bluuebunny/crossref_metadata_2025_split huggingface dataset:
mGluR5 and GABAA receptor‐specific parametric PET atlas construction—PET/MR data processing pipeline, validation, and application
Authors: Kaulen Nicolas , Rajkumar Ravichandran , Régio Brambilla Cláudia , Mauler Jörg , Ramkiran Shukti , Orth Linda , Sbaihat Hasan , Lang Markus , Wyss Christine , Rota Kops Elena , Scheins Jürgen , Neumaier Bernd , Ermert Johannes , Herzog Hans , Langen Karl‐Joseph , Lerche Christoph , Shah N. Jon , Veselinović Tanja , Neuner Irene 
Published: January 2022

AbstractThe glutamate and γ‐aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non‐displaceable binding potential (BPND), and total distribution volume (VT) based on simultaneously acquired bolus‐infusion positron emission tomography (PET) and MR data. The pipeline was applied to [11C]ABP688‐PET/MR (13 healthy male non‐smokers, 26.6 ± 7.0 years) and [11C]Flumazenil‐PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as VT and BPND atlases of mGluR5 and GABAA, were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δABP = 3.0 ± 1.0% and δFMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σABP = 4.0%–16.0%, σFMZ = 3.9%–9.5%). An evaluation of PET‐to‐PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [15O]H2O‐template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions.
The differences in distant metastatic patterns and their corresponding survival between thyroid cancer subtypes
Authors: Vuong Huy Gia , Le Minh‐Khang , Hassell Lewis , Kondo Tetsuo , Kakudo Kennichi 
Published: January 2022

AbstractIntroductionThis study aimed to systematically elucidate the metastatic patterns and their corresponding survival of each thyroid cancer subtype at time of diagnosis.MethodsWe accessed the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 to search for primary thyroid cancers with DM at presentation (M1).ResultsWe included 2787 M1 thyroid cancers for statistical analyses and the incidence of DM at presentation was 2.4%. Lung was the most common metastatic site for anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and oncocytic (Hurthle) cell carcinoma (HCC) whereas bone is the favorable disseminated site of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC). Patients with multi‐organ metastases had the worst survival whereas bone metastases were associated with a favorable outcome (p < 0.001).ConclusionThere are significant differences in DM patterns of thyroid cancer subtypes and their corresponding survival.
Therapeutic efficacy of FASN inhibition in preclinical models of HCC
Authors: Wang Haichuan , Zhou Yi , Xu Hongwei , Wang Xue , Zhang Yi , Shang Runze , O'Farrell Marie , Roessler Stephanie , Sticht Carsten , Stahl Andreas , Evert Matthias , Calvisi Diego F. , Zeng Yong , Chen Xin 
Published: January 2022

Abstract

Background and Aims
Aberrant activation of fatty acid synthase (FASN) is a major metabolic event during the development of HCC. We evaluated the therapeutic efficacy of TVB3664, a FASN inhibitor, either alone or in combination, for HCC treatment.

Approach and Results
The therapeutic efficacy and the molecular pathways targeted by TVB3664, either alone or with tyrosine kinase inhibitors or the checkpoint inhibitor anti–programmed death ligand 1 antibody, were assessed in human HCC cell lines and multiple oncogene‐driven HCC mouse models. RNA sequencing was performed to elucidate the effects of TVB3664 on global gene expression and tumor metabolism. TVB3664 significantly ameliorated the fatty liver phenotype in the aged mice and AKT‐induced hepatic steatosis. TVB3664 monotherapy showed moderate efficacy in NASH‐related murine HCCs, induced by loss of phosphatase and tensin homolog and MET proto‐oncogene, receptor tyrosine kinase (c‐MET) overexpression. TVB3664, in combination with cabozantinib, triggered tumor regression in this murine model but did not improve the responsiveness to immunotherapy. Global gene expression revealed that TVB3664 predominantly modulated metabolic processes, whereas TVB3664 synergized with cabozantinib to down‐regulate multiple cancer‐related pathways, especially the AKT/mammalian target of rapamycin pathway and cell proliferation genes. TVB3664 also improved the therapeutic efficacy of sorafenib and cabozantinib in the FASN‐dependent c‐MYC‐driven HCC model. However, TVB3664 had no efficacy nor synergistic effects in FASN‐independent murine HCC models.

