bluuebunny/crossref_metadata_2025_split huggingface dataset:
The economic burden of malaria on households and the health system in a high transmission district of Mozambique
Authors: Alonso Sergi , Chaccour Carlos J. , Elobolobo Eldo , Nacima Amilcar , Candrinho Baltazar , Saifodine Abuchahama , Saute Francisco , Robertson Molly , Zulliger Rose 
Published: November 2019

Abstract

Background
Malaria remains a leading cause of morbidity and mortality in Mozambique. Increased investments in malaria control have reduced the burden, but few studies have estimated the costs of malaria in the country. This paper estimates the economic costs associated with malaria care to households and to the health system in the high burden district of Mopeia in central Mozambique.

Methods
Malaria care-seeking and morbidity costs were routinely collected among 1373 households with at least one child enrolled in an active case detection (ACD) cohort in Mopeia, and through cross-sectional surveys with 824 families in 2017 and 805 families in 2018. Household costs included direct medical expenses, transportation and opportunity costs of the time lost due to illness. Structured questionnaires were used to estimate the health system costs associated with malaria care in all 13 district health facilities. Cost estimations followed an ingredient-based approach with a top-down allocation approach for health system expenses.

Results
Among participants in cross-sectional studies, households sought care for nine severe malaria cases requiring hospital admission and for 679 uncomplicated malaria cases. Median household costs associated with uncomplicated malaria among individuals of all ages were US$ 3.46 (IQR US$ 0.07–22.41) and US$ 81.08 (IQR US$ 39.34–88.38) per severe case. Median household costs were lower among children under five (ACD cohort): US$ 1.63 (IQR US$ 0.00–7.79) per uncomplicated case and US$ 64.90 (IQR US$ 49.76–80.96) per severe case. Opportunity costs were the main source of household costs. Median health system costs associated with malaria among patients of all ages were US$ 4.34 (IQR US$ 4.32–4.35) per uncomplicated case and US$ 26.56 (IQR US$ 18.03–44.09) per severe case. Considering household and health system costs, the overall cost of malaria care to society was US$ 7.80 per uncomplicated case and US$ 107.64 per severe case, representing an economic malaria burden of US$ 332,286.24 (IQR US$ 186,355.84–1,091,212.90) per year only in Mopeia.

Conclusions
Despite the provision of free malaria services, households in Mopeia incur significant direct and indirect costs associated with the disease. Furthermore, the high malaria cost on the Mozambican health system underscores the need to strengthen malaria prevention to reduce the high burden and improve productivity in the region.
Adherence to the pro-inflammatory diet in relation to prevalence of irritable bowel syndrome
Authors: Salari-Moghaddam Asma , Keshteli Ammar Hassanzadeh , Esmaillzadeh Ahmad , Adibi Peyman 
Published: November 2019

Abstract

Objective
There is no prior study that examined the association between nutrient-based dietary inflammatory index (DII) and odds of Irritable Bowel Syndrome (IBS). We examined the association between DII score and odds of IBS and its severity among Iranian adults.

Methods
In this cross-sectional study, dietary intakes of 3363 Iranian adults were examined using a validated Dish-based 106-item Semi-quantitative Food Frequency Questionnaire (DS-FFQ). DII was calculated based on dietary intakes derived from DS-FFQ. IBS was assessed using a modified Persian version of Rome III questionnaire.

Results
After adjustment for potential confounders, we found that participants in the highest quintile of DII score had greater chance for IBS compared with those in the lowest quintile (OR: 1.36; 95% CI: 1.03–1.80). By gender, we found a significant association between DII score and IBS among women (OR: 1.41; 95% CI: 1.00–2.00). By BMI status, overweight or obese (BMI ≥ 25 kg/m2) individuals in top quintile of DII score had greater odds for IBS than those in the bottom quintile (OR: 1.64; 95% CI: 1.07–2.53). No significant association was observed between a pro-inflammatory diet and severity of IBS symptoms.

Conclusions
Consumption of a pro-inflammatory diet was associated with increased odds of IBS, in particular among women and those with BMI ≥ 25 kg/m2.
Evaluating adherence to recommended diets in adults 1991–2015: revised China dietary guidelines index
Authors: Huang Feifei , Wang Zhihong , Wang Liusen , Wang Huijun , Zhang Jiguo , Du Wenwen , Su Chang , Jia Xiaofang , Ouyang Yifei , Wang Yun , Li Li , Jiang Hongru , Zhang Bing 
Published: November 2019

