bluuebunny/crossref_metadata_2025_split huggingface dataset:
A “Swiss paradox” in the United States? Level of spatial aggregation changes the association between income inequality and morbidity for older Americans
Authors: Cohen Steven A. , Greaney Mary L. , Klassen Ann C. 
Published: November 2019

AbstractAlthough a preponderance of research indicates that increased income inequality negatively impacts population health, several international studies found that a greater income inequality was associated with better population health when measured on a fine geographic level of aggregation. This finding is known as a “Swiss paradox”. To date, no studies have examined variability in the associations between income inequality and health outcomes by spatial aggregation level in the US. Therefore, this study examined associations between income inequality (Gini index, GI) and population health by geographic level using a large, nationally representative dataset of older adults. We geographically linked respondents’ county data from the 2012 Behavioral Risk Factor Surveillance System to 2012 American Community Survey data. Using generalized linear models, we estimated the association between GI decile on the state and county levels and five population health outcomes (diabetes, obesity, smoking, sedentary lifestyle and self-rated health), accounting for confounders and complex sampling. Although state-level GI was not significantly associated with obesity rates (b = − 0.245, 95% CI − 0.497, 0.008), there was a significant, negative association between county-level GI and obesity rates (b = − 0.416, 95% CI − 0.629, − 0.202). State-level GI also associated with an increased diabetes rate (b = 0.304, 95% CI 0.063, 0.546), but the association was not significant for county-level GI and diabetes rate (b = − 0.101, 95% CI − 0.305, 0.104). Associations between both county-level GI and state-level GI and current smoking status were also not significant. These findings show the associations between income inequality and health vary by spatial aggregation level and challenge the preponderance of evidence suggesting that income inequality is consistently associated with worse health. Further research is needed to understand the nuances behind these observed associations to design informed policies and programs designed to reduce socioeconomic health inequities among older adults.
Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance
Authors: Batta Nishant , Pandey Manoj 
Published: November 2019

Abstract
Oral squamous cell cancer (OSCC) is a common malignancy attributed to use of chewing smokeless tobacco and smoking. Most of the targeted strategies are based on EGFR expression and mutation; however, none of them has shown significant improvement in survival and response rates. We carried out this study to evaluate mutational profile of tobacco associated oral carcinoma with special emphasis on EGFR and its downstream events.

Patients and methods
A total of 46 histologically proven cases were recruited between January 2017 and January 2019. Apart from detailed clinical and histological studies, the paraffin-embedded tissue was submitted for expression of 50 genes using Next Generation Sequencing using Ion Ampliseq Cancer Hotspot Panel v2.

Results
The mean age of patients was 47.8 ± 10.9 years. Majority had tumors on buccal mucosa (24) and tongue (13). Nineteen of these tumors were larger than 4 cm, and 5 had adjacent site involvement. Thirty one were node positive. TP53 mutations were commonest seen in 19 followed by CDKN2A in 11, HRAS in 8, PIK3CA in 3, SMARCB1 in 2, and KIT, EGFR, BRAF, STK11, ABL1, RB1 in one case each. Concomitant TP53 mutation was identified with other mutations like CDKN2A, HRAS, KIT, PIK3CA, STK11, SMARCB1, ABL1, and RB1 making tobacco-associated OSCC as a heterogeneous mutational tumor with multiple events. A patient with TP53 mutations has poor disease free survival (47.4 vs 63% p = 0.17); however, this was not statistically significant.

Conclusion
The study shows a heterogeneous mutational spectrum with multiple mutational events in OSCC. The low EGFR mutation rates and higher mutations in EGFR downstream pathways including that in TP53 and HRAS suggest that anti EGFR strategies may not succeed in these tumors and newer agents and therapeutic combinations need to be tried.
Medicinal plants of the Bible—revisited
Authors: Dafni Amots , Böck Barbara 
Published: November 2019

