bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early
Authors: Morelli Mariangela , Lessi Francesca , Barachini Serena , Liotti Romano , Montemurro Nicola , Perrini Paolo , Santonocito Orazio Santo , Gambacciani Carlo , Snuderl Matija , Pieri Francesco , Aquila Filippo , Farnesi Azzurra , Naccarato Antonio Giuseppe , Viacava Paolo , Cardarelli Francesco , Ferri Gianmarco , Mulholland Paul , Ottaviani Diego , Paiar Fabiola , Liberti Gaetano , Pasqualetti Francesco , Menicagli Michele , Aretini Paolo , Signore Giovanni , Franceschi Sara , Mazzanti Chiara Maria 
Published: September 2022

BackgroundGlioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients.MethodsGB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification.ResultsOur functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker.ConclusionsFor the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.
Integrating pharmacological evaluation and computational identification for deciphering the action mechanism of Yunpi-Huoxue-Sanjie formula alleviates diabetic cardiomyopathy
Authors: Zhang Xin , You Li-Yan , Zhang Ze-Yu , Jiang Dong-Xiao , Qiu Yu , Ruan Ye-Ping , Mao Zhu-Jun 
Published: September 2022

Background: Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as Diabetic cardiomyopathy (DCM). However, potential targets and molecular mechanisms remain unclear. Therefore, our research was designed to evaluate rat myocardial morphology, fat metabolism and oxidative stress to verify myocardial protective effect of YP-SJ formula in vivo. And then to explore and validate its probable mechanism through network pharmacology and experiments in vitro and in vivo.Methods: In this study, DCM rats were randomly divided into five groups: control group, model group, and three YP-SJ formula groups (low-dose, middle-dose, and high-dose groups). Experimental rats were treated with 6 g/kg/d, 12 g/kg/d and 24 g/kg/d YP-SJ formula by gavage for 10 weeks, respectively. Cardiac function of rats was measured by high-resolution small-animal imaging system. The cells were divided into control group, high glucose group, high glucose + control serum group, high glucose + dosed serum group, high glucose + NC-siRNA group, high glucose + siRNA-FoxO1 group. The extent of autophagy was measured by flow cytometry, immunofluorescence, and western blotting.Results: It was found that YP-SJ formula could effectively improve cardiac systolic function in DCM rats. We identified 46 major candidate YP-SJ formula targets that are closely related to the progression of DCM. Enrichment analysis revealed key targets of YP-SJ formula related to environmental information processing, organic systems, and the metabolic occurrence of reactive oxygen species. Meanwhile, we verified that YP-SJ formula can increase the expression of forkhead box protein O1 (FoxO1), autophagy-related protein 7 (Atg7), Beclin 1, and light chain 3 (LC3), and decrease the expression of phosphorylated FoxO1 in vitro and in vivo. The results showed that YP-SJ formula could activate the FoxO1 signaling pathway associated with DCM rats. Further experiments showed that YP-SJ formula could improve cardiac function by regulating autophagy.Conclusion: YP-SJ formula treats DCM by modulating targets that play a key role in autophagy, improving myocardial function through a multi-component, multi-level, multi-target, multi-pathway, and multi-mechanism approach.
Parkinson’s disease, dopaminergic drugs and the plant world
Authors: Kempster Peter , Ma Andrew 
Published: September 2022

