bluuebunny/crossref_metadata_2025 huggingface dataset:
O-serogroups, virulence genes, antimicrobial susceptibility, and MLST genotypes of Shiga toxin-producing Escherichia coli from swine and cattle in Central China
Authors: Peng Zhong , Liang Wan , Hu Zizhe , Li Xiaosong , Guo Rui , Hua Lin , Tang Xibiao , Tan Chen , Chen Huanchun , Wang Xiangru , Wu Bin
Published: November 2019

Background

Shiga toxin-producing Escherichia coli (STEC) is a leading cause of worldwide food-borne and waterborne infections. Despite an increase in the number of STEC outbreaks, there is a lack of data on prevalence of STEC at the farm level, distribution of serogroups, and virulence factors.

Results

In the present study, a total of 91 (6.16%) STEC strains were isolated from 1477 samples including pig intestines, pig feces, cattle feces, milk, and water from dairy farms. The isolation rates of STEC strains from pig intestines, pig feces, and cattle feces were 7.41% (32/432), 4.38% (21/480), and 9.57% (38/397), respectively. No STEC was isolated from the fresh milk and water samples. By O-serotyping methods, a total of 30 types of O-antigens were determined, and the main types were O100, O97, O91, O149, O26, O92, O102, O157, and O34. Detection of selected virulence genes (stx1, stx2, eae, ehxA, saa) revealed that over 94.51% (86/91) of the isolates carried more than two types of virulence associated genes, and approximately 71.43% (65/91) of the isolates carried both stx1 and stx2, simultaneously. Antimicrobial susceptibility tests showed that most of the STEC isolates were susceptible to ofloxacin and norfloxacin, but showed resistance to tetracycline, kanamycin, trimethoprim-sulfamethoxazole, streptomycin, amoxicillin, and ampicillin. MLST determined 13 categories of sequence types (STs), and ST297 (31.87%; 29/91) was the most dominant clone. This clone displayed a close relationship to virulent strains STEC ST678 (O104: H4). The prevalence of ST297 clones should receive more attentions.

Conclusions

Our preliminary data revealed that a heterogeneous group of STEC is present, but the non-O157 serogroups and some ST clones such as ST297 should receive more attentions.
Reinterpretation, reclassification, and its downstream effects: challenges for clinical laboratory geneticists
Authors: El Mecky Julia , Johansson Lennart , Plantinga Mirjam , Fenwick Angela , Lucassen Anneke , Dijkhuizen Trijnie , van der Hout Annemieke , Lyle Kate , van Langen Irene
Published: November 2019

Background

In recent years, the amount of genomic data produced in clinical genetics services has increased significantly due to the advent of next-generation sequencing. This influx of genomic information leads to continuous changes in knowledge on how genetic variants relate to hereditary disease. These changes can have important consequences for patients who have had genetic testing in the past, as new information may affect their clinical management. When and how patients should be recontacted after new genetic information becomes available has been investigated extensively. However, the issue of how to handle the changing nature of genetic information remains underexplored in a laboratory setting, despite it being the first stage at which changes in genetic data are identified and managed.

Methods

The authors organized a 7-day online focus group discussion. Fifteen clinical laboratory geneticists took part. All (nine) Dutch clinical molecular genetics diagnostic laboratories were represented.

Results

Laboratories in our study reinterpret genetic variants reactively, e.g. at the request of a clinician or following identification of a previously classified variant in a new patient. Participants currently deemed active, periodic reinterpretation to be unfeasible and opinions differed on whether it is desirable, particularly regarding patient autonomy and the main responsibilities of the laboratory. The efficacy of reinterpretation was questioned in the presence of other strategies, such as reanalysis and resequencing of DNA. Despite absence of formal policy regarding when to issue a new report for clinicians due to reclassified genetic data, participants indicated similar practice across all laboratories. However, practice differed significantly between laboratory geneticists regarding the reporting of VUS reclassifications.

Conclusion

Based on the results, the authors formulated five challenges needing to be addressed in future laboratory guidelines: 1. Should active reinterpretation of variants be conducted by the laboratory as a routine practice? 2. How does reinterpretation initiated by the laboratory relate to patient expectations and consent? 3. When should reinterpreted data be considered clinically significant and communicated from laboratory to clinician? 4. Should reinterpretation, reanalysis or a new test be conducted? 5. How are reclassifications perceived and how might this affect laboratory practice?
Advances and opportunities in gene editing and gene regulation technology for Yarrowia lipolytica
Authors: Ganesan Vijaydev , Spagnuolo Michael , Agrawal Ayushi , Smith Spencer , Gao Difeng , Blenner Mark
Published: November 2019

Yarrowia lipolytica has emerged as a biomanufacturing platform for a variety of industrial applications. It has been demonstrated to be a robust cell factory for the production of renewable chemicals and enzymes for fuel, feed, oleochemical, nutraceutical and pharmaceutical applications. Metabolic engineering of this non-conventional yeast started through conventional molecular genetic engineering tools; however, recent advances in gene/genome editing systems, such as CRISPR–Cas9, transposons, and TALENs, has greatly expanded the applications of synthetic biology, metabolic engineering and functional genomics of Y. lipolytica. In this review we summarize the work to develop these tools and their demonstrated uses in engineering Y. lipolytica, discuss important subtleties and challenges to using these tools, and give our perspective on important gaps in gene/genome editing tools in Y. lipolytica.
Cisplatin-resistant A549 non-small cell lung cancer cells can be identified by increased mitochondrial mass and are sensitive to pemetrexed treatment
Authors: Gao Yanyun , Dorn Patrick , Liu Shengchen , Deng Haibin , Hall Sean R. R. , Peng Ren-Wang , Schmid Ralph A. , Marti Thomas M.
Published: November 2019

