bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐occurrence of CDKN2A/B and IFN‐I homozygous deletions correlates with an immunosuppressive phenotype and poor prognosis in lung adenocarcinoma
Authors: Peng Yuan , Chen Yonghong , Song Mengmeng , Zhang Xiaoyue , Li Pansong , Yu Xian , Huang Yusheng , Zhang Ni , Ji Liyan , Xia Lei , Xia Xuefeng , Yi Xin , Tan Benxu , Yang Zhenzhou
Published: March 2022

Homozygous deletion (HD) of CDKN2A and CDKN2B (CDKN2A/BHD) is the most frequent copy‐number variation (CNV) in lung adenocarcinoma (LUAD). CDKN2A/BHD has been associated with poor outcomes in LUAD; however, the mechanisms of its prognostic effect remain unknown. We analyzed genome, transcriptome, and clinical data from 517 patients with LUAD from the Cancer Genome Atlas (TCGA) and from 788 primary LUAD tumor and matched control samples from the MSK‐IMPACT clinical cohort. CDKN2A/BHD was present in 19.1% of the TCGA‐LUAD cohort and in 5.7% of the MSK‐IMPACT cohort. CDKN2A/BHD patients had shorter disease‐free survival and overall survival compared with CDKN2A/BWT individuals in both cohorts. Differences in clinical features did not influence the outcomes in the CDKN2A/BHD population. Mutation analyses showed that overall tumor mutational burden and mutations in classical drivers such as EGFR and RB1 were not associated with CDKN2A/BHD. In contrast, homozygous deletion of type I interferons (IFN‐IHD) frequently co‐occurred with CDKN2A/BHD. CDKN2A/B and IFN‐I are co‐located in the same p21.3 region of chromosome 9. The co‐occurrence of CDKN2A/BHD and IFN‐IHD was not related to whole‐genome doubling, chromosome instability, or aneuploidy. Patients with co‐occurring CDKN2A/BHD and IFN‐IHD had shorter disease‐free survival and overall survival compared with CDKN2A/BWT patients. CDKN2A/BHDIFN‐IHD had downregulated several key immune response pathways, suggesting that poor prognosis in CDKN2A/BHD LUAD could potentially be attributed to an immunosuppressive tumor microenvironment as a result of IFN‐I depletion.
The devil is not in the detail: Reply to Belli (2022)
Authors: Blank Hartmut , Skopicz‐Radkiewicz Ewa , Reddy Vasudevi
Published: March 2022

We welcome Belli's (Applied Cognitive Psychology, 2022, 36, 477) comments on our double misinformation research and the opportunity to discuss the involved processes. We agree that our studies do not rule out (some of) the interference mechanisms specified by Belli (Applied Cognitive Psychology, 2022, 36, 477)—because they were never designed for this purpose. Instead, the logic of our studies is at a molar level, potentially involving different molecular‐level interference or non‐interference mechanisms. We concede that specific interference mechanisms may operate in specific circumstances but maintain that our new research approach—adding further contradictory misinformation on top of existing misinformation to reduce the misinformation effect—does pose a challenge for interference accounts in general.
Reduced Graphene Oxide/MXene Composite Foam with Multilayer Structure for Electromagnetic Interference Shielding and Heat Insulation Applications
Authors: Chen Qiguo , Zhang Kai , Huang Li , Li Yibin , Yuan Ye
Published: March 2022

The electromagnetic interference (EMI) shielding performance of reduced graphene oxide (rGO) foam is restricted to its poor conductivity and macro‐monotonic structure. In this work, highly conductive MXene nanosheets are introduced into graphene oxide (GO) solution and multilayer structures were designed to improve the EMI shielding performance of graphene foam. The multilayer rGO/MXene composite foam shows an excellent EMI shielding effectiveness of more than ≈28 dB in C and ≈35 dB in X band. Meanwhile, it reveals an outstanding heat insulation performance equaling to air (0.025 W m−1 K). The macro multilayer and microporous structure plays a prominent role in the EMI shielding and heat insulation performance. This work provides valuable ideas for designing multifunctional EMI shielding materials for the next generation of smart electronic devices.
Vertically Oriented MXene Bridging the Frequency Response and Capacity Density Gap for AC‐Filtering Pseudocapacitors
Authors: Wen Yeye , Chen Hongwu , Wu Mingmao , Li Chun
Published: March 2022

Electrochemical capacitors (ECs) with high‐rate characteristics demonstrate great promise for replacing bulky aluminum electrolytic capacitors with alternate current (AC)‐filtering functions. Currently, the performance of AC‐line filtering ECs is limited by the vast gap between the ionic transport kinetics and capacity density of electrode materials. Herein, vertically oriented MXene and reduced graphene oxide composite (VMG) electrodes are prepared by electrochemical co‐deposition to bridge the performance gap for AC‐line filtering ECs. Benefiting from the unique pseudocapacitive characteristic and vertically interconnected microstructure, the VMG‐based EC exhibits an outstanding areal capacitance of 1.14 mF cm−2 with a phase angle of −80° at 120 Hz. Moreover, by utilizing the advantages of MXene at negative potential, an asymmetric pseudocapacitor is constructed with an energy density up to 805 µF V2 cm−2 at 120 Hz, which can be further incorporated in portable and wearable devices with excellent environmental ripple filtering capability in diverse scenarios.
Porous Nanofiber Membrane: Rational Platform for Highly Sensitive Thermochromic Sensor
Authors: Kim Dong‐Ha , Bae Jaehyeong , Lee Jiyoung , Ahn Jaewan , Hwang Won‐Tae , Ko Jaehyun , Kim Il‐Doo
Published: March 2022

