bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bile acid metabolism dysregulation associates with cancer cachexia: roles of liver and gut microbiome
Authors: Feng Lixing , Zhang Wanli , Shen Qiang , Miao Chunxiao , Chen Lijuan , Li Yiwei , Gu Xiaofan , Fan Meng , Ma Yushui , Wang Hui , Liu Xuan , Zhang Xiongwen 
Published: September 2021

AbstractBackgroundCancer cachexia is a multifactorial metabolic syndrome in which bile acid (BA) metabolism might be involved. The aim of the present study was to clarify the contribution of liver and gut microbiota to BA metabolism disturbance in cancer cachexia and to check the possibility of targeting BA metabolism using agents such as tauroursodeoxycholic acid (TUDCA) for cancer cachexia therapy.MethodsThe BA profiles in liver, intestine, and serum of mice with cancer cachexia induced by inoculation of colon C26 tumour cells were analysed using metabolomics methods and compared with that of control mice. Proteomic analysis of liver protein expression profile and 16S rRNA gene sequencing analysis of gut microbiota composition in cancer cachexia mice were conducted. Expression levels of genes related to farnesoid X receptor (FXR) signalling pathway in the intestine and liver tissues were analysed using RT–PCR analysis. The BA profiles in serum of clinical colon cancer patients with or without cachexia were also analysed and compared with that of healthy volunteers. The effects of TUDCA in treating cancer cachexia mice were observed.ResultsIn the liver of cancer cachexia mice, expression of BA synthesis enzymes was inhibited while the amount of total BAs increased (P < 0.05). The ratios of conjugated BAs/un‐conjugated BAs significantly increased in cancer cachexia mice liver (P < 0.01). Gut microbiota dysbiosis such as decrease in Lachnospiraceae and increase in Enterobacteriaceae was observed in the intestine of cancer cachexia mice, and microbial metabolism of BAs was reduced. Increase in expression of FGF15 in intestine (P < 0.01) suggested the activation of FXR signalling pathway which might contribute to the regulation of BA synthesis enzymes, transporters, and metabolic enzymes. Increase in the BA conjugation was observed in the serum of cancer cachexia mice. Results of clinical patients showed changes in BA metabolism, especially the increase in BA conjugation, and also suggested compensatory mechanism in BA metabolism regulation. Oral administration of 50 mg/kg TUDCA could significantly ameliorate the decrease in body weight (P < 0.001), muscle loss (P < 0.001), and atrophy of heart and liver (P < 0.05) in cancer cachexia mice without influence on tumour growth.ConclusionsBile acid metabolism dysregulation such as decrease in BA synthesis, increase in BA conjugation, and decrease in BA microbial metabolism was involved in development of cancer cachexia in mice. Targeting BA metabolism using agents such as TUDCA might be helpful for cancer cachexia therapy.
Myasthenia gravis and paroxysmal nocturnal hemoglobinuria after thymectomy: A rare association
Authors: Galtier Jean , Duval Fanny , Machelart Irène , Greib Carine , Lazaro Estibaliz , Pellegrin Jean‐Luc , Viallard Jean‐François , de la Tour Regis Peffault , Rivière Etienne 
Published: September 2021

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a very rare clonal autoimmune disease manifesting with hemolysis, thrombosis, or bone marrow failure. We present an atypical association of myasthenia gravis, aplastic anemia, and PNH occurring years after thymectomy. While this association might be extremely rare, it may not be coincidental as there is a common pathophysiology between PNH and aplastic anemia, with the latter reported in several thymoma/thymectomy cases. Eculizumab was introduced with good efficacy and without safety concern in our patient, leading to long‐term control of PNH without worsening of myasthenia gravis.
Mechanism of chlorogenic acid in alveolar macrophage polarization in Klebsiella pneumoniae-induced pneumonia
Authors: Li Qing Rong , Tan Shi Rui , Yang Lu , He Wei , Chen Li , Shen Fen Xiu , Wang Zhuo , Wang Hai Feng 
Published: September 2021