Background

Cisplatin plus pemetrexed combination therapy is considered the standard treatment for patients with advanced, non-squamous, non-small-cell lung cancer (NSCLC). However, advanced NSCLC has a 5-year survival rate of below 10%, which is mainly due to therapy resistance. We previously showed that the NSCLC cell line A549 harbors different subpopulations including a mesenchymal-like subpopulation characterized by increased chemo- and radiotherapy resistance. Recently, therapy resistance in hematological and solid tumors has been associated with increased mitochondrial activity. Thus, the aim of this study was to investigate the role of the mitochondrial activity in NSCLC chemotherapy resistance.

Methods

Based on MitoTracker staining, subpopulations characterized by the highest 10% (Mito-High) or lowest 10% (Mito-Low) mitochondrial mass content were sorted by FACS (Fluorescence-Activated Cell Sorting) from paraclonal cultures of the NSCLC A549 cell line . Mitochondrial DNA copy numbers were quantified by real-time PCR whereas basal cellular respiration was measured by high-resolution respirometry. Cisplatin and pemetrexed response were quantified by proliferation and colony formation assay.

Results

Pemetrexed treatment of parental A549 cells increased mitochondrial mass over time. FACS-sorted paraclonal Mito-High cells featured increased mitochondrial mass and mitochondrial DNA copy number compared to the Mito-Low cells. Paraclonal Mito-High cells featured an increased proliferation rate and were significantly more resistant to cisplatin treatment than Mito-Low cells. Interestingly, cisplatin-resistant, paraclonal Mito-High cells were significantly more sensitive to pemetrexed treatment than Mito-Low cells. We provide a working model explaining the molecular mechanism underlying the increased cisplatin- and decreased pemetrexed resistance of a distinct subpopulation characterized by high mitochondrial mass.

Conclusions

This study revealed that cisplatin resistant A549 lung cancer cells can be identified by their increased levels of mitochondrial mass. However, Mito-High cells feature an increased sensitivity to pemetrexed treatment. Thus, pemetrexed and cisplatin target reciprocal lung cancer subpopulations, which could explain the increased efficacy of the combination therapy in the clinical setting.
High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients
Authors: Chen Yangshan , Sun Yu , Cui Yongmei , Lei Yiyan , Jiang Neng , Jiang Wenting , Wang Han , Chen Lili , Luo Jiping , Chen Yanyang , Tang Kejing , Zhou Chengzhi , Ke Zunfu
Published: November 2019

Background

This study aimed to investigate the prognostic value of the potential biomarker collagen triple helix repeat containing 1 (CTHRC1) in lung adenocarcinoma (LUAD) patients.

Methods

A total of 210 LUAD patients diagnosed between 2003 and 2016 in the Department of Pathology of the First Affiliated Hospital of Sun Yat-sen University were included in this study. The expression of CTHRC1 and vascular endothelial growth factor (VEGF), and microvessel density (MVD, determined by CD34 immunostaining) were evaluated by immunohistochemistry in LUAD tissues. The association between the expression of these proteins and clinicopathological features or clinical outcomes was analyzed.

Results

Here, we confirmed that CTHRC1 expression was associated with prognosis and can serve as a significant predictor for overall survival (OS) and progression-free survival (PFS) in LUAD. Additionally, we observed that CTHRC1 expression was positively associated with tumor angiogenesis markers, such as VEGF expression (P < 0.001) and MVD (P < 0.01). Then, we performed gene set enrichment analysis (GESA) and cell experiments to confirm that enhanced CTHRC1 expression can promote VEGF levels. Based on and cox regression analysis, a predictive model that included CTHRC1, VEGF and MVD was constructed and confirmed as a more accurate independent predictor for OS (P = 0.001) and PFS (P < 0.001) in LUAD than other parameters.

Conclusions

These results demonstrated that high CTHRC1 expression may be closely related to tumor angiogenesis and poor prognosis in LUAD. The predictive model based on the CTHRC1 level and tumor angiogenesis markers can be used to predict LUAD patient prognosis more accurately.
Melatonin: an anti-tumor agent for osteosarcoma
Authors: Fathizadeh Hadis , Mirzaei Hamed , Asemi Zatollah
Published: November 2019

Osteosarcoma is the most common bone tumors which consisted of malignant mesenchymal cells generating osteoid and immature bone. It has been showed that osteosarcoma is common in children and adolescents and shows high mortality rate. A variety of therapeutic approaches (i.e., resection surgery, combined with chemotherapy and radiotherapy) have been used as conventional treatments in patients with osteosarcoma. Despite several attempts to improve therapeutic response, the rate of survival for osteosarcoma has not changed during the past 3 decades. Therefore, the discovery and developing new effective therapeutic platforms are required. Along to the established anti-cancer agents, some physiological regulators such melatonin, have been emerged as new anti-cancer agents. Melatonin is an indolamine hormone which is secreted from the pineal glands during the night and acts as physiological regulator. Given that melatonin shows a wide spectrum anti-tumor impacts. Besides different biologic activities of melatonin (e.g., immunomodulation and antioxidant properties), melatonin has a crucial role in the formation of bones, and its deficiency could be directly related to bone cancers. Several in vitro and in vivo experiments evaluated the effects of melatonin on osteosarcoma and other types of bone cancer. Taken together, the results of these studies indicated that melatonin could be introduced as new therapeutic candidate or as adjuvant in combination with other anti-tumor agents in the treatment of osteosarcoma. Herein, we summarized the anti-tumor effects of melatonin for osteosarcoma cancer as well as its mechanism of action.
Cooking frequency and hypertension with gender as a modifier
Authors: Zhang Yu , Tang Tianyu , Tang Kun
Published: November 2019

