bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of congenital thrombocytopenia and decreased collagen reactivity in G6b-B–deficient mice
Authors: Mazharian Alexandra , Maître Blandine , Bornert Alicia , Hennequin Desline , Lourenco-Rodrigues Marc , Geer Mitchell J. , Smith Christopher W. , Heising Silke , Walter Michaela , Montel Florian , Walker Lucy S. K. , de la Salle Henri , Watson Steve P. , Gachet Christian , Senis Yotis A. 
Published: October 2022

Abstract
Mice lacking the immunoreceptor tyrosine-based inhibition motif-containing co-inhibitory receptor G6b-B (Mpig6b, G6b knockout, KO) are born with a complex megakaryocyte (MK) per platelet phenotype, characterized by severe macrothrombocytopenia, expansion of the MK population, and focal myelofibrosis in the bone marrow and spleen. Platelets are almost completely devoid of the glycoprotein VI (GPVI)-FcRγ-chain collagen receptor complex, have reduced collagen integrin α2β1, elevated Syk tyrosine kinase activity, and a subset has increased surface immunoglobulins. A similar phenotype was recently reported in patients with null and loss-of-function mutations in MPIG6B. To better understand the cause and treatment of this pathology, we used pharmacological- and genetic-based approaches to rescue platelet counts and function in G6b KO mice. Intravenous immunoglobulin resulted in a transient partial recovery of platelet counts, whereas immune deficiency did not affect platelet counts or receptor expression in G6b KO mice. Syk loss-of-function (R41A) rescued macrothrombocytopenia, GPVI and α2β1 expression in G6b KO mice, whereas treatment with the Syk kinase inhibitor BI1002494 partially rescued platelet count but had no effect on GPVI and α2β1 expression or bleeding. The Src family kinase inhibitor dasatinib was not beneficial in G6b KO mice. In contrast, treatment with the thrombopoietin mimetic romiplostim rescued thrombocytopenia, GPVI expression, and platelet reactivity to collagen, suggesting that it may be a promising therapeutic option for patients lacking functional G6b-B. Intriguingly, GPVI and α2β1 expression were significantly downregulated in romiplostim-treated wild-type mice, whereas GPVI was upregulated in romiplostim-treated G6b KO mice, suggesting a cell intrinsic feedback mechanism that autoregulates platelet reactivity depending on physiological needs.
Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy
Authors: Kong Fang-Fang , Pan Guang-Sen , Zhai Rui-Ping , Du Cheng-Run , He Xia-Yun , Shen Chun-Ying , Lu Xue-Guan , Sun Tuan-Qi , Wang Yu , Ji Qing-Hai , Hu Chao-Su , Ying Hong-Mei 
Published: October 2022

AbstractBackgroundTo review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT).MethodsFrom April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28–30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.ResultsAmong the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153).ConclusionDistant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.
Age in combination with gender is a valuable parameter in differential diagnosis of solid pseudopapillary tumors and pancreatic neuroendocrine neoplasm
Authors: Wu Leshuang , Zou Tianle , Shi Dan , Cheng Huan , Shahbaz Muhammad , Umar Muhammad , Li Tianfeng , Zhang Xianbin , Gong Peng , Wei Yushan 
Published: October 2022

AbstractBackgroundThe clinicopathological characteristics of solid pseudopapillary tumor (SPT) and pancreatic neuroendocrine neoplasm (pNEN) are different. We, therefore, systematically investigated the performance of the clinicopathological characteristics in distinguishing SPT from pNEN.MethodsWe collected the cases from the Surveillance, Epidemiology, and End Results Program. The International Classification of Diseases for Oncology, third edition (ICD-O-3) for tumors was used to identify patients with pNEN or patients with SPT. To determine the performance of age in combination with gender in distinguishing SPT from pNEN, a nomogram was developed and the performance of this nomogram was evaluated by the receiver operating characteristic curve and the area under the curve (AUC).ResultsIn the training cohort, 563 patients with pNENs and 30 patients with SPTs were recruited. The logistic regression and receiver operating characteristic curves suggest that age, gender, T-stage, N-stage, and M-stage could discriminate SPT and pNEN. The AUC of age, gender, T-stage, N-stage, and M-stage was 0.82, 0.75, 0.65, 0.69, and 0.70, respectively. Based on the nomogram, we observed that the AUC of age and gender is significantly high than that of the T-stage, N-stage, and M-stage.ConclusionsThe present study proposes a non-invasive nomogram that could aid in the differential diagnosis of pNEN and SPT. This might help the clinicians to distinguish SPT from pNEN and choose the appropriate treatments for the patients.
Hotspots and determinants of women’s discriminatory attitude towards people living with HIV; evidence from ethiopian demographic and health survey data
Authors: Muluneh Atalay Goshu , Merid Mehari Woldemariam , Kassa Getahun Molla , Bitew Desalegn Anmut , Ferede Menberesibhat Getie 
Published: October 2022