AbstractChlorogenic acid (CA) has been discovered to regulate macrophage polarization in pneumonia. This study aims to analyze the functional mechanism of CA in alveolar macrophage (AM) polarization and provide a theoretical basis for treatment of Klebsiella pneumoniae (Kp)-induced pneumonia. Mice were infected with Kp, and treated with CA and silent information regulator 1 (SIRT1) inhibitor (Selisistat). Mouse survival rate was recorded and bacterial burden was detected. AM polarization and pathologic change of lung tissues were evaluated. Expressions of SIRT1 and HMGB1 and cytokine levels were detected. MH-S cells were infected with Kp to establish the pneumonia cell model, followed by transfection of si-SIRT1 and HMGB1 overexpression vector. The HMGB1 expression in the nucleus and cytoplasm was detected. HMGB1 subcellular localization and HMGB1 acetylation level were detected. Kp led to high death rates, SIRT down-regulation and increases in inflammatory factor level and bacterial burden, and promoted M1 polarization. CA treatment improved mouse survival rate and promoted M2 polarization and SIRT1 expression. SIRT1 decreased HMGB1 acetylation level to inhibit nuclear to the cytoplasm translocation. Silencing SIRT1 or HMGB1 overexpression reversed the effect of CA on Kp-induced pneumonia. Overall, CA activated SIRT1 to inhibit HMGB1 acetylation level and nuclear translocation, thereby promoting M2 polarization in AMs and alleviating Kp-induced pneumonia.
Infantile onset carnitine palmitoyltransferase 2 deficiency: Cortical polymicrogyria, schizencephaly, and gray matter heterotopias in an adolescent with normal development
Authors: Shelihan Ivan , Rossignol Elsa , Décarie Jean‐Claude , Bonnefont Jean‐Paul , Brivet Michèle , Brunel‐Guitton Catherine , Mitchell Grant A. 
Published: September 2021

AbstractObjectiveTo report an adolescent with infantile‐onset carnitine palmitoyltransferase 2 (CPT2) deficiency and cerebral malformations and to review the occurrence of brain malformations in CPT2 deficiency. The patient presented clinically at age 5 months with dehydration and hepatomegaly. He also has an unrelated condition, X‐linked nephrogenic diabetes insipidus. He had recurrent rhabdomyolysis but normal psychomotor development. At age 17 years, he developed spontaneous focal seizures. Cerebral magnetic resonance imaging revealed extensive left temporo‐parieto‐occipital polymicrogyria, white matter heterotopias, and schizencephaly. Neuronal migration defects were previously reported in lethal neonatal CPT2 deficiency but not in later‐onset forms.Design and MethodsWe searched PubMed, Google Scholar, and the bibliographies of the articles found by these searches, for cerebral malformations in CPT2 deficiency. All antenatal, neonatal, infantile, and adult‐onset cases were included. Exclusion criteria included insufficient information about age of clinical onset and lack of confirmation of CPT2 deficiency by enzymatic assay or genetic testing. For each report, we noted the presence of cerebral malformations on brain imaging or pathological examination.ResultsOf 26 neonatal‐onset CPT2‐deficient patients who met the inclusion criteria, brain malformations were reported in 16 (61.5%). In 19 infantile‐onset cases, brain malformations were not reported, but only 3 of the 19 reports (15.8%) include brain imaging or neuropathology data. In 276 adult‐onset cases, no brain malformations were reported.ConclusionTo the best of our knowledge, this is the first report of cerebral malformations in an infantile onset CPT2‐deficient patient. Brain imaging should be considered in patients with CPTII deficiency and neurological manifestations, even in those with later clinical onset.
The evaluation of both the expression and serum protein levels of Caspase‐3 gene in patients with different degrees of SARS‐CoV2 infection
Authors: Yildiz Gulhan Pinar , Eroz Recep , Ataoglu Ozlem , İnce Nevin , Davran Fatih , Öztürk Cihadiye Elif , Gamsızkan Zerrin , Balbay Oner Abidin 
Published: September 2021

