bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic landscape of non‐small‐cell lung cancer with methylthioadenosine phosphorylase (MTAP) deficiency
Authors: Ashok Kumar Prashanth , Graziano Stephen L. , Danziger Natalie , Pavlick Dean , Severson Eric A. , Ramkissoon Shakti H. , Huang Richard S. P. , Decker Brennan , Ross Jeffrey S. 
Published: June 2022

AbstractIntroductionNew treatment strategies for advanced non‐small‐cell lung carcinoma (NSCLC) include synthetic lethality targets focused on protein arginine methyl transferases such as PRMT5 that exploit the impact of genomic loss of methylthioadenosine phosphorylase (MTAP).MethodsTwenty nine thousand three hundred seventy nine advanced NSCLC cases underwent hybrid‐capture based comprehensive genomic profiling between June 1, 2018 and May 31, 2020. PD‐L1 expression was determined by immunohistochemistry (Dako 22C3 PharmDx assay).Results13.4% (3928/29,379) NSCLC cases exhibited MTAP loss distributed in adenocarcinoma (59%), squamous cell carcinoma (22%), NSCLC not otherwise specified (16%), and 1% each for large‐cell neuroendocrine, sarcomatoid, and adenosquamous carcinoma. Statistically significant differences in mitogenic driver alterations included more KRAS G12C mutations in MTAP‐intact versus MTAP‐lost (12% vs. 10%, p = 0.0003) and fewer EGFR short variant mutations in MTAP‐intact versus MTAP‐lost NSCLC (10% vs. 13%, p < 0.0001). Statistically significant differences in currently untargetable genomic alterations included higher frequencies of TP53 (70% vs. 63%, p < 0.0001) and RB1 inactivation (10% vs. 2%, p < 0.0001) in MTAP‐intact compared to MTAP‐lost NSCLC. SMARCA4 inactivation (7% vs. 10%, p < 0.0001) was less frequent in MTAP‐intact versus MTAP‐lost NSCLC. Alterations in ERBB2, MET, ALK, ROS1, and NTRK1 did not significantly differ between the two groups. Predictors of immunotherapy efficacy were higher in MTAP‐intact versus MTAP‐lost NSCLC including tumor mutational burden (9.4 vs. 8.6 mut/Mb, p = 0.001) and low (30% vs. 28%, p = 0.01) and high PD‐L1 (32% vs. 30%, p = 0.01) expression. Alterations in biomarkers potentially predictive of immune checkpoint inhibitor resistance (STK11, KEAP1, and MDM2) were similar in the two groups.ConclusionsMTAP loss occurs in 13% of NSCLC, supporting the development of targeted therapies to exploit PRMT5 hyper‐dependence. MTAP loss is accompanied by small differences in targeted and immunotherapy options which may impact future combination strategies.
Iron Oxide Nanoparticles Functionalized with Fucoidan: a Potential Theranostic Nanotool for Hepatocellular Carcinoma
Authors: Geinguenaud Frédéric , Sainte‐Catherine Odile , Poirier Florence , Besnard Valérie , Haddad Oualid , Chaubet Frédéric , Lalatonne Yoann , Lutomski Didier , Sutton Angela , Motte Laurence 
Published: June 2022

AbstractFucoidan is a natural sulfated polysaccharide with a large range of biological activities including anticancer and anti‐oxidation activities. Hepatocellular carcinoma is the fourth most common aggressive cancer type. The aim of this study was to investigate the bioactivity of free fucoidan versus its vectorization using nanoparticles (NPs) in human hepatoma cells, Huh‐7. Iron oxide NPs were functionalized with fucoidan by a one‐step surface complexation. NP cellular uptake was quantified by magnetic measurement at various extracellular iron concentrations. Cell invasion and migration were reduced with NPs while free fucoidan increases these events at low fucoidan concentration (≤0.5 μM). Concomitantly, a high decrease of reactive oxygen species production related with a decrease of the matrix metalloproteinase‐9 activity and an increase of its expression was observed with NPs compared to free fucoidan. A proteomic analysis evidenced that some fucoidan regulated proteins appeared, which were related to protein synthesis, N‐glycan processing, and cellular stress. To our knowledge, this is the first study which reveals such activity induced by fucoidan. These results pave the way for USPIO‐fucoidan‐NPs as potential theranostic nanotools for hepatocellular carcinoma treatment.
Effective Controlling of Ni3S2/MoS2 Porous Hollow Spheres on Ni Foam by Non‐ionic Surfactant Micelles for Oxygen Evolution Reaction
Authors: Xu Xuequan , Zhang Jinying , Yang Na , Zhao Xuewen , Gu Mengyue , Cheng Yonghong , Niu Chunming 
Published: June 2022