A large proportion of drugs used for the treatment of neurological disorders relate to naturally occurring compounds, many of which are plant alkaloids. This is particularly true of Parkinson’s disease (PD). The pharmacopoeia of PD has strong botanical origins, while major discoveries about the neurochemistry of the basal ganglia came from the study of phytochemicals. This article narrates the development of pharmacotherapy for PD in terms of historically important plant-derived substances—tropane and hamala alkaloids, reserpine, levodopa, apomorphine, and ergoline dopamine receptor agonists. Alkaloids are nitrogen-containing secondary metabolic products that tend to be biologically active. They appear to be involved in plants’ adaptation to herbivorous animals, though their exact purpose and the ways in which they work are uncertain. A sizable group of alkaloids influence animal dopaminergic systems, highlighting a key biological relationship. While animals must acquire the energy that plants harness, plants need to engage with the animal attribute that they lack—movement—in order to maximize their reproductive fitness. Neuroactive flowering plant compounds have been interacting with vertebrate and invertebrate motor systems for 100 million years. A deep evolutionary connection helps to explain why the pharmacological treatment of PD is imprinted with the power of these mysterious botanical chemicals.
Regulation of the microvasculature during small muscle mass exercise in chronic obstructive pulmonary disease vs. chronic heart failure
Authors: Hartmann Jacob Peter , Dahl Rasmus H. , Nymand Stine , Munch Gregers W. , Ryrsø Camilla K. , Pedersen Bente K. , Thaning Pia , Mortensen Stefan P. , Berg Ronan M. G. , Iepsen Ulrik Winning 
Published: September 2022

Aim: Skeletal muscle convective and diffusive oxygen (O2) transport are peripheral determinants of exercise capacity in both patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). We hypothesised that differences in these peripheral determinants of performance between COPD and CHF patients are revealed during small muscle mass exercise, where the cardiorespiratory limitations to exercise are diminished.Methods: Eight patients with moderate to severe COPD, eight patients with CHF (NYHA II), and eight age- and sex-matched controls were studied. We measured leg blood flow (Q̇leg) by Doppler ultrasound during submaximal one-legged knee-extensor exercise (KEE), while sampling arterio-venous variables across the leg. The capillary oxyhaemoglobin dissociation curve was reconstructed from paired femoral arterial-venous oxygen tensions and saturations, which enabled the estimation of O2 parameters at the microvascular level within skeletal muscle, so that skeletal muscle oxygen conductance (DSMO2) could be calculated and adjusted for flow (DSMO2/Q̇leg) to distinguish convective from diffusive oxygen transport.Results: During KEE, Q̇leg increased to a similar extent in CHF (2.0 (0.4) L/min) and controls (2.3 (0.3) L/min), but less in COPD patients (1.8 (0.3) L/min) (p &lt;0.03). There was no difference in resting DSMO2 between COPD and CHF and when adjusting for flow, the DSMO2 was higher in both groups compared to controls (COPD: 0.97 (0.23) vs. controls 0.63 (0.24) mM/kPa, p= 0.02; CHF 0.98 (0.11) mM/kPa vs. controls, p= 0.001). The Q̇-adjusted DSMO2 was not different in COPD and CHF during KEE (COPD: 1.19 (0.11) vs. CHF: 1.00 (0.18) mM/kPa; p= 0.24) but higher in COPD vs. controls: 0.87 (0.28) mM/kPa (p= 0.02), and only CHF did not increase Q̇-adjusted DSMO2 from rest (p= 0.2).Conclusion: Disease-specific factors may play a role in peripheral exercise limitation in patients with COPD compared with CHF. Thus, low convective O2 transport to contracting muscle seemed to predominate in COPD, whereas muscle diffusive O2 transport was unresponsive in CHF.
Effects of pre-exercise H2 inhalation on physical fatigue and related prefrontal cortex activation during and after high-intensity exercise
Authors: Hong Yinglu , Dong Gengxin , Li Qian , Wang Vienna , Liu Meng , Jiang Guole , Bao Dapeng , Zhou Junhong 
Published: September 2022