Conclusions
This preclinical study suggests the limited efficacy of targeting FASN as monotherapy for HCC treatment. However, FASN inhibitors could be combined with other drugs for improved effectiveness. These combination therapies could be developed based on the driver oncogenes, supporting precision medicine approaches for HCC treatment.
The DESC catchments: Long‐term monitoring of inland Precambrian shield catchment streamflow and water chemistry in Central Ontario, Canada
Authors: James April L. , Yao Huaxia , McConnell Christopher , Field Timothy , Yang Yinan 
Published: January 2022

AbstractSince the early 1970s, the Dorset Environmental Science Centre (DESC) research catchments have been home to long‐term monitoring and study of terrestrial headwater catchment processes, their linkages to inland aquatic ecosystems and the influence of both natural variation and human activities. Located on the Precambrian Shield in central Ontario, Canada, covered by mixed Great Lakes‐St. Lawrence forest, the 29 catchments, defined by inflows and outflows to eight lakes, have been monitored for streamflow, meteorology and water chemistry, with long‐term datasets spanning from 1976 to the present. These datasets have provided insights into cold region hydrologic processes such as runoff generation, wetland and groundwater–surface water interactions, snow and ice processes, and catchment linkages to lake nutrient budgets and ecology. The datasets have supported catchment transit time estimates, hydrological modelling and cold region intercomparison studies. Starting with early research efforts driven by concerns over impacts from cottage development and acid deposition on soils, rivers and lakes, the DESC catchment datasets have supported study of impacts of stressors of forest harvesting, calcium depletion, road salt application and climate change. Ongoing monitoring of streamflow, meteorology and water chemistry in the DESC catchments continues to offer unique opportunities for investigation of critical zone processes in Precambrian shield catchments, their model representation and anthropogenic impacts.
Use of external cephalic version in Portuguese public hospitals
Authors: Pinto Luísa , Clode Nuno , Ayres‐de‐Campos Diogo 
Published: January 2022

AbstractObjectiveTo evaluate the use of external cephalic version (ECV) in Portuguese public hospitals with maternity services, as well as exploring the main motives for not offering the technique.MethodsA cross‐sectional observational study was conducted involving an online survey with 34 questions, accessed via an email addressed to all Heads of Department of Portuguese state‐owned hospitals with maternity services. In centers where the technique was performed, information was requested on success rates, contraindications for the procedure, and practical aspects related to its use. In centers where ECV was not offered, the underlying reasons for this were queried.ResultsAnswers were received from 41 out of the 43 state hospitals with maternity services (95.3%). Sixteen hospitals perform the technique (39%), with reported annual numbers ranging from 3 to 51, and success rates ranging from 25% to 85% (12 respondents). The main reasons for not offering the technique were lack of experience and lack of conditions to perform it safely. Most centers (87.8%) reported that they would welcome hands‐on training in ECV.ConclusionECV is used in a minority of Portuguese state‐owned hospitals. Efforts are needed to achieve a wider implementation of the technique, with a particular focus on simulation‐based training.
Rational design of anti‐inflammatory lipid nanoparticles for mRNA delivery
Authors: Zhang Hanwen , Han Xuexiang , Alameh Mohamad‐Gabriel , Shepherd Sarah J. , Padilla Marshall S. , Xue Lulu , Butowska Kamila , Weissman Drew , Mitchell Michael J. 
Published: January 2022