AbstractThe hollow sphere structure has attracted various attention in the catalytic field due to its high specific surface. The good dispersion and morphology of hollow spheres are important to provide high active sites. It is a big challenge to control the morphology and distribution of the active materials during synthesis. Serious deformation and uneven distribution of the spheres were usually obtained due to inappropriate templates. A facile one‐step hydrothermal method using micelles of triblock copolymer surfactant P123 was adopted to in‐situ grow Ni3S2/MoS2 porous hollow spheres on Ni foam with uniform distribution. The as‐produced Ni3S2/MoS2 porous hollow spheres have been demonstrated to have excellent oxygen evolution reaction catalytic performance as integrated electrodes. Low overpotentials of 314 mV and 337 mV have been achieved at current densities of 50 mA cm−2 and 100 mA cm−2 with a Tafel slope of 57 mV dec−1 and an excellent long‐term stability, which is better than other Ni‐base material.
Development of a Bacterial Enzyme‐Based Biosensor for the Detection and Quantification of Selenate
Authors: Motlagh Mozhgan Khorasani , Noroozifar Meissam , Sodhi Rana N. S. , Kraatz Heinz‐Bernhard 
Published: June 2022

AbstractAn enzymatic biosensor has been developed for the determination of selenate (SeO42−), in which selenate reductase (SeR) is chemically attached to a gold disk electrode by lipoic acid N‐hydroxysuccinimide ester as linker, allowing the catalytic reduction of the SeO42− to SeO32−. Modification of the gold electrode was characterized by X‐ray photoelectron spectroscopy (XPS), time‐of‐flight secondary ion mass spectroscopy (ToF‐SIMS), and electrochemistry. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements were performed in different buffers for selenate determination. Under optimum conditions, the calibration curve was linear over the range 7.0–3900.0 μg L−1 with limits of detection and quantification of 4.97 and 15.56 μg L−1, respectively. The possible interference of the relevant oxyanions SO42−, NO3−, NO2−, PO43− and AsO43− in the determination of SeO42− was studied. Finally, the proposed biosensor was used to determine SeO42− with recovery between 95.2 and 102.4 % in different real water samples.
Proton and Lithium Cations Linked to π‐Electron and σ‐Electron Systems: Are Such Interactions beyond or within the Definition of Hydrogen/Lithium Bond?
Authors: Gholami Samira , Aarabi Mohammad , Grabowski Sławomir J. 
Published: June 2022

AbstractMP2/aug‐cc‐pVTZ calculations were performed on systems containing a proton or a lithium cation located between two π‐electron systems or between π‐electron and σ‐electron units. The proton or the lithium cation attached to the acetylene or its derivative may be treated as the Lewis acid unit while the remaining part of the complex, the π‐electron species or the dihydrogen, act as the Lewis base through their π‐electrons or σ‐electrons, respectively. The complexes analysed here are linked by the π⋅⋅⋅H+/Li+⋅⋅⋅π and π⋅⋅⋅H+/Li+⋅⋅⋅σ interactions. It is discussed whether these interactions are classified as hydrogen and lithium bonds. Therefore, different definitions of the latter interactions are presented. The Electron Localization Function (ELF) and the Natural Bond Orbital (NBO) approaches were applied to analyse the above‐mentioned complexes. The unique properties of interactions with the proton and with the lithium cation that occur in complexes analysed here are described.
Quercetin ameliorates salivary gland apoptosis and inflammation in primary Sjögren's syndrome through regulation of the leptin/OB‐R signaling
Authors: Chang Lihua , Kong Aibin , Guo Yun , Zhang Jing , Sun Yue , Chen Penglu , Wang Xiaofei 
Published: June 2022