Objective: In this study, we examined the effects of pre-exercise H2 gas inhalation on physical fatigue (PF) and prefrontal cortex (PFC) activation during and after high-intensity cycling exercise.Methods: Twenty-four young men completed four study visits. On the first two visits, the maximum workload (Wmax) of cycling exercise of each participant was determined. On each of the other two visits, participants inhaled 20 min of either H2 gas or placebo gas after a baseline test of maximal voluntary isometric contraction (MVIC) of thigh. Then participants performed cycling exercise under their maximum workload. Ratings of perceived exertion (RPE), heart rate (HR) and the PFC activation by using functional near-infrared spectroscopy (fNIRS) was measured throughout cycling exercise. The MVIC was measured again after the cycling.Results: It was observed that compared to control, after inhaling H2 gas, participants had significantly lower RPE at each workload phase (p &lt; 0.032) and lower HR at 50% Wmax, 75% Wmax, and 100% Wmax during cycling exercise (p &lt; 0.037); the PFC activation was also significantly increased at 75 and 100% Wmax (p &lt; 0.011). Moreover, the H2-induced changes in PF were significantly associated with that in PFC activation, that is, those who had higher PFC activation had lower RPE at 75% Wmax (p = 0.010) and lower HR at 100% Wmax (p = 0.016), respectively.Conclusion: This study demonstrated that pre-exercise inhalation of H2 gas can alleviate PF, potentially by maintaining high PFC activation during high-intensity exercise in healthy young adults.
Surgical management of primary mediastinal mature teratoma: A single-center 20 years’ experience
Authors: Zhang Zhedong , Wang Xun , Zhou Zuli , Jiang Guanchao , Li Yun 
Published: September 2022

BackgroundThis study aims to investigate the clinical efficacy of video-assisted thoracic surgery (VATS) in treating mediastinal mature teratoma (MMT) and explore the clinical factors that increase the difficulties associated with VATS.MethodWe retrospectively reviewed 101 consecutive patients with MMT who underwent surgical excision between November 2001 and June 2021. Follow-up was done by telephone or at an outpatient clinic. The deadline for follow-up was February 2022.ResultsThe operative time, the chest tube indwelling time, and the hospital stay duration were significantly shorter in the VATS group compared with the thoracotomy group. The intraoperative and postoperative complication rates in the VATS group were lower than that of the thoracotomy group (P &lt; .05). In thoracoscopic surgery, the clinical symptoms during the course of the disease were significantly associated with bleeding loss increasing [odds ratio (OR) = 3.562; 95% confidence interval (CI) 1.180–10.753, P = .024] and operation time extension (OR = 5.697; 95% CI 1.529–21.221, P = .010). The relationship between lesions and superior vena cava or innominate vein from preoperative CT imaging was significantly associated with bleeding loss increasing (OR = 4.629; 95% CI 1.463–14.639, P = .009). A maximal lesion diameter greater than 7 cm was significantly associated with increased risks of operation time extension (OR = 5.019; 95% CI 1.641–15.348, P = .005).ConclusionCompared with traditional thoracotomy surgery, VATS can be performed safely in selected patients with MMT. A surgical method for complete resection needs to be determined according to preoperative imaging and intraoperative conditions to reduce the unnecessary damage.
The clinicopathological characteristics and prognosis of young patients with chondrosarcoma of bone
Authors: Xie Tao , Sun Yuanyuan , Han Xiao , Zhang Jian 
Published: September 2022