AbstractBackgroundPrevious lists number from 55 to 176 plant species as “Biblical Medicinal Plants.” Modern studies attest that many names on these lists are no longer valid. This situation arose due to old mistranslations and/or mistakes in botanical identification. Many previously recognized Biblical plants are in no way related to the flora of the Bible lands. Accordingly, the list needs revision.MethodsWe re-examine the list of possible medicinal plants in the Bible based on new studies in Hebrew Biblical philology and etymology, new studies on the Egyptian and Mesopotamian medicinal use of plants, on ethnobotany and on archaeobotany.ResultsIn our survey, we suggest reducing this list to 45 plant species. Our contribution comprises 20 “newly” suggested Biblical Medicinal Plants. Only five species are mentioned directly as medicinal plants in the Bible: Fig (Ficus carica), Nard (Nardostachys jatamansi), Hyssop (Origanum syriacum), balm of Gilead (Commiphora gileadensis) and Mandrake (Mandragora officinarum). No fewer than 18 medicinal plants are mentioned in old Jewish post-Biblical sources, in addition to those in the Bible. Most of these plants (15) are known also in Egypt and Mesopotamia while three are from Egypt only. Seven of our suggested species are not mentioned in the Bible or in the Jewish post-Biblical literature but were recorded as medicinal plants from Egypt, as well as from Mesopotamia. It is quite logical to assume that they can be included as Biblical Medicinal Plants.ConclusionsAll our suggested Biblical Medicinal Plants are known as such in Ancient Egypt and/or Mesopotamia also. Examination of our list shows that all these plants have been in continuous medicinal use in the Middle East down the generations, as well as being used in the Holy Land today. Precisely in King Solomon’s words, “That which has been is what will be, that which is done is what will be done. And there is nothing new under the sun” (Ecclesiastes 1:9).
Early clinical outcomes of simple pannus removal for mechanical aortic valve stenosis
Authors: Cui Huimin , Zhang Lin , Wei Shixiong , Jiang Shengli 
Published: November 2019

Abstract
Background
This study aimed to confirm the safety and feasibility of simple pannus removal in patients with mechanical aortic valve dysfunction for pannus overgrowth by evaluating its early clinical outcomes.

Methods
From March 2015 to April 2019, 24 consecutive patients with mechanical aortic valve dysfunction due to subaortic pannus underwent reoperation. In 12 patients the repeat aortic valve replacement (AVR) was performed, and 12 received the simple pannus removal to preserve the previously implanted prosthesis.

Results
There was only 1 in-hospital death in simple pannus removal group. Significant differences were obtained between procedures in cardiopulmonary bypass (CPB) and aortic cross-clamp time (128.7 vs 179.7 and 74.2 vs 132.7 mins, respectively, P < 0.05). The C-reactive protein (CRP) in simple pannus removal group was lower on the first day (0.13 ± 0.09 vs 0.31 ± 0.22 mg/dl, P < 0.05) and continued to be lower within 1 week after operation. There was no significant difference between procedures in aortic transvalvular peak velocity and transvalvular mean pressure gradient (TMPG) (2.6 ± 0.4 vs 2.5 ± 0.4 m/s and 13.2 ± 3.6 vs 11.6 ± 2.6 mmHg, respectively, P > 0.05) in echocardiography 1 week after operation. In addition, the aortic transvalvular peak velocity and TMPG in echocardiography 1 week after operation in pannus removal group between the repeat and initial surgery were not statistically significant (2.6 ± 0.4 vs. 2.5 ± 0.3 m/s, 13.2 ± 3.6 vs. 13.0 ± 3.5 mmHg, P > 0.05).

Conclusions
Simple pannus removal was a safe and effective procedure with satisfied early clinical outcomes for pannus overgrowth in mechanical aortic valve. However, further randomized and long-term follow-up studies were warranted to determine the clinical effects of the simple aortic pannus removal.
Clinical application and observation of modified Ivor-Lewis surgery in Siewert type II adenocarcinoma of the Esophagogastric junction
Authors: Yin Qifan , Wang Wenhao , Liu Huining , Yang Guang , Zhou Shaohui , Liu Lijun 
Published: November 2019

Abstract
Background
The surgical approach (transthoracic or transabdominal) for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) still remains controversial. We made a bold attempt to adopt the modified Ivor-Lewis surgery, No turning over, thoraco-laparoscopic esophagogastrectomy, two-field lymphadenectomy and intrathoracic anastomosis, to observe the clinical application and effect.

Method
Data of patients with Siewert type II AEG were collected in the Hebei General Hospital from June 2017 to February 2019. The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, postoperative complications, the length of postoperative hospital stay were collected to assess the safety and feasibility of modified Ivor-Lewis surgery.

