the current stage, and explores new directions for future development.
The impact of peroxisome proliferator‐activated receptor‐γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy
Authors: Chiang Cho‐Han , Chang Yu‐Cheng , Wang Shih‐Syuan , Chen Yuan‐Jen , See Xin Ya , Peng Chun‐Yu , Hsia Yuan Ping , Chiang Cho‐Hsien , Chiang Cho‐Hung , Peng Cheng‐Ming
Published: February 2023

Background

Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte‐mediated antitumor activity.

Methods

We conducted a retrospective cohort study to investigate the impact of PPAR‐γ‐activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers.

Results

A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non‐PPAR‐γ‐ARB users (n = 102), PPAR‐γ‐ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0—not reached] vs. 18.6 [IQR, 6.1–38.6] months) and progression‐free survival (17.3 [IQR, 5.1—not reached] vs. 8.2 [IQR, 2.4–18.6] months). In Cox regression analysis, the use of PPAR‐γ‐activating ARBs had an approximately 50% reduction in all‐cause mortality and disease progression. Patients who received PPAR‐γ‐activating ARBs also had higher clinical benefit rates than non‐PPAR‐γ‐ARB users (82% vs. 61%, p = 0.005).

Conclusion

The use of ARBs with PPAR‐γ‐activating property is linked with better survival among patients receiving ICIs.
Framing, risk perception and social health campaigns: A neuroscientific analysis
Authors: Fernandez‐Lores Susana , Crespo‐Tejero Natividad , Fernández‐Hernández Ruth , García‐Muiña Fernando E.
Published: February 2023

Health authorities have widely used social health campaigns to improve the attitudes and healthy behaviours of the population. During the COVID‐19 pandemic, they became an essential tool in increasing compliance with health measures, especially among the young population, a particularly reluctant group. The aim of this study was to analyse the effectiveness of different campaigns in improving young people's intention to change their behaviour towards compliance with health measures. For this purpose, an experimental study was conducted using neurophysiological tools (electroencephalogram and galvanic skin response) as well as self‐reported data from a questionnaire. The experiment analysed three health campaigns with different narrative frames and emotions in the messages. The results showed different degrees of persuasive effectiveness depending on the framing, emotions used, and level of intensity of such emotions. Overall, it was concluded that negative framing strategies and high levels of intensity worked effectively. The influence of the perceived risk declared by the participants on the impact of the different campaigns was also analysed. In this case, for the most difficult target to activate, subjects with low perceived risk, negative and low‐intensity framing strategies were revealed to be the most effective. Implications for the design of campaigns were derived, and limitations and future lines of research were addressed.
Strategies for Synthesizing and Enhancing the Immune Response of Cancer Vaccines Based on MUC1 Glycopeptide Antigens
Authors: Yin Lixin , Zhou Yang , Hong Sheng , Ding Feiqing , Cai Hui
Published: February 2023

Cancer vaccines are based on a vaccinology strategy whereby the patient's immune system is harnessed to induce a specific immune response to kill cancer cells and comprises two categories: prophylactic and therapeutic. Glycoprotein mucin 1 (MUC1), which is overexpressed and poorly glycosylated on cancer cells, is one of the most promising candidates for the development of new cancer vaccines. However, it should be noted that mucin‐like glycopeptides are poorly immunogenic and unable to elicit effective and long‐lasting immune responses. Therefore, MUC1‐derived tumor antigens need to be conjugated with immune activators. This review focuses on the synthesis of MUC1 glycopeptides, provides an overview of recently advanced designs of vaccines based on MUC1, and compares the advantages and disadvantages of the various strategies devised to date.
Burkitt lymphoma presenting as cecum mass and spontaneous tumor lysis syndrome with hypercalcemia
Authors: Shafie Mahan , Shahmohamadi Elnaz , Ghasemi Hoomaan , Zarei Jalalabadi Narjes , Parsa Samaneh
Published: February 2023

Burkitt's lymphoma (BL) could be primarily presented with various symptoms. We reported a woman with abdominal pain and mass who later developed spontaneous TLS with hypercalcemia, and was diagnosed with BL. Clinicians should suspect BL in case of any abdominal mass, especially with an aggressive course, to avoid further complications.
Copper‐Catalyzed Oxidative [1+2+1+2] Cascade Cyclization of N,N‐Dimethyl Enaminones with Benzylamines: A Facile Access to Functionalized 1,4‐Dihydropyridines
Authors: Sun Yulin , Chai Zhangmengjie , Liu Donghan , Zhang Mingshuai , Chen Longkun , Liu Zhuoyuan , Wang Yongchao , Yu Fuchao
Published: February 2023