AbstractDry mouth is the main manifestation of Sjögren syndrome (SS). Quercetin has been reported to alleviate radiation‐induced salivary gland damage, yet the effect of quercetin on SS‐caused salivary gland damage remains unclear. This study aimed to investigate the effects of quercetin on SS‐induced salivary gland damage and the mechanism underlying its therapeutic potential in SS. Here, NOD/Ltj mice were used to spontaneously mimic SS‐induced salivary gland inflammation in vivo and salivary gland epithelial cells (SGECs) were stimulated by interferon‐γ (IFN‐γ) to mimic cell inflammation in vitro. Results showed that quercetin significantly reduced loss of saliva flow, salivary gland damage, cell apoptosis, and inflammatory response in NOD/Ltj mice. Quercetin treatment also significantly reduced the increased serum leptin (LP) levels in NOD/Ltj mice. Furthermore, quercetin blocked the increases in the expression of obesity receptor (OB‐R) and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling in the salivary glands. In vitro experiments confirmed that quercetin could protect SGECs from IFN‐γ‐induced cell apoptosis and inflammation through the LP/OB‐R‐activated JAK2/STAT3 signaling. Hence, quercetin might protect against SS‐induced salivary gland damage by relieving cell apoptosis and inflammation by inhibiting the LP/OB‐R signaling, providing a new perspective for treating SS‐induced dry mouth.
Analysis of dried blood spots is a feasible alternative for detecting ephedrine in doping control
Authors: Solheim Sara Amalie , Thomas Andreas , Ringsted Thomas Kamm , Thevis Mario , Breenfeldt Andersen Andreas , Holm‐Sørensen Henrik , Nordsborg Nikolai B. , Mørkeberg Jakob 
Published: June 2022

AbstractDried blood spot (DBS) testing allows fast, easy and minimally invasive collection of microvolumes of blood. In an anti‐doping context, DBS testing has particular relevance for substances prohibited in‐competition only such as ephedrine, which is currently detected by urine analysis, because DBS can add information about the blood drug concentrations during the in‐competition period. Several collection methods and devices exist for DBS collection from different anatomical sites. Thus, agreements between concentrations of target analytes in DBS samples from different sampling sites, along with between DBS and those in conventional venous plasma samples, need to be evaluated. Herein, we collected matched upper‐arm DBS, fingerprick DBS and venous plasma samples from eight healthy male subjects in an 8‐h period following oral administrations of 20 mg (‘low dose’) and 60 mg (‘high dose’) of ephedrine. We show that the use of alternative sampling sites and matrices is a feasible possibility for ephedrine analysis in doping control. We observed very good agreement between collection sites and that specificity and sensitivity can be upheld despite use of an alternative collection site. However, potential concentration differences between DBS and venous plasma should be considered, and distinct threshold might be necessary if implementing both blood matrices in ephedrine analysis.
Evaluation of factors affecting tetracycline and diclofenac adsorption by agricultural soils using response surface methodology
Authors: Guler Ulker Asli , Tuncel Eliza , Ersan Mehtap 
Published: June 2022

AbstractThe adsorption process of the pharmaceutical pollutant in the soil is affected by its physicochemical properties and soil properties. In this study, the factors affecting the adsorption of tetracycline and diclofenac onto two different soils (S and M) were investigated using response surface methodology (RSM). The RSM design was used to optimize the five variable factors (pH (2–10), contact time (5–180 min), soil amount (1–10 g/L), temperature (25–45°C)) on the adsorption of tetracycline and diclofenac. The predicted optimal conditions obtained by RSM showed that pH was the most important variable affecting the adsorption of tetracycline and diclofenac. The optimum pH for the adsorption of tetracycline and diclofenac onto the soil samples S and M were found to be 4 and 2, respectively. The adsorbed amounts of tetracycline and diclofenac onto the soils S and M were calculated to be 14.82 mg/g, 12.43 mg/g, 189.40 mg/g, and 144.81 mg/g, respectively. In addition, the effects of soil organic matter, salt, and divalent cations on the adsorption of tetracycline and diclofenac onto soils were studied. The removal of soil organic matter slightly increased tetracycline adsorption, while inhibiting diclofenac adsorption. The presence of salt and divalent cations prominently suppressed the adsorption of tetracycline and diclofenac onto soils. A possible complex mechanism was proposed for TC and DCF adsorption, including ion exchange, electrostatic interaction, and some chemical bonds.
Placental location and obstetrical‐neonatal outcomes: A retrospective study
Authors: Doctory Neta , Romano Asaf , Navon Inbal , Barbash‐Hazan Shiri , Bardin Ron , Hadar Eran 
Published: June 2022