AbstractLipid nanoparticles (LNPs) play a crucial role in delivering messenger RNA (mRNA) therapeutics for clinical applications, including COVID‐19 mRNA vaccines. While mRNA can be chemically modified to become immune‐silent and increase protein expression, LNPs can still trigger innate immune responses and cause inflammation‐related adverse effects. Inflammation can in turn suppress mRNA translation and reduce the therapeutic effect. Dexamethasone (Dex) is a widely used anti‐inflammatory corticosteroid medication that is structurally similar to cholesterol, a key component of LNPs. Here, we developed LNP formulations with anti‐inflammatory properties by partially substituting cholesterol with Dex as a means to reduce inflammation. We demonstrated that Dex‐incorporated LNPs effectively abrogated the induction of tumor necrosis factor alpha (TNF‐ɑ) in vitro and significantly reduced its expression in vivo. Reduction of inflammation using this strategy improved in vivo mRNA expression in mice by 1.5‐fold. Thus, we envision that our Dex‐incorporated LNPs could potentially be used to broadly to reduce the inflammatory responses of LNPs and enhance protein expression of a range of mRNA therapeutics.
Molecularly aligned films of [1]benzothieno[3,2‐b][1]benzothiophene derivatives by solution shearing: Effect of alkyl substitution on morphology and charge transporting property
Authors: Prakoso Suhendro Purbo , Ke Yao‐Jin , Huang Ding‐Chi , Wang Chien‐Lung , Tao Yu‐Tai 
Published: January 2022

AbstractThe self‐assembly behaviors, crystal morphologies, and charge transporting properties of π–conjugated framework can be strongly affected by the functional group/substituent it carries, as well as the way the film is prepared. In this work, thin films of mono‐ and di‐alkylated [1]benzothieno[3,2‐b][1]‐benzothiophene (BTBT) derivatives were prepared on a silicon substrate by solution‐shearing method. Their film morphologies and crystal packing details were examined using polarized optical microscope, grazing incident wide‐angle X‐ray scattering, and atomic force microscope. With 2‐tridecyl[1]benzothieno[3,2‐b][1]‐benzothiophene (C13‐BTBT), a film with well‐aligned molecules packed in face‐to‐face π‐stacking arrangement was obtained, rendering a 1D‐like charge conduction channel. For 2,7‐bis‐tridecyl[1]benzothieno[3,2‐b][1]‐benzothiophene (C13‐BTBT‐C13), well‐aligned molecules packed in a layered‐herringbone arrangement were obtained. With these films as a conducting channel in transistor fabrication, high‐field‐effect mobility was realized for C13‐BTBT‐C13, with a maximum mobility (μh) of 0.645 cm2 /Vs and low anisotropic effect, presumably owing to the 2D growth of the π–conjugated skeleton in LHB packing. This study demonstrated the advantage of 2D semiconducting channels formed from C13‐BTBT‐C13 by low‐cost and scalable solution‐shearing processes, necessary for practical use in industry‐level and future flexible electronics.
Medication Optimization Using Pharmacogenomic Testing in a Complex Mental Health Population Prescribed Psychiatric Polypharmacy
Authors: Wood Amanda Ernst , Agrawal Deepika , Deem Alison P. , Dupper Knoper Terri L. , Merino Rosa F. , Molzof Hylton E. , Maus Laurie E. , Kim Floreen , Lodin Zohra , Lim Sonia 
Published: January 2022

AbstractThe use of polypharmacy has become significantly more common over the past two decades, increasing the risk of drug–drug interactions and adverse drug reactions. Pharmacogenomic (PGx) assays have the purported benefit of being able to predict an individual's response to a specific medication based on genetic markers, which may facilitate the development of optimized medication regimens for patients prescribed polypharmacy. This 12‐week pilot study examined the impact of the PGx results on the clinical management of Veterans who were prescribed psychiatric polypharmacy. Psychiatric medication providers were given access to the PGx assay results, including notification of drug–drug–gene interactions computed from an algorithm decision tool, to assist with medication management decisions. Veteran outpatients (N = 53) prescribed polypharmacy (mean = 13.15 medications) were enrolled into the study. In 92.4% of cases, providers changed medications at baseline, with 83% of providers indicating that they changed their original medication plan based on the PGx results. Clinical improvement over the 12‐week treatment phase was seen in depression (F(1.63, 45) = 5.45, P = .01, η2 = .11) and mental health quality of life (F(2.00, 45) = 4.16, P < .05, η2 = .16). Adverse drug effects were unchanged or improved over time. Rates of polypharmacy remained unchanged. The results suggest that medication changes based on the PGx assay may be beneficial in a complex patient population prescribed polypharmacy.
Impact of protocol‐based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients
Authors: Carbon Niklas M. , Engelhardt Lilian J. , Wollersheim Tobias , Grunow Julius J. , Spies Claudia D. , Märdian Sven , Mai Knut , Spranger Joachim , Weber‐Carstens Steffen 
Published: January 2022