Background

The effect of cooking frequency on hypertension is understudied. This study aimed to examine the effect of cooking on hypertension with a particular focus on gender differences.

Methods

The present study utilized cross-sectional data from China Kadoorie Biobank with a 512,891-population of China. Hypertension was identified by established diagnosis or by the 1999 WHO/ISH Guidelines for the Management of Hypertension on examination. Cooking frequency was obtained from a self-reported questionnaire and categorized as daily cooking, weekly or monthly cooking and never cooking. Multivariable logistic regression models were employed to examine the associations between cooking frequency and hypertension in men and women, respectively. Stratified analyses by demographic and socio-economic characteristics were conducted.

Results

Men who ever cooked had higher odds of hypertension compared with those who never cooked (weekly or monthly cooking adjusted odds ratio (AOR): 1.05, 95% CI: 1.02–1.07; Daily cooking AOR: 1.09, 95% CI: 1.06–1.11), while protective effects of cooking against hypertension were observed in women (weekly or monthly cooking AOR: 0.94, 95% CI: 0.89–0.99; daily cooking AOR: 0.96, 95% CI: 0.92–0.99). Socio-economic status including occupation, household income, education and region could further modify the effect of daily cooking on hypertension among men and women, respectively.

Conclusion

The present study highlighted the effect of cooking on hypertension. We found the opposite trends in men and women with regards to the association between cooking and hypertension. Factors relating to socio-economic status such as education, household income and occupation could further modify the gender-specific effects. Interventions to reduce hypertension should consider the gender differences in food choice and psycho-social stress related to cooking.
Ultrasmall nanostructured drug based pH-sensitive liposome for effective treatment of drug-resistant tumor
Authors: Li Yanyan , Zhai Yongxia , Liu Wei , Zhang Kaixiang , Liu Junjie , Shi Jinjin , Zhang Zhenzhong
Published: November 2019

Background

Cancer cells always develop ways to resist and evade chemotherapy. To overcome this obstacle, herein, we introduce a programmatic release drug delivery system that imparts avoiding drug efflux and nuclear transport in synchrony via a simple nanostructured drug strategy.

Results

The programmatic liposome-based nanostructured drugs (LNSD) contained two modules: doxorubicin (DOX) loaded into tetrahedral DNA (TD, ~ 10 nm) to form small nanostructured DOX, and the nanostructured DOX was encapsulated into the pH-sensitive liposomes. In the in vitro and in vivo studies, LNSD shows multiple benefits for drug resistance tumor treatment: (1) not only enhanced the cellular DOX uptake, but also maintained DOX concentration in an optimum level in resistant tumor cells via nanostructure induced anti-efflux effect; (2) small nanostructured DOX efficiently entered into cell nuclear via size depended nuclear-transport for enhanced treatment; (3) improved the pharmacokinetics and biodistribution via reducing DOX leakage during circulation.

Conclusions

The system developed in this study has the potential to provide new therapies for drug-resistant tumor.
The relationship between individual-level deprivation and health-related quality of life
Authors: Kashem Tahmid , Al Sayah Fatima , Tawiah Andrews , Ohinmaa Arto , Johnson Jeffery A.
Published: November 2019

Objective

To examine the association between individual-level deprivation and health-related quality of life (HRQL) in the general population.

Methods

Data from a population-based survey in the Canadian province of Alberta were used. Individual-level deprivation was assessed using the Canadian Deprivation Index (CDI) and the Ontario Deprivation Index (ODI). HRQL was assessed using the EQ-5D-5 L. Differences in problems in the EQ-5D-5 L dimensions, index and visual analogue scale (VAS) scores across levels of deprivation were examined. Multivariate logistic and linear regression models adjusted for socio-demographic and other characteristics were used to examine the independent association between deprivation and HRQL.

Results

Of the 6314 respondents, 39% were aged between 18 and 44 years and 38% between 45 and 64 years; 60% were female. Mean EQ-5D-5 L index and VAS scores were 0.85 (standard deviation [SD] 0.14) and 79.6 (SD 17.7), respectively. Almost one-third (30.6%) of respondents reported no problems on all EQ-5D-5 L dimensions. Few participants reported some problems with mobility (23.8%), self-care (6.2%) and usual activities (25.2%), while 59.3 and 35.5% reported some levels of pain/discomfort and anxiety/depression, respectively. Differences between the most and least deprived in reporting problems in EQ-5D-5 L dimensions, index and VAS scores were statistically significant and clinically important. In adjusted regression models for both deprivation indices, the least well-off, compared to the most well-off, had higher likelihood of reporting problems in all EQ-5D-5 L dimensions. Compared to the most well-off, the least well-off had an EQ-5D-5 L index score decrement of 0.18 (p < 0.01) and 0.17 (p < 0.01) for the CDI and ODI, respectively. Similarly, an inverse association was found between the VAS score and the CDI (β = − 17.3, p < 0.01) as well as the ODI (β = − 13.3, p < 0.01).

