bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupting Cholesterol-FOXO3-KRT14 axis suppresses metastasis of triple-negative breast cancer
Authors: Dong Jie , Kong Lingkai , Xia Mao , Wei Jiwu 
Published: October 2021

Abstract
High metastatic propensity is a devastating challenge to effective therapy of solid tumors, including triple-negative breast cancer (TNBC). In this study, we performed a genome-scale screen and found that cholesterol homeostasis is essential for tumor progression in immunocompetent mice. In an orthotopic TNBC model, intracellular cholesterol promoted lung metastasis by sustaining the expression of keratin 14 (KRT14) and decreasing MHC II, which was indispensable for the cluster metastasis of TNBC. Mechanistic studies demonstrated that FOXO3a regulated the transcription of KRT14. FOXO3a recognized and directly bound to the promoter of KRT14 to inhibit its expression. Cholesterol disrupted the nuclear translocation of FOXO3a by sustaining its phosphorylation, which was regulated by IKK, one of the major upstream kinases of FOXO3a. Apolipoprotein A1 (ApoA1) increased cholesterol efflux and inhibited TNBC metastasis by regulating the IKK-FOXO3a-KRT14 axis. The recombinant adenovirus encoding ApoA1 (ADV-ApoA1) promoted cholesterol efflux, dampened metastasis, and prolonged survival in mice bearing TNBC. Finally, we provided preliminary data showing that high doses of ADV-ApoA1 were well tolerated in rhesus monkeys and Syrian hamsters injected both intravenously and hypodermically. Taken together, cholesterol promotes metastasis via the IKK-FOXO3a-KRT14 axis in TNBC, and facilitating cholesterol efflux from TNBC cells is a promising therapeutic strategy for TNBC clinical treatment.
The Impact of Zinc Supplementation on Oxidative Stress and Inflammatory Biomarkers in Opioid Addicts-Withdrawal Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Keshavarzi Amir , Hassanalizade Ali , Ranjbar Akram , Ghaleiha Ali , Vafaei Seyed Yaser , Rezaei Sara , Amini Shiva , Faryadras Mohammad , Moridi Heresh , Ghaffari Fatemeh , Ataei Sara 
Published: October 2021

Abstract
Background

Opioid withdrawal can induce oxidative stress in opioid addicts. This interventional study aimed to investigate the effect of zinc supplementation on the oxidative profile of patients with an opioid withdrawal syndrome.
Methods

In the current study, 40 patients aged 18 to 65 years with opioid withdrawal syndrome were randomly assigned to intervention and control groups, each with 20 subjects. In addition to standard treatment, the intervention group received 30 mg of zinc daily, while the control group was given a placebo for one month. They were evaluated using Beck Depression Inventory (BDI), Clinical Opiate Withdrawal Scale (COWS), and Young Mania Rating Scale (YMRS) for withdrawal symptoms. Moreover, other parameters included catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and levels of total antioxidant capacity (TAC), total thiol groups (TTG), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA).
Results

The rate of withdrawal symptoms (COWS) was statistically significantly lower in the treated group in comparison to the control group (P < 0.05). In the treatment group, the levels of TAC, CAT, SOD, and GPx increased significantly compared to the control group (P < 0.05). In the treatment group compared to the control group, there was a statistically significant decrease in hs-CRP, MDA, and TNFα (P < 0.05).
Conclusions

The results revealed that zinc supplementation could effectively reduce withdrawal symptoms by increasing antioxidant activity and reducing the lipid peroxidation index.
Carrying G allele in rs786204926 involved in alternative splicing of PTEN is associated with chemosensitivity in breast cancer
Authors: Wang Jing , Zhang Shasha , Zhang Jiaxin , Zhang Zhongliang , Ma Qinglong , Fu Wenkang , Chen Xiaohua , Zhao Dapeng , Zhao Meie , Wang Chunwei , Di Cuixia , Xie Xiaodong 
Published: October 2021

Abstract
Background

Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemoresistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between novel PTEN gene polymorphism and breast chemoresistance in Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism.
Methods