Thermochromic sensors provide an intuitive and real‐time solution for monitoring the local temperature with naked eyes. Conventional thermochromic sensors often utilize either solution‐type or dense film‐type platforms, which are suboptimal morphologies for exposing a large number of dye molecules to the surface, leading to low sensitivity and sluggish responding speeds. Herein, this article introduces rational synthetic routes to fabricate highly sensitive nanofiber (NF) sensor membranes loaded with thermochromic dyes (C3H6N6·CH2O)x‐loaded nanofibers (NFs) sensor membranes by alignment‐controllable electrospinning techniques (x–y perpendicular and rotary). The NF‐based porous sensor membranes exhibit two‐ to fivefold improved thermochromic sensitivity (ΔRGB) compared to those of dense film‐type sensors at 31.6–42.7 °C. This is attributed to the uniform distribution of dyes throughout the porous NF structure (≈95.7%), which exhibits excellent light transmittance that is 10–30‐fold higher than that of film‐type sensors. Based on the available shape‐conforming synthetic strategies, this article further demonstrates wearable thermochromic sensors in the forms of mask‐, patch‐, and bracelet‐type devices, which can accurately monitor body temperature in real time.
Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth
Authors: Fan Lei , Liu Can , Chen Xiuxing , Zheng Lei , Zou Yan , Wen Huiquan , Guan Pengfei , Lu Fang , Luo Yian , Tan Guoxin , Yu Peng , Chen Dafu , Deng Chunlin , Sun Yongjian , Zhou Lei , Ning Chengyun
Published: March 2022

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair.
Ferroelectric Engineered Electrode‐Composite Polymer Electrolyte Interfaces for All‐Solid‐State Sodium Metal Battery
Authors: Wang Yumei , Wang Zhongting , Zheng Feng , Sun Jianguo , Oh Jin An Sam , Wu Tian , Chen Gongxuan , Huang Qing , Kotobuki Masashi , Zeng Kaiyang , Lu Li
Published: March 2022

To enhance the compatibility between the polymer‐based electrolytes and electrodes, and promote the interfacial ion conduction, a novel approach to engineer the interfaces between all‐solid‐state composite polymer electrolyte and electrodes using thin layers of ferroelectrics is introduced. The well‐designed and ferroelectric‐engineered composite polymer electrolyte demonstrates an attractive ionic conductivity of 7.9 × 10–5 S cm–1 at room temperature. Furthermore, the ferroelectric engineering is able to effectively suppress the growth of solid electrolyte interphase (SEI) at the interface between polymer electrolytes and Na metal electrodes, and it can also enhance the ion diffusion across the electrolyte‐ferroelectric‐cathode/anode interfaces. Notably, an extraordinarily high discharge capacity of 160.3 mAh g–1, with 97.4% in retention, is achieved in the ferroelectric‐engineered all‐solid‐state Na metal cell after 165 cycles at room temperature. Moreover, outstanding stability is demonstrated that a high discharge capacity retention of 86.0% is achieved over 180 full charge/discharge cycles, even though the cell has been aged for 2 months. This work provides new insights in enhancing the long‐cyclability and stability of solid‐state rechargeable batteries.
A de novo heterozygous HOXA11 variant in a patient with mesomelic dysplasia with urogenital abnormalities
Authors: Sezer Abdullah , Perçin Ferda Emriye , Kazan Hasan Huseyin , Kayhan Gulsum , Akturk Mujde
Published: March 2022

Mesomelic dysplasias are a genetically and clinically heterogeneous group of diseases with more than 10 types defined. This article presents an 18‐year‐old female patient with normal intelligence and a multisystem phenotype including disproportionate short stature, scoliosis, mesomelic limb shortening, radial bowing, short fourth to fifth metacarpals and metatarsals, fusions in the carpal/tarsal bones, operated pes equinovarus, primary amenorrhea, uterine hypoplasia, vesicoureteral reflux, and chronic kidney disease. Whole‐exome sequencing revealed a de novo heterozygous c.881T>G (p.Met294Arg) variant in HOXA11 (NM_005523.6) gene. The variant was located in the homeodomain of HOXA11 and predicted to alter DNA‐binding ability of the protein. In silico analyses indicated that the variant could promote the alterations in the protein–protein interaction. The possible functional effect of the variant was supposed as dominant‐negative. Hoxa11‐mutant mice have been reported to exhibit homeotic transformations in the thoracic and sacral vertebrae, zeugopodal phenotype in forelimb and hindlimb, and urogenital abnormalities. Although mice models were reported as mesomelic dysplasia and urogenital abnormalities (MDUGA), this phenotype has not yet been reported in humans. This was the first case with MDUGA putatively related to a de novo variant in HOXA11.
Recent Advances Towards the Synthesis of Dihydrobenzofurans and Dihydroisobenzofurans
Authors: Dapkekar Anil Balajirao , Sreenivasulu Chinnabattigalla , Ravi Kishore Dakoju , Satyanarayana Gedu
Published: March 2022