Abstract
Background
Human Immunodeficiency Virus (HIV) is the major public health concern in Ethiopia with more profound effect on women. Discriminatory attitude towards people living with HIV (PLWH) impose a significant impact on patient outcomes and related issues. Hence, this study aimed to investigate the hotspot areas and determinant factors of women’s discriminatory attitude towards people living with HIV.

Methods
An in-depth secondary data analysis was conducted based on Ethiopian demographic and health survey (EDHS) 2016. A total of weighed 13,822 reproductive-age women were included in the analysis. The non-spatial analysis was conducted using Stata 16. A mixed effect multi-level logistic regression model was fitted to identify determinant factors of discriminatory attitude towards PLWH. A p-value < 0.2 and 0.05 were used as a cut-off point to declare statistical significance for the bi- and multi-variable regression models, respectively. Four separate models i.e. the null, individual, community level model, and a fourth combined model were fitted. Model comparison was done using deviance. Random effect parameters such as correlation coefficient, median odds ratio, and proportional change in variance were used to explain the variation between and within clusters. Global and local level spatial analyses were conducted using Global Moran’s index, GetisOrd Gi* statistics, and Spatial scan statistics were conducted.

Results
The magnitude of women’s discriminatory attitude towards PLWH was 62.66% (95%CI: 60.12, 65.10). The discriminatory attitude of women towards PLWH was spatially clustered (Moran’s index = 0.41, P < 0.01). The hotspots of discriminatory attitude towards PLWH were detected in most parts of the Tigray region; Northern, and southeast borders of the Amhara region; Addis Ababa city; Central, Southern, and western Oromiya region; and East, south, and northeastern parts of South Nations, Nationalities and Peoples Region (SNNPR). Being rural resident, and having no media exposure were positively associated while better educational statuses, better wealth index, unmarried, having comprehensive HIV knowledge, Orthodox religion fellow, and ever being tested for HIV were negatively associated with women’s discriminatory attitude towards people living with HIV.

Conclusion
Discriminatory attitude of women towards PLWH was high in Ethiopia. Hotspots were detected in Amhara, Oromiya, SNNPR, Tigray regions, and Addis Ababa city. Socio-demographic, socio-economic, and HIV knowledge-related factors determine the women’s discriminatory attitude towards PLWH.
Impact of hypoglycemia at the time of hospitalization for heart failure from emergency department on major adverse cardiovascular events in patients with and without type 2 diabetes
Authors: Cha Seon-Ah , Yun Jae-Seung , Kim Gee-Hee , Ahn Yu-Bae 
Published: October 2022

Abstract
Background
Few studies have examined the association between hypoglycemic episodes among people with type 2 diabetes (T2DM) at the time of hospitalization for heart failure (HF) and cardiovascular outcomes.

Methods
From March 2016 to June 2018, we conducted a retrospective cohort study to investigate hypoglycemia during HF hospitalization in the emergency department, three-point major adverse cardiovascular events (3P-MACE), and all-cause mortality; these were followed up through June 2021. HF hospitalization was defined according to American Heart Association criteria. Hypoglycemia was defined as a glucose level < 3.9 mmol/L at the time of HF hospitalization. We classified the enrolled patients into three groups (reference group, those without T2DM or hypoglycemia; those diagnosed with T2DM without hypoglycemia; and those with hypoglycemia and T2DM). We used Cox proportional hazard regression analysis to investigate the association between the three groups and the development of the first occurrence of 3P-MACE and all-cause mortality.

