bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modeling and simulation of thyroid homeostasis: Implications for the Allan-Herndon-Dudley syndrome
Authors: Wolff Tobias M. , Veil Carina , Dietrich Johannes W. , Müller Matthias A. 
Published: December 2022

IntroductionA mathematical model of the pituitary-thyroid feedback loop is extended to deepen the understanding of the Allan-Herndon-Dudley syndrome (AHDS). The AHDS is characterized by unusual thyroid hormone concentrations and a mutation in the SLC16A2 gene encoding for the monocarboxylate transporter 8 (MCT8). This mutation leads to a loss of thyroid hormone transport activity. One hypothesis to explain the unusual hormone concentrations of AHDS patients is that due to the loss of thyroid hormone transport activity, thyroxine (T4) is partially retained in thyroid cells.MethodsThis hypothesis is investigated by extending a mathematical model of the pituitary-thyroid feedback loop to include a model of the net effects of membrane transporters such that the thyroid hormone transport activity can be considered. A nonlinear modeling approach based on the Michaelis-Menten kinetics and its linear approximation are employed to consider the membrane transporters. The unknown parameters are estimated through a constrained parameter optimization.ResultsIn dynamic simulations, damaged membrane transporters result in a retention of T4 in thyroid cells and ultimately in the unusual hormone concentrations of AHDS patients. The Michaelis-Menten modeling approach and its linear approximation lead to similar results.DiscussionThe results support the hypothesis that a partial retention of T4 in thyroid cells represents one mechanism responsible for the unusual hormone concentrations of AHDS patients. Moreover, our results suggest that the retention of T4 in thyroid cells could be the main reason for the unusual hormone concentrations of AHDS patients.
A grid-tied PV-fuel cell multilevel inverter under PQ open-loop control scheme
Authors: Muftah Magdi G. , Salem Mohamed , Buswig Yonis M. , Hamad Khlid Ben , Luta Doudou N. , Kamarol Mohamad 
Published: December 2022

Power generating entities’ connection to utility grids requires power converters to achieve high efficiency and low injected current harmonic distortion. The control of the power converter plays a crucial role in the grid-tied power converter’s performance. Various control techniques for grid-tied inverters ranging from classical to intelligent are introduced in several exist. Evaluating the current state and trend in grid-tied power inverters and related control methods, research shows that most works in this area focus on grid integration using the close-loop and other advanced control approaches. This is because these control methods are preferred since they provide adequate performance in case of uncertainties in the system. This investigation can aprove that PQ open-loop control technique can operate sufficiently and cost-effectively in grid-tied renewable and alternative power systems under normal operating conditions. Hence, this paper aims to assess the performance of a centralized single-stage grid-tied three-level diode clamped inverter connected to a PV-Fuel cell unit. An active and reactive power open-loop control scheme is employed to operate the inverter and achieves a current harmonic distortion below 5%. The system comprises a 150 kW/700 V PV, a 150 kW/1400 V fuel cell, a 265 kW multilevel inverter operating at a rated voltage of 415 V, and an LCL filter. Two operating scenarios are adopted to investigate the system’s responses further. In the first scenario, a local load of 509.2 kW is supplied from the PV-fuel cell inverter. The load also receives the grid’s power to meet the demand as the PV-fuel cell inverter provides only 265 kW. Whereas in the other scenario, the PV-fuel cell unit provides power to supply a local load while transporting the surplus to the grid. The results reveal the developed model’s good performance with a current harmonic distortion of 0.33%.
Spatial variation in groundwater depletion across China under multiple stresses
Authors: Lin Xuemin , Li Weifeng , Bai Xueding , Han Lijian , Ming Dongping 
Published: December 2022

