bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Treatment Outcome of Culture-positive Tuberculosis Patients among Rural and Urban Residents in Jiangxi, China: a Cross-sectional Study
Authors: Zhang Jiahuan , Chen Guimei , Xiong Guangchu , Luo Dong , Peng Yiping , Chen Xiaowen , Zeng Lingbing , Chen Kaisen 
Published: June 2021

Abstract
BackgroundTuberculosis remains a serious public health challenge in China and disproportionately affects urban and rural population. This study aimed to investigate the characteristics and treatment outcome of tuberculosis patients among a population with mixed rural and urban inhabitants.MethodsClinical and socio-demographic information was collected for each culture-confirmed tuberculosis (TB) patients (with >15 yrs) from January 1st, 2015 to July 31st, 2017 in a provincial TB designated hospital in Jiangxi, China. We conducted both first- and second-line drug susceptibility testing. A multivariate logistic regression analysis was employed to calculate odds ratios for factors associated with the rural and urban culture-positive tuberculosis patients. ResultsOverall, 381 culture-confirmed TB patients were enrolled, of which 302 were from rural and 79 from urban region. Rural patients were more likely to have previous treatment history, be unemployed, less educated, and had a slightly higher rate of multidrug-resistant TB. Urban TB patients had a similar rate (40.5%) of treatment failure with that among rural patients (34.8%). In the final model, individuals with less education (aOR, 3.32, 95%CI [1.31-8.39]), having sputum smear positive results (2.14 [1.34-3.42]), and with multidrug-resistant TB (4.49 [1.09-18.55]) were associated with treatment failure. ConclusionsDespite the distinct social-demographic characteristics, both TB patients from rural and urban population had high unfavorable treatment outcome.
Small Cell Carcinoma Esophagus: Experience of an Indian Tertiary Cancer Center
Authors: Panda Goutam Santosh , Noronha Vanita , Yadav Subhash , Joshi Amit , Patil Vijay , Menon Nandini , Kumar Rajiv , Janu Amit , Mahajan Abhishek , Purandare Nilendu , Agarwal Jai Prakash , Karimundackal George , Prabhash Kumar 
Published: June 2021

Abstract
Background: Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive tumor with no established standard treatment.Methods: This is a retrospective study of adult patients with histologically proven SCCE registered between February 2011 and March 2020 at Tata Memorial Hospital in Mumbai.Results: There were 56 patients with 29 (51.8%) having limited-stage disease (LD) and 27 (48.2%) having extensive-stage disease (ED). The median age was 58 (IQR 51-65) years, 57.1% were men, 40% were smokers. Amongst LD-SCCE patients, 23 underwent local therapy i.e. radiation (19, 65.5%), surgery (4, 13.8%) and 27received chemotherapy in neoadjuvant (23, 79.3%), concurrent (18, 62.1%) and adjuvant (4,13.8%) settings. Total 19 ED-SCCE patients (70.4%) received chemotherapy. Prophylactic cranial irradiation (PCI) was delivered to 11(37.9%) and 7(25.9%) patients with LD-SCCE and ED-SCCE, respectively. Signiﬁcant grade ≥3 chemo-toxicities in patients with LD-SCCE and ED-SCCE included febrile neutropenia in 33.3% and 23.5%, anemia in 9.5% and 17.6%, and dyselectrolytemia in 14.3% and 11.8%, respectively. The median overall survival (OS) in LD-SCCE and ED-SCCE were 22.9 (95% CI 1.8-44.1) months and 11.8 (95% CI 7.3-16.4) months, respectively. Age <60years (p=0.004) and tumor epicenter in lower third esophagus (p=0.002) were good prognostic factors for OS in LD-SCCE and ED-SCCE patients respectively. The incidence of brain metastasis was low, both at presentation (1/27, 3.7%) and at relapse (5/56, 8.9%).Conclusion: Although the median overall survival of LD-SCCE is better than ED-SCCE, it is still under 2 years. Brain metastases are uncommon and the role of PCI is uncertain.
Penetration Driving Force of Metformin Hydrochloride via Paracellular Pathway in Relation to its Pharmacodynamic Effect
Authors: Mady Omar Y. , Al-Shoubki Adam A. , Donia Ahmed A. , Qasim Waseem 
Published: June 2021