Results
A total of 20 patients with Siewert type II AEG were analyzed in our research, there was no case of turning to thoracotomy, laparotomy or death during the operation.The average operation time, surgical blood loss, amount of dissected lymph nodes, duration of drainage tube, postoperative hospital stay of all enrolled patients was 4.67, 0.57 h, 156, 56.80 ml, 22.55, 3.91, 8.6, 2.21 days, 12.85, 2.5 days respectively. Among all the enrolled patients, one patient(5%) developed anastomotic fistula and one patient(5%) developed hematemesis after operation, eventually, these two patients were discharged successfully.

Conclusion
For patients with Siewert type II AEG, The modified Ivor-Lewis surgery, No turning over, thoraco-laparoscopic esophagogastrectomy, two-field lymphadenectomy and intrathoracic anastomosis, is safe and feasible. The feasibility and safety could be further and better investigated with a RCT to achieve more conclusive results.
Qualitative assessment of EOB-GD-DTPA and Gd-BT-DO3A MR contrast studies in HCC patients and colorectal liver metastases
Authors: Granata Vincenza , Fusco Roberta , Maio Francesca , Avallone Antonio , Nasti Guglielmo , Palaia Raffaele , Albino Vittorio , Grassi Roberto , Izzo Francesco , Petrillo Antonella 
Published: November 2019

Abstract
Aim
To compare liver-specific EOB-GD-DTPA and liver-non-specific Gd-BT-DO3A MR, in hepatocellular carcinoma (HCC) and liver colorectal metastases.

Material and methods
Seventy HCC patients with 158 nodules and 90 colorectal liver metastases (mCRC) with 370 lesions were included in the retrospective analysis. HCC patients underwent MR at 0 time (MR0), after 3 (MR3) and 6 months (MR6) using two different CM; 69 mCRC patients underwent MR with Gd-EOB-BTPA and 21 mCRC patients with Gd-BT-DO3A. We evaluated arterial phase hyperenhancement, lesion-to-liver contrast during portal phase, hepatobiliary phase parenchymal hyperenhancement.

Results
In HCC patients arterial phase hyperenhancement degree was statistically higher (p = 0.03) with Gd-BT-DO3A (mean 4) than GD-EOB-DTPA (mean 2.6), while we found no significant statistical differences among mean (2.6) values at MR0 and MR6 using GD-EOB-DTPA. For all 209 patients underwent Gd-EOB-DTPA, we found that lesion-to-liver contrast during portal phase mean value was 4 while for patients underwent MR with Gd-BT-DO3A was 3 (p = 0.04). For HCC hepatobiliary phase parenchymal hyperenhancement mean value was 2.4. For mCRC patients: among 63 patients underwent previous chemotherapy hepatobiliary phase parenchymal hyperenhancement mean value was 3.1 while for 6 patients no underwent previous chemotherapy was 4 (p = 0.05).

Conclusions
Gd-EOB-DTPA should be chosen in pre surgical setting in patients with colorectal liver metastases.
Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer
Authors: Pan Yu , Lu Fengchun , Fei Qinglin , Yu Xingxing , Xiong Ping , Yu Xunbin , Dang Yuan , Hou Zelin , Lin Wenji , Lin Xianchao , Zhang Zheyang , Pan Minggui , Huang Heguang 
Published: November 2019

Abstract
Background
Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME.

Methods
Using immunohistochemistry, we examined tumor-infiltrating CD68+ pan-macrophages (CD68+ M) and CD163+ M2 macrophages (CD163+ M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45+ immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline.

Results
We found that CD47 expression correlated with the level of CD68+ M but not CD163+ M2. High levels of tumor-infiltrating CD68+ M, CD163+ M2, and CD47 expression were significantly associated with worse survival. CD47high/CD68+ Mhigh and CD47high/CD163+ M2high correlated significantly with shorter survival, whereas CD47low/CD68+ Mlow and CD47low/CD163+ M2low correlated with longer survival. Intriguingly, CD47 blockade decreased the tumor burden in the Panc02 but not in the MPC-83 syngeneic mouse model. Using scRNA-seq, we showed that anti-CD47 treatment significantly remodeled the intratumoral lymphocyte and macrophage compartments in Panc02 tumor-bearing mice by increasing the pro-inflammatory macrophages that exhibit anti-tumor function, while reducing the anti-inflammatory macrophages. Moreover, CD47 blockade not only increased the number of intratumoral CD8+ T cells, but also remodeled the T cell cluster toward a more activated one. Further, combination therapy targeting both CD47 and PD-L1 resulted in synergistic inhibition of PDAC growth in the MPC-83 but not in Panc02 model. MPC-83 but not Panc02 mice treated with both anti-CD47 and anti-PD-L1 showed increased number of PD-1+CD8+ T cells and enhanced expression of key immune activating genes.