The study included 234 patients with breast cancer chemotherapy, 157 chemosensitive cases and 77 chemoresistant case. rs786204926, rs701848, rs12402181, rs35770269 were analysed using Sanger sequence and Sequenom MassArray typing technology. Silicon analysis was used to predict whether and how the polymorphism affects alternative splicing. Semi-quantitative RT-PCR and Western blot were further used to validate the silicon analysis.
Results

It is showed that there was a significant association between rs786204926 polymorphism and breast cancer chemoresistance. Carrying G allele or AG genotype will increase the risk of chemosensitivity in breast cancer. Additionally, Logistic multivariate regression analysis showed that age, lymph node metastasis and rs786204926 genotype are risk factors for breast cancer chemoresistance. Furthermore, Silico analysis showed that carrying G allele or AG genotype in chemosensitivity samples produced a new receptor site of alternative splicing, which increases the possibility of a new mutant PTEN isoform production. Interestingly, further experiments also verify this possibility.
Conclusion

We speculate that the mechanism of breast cancer chemosensitivity might be caused by a change in alternative splicing caused by the rs786204926 of PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.
Ten Years Trend of Malaria Prevalence in Ziway Dugda District, Arsi Zone, Ethiopia 2011-2020
Authors: Mesfun Million Getachew , Ayalneh Shimelis Teshome 
Published: October 2021

Abstract
Background: Malaria has been one of the major public health problems in Ethiopia for decades. Recent reports from different part of the country showed that the trend of malaria is declining. However, there is a need for periodic assessing the trend of malaria in different malaria endemic areas of the country as part of the planed malaria elimination strategies. Methods: Ten years retrospective data of blood film examination was collected from the laboratory registration book and monthly report of Ogolcho health center and analyzed to assess the trend of malaria prevalence in Ziway dugda distric, one of the malaria endemic areas in Arsi zone, Ethiopia. Result: From the total of 38,094 malaria suspected patients, 4,863(12.8%) patients were malaria positive microscopically, with 3,301(67.9%) P.vivax, 1545(31.8%) P.falciparum and 17(0.35%) mixed infection. There was a fluctuating trend of malaria within the last ten years, with annual total cases of malaria ranged from 1685 in 2013 to 103 in 2020 and there was successive reduction in malaria prevalence from 2013 onwards. Conclusion: Trend of malaria was declining in Ziway dugda district with shift in dominancy of the circulating species (P.vivax).
Hyperthermia Affects Immune and Oxidative Stress Indices of Immune Organs of Broilers by Changing the Expressions of ABCG2, SVCT-2 and MCU
Authors: Xue Xiuheng , Ren Chunhuan , Wang Luping , Xu Mengzhu Xu , Fan Caiyun , Fang Fugui , Peng Mengling , Cheng Jianbo , Wang Juhua 
Published: October 2021