Results
During a median of 25 months of follow-up, a total of 783 patients admitted due to HF were analyzed. In total, 159 (20.3%) cases of 3P-MACE were identified, and the mortality rate was 20.2% (n = 158). The median age of patients was 76.0 (65.0–82.0) years, and 49.0% were men. Patients with 3P-MACE had a lower body mass index (22.6 [20.4–25.1] vs. 23.8 [21.3–26.7]), higher frequency of previous history of HF (24.5% vs. 15.7%), T2DM (64.2% vs. 47.3%), higher rates of hypoglycemia at the time of HF hospitalization (19.5% vs. 7.7%), and lower eGFR levels (61.1 [36.0–80.7] mL/min/1.73 m2 vs. 69.2 [45.8–89.5] mL/min/1.73 m2) than those without 3P-MACE. The multivariable adjusted HR of 3P-MACE was as follows: group with hypoglycemia and T2DM: HR, 2.29; 95% CI: 1.04–5.06; group with T2DM without hypoglycemia: HR: 1.42; 95% CI: 0.86–2.33; and all-cause mortality group with hypoglycemia and T2DM: HR: 2.58; 95% CI: 1.26–5.31, group with T2DM without hypoglycemia: HR: 1.32; 95% CI: 0.81–2.16; compared to the reference group (group without T2DM or hypoglycemia).

Conclusions
T2DM and hypoglycemia are independent risk factors for 3P-MACE and all-cause mortality compared to those without hypoglycemia during HF hospitalization.
Thoracolumbar fascia mobility and chronic low back pain: Phase 2 of a pilot and feasibility study including multimodal chiropractic care
Authors: Vining Robert , Onifer Stephen M. , Twist Elissa , Ziegler Anna-Marie , Corber Lance , Long Cynthia R. 
Published: October 2022

Abstract
Background
Thoracolumbar fascia mobility observed with ultrasound imaging and calculated as shear strain is lower in persons with chronic low back pain. This pilot and feasibility trial assessed thoracolumbar shear strain in persons with chronic low back pain following spinal manipulation and over an 8-week course of multimodal chiropractic care.

Methods
Adults self-reporting chronic low back pain ≥ 1 year participated between September 2019 and April 2021 in a trial using ultrasound imaging to measure thoracolumbar shear strain. Ultrasound imaging occurred 2–3 cm lateral to L2-3 while participants relaxed prone on an automated table moving the lower extremities downward 15 degrees, for 5 cycles at 0.5 Hz. Pain intensity on an 11-point numerical rating scale, disability, pain interference, and global improvement were also collected. Participants received 8-weeks of twice-weekly chiropractic care including spinal manipulation, education, exercise, self-management advice and myofascial therapies. Shear strain was computed using 2 methods. The highest shear strain from movement cycles 2, 3, or 4 was averaged over right and left sides for each participant. Alternately, the highest shear strain from movement cycle 3 was used. All data were analyzed over time using mixed-effects models. Estimated mean changes are reported.

Results
Of 20 participants completing 8-weeks of chiropractic care (female n = 11), mean (SD) age was 41 years (12.6); mean BMI was 28.5 (6.2). All clinical outcomes improved at 8-weeks. Mean (95% confidence interval) pain intensity decreased 2.7 points (− 4.1 to − 1.4) for females and 2.1 points (− 3.7 to 0.4) for males. Mean Roland–Morris disability score decreased by 5 points (− 7.2 to − 2.8) for females, 2.3 points (− 4.9 to 0.2) for males. Mean PROMIS pain interference T-score decreased by 8.7 points (− 11.8 to − 5.5) for females, 5.6 points (− 9.5 to − 1.6) for males. Mean shear strain at 8-weeks increased in females 5.4% (− 9.9 to 20.8) or 15% (− 0.5 to 30.6), decreasing in males 6.0% (− 24.2 to 12.2) or 2% (− 21.0 to 16.8) depending on computational method.