Abstract
Background: Penetration enhancement of metformin hydrochloride via its molecular dispersion in sorbitan monostearate microparticles is reported. Metformin dispersion in sorbitan monostearate as a carrier was thought to be the basic philosophy to maximize its entrapment in the matrix for maximum penetration effect.Methods: Drug dispersion in sorbitan monostearate with different theoretical drug contents (TDC) were prepared. Results: All products showed excellent micromeritics and actual drug content (ADC) increased by increasing TDC. These two features are essential for industry concerning processing and cost. The partition coefficient of the drug products showed huge improvement. This indicates the drug entrapment should be in the polar part of sorbitan monostearate as a special image. The drug entrapment process was also reflected in the drug release process due to the insolubility of the matrix in the dissolution medium. The drug permeation profiles from the different drug-sorbitan monostearate products are overlapped and its permeation parameters (permeation coefficient, total drug permeation percent & drug absorption enhancement percent) are nearly equal. The results of the permeation study by using modified non-everted sac suggested the main driving force for 11 improving the drug paracellular pathway is its dispersion in sorbitan monostearate (special image) and is independent of ADC. Pharmacodynamic of the drug products showed a significant improvement than that from the drug alone at p ˂ 0.05. ANOVA test indicated the insignificant pharmacodynamic difference between the low, middle, and high ADC of the products. There is an excellent point-to-point correlation between the drug permeation percent and the drug pharmacodynamic percent. The total amount of the drug permeation percent is equal to the mean of the total drug pharmacodynamic percent. Conclusion: The results concluded that the drug permeation driving force via the paracellular pathway is its entrapment in sorbitan monostearate as a special image and it does not depend on ADC. This entrapment mechanism improved the drug pharmacodynamic effect. The technique is simple and the products are easy to process due to having an excellent micromeritics property.
The Frequency and Clinical Implication of Mismatch Repair Protein Deficiency in Chinese Patients with Ovarian Clear Cell Carcinoma
Authors: Ye Shuang , Zhou Shuling , Zhong Siyuan , Shan Boer , Jiang Wenhua , Yang Wentao , Cai Xu , Yang Huijuan 
Published: June 2021

Abstract
Background: To assess the prevalence of deficient mismatch repair (MMR) in Chinese ovarian clear cell carcinoma (CCC) patients and its association with clinicopathologic features.Methods: Immunohistochemistry with four antibodies against MLH1, PMS2, MSH2 and MSH6 were performed on whole section slides. Results were correlated with clinicopathologic variables.Results: A total of 108 cases were included in the study, with a median age of 52 years at first diagnosis. Early-stage disease and platinum-sensitive recurrence accounted for 62.3% and 69.6%, respectively. Overall, the estimated 5-year overall survival was 70.3% and 20.7% in patients with early and late stage tumor, respectively. Deficient MMR were identified in 5.6% (6/108) of the cohort and included MSH2/MSH6 (n=4) and MLH1/PMS2 (n=2). The average age of the six patients was 45.6 years. The rate of MMR-deficient tumors in women ≤ 50 years was relatively higher than that those over 50 years (10.0% Vs. 2.9%; P=0.266). A half of the patients with deficient MMR were diagnosed with a synchronous (endometrial or colorectal) and metachronous (endometrial) cancer, significantly more than those intact counterparts (P=0.002). All the six patients had early-stage tumor and the majority (83.3%) were platinum-sensitive. The median progression-free survival was slightly higher in patients with defective MMR expression than those intact counterparts (30 months Vs. 27 months), although significance was not achieved (P=0.471). Conclusions: Ovarian CCC patients with young age and concurrent diagnosis of endometrial and colorectal cancer are more likely to have MMR-deficient tumors. It merits further evaluation whether patients harboring MMR abnormality has favorable prognosis.
Fundamental laws of nature confirmed by free fall
Authors: kalies Grit 
Published: June 2021