AbstractBackgroundThe impact of physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients is not well understood.MethodsThis pooled analysis investigates the impact of different physiotherapeutic strategies on insulin sensitivity in critically ill patients. We pooled data from two previous trials in adult patients with sequential organ failure assessment score (SOFA)≥ 9 within 72 h of intensive care unit (ICU) admission, who received hyperinsulinaemic euglycaemic (HE) clamps. Patients were divided into three groups: standard physiotherapy (sPT, n = 22), protocol‐based physiotherapy (pPT, n = 8), and pPT with added muscle activating measures (pPT+, n = 20). Insulin sensitivity index (ISI) was determined by HE clamp. Muscle metabolites lactate, pyruvate, and glycerol were measured in the M. vastus lateralis via microdialysis during the HE clamp. Histochemical visualization of glucose transporter‐4 (GLUT4) translocation was performed in surgically extracted muscle biopsies. All data are reported as median (25th/75th percentile) (trial registry: ISRCTN77569430 and ISRCTN19392591/ethics approval: Charité‐EA2/061/06 and Charité‐EA2/041/10).ResultsFifty critically ill patients (admission SOFA 13) showed markedly decreased ISIs on Day 17 (interquartile range) 0.029 (0.022/0.048) (mg/min/kg)/(mU/L) compared with healthy controls 0.103 (0.087/0.111), P < 0.001. ISI correlated with muscle strength measured by medical research council (MRC) score at first awakening (r = 0.383, P = 0.026) and at ICU discharge (r = 0.503, P = 0.002). Different physiotherapeutic strategies showed no effect on the ISI [sPT 0.029 (0.019/0.053) (mg/min/kg)/(mU/L) vs. pPT 0.026 (0.023/0.041) (mg/min/kg)/(mU/L) vs. pPT+ 0.029 (0.023/0.042) (mg/min/kg)/(mU/L); P = 0.919]. Regardless of the physiotherapeutic strategy metabolic flexibility was reduced. Relative change of lactate/pyruvate ratio during HE clamp is as follows: sPT 0.09 (−0.13/0.27) vs. pPT 0.07 (−0.16/0.31) vs. pPT+ −0.06 (−0.19/0.16), P = 0.729, and relative change of glycerol concentration: sPT −0.39 (−0.8/−0.12) vs. pPT −0.21 (−0.33/0.07) vs. pPT+ −0.21 (−0.44/−0.03), P = 0.257. The majority of ICU patients showed abnormal localization of GLUT4 with membranous GLUT4 distribution in 37.5% (3 of 8) of ICU patients receiving sPT, in 42.9% (3 of 7) of ICU patients receiving pPT, and in 53.8% (7 of 13) of ICU patients receiving pPT+ (no statistical testing possible).ConclusionsOur data suggest that a higher duration of muscle activating measures had no impact on insulin sensitivity or metabolic flexibility in critically ill patients with sepsis‐related multiple organ failure.
Uptake of community‐ versus clinic‐based antiretroviral therapy dispensing in the Central Chronic Medication Dispensing and Distribution program in South Africa
Authors: Bassett Ingrid V. , Yan Joyce , Govere Sabina , Khumalo Anele , Ngobese Nompumelelo , Shazi Zinhle , Nzuza Mpilonhle , Bunda Bridget A. , Wara Nafisa J. , Stuckwisch Ashley , Zionts Dani , Dube Nduduzo , Tshabalala Sandile , Bogart Laura M. , Parker Robert A. 
Published: January 2022