The 2,3‐dihydrobenzofuran heterocyclic systems are found in various biologically active natural and pharmaceutical products of biological relevance such as Phalarine, Rocaglamide, and Furaquinocin A. The interest in the study of 2,3‐dihydrobenzofurans is constantly increasing because of their numerous biological properties such as anti‐tumor, anti‐cancer, anti‐tubercular, and anti‐malarial activities. Different methods have been established towards the synthesis of 2,3‐dihydrobenzofurans involved via intra‐ and inter‐molecular reactions. Besides, the 1,3‐dihydroisobenzofuran structure has been identified as a fundamental nucleus in many natural products, bioactive compounds, and functional molecules (e. g., Pestacin, Isopestacin, Citalopram, Xylarinol B, Matriisobenzofuran, Thunberginol F7‐O‐β‐D‐glucopyranoside). On the other hand, 1,3‐disubstituted isobenzofurans are powerful structural motifs with a wide range of biological activities, like anti‐inflammatory, anti‐histaminic, and anti‐HIV. In the last few years, a decent number of diligent synthetic approaches have been demonstrated toward synthesizing 1,3‐disubstituted isobenzofurans. This review focuses on the effective synthetic routes developed to construct 2,3‐dihydrobenzofurans and 1,3‐dihydroisobenzofurans and their applications in recent years.
Human CASPR2 Antibodies Reversibly Alter Memory and the CASPR2 Protein Complex
Authors: Joubert Bastien , Petit‐Pedrol Mar , Planagumà Jesús , Mannara Francesco , Radosevic Marija , Marsal Maria , Maudes Estibaliz , García‐Serra Anna , Aguilar Esther , Andrés‐Bilbé Alba , Gasull Xavier , Loza‐Alvarez Pablo , Sabater Lidia , Rosenfeld Myrna R. , Dalmau Josep
Published: March 2022

Objective

The encephalitis associated with antibodies against contactin‐associated proteinlike 2 (CASPR2) is presumably antibody‐mediated, but the antibody effects and whether they cause behavioral alterations are not well known. Here, we used a mouse model of patients' immunoglobulin G (IgG) transfer and super‐resolution microscopy to demonstrate the antibody pathogenicity.

Methods

IgG from patients with anti‐CASPR2 encephalitis or healthy controls was infused into the cerebroventricular system of mice. The levels and colocalization of CASPR2 with transient axonal glycoprotein 1 (TAG1) were determined with stimulated emission depletion microscopy (40–70μm lateral resolution). Hippocampal clusters of Kv1.1 voltage‐gated potassium channels (VGKCs) and GluA1‐containing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs) were quantified with confocal microscopy. Behavioral alterations were assessed with standard behavioral paradigms. Cultured neurons were used to determine the levels of intracellular CASPR2 and TAG1 after exposure to patients' IgG.

Results

Infusion of patients' IgG, but not controls' IgG, caused memory impairment along with hippocampal reduction of surface CASPR2 clusters and decreased CASPR2/TAG1 colocalization. In cultured neurons, patients' IgG led to an increase of intracellular CASPR2 without affecting TAG1, suggesting selective CASPR2 internalization. Additionally, mice infused with patients' IgG showed decreased levels of Kv1.1 and GluA1 (two CASPR2‐regulated proteins). All these alterations and the memory deficit reverted to normal after removing patients' IgG.

Interpretation

IgG from patients with anti‐CASPR2 encephalitis causes reversible memory impairment, inhibits the interaction of CASPR2/TAG1, and decreases the levels of CASPR2 and related proteins (VGKC, AMPAR). These findings fulfill the postulates of antibody‐mediated disease and provide a biological basis for antibody‐removing treatment approaches. ANN NEUROL 2022;91:801–813
Cylindrical C96 Fullertubes: A Highly Active Metal‐Free O2‐Reduction Electrocatalyst
Authors: Sanad Mohamed Fathi , Franklin Hannah M. , Ali Basant A. , Puente Santiago Alain R. , Nair Aruna N. , Chava Venkata S. N. , Fernandez‐Delgado Olivia , Allam Nageh K. , Stevenson Steven , Sreenivasan Sreeprasad T. , Echegoyen Luis
Published: March 2022

A new isolation protocol was recently reported for highly purified metallic Fullertubes D5h‐C90, D3d‐C96, and D5d‐C100, which exhibit unique electronic features. Here, we report the oxygen reduction electrocatalytic behavior of C60, C70 (spheroidal fullerenes), and C90, C96, and C100 (tubular fullerenes) using a combination of experimental and theoretical approaches. C96 (a metal‐free catalyst) displayed remarkable oxygen reduction reaction (ORR) activity, with an onset potential of 0.85 V and a halfway potential of 0.75 V, which are close to the state‐of‐the‐art Pt/C benchmark catalyst values. We achieved an excellent power density of 0.75 W cm−2 using C96 as a modified cathode in a proton‐exchange membrane fuel cell, comparable to other recently reported efficient metal‐free catalysts. Combined band structure (experimentally calculated) and free‐energy (DFT) investigations show that both favorable energy‐level alignment active catalytic sites on the carbon cage are responsible for the superior activity of C96.
Microwave assisted synthesis of low band gap water soluble dyad materials using polythiophene carboxylic acids as donor and fullerenol as acceptor
Authors: Jaiswal Rimpa , Saha Uttam , Prasad N. Eswara , Goswami Thako Hari
Published: March 2022