AbstractBackgroundThe China Dietary Guidelines Index (CDGI) is a diet quality evaluation index that can present the overall diet quality and is comparable between individuals. The aim of this study was to revise CDGI for Chinese adults according to the Chinese Dietary Guidelines 2016 (CDG-2016), evaluate adherence to recommended diets between 1991 and 2015, and analyze the trend, variation, and determinants of diet quality.MethodsFood, cooking oil, and condiment intakes were estimated based on twenty-four-hour dietary recalls over three consecutive days and the household weighing method. Based on the food and nutrients recommendations for people with different energy requirements in CDG-2016, CDGI was revised as China Dietary Guidelines Index (2019)-Adults (CDGI(2019)-A) by equal weight continuity scoring. Three-level random intercept-slope growth models were applied to analyze the trend, variation, and determinants at both the community and individual levels.ResultsCDGI(2019)-A, the sum of fourteen component scores with a range of 0–110 points, increased significantly from 38.2 in 1991 to 47.3 in 2015. Components with a score of less than half were milk (91.6%), fruits (72.0%), nuts (82.5%), other cereals and beans (82.6%), and seafood (77.7%). Between-individual accounted for 25.6% of the total score variation, of which 87.4% derived from the community level. CDGI(2019)-A score displayed a positive association with being female, having higher education, having higher income, living in an urban area, and knowing the CDG-2016 recommendations. The impact of income and awareness of CDG-2016 varied significantly across communities.ConclusionsAlthough quality of diet has been improving in China, overall quality remains poor, primarily because of inadequate intake of milk and dairy products, nuts, fruits, other cereals and miscellaneous beans, and seafood. Intervention at the community level may improve diet quality more efficiently than at the individual level, and the most effective intervention should be selected in different communities according to local conditions.
Role of hypoxia in cancer therapy by regulating the tumor microenvironment
Authors: Jing Xinming , Yang Fengming , Shao Chuchu , Wei Ke , Xie Mengyan , Shen Hua , Shu Yongqian 
Published: November 2019

AbstractAimClinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy.MethodsRelevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms.ResultsRecent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux.ConclusionHypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.
Multilayered stable 2D nano-sheets of Ti2NTx MXene: synthesis, characterization, and anticancer activity
Authors: Szuplewska A. , Rozmysłowska-Wojciechowska A. , Poźniak S. , Wojciechowski T. , Birowska M. , Popielski M. , Chudy M. , Ziemkowska W. , Chlubny L. , Moszczyńska D. , Olszyna A. , Majewski J. A. , Jastrzębska A. M. 
Published: November 2019

Abstract

Background
The biological activity of MXenes has been studied for several years because of their potential biomedical applications; however, investigations have so far been limited to 2D titanium carbides. Although monolayered Ti2NTx MXene has been expected to have biological activity, experimental studies revealed significant difficulties due to obstacles to its synthesis, its low stability and its susceptibility to oxidation and decomposition.

Results
In this paper, we report our theoretical calculations showing the higher likelihood of forming multilayered Ti2NTx structures during the preparation process in comparison to single-layered structures. As a result of our experimental work, we successfully synthesized multilayered Ti2NTx MXene that was suitable for biological studies by the etching of the Ti2AlN MAX phase and further delamination. The biocompatibility of Ti2NTx MXene was evaluated in vitro towards human skin malignant melanoma cells, human immortalized keratinocytes, human breast cancer cells, and normal human mammary epithelial cells. Additionally, the potential mode of action of 2D Ti2NTx was investigated using reactive oxygen tests as well as SEM observations. Our results indicated that multilayered 2D sheets of Ti2NTx showed higher toxicity towards cancerous cell lines in comparison to normal ones. The decrease in cell viabilities was dose-dependent. The generation of reactive oxygen species as well as the internalization of the 2D sheets play a decisive role in the mechanisms of toxicity.

Conclusions
We have shown that 2D Ti2NTx in the form of multilayered nanoflakes exhibits fair stability and can be used for in vitro studies. These results show promise for its future applications in biotechnology and nanomedicine.
Non-doctoral factors influencing the surgical choice of Chinese patients with breast cancer who were eligible for breast-conserving surgery
Authors: Chen Rui , You Sainan , Yin Zinan , Zhu Qiannan , Jiang Chaojun , Li Shuo , Li Yan , Zha Xiaoming , Wang Jue 
Published: November 2019

Abstract

Background
The rate of breast-conserving surgery (BCS) is low in China. Many patients choose mastectomy even when informed that there is no difference in the overall survival rate compared with that of BCS plus radiotherapy. This study aimed to investigate the factors that influenced the surgical choice in patients eligible for BCS.

Methods
Female patients with breast carcinoma were enrolled in a single center from March 2016 to January 2017. They made their own decision regarding the surgical approach. Univariate analysis was employed to determine the factors associated with the different breast surgical approaches. Significant factors (defined as P < 0.05) were then incorporated into multivariate logistic regression models to determine the factors that independently influenced patients’ decision.