Conclusion
Our data indicate that CD47 targeting induces compartmental remodeling of tumor-infiltrating immune cells of the TME in PDAC. Different PDAC mouse models exhibited differential response to the anti-CD47 and anti-PD-L1 blockade due to the differential effect of this combination treatment on the infiltrating immune cells and key immune activating genes in the TME established by the different PDAC cell lines.
Loss of SIM2s inhibits RAD51 binding and leads to unresolved replication stress
Authors: Pearson Scott J. , Elswood Jessica , Barhoumi Rola , Ming-Whitfield Brittini , Rijnkels Monique , Porter Weston W. 
Published: November 2019

Abstract
Background
Mutations in genes associated with homologous recombination (HR) increase an individual’s risk of developing triple-negative breast cancer (TNBC). Although known for their role in repairing dsDNA breaks, HR repair elements also stabilize and restart stalled replication forks. Essential to these functions are RAD51 and its paralogs, each of which has a unique role in preventing replication fork collapse and restart. However, progress toward understanding the regulation of these factors has been slow. With such a pivotal role in the maintenance of genomic integrity, furthering our understanding of this pathway through the discovery of new factors involved in HR is important. Recently, we showed that singleminded-2s (SIM2s) is stabilized in response to dsDNA breaks and is required for effective HR.

Methods
Initial analysis of the effect loss of SIM2s has on replication stress resolution was conducted using DNA combing assays in established breast cancer cell lines. Further analysis was conducted via immunostaining to determine the effect loss of SIM2s has on factor recruitment. In vivo confirmation was achieved through the use of a mammary epithelial cell conditional knockout mouse model before SIM2s’ role in RAD51 recruitment was determined by immunoblotting.

Results
Here, we show loss of SIM2s decreases replication fork stability, leading to fork collapse in response to genotoxic stress. Furthermore, loss of SIM2s results in aberrant separation of sister chromatids during mitosis, which has been previously shown to result in chromosomal fragmentation and aneuploidy. Interestingly, loss of SIM2s was shown to result in failure of RAD51 to localize to sites of replication stress in both breast cancer cell lines and primary mammary epithelial cells. Finally, we observed SIM2 is stabilized in response to genotoxic stress and interacts with RAD51, which is necessary for RAD51-DNA binding.

Conclusions
Together, these results show a role for SIM2s in the resolution of replication stress and further characterize the necessity of SIM2s for effective RAD51 loading in response to DNA damage or stress, ultimately promoting genomic integrity and thus preventing the accumulation of cancer-promoting mutations.
Microtubule destabilization caused by silicate via HDAC6 activation contributes to autophagic dysfunction in bone mesenchymal stem cells
Authors: Li Zheng , Liu Shuhao , Fu Tengfei , Peng Yi , Zhang Jian 
Published: November 2019

Abstract
Background
Silicon-modified biomaterials have been extensively studied in bone tissue engineering. In recent years, the toxicity of silicon-doped biomaterials has gradually attracted attention but requires further elucidation. This study was designed to explore whether high-dose silicate can induce a cytotoxicity effect in bone mesenchymal stem cells (BMSCs) and the role of autophagy in its cytotoxicity and mechanism.

Methods
Morphologic changes and cell viability of BMSCs were detected after different doses of silicate exposure. Autophagic proteins (LC3, p62), LC3 turnover assay, and RFP-GFP-LC3 assay were applied to detect the changes of autophagic flux following silicate treatment. Furthermore, to identify the potential mechanism of autophagic dysfunction, we tested the acetyl-α-tubulin protein level and histone deacetylase 6 (HDAC6) activity after high-dose silicate exposure as well as the changes in microtubule and autophagic activity after HDAC6 siRNA was applied.

Results
It was found that a high dose of silicate could induce a decrease in cell viability; LC3-II and p62 simultaneously increased after high-dose silicate exposure. A high concentration of silicate could induce autophagic dysfunction and cause autophagosomes to accumulate via microtubule destabilization. Results showed that acetyl-α-tubulin decreased significantly with high-dose silicate treatment, and inhibition of HDAC6 activity can restore microtubule structure and autophagic flux.