PurposeClinicopathologic characteristics and treatment outcomes for young patients (less than 40 years) with chondrosarcoma of bone are rarely documented. The purpose of this study is to determine the clinicopathological characteristics and identify the survival predictors for this rare population.Patients and MethodsWe used the Surveillance, Epidemiology, and End Results (SEER) database to identify young patients with chondrosarcoma of bone between 1973 and 2016. Univariate and multivariate Cox regression analyses were conducted to determine the independent risk factors. Kaplan-Meier method was used to intuitively show the survival difference stratified by different treatments.ResultsA total of 1312 eligible young patients with chondrosarcoma of bone were analyzed this study. The mean age at diagnosis was 28.5 ± 0.2 years old (ranging from 1 to 40 years). 51.1% of cases were located in the extremity. More than two-thirds of patients (71.4%) were high grade. The majority of the patients (92.0%) received surgery, only 11.8% of patients received radiotherapy, and only 10.4% of patients received chemotherapy. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates of this cohort were 88.5% and 89.1%, respectively. According to the results of multivariate analysis, nine variables were significantly correlated with OS and CSS, including gender, year of diagnosis, tumor site, tumor grade, tumor subtype, distant metastasis, tumor size, surgery, and chemotherapy.ConclusionYoung patients with chondrosarcoma of bone experienced better prognosis. Surgery was significantly correlated with increased survival, while chemotherapy was significantly correlated with decreased survival. Radiotherapy was not a meaningful survival predictor of young patients with chondrosarcoma of bone. Prospective clinical trials are needed in the future to determine the effect of radiotherapy and chemotherapy on prognosis of those patients.
Pulmonary embolism following urological non-oncological surgery: The clinical features, management, and long-term follow-up outcome from a tertiary hospital of China
Authors: Wu Ziqiang , Liu Xuesong , Zhu Quan , Li Haozhen , Li Kaixuan , Wang Guilin , Tang Zhengyan , Wang Zhao 
Published: September 2022

ObjectiveTo evaluate the clinical features, treatment, and outcomes of pulmonary embolism (PE) after urological non-oncological surgery in a tertiary hospital of China.MethodsA total of eight patients who suffered from PE after urological non-oncological surgery from 2016 to 2019 were recruited to the study. Clinical data such as symptoms, vital signs, electrocardiogram, echocardiography, and computed tomographic pulmonary arteriography (CTPA) were reviewed. In addition, the management and long-term follow-up outcome of PE were reported. Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire was applied for five patients to evaluate health-related quality of life after PE.ResultsAll patients survived during their hospitalization, and five patients were contacted during follow-up. Five of the eight patients were anticoagulated regularly until the re-examination results of CTPA and lower extremities ultrasound were normal. The period of anticoagulant sustained at least one month for each patient. The long-term follow-up outcomes showed that PE had little impact on the patients' quality of life.ConclusionsThe study demonstrated that the prognosis of PE patients was not as terrible as feared when treated immediately in the ward. Early diagnosis and treatment of PE is vital for prognosis. However, further verifications based on the results of large studies are still needed.
Construction of Photoresponsive 3D Structures Based on Triphenylethylene Photochromic Building Blocks
Authors: Zhang Xiayu , Liu Fukang , Du Beibei , Huang Rongjuan , Zhang Simin , He Yunfei , Wang Hailan , Cui Jingjing , Zhang Biao , Yu Tao , Huang Wei 
Published: September 2022

Photoresponsive materials have been widely used in sensing, bioimaging, molecular switches, information storage, and encryption nowadays. Although a large amount of photoresponsive materials have been reported, the construction of these smart materials into precisely prescribed complex 3D geometries is rarely studied. Here we designed a novel photoresponsive material methyl methacrylate containing triphenylethylene (TrPEF
2
-MA) that can be directly used for digital light processing (DLP) 3D printing. Based on TrPEF
2
-MA, a series of photoresponsive 3D structures with reversible color switching under ultraviolet/visible light irradiations were fabricated. These complex photoresponsive 3D structures show high resolutions (50
μ
m), excellent repeatability (25 cycles without fatigue), and tunable saturate color degrees. Multicomponent DLP 3D printing processes were also carried out to demonstrate their great properties in information hiding and information-carrying properties. This design strategy for constructing photoresponsive 3D structures is attractive in the area of adaptive camouflage, information hiding, information storage, and flexible electronics.
Cuando el abuso sexual se pone preservativo:
Authors: Galoviche María Sol 
Published: September 2022