Groundwater, an essential component of the hydrological cycle, has been subject to intense pressure worldwide over recent decades, such that reserves have changed appreciably, challenging our ability to deliver on water resource protection goals. While the changes in storage can be quantified, there is little information about what drives the changes in groundwater storage (GWS) and how the impacts of those drivers vary spatially and temporally. In this study, the spatial and temporal variations in GWS across China from 2002 to 2016 are studied, and how GWS was influenced by natural and anthropogenic drivers at multiple scales is examined using Gravity Recovery and Climate Experiment (GRACE) satellite data. The national-scale GWS declined continuously at a rate of −0.27 cm/a over the study period. Interesingly, the difference in the GWS change between the south (increasing) and the north (decreasing) was decreasing, while the gap between the east (increasing) and the west (decreasing) was becoming wider. The main drivers of GWS changes at the national and regional scales were precipitation, agricultural water consumption, and the total population, while industrial water consumption, domestic water consumption, and evapotranspiration were important at the regional and provincial scales. Policies recently implemented to protect GWS have been effective. Given the potential for GWS changes to have impacts at multiple scales, policies and goals should address the drivers of GWS changes at different scales.
Successful treatment of rituximab-unresponsive elderly-onset neuromyelitis optica spectrum disorder and hypogammaglobulinemia with ofatumumab plus intravenous immunoglobulin therapy in a patient with mutant FCGR3A genotype: A case report
Authors: Zhang Weihe , Jiao Yujuan , Jiao Jinsong , Jin Ming , Peng Dantao 
Published: December 2022

BackgroundElderly-onset neuromyelitis optica spectrum disorder (NMOSD) is a rare entity that poses a therapeutic challenge. We report a case of elderly-onset NMOSD with mutant FCGR3A genotype who was successfully treated with ofatumumab after multiple episodes of relapse.Case ReportThe patient was a 67-year-old woman who was diagnosed with NMOSD with high disease activity. She experienced six episodes of relapse over a period of 2 years despite immunosuppressant therapy with intravenous rituximab (RTX), oral steroids, mycophenolate mofetil, and tacrolimus. At the last relapse, she was unable to walk and developed immunosuppressant-induced hypogammaglobulinemia. Based on the insufficient B cell depletion and FCGR3A-FF genotype carrier, the patient was diagnosed as RTX non-responder. After subcutaneous ofatumumab plus intravenous immunoglobulin replacement therapy, she was able to walk independently, and experienced no further relapse. Ofatumumab was well-tolerated, and sufficiently depleted the circulating B cells.ConclusionOfatumumab might be an effective alternative in RTX-unresponsive NMOSD, and seems to be safe in elderly patients.
Patients with positive HER-2 amplification advanced gastroesophageal junction cancer achieved complete response with combined chemotherapy of AK104/cadonilimab (PD-1/CTLA-4 bispecific): A case report
Authors: Peng Jieqiong , Zhu Qiang , Peng Ziru , Chen Zhen , Liu Yuantao , Liu Bo 
Published: December 2022

BackgroundHuman epidermal growth factor receptor 2 (HER2) is the most prominent therapeutic target for advanced gastric (G)/GEJ cancer. However, targeted therapy did not significantly improve survival. Currently, there are no regimens for the treatment of HER-2 amplification that exclude targeted agents.Case presentationA 42-year-old man was diagnosed with adenocarcinoma of GEJ (stage IV) with liver metastasis and lung metastasis. The patient was enrolled in a trial that excluded patients with known HER2-positivity: AK104, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy (mXELOX) as first-line therapy for advanced gastric G/GEJ cancer (NCT03852251). After six cycles of AK104 combined with chemotherapy therapy, immune-related pulmonary toxicity was observed. We rechallenged AK104 after hormone therapy, and no further pulmonary toxicity was observed. Immune-related hepatitis occurred in the patient during immunotherapy combined with single-drug capecitabine therapy. After combining steroid therapy with mycophenolate mofetil, the patient’s immune hepatitis improved. Nevertheless, the patient was excluded from the clinical study due to the long-term absence of medication. Antitumor therapy was also discontinued in view of the patient’s adverse immune response. The patient did not receive subsequent immune antitumor therapy, and immune-related hepatitis still occurred intermittently, but the disease evaluation was maintained at PR. A complete response was confirmed by PET/CT and the biopsy specimen from gastroscopy on 2020-06-10. Next generation sequencing of biopsy tissue was used to guide subsequent therapy at a recent follow-up visit. The results indicated that ERBB2 mutations occurred at copy number 58.4934 (HER-2), TMB = 3.1, MSS. IHC: EBV (−), PD-L1 CPS = 3, HER-2 (3+).ConclusionPatients with HER-2-positive advanced GEJ cancer received PD-1/CTLA-4 bispecific immunotherapy combined with chemotherapy and achieved complete remission. It offers a novel, highly specific, and highly potent therapeutic option for HER-2-positive patients. Its use should be considered as a new treatment when trastuzumab is not viable. Currently, we are working to overcome this resistance.
Application of interpolation methodology with dynamical constraint to the suspended particulate matter in the Liaodong Bay
Authors: Geng Haoyi , Peng Haohong , Shi Jie , Mao Xinyan , Lv Xianqing 
Published: December 2022

