bluuebunny/crossref_metadata_2025_split huggingface dataset:
l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study
Authors: Zhao Jie V. , Burgess Stephen , Fan Bohan , Schooling C. Mary 
Published: September 2022

AbstractBackgroundl-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety ofl-carnitine, we assessed how genetically different levels ofl-carnitine are associated with CVD risk and its risk factors. Given higher CVD incidence andl-carnitine in men, we also examined sex-specific associations.MethodsWe used Mendelian randomization to obtain unconfounded estimates. Specifically, we used genetic variants to predictl-carnitine, and obtained their associations with coronary artery disease (CAD), ischemic stroke, heart failure, and atrial fibrillation, as well as CVD risk factors (type 2 diabetes, glucose, HbA1c, insulin, lipid profile, blood pressure and body mass index) in large consortia and established cohorts, as well as sex-specific association in the UK Biobank. We obtained the Wald estimates (genetic association with CVD and its risk factors divided by the genetic association withl-carnitine) and combined them using inverse variance weighting. In sensitivity analysis, we used different analysis methods robust to pleiotropy and replicated using anl-carnitine isoform, acetyl-carnitine.ResultsGenetically predictedl-carnitine was nominally associated with higher risk of CAD overall (OR 1.07 per standard deviation (SD) increase inl-carnitine, 95% CI 1.02 to 1.11) and in men (OR 1.09, 95% CI 1.02 to 1.16) but had a null association in women (OR 1.00, 95% CI 0.92 to 1.09). These associations were also robust to different methods and evident for acetyl-carnitine.ConclusionsOur findings do not support a beneficial association ofl-carnitine with CVD and its risk factors but suggest potential harm.l-carnitine may also exert a sex-specific role in CAD. Consideration of the possible sex disparity and exploration of the underlying pathways would be worthwhile.
Combination treatment with hENT1 and miR-143 reverses gemcitabine resistance in triple-negative breast cancer
Authors: Xi Yue , Li Ting , Xi Yun , Zeng Xinyi , Miao Ying , Guo Rui , Zhang Min , Li Biao 
Published: September 2022

AbstractBackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and is susceptible to develop gemcitabine (GEM) resistance. Decreased expression of human equilibrative nucleoside transporter 1 (hENT1) accompanied by compensatory increase of glycolysis is strongly associated with GEM resistance in TNBC. In this study, we investigated the treatment feasibility of combined hENT1 upregulation and miR-143-mediated inhibition of glycolysis for reversing GEM resistance in TNBC.MethodsExperiments were performed in vitro and in vivo to compare the efficacy of GEM therapies. In this study, we established stable drug-resistant cell line, GEM-R cells, from parental cells (MDA-MB-231) through exposure to GEM following a stepwise incremental dosing strategy. Then GEM-R cells were transfected by lentiviral plasmids and GEM-R cells overexpressing hENT1 (GEM-R-hENT1) were established. The viability and apoptosis of wild-type (MDA-MB-231), GEM-R, and GEM-R-hENT1 cells treated with GEM or GEM + miR-143 were analyzed by CCK8 assay and flow cytometry. The RNA expression and protein expression were measured by RT-PCR and western blotting respectively. GEM uptake was determined by multiple reaction monitoring (MRM) analysis. Glycolysis was measured by glucose assay and18F-FDG uptake. The antitumor effect was assessed in vivo in a tumor xenograft model by evaluating toxicity, tumor volume, and maximum standardized uptake value in18F-FDG PET. Immunohistochemistry and fluorescence photography were taken in tumor samples. Pairwise comparisons were performed using Student’s t-test.ResultsOur results represented that overexpression of hENT1 reversed GEM resistance in GEM-R cells by showing lower IC50and higher rate of apoptosis. MiR-143 suppressed glycolysis in GEM-R cells and enhanced the effect of reversing GEM resistance in GEM-R-hENT1 cells. The therapeutic efficacy was validated using a xenograft mouse model. Combination treatment decreased tumor growth rate and maximum standardized uptake value in18F-FDG PET more effectively.ConclusionsCombined therapy of exogenous upregulation of hENT1 expression and miR-143 mimic administration was effective in reversing GEM resistance, providing a promising strategy for treating GEM-resistant TNBC.
Burden of malaria infection among individuals of varied blood groups in Kenya
Authors: Yeda Redemptah , Okudo Charles , Owiti Eunice , Biwot Gladys , Momanyi Cliff , Korir Winnie , Mitsanze Thoya , Tegerei Caroline , Juma Dennis , Opot Benjamin , Mwakio Edwin , Chemwor Gladys , Okoth Raphael , Ochora Douglas O. , Cheruiyot Agnes C. , Roth Amanda , Akala Hoseah M. , Andagalu Ben 
Published: September 2022