Conclusion

Individual-level deprivation is associated with worse HRQL. Poverty reduction strategies should consider the effects of not only neighbourhood-level deprivation, but also that of individual-level deprivation to improve overall health.
Restriction factors in human retrovirus infections and the unprecedented case of CIITA as link of intrinsic and adaptive immunity against HTLV-1
Authors: Forlani Greta , Shallak Mariam , Ramia Elise , Tedeschi Alessandra , Accolla Roberto S.
Published: November 2019

Background

Immunity against pathogens evolved through complex mechanisms that only for sake of simplicity are defined as innate immunity and adaptive immunity. Indeed innate and adaptive immunity are strongly intertwined each other during evolution. The complexity is further increased by intrinsic mechanisms of immunity that rely on the action of intracellular molecules defined as restriction factors (RFs) that, particularly in virus infections, counteract the action of pathogen gene products acting at different steps of virus life cycle.

Main body and conclusion

Here we provide an overview on the nature and the mode of action of restriction factors involved in retrovirus infection, particularly Human T Leukemia/Lymphoma Virus 1 (HTLV-1) infection. As it has been extensively studied by our group, special emphasis is given to the involvement of the MHC class II transactivator CIITA discovered in our laboratory as regulator of adaptive immunity and subsequently as restriction factor against HIV-1 and HTLV-1, a unique example of dual function linking adaptive and intrinsic immunity during evolution. We describe the multiple molecular mechanisms through which CIITA exerts its restriction on retroviruses. Of relevance, we review the unprecedented findings pointing to a concerted action of several restriction factors such as CIITA, TRIM22 and TRIM19/PML in synergizing against retroviral replication. Finally, as CIITA profoundly affects HTLV-1 replication by interacting and inhibiting the function of HTLV-1 Tax-1 molecule, the major viral product associated to the virus oncogenicity, we also put forward the hypothesis of CIITA as counteractor of HTLV-1-mediated cancer initiation.
Development of a new high sensitivity mechanical switch for augmentative and alternative communication access in people with amyotrophic lateral sclerosis
Authors: Caligari M. , Godi M. , Giardini M. , Colombo R.
Published: November 2019

Background

People with Amyotrophic Lateral Sclerosis (PwALS) in the advanced phase are critically affected by an almost total loss of mobility and severe communication problems. Scanning access based on the patient’s interaction with a sensor (or switch) that intercepts even a weak body movement is a valid communication aid. However, its use becomes limited with the progressive decline of residual movements. To overcome this problem, we designed a new sensor, the Lever Magnetic-spring Mechanical Switch (LeMMS), allowing repeated activation/release cycles requiring a very small activation force.

Methods

The LeMMS was applied and validated in a group of 20 PwALS in an advanced stage of disease. All subjects were regular users of communication aids employing other sensors, but which they could no longer operate their sensors (different from LeMMS). Patients were assessed at baseline (t0) and after one (t1), 6 (t2) and 12 (t3) months. Assessment at t0 included administration of standardized clinical scales, the Click-Test-30 counting the maximum number of LeMMS activations in 30 s, and thumb/fingers strength assessment with the Kendall scale. The QUEST 2.0-Dev questionnaire was administered at t1. Some use-related information and the Click-Test-30 were collected at t1, t2 and t3.

Results

After one training session, all patients could operate the LeMMS with minimal residual movement of one finger. At t1, they used it on average 5.45 h/day. The mean score of the QUEST 2.0-Dev was 4.63, suggesting strong satisfaction with the LeMMS. Regarding Click-Test-30 scores, no significant difference was found between t0 and t1, but performance at t2 and t3 declined significantly (p < 0.005 vs. t0). At t3, 9/20 patients were still able to use their communication aid.

Conclusions

This new switch sensor can enable PwALS to use their communication aids for a prolonged time even in the advanced phase of disease. It is easy to use, reliable and cheap, thus representing an intermediate alternative to more sophisticated and costly devices.
Comparison of arthrodesis and arthroplasty of Chinese thumb carpometacarpal osteoarthritis
Authors: Li Jianfeng , Li Dacun , Tian Guanglei , Zhang Wentong
Published: November 2019

Background

The thumb carpometacarpal (CMC) osteoarthritis is very common. Multiple methods are used to treat progressive thumb CMC osteoarthritis, among which trapeziometacarpal arthrodesis and trapezial excision with ligament reconstruction and tendon interposition (LRTI) are the most common. These two surgical treatment methods have received mixed reviews in previous studies in the west patients. This retrospective study studied the effects, advantages, and disadvantages of arthrodesis and arthroplasty for treating thumb carpometacarpal osteoarthritis in Chinese patients.

Methods

Between February 2012 and September 2017, 39 Chinese patients with stage II or III thumb carpometacarpal osteoarthritis underwent surgery (trapeziometacarpal arthrodesis in 22, trapezial excision with ligament reconstruction and tendon interposition in 17). Postoperative objective and subjective evaluations were performed. The objective evaluation involved grip strength, pinch strength, thumb abduction degree (palmar and radial), and Kapandji opposition scores. The subjective evaluation involved visual analog scale (VAS) and Disabilities of the Arm, Shoulder, and Hand (DASH) scores.