A partir de las aproximaciones teóricas de R.Segato y E.Dorlin, se tiene como objetivo analizar la resolución judicial del Juez Rodolfo Mingarini de junio de 2021 en la provincia de Santa Fe. La misma dejó libre con medidas de restricción a un hombre imputado por abuso sexual debido al uso de profiláctico por parte del victimario/acusado.
Se reconstruye la línea de hechos y de fenómenos relativos a la resolución judicial a través de la recopilación documental, realizando un análisis de discurso desde una perspectiva feminista y de derechos humanos. Primero, se mencionan avances en materia de género/s y de políticas públicas. Segundo, se introducen puntos relevantes de las propuestas teóricas de R.Segato y E. Dorlin. Luego se desarrolla la reconstrucción documental del caso teniendo en cuenta el análisis interpretativo desde los referentes conceptuales mencionados. Por último, algunas reflexiones son expuestas respecto del consentimiento, el Estado, la defensa y algunos futuros posibles.
Urbi et Orbi:
Authors: González Alberdi Tomás 
Published: September 2022

La renuncia de Benedicto XVI y la elección de Francisco están signadas por la crisis. La crisis de gobernabilidad de la monarquía vaticana produjo la abdicación del alemán y la posterior llegada del argentino. En ese contexto, el papa Francisco deberá restituir la gobernabilidad del Vaticano y, fundamentalmente, revertir la crisis de legitimidad papal.
A la par de la decadencia de la Iglesia católica, Occidente atraviesa una profunda crisis de sus instituciones democráticas. Este artículo propone abordar el pontificado de Francisco en el marco de la crisis de Occidente. Con ello, se intentará descifrar en la eclesiología de Francisco posibles resonancias para la crisis de las democracias occidentales.
Género y guerra:
Authors: Barbás Juan Martín 
Published: September 2022

La relación entre género y guerra constituye una temática poco –o mal– abordada, incluso por quienes se identifican con posiciones políticas y epistemológicas que hacen foco en la necesidad de utilizar una perspectiva de género para problematizar en profundidad las desigualdades existentes en todos los planos de la vida social. Ante este panorama, el pensamiento de Joan Scott brinda un andamiaje teórico y metodológico fundamental, tanto para entender la relevancia de llevar a cabo análisis a partir de la categoría género, como para, en efecto, llevar a buen término dichos análisis.
El presente trabajo toma algunos de los principales elementos conceptuales de dicha autora para, a partir de los mismos, reflexionar en torno a cuatro cuestiones. En primer lugar, la importancia de pensar los conflictos armados en clave de género; en segundo lugar, la necesidad de deconstruir las nociones tradicionales de masculinidad y feminidad, en tanto las mismas distorsionan la comprensión sobre el modo en el cual hombres y mujeres se vinculan con el fenómeno de la guerra; en tercer lugar, la valoración de la cada vez mayor presencia de mujeres al interior de las Fuerzas Armadas; y por último, el modo en el cual el recurso de la violencia puede ser visto como parte de la capacidad de agencia de las mujeres.
DEVELOPMENT OF DIGITAL MEDIA AND LUDO EKSPONEN TO IMPROVE LEARNING OUTCOMES OF GRADE IX JUNIOR HIGH SCHOOL STUDENTS
Authors: Kobandaha Putri Ekawaty , Tonra Winda Syam , Anam Ahmad Choirul 
Published: September 2022

This study aims to analyze the use of digital media and Ludo Eksponen which has been developed using the ADDIE model in Team Games Tournament (TGT) type cooperative learning. Furthermore, at the stage of implementation and evaluation of the media, it was seen its effectiveness on mathematics learning outcomes, for junior high school students in class IX on the square number and square root material. The subjects of this study were 30 students at one of The Al-Amien Junior High Schools in Sumenep Regency. The data collection technique used direct observation and giving pretests and pot-tests to research subjects. As a result, there was an increase in the average value between the pretest and post-test results, which was 7.54 and 53.65, respectively. By using a Paired Test sample t-test. Based on the results of the study, it can be concluded that the use of digital media and Ludo Eksponen as manual media in cooperative learning type Team Games Tournament (TGT) was quite effective in improving student learning outcomes on the square number and square root.