Abstract
Background: As global temperatures rise, heat stress has become one of the major environmental stressors in the poultry industry. The purpose of the study was to investigate the effects of heat stress on immune function and oxidative stress, and further reveal the possible mechanisms of oxidative stress induced by heat stress for thymus and spleen of broilers. Methods: At the age of 28 days, thirty broilers were randomly divided into the control group (25 ± 2°C; 24 h/day) and the heat stress group (36 ± 2°C; 8 h/day); the experience was lasted for 1 week. At the end of the experience, the broilers per group were respectively euthanized and collected some samples, then to be analyzed. Results: The results showed that the levels of heat shock proteins 70 (HSP70,P＜ 0.01), corticosterone (CORT,P＜ 0.01), the contents of malondialdehyde (MDA, P＜ 0.05), interleukin-6 (IL-6, P＜ 0.01) and tumor necrosis factor-alpha (TNF-α, P＜ 0.01) in serum were significantly higher in heat stress group than that in the control group; The activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and contents of glutathione (GSH) in heat stress group significantly reduced (P＜ 0.05) in serum. Compared with the control group, the birds subjected to heat stress reduced the weight (P＜ 0.01) and the indices of thymus (P＜ 0.01), the activities of T-AOC (P＜ 0.01) and SOD (P＜ 0.05) of spleen, and levels of IL-10 (P＜ 0.05) and the GSH-PX (P＜ 0.05) in thymus and spleen, and increased the IL-6 content of thymus (P＜ 0.05), the MDA content (P＜ 0.01), and the reactive oxygen species (ROS) levels (P＜ 0.01) in thymus and spleen. Moreover, the expression of immunoglobulin G (IgG) gene in thymus and spleen of heat stressed broiler significantly increased by reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR (qRT-PCR; P＜ 0.05); However, the expression of immunoglobulin M (IgM) gene in spleen significantly increased (P＜ 0.05), and had no significant difference (P＞ 0.05) in thymus of heat-stressed broiler. Furthermore, the relative expression of ATP binding cassette subfamily G member 2 (ABCG2) in thymus and spleen (P＜ 0.05), sodium dependent vitamin C transporter-2 (SVCT-2, P＜ 0.01) and mitochondria calcium uniporter (MCU, P＜ 0.01) mRNA in thymus of heat stressed broilers significantly increased; and the expression of ABCG2 (P＜ 0.05), SVCT-2 (P＜ 0.01) and MCU (P＜ 0.01) protein of thymus and spleen in the heat-stressed broiler increased significantly compared with the control group. Conclusions: In summary, the study confirmed that heat stress caused oxidative stress to immune organs of broilers, further reduced immune function. Moreover, the potential mechanisms of heat stress-induced oxidative stress for thymus and spleen was further reveal in broilers.
Identifying Who Engages in Sustainable Adaptation in Large-Scale Commodity Agriculture
Authors: Wilson Robyn S. , Walpole Hugh 
Published: October 2021

Abstract
Global climate change is projected to negatively impact agriculture through increasingly severe weather. In the eastern Corn Belt of the United States, it is projected to get warmer and wetter overall, with more variability in the seasonal timing of rainfall. This will make it more difficult to get into the fields in the spring and fall due to wet conditions, while higher overall temperatures and decreased rainfall in the summer may limit crop growth. While there are multiple adaptations to reduce the vulnerability of agricultural production to a changing climate, these adaptations have varying implications for soil health, carbon sequestration and water quality. We explore the drivers of adaptations that vary in their provisioning of a variety of ecosystem services. We find that adaptation is driven in large part by self-reported past negative experiences with climate change that drive up concern about future climate change. Adaptation is also more likely among farmers that are younger, more educated, and more conservation minded, and who operate farms that are larger, more extensively insured, and will be passed on to a family member. However, increasing tile drainage will be the most common strategy in response to increased and more variable rainfall, indicating potential negative impacts for water quality. Practices that promote soil health and sequestration will be less common, and more driven by the identity of farmers as conservationists than by the weather. There will be a need to offset the potential negative impacts of increasing drainage through the promotion of edge-of-field filtration practices.
Comparing the surgical efficacy of a newly designed endoscopic visualized trephine and a conventional trephine for percutaneous endoscopic lumbar discectomy with foraminoplasty for patients with single-segment lumbar disc herniation: A retrospective case -control study
Authors: Niu Shangbo , Yang Dehong , Li Jie , Diao Wenbo , Gao Jian , Li Yiming 
Published: October 2021

Abstract
Background

Owing to the remarkable evolution of percutaneous endoscopic lumbar discectomy (PELD), the application of spinal endoscopy is shifting from the treatment of soft disk herniation to complex lumbar spinal stenosis. This study aim to compare the surgical efficacy of a newly designed endoscopic visualized trephine and a conventional trephine for PELD with foraminoplasty for patients with single-segment lumbar disc herniation (LDH).
Methods