AbstractIntroductionSouth Africa's government‐led Central Chronic Medication Dispensing and Distribution (CCMDD) program offers people living with HIV the option to collect antiretroviral therapy at their choice of community‐ or clinic‐based pick‐up points intended to increase convenience and decongest clinics. To understand CCMDD pick‐up point use among people living with HIV, we evaluated factors associated with uptake of a community‐ versus clinic‐based pick‐up point at CCMDD enrolment.MethodsWe collected baseline data from October 2018 to March 2020 on adults (≥18 years) who met CCMDD clinical eligibility criteria (non‐pregnant, on antiretroviral therapy for ≥1 year and virologically suppressed) as part of an observational cohort in seven public clinics in KwaZulu‐Natal. We identified factors associated with community‐based pick‐up point uptake and fit a multivariable logistic regression model, including age, gender, employment status, self‐perceived barriers to care, self‐efficacy, HIV‐related discrimination, and perceived benefits and challenges of CCMDD.Results and DiscussionAmong 1521 participants, 67% were females, with median age 36 years (IQR 30–44). Uptake of a community‐based pick‐up point was associated with younger age (aOR 1.18 per 10‐year decrease, 95% CI 1.05–1.33), being employed ≥40 hours per week (aOR 1.42, 95% CI 1.10–1.83) versus being unemployed, no self‐perceived barriers to care (aOR 1.42, 95% CI 1.09–1.86) and scoring between 36 and 39 (aOR 1.44, 95% CI 1.03–2.01) or 40 (aOR 1.91, 95% CI 1.39–2.63) versus 10–35 on the self‐efficacy scale, where higher scores indicate greater self‐efficacy. Additional factors included more convenient pick‐up point location (aOR 2.32, 95% CI 1.77–3.04) or hours (aOR 5.09, 95% CI 3.71–6.98) as perceived benefits of CCMDD, and lack of in‐clinic follow‐up after a missed collection date as a perceived challenge of CCMDD (aOR 4.37, 95% CI 2.30–8.31).ConclusionsUptake of community‐based pick‐up was associated with younger age, full‐time employment, and systemic and structural factors of living with HIV (no self‐perceived barriers to care and high self‐efficacy), as well as perceptions of CCMDD (convenient pick‐up point location and hours, lack of in‐clinic follow‐up). Strategies to facilitate community‐based pick‐up point uptake should be tailored to patients’ age, employment, self‐perceived barriers to care and self‐efficacy to maximize the impact of CCMDD in decongesting clinics.
Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology
Authors: Singh Amit Kumar , Kasarpalkar Nandini , Bhowmick Shilpa , Paradkar Gaurav , Talreja Mayur , Shah Karan , Tiwari Abhishek , Palav Harsha , Kaginkar Snehal , Kulkarni Rajiv , Patil Ashwini , Kalsurkar Varsha , Agrawal Sachee , Shastri Jayanthi , Dere Rajesh , Bharmal Ramesh , Mahale Smita D , Bhor Vikrant M , Patel Vainav 
Published: January 2022

AbstractImmune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.
Interaction mechanism of pelargonidin against tyrosinase by multi‐spectroscopy and molecular docking
Authors: Tao Yanzhou , Chen Rongda , Fan Yangyang , Liu Guiming , Wang Meizi , Wang Suqing , Li Li 
Published: January 2022

AbstractThe interaction mechanism of pelargonidin (PG) with tyrosinase was investigated by multi‐spectroscopy and molecular docking. As a result, PG had strong inhibitory activity on tyrosinase with the IC50 value of 41.94 × 10−6 mol·L−1. The inhibition type of PG against tyrosinase was determined as a mixed‐mode. Meanwhile, the fluorescence of tyrosinase was quenched statically by PG, and accompanied by non‐radiative energy transfer. The three‐dimensional (3‐D) fluorescence, ultraviolet‐visible spectroscopy (UV‐Vis) and circular dichroism spectroscopies (CD) indicated that PG decreased the hydrophobicity of the micro‐environment around tryptophan (Trp) and tyrosine (Tyr), which resulted in the conformational change of tyrosinase. In addition, fluorescence and molecular docking analysis indicated that PG bound to tyrosinase via hydrogen bonds (H‐bonds) and van der Waals force (vdW force). We herein recommended that PG might be a potential candidate drug for the treatment of melanin‐related diseases.