Results
Of the 271 patients included, 149 were eligible for BCS; 65 chose BCS and 84 chose mastectomy. On the basis of univariate analysis, patients with younger age, higher income and education, shorter admission to surgery interval, and shorter confirmed diagnosis to surgery interval were more likely to choose BCS than mastectomy (P < 0.05). Meanwhile, patients who resided in rural regions, did not have general medicare insurance, and were diagnosed with breast cancer preoperatively were more inclined to choose mastectomy than BCS (P < 0.05). The multivariate model revealed three independent influencing factors: age at diagnosis (P = 0.009), insurance status (P = 0.035), and confirmed diagnosis to surgery interval (P = 0.037). In addition, patients receiving neoadjuvant chemotherapy (NCT) were more inclined to choose mastectomy.

Conclusion
Surgical choice of patients eligible for BCS was affected by several factors, and age at diagnosis, confirmed diagnosis to surgery interval, and insurance status were independent factors.
Laparoscopic surgery for colorectal cancer with persistent descending mesocolon
Authors: Hiyoshi Yukiharu , Miyamoto Yuji , Eto Kojiro , Nagai Yohei , Iwatsuki Masaaki , Iwagami Shiro , Baba Yoshifumi , Yoshida Naoya , Baba Hideo 
Published: November 2019

Abstract

Background
Persistent descending mesocolon (PDM) is caused by the absence of fusion of the descending colon to the retroperitoneum. We herein report two colorectal cancer cases with PDM that were treated with laparoscopic surgery.

Case presentation
Case 1: a 50-year-old man with sigmoid colon cancer and synchronous liver metastasis. After neoadjuvant chemotherapy, he underwent laparoscopic sigmoidectomy with lymph node dissection cutting the root of the inferior mesenteric artery (IMA) and synchronous liver resection. He experienced postoperative stenosis of the reconstructed colon possibly due to an impaired arterial blood flow in the reconstructed colon.
Case 2: a 77-year-old man with rectal cancer. Laparoscopic low anterior resection preserving the left colic artery (LCA) was performed. Intraoperative infrared ray (IR) imaging using indocyanine green (ICG) showed good blood flow of the reconstructed colon. He had no postoperative complications. In cases of PDM, the mesentery of the descending and sigmoid colon containing the LCA is often shortened, and the marginal artery of the reconstructed colon is located close to the root of the LCA. Lymph node dissection accompanied by cutting the LCA carries a risk of marginal artery injury. Therefore, we recommend lymph node dissection preserving the LCA in colorectal cancer patients with PDM in order to maintain the blood flow of the reconstructed colon. If the IMA and LCA absolutely need to be cut for complete lymph node dissection, the marginal artery should be clearly identified and preserved. In addition, intraoperative IR imaging is extremely useful for evaluating colonic perfusion and reducing the risk of anastomotic complications.

Conclusion
In colorectal cancer surgery in patients with PDM, surgeons should be aware of these tips for maintaining the blood flow of the reconstructed colon and thereby avoid postoperative complications caused by an impaired blood flow.
Circulating PCSK9 and cardiovascular events in FH patients with standard lipid-lowering therapy
Authors: Cao Ye-Xuan , Jin Jing-Lu , Sun Di , Liu Hui-Hui , Guo Yuan-Lin , Wu Na-Qiong , Xu Rui-Xia , Zhu Cheng-Gang , Dong Qian , Sun Jing , Li Jian-Jun 
Published: November 2019

Abstract

Background
Proprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy.

Methods
A total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score ≥ 6) was enrolled and followed up for the occurrence of MACEs. Multidetector CT and coronary angiography were performed to determine coronary artery calcification score (CACS) and Gensini score (GS). Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma PCSK9 concentrations were determined by enzyme immunoassay.

Results
PCSK9 was independently and positively associated CACS and GS at baseline. During a mean follow-up of 3 years, 33 (9.8%) events occurred. Patients with MACEs had higher median PCSK9 compared with those without (332.47 vs. 311.89 ng/mL, p = 0.038). Kaplan–Meier analysis revealed that patients with higher PCSK9 presented lower event-free survival (p = 0.0017). PCSK9 was statistically correlated with MACEs after adjusting for confounding factors, with the HR per SD being 1.86 (1.31–2.65) and 3.70 (1.16–11.82) for the highest tertile compared with the lowest tertile. Adding PCSK9 to Cox prediction model led to a statistical improvement in net reclassification and integrated discrimination.

Conclusion
Elevated levels of PCSK9 were positively associated with the development of CAD and future cardiovascular events, suggesting that measurement of PCSK9 concentration might be useful for cardiovascular risk stratification. Further studies are needed to confirm our results.
Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage
Authors: Ahn Sung-Ho , Savarraj Jude P. J. , Parsha Kaushik , Hergenroeder Georgene W. , Chang Tiffany R. , Kim Dong H. , Kitagawa Ryan S. , Blackburn Spiros L. , Choi H. Alex 
Published: November 2019

Abstract

Background
Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions.