Conclusion
Spinal manipulation does not likely disrupt adhesions or relax paraspinal muscles enough to immediately affect shear strain. Clinical outcomes improved in both groups, however, shear strain only increased in females following 8-weeks of multimodal chiropractic care.
Trial registration ClinicalTrials.gov registration is NCT03916705.
An unsupervised image segmentation algorithm for coronary angiography
Authors: Yin Zong-Xian , Xu Hong-Ming 
Published: October 2022

AbstractComputer visual systems can rapidly obtain a large amount of data and automatically process them with ease. These characteristics constitute advantages for the application of such systems in the automatic analysis of medical images, as well as in processing technology. The precision of image segmentation, which plays a critical role in computer visual systems, directly affects the quality of processing results. Coronary angiographs feature various background colors, complex patterns, and blurry edges. The image areas containing blood vessels cannot be precisely segmented through regular methods. Therefore, this study proposed an unsupervised learning algorithm that uses regional parameter expansion (RPE). This method was derived from the flood fill algorithm, which can effectively segment image areas containing blood vessels despite a complex background or uneven light and shadow. An optimal cover tree (OCT) algorithm was proposed for the establishment of coronary arteries and the estimation of vessel diameter. Through the region growing method, spanning trees were used to record the cover length of adjacent connections, thereby establishing vessel paths, and the length can be used to track changes in vessel diameter.
Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy
Authors: Chiriaco Cristina , Donini Chiara , Cortese Marco , Ughetto Stefano , Modica Chiara , Martinelli Ilaria , Proment Alessia , Vitali Letizia , Fontani Lara , Casucci Monica , Comoglio Paolo Maria , Giordano Silvia , Sangiolo Dario , Leuci Valeria , Vigna Elisa 
Published: October 2022

Abstract
Background
Aberrant activation of the MET receptor in cancer is sustained by genetic alterations or, more frequently, by transcriptional upregulations. A fraction of MET-amplified or mutated tumors are sensible to MET targeting agents, but their responsiveness is typically short-lasting, as secondary resistance eventually occurs. Since in the absence of genetic alterations MET is usually not a tumor driver, MET overexpressing tumors are not/poorly responsive to MET targeted therapies. Consequently, the vast majority of tumors exhibiting MET activation still represent an unmet medical need.

Methods
Here we propose an immunotherapy strategy based on T lymphocytes expressing a Chimeric Antigen Receptor (CAR) targeting MET overexpressing tumors of different histotypes. We engineered two different MET-CAR constructs and tested MET-CAR-T cell cytotoxic activity against different MET overexpressing models, including tumor cell lines, primary cancer cells, organoids, and xenografts in immune-deficient mice.

Results
We proved that MET-CAR-T exerted a specific cytotoxic activity against MET expressing cells. Cell killing was proportional to the level of MET expressed on the cell surface. While CAR-T cytotoxicity was minimal versus cells carrying MET at physiological levels, essentially sparing normal cells, the activity versus MET overexpressing tumors was robust, significantly controlling tumor cell growth in vitro and in vivo. Notably, MET-CAR-T cells were also able to brake acquired resistance to MET targeting agents in MET amplified cancer cells carrying secondary mutations in downstream signal transducers.

Conclusions
We set and validated at the pre-clinical level a MET-CAR immunotherapy strategy potentially beneficial for cancers not eligible for MET targeted therapy with inhibitory molecules, including those exhibiting primary or secondary resistance.
Smart stability indicating spectrophotometric methods for determination of modafinil: the promising treatment for post-covid neurological syndrome
Authors: Elsheikh Soha G. , El-Mosallamy Sally S. , Fayez Yasmin M. , Hassan Abeer M. E. 
Published: October 2022