Conclusions
Microtubule destabilization caused by a high concentration of silicate via HDAC6 activation contributed to autophagic dysfunction in BMSCs, and inhibition of HDAC6 exerted a cytoprotection effect through restoration of the microtubule structure and autophagic flux.
Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients
Authors: Mousseaux Cyril , Dupont Axelle , Rafat Cédric , Ekpe Kenneth , Ghrenassia Etienne , Kerhuel Lionel , Ardisson Fanny , Mariotte Eric , Lemiale Virginie , Schlemmer Benoît , Azoulay Elie , Zafrani Lara 
Published: November 2019

AbstractBackgroundSevere hypercalcemia (HCM) is a common reason for admission in intensive-care unit (ICU). This case series aims to describe the clinical and biological features, etiologies, treatments, and outcome associated with severe HCM. This study included all patients with a total calcemia above 12 mg/dL (3 mmol/L) admitted in two ICUs from January 2007 to February 2017.Results131 patients with HCM were included. HCM was related to hematologic malignancy in 58 (44.3%), solid tumors in 29 (22.1%), endocrinopathies in 16 (12.2%), and other causes in 28 (21.3%) patients. 108 (82.4%) patients fulfilled acute kidney injury (AKI) criteria. Among them, 25 (19%) patients required renal replacement therapy (RRT). 51 (38.9%) patients presented with neurological symptoms, 73 (55.7%) patients had cardiovascular manifestations, and 50 (38.1%) patients had digestive manifestations. The use of bisphosphonates (HR, 0.42; 95% CI, 0.27–0.67;P < 0.001) was the only treatment significantly associated with a decrease of total calcemia below 12 mg/dL (3 mmol/L) at day 5. ICU and Hospital mortality rates were, respectively, 9.9% and 21.3%. Simplified Acute Physiologic Score (SAPS II) (OR, 1.05; 95% CI 1.01–1.1;P = 0.03) and an underlying solid tumor (OR, 13.83; 95% CI 2.24–141.25;P = 0.01) were two independent factors associated with hospital mortality in multivariate analysis.ConclusionsHCM is associated with high mortality rates, mainly due to underlying malignancies. The course of HCM may be complicated by organ failures which are most of the time reversible with early ICU management. Early ICU admission and prompt HCM management are crucial, especially in patients with an underlying solid tumor presenting with neurological symptoms.
Error bounds of block sparse signal recovery based on q-ratio block constrained minimal singular values
Authors: Wang Jianfeng , Zhou Zhiyong , Yu Jun 
Published: November 2019

AbstractIn this paper, we introduce the q-ratio block constrained minimal singular values (BCMSV) as a new measure of measurement matrix in compressive sensing of block sparse/compressive signals and present an algorithm for computing this new measure. Both the mixed ℓ2/ℓq and the mixed ℓ2/ℓ1 norms of the reconstruction errors for stable and robust recovery using block basis pursuit (BBP), the block Dantzig selector (BDS), and the group lasso in terms of the q-ratio BCMSV are investigated. We establish a sufficient condition based on the q-ratio block sparsity for the exact recovery from the noise-free BBP and developed a convex-concave procedure to solve the corresponding non-convex problem in the condition. Furthermore, we prove that for sub-Gaussian random matrices, the q-ratio BCMSV is bounded away from zero with high probability when the number of measurements is reasonably large. Numerical experiments are implemented to illustrate the theoretical results. In addition, we demonstrate that the q-ratio BCMSV-based error bounds are tighter than the block-restricted isotropic constant-based bounds.
Multiple periodic orbits of high-dimensional differential delay systems
Authors: Sun Zhongmin , Ge Weigao , Li Lin 
Published: November 2019

AbstractIn this paper, we consider differential delay systems of the form
$$x'(t)=-\sum_{s=1}^{2k-1}(-1)^{s+1} \nabla F \bigl(x(t-s) \bigr), $$x′(t)=−∑s=12k−1(−1)s+1∇F(x(t−s)), in which the coefficients of the nonlinear terms with different hysteresis have different signs. Such systems have not been studied before. The multiplicity of the periodic orbits is related to the eigenvalues of the limit matrix. The results provide a theoretical basis for the study of differential delay systems.