AbstractTo evaluate the effects of Caspase‐3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. A total of 41 individuals (male: 21; female: 20) with SARS‐CoV‐2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3 (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 levels and hemoglobin (p = 0.023), between CASP3 levels and C‐reactive protein (CRP) (p = 0.001), between CASP3 levels and ferritin (p = 0.003), between CASP3 levels and lactate dehydrogenase (p =  0.001), and between CASP3 levels and SpO2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS‐CoV‐2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease.
Therapeutic strategies for systemic therapies of human papillomavirus‐related oropharyngeal cancer
Authors: Hung Tony K. W. , Ho Alan L. , Pfister David G. 
Published: September 2021

AbstractOur understanding of human papillomavirus (HPV)‐related oropharyngeal cancer (OPC) and its molecular basis continues to evolve and produce important insights into customized therapeutic strategies. Novel therapeutics exploiting HPV‐related targets are being evaluated in the incurable setting, while the favorable prognosis of locoregionally advanced disease has stimulated investigation into de‐escalation strategies. There is much opportunity for better personalization of standard therapy according to HPV status. This review discusses both current and investigational therapeutic strategies for HPV‐related OPC.
Evaluation of triage tool for low‐grade cartilage tumors: Four‐quadrant approach
Authors: Schumacher Katherine M. , Damron Timothy A. 
Published: September 2021

AbstractBackground and ObjectivesThe “four‐quadrant approach” (FQA) for triage of benign enchondromas (E) and low‐grade malignant chondrosarcomas (LGC) divides patients into treatment categories based on the presence or absence of pain and observation of aggressive or benign radiographic features. This article evaluates the usefulness of the FQA in predicting E versus LGC and operative versus nonoperative outcome.MethodsPatients had working diagnosis of E or LGC, 1‐year minimum follow‐up, imaging, clinical data, outcomes, and no radiographic evidence of high‐grade chondrosarcoma. Statistical analysis determined whether quadrant distribution correlated to E versus LGC and operative versus nonoperative intervention.ResultsOf 56 lesions (49 patients), 9 were LGC and 47 E. Twenty‐five lesions (all 9 LGC, 16 E) were treated operatively and 31 (all E) nonoperatively. There were statistically significant correlations between quadrant distribution and both tumor type (p = 1.9 × 10−6) and operative intervention (p = 6.28 × 10−6).ConclusionsThe FQA is a promising diagnostic tool to distinguish between E and LGC hyaline cartilage tumors, along with determining operative versus nonoperative intervention. Prospective evaluation is warranted.
Pancreas cancer trials for early stage disease: Surgeons leading therapeutic cooperative group trials
Authors: Snyder Rebecca A. , Ahmad Syed , Katz Matthew H. G. 
Published: September 2021

AbstractSurgeon‐led clinical trials have defined the standard of care for locoregional pancreatic cancer to date. The infrastructure and collaborative nature of cooperative oncology groups offer many advantages, such as providing an ideal mechanism through which multidisciplinary pancreatic cancer trials are performed. As key members of the treatment team, surgeons bring experience and expertise to the design of surgical and multidisciplinary trials and are uniquely poised to be leaders of future pancreatic cancer trials.
Substrate integrated waveguide leaky wave antenna with circular polarization and improvement of the scan angle
Authors: Masoumi Mohsen , Dalili Oskouei Hamid Reza , Mohammadi Shirkolaei Mortez , Mirtaheri Ali Reza 
Published: September 2021