IntroductionSuspended Particulate Matter (SPM) influences the primary production and the distributions of pollutants in the ocean. Besides, the regulation mechanisms of SPM in the Liaodong Bay were complicated.MethodTo analyze the distributions and influencing factors of SPM, based on the adjoint assimilation method, an interpolation method with dynamical constraint was established in the Liaodong Bay.ResultIn two ideal experiments, the cost function, Mean Absolute Error (MAE) and Normalized Mean Error (NME) all had reduced by more than 90%, which proved the accuracy of the interpolation method. Based on conventional observations of SPM, the distributions of dynamically constrained, Kriging and radial basis function (RBF) interpolations in March, May, August and October of 2015 were obtained.DiscussionThe cross-validation was carried out to compare the dynamically constrained interpolation and the unconstrained interpolations. Among seven unconstrained interpolation methods, the averaged MAE of RBF interpolation was the lowest, which was 10.976 mg/L. The averaged MAE of dynamically constrained interpolation was 7.703 mg/L, reduced by 29.8% compared with the RBF interpolation. It was indicated that RBF interpolation was the most accurate among the seven unconstrained interpolations and dynamically constrained interpolation was more accurate than unconstrained interpolations at the observation stations. The distributions of dynamically constrained and RBF interpolations were compared with Korean Geostationary Ocean Color Imager (GOCI) satellite-derived distributions of SPM concentrations in the Liaodong Bay. Fully considering the influences of the hydrodynamic processes, the dynamically constrained interpolation provided distributions more consistent with the satellite-derived distributions. However, due to the lack of observations in some areas and ignoring the influences of currents, some high values of SPM concentration were not captured by the distributions of RBF interpolation. Moreover, in accordance with the results of dynamically constrained interpolation, it was found that the SPM concentrations in the bay were affected by the SPM discharge from the Liao River Basin.
Estimation of sound speed profiles based on remote sensing parameters using a scalable end-to-end tree boosting model
Authors: Ou Zhenyi , Qu Ke , Shi Min , Wang Yafen , Zhou Jianbo 
Published: December 2022

IntroductionIn underwater acoustic applications, the three-dimensional sound speed distribution has a significant impact on signal propagation. However, the traditional sound speed profile (SSP) measurement method requires a lot of manpower and time, and it is difficult to popularize. Satellite remote sensing can collect information on a large ocean surface area, from which the underwater information can be derived.MethodIn this paper, we propose a method for reconstructing the SSP based on an extensible end-to-end tree boosting (XGBoost) model. Combined with satellite remote sensing data and Argo profile data, it extracts the characteristic matrix of the SSP and analyzes the contribution rate of each order matrix to reduce the introduction of noise. The model inverts the SSP above 1000 m in the South China Sea by using the root mean square error (RMSE) as the precision evaluation index.ResultThe results showed that the XGBoost model could better reconstruct the SSP above 1000 m, with a RMSE of 1.75 m/s. Compared with the single empirical orthogonal function regression (sEOF-r) model of the linear regression method, the RMSE of the XGBoost model was reduced by 0.59 m/s.DiscussionFor this model, the RMSE of the inversion results was smaller, the robustness was better, and the regression performance was superior to that of the sEOF-r model at different depths. This study provided an efficient tree boosting model for SSP reconstruction, which could reliably and instantaneously monitor the 3D sound speed distribution.
Insoluble chitosan complex as a potential adsorbent for aflatoxin B1 in poultry feed
Authors: Delgado-Cedeño Armando , Hernández-Martínez Sara Paola , Ramos-Zayas Yareellys , Marroquín-Cardona Alicia Guadalupe , Méndez-Zamora Gerardo , Franco-Molina Moisés Armides , Kawas Jorge R. 
Published: December 2022