Results

Intergroup differences in pinch strength, thumb abduction degrees (palmar and radial), and Kapandji opposition scores were obvious, whereas those in grip strength, VAS score, and DASH score were not.

Conclusion

In Chinese patients, both techniques relieved pain and improve grip strength. Arthrodesis displayed better pinch strength, while arthroplasty displayed better motor function. Patients were satisfied with the effects of both techniques.
Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model
Authors: Kanezaki Shozo , Miyazaki Masashi , Ishihara Toshinobu , Notani Naoki , Abe Tetsutaro , Tsubouchi Yuhta , Kataoka Masashi , Tsumura Hiroshi
Published: November 2019

Background

Nonunion in cases of open fracture is common. Both bone morphogenetic protein 2 (BMP-2) and parathyroid hormone (PTH) have been used to enhance bone healing. We investigated the combination of BMP-2 and PTH and examined the effects on a rat model of open femoral fractures.

Methods

Group I (n = 11) was implanted with control carrier. Group II (n = 12) was implanted with carrier containing 1 μg of recombinant human BMP-2 (rhBMP-2). Group III (n = 12) was implanted with carrier alone, followed by injections of PTH 1-34. Group IV (n = 11) was implanted with carrier containing 1 μg of rhBMP-2, followed by injections of PTH 1-34. Group V (n = 11) was implanted with carrier containing 10 μg of rhBMP-2. Group VI (n = 11) was implanted with carrier containing 10 μg of rhBMP-2, followed by injections of PTH 1-34. Rats were euthanized after 8 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, micro-computerized tomography, and histological analysis.

Results

Manual palpation tests showed that the fusion rates of groups III (66.7%), IV (63.6%), V (81.8%), and VI (81.8%) were considerably higher than those of group I. Groups V and VI had higher radiographic scores compared to group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in groups V (61.88 ± 3.16%) and VI (71.14 ± 3.89%) versus group I (58.26 ± 1.86%). A histological analysis indicated that group VI had enhanced remodeling.

Conclusion

The combination of abundant rhBMP-2 and PTH enhanced bone healing and remodeling of newly formed bone in a rat femoral open fracture model.
Excessive intravenous crystalloid infusion after video-assisted thoracoscopic surgery lobectomy is associated with postoperative pneumonia
Authors: Yang Rong , Du Chengli , Xu Jinming , Yao Linpeng , Zhang Siying , Wu Yihe
Published: November 2019

Background

Video-assisted thoracoscopic surgery has been widely used in thoracic surgery worldwide. Our goal was to identify the risk factors for postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery lobectomy.

Methods

A retrospective analysis of adult patients undergoing video-assisted thoracoscopic surgery lobectomy between 2016 and 05 and 2017–04 was performed. We used univariate analyses and multivariate analyses to examine risk factors for postoperative pneumonia after lobectomy.

Results

The incidence of postoperative pneumonia was 19.7% (n = 143/727). Patients with postoperative pneumonia had a higher postoperative length of stay and total hospital care costs when compared to those without postoperative pneumonia. Multivariate analysis showed that body mass index grading ≥24.0 kg/m2 (vs. <24.0 kg/m2: odds ratio 1.904, 95% confidence interval 1.294–2.802, P = 0.001) and right lung lobe surgery (vs. left lung lobe surgery: odds ratio 1.836, 95% confidence interval 1.216–2.771, P = 0.004) were independent risk factors of postoperative pneumonia. Total intravenous crystalloid infusion grading in the postoperative 24 h ≥ 1500 mL was also identified as the risk factors (vs. 1000 to < 1500 mL: odds ratio 2.060, 95% confidence interval 1.302–3.260, P = 0.002).

Conclusions

Major risk factors for postoperative pneumonia following video-assisted thoracoscopic surgery lobectomy are body mass index grading ≥24.0 kg/m2, right lung lobe surgery and total intravenous crystalloid infusion grading in the postoperative 24 h ≥ 1500 mL.
Cancer cases detected in the prevention and control service of a private cancer clinic in Peru
Authors: Revilla-López José , Anampa-Guzmán Andrea , Marquez Luis Casanova , Weeks Katrina , Pollard Suzanne , Olórtegui-Yzú Adriel , Ruiz-Velazco María , Davila-Edquen Alba , Castro-Dorer Daniel , Wong-Barrenechea Juan , Abad-Seminario Jossira , Gonzáles-Ramos Pamela , Rivera-Sandoval Fiorella , Carracedo-Gonzáles Carlos
Published: November 2019

Purpose

Describe the characteristics of patients seen at the Cancer Prevention and Control Service at a Peruvian private cancer clinic in 2014.

Patients and methods

This retrospective clinical study analyzed the prevalence of 10 cancers and characteristics of patients seen at a private cancer center located in Lima, Peru. The study sample included 7680 adults, and data were collected from de-identified medical records.

Results

The average age of the patients was 44.71 years and 98,82% of them had private insurance. The majority of patients were women (67.69%). Our gross incidence rate of cancer was 35.16 per 100,000 in the Cancer Prevention and Control Service in 2014. Only 0.35% had cancer, and most of those diagnosed with cancer (77.78%) were diagnosed in the early stages, stages I and II. The two most common cancers observed were breast and thyroid cancer.