A facile synthesis of low band gap water soluble dyad materials comprising of fullerenol and poly thiophene carboxylic acids is demonstrated. Fullerene‐conjugated polyelectrolytes dyad materials were prepared using polythiophene‐3‐acetic acid (PT3AA) and polythiophene‐3‐malonic acid (PT3MA) as donors and fullerenol as acceptor in microwave synthesizer at 70°C. The reaction has several advantages over conventional reflux methods; easy to handle, fast reaction and good quality products. Fullerene core star‐like dyad structures having single‐ or di‐carboxylic acid group in each thiophene ring were synthesized. Thermal methods (TGA & DSC) estimated about six to seven exohedrally attached polymer units to fullerene core. The electrochemical band gaps of ~1.17 and 1.21 eV were recorded for fullerenol poly thiophene 3‐acetic acid (FPT3AA) and fullerenol polythiophene‐3‐malonic acid (FPT3MA) dyads, respectively. The UV–vis analyses record a red shifting of absorbance maxima for mono carboxylic acid (408 nm FPT3AA vs. 263 nm PT3AA) and blue shifting in di‐carboxylic acid (263 nm FPT3MA vs. 396 nm PT3MA). The strong quenching and substantial red shifting of emission peaks of dyad materials compared to both fullerenol and polymers demonstrate charge transfer exciplex formation in excited state.
Accelerating gametophytic growth in the model hornwort Anthoceros agrestis
Authors: Gunadi Andika , Li Fay‐Wei , Van Eck Joyce
Published: March 2022

Premise

Hornworts belong to a unique lineage of bryophytes with critical traits for elucidating the evolution of land plants; however, the development of functional genetic tools for hornworts has been hampered by their relatively slow gametophytic growth.

Methods

To identify the external factors that influence the development of hornwort gametophytes and potentially augment their growth, we evaluated the contributions of several culture medium components on the axenic gametophytic growth of Anthoceros agrestis, a model hornwort. A streamlined growth assay utilizing semiautomated image analysis was developed to rapidly quantify and compare tissue development spanning four weeks of culture on solidified medium.

Results

The addition of sucrose, ammonium nitrate, activated charcoal, pH buffering, and growth regulators (2,4‐dichlorophenoxyacetic acid, 6‐benzylaminopurine, and thidiazuron) affected gametophyte tissue survival, growth patterns, and the rate of thalli growth. Subsequently, an optimized medium composition and growth regimen for accelerating A. agrestis gametophytic growth were formulated, which at four weeks of culture increased the tissue wet weight by 2.1‐ to 8.5‐fold compared with other previously utilized hornwort growth media.

Discussion

Our protocol for generating vigorous starting material and accelerated tissue regeneration is pertinent for advancing gene function characterization and genome editing in hornworts.
How artificial intelligence might change academic library work: Applying the competencies literature and the theory of the professions
Authors: Cox Andrew
Published: March 2022

The probable impact of artificial intelligence (AI) on work, including professional work, is contested, but it is unlikely to leave them untouched. The purpose of this conceptual paper is to consider the likelihood of the adoption of different approaches to AI in academic libraries. As theoretical lenses to guide the analysis the paper draws on both the library and information science (LIS) literature on librarians' competencies and the notions of jurisdiction and hybrid logics drawn from the sociological theory of the professions. The paper starts by outlining these theories and then reviews the nature of AI and the range of its potential uses in academic libraries. The main focus of the paper is on the application of AI to knowledge discovery. Eleven different potential approaches libraries might adopt to such AI applications are analyzed and their likelihood evaluated. Then it is considered how a range of internal and external factors might influence the adoption of AI. In addition to reflecting on the possible impact of AI on librarianship the paper contributes to understanding how to synthesize the competencies literature with the theory of the profession and presents a new understanding of librarians as hybrid.
Technische Herausforderungen bei der Planung von Spannbetonfertigteilträgern mit trockenen und geschliffenen Stoßfugen im Brückenbau
Authors: Behrmann Tilo , Fröhlich Manuel , Wenger Philipp , Hierl Martin
Published: March 2022

Am Frankfurter Flughafen wird derzeit ein drittes Terminal errichtet. Die Anbindung des Terminals 3 an den Hauptkomplex des Flughafens erfolgt durch ein neues, autonomes Passagiertransportsystem (PTS), welches auf einer Länge von ca. 2,5 km in Hochlage auf einem Brückenzug fahren wird. Für den Brückenzug sind u. a. neuartige, bis zu 40 m lange Tragwerke als vorgespannte Betonfertigteilträger vorgesehen. Die Besonderheit besteht hier in der Art der Fügung der Trägersegmente – die Segmente werden als Vollfertigteile mit geschliffenen, trockenen und unverzahnten Fugen im Werk hergestellt und mittels Vorspannung mit nachträglichem Verbund zusammengefügt. Im Gegensatz zu üblichen, verzahnten Fugen mit entsprechend formschlüssiger Querkraftübertragung wird der Kraftschluss bei den plangeschliffenen Fugen ausschließlich über die durch die Vorspannung erzeugte Reibung in der Stoßfuge erzeugt. Zwar gibt es zu geschliffenen, über Reibung lastabtragenden Fugen bereits Erkenntnisse und Erfahrungen (z. B. bei Windenergieanlagen), die Besonderheit beim PTS in Frankfurt besteht jedoch in der erstmaligen Anwendung dieses Konstruktionsprinzips im Brückenbau durch die Firma Max Bögl für einen hoch frequentierten Fahrweg mit entsprechend hohen ermüdungsrelevanten Beanspruchungen. Der vorliegende Beitrag befasst sich mit den Besonderheiten der Bemessung und Nachweisführung sowie den hohen Anforderungen an die geschliffene Fuge beim Herstellungsprozess.
Chemical constituents fromHibiscus hamaboand their antiphotoaging effects onUVA‐inducedCCD‐986sk
Authors: Park Gwee Kyo , Jang Wookju , Kim Bo Yun , Oh Kyung‐Eon , Kim You Ah. , Kwon Hyuk Joon , Kim Soo‐Young , Park Byoung Jun
Published: March 2022