AbstractObjectiveTo explore the potential association of lateral placentation with pregnancy outcome.MethodsThe database of a tertiary medical center was searched for women who gave birth to a singleton neonate from 2012 to 2020 for whom placental location was documented during antepartum sonographic examination. Clinical data were compared between patients with a central (anterior/posterior/fundal) or lateral placenta using standard statistics. The primary outcome measure was neonatal birthweight, and secondary outcome measures were pregnancy complications and mode of delivery.ResultsThe cohort included 12 306 women: 11 608 (94%) with a central placenta and 698 (5.6%) with a lateral placenta. The lateral placenta group had higher rates (P < 0.05) of prior and current cesarean delivery, assisted delivery, and preterm birth. On multivariate regression analyses, placental location (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.11–1.66) and maternal age (aOR, 1.02; 95% CI, 1.01–1.03) were associated with risk of preterm birth. Lateral placenta (aOR, 1.22; 95% CI, 1.02–1.47), maternal age (aOR, 1.07; 95% CI, 1.06–1.08), parity (aOR, 0.32; 95% CI, 0.28–0.35), and prior cesarean delivery (aOR, 12.00; 95% CI, 10.60–13.60) were associated with risk of current cesarean delivery.ConclusionThe findings suggest that lateral placentation may pose a risk of preterm birth and cesarean delivery compared with central placentation.
Squamous cell carcinoma of the prostate with SMARCA4 alteration in a Japanese patient
Authors: Kaneko Yuta , Kosaka Takeo , Nakamura Kohei , Mikami Shuji , Nishihara Hiroshi , Oya Mototsugu 
Published: June 2022

IntroductionSquamous cell carcinoma of the prostate is very rare. Due to difficulty in diagnosis, it is often detected in advanced stages. Effective treatment of squamous cell carcinoma and the genetic profiling has not yet been established.Case presentationWe experienced the case of a 79‐year‐old man who was diagnosed with primary squamous cell carcinoma of the prostate. He had multiple lymph node metastases, liver metastases, and lung metastases, and he was treated with gemcitabine and carboplatin. However, he had poor patient status: it became difficult to continue after one course, and best supportive care was provided. We also performed targeted next‐generation sequencing of 160 cancer‐related genes and detected SMARCA4 mutation.ConclusionThis is the first study reporting the genomic profiling of squamous cell carcinoma of prostate in Japan.
Composition, host responses and clinical applications of bioadhesives
Authors: Dhandapani Vignesh , Ringuette Vickie , Desrochers Monika , Sirois Marco , Vermette Patrick 
Published: June 2022

AbstractBioadhesives are medical devices used to join or seal tissues that have been injured or incised. They have been classified into tissue adhesives, sealants, and hemostatic agents. Bioadhesives such as FloSeal®, CoSeal®, BioGlue®, Evicel®, Tisseel®, Progel™ PALS, and TissuGlu® have been commercialized and used in clinical setting. They can be formulated with natural or synthetic components or a combination of both including albumin, glutaraldehyde, chitosan, cyanoacrylate, fibrin and thrombin, gelatin, polyethylene glycol (PEG), along with urethanes. Each formulation has intrinsic properties and has been developed and validated for a specific application. This review article briefs the mechanisms by which bioadhesives forms adhesion to tissues and highlights the correlation between bioadhesives composition and their potential host responses. Furthermore, clinical applications of bioadhesives and their application‐driven requirements are outlined.
Early differentiated CD28+ CD27+ T lymphocytes as a biomarker for short and long-term outcomes in older patients with pneumonia
Authors: Franco-Leyva Teresa , Torres Olga H , Saez Prieto María Encarnación , Boera-Carnicero Gemma , Santos Álvaro , Clotet Sandra , Albert-Jares Daniel , El-Ebiary Yasmin , Agustí-Martí Manuela , Casademont Jordi , Juárez Cándido , Martínez-Martínez Laura 
Published: June 2022

AbstractThis study tested the hypothesis that a more senescent immune system would predict a worse outcome in older patients hospitalized for community-acquired pneumonia (CAP). CAP has long been responsible for high rates of mortality and readmissions among older people. Although immunosenescence is a key factor in the increased susceptibility to infections, there are no related biomarkers currently available in clinical practice. In this context, the aim of this prospective study was to identify immunosenescence-related biomarkers to predict outcomes in patients older than 65 years hospitalized for CAP. We evaluated 97 patients admitted to our hospital for CAP in 2019 and 2020. All patients were followed for 1 year. Our findings showed that elevated levels of early differentiated CD28+ CD27+ T cells at admission were associated with better short (2 months) and long-term (1 year) outcomes in terms of mortality and readmissions. Early differentiated CD28+ CD27+ CD4+ T cell counts were even better long-term predictors. In conclusion, early differentiated CD28+ CD27+ T cells could be useful biomarkers to identify high-risk older patients with CAP, helping clinicians with risk stratification and follow-up.
Improvement of photoprotection with sunscreen formulas containing the cyclic merocyanine UVA1 absorber MCE: In vivo demonstration under simulated and real sun exposure conditions in three randomised controlled trials
Authors: de Dormael Romain , Bernerd Francoise , Bastien Philippe , Candau Didier , Roudot Angelina , Tricaud Caroline 
Published: June 2022