Conclusions

The high rates of early, rather than late-stage diagnoses at this clinic are dramatically different than national rates. This difference may be because we are analyzing data from a prevention service seeing mainly patients with private insurance as opposed to national data, which consists primarily of patients seen in oncologic services with national insurance.
HIV status, age at cervical Cancer screening and cervical cytology outcomes in an opportunistic screening setting in Nigeria: a 10-year Cross sectional data analysis
Authors: Musa Jonah , Achenbach Chad J. , Evans Charlesnika T. , Jordan Neil , Daru Patrick H. , Silas Olugbenga , Sagay Atiene S. , Anorlu Rose , Mehta Supriya D. , Wehbe Firas , Simon Melissa A. , Adewole Isaac F. , Hou Lifang , Murphy Robert L.
Published: November 2019

Background

Invasive cervical cancer (ICC) is more prevalent in HIV infected women and occurs at younger median age than in HIV negative women. Organized cervical cancer screening (CCS) is presently lacking in Nigeria, and the age at CCS is not known in this population. We sought to examine the age at CCS, the cytology outcomes and whether outcomes differ by HIV infection status in an opportunistic screening setting.

Methods

Cross-sectional analysis of data on a sample of women who had received a CCS in an opportunistic screening service in Jos, Nigeria over a 10-year time period (2006–2016). We used logistic regression models to estimate the independent effect of patient-reported HIV and age at CCS and odds ratios for abnormal cytology outcomes adjusting for other covariates. We also assessed the correlation between median age at CCS and severity of abnormal cervical cytology outcomes. Statistical analyses were done on STATA version 14, College Station, Texas, USA.

Results

In a sample of 14,088, the median age at CCS was 37 years (IQR; 30–45). For HIV infected women vs. uninfected women, CCS occurred at earlier ages (35.0 ± 7.4 vs 38.2 ± 10.2 years, p < 0.001). All women, regardless of HIV status, who completed at least 7 or more years of education were 1.27 to 3.51 times more likely to have CCS before age 35 than women with less education. The predictors of an abnormal cervical cytology outcome at CCS were: age at CCS ≥ 35 (aOR = 3.57; 95% CI: 2.74, 4.64), multiparity ≥5 (aOR = 1.27; 95% CI: 1.03, 1.56), and provider-referral (aOR = 1.34; 95% CI: 1.09, 1.64). Irrespective of reported HIV status, we found a positive correlation between median age at CCS and severity of cytology outcome.

Discussion

The age at CCS in women who have utilized cervical cancer screening in the study population is relatively late compared to the recommended age by most guidelines from developed settings. Late age at CCS correlates positively with severity of abnormal cytology outcome irrespective of HIV status. More educated women are more likely to have CCS at early age and less likely to have underlying abnormal cytology outcomes.
Inhibition of lung cancer growth and metastasis by DHA and its metabolite, RvD1, through miR-138-5p/FOXC1 pathway
Authors: Bai Xiaoming , Shao Jiaofang , Zhou Sujin , Zhao Zhenggang , Li Fanghong , Xiang Rong , Zhao Allan Z. , Pan Jinshun
Published: November 2019

Background

Non small cell lung cancer (NSCLC) is one of the most common cancers in the world. DHA is known to be capable of suppressing NSCLC cell proliferation and metastasis. However, the mechanisms by which DHA exhibits its antitumor effects are unknown. Here we aimed to identify the effects and mechanisms of DHA and its metabolites on lung cancer cell growth and invasion.

Methods

As measures of cell proliferation and invasion ability, the cell viability and transwell assays were used in vitro. Transgenic mfat-1 mice, which convert ω-6 PUFAs to ω-3 PUFAs, were used to detect the effect of endogenous DHA on tumor transplantation. An LC − MS/MS analysis identified the elevation of several eicosanoid metabolites of DHA. By using qPCR miRNA microarray, online prediction software, luciferase reporter assays and Western blot analysis, we further elucidated the mechanisms.

Results

Addition of exogenous DHA inhibited the growth and invasion in NSCLC cells in vitro. Endogenously produced DHA attenuated LLC-derived tumor growth and metastasis in the transgenic mfat-1 mice. Among the elevation of DHA metabolites, resolvin D1 (RvD1) significantly contributed to the inhibition in cell growth and invasion. MiRNA microarray revealed that the level of miR-138-5p was significantly increased after RvD1 treatment. MiR-138-5p mimics decreased cell viability and invasion; while miR-138-5p inhibitor abolished RvD1-mediated suppression of cell viability and invasion. The expression of FOXC1 was significantly reduced upon overexpression of miR-138-5p while luciferase reporter assay showed that FOXC1 was a direct target of miR-138-5p. In vivo, endogenous DHA by the mfat-1 transgene enhanced miR-138-5p expression and decreased FOXC1 expression. Furthermore, overexpression of FOXC1 reversed the inhibition in cell viability and invasion induced by RvD1 treatment.