Abstract
The principle of conservation of energy is often demonstrated by means of free fall. In mechanics, states of a body with potential and kinetic energy are energetically compared. Based on the mass concept of relativistic mechanics, energy conservation is considered to be linked with mass conservation. We show that the process of free fall can be interpreted more thoroughly, if the cause-effect principle and the mass concept of thermodynamics are applied. For the first time in the history of physics, the mechanism of energy conversion in free fall can be shown, which is valid for any object, whether body or elementary particle. The phenomenon of falling confirms the following facts to be valid of on a fundamental level: i) The principle of conservation of energy, ii) The equivalence of inertial and gravitational mass, iii) The real mass increase of any object with its velocity, and iv) The continuousness of space and time. At the end of the article we explain why the theory of general relativity is unsuitable to demonstrate the conservation of energy during free fall.
Do somatic USP8, USP48 and BRAF mutations differ in their genotype-phenotype correlation in Asian Indian patients with Cushing’s disease?
Authors: Abraham Ananth P , Pai Rekha , Beno Daniel L , Chacko Geeta , Asha Hesarghatta Shyamasunder , Rajaratnam Simon , Kapoor Nitin , Thomas Nihal , Chacko Ari George 
Published: June 2021

Abstract
Purpose

To estimate the prevalence of USP8, USP48 and BRAF mutations in patients with Cushing’s disease (CD) from the Indian subcontinent, and determine their genotype-phenotype correlation.
Methods

We prospectively recruited 46 patients with CD who underwent surgery between September 2015 and July 2019 at our institute. Fresh frozen tumour tissue was obtained in all patients. Using Sanger sequencing, the presence of somatic USP8 mutations was documented and the frequency of USP48 and BRAF mutations in USP8 wild-type corticotroph adenomas was determined. Clinical, hormonal and surgical data were then compared between USP8-, USP48- and BRAF-variant carriers and patients with wild-type tumours.
Results

Signature USP8 mutations were detected in 17 (37%) patients. Of the 29 USP8 wild-type adenomas, 4 (13.8%) harboured USP48 mutations, one of them being a splice-site mutation that has previously not been described. BRAF mutations were not found in any of the 29 patients. Corticotroph adenomas with USP8 mutations had a higher incidence of Crooke’s hyaline change than wild-type tumours (70.6% vs. 37.9%, p = 0.032). Adenomas with USP48 mutations had a higher rate of cavernous sinus invasion than their wild-type counterparts (50% vs. 4%, p = 0.042). No other significant phenotypic difference could be established between mutant and wild-type tumours.
Conclusions

The prevalence of USP8 mutations in our series of patients with CD was 37%. The prevalence of USP48 mutations in USP8 wild-type adenomas was 13.8%, including a novel splice-site mutation. BRAF mutations were not found in any USP8 wild-type tumour. USP8-mutants showed significantly more Crooke’s hyaline change and USP48-mutants were more likely to demonstrate cavernous sinus invasion.
Delivery of High Mobility Group Box-1 via Engineered Exosomes Improves Cavernosa I njury -Induced Erectile Dysfunction in Rats
Authors: Yu Lan , Zhou Shiyu , Fu Xin , Liao Chen , Peng Tianwen , Liu Min , Zhang Wen 
Published: June 2021

Abstract
BackgroundCavernous is a vascular-rich tissue. Thus, vascular reconstruction is suggested to be essential for the treatment of erectile dysfunction (ED) caused by cavernosa injury. High mobility group box-1 (HMGB1) has been involved in the regulation of growth and differentiation of vascular endothelial cell. In this study, the therapeutic efficiency of engineering HMGB1/Exosomes (exos) derived from adipose tissue derived stem cells (ADSCs) were determined on injured cavernosa.MethodsWe constructed engineered HMGB1/exos and CD63-HMGB1/exos derived from ADSCs. MTT assay, migration assay, and angiogenesis assay were performed in vitro, and erectile and vascular function were detected in a mouse model.ResultsHMGB1 could be successfully delivered to human umbilical venous endothelial cells (HUVECs) via engineered CD63-HMGB1/exos. Treatment with CD63- HMGB1/exos resulted in a significant increase in the proliferation, migration, and angiogenesis of HUVECs. In vivo experiments showed that rats of CD63- HMGB1/exos group had the highest ICP/MAP values at 14 and 28 days after injection. Meanwhile, treatment of CD63- HMGB1/exos remarkably increased the content of smooth muscle. The expression of CD31and vascular endothelial factors were increased after the treatment of CD63-HMGB1/exos, which indicating improved vascular function.ConclusionsEngineering CD63- HMGB1/exos derived from ADSCs notably repaired injured cavernosa-induced ED via promoting vascular reconstruction.
Translational medicine: What views and challenges do the fracture mapping?
Authors: Shi Guang , Liu Wei , Su Xiu yun , Cai Xi yu 
Published: June 2021