A total of 54 patients who were diagnosed with single-segment LDH and received PELD with foraminoplasty at Xuzhou Central Hospital (Xuzhou, China) from January 2016 to June 2020 were included in this case-control study. Data related to the length of incision, amount of intraoperative bleeding, the time required to create the working channel, and intraoperative and postoperative complications were recorded. The Visual Analog Scale (VAS) score was used to assess low back pain and leg pain. Besides, the Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) scores were utilized to evaluate patients’ pain intensity and their sitting and standing abilities. The X-ray fluoroscopy was performed to measure the horizontal and angular displacements of lumbar extension-flexion, and to evaluate the stability of lumbar spine.
Results

All the patients successfully underwent surgical procedures, except for two patients with injuries in the spinal nerve root of the responsible segment in the conventional trephine group, who were given nutritional supplements for nerve treatment. Besides, there was no significant difference in incision length and operative blood loss between the modern trephine and the conventional trephine groups. However, the time required to create the channel and the duration of fluoroscopy in the modern trephine group were significantly less than those in the conventional trephine group (34.24 ± 5.38 vs. 44.76 ± 6.37 min, P < 0.05). In addition, the VAS, ODI, and JOA scores significantly decreased postoperatively in the two groups. We also found no significant difference in horizontal and angular displacements of lumbar extension-flexion between the two groups pre-operation and at 3- and 12-month post-operation.
Conclusion

In spite of similar surgical efficacy of the two techniques, the newly designed endoscopic visualized trephine outperformed in terms of operation time and duration of fluoroscopy.
Comparison of Clinical Efficacy Between Arthroscopically Assisted Gracilis Autograft With Suture Reinforcement Technique and Transtibial Pull-out Technique in Treating Medial Meniscus Posterior Root Tears
Authors: Nie Si Si , Li Hongbo , He Jianyin , Liao Guanxiang , Ke Xuelei , Lan Min 
Published: October 2021

Abstract
Background: To compare the short-term efficacy of the transtibial pull-out technique and gracilis autograft with suture reinforcement technique in the treatment of medial meniscus posterior root tears. Methods: A total of 64 patients with medial meniscus posterior root tears received reconstruction of the posterior root of the meniscus attachment point through the tibial tunnel between June 2018 and April 2019 were included in this study, patients were divided into 2 groups (transtibial pull-out technique group: 35 cases; gracilis autograft with suture reinforcement technique group: 29 cases) according to the different posterior meniscus root tear repair methods. Clinical outcomes were evaluated by the visual analogue scale (VAS) and Lysholm score and IKDC score, and the demographics and functional recovery of the knee were compared between the two groups.Results: Intraoperative and postsurgical complications such as infection were not found in the two groups, and there was a statistically significant improvement in the Lysholm score，IKDC score and VAS score (P<0.001; respectively). All the patients were very satisfied with the function of their knee at the last follow-up. However, compared with the transtibial pull-out repair group, the reinforced medial meniscal root reconstruction technique with gracilis autograft group were significant improvement in the meniscus healing rates and Lysholm score, IKDC score and VAS score at the end of follow-up (P<0.05; respectively).Conclusions: Compared with the transtibial pull-out technique, the reinforced medial meniscal root reconstruction technique with gracilis autograft is advantageous for treating these patients because it is a minimally invasive procedure with superior clinical outcome and meniscus healing rates.Levels of Evidence: Ⅲ, Case-control study Retrospective comparative study
CpG-activated Regulatory B-cell Progenitors Alleviate Murine Sclerodermatous Chronic GVHD
Authors: Agbogan Viviane A , Gastineau Pauline , Tejerina Emmanuel , Karray Saoussen , Zavala Flora 
Published: October 2021