Conclusions

These data identified the RvD1/miR-138-5p/FOXC1 pathway as a novel mechanism by DHA and its metabolite, RvD1, and the potential of targeting such pathway as a therapeutic strategy in treating NSCLC.
Cross-talk between SIM2s and NFκB regulates cyclooxygenase 2 expression in breast cancer
Authors: Wyatt Garhett L. , Crump Lyndsey S. , Young Chloe M. , Wessells Veronica M. , McQueen Cole M. , Wall Steven W. , Gustafson Tanya L. , Fan Yang-Yi , Chapkin Robert S. , Porter Weston W. , Lyons Traci R.
Published: November 2019

Background

Breast cancer is a leading cause of cancer-related death for women in the USA. Thus, there is an increasing need to investigate novel prognostic markers and therapeutic methods. Inflammation raises challenges in treating and preventing the spread of breast cancer. Specifically, the nuclear factor kappa b (NFκB) pathway contributes to cancer progression by stimulating proliferation and preventing apoptosis. One target gene of this pathway is PTGS2, which encodes for cyclooxygenase 2 (COX-2) and is upregulated in 40% of human breast carcinomas. COX-2 is an enzyme involved in the production of prostaglandins, which mediate inflammation. Here, we investigate the effect of Singleminded-2s (SIM2s), a transcriptional tumor suppressor that is implicated in inhibition of tumor growth and metastasis, in regulating NFκB signaling and COX-2.

Methods

For in vitro experiments, reporter luciferase assays were utilized in MCF7 cells to investigate promoter activity of NFκB and SIM2. Real-time PCR, immunoblotting, immunohistochemistry, and chromatin immunoprecipitation assays were performed in SUM159 and MCF7 cells. For in vivo experiments, MCF10DCIS.COM cells stably expressing SIM2s-FLAG or shPTGS2 were injected into SCID mice and subsequent tumors harvested for immunostaining and analysis.

Results

Our results reveal that SIM2 attenuates the activation of NFκB as measured using NFκB-luciferase reporter assay. Furthermore, immunostaining of lysates from breast cancer cells overexpressing SIM2s showed reduction in various NFκB signaling proteins, as well as pAkt, whereas knockdown of SIM2 revealed increases in NFκB signaling proteins and pAkt. Additionally, we show that NFκB signaling can act in a reciprocal manner to decrease expression of SIM2s. Likewise, suppressing NFκB translocation in DCIS.COM cells increased SIM2s expression. We also found that NFκB/p65 represses SIM2 in a dose-dependent manner, and when NFκB is suppressed, the effect on the SIM2 is negated. Additionally, our ChIP analysis confirms that NFκB/p65 binds directly to SIM2 promoter site and that the NFκB sites in the SIM2 promoter are required for NFκB-mediated suppression of SIM2s. Finally, overexpression of SIM2s decreases PTGS2 in vitro, and COX-2 staining in vivo while decreasing PTGS2 and/or COX-2 activity results in re-expression of SIM2.

Conclusion

Our findings identify a novel role for SIM2s in NFκB signaling and COX-2 expression.
methylCC: technology-independent estimation of cell type composition using differentially methylated regions
Authors: Hicks Stephanie C. , Irizarry Rafael A.
Published: November 2019

A major challenge in the analysis of DNA methylation (DNAm) data is variability introduced from intra-sample cellular heterogeneity, such as whole blood which is a convolution of DNAm profiles across a unique cell type. When this source of variability is confounded with an outcome of interest, if unaccounted for, false positives ensue. Current methods to estimate the cell type proportions in whole blood DNAm samples are only appropriate for one technology and lead to technology-specific biases if applied to data generated from other technologies. Here, we propose the technology-independent alternative: methylCC, which is available at https://github.com/stephaniehicks/methylCC.
Identification of a TRBD zinc finger-interacting protein in Giardia duodenalis and its regulation of telomerase
Authors: Zheng Jing-Tong , Zhang Nan , Yu Yan-Hui , Gong Peng-Tao , Li Xian-He , Wu Na , Wang Can , Wang Xiao-Cen , Li Xin , Li Jian-Hua , Zhang Xi-Chen
Published: November 2019

Background

Giardia duodenalis causes giardiasis, with diarrhea as the primary symptom. The trophozoite proliferation of this zoonotic parasite is mainly affected by telomerase, although the mechanism of telomerase regulation has not been thoroughly analyzed.

Methods

This study was performed to identify the telomerase RNA-binding domain (TRBD)-interacting protein in G. duodenalis and its regulation of telomerase. Interaction between TRBD and interacting proteins was verified via pulldown assays and co-immunoprecipitation (co-IP) techniques, and the subcellular localization of the protein interactions was determined in vivo via split SNAP-tag labeling. The hammerhead ribozyme was designed to deplete the mRNA of TRBD-interacting proteins.

Results

Using TRBD as bait, we identified zinc-finger domain (ZFD)-containing proteins and verified it via pulldown and co-IP experiments. Protein-protein interaction occurred in the nuclei of 293T cells and both nuclei of G. duodenalis. The hammerhead ribozyme depleted ZFD mRNA levels, which reduced the reproduction rate of G. duodenalis, telomerase activity and telomere length.

Conclusions

Our findings suggest that ZFD may regulate telomere function in G. duodenalis nuclei.
Genetic characterization of Cryptosporidium spp. and Giardia duodenalis in dogs and cats in Guangdong, China
Authors: Li Jiayu , Dan Xiaoyu , Zhu Kexin , Li Na , Guo Yaqiong , Zheng Zezhong , Feng Yaoyu , Xiao Lihua
Published: November 2019

Background

There are only limited number of reports on molecular epidemiology of Cryptosporidium spp. and Giardia duodenalis in dogs and cats in China. This study was conducted to assess the infection rates, genetic identity, and public health potential of these parasites in dogs and cats in Guangdong, China.