To investigate the phytochemical constituents ofHibiscus hamabo, a chromatographic method was used. A new phenolic glucoside, woodorien A (1), along with 10 known compounds, rutin (2), isoquercetin (3), nicotiflorin (4), astragalin (5),trans‐tiliroside (6),N‐trans‐feruloyltyramine (7),N‐trans‐caffeoyltyramine (8), woodorien (9), quercetin 3′‐galactopyranoside (10), andcis‐tiliroside (11), was isolated. The structure of1was identified as ethyl 3‐O‐β‐d‐glucopyranosyl‐4‐hydroxybenzoate. Compounds8,9, and11were isolated from genusHibiscus, and2–7and10were isolated fromH. hamabofor the first time. Their chemical structures were determined through the interpretation of spectroscopic data. The properties of the UVA photoaging induction assay of all isolated compounds were measured. Compounds3,8, and10exhibited recovery from photoaging induced by UVA in CCD‐986sk. These results suggest thatH. hamabois a potential source of natural antiphotoaging ingredients and can be used in cosmetic applications.
Photoresponsive prodrug‐dye nanoassembly for in‐situ monitorable cancer therapy
Authors: Long Kaiqi , Wang Yifan , Lv Wen , Yang Yang , Xu Shuting , Zhan Changyou , Wang Weiping
Published: March 2022

Photocleavable prodrugs enable controllable drug delivery to target sites modulated by light irradiation. However, the in vivo utility is usually hindered by their insolubility and inefficient delivery. In this study, we report a simple strategy of co‐assembling boron‐dipyrromethene‐chlorambucil prodrug and near‐infrared dye IR783 to fabricate photoresponsive nanoassemblies, which achieved both high prodrug loading capacity (~99%) and efficient light‐triggered prodrug activation. The incorporated IR783 dye not only stabilized the nanoparticles and contributed tumor targeting as usual, but also exhibited degradation after light irradiation and in‐situ monitoring of nanoparticle dissociation by fluorescent imaging. Systemic administration of the nanoparticles and localized light irradiation at tumor sites enabled monitorable and efficient drug release in vivo. Our results demonstrate that such prodrug‐dye co‐assembled nanomedicine is a promising formulation for photoresponsive drug delivery, which would advance the translation of photoresponsive nanomedicines.
Isolation and molecular characterization of circulating extracellular vesicles from blood of chronic Chagas disease patients
Authors: Madeira Rafael P. , Meneghetti Paula , de Barros Lucas A. , de Cassia Buck Paula , Mady Charles , Ianni Barbara M. , Fernandez‐Becerra Carmen , Torrecilhas Ana C.
Published: March 2022

Extracellular vesicles (EVs) are lipid bilayer envelopes that encase several types of molecules. Their contents mostly reflect their cell origin and possible targets at other locations in the organism and can be modified in pathological conditions to interfere with intercellular communication, thus promoting disease establishment and development. These characteristics, in addition to their presence in virtually all body fluids, make such vesicles ideal for biomarker discovery in human diseases. Here, we describe the effect of different anticoagulants and the combination of two purification methods for isolation and characterization of circulating EVs from blood of chronic Chagas disease (CCD) patients. We illustrated this procedure by studying a population of patients with Chagas disease at the indeterminate chronic stage, in which the Trypanosoma cruzi is very scarce in circulation. EVs were harvested from blood collected without or with different anticoagulants. Protein and nanoparticle tracking analysis was used to measure EVs size and concentration. The EVs were purified by ultracentrifugation, followed by size‐exclusion chromatography and characterized by chemiluminescent enzyme‐linked immunosorbent assay and dot blot using antibodies that recognized parasite‐derived EVs, such as hyperimmune sera, polyclonal and monoclonal antibodies against trans‐sialidase and mucins. In parallel, antibodies against classical human EV markers CD9, CD63, CD81, and CD82, were also analyzed. The results showed that anticoagulants did not interfere with the analyzed parameters and circulating EVs from CCD patients contain T. cruzi antigens and classical human exosomal markers. Overall, our protocol is adequate for the isolation of the total circulating EVs and can serve as an important basis for further studies on biomarker discovery in Chagas' disease.
The Gore Cardioform Atrial Septal Defect Occluder: A novel solution to the management of severe hemolysis following transcatheter septal defect closure
Authors: Naimi Iman , Jones Thomas K. , Steinberg Zachary
Published: March 2022

Significant hemolysis is a recognized complication of transcatheter high‐velocity shunt occlusion using some Amplatzer devices. We describe a case of severe hemolysis following occlusion of an iatrogenic Gerbode defect with an Amplatzer muscular ventricular septal defect occluder successfully managed by transcatheter device removal and reocclusion with a Gore Cardioform Atrial Septal Defect Occluder.
Bronchogenic cyst of the posterior neck mimicking lymphatic malformation
Authors: Yee Addison , Navuluri Sriram , Sun Ravi , Lindsey Miki , Gonzalez‐Krellwitz Laura A , Strub Graham M
Published: March 2022

Bronchogenic cysts are embryologic malformations of the foregut and are rarely found head and neck region. Here we present a case of an upper scapular/lower posterior neck cystic mass which was initially suspicious for lymphatic malformation but confirmed by pathology to be an ectopic bronchogenic cyst.
Accidental ingestion of a dental bur in an 84‐year‐old male
Authors: Mulita Francesk , Panagiotopoulos Ioannis , Verras Georgios‐Ioannis , Liolis Elias , Tchabashvili Levan , Paraskevas Themistoklis , Iliopoulos Fotios , Bousis Dimitrios , Michailides Christos , Kaplanis Charalampos , Perdikaris Ioannis , Bouchagier Konstantinos , Filis Dimitrios , Velissaris Dimitrios
Published: March 2022