AbstractModafinil (MDF) is one of the neurostimulants with a potential effect in the COVID-19 ICU ventilated patients and post-COVID neurological syndrome treatment. Four rapid, simple and cost-effective stability indicating spectrophotometric methods were used for estimation of MDF in the presence of its acidic degradation product, namely; ratio difference (RD), first derivative of the ratio spectra (1DD), mean centering (MCR) and ratio subtraction method (RS). These methods were validated according to ICH guidelines and all methods revealed a good linearity in concentration range of (5-30 µg/mL) in addition to a good accuracy and precision with mean percentage recovery of 99.97 ± 0.305 for (RD), 100.10 ± 0.560 for (1DD), 100.02 ± 0.483 for (MCR) & 99.18 ± 1.145 for (RS) method. Specificity of the proposed methods was assessed and MDF was determined in the presence of up to 80% of its acidic degradation product for RD, 1DD, MCR and RS methods. The proposed methods were successfully applied for the determination of MDF in bulk powder and its tablet dosage form with mean percentage recovery of 100.33 ± 0.915 for (RD), 100.62 ± 0.985 for (1DD), 99.70 ± 0.379 for (MCR) and 100.21 ± 0.313 for (RS) method. The results obtained were statistically compared with those of official HPLC method and showed no significant difference with relevance accuracy and precision.
Plumbagin attenuates Bleomycin-induced lung fibrosis in mice
Authors: Mehdizadeh Saber , Taherian Marjan , Bayati Paria , Mousavizadeh Kazem , Pashangzadeh Salar , Anisian Ali , Mojtabavi Nazanin 
Published: October 2022

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with limited treatment options. Plumbagin (PL) is an herbal extract with diverse pharmacological effects that have been recently used to treat various types of cancer. This study aims to explore the anti-fibrotic effect of PL and possible underlying mechanisms in IPF.

Methods
We used a bleomycin-induced experimental mouse model of lung fibrosis to assess the potential anti-fibrotic effect of PL. Histological analysis of lung tissue samples by H&E and Masson’s trichrome staining and hydroxyproline assay was performed to evaluate the fibrotic alterations. ELISA and real-time quantitative PCR were conducted to determine the amount of tumor necrosis factor-alpha (TNFα), tumor growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and endothelin-1 (ET-1).

Results
Bleomycin exposure induced lung fibrosis, which was indicated by inflammation, collagen deposition, and structural damage. PL remarkably prevented bleomycin-induced lung fibrosis. Furthermore, PL significantly inhibited TNF-α and TGF-β production. PL also diminished the upregulated expression of CTGF and ET-1 induced by bleomycin.

Conclusion
Overall, our findings suggest PL as an anti-fibrotic agent acting via down-regulation of TGF-β/CTGF or ET-1 axis, as well as TNF-α, to improve lung fibrosis.
Health shock, medical insurance and financial asset allocation: evidence from CHFS in China
Authors: Liu Yaxuan , Hao Yu , Lu Zhi-Nan 
Published: October 2022

Abstract
Background
As health care cost is taking an increasingly substantial proportion of national wealth, health shocks and the subsequent medical expenditures have become increasingly vital contributions to financial risks. However, the individual or combined effects of social and financial medical insurance on household financial behaviors are poorly understood. This research aims to examine the effect of health shocks on financial asset mobility and portfolio allocation of the household. Also, whether medical insurance positively affects the financial market will be analyzed.

Methods
Linear-regression models are used to determine the relationship between health shock, medical insurance, and household financial behaviors, including liquidity measures and financial portfolio (risk and risk-free assets). Two types of variables (transition probability and upward mobility) are constructed to measure the aggregate-level financial asset mobility. The portfolio of financial assets is categorized according to the risk it bears.

Results
Households which experience health shocks are found to exhibit lower transition probability and upward mobility of financial assets than households that do not, and health shocks pose a more serious threat to low-income households. From the inter-temporal perspective, households that have medical insurance exhibit a higher probability of raising their position within the national financial asset distribution, and are more inclined to invest in the risky financial assets. Commercial insurance displays a larger marginal effect on financial asset allocation than social insurance. Our study results highlight an essential link between health shocks, medical insurance, and household financial behavior.

Conclusion
This work identified and described the relationship between health-related factors (health shock and two types of medical insurance) and household financial behaviors (risky investment involvement and class mobility in financial asset). A strong link exists between the health and financial market, with heterogenous effects between urban and rural groups, households with distinct income levels, etc. A multilayered insurance system would be helpful to facilitate household income, financial consumption, and economic growth.