AbstractBackgroundChronic sun exposure induces skin damage leading to skin ageing and skin colour heterogeneity with hyperpigmented spots. In this process ultra violet A (UVA) rays highly contribute, especially long‐UVA (UVA1) supporting the need for an efficient photoprotection over the whole UV spectrum. A new UVA1 filter, methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE), with a pic of absorption at 385 nm, has been recently approved for use in sunscreen products.ObjectiveThree randomised clinical studies were performed to evaluate the additional photoprotection afforded by a sunscreen formula containing MCE compared to state‐of‐the‐art sunscreen lacking absorption in the longest UVA1 wavelengths. Two studies were performed on European volunteers with UV‐controlled (UVA1, ultra violet B (UVB) + UVA) exposures and one on Indian volunteers under real sun exposures.MethodsThree intraindividual trials (two randomised UV‐controlled and one real sun) were conducted on a total of 62 healthy subjects with Fitzpatrick III–IV and individual typology angle (ITA°) values between −18° and 35°. The MCE at 2% was formulated in a state‐of‐the‐art sun protection factor 30 sunscreen reference allowing to enlarge the absorption profile up to 400 nm. UV‐induced pigmentation was assessed by colorimetric measures and visual scoring at different time points after a single exposure to UVA1 (Study 1) or repeated exposures to daily UV radiation comprising both UVB and UVA (Study 2) or under real sun (Study 3).ResultsWhatever the study exposure condition (UVA1, UVB + UVA, real sun), the level of pigmentation was increased as attested by colorimetric parameters (decreased luminance L* and ITA° values) and visual scorings. In the three studies, the comparison showed higher prevention of hyperpigmentation with the sunscreen enlarged in the longest UVA1 wavelengths with MCE compared to the state‐of‐the‐art sunscreen. No side effects were reported.ConclusionsMCE is a valuable UVA1 filter to improve photoprotection over the entire UV spectrum in state‐of‐the‐art sunscreens and limits the impact of UVA1 rays.
Beyond prediction: Off‐target uses of artificial intelligence‐based predictive analytics in a learning health system
Authors: Keim‐Malpass Jessica , Moorman Liza P. , Monfredi Oliver J. , Clark Matthew T. , Bourque Jamieson M. 
Published: June 2022

AbstractIntroductionArtificial‐intelligence (AI)‐based predictive analytics provide new opportunities to leverage rich sources of continuous data to improve patient care through early warning of the risk of clinical deterioration and improved situational awareness.Part of the success of predictive analytic implementation relies on integration of the analytic within complex clinical workflows. Pharmaceutical interventions have off‐target uses where a drug indication has not been formally studied for a different indication but has potential for clinical benefit. An analog has not been described in the context of AI‐based predictive analytics, that is, when a predictive analytic has been trained on one outcome of interest but is used for additional applications in clinical practice.MethodsIn this manuscript we present three clinical vignettes describing off‐target use of AI‐based predictive analytics that evolved organically through real‐world practice.ResultsOff‐target uses included:real‐time feedback about treatment effectiveness, indication of readiness to discharge, and indication of the acuity of a hospital unit.ConclusionSuch practice fits well with the learning health system goals to continuously integrate data and experience to provide.
Further validation of the THINC‐it tool and extension of the normative data set in a study ofn = 10.019 typical controls
Authors: Dalby Maria , Annas Peter ,   23andMe Research Team, Harrison John E. 
Published: June 2022

AbstractIntroductionWe report further validation and normative data for the THINC‐Integrated Tool (THINC‐it), a measure of cognitive function designed for use with individuals living with Major Depressive Disorder, but which is finding use in further psychiatric and neurological diseases. THINC‐it comprises four objective computerised cognitive tests based on traditional psychological paradigms and a version of the Perceived Deficits Questionnaire assessment.MethodsSample size ofn = 10.019 typical control study participants were tested on one to two occasions to further validate the reliability of THINC‐it. Temporal reliability was assessed across 120–180 days.ResultsTest‐retest reliability correlations varied betweenr = 0.50 and 0.72 for the component measures andr = 0.75 (95% confidence intervals 0.74, 0.76) for the THINC‐it composite score. Normative data categorised by Age, Sex and Years of Education were calculated and the effect on task performance was reported.DiscussionOur analysis confirms previously reported levels of reliability and validates previously reported normative data values.