This report describes the case of an 84‐year‐old male who was brought to the emergency room because a dental bur was swallowed accidentally during a dental procedure. The foreign body was successfully removed by gastroenterologists endoscopically 8 days after the ingestion and was identified as a 2‐cm‐long dental bur.
Simulation of a Depropanizer Distillation Column and Validation of Results by Industrial Data
Authors: Ayazi Arvin , Babakhani Davoud , Soleymani Meysam
Published: March 2022

A depropanizer distillation column (DDC) that is widely used in oil refineries, was simulated by Aspen Plus using both equilibrium and non‐equilibrium models. The purpose of this simulation was selecting the most appropriate model to accurately predict the separation process in the DDC. Considering the temperature profile and mole fraction diagrams of the desired product (propane) in the distillation column, it was found that the equilibrium and non‐equilibrium models differ significantly in predicting the column behavior. Comparing the industrial data of the DDC with the results of the two mentioned approaches, it can be concluded that the non‐equilibrium model with the mass transfer coefficient from Chen and Chuang (1993) can simulate the DDC accurately.
Formation and Photoinduced Electron Transfer in Porphyrin‐ and Phthalocyanine‐Bearing N‐Doped Graphene Hybrids Synthesized by Click Chemistry
Authors: Arellano Luis M. , Gobeze Habtom B. , Jang Youngwoo , Barrejón Myriam , Parejo Concepción , Álvarez Julio C. , Gómez‐Escalonilla María J. , Sastre‐Santos Ángela , D'Souza Francis , Langa Fernando
Published: March 2022

Graphene doped with heteroatoms such as nitrogen, boron, and phosphorous by replacing some of the skeletal carbon atoms is emerging as an important class of two‐dimensional materials as it offers the much‐needed bandgap for optoelectronic applications and provides better access for chemical functionalization at the heteroatom sites. Covalent grafting of photosensitizers onto such doped graphenes makes them extremely useful for light‐induced applications. Herein, we report the covalent functionalization of N‐doped graphene (NG) with two well‐known electron donor photosensitizers, namely, zinc porphyrin (ZnP) and zinc phthalocyanine (ZnPc), using the simple click chemistry approach. Covalent attachment of ZnP and ZnPc at the N‐sites of NG in NG−ZnP and NG−ZnPc hybrids was confirmed by using a range of spectroscopic, thermogravimetric and imaging techniques. Ground‐ and excited‐state interactions in NG−ZnP and NG−ZnPc were monitored by using spectral and electrochemical techniques. Efficient quenching of photosensitizer fluorescence in these hybrids was observed, and the relatively easier oxidations of ZnP and ZnPc supported excited‐state charge‐separation events. Photoinduced charge separation in NG−ZnP and NG−ZnPc hybrids was confirmed by using the ultrafast pump‐probe technique. The measured rate constants were of the order of 1010 s,−1 thus indicating ultrafast electron transfer phenomena.
Experimental methods in chemical engineering: Gas chromatography—GC
Authors: Laajimi Hela , Galli Federico , Patience Gregory S. , Schieppati Dalma
Published: March 2022

Gas chromatography (GC) separates volatile and semi‐volatile liquids and gases based on their affinity for a stationary phase, either a thin liquid or a polymer layer on a solid. A gaseous mobile phase carries the volatile compounds from an injection port to a column with the stationary phase and then to an amdetector. The most common detectors are based on mass spectrometry (MS), thermal conductivity, and flame ionization. A furnace houses the columns and maintains or ramps temperatures to increase the separation efficiency—reduce run time or increase peak separation (resolution). The analyst chooses the chemistry of the stationary phase and the physical structure of the columns based on the polarity and functional groups of the solute. Packed columns tolerate impurities better than capillary columns that have a greater separating power and bleed the functional groups less. Efficiency is best when the sample polarity matches the column polarity. High temperatures and contamination cause columns to bleed the active components, which reduces the resolution but might also introduce ghost peaks to the chromatogram. The Web of Science assigned 15 000 articles to chemical engineering that mention GC and gas chromatography as keywords. Since 2017, it has indexed close to 1000 new articles every year. A bibliometric analysis classifies these contributions into four clusters: (1) pyrolysis and biomass, (2) GC–MS and extraction, (3) lignin and aromatics, and (4) decomposition and kinetics.
Conception and Evaluation of Fluorescent Phosphine‐Gold Complexes: From Synthesis to in vivo Investigations
Authors: Rousselle Benjamin , Massot Aurélie , Privat Malorie , Dondaine Lucile , Trommenschlager Audrey , Bouyer Florence , Bayardon Jérôme , Ghiringhelli François , Bettaieb Ali , Goze Christine , Paul Catherine , Malacea‐Kabbara Raluca , Bodio Ewen
Published: March 2022

A phosphine gold(I) and phosphine‐phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked in vitro thanks to two‐photon imaging. Their in vitro and in vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor‐bearing BALB/c mice. They displayed moderate to strong antiproliferative properties and the phosphine‐phosphonium gold(I) complex induced significant in vivo anti‐cancer effect.
Estimands and Complex Innovative Designs
Authors: Collignon Olivier , Schiel Anja , Burman Carl‐Fredrik , Rufibach Kaspar , Posch Martin , Bretz Frank
Published: March 2022