Abstract
BackgroundTranslational medicine（TM）is a bridge between basic science and clinical medicine. The purpose of this study is to systematically review the literature with respect to fracture mapping(FM) in orthopedics, to clarify what insights and challenges facing FM. MethodsA systematic review was conducted according to PRISMA guidelines. We systematically searched the PubMed, Scopus, IEEE Digital Library, Web of Science database and references of relevant studies, from the establishment of the database through December 2020, for any and all data regarding the application of FM in orthopedics. ResultsA total of 2777 articles were retrieved, and 28 articles met the inclusion criteria. The application of fracture FM in orthopaedics was as follows: upper limbs (n=10, 35.71%), lower limbs (n=17, 60.71%), thoracolumbar spine (n=1, 3.58%). FM guided preoperative planning (n = 12, 42.86%), and conduce to identify the specific patterns of fractures (n=9, 32.14%), and illustrated the fracture morphology and guided clinical treatment (n=7, 25.00%). ConclusionFM represents a promising technique for describing the morphology of fracture. Moreover, potential promotion classification, preoperative planning, development of fixation concepts, and analysis of internal structure, but its clinical application is still limited. Thus, much further research is needed to determine the potential advantages of this new technique. If possible, guidelines are needed to facilitate the development of FM with regard to the required for developing this technic.
Kidney-lung crosstalk during SARS-CoV-2 infection: In silico hypothesis-generating method for COVID-19 models
Authors: Grigoryev Dmitry N , Rabb Hamid 
Published: June 2021

Abstract
BackgroundPublicly available genomics datasets have been growing drastically during the past decades. Although most of these datasets were initially generated to answer a pre-defined scientific question, their re-purposing became useful when new challenges such as COVID-19 arise. While the establishment and use of experimental models of COVID-19 are in progress, the potential hypotheses for mechanisms of onset and progression of COVID-19 can be generated by using in silico analysis of known COVID-19 conditions and SARS-CoV-2 targets. MethodsSelecting condition: COVID-19 infection leads to acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). There is increasing data demonstrating mechanistic links between AKI and ARDS. Selecting targets: SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) for cell entry. We hypothesized that modeling AKI and ARDS would lead to changes in kidney and lung ACE2 and TMPRSS2. We therefore evaluated expression of ACE2 and TMPRSS2 as well as other novel molecular players of AKI and AKI-lung cross-talk in publicly available microarray datasets GSE6730 and GSE60088, which represented gene expression of lungs and kidneys in mouse models that resembled lung-kidney injury seen during SARS-CoV-2 infection.ResultsExpression of COVID-19 related genes ACE2 and TMPRSS2 was downregulated in lungs at early stages of injury. At a later stage, the expression of ACE2 decreased further, while expression of TMPRSS2 recovered. In kidneys, both genes were downregulated by AKI, but not by distant lung injury. We also identified 53 kidney genes upregulated by pneumonia and mechanical ventilation (PMV); and 254 lung genes upregulated by AKI, 9 genes of which were common to both organs. 3 of 9 genes were previously linked to kidney-lung cross-talk: Lcn2 (Fold Change (FC)Lung(L) =18.6, FCKidney(K) =6.32), Socs3 (FCL =10.5, FCK =10.4), Inhbb (FCL =6.20, FCK =6.17). This finding validates the current approach and reveals new 6 candidates, including Maff (FCL =7.21, FCK =5.98).ConclusionsUsing our in-silico approach, we identified changes in COVID-19 related genes ACE2 and TMPRSS2 in traditional mouse models of AKI and lung cross-talk. We also found changes in the new candidate genes, which could be involved in the combined kidney-lung injury during COVID-19
Efficacy and safety of oral zolmitriptan in the preictal phase of episodic cluster headache
Authors: Liu Wei , Lu Jiajie , Guo Xiaoning , Xu Chunyang , Yan Manyun , Zhang Quanquan , Ni Jianqiang , Lu Haifeng , Zhao Hongru 
Published: June 2021