Abstract
Background
The ABO blood groups consist of A, B, and H carbohydrate antigens, which regulate protein activities during malaria infection in humans. Understanding the interplay between the malaria parasite and blood group antigens is essential in understanding new interventions to reduce the global burden of malaria. This study assessed the burden of malaria infection among individuals with varying blood groups seeking treatment at selected hospitals in Kenya.

Methods
A total of 366 samples from an ongoing malaria surveillance study were diagnosed for malaria by microscopy and further typed for blood group using ABO blood grouping. Age and sex were recorded in a data sheet, and analysed using R software version 4. Groups’ proportions (blood group, malaria infection, age and sex) were compared using Pearson’s Chi-square and Fischer exact tests. Wilcoxon and Kruskal-Wallis tests were performed and P-value < 0.05 was considered significant after Bonferroni correction for multiple comparisons. To understand the effect of each blood group on parasitaemia, multivariate logistic regression was used to model ABO blood group in relation to parasitaemia.

Results
Of the 366 samples analysed, 312 were malaria positive, mean age was 9.83 years (< 5 years n = 152 (48.41%), 6 to 17 years n = 101 (32.16%) and > 18 years n = 61 (19.43%)). Malaria prevalence was higher among females than males, 54.46% and 45.54%, respectively. Kisumu enrolled the highest number 109 (35%)) of malaria cases, Kombewa 108 (35%), Malindi 32 (10%), Kisii 28 (9%), Marigat 23 (7%), and Kericho 12 (4%). Blood group O+ was the most prevalent among the enrolled individuals (46.50%), A+ (27.71%), B+ (21.02%) and AB+ (4.78%) respectively. Compared to blood group O+, blood group B+ individuals were (14%) were more likely to habour Plasmodium falciparum infection as opposed to A+ and AB+ individuals, that were 7% and 20%, respectively,. Those living in malaria-endemic zones presented with higher parasite densities compared to those living in malaria-epidemic (p = 0.0061). Individuals bearing B + blood group are more likely to habour high parasitaemia compared to O + blood group bearers (OR = 4.47, CI = 1.53–13.05, p = 0.006).

Conclusion
Individuals of blood group B harbour high parasitaemia compared with the blood group O, Additionally, blood group A and B present with symptoms at lower parasitaemia than blood group O. Regardles of malaria transmission zones, individuals from endemic zones showed up with high parasitaemia and among them were more individuals of blood groups A and B than individuals of blood group O. Implying that these individuals were more at risk and require additional attention and effective case management.

Garphical Abstract
Potential application of the haematology analyser XN-31 prototype for field malaria surveillance in Kenya
Authors: Kagaya Wataru , Takehara Ikki , Kurihara Kyoko , Maina Michael , Chan Chim W. , Okomo Gordon , Kongere James , Gitaka Jesse , Kaneko Akira 
Published: September 2022

Abstract
Background
Simple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results.

Methods
Paired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15–25 °C) or chilled temperatures (2–8 °C).

Results
Identical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p.

Conclusion
These results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model.
Does the level of inferior mesenteric artery ligation affect short-term and long-term outcomes of patients with sigmoid colon cancer or rectal cancer? A single-center retrospective study
Authors: Wang Yawei , Wang Yan , Zou Liaonan , Deng Lingna , Wu Tianchong , Liu Linsen , Jiang Jiling , An Tailai 
Published: September 2022

Abstract
Background
For sigmoid colon or rectal cancer, a definite consensus regarding the optimal level ligating the inferior mesenteric artery (IMA) has not been reached. We performed this study to determine whether the ligation level significantly affected short-term and long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.

Methods
Medical records of patients with sigmoid colon or rectal cancer who had undergone curative laparoscopic surgery between January 2008 and December 2014 at the Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine were reviewed. Then, the high tie group (HTG) was compared with the low tie group (LTG) in terms of short-term and long-term outcomes.