Since the release of the ICH E9(R1) (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials) document in 2019, the estimand framework has become a fundamental part of clinical trial protocols. In parallel, complex innovative designs have gained increased popularity in drug development, in particular in early development phases or in difficult experimental situations. While the estimand framework is relevant to any study in which a treatment effect is estimated, experience is lacking as regards its application to these designs. In a basket trial for example, should a different estimand be specified for each subpopulation of interest, defined, for example, by cancer site? Or can a single estimand focusing on the general population (defined, for example, by the positivity to a certain biomarker) be used? In the case of platform trials, should a different estimand be proposed for each drug investigated? In this work we discuss possible ways of implementing the estimand framework for different types of complex innovative designs. We consider trials that allow adding or selecting experimental treatment arms, modifying the control arm or the standard of care, and selecting or pooling populations. We also address the potentially data‐driven, adaptive selection of estimands in an ongoing trial and disentangle certain statistical issues that pertain to estimation rather than to estimands, such as the borrowing of nonconcurrent information. We hope this discussion will facilitate the implementation of the estimand framework and its description in the study protocol when the objectives of the trial require complex innovative designs.
The Application of Bi‐Doped TiO2 for the Photocatalytic Oxidation of Formaldehyde
Authors: Sun Yiran , Feng Bowen , Li Qianchen , Tian Chengcheng , Ma Liang , Li Zongzhe
Published: March 2022

The photocatalytic oxidation technology has a great potential for the removal of volatile organic compounds (VOCs). In this research, a novel TiO2/Bi2O3 catalyst is developed to degrade indoor formaldehyde by the photocatalytic oxidation technology. The TiO2/Bi2O3 catalysts with different mass fractions of Bismuth(Bi) are prepared by impregnation method. The characterizations of the TiO2/Bi2O3 catalysts by X‐ray diffraction (XRD), ultraviolet–visible (UV–vis) spectrophotometry, and Brunauer–Emmett–Teller analyses suggest that the doping of TiO2 with Bi neither changes the crystal structure nor the crystal phase of the TiO2, but increases the number of mesopores on the TiO2/Bi2O3 surface and the specific surface area of the TiO2/Bi2O3. By optimizing such parameters as the flow rate; the concentration; and the relative humidity of formaldehyde, the mass fraction of Bi, and the loading amount of the catalyst, a formaldehyde degradation efficiency as high as 96% is obtained.
Astragaloside IV alleviates oxidative stress‑related damage via inhibiting NLRP3 inflammasome in a MAPK signaling dependent pathway in human lens epithelial cells
Authors: Xiao Xili , Zheng Yanlin , Mo Ya , Wang Wanjie , Li Xiang , Wang Juan
Published: March 2022

Oxidative stress alters cellular microenvironment, facilitating cell apoptosis and inflammatory response, and oxidation of lens constituents may ultimately result in cataracts. Astragaloside IV (AS‐IV) exhibits a variety of pharmacological activities, such as antioxidative and anti‐inflammatory activity via regulating various signaling pathways. However, the effect of AS‐IV on lens epithelial cells and its potential therapeutic role in cataracts remained to be investigated. In this study, AS‐IV prevented H2O2‐induced injury and inflammatory response in human lens epithelial cell line HLE‐B3 through inhibiting NLRP3 inflammasome in a mitogen‐activated protein kinase‐dependent pathway, providing a potential novel therapeutic strategy for cataracts.
Ultrasonic cleaning is effective in removing carbonized clots and tissue from the insulation‐tipped diathermic knife‐2
Authors: Murakami Kei , Hirata Daizen , Haraguchi Kengo , Arai Noriko , Inoue Koji , Miyazaki Yuka , Funase Kimihiro , Nakashige Tadao , Teramoto Akira , Iwatate Mineo , Hattori Santa , Fujita Mikio , Sano Wataru , Sano Yasushi
Published: March 2022

Objectives

Since carbonized clots and tissue (debris) tend to adhere firmly to the tip of the endoscopic submucosal dissection (ESD) knife as the procedure proceeds, manual removing the firm debris is often challenging and time‐consuming. Recently, effective ultrasonic cleaning for other medical devices has been reported. The aim of the present study was to clarify whether ultrasonic cleaning is effective in removing the debris on the insulation‐tipped diathermic (IT) knife‐2.

Methods

This study was an ex‐vivo experimental randomized study. A total of 40 IT knife‐2 knives with debris on their tip surfaces were prepared and randomly assigned to two groups (Group A and Group B). The knives in Group A were cleaned using the conventional scrubbing method for 30 s (conventional cleaning method), while those in Group B were cleaned using a combined method of scrubbing for 20 s and ultrasonic cleaning for 10 s (combined ultrasonic cleaning method). The tip electrode of the knife after cleaning was photographed under a microscope (40x). The 40 images of the knives were evaluated by independent three endoscopists and two clinical engineers using the five‐step evaluation criteria ranging from cleaning score 1 (dirty) to 5 (clean).

Results

The mean cleaning score of 3.78 (range: 2.33–4.67) in Group B was significantly higher than that of 1.68 (range: 1.00–2.83) in Group A.