Using benzylamines as the C4 source of 1,4‐dihydropyridines (1,4‐DHPs), a Cu‐catalyzed oxidative [1+2+1+2] cascade cyclization for the synthesis of 1,4‐DHPs was firstly developed. A broad range of easily available N,N‐dimethyl enaminones and benzylamines are employed smoothly to provide a diverse range of 1,4‐DHPs with high efficiency. This method is performed by a one‐pot cascade C(sp3)−H bond functionalization/C(sp3)−N cleavage/cyclization strategy to form simultaneously two C(sp3)−C(sp2) bonds, two C(sp2)−N bonds, and a 1,4‐DHP ring.
Single‐Molecule Measurement of Carbonic Anhydrase in Cation Coordinated Environment Using MspA Nanopore†
Authors: Song Dandan , Wang Yunjiao , Zhang Shaoxia , Zhao Lingyu , Gong Linyu , Liang Liyuan , Wang Liang
Published: February 2023

Comprehensive Summary

Carbonic anhydrase accounts for catalytic reaction of CO2/HCO3– transformation, thus resulting in neutralization and acidification of the cellular environment, thereby favoring tumor development. Hence, it is a classical protein model of greatly biocatalytic significance as well as a highly expressed biomarker with renal tumor. We herein proposed a single‐molecule measurement on carbonic anhydrase using MspA nanopore, in [BMIM+] and asymmetric K+/Ca2+ cationic coordinated environment, instead of usual symmetric KCl/NaCl electrolyte. Significantly, our empirical analysis showed that asymmetric K+/Ca2+ cationic environment contributes to distinguishable current modulations, thus yielding better resolution for carbonic anhydrase measurement, which is independent of applied voltage and more importantly, is stable enough at varied pH conditions and for very low concentration test in urine sample. Our results provide a classical model for nanopore protein analysis, and may also permit biocatalytic measurement at single‐molecule level.
A cloud database route scheduling method using a hybrid optimization algorithm
Authors: Shokri Baghi Zahra , Jafari Navimipour Nima
Published: February 2023

Cloud computing has appeared as a technology allowing a company to employ computing resources such as applications, software, and hardware to calculate over the Internet. Scholars have paid great attention to cloud computing because of its cutting‐edge availability, cost decrement, and boundless applications. A cloud database is a data storage site on the web where the optimal path is spotted to access the needed database. So, placing the ideal path to a database is crucial. The cloud database defined the scheduling problem to choose the perfect route. Cloud database path scheduling is a multifaceted procedure consisting of congestion control, routing list, and network flow distribution. It has a postponement in searching for the needed source route from the cloud database. Offering numerous infinite resources with the growing database workload is an NP‐Hard optimization problem where the query request needs optimal schedules to respond to the required services. So, we have used a hybrid cuckoo search (CS) and genetic algorithm (GA), motivated by a social bird's phenomenon, to solve this problem. Integrating genetic operators has dramatically enhanced the balance between the capability of searching and utilization.
Transcriptomic thermal plasticity underlying gonadal development in a turtle with ZZ/ZW sex chromosomes despite canalized genotypic sex determination
Authors: Gessler Thea B. , Wu Zhiqiang , Valenzuela Nicole
Published: February 2023

Understanding genome‐wide responses to environmental conditions during embryogenesis is essential for discerning the evolution of developmental plasticity and canalization, two processes generating phenotypic variation targeted by natural selection. Here, we present the first comparative trajectory analysis of matched transcriptomic developmental time series from two reptiles incubated under identical conditions, a turtle with a ZZ/ZW system of genotypic sex determination (GSD), Apalone spinifera, and a turtle with temperature‐dependent sex determination (TSD), Chrysemys picta. Results from our genome‐wide, hypervariate gene expression analysis of sexed embryos across five developmental stages revealed that substantial transcriptional plasticity in the developing gonads can persist for >145 Myr, long after the canalization of sex determination via the evolution of sex chromosomes, while some gene‐specific thermal sensitivity drifts or evolves anew. Such standing thermosensitivity represents an underappreciated evolutionary potential harbored by GSD species that may be co‐opted during future adaptive shifts in developmental programing, such as a GSD to TSD reversal, if favored by ecological conditions. Additionally, we identified novel candidate regulators of vertebrate sexual development in GSD reptiles, including sex‐determining candidate genes in a ZZ/ZW turtle.
Latitudinal variation and plasticity in response to temperature in Geukensia demissa
Authors: Erlenbach Theresa R. , Wares John P.
Published: February 2023