AbstractIn this paper, a leaky wave antenna is presented based on the substrate integrated waveguide structure. The proposed antenna has a periodic structure with a combination of rectangular and H‐shaped slots on the top of the antenna. By providing this new design for slots, a better angular scanning achieved rather than the previous designs from broadside to end‐fire, so that with this design, the leaky wave antenna can scan from 2.5 to 87° by changing the feeding frequency, which is the highest scanning angle relative to the design of uniform rectangular slots, the butterfly shaped slots and the H‐shaped slots. The proposed antenna was designed to have circular polarization in the entire operating frequency range.
Implementation and experimental validation of a robust hybrid direct aperture optimization approach for mixed‐beam radiotherapy
Authors: Heath Emily , Mueller Silvan , Guyer Gian , Duetschler Alisha , Elicin Olgun , Aebersold Daniel , Fix Michael K. , Manser Peter 
Published: September 2021

AbstractPurposeThe objectives of the work presented in this paper were to (1) implement a robust‐optimization method for deliverable mixed‐beam radiotherapy (MBRT) plans within a previously developed MBRT planning framework; (2) perform an experimental validation of the delivery of robust‐optimized MBRT plans; and (3) compare PTV‐based and robust‐optimized MBRT plans in terms of target dose robustness and organs at risk (OAR) sparing for clinical head and neck and brain patient cases.MethodsA robust‐optimization method, which accounts for translational setup errors, was implemented within a previously developed treatment planning framework for MBRT. The framework uses a hybrid direct aperture optimization method combining column generation and simulated annealing. A robust plan was developed and then delivered to an anthropomorphic head phantom using the Developer Mode of a TrueBeam linac. Planar dose distributions were measured and compared to the planned dose. Robust‐optimized and PTV‐based plans were developed for three clinical patient cases consisting of two head and neck cases and one brain case. The plans were compared in terms of the robustness to 5 mm shifts of the target volume dose as well as in terms of OAR sparing.ResultsUsing a gamma criterion of 3%/2 mm and a dose threshold of 10%, the agreement between film measurements and dose calculations was better than 97.7% for the total plan and better than 95.5% for the electron component of the plan. For the two head and neck patient cases, the average clinical target volume (CTV) dose homogeneity index (V95%–V107%) over all the considered setup error scenarios was on average 19% lower for the PTV‐based plans and it had a larger standard deviation. The robust‐optimized plans achieved, on average, a 20% reduction in the OAR doses compared to the PTV‐based plans. For the brain patient case, the CTV dose homogeneity index was similar for the two plans, while the OAR doses were 22% lower, on average, for the robust‐optimized plan. No clear trend in terms of electron contributions was found across the three patient cases, although robust‐optimized plans tended toward higher electron beam energies.ConclusionsA framework for robust optimization of deliverable MBRT plans has been developed and validated. PTV‐based MBRT were found to not be robust to setup errors, while the dose delivered by the robust‐optimized plans were clinically acceptable for all considered error scenarios and had better OAR sparing. This study shows that the robust optimization is a promising alternative to conventional PTV margins for MBRT.
Instant determination of the artemisinin from various Artemisia annua L. extracts by LC‐ESI‐MS/MS and their in‐silico modelling and in vitro antiviral activity studies against SARS‐CoV‐2
Authors: Dogan Kubra , Erol Ebru , Didem Orhan Muge , Degirmenci Zehra , Kan Tugce , Gungor Aysen , Yasa Belkis , Avsar Timucin , Cetin Yuksel , Durdagi Serdar , Guzel Mustafa 
Published: September 2021

AbstractIntroductionNumerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS‐CoV‐2.ObjectiveThe main objective of our study was to determine artemisinin content by liquid chromatography electrospray ionisation tandem mass spectrometry (LC‐ESI‐MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS‐CoV‐2 using molecular modelling.MethodologyTwenty‐one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra‐rapid determined artemisinin active molecules by LC‐ESI‐MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS‐CoV‐2 virus was assessed by time resolved fluorescence energy transfer (TR‐FRET) assay.ResultsArtemisinin content in the range 0.062–0.066%. Artemisinin showed significant inhibition of 3CL protease activity but not Spike/ACE‐2 binding. The 50% effective concentration (EC50) of artemisinin against SARS‐CoV‐2 Spike pseudovirus was found greater than 50 μM (EC45) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF‐α production on both pseudovirus and lipopolysaccharide (LPS)‐induced THP‐1 cells were found significant in a dose dependent manner.ConclusionFurther studies of these extracts for COVID‐19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.
Comparing newborn outcomes after prenatal exposure to individual antidepressants: A retrospective cohort study
Authors: Marks Claire , Silvola Rebecca , Teal Evgennia , Quinney Sara K. , Haas David M. 
Published: September 2021

AbstractObjectiveTo compare associations between individual antidepressants and newborn outcomes.DesignRetrospective cohort study.SettingDeliveries in a large, US medical system.PopulationWomen who received at least one antidepressant prescription 3 months prior to conception through delivery.MethodsEligible women had maternal characteristics and newborn outcomes extracted from medical record data. Exposure was defined by the timing of the prescription during pregnancy.Main outcome measuresNewborn outcomes (any adaptation syndrome, neonatal intensive care unit (NICU) admission) were analyzed for each antidepressant and compared using standard statistics and multivariable regression compared to exposure to bupropion. Odds of outcomes based on timing of exposure were also explored.ResultsA total of 3,694 women were analyzed. Rates of any adaptation syndrome (p < 0.001), NICU admission (p < 0.001), and transient tachypnea of newborn (TTN) (p = 0.006) were significantly different between drugs. Infants exposed to duloxetine had the highest rates of NICU admissions (39.6%) and adaptation syndromes (15.1%). Venlafaxine‐exposed infants had the highest rates of TTN (18.2%). Controlling for maternal age, race, insurance, and gestational age at delivery, early pregnancy antidepressant exposure was associated with adaptation syndrome and NICU admission for both duloxetine (adjusted odds ratio (aOR) 2.31 [95% Confidence Interval (CI) 1.11–4.80] and aOR 2.47 [95% CI 1.40–4.34], respectively) and escitalopram (aOR 1.72 [95% CI 1.09–2.70] and aOR 1.64 [95% CI 1.21–2.22], respectively). Exposure in the third trimester was associated with any adaptation syndrome for citalopram, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine and NICU admission for bupropion, citalopram, duloxetine, escitalopram, and fluoxetine.ConclusionDuloxetine and escitalopram appear to have the strongest associations with any adaptation syndrome and NICU admission whereas bupropion and sertraline tended to have among the lowest risks of these outcomes. These results can help providers and patients discuss choice of individual antidepressant drugs during pregnancy.
Improving the accuracy of energy yield calculations of tandem solar cell‐based CPV‐modules
Authors: Steiner Marc , Mathur Paresh , Sarkar Subrata , Siefer Gerald 
Published: September 2021

AbstractEnergy yield calculations for CPV modules that use tandem solar cell technology have been performed and analysed in this work. Two BSQ D280 CPV modules were used as specimen: one located in Freiburg, Germany, and one in Greater Noida, India. The current–voltage curves of both modules were measured for several months together with the prevailing ambient conditions. The energy yield in the respective measurement periods were calculated using the software PVsyst. It has been found that the energy yield modelled with PVsyst has a good agreement with the one measured in Freiburg, but deviates by 10% from the one measured in Greater Noida. The reason is most likely the high aerosol content in Greater Noida and thus the non‐appropriate consideration of spectral irradiance impact by PVsyst, which uses air mass and DNI as the only atmospherical parameters. The accuracy of the PVsyst calculation has been strongly improved in this work by using SMR corrected DNI values as input for the PVsyst calculation. In this manner, the impact of spectral irradiance variation on (C)PV module power output can be considered in energy yield calculations by PVsyst. The deviation of the calculated and measured energy yield could be reduced to below 1%.