Results
Five-hundred ninety patients were included. No significant differences between two groups regarding baseline characteristics existed. HTG had a significantly higher risk of anastomotic fistula than LTG (21/283 vs 11/307, P = 0.040). Additionally, high ligation was proven by multivariate logistic regression analysis to be an independent factor for anastomotic fistula (P = 0.038, OR = 2.232, 95% CI: 1.047–4.758). Furthermore, LT resulted in better preserved urinary function. However, LTG was not significantly different from HTG regarding operative time (P = 0.075), blood transfusion (P = 1.000), estimated blood loss (P = 0.239), 30-day mortality (P = 1.000), ICU stay (P = 0.674), postoperative hospital stay (days) (P = 0.636), bowel obstruction (P = 0.659), ileus (P = 0.637), surgical site infection (SSI) (P = 0.121), number of retrieved lymph nodes (P = 0.501), and number of metastatic lymph nodes (P = 0.131). Subsequently, it was revealed that level of IMA ligation did not significantly influence overall survival (OS) (P = 0.474) and relapse-free survival (RFS) (P = 0.722). Additionally, it was revealed that ligation level did not significantly affect OS (P = 0.460) and RFS (P = 0.979) of patients with stage 1 cancer, which was also observed among patients with stage 2 or stage 3 cancer. Ultimately, ligation level was not an independent predictive factor for either OS or RFS.

Conclusions
HT resulted in a significantly higher incidence of anastomotic fistula and worse preservation of urinary function. Level of IMA ligation did not significantly affect long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.
Development, validation and item reduction of a food literacy questionnaire (IFLQ-19) with Australian adults
Authors: Thompson Courtney , Byrne Rebecca , Adams Jean , Vidgen Helen Anna 
Published: September 2022

Abstract
Background
Food literacy is theorised to improve diet quality, nutrition behaviours, social connectedness and food security. The definition and conceptualisation by Vidgen & Gallegos, consisting of 11 theoretical components within the four domains of planning and managing, selecting, preparing and eating, is currently the most highly cited framework. However, a valid and reliable questionnaire is needed to comprehensively measure this conceptualisation. Therefore, this study draws on existing item pools to develop a comprehensive food literacy questionnaire using item response theory.

Methods
Five hundred Australian adults were recruited in Study 1 to refine a food literacy item pool using principal component analysis (PCA) and item response theory (IRT) which involved detailed item analysis on targeting, responsiveness, validity and reliability. Another 500 participants were recruited in Study 2 to replicate item analysis on validity and reliability on the refined item pool, and 250 of these participants re-completed the food literacy questionnaire to determine its test–retest reliability.

Results
The PCA saw the 171-item pool reduced to 100-items across 19 statistical components of food literacy. After the thresholds of 26 items were combined, responses to the food literacy questionnaire had ordered thresholds (targeting), acceptable item locations (< -0.01 to + 1.53) and appropriateness of the measurement model (n = 92% expected responses) (responsiveness), met outfit mean-squares MSQ (0.48—1.42) (validity) and had high person, item separation (> 0.99) and test–retest (ICC 2,1 0.55–0.88) scores (reliability).

Conclusions
We developed a 100-item food literacy questionnaire, the IFLQ-19 to comprehensively address the Vidgen & Gallegos theoretical domains and components with good targeting, responsiveness, reliability and validity in a diverse sample of Australian adults.
Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway
Authors: Yao Chongjie , Ren Jun , Huang Ruixin , Tang Cheng , Cheng Yanbin , Lv Zhizhen , Kong Lingjun , Fang Sitong , Tao Jiming , Fu Yangyang , Zhu Qingguang , Fang Min 
Published: September 2022

AbstractBackgroundLocal neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT.MethodsWe used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats.ResultsCompared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects.ConclusionsIn rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.
IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes
Authors: Lemaître Florent , Farzam-kia Negar , Carmena Moratalla Ana , Carpentier Solorio Yves , Clenet Marie-Laure , Tastet Olivier , Cleret-Buhot Aurélie , Guimond Jean Victor , Haddad Elie , Duquette Pierre , Girard J. Marc , Prat Alexandre , Larochelle Catherine , Arbour Nathalie 
Published: September 2022

Abstract
Background
Interleukin-27 (IL-27) can trigger both pro- and anti-inflammatory responses. This cytokine is elevated in the central nervous system (CNS) of multiple sclerosis (MS) patients, but how it influences neuroinflammatory processes remains unclear. As astrocytes express the receptor for IL-27, we sought to determine how these glial cells respond to this cytokine and whether such exposure alters their interactions with infiltrating activated T lymphocytes. To determine whether inflammation shapes the impact of IL-27, we compared the effects of this cytokine in non-inflamed and inflamed conditions induced by an IL-1β exposure.