Methods

PCR and sequence analyses were used to identify and genotype Cryptosporidium spp. and G. duodenalis in fecal samples from 641 dogs and 418 cats in Guangdong. Chi-square test and odds ratio analysis were used to compare the occurrence rates of these pathogens and identify risk factors for infection.

Results

The overall infection rates of Cryptosporidium spp. and G. duodenalis were 6.9% (44/641) and 9.4% (60/641) in dogs, and 6.2% (26/418) and 3.6% (15/418) in cats. Purebred cats (12.4%; χ2 = 5.110, OR = 2.8, P = 0.024) and dogs (10.8%; χ2 = 5.597, OR = 4.8, P = 0.018) were more likely to be infected by Cryptosporidium spp. and G. duodenalis, respectively. Dogs (12.0%; χ2 = 7.589, OR = 2.6, P = 0.006) and cats (13.6%; χ2 = 8.235, OR = 3.5, P = 0.004) under 6 months had significantly higher infection rates of Cryptosporidium spp. than older animals. Household (13.9%; χ2 = 10.279, OR = 2.6, P = 0.008) and pet shop dogs (11.0%; χ2 = 7.182, OR = 2.0, P = 0.048) had higher occurrence of Cryptosporidium spp., as was the case for G. duodenalis occurrence in experimental dogs (13.4%; χ2 = 9.223, OR = 1.9, P = 0.017). Cryptosporidium canis (n = 42), C. muris (n = 1) and Cryptosporidium rat genotype IV (n = 1) were identified in dogs, while C. felis (n = 21), C. parvum (n = 3), C. muris (n = 1) and Cryptosporidium rat genotype IV (n = 1) were identified in cats. In contrast, the canine-specific assemblages C (n = 27) and D (n = 26) and the feline-specific assemblage F (n = 14) were almost exclusively the only genotypes of G. duodenalis in dogs and cats, respectively. There was no significant difference in infection rates of Cryptosporidium spp. and G. duodenalis between diarrheal and non-diarrheal pets.

Conclusions

While domestic pets in Guangdong are infected with zoonotic Cryptosporidium species, they are mainly infected with host-specific G. duodenalis genotypes. Risk factors for infections differ between Cryptosporidium spp. and G. duodenalis and between dogs and cats.
Association between pain phenotype and disease activity in rheumatoid arthritis patients: a non-interventional, longitudinal cohort study
Authors: ten Klooster P. M. , de Graaf N. , Vonkeman H. E.
Published: November 2019

Background

In well-controlled rheumatoid arthritis (RA) without significant joint damage, a substantial proportion of patients complain of persistent pain. Previous studies have identified different pain phenotypes in RA, in which non-nociceptive pain phenotypes are associated with higher concurrent disease activity scores. In this longitudinal study, we explored associations between pain phenotypes and long-term disease activity outcome in RA patients. Secondly, we explored whether pain phenotype is associated with comorbid conditions.

Methods

One hundred eighty established RA patients were classified with a nociceptive (61%) or a non-nociceptive (39%) pain phenotype, based on their responses to the painDETECT-questionnaire. Two years of clinical follow-up data on disease activity outcomes were collected. Information on comorbid diseases was derived from electronic patient files.

Results

Patients with a non-nociceptive pain phenotype showed higher mean disease activity scores (DAS28, 2.57; 95% CI, 2.37–2.77 vs. 2.11; 95% CI, 1.94–2.27; p < 0.001) and a twofold lower chance of achieving sustained DAS28 remission (OR = 0.49; 95% CI, 0.26–0.92; p = 0.020). Only the tender joint count and patient global health significantly differed between the pain phenotype groups. Patients with a non-nociceptive pain phenotype had more often been diagnosed with concurrent fibromyalgia (9.9% vs. 0.9%; p = 0.007) and other pain-associated comorbid diseases (52.1% vs. 35.8%; p = 0.030) compared with patients with a nociceptive pain phenotype.

Conclusion

This longitudinal study showed consistently worse long-term disease activity outcomes in RA patients with a non-nociceptive pain phenotype which appeared to be mainly due to differences in the subjective components of the disease activity score.

Trial registration

The DREAM cohort study is registered in the Netherlands Trial Register: NTR578.
Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus
Authors: Sohrabian Azita , Parodis Ioannis , Carlströmer-Berthén Nellie , Frodlund Martina , Jönsen Andreas , Zickert Agneta , Sjöwall Christopher , Bengtsson Anders A. , Gunnarsson Iva , Rönnelid Johan
Published: November 2019

Introduction

Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value.

Methods

A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment.

Results

High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 andp = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 andp = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers.

Conclusion

Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.
Magnitude and associated factors of diabetic complication among diabetic patients attending Gurage zone hospitals, South West Ethiopia
Authors: Gebre Bereket Beyene , Assefa Zebene Mekonnen
Published: November 2019

Objective

To assess the magnitude of diabetic complication and associated factors among diabetes mellitus patients attending in Gurage zone hospitals.

Results

According to this study the magnitude of diabetic complication among diabetic patients were 61% and the marital status; divorced [AOR: 0.252 (0.11, 0.59); p = 0.002], poor glycemic control [AOR: 1.88 (1.04, 3.39); p = 0.036], body mass index > 25 [AOR: 4.42 (1.32, 14.86); p = 0.016] and duration of illness > 6 years [AOR :1.79 (1.02, 3.17); p = 0.044] and 10 years [AOR: 4.68 (2.07, 10.61); p = < 0.001] were significantly associated with diabetic complication.