As a class of secondary metabolites or toxins produced by fungi, aflatoxins can poison humans and animals; among them, aflatoxin B1 (AFB1) is the most dangerous one owing to its carcinogenic and mutagenic properties that increase risks for hepatocellular carcinoma in humans; hence, adsorbents such as smectites are commonly included in poultry feed to mitigate their effects. In this study, chitosan was crosslinked with sodium dodecyl sulfate (SDS) to form an insoluble polymer complex that is stable at the relevant physiological pH levels. The characterization via Fourier transforms infrared spectroscopy revealed the interaction between the sulfate groups of the SDS and the amine group of chitosan (1,016 and 819 cm−1); this result was further confirmed by the X-ray diffraction patterns with a change in the crystalline structure of the chitosan-insoluble complex (2θ = 4.76°, 7°, and 22°). The morphology of the chitosan-insoluble complex obtained using a field emission scanning electron microscope (FE-SEM) revealed that particles were slightly porous. After characterization, the performance of the chemically modified polymer complex was evaluated as an adsorbent for AFB1 and compared with those of the unmodified chitosan, soluble chitosan complex, and commercial montmorillonite clay binder. In addition, the polymer complex was investigated as an adsorbent in an in vitro model for the poultry gastrointestinal system. Sequestration of AFB1 by a chemically modified polymer complex was 93.4%, equivalent to that of commercial montmorillonite clay (99.5%). However, these treatments also sequestered microminerals, particularly selenium and iron. This pH-stable, high-capacity adsorbent could be used in poultry feed to reduce the uptake of AFB1.
AAV8-mediated sVEGFR2 and sVEGFR3 gene therapy combined with chemotherapy reduces the growth and microvasculature of human ovarian cancer and prolongs the survival in mice
Authors: Kujala Anni , Valkonen Elina , Sallinen Hanna , Tuppurainen Laura , Laakso Hanne , Ylä-Herttuala Elias , Liimatainen Timo , Kujala Jouni , Jokelainen Otto , Sironen Reijo , Anttila Maarit , Ylä-Herttuala Seppo 
Published: December 2022

BackgroundVascular endothelial growth factors (VEGFs) are major regulators of intratumoral angiogenesis in ovarian cancer (OVCA). Overexpression of VEGFs is associated with increased tumor growth and metastatic tendency and VEGF-targeting therapies are thus considered as potential treatments for OVCA. Here, we examined the antiangiogenic and antitumoral effects on OVCA of adeno-associated virus 8 (AAV8)-mediated expression of soluble VEGF receptors (sVEGFRs) sVEGFR2 and sVEGFR3 together with paclitaxel and carboplatin chemotherapy.Materials and methodsImmunodeficient mice were inoculated with human OVCA cell line SKOV-3m. Development of tumors was confirmed with magnetic resonance imaging (MRI) and mice were treated with gene therapy and paclitaxel and carboplatin chemotherapy. The study groups included (I) non-treated control group, (II) blank control vector AAV8-CMV, (III) AAV8-CMV with chemotherapy, (IV) AAV8-sVEGFR2, (V) AAV8-sVEGFR3, (VI) AAV8-sVEGFR2 and AAV8-sVEGFR3, and (VII) AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy. Antiangiogenic and antitumoral effects were evaluated with immunohistochemical stainings and serial MRI.ResultsReduced intratumoral angiogenesis was observed in all antiangiogenic gene therapy groups. The combined use of AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy suppressed ascites fluid formation and tumor growth, thus improving the overall survival of mice. Antitumoral effect was mainly caused by AAV8-sVEGFR2 while the benefits of AAV8-sVEGFR3 and chemotherapy were less prominent.ConclusionCombined use of the AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy reduces intratumoral angiogenesis and tumor growth in OVCA mouse model. Results provide preclinical proof-of-concept for the use of soluble decoy VEGFRs and especially the AAV8-sVEGFR2 in the treatment of OVCA.
Reduced blood-brain barrier penetration of acne vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity
Authors: Grada Ayman , Del Rosso James Q. , Moore Angela Y. , Stein Gold Linda , Harper Julie , Damiani Giovanni , Shaw Katharina , Obagi Sabine , Salem Raidah J. , Tanaka S. Ken , Bunick Christopher G. 
Published: December 2022