Abstract
BackgroundRecent studies on cluster headache suggested that headache includes three phases.Oral zolmitriptan is effective in the treatment of acute headache attack.We aim to describe the clinical characteristics of different phases of episodic cluster headache(eCH) and observe the efficacy and safety of oral zolmitriptan in preictal phase of eCH attacks.MethodsForty-eight patients with eCH were enrolled in this study. We divided the CH attack into three phases: preictal, ictal and postictal phase and analyzed the clinical features of each phase. We collected the data of twenty-three patients who took zolmitriptan in the preictal phase of three consecutive CH attacks. The Visual Analogue Scale (VAS) score and duration of headache after three consecutive treatments were compared with the baseline respectively. Chi square test, t test, Mann Whitney U test, Pearson linear correlation analysis, paired t-test and paired non-parametric rank-sum test were used for statistical analysis.ResultsForty-five patients (93.8%) reported the presence of preictal symptoms. The most frequent preictal symptom was mild to moderate head discomfort in the area of the subsequent serious headache, accounting for 87.5%. The duration of preictal period was positively correlated with the duration of headache. The Pearson correlation coefficient was 0.313 (P=0.018). Among the twenty-three patients taking oral zolmitriptan in the preictal phase, the VAS max score was significantly lower than that of baseline headache (P<0.01). The duration of headache after three preictal administration was significantly shorter than that of baseline headache (P<0.01). The incidence of adverse reactions after taking zolmitriptan was 10.1%, including head drowsiness, neck stiffness and mild chest tightness.Conclusions Preictal symptoms were common in CH. Mild to moderate discomfort in the subsequent serious headache was the most common symptom in the preictal phase. Oral administration of zolmitriptan in the preictal period could reduce the severity of headache and shorten the duration of headache in a cluster period without serious adverse reactions.
Water contamination in an energy balance model of climate with coupled iceline
Authors: Radulescu Anca , Morasse Monika 
Published: June 2021

Abstract
Budyko's energy balance model with coupled iceline is a historic system of differential equations, which incorporates water albedo as a major determinant to climate trends. In this class of models, the position of the Earth's iceline, and its coupling with temperature, play a very important role in determining long term climate patterns (which may range between extremes such as a water covered or an ice covered Earth, but also allow for stable states with intermediate icelines). Some extensions of this model have specifically focused on studying the contribution of greenhouse effects to the temperature-iceline long term dynamics. Our model builds upon this existing work, and studies in a computational setup the potential effects of global perturbations in ocean water purity. We found that small changes in physical parameters such as water salinity or chemical/biological contamination may lead to sizeable changes in long term climatic outcomes. Moreover, these effects appear to be enhanced when occurring in combination, and even more so when in the presence of elevated greenhouse effects.
Predictive Analysis of COVID-19 Pandemic in India Based on SIR-F Model
Authors: P. Gopinath M. , C. Satyam S. , M. Jenil S. , P. Shashank 
Published: June 2021

Abstract
Impact of COVID-19 has been devastating worldwide, it has disrupted lives of people, economy has fallen and millions of people have lost their jobs. Second peak of COVID-19 is making it even worse for many developing countries. In India, the second peak is reaching nearly 4 times the cases that were reported during the first peak, thus making it a challenge for the government to plan for the future without affecting the economy further. According to WHO, millions of enterprises are at existential threat, nearly half of the global workforce is at risk of losing their jobs and the entire food chain has been disrupted. In order to provide some assistance to the situation, this study aims to use the SIR-F Model, which is a variation of the SIR model. W. O. Kermack and A. G. McKendrick in 1927, proposed the model in which they classified a fixed population into three compartments: S(t), susceptible; I(t), Infected; R(t), Recovered. We have used the SIR-F model which differentiates between Recovered (meaning people infected and later recovered and thus now immune) and Fatality. We have simulated two scenarios including one in which we study the impact of medicine on future cases and also inspected various parameters which shed light on reasons behind increasing and decreasing the number of covid cases in India. In the future, this work can be extended further to develop a completely new model to consider those cases in which people have recovered but are still at a risk of reinfection.