Abstract
BackgroundDevelopment of chronic Graft Versus Host Disease (cGVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). This disorder is associated with severe impairment of B-cell homeostasis, regulatory B-cell function and distribution. Conversely, the presence of bone marrow and circulating hematogones is associated with reduced GVHD risks. These findings raised the question whether B-cell progenitors, which provide protection in various autoimmune disease models following activation with the TLR-9 agonist CpG (CpG-proBs), could likewise reduce disease symptoms in a sclerodermatous model of cGVHD. MethodsChronic sclerodermatous GVHD was induced in irradiated Balb/c recipients reconstituted with T- and B-cell-depleted bone marrow cells and splenocytes from C57BL/6J donors. CpG-proB-cell progenitors sorted from in vitro CpG-activated bone marrow cells were then adoptively transferred into GVHD recipients. Their effect on disease symptoms, such as diarrhea, skin fibrosis and survival was evaluated in the therapeutic window defined beforehand. Transferred progenitors were analyzed for migration, differentiation and cytokine expression using flow cytofluorimetric methods, which were also used to establish their impact on T-cell cytokine expression and follicular helper/regulatory T-cell ratios (Tfh/Tfr) in peripheral and mesenteric lymph nodes. Skin fibrosis was assessed by histology, identification of infiltrating cells and gene expression profiles of cytokines and molecules involved in the fibrotic process, using qRT-PCR microarrays in all tissue samples.ResultsWe found that CpG-proBs, adoptively transferred during the initial phase of disease, reduced the diarrhea score and mostly prevented cutaneous fibrosis. Progenitors migrated to the draining lymph nodes and to the skin where they mainly differentiated into follicular B cells. CpG activation and IFN-γ expression were required for the protective effect, which resulted in reduced CD4+ T-cell-derived production of cytokines critically involved in cGVHD, such as TGF-β, IL-13 and IL-21. Adoptive transfer increased the Tfr/Tfh ratio. Moreover, CpG-proBs privileged the accumulation of IL-10-positive CD8+ T cells, B cells and dendritic cells in the skin. ConclusionOur findings support the notion that adoptively transferred CpG-proBs provide an efficient strategy for alleviating sclerodermatous cGVHD either per se or as a beneficial adjunct to the HSC graft.
Association Between Primary School Students’ Unhealthful Behaviors and Overweight/Obesity: A Cross-Sectional Analysis in Urban Kenya
Authors: Gewa Constance A , Onyango Agatha Christine , Opiyo Rose Okoyo , Gittelsohn Joel , Cheskin Lawrence J. 
Published: October 2021

Abstract
Introduction

: Although obesity prevalence is known to be rising in East Africa, research on childhood obesity is still minimal. We conducted a cross-sectional study to examine the prevalence of unhealthful dietary patterns, physical activity and sleep behaviors among primary school children in two urban settings in Kenya and explored the association between the behaviors and overweight/obesity among the children.
Methods

Six public schools, with children from low-, medium- and high-income households in Nairobi and Kisumu cities were purposively selected to participate in the study. Data was collected on randomly-selected students aged 10–12 years at each school. Students’ weights, heights, waist circumferences, and tricep, bicep, subscapular and suprailiac skinfolds were measured. Body-mass-index-for-age z-scores were used to classify students into underweight, healthy weight, overweight and obese categories. Waist-circumference-to-height ratio above 0.5 was used to define abdominal obesity and the total amount of body fat was estimated from the sum of skinfold measures. Parents, with the help of their children, completed questionnaires on student’s dietary, physical activity, and sleep behaviors. Anthropometric measurements and questionnaires were available for 390 students. We utilized prevalence ratio analysis to examine the association between socio-economic/demographic characteristics, unhealthful behaviors and overweight/obesity.
Results

Overall, 21% of the students were overweight or obese and 9% of them had abdominal obesity. Median total skinfold measurements was 32.5 mm. Prevalence of unhealthful behaviors varied significantly by student’s age, gender, school income levels, city, and frequency of consumption of restaurant foods. Students who consumed less than recommended amount of fruit servings had 1.68 times the risk of being overweight/obese, 2.49 times the risk of having abdominal obesity and 1.47 times the risk of having high total skinfold values compared to students with adequate fruit intake. Students with high frequency of consumption of red/processed meats had 1.50 times the risk of being overweight/obesity compared to students with less-frequent consumption.
Conclusion

We found a rather high prevalence of unhealthful dietary behaviors among primary school students in Kenya, identified their determinants, and the association between specific behaviors and overweight/obesity. These results can guide childhood obesity prevention measures in Kenya and other nations in East Africa.