BackgroundVestibular side effects such as dizziness and vertigo can be a limitation for some antibiotics commonly used to treat acne, rosacea, and other dermatology indications.ObjectiveUnlike minocycline, which is a second-generation tetracycline, sarecycline, a narrow-spectrum third-generation tetracycline-class agent approved to treat acne vulgaris, has demonstrated low rates of vestibular-related adverse events in clinical trials. In this work, we evaluate the brain-penetrative and lipophilic attributes of sarecycline in 2 non-clinical studies and discuss potential associations with vestibular adverse events.MethodsRats received either intravenous sarecycline or minocycline (1.0 mg/kg). Blood-brain penetrance was measured at 1, 3, and 6 h postdosing. In another analysis, the lipophilicity of sarecycline, minocycline, and doxycycline was measured via octanol/water and chloroform/water distribution coefficients (logD) at pH 3.5, 5.5, and 7.4.ResultsUnlike minocycline, sarecycline was not detected in brain samples postdosing. In the octanol/water solvent system, sarecycline had a numerically lower lipophilicity profile than minocycline and doxycycline at pH 5.5 and 7.4.ConclusionThe reduced blood-brain penetrance and lipophilicity of sarecycline compared with other tetracyclines may explain low rates of vestibular-related adverse events seen in clinical trials.
Recent estimates and predictions of 5-year survival rate in patients with pancreatic cancer: A model-based period analysis
Authors: Li Jing , Li Yunmei , Chen Chong , Guo Jiayu , Qiao Mengmeng , Lyu Jun 
Published: December 2022

BackgroundThe 5-year survival rate for pancreatic cancer (PC) is incredibly low, resulting in this often being a fatal disease. Timely and accurate assessment of the survival rate and prognosis of patients with PC is of great significance for the development of new programs for prevention, monitoring, and treatment.MethodsPeriod analysis and further stratified analysis were used to determine the 5-year relative survival rate (RSR) of patients with PC from 2002 to 2016 using the Surveillance, Epidemiology, and End Results (SEER) project database of the National Cancer Institute. Based on this, a generalized linear model was created to predict the survival rate of patients from 2017 to 2021.ResultDuring 2002–2016, the 5-year RSR of patients with PC increased from 7.9 to 23.7%. The generalized linear model predicted that the survival rate had increased to 33.9% during 2017–2021, and hence, it was still unacceptably low. The survival rate of patients aged ≥75 years at diagnosis was the lowest among all age groups and was predicted to be only 21.4% during 2017–2021. Notably, the survival rate of patients with differentiation grade III at diagnosis remains particularly low at 7.6%.ConclusionThe survival rates of patients with PC, although slightly improved, remain extremely low. Timely assessment of the trend of survival rate changes in patients with PC further improves the prognosis of tumor patients and provides data support for relevant medical works to formulate effective tumor prevention and control policies.
Comparison of lens refractive parameters in myopic and hyperopic eyes of 6–12-year-old children
Authors: Shang Jianming , Hua Yanjun , Wang Yuliang , He Ji C. , Zhou Xingtao , Qu Xiaomei 
Published: December 2022

Background/aimsTo evaluate the influence of cycloplegia on lens refractive parameters in 6–12-year-old children with myopia and hyperopia for exploring the pathogenesis of myopia.MethodsOne hundred eyes of 100 patients (50 boys) were included. In the myopic group, 50 subjects (25 boys and 25 right eyes) were enrolled with a mean age of 9.20 ± 1.69 years. IOLMaster 700 measurements were performed pre- and post-cycloplegia. The pictures were marked using semi-automatic software. The lens curvature and power were obtained using MATLAB image processing software. Paired and independent samplet-tests were used for data analysis. Statistical significance was set atP&lt; 0.05.ResultsAnterior and posterior lens curvature radius in myopic eyes were larger than those in hyperopic eyes, both pre- and post-cycloplegia (bothP&lt; 0.001). The refractive power in myopic eyes was lower than that in hyperopic eyes without cycloplegia, both pre- and post-cycloplegia (bothP&lt; 0.001). The changes in anterior lens curvature and refractive power between pre- and post-cycloplegia in hyperopic eyes were larger than those in myopic eyes (bothP&lt; 0.05). No significant difference was found in the change in posterior lens curvature and refractive power after cycloplegia in hyperopic and myopic eyes (P&gt; 0.05).ConclusionAnterior and posterior surfaces of the lens were flatter, and the refractive power was lower in the myopia group than in the hyperopia group. Myopic and hyperopic patients showed a tendency for lens flattening and refractive power decrease after cycloplegia. Hyperopic patients had more changes in anterior lens curvature and refractive power after cycloplegia.