Main body
Transcriptomic analysis of IL-27-exposed human astrocytes showed an upregulation of multiple immune genes. Human astrocytes increased the secretion of chemokines (CXCL9, CXCL10, and CXCL11) and the surface expression of proteins (PD-L1, HLA-E, and ICAM-1) following IL-27 exposure. To assess whether exposure of astrocytes to IL-27 influences the profile of activated T lymphocytes infiltrating the CNS, we used an astrocyte/T lymphocyte co-culture model. Activated human CD4+ or CD8+ T lymphocytes were co-cultured with astrocytes that have been either untreated or pre-exposed to IL‑27 or IL-1β. After 24 h, we analyzed T lymphocytes by flow cytometry for transcription factors and immune molecules. The contact with IL-27-exposed astrocytes increased the percentages of T-bet, Eomes, CD95, IL-18Rα, ICAM-1, and PD-L1 expressing CD4+ and CD8+ T lymphocytes and reduced the proportion of CXCR3-positive CD8+ T lymphocytes. Human CD8+ T lymphocytes co-cultured with human IL-27-treated astrocytes exhibited higher motility than when in contact with untreated astrocytes. These results suggested a preponderance of kinapse-like over synapse-like interactions between CD8+ T lymphocytes and IL-27-treated astrocytes. Finally, CD8+ T lymphocytes from MS patients showed higher motility in contact with IL-27-exposed astrocytes compared to healthy donors’ cells.

Conclusion
Our results establish that IL-27 alters the immune functions of human astrocytes and shapes the profile and motility of encountered T lymphocytes, especially CD8+ T lymphocytes from MS patients.
Women’s experience of unintended pregnancy and changes in contraceptive methods: evidence from a nationally representative survey
Authors: Khan Md Nuruzzaman , Islam M. Mofizul 
Published: September 2022

Abstract
Background
Ineffective or no use of contraception following an unintended pregnancy contributes to a subsequent unintended pregnancy. This study aimed to determine whether women’s experiences of unintended pregnancies affect changing their contraceptive using patterns.

Methods
We analysed the 2017/2018 Bangladesh Demographic and Health Survey data. The contraceptive switching pattern was computed by comparing women’s contraceptives using data before and after pregnancy. Women were categorised into the following three groups, depending on their patterns of contraceptive use before and after pregnancy: no change, if there were no change in contraceptive using pattern; switched to higher effective contraceptives, if changed from pre-pregnancy less effective contraceptives to post-pregnancy more effective contraceptives; switched to less effective contraceptives, if changed from pre-pregnancy more effective contraceptives to post-pregnancy less effective contraceptives. Women’s intention in the most recent pregnancy was our primary explanatory variable, classified as wanted, mistimed and unwanted. Multinomial multilevel logistics regression was used to determine the association between women’s intention in the most recent pregnancy and women’s contraceptive methods switching patterns from before to after pregnancy.

Results
Around 20% of the most recent pregnancies that ended with a live birth were unintended at conception. No contraceptive use was reported by 37% of women before their pregnancies which decreased to 24% after pregnancies. Overall, around 54% of women who reported no contraceptive use before pregnancy used modern contraceptives after pregnancy. The rate was higher among women who experienced unwanted pregnancy (73.4%) than mistimed (58.8%) and wanted (53.4%) pregnancy. Experience of mistimed pregnancy was associated with a higher likelihood of no contraceptive change (aOR, 1.84, 95% CI 1.41–2.39) and switching to less effective contraceptives (aOR, 1.58, 95% CI 1.10–2.26) than switching to more effective contraceptives. However, unwanted pregnancy was not associated with any significant change in contraceptives use from before to after pregnancy.

Conclusion
Experience of unintended pregnancy did not change women’s contraception using patterns, which indicates the risk of repeat unintended pregnancies and associated adverse consequences, including maternal and child morbidity and mortality. Policies to ensure access to and use of modern contraceptives among women facing unwanted or mistimed pregnancies are recommended.