Methods
Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (< 24 h, 24–48 h, 3–5 days, and 6–8 days after SAH) and concentration levels of 41 cytokines were measured by multiplex immunoassay. Logistic regression analysis was used to identify cytokines associated with DCI and poor functional outcomes. Correlation networks were constructed to identify cytokine clusters.

Results
Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes.

Conclusions
Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.
Peripheral loss of EphA4 ameliorates TBI-induced neuroinflammation and tissue damage
Authors: Kowalski Elizabeth A. , Chen Jiang , Hazy Amanda , Fritsch Lauren E. , Gudenschwager-Basso Erwin Kristobal , Chen Michael , Wang Xia , Qian Yun , Zhou Mingjun , Byerly Matthew , Pickrell Alicia M. , Matson John B. , Allen Irving Coy , Theus Michelle H. 
Published: November 2019

AbstractBackgroundThe continuum of pro- and anti-inflammatory response elicited by traumatic brain injury (TBI) is suggested to play a key role in the outcome of TBI; however, the underlying mechanisms remain ill -defined.MethodsHere, we demonstrate that using bone marrow chimeric mice and systemic inhibition of EphA4 receptor shifts the pro-inflammatory milieu to pro-resolving following acute TBI.ResultsEphA4 expression is increased in the injured cortex as early as 2 h post-TBI and on CX3CR1gfp-positive cells in the peri-lesion. Systemic inhibition or genetic deletion of EphA4 significantly reduced cortical lesion volume and shifted the inflammatory profile of peripheral-derived immune cells to pro-resolving in the damaged cortex. These findings were consistent with in vitro studies showing EphA4 inhibition or deletion altered the inflammatory state of LPS-stimulated monocyte/macrophages towards anti-inflammatory. Phosphoarray analysis revealed that EphA4 may regulate pro-inflammatory gene expression by suppressing the mTOR, Akt, and NF-κB pathways. Our human metadata analysis further demonstrates increasedEPHA4and pro-inflammatory gene expression, which correlates with reduced AKT concurrent with increased brain injury severity in patients.ConclusionsOverall, these findings implicate EphA4 as a novel mediator of cortical tissue damage and neuroinflammation following TBI.
Heterogeneity in HIV and cellular transcription profiles in cell line models of latent and productive infection: implications for HIV latency
Authors: Telwatte Sushama , Morón-López Sara , Aran Dvir , Kim Peggy , Hsieh Christine , Joshi Sunil , Montano Mauricio , Greene Warner C. , Butte Atul J. , Wong Joseph K. , Yukl Steven A. 
Published: November 2019

AbstractBackgroundHIV-infected cell lines are widely used to study latent HIV infection, which is considered the main barrier to HIV cure. We hypothesized that these cell lines differ from each other and from cells from HIV-infected individuals in the mechanisms underlying latency.ResultsTo quantify the degree to which HIV expression is inhibited by blocks at different stages of HIV transcription, we employed a recently-described panel of RT-ddPCR assays to measure levels of 7 HIV transcripts (“read-through,” initiated, 5′ elongated, mid-transcribed/unspliced [Pol], distal-transcribed [Nef], polyadenylated, and multiply-sliced [Tat-Rev]) in bulk populations of latently-infected (U1, ACH-2, J-Lat) and productively-infected (8E5, activated J-Lat) cell lines. To assess single-cell variation and investigate cellular genes associated with HIV transcriptional blocks, we developed a novel multiplex qPCR panel and quantified single cell levels of 7 HIV targets and 89 cellular transcripts in latently- and productively-infected cell lines. The bulk cell HIV transcription profile differed dramatically between cell lines and cells from ART-suppressed individuals. Compared to cells from ART-suppressed individuals, latent cell lines showed lower levels of HIV transcriptional initiation and higher levels of polyadenylation and splicing. ACH-2 and J-Lat cells showed different forms of transcriptional interference, while U1 cells showed a block to elongation. Single-cell studies revealed marked variation between/within cell lines in expression of HIV transcripts, T cell phenotypic markers, antiviral factors, and genes implicated in latency. Expression of multiply-spliced HIV Tat-Rev was associated with expression of cellular genes involved in activation, tissue retention, T cell transcription, and apoptosis/survival.ConclusionsHIV-infected cell lines differ from each other and from cells from ART-treated individuals in the mechanisms governing latent HIV infection. These differences in viral and cellular gene expression must be considered when gauging the suitability of a given cell line for future research on HIV. At the same time, some features were shared across cell lines, such as low expression of antiviral defense genes and a relationship between productive infection and genes involved in survival. These features may contribute to HIV latency or persistence in vivo, and deserve further study using novel single cell assays such as those described in this manuscript.