Conclusions

The combined ultrasonic cleaning method could remove debris adhering to the IT knife‐2 more effectively than the conventional cleaning method. Ultrasonic cleaning may be applied for real‐world ESD.
Focus on individual student needs to help students transition to college
Authors: Hope Joan
Published: March 2022

Proactive communication and one‐on‐one support are keys to helping students with disabilities at Germanna Community College succeed. That starts with providing transitioning services, said Win Stevens, Coordinator of the Office of Accessibility Resources.
Academic discipline
Authors: Lyerly Eric
Published: March 2022

An overview of the key topics faced by disability services providers with citations to noteworthy cases, statutes, regulations, and additional sources.
Mechanisms of biodiversity between Campylobacter sequence types in a flock of broiler–breeder chickens
Authors: Rawson Thomas , Colles Frances M. , Terry J. Christopher D. , Bonsall Michael B.
Published: March 2022

Commercial poultry flocks frequently harbor the dangerous bacterial pathogen Campylobacter. As exclusion efforts frequently fail, there is interest in potential ecologically informed solutions. A long‐term study of Campylobacter sequence types was used to investigate the competitive framework of the Campylobacter metacommunity and understand how multiple sequence types simultaneously co‐occur in a flock of chickens. A combination of matrix and patch‐occupancy models was used to estimate parameters describing the competition, transmission, and mortality of each sequence type. It was found that Campylobacter sequence types form a strong hierarchical framework within a flock of chickens and occupied a broad spectrum of transmission–mortality trade‐offs. Upon further investigation of how biodiversity is thus maintained within the flock, it was found that the demographic capabilities of Campylobacter, such as mortality and transmission, could not explain the broad biodiversity of sequence types seen, suggesting that external factors such as host‐bird health and seasonality are important elements in maintaining biodiversity of Campylobacter sequence types.
Habitat occupancy of sloth bear Melursus ursinus in Chitwan National Park, Nepal
Authors: Paudel Rajan Prasad , Kadariya Rabin , Lamichhane Babu Ram , Subedi Naresh , Sashika Mariko , Shimozuru Michito , Tsubota Toshio
Published: March 2022

Mammals have experienced a massive decline in their populations and geographic ranges worldwide. The sloth bear, Melursus ursinus (Shaw, 1791), is one of many species facing conservation threats. Despite being endangered in Nepal, decades of inattention to the situation have hindered their conservation and management. We assessed the distribution and patterns of habitat use by sloth bears in Chitwan National Park (CNP), Nepal. We conducted sign surveys from March to June, 2020, in 4 × 4 km grids (n = 45). We collected detection/non‐detection data along a 4‐km trail that was divided into 20 continuous segments of 200 m each. We obtained environmental, ecological, and anthropogenic covariates to understand determinants of sloth bear habitat occupancy. The data were analyzed using the single‐species single‐season occupancy method, with a spatially correlated detection. Using repeated observations, these models accounted for the imperfect detectability of the species to provide robust estimates of habitat occupancy. The model‐averaged occupancy estimate for the sloth bear was 69% and the detection probability was 0.25. The probability of habitat occupancy by sloth bears increased with the presence of termites and fruits and in rugged, dry, open, undisturbed habitats. Our results indicate that the sloth bear is elusive, functionally unique, and widespread in CNP. Future conservation interventions and action plans aimed at sloth bear management must adequately consider their habitat requirements.
Native forest metacommunity structures in Uruguay shaped by novel land‐use types in their surroundings
Authors: Ramírez Leonardo R. , Säumel Ina
Published: March 2022

We explore the effect of land‐use change from extensively used grasslands to intensified silvi‐ and agricultural monocultures on metacommunity structure of native forests in Uruguay. We integrated methods from metacommunity studies, remote sensing, and landscape ecology to explore how woody species distribution was influenced by land‐use change from local to regional scale. We recorded richness and composition of adult and juvenile woody species from 32 native forests, created land‐use maps from satellite image to calculate spatial metrics at landscape, class, and patch levels. We also analyzed the influence of land use pattern, climate, topography, and geographic distance between sites (d) on metacommunity, and created maps to visualize species richness and (dis)similarity between communities across the country. Woody species communities were distributed in a discrete pattern across Uruguay. Precipitation and temperature seasonality shaped species distribution pattern. Species richness and community dissimilarity increased from West to East. Latitude did not influence these patterns. Number of patches, landscape complexity, and interspersion and juxtaposition indexes determine woody species distribution at landscape level. Increasing areas covered by crops and timber plantation reduced species richness and increased community dissimilarity. The spatial metrics of native forest fragments at patch level did not influence metacommunity structure, species richness, and community dissimilarity. In conclusion, Uruguayan native forests display a high range of dissimilarity. Pressure of neighborhood land uses was the predominant factor for species assemblages. Conserving landscape structures that assure connectivity within and among native forest patches is crucial. On sites with rare target species, the creation of alliances between governmental institution and landowner complemented by incentives for biodiversity conservation provides opportunities to advance in species protection focused on those less tolerant to land‐use change.
Metabolic dynamics instruct CD8+ T‐cell differentiation and functions
Authors: Bevilacqua Alessio , Li Zhiyu , Ho Ping‐Chih
Published: March 2022

Cytotoxic CD8+ T cells are a key element of the adaptative immune system to protect the organism against infections and malignant cells. During their activation and response, T cells undergo different metabolic pathways to support their energetic needs according to their localization and function. However, it has also been recently appreciated that this metabolic reprogramming also directly supports T‐cell lineage differentiation. Accordingly, metabolic deficiencies and prolonged stress exposure can impact T‐cell differentiation and skew them into an exhausted state. Here, we review how metabolism defines CD8+ T‐cell differentiation and function. Moreover, we cover the principal metabolic dysregulation that promotes the exhausted phenotype under tumor or chronic virus conditions. Finally, we summarize recent strategies to reprogram impaired metabolic pathways to promote CD8+ T‐cell effector function and survival.