As global temperatures warm, species must adapt to a changing climate or transition to a different location suitable for their survival. Understanding the extent to which species are able to do so, particularly keystone species, is imperative to ensuring the survival of key ecosystems. The ribbed mussel Geukensia demissa is an integral part of salt marshes along the Atlantic coast of North America. Spatial patterns of genomic and phenotypic divergence have been previously documented, although their link with coastal environmental variation is unknown. Here, we study how populations of G. demissa in the northern (Massachusetts) and southern (Georgia) portions of the species range respond to changes in temperature. We combine assays of variation in oxygen consumption and RNA transcriptomic data with genomic divergence analyses to identify how separate populations of G. demissa may vary in distinct thermal environments. Our results show differences in constitutive oxygen consumption between mussels from Georgia and Massachusetts, as well as shared and disparate patterns of gene expression across temperature profiles. We also find that metabolic genes seem to be a strong component of divergence between these two populations. Our analysis highlights the importance of studying integrative patterns of genomic and phenotypic variation in species that are key for particular ecosystems, and how they might respond to further changes in climate.
The interaction between physical frailty and prognostic impact of heart failure medication in elderly patients
Authors: Abe Takuro , Jujo Kentaro , Maeda Daichi , Saito Katsumi , Ogasahara Yuki , Saito Kazuya , Saito Hiroshi , Iwata Kentaro , Konishi Masaaki , Kitai Takeshi , Kasai Takatoshi , Wada Hiroshi , Momomura Shin‐ichi , Kagiyama Nobuyuki , Kamiya Kentaro , Yamashita Masashi , Hamazaki Nobuaki , Nozaki Kohei , Maekawa Emi , Ako Junya , Matsue Yuya
Published: February 2023

Aims

Frailty is highly prevalent and associated with poor prognoses in elderly patients with heart failure (HF). However, the potential effects of physical frailty on the benefits of HF medications in elderly patients with HF are unclear. We aimed to determine the influence of physical frailty on the prognosis of HF medications in elderly patients with HF with reduced and mildly reduced ejection fraction (HFr/mrEF).

Methods and results

From the combined HF database of the FRAGILE‐HF and Kitasato cohorts, hospitalized HF patients with a left ventricular ejection fraction < 50% and age ≥ 65 years were analysed. Patients treated with or without renin‐angiotensin‐aldosterone system inhibitors (RAASi) and beta‐blockers at discharge were compared. Physical frailty was defined by the presence of ≥3 items on the Japanese version of the Cardiovascular Health Study criteria. The primary endpoint was all‐cause mortality rate. Among the 1021 enrolled patients, 604 patients (59%) received both RAASi and beta‐blockers, and 604 patients (59%) were diagnosed as physically frail. Patients receiving both RAASi and beta‐blockers showed a significantly lower 1 year mortality than those not receiving either, even after adjusting for covariates (hazard ratio: 0.50, 95% confidence interval: 0.34–0.75). This beneficial effect of both medications on 1 year mortality was comparable between patients with and without physical frailty (hazard ratio: 0.53 and 0.51, respectively; P for interaction = 0.77).

Conclusions

The presence of physical frailty did not interact with the beneficial prognostic impact of RAASi and beta‐blocker combination therapy in elderly patients with HFr/mrEF.
Association between serum albumin and outcomes in heart failure and secondary mitral regurgitation: the COAPT trial
Authors: Feng Kent Y. , Ambrosy Andrew P. , Zhou Zhipeng , Li Ditian , Kong Jeremy , Zaroff Jonathan G. , Mishell Jacob M. , Ku Ivy A. , Scotti Andrea , Coisne Augustin , Redfors Björn , Mack Michael J. , Abraham William T. , Lindenfeld JoAnn , Stone Gregg W. ,   COAPT Trial Investigators
Published: February 2023

Aims

Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR) has not been described.

Methods and results

The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge‐to‐edge repair (TEER) with the MitraClipTM plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate‐to‐severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7–4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4‐year rates of all‐cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02–1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all‐cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (pinteraction = 0.19 and 0.35 for death and HFH, respectively).

Conclusion

Low baseline serum albumin levels were independently associated with reduced 4‐year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level.
Enantioselective Desymmetrization of Curcumins with 3‐Olefinic Oxindoles for the Synthesis of Spirocyclohexanoneoxindoles
Authors: Siva Sankara Chenikkayala , Bhagat Shweta , Chandra Ajeet , Namboothiri Irishi N. N.
Published: February 2023

An enantioselective desymmetrization of curcumins with 3‐olefinic oxindoles involving a cascade double‐Michael addition strategy provides direct access to spirocyclohexanone‐oxindoles with complete regio‐ and diastereoselectivities and excellent enantioselectivities, besides good to excellent yields. The products possess three contiguous chiral centers and multiple reactive functionalities. The observed selectivities were rationalized by transitions state energy calculations at B3LYP//6‐31g(d) level of DFT.