bluuebunny/crossref_metadata_2025 huggingface dataset:
Fungi and Aflatoxin Levels in Traditionally Processed Cassava (Manihot esculenta Crantz) Products in Homa Bay County, Kenya
Authors: Obong’o Boniface Oure , Ayodo George , Kawaka Fanuel , Adalla Morelly Kathy
Published: August 2020

Cassava (Manihot esculenta Crantz) is a major source of carbohydrates, calcium, vitamins (B and C), and essential minerals and is the third most important source of calories in the tropics. However, it is not clear if the traditional processing methods expose the products to microbial contamination. This study assessed the levels of fungi and aflatoxin contamination in traditionally processed cassava products (Akuoga and Abeta). A total of 38 samples were collected from the local markets in 7 subcounties in Homa Bay County, Kenya. The levels of aflatoxin were determined using an indirect competitive ELISA protocol. Yeast and mould contamination was determined using ISO 21527-2 method. Mean aflatoxin levels in chopped, fermented, and sun-dried cassava (Akuoga) were 0.36 μg/kg compared to 0.25 μg/kg in chopped and sun-dried (Abeta) products. Aflatoxin contamination was detected in 55% of the samples and ranged from 0–5.33 μg/kg. These levels are within 10 μg/kg recommended by the CODEX STAN 193-1995. Yeast and mould counts in fermented and chopped sun-dried products were 3.16 log Cfu/g and 2.92 log Cfu/g, respectively. The yeast and mould counts were above standards set by East African Standard 739:2010 in 62% (Akuoga) and 58% (Abeta). The most prevalent fungal species were Saccharomyces cerevisiae (68.4%) and Candida rugosa (68%) followed by Candida parapsilosis (18.4%), Candida tropicalis (15.8%), Candida humilis (15.8%), and Aspergillus spp. (5.3%). Aspergillus spp. was the only mycotoxigenic mould isolated from the samples. The study shows that cassava consumers are exposed to the risk of aflatoxin poisoning. The study, therefore, recommends appropriate surveillance to ensure safety standards.
Assessment of Cascading Accidents of Frostbite, Fire, and Explosion Caused by Liquefied Natural Gas Leakage
Authors: Yue Chengjun , Chen Li , Xiang Hengbo , Xu Linfeng , Yang Shigang , Li Zhan , Xia Chenxi , Fang Qin
Published: August 2020

Liquefied natural gas (LNG) leaks often lead to cascading accident disasters, including vapor cloud release, explosion, fire, and toxic gas release. The origin and evolution of each accidental disaster must be considered when assessing safety. This paper discusses the safety assessment project of an LNG gas storage station in Xuzhou, China. Multiple conceivable disasters due to the leakage of LNG storage tanks are simulated and analyzed using the computational fluid dynamic software FLACS. We studied different wind speeds interacting with the flammable vapor cloud area and creating frostbite in areas of low temperature. Diffusion simulations of vapor cloud explosion (VCE), thermal radiation, and the distribution of toxic substances were performed. The overpressure‐impulse criterion was used to calculate the influence range of VCE. Heat flux, heat dose, and heat flux‐heat dose criteria were used to calculate the safe distance for personnel in the event of fire. Based on the calculation results of the three latter criteria, this paper recommends using the heat flux criterion to evaluate fire accidents. The danger zone of each accident was compared. VCE accidents yielded the largest area.
Surgical Treatment for Spinal Tuberculosis without Elevation of Inflammatory Biomarkers at the Initial Visit Mimicking Spinal Metastasis
Authors: Sakamoto Takuya , Takahashi Hiroshi , Saito Junya , Matsuzawa Yasuo , Aoki Yasuchika , Nakajima Arata , Sonobe Masato , Akatsu Yorikazu , Yamada Manabu , Akiyama Yuki , Iwai Tatsunori , Yanagisawa Keita , Shiga Yasuhiro , Inage Kazuhide , Orita Sumihisa , Eguchi Yawara , Maki Satoshi , Furuya Takeo , Akazawa Tsutomu , Koda Masao , Yamazaki Masashi , Ohtori Seiji , Nakagawa Koichi
Published: August 2020

Here, we report a case of spinal tuberculosis without elevation of C-reactive protein (CRP) at the initial visit mimicking spinal metastasis. A 70-year-old woman developed progressive paraplegia without a history of injury and came to our hospital for evaluation. Severe compression to the spinal cord with osteolytic destruction of the spinal vertebrae at T6-7 was observed without elevation of CRP. A T4-9 posterior decompression and fusion were performed. Although the pathology revealed no malignant tumor cells, a positron emission tomography-computed tomography (PET-CT) showed upregulation of the thyroid gland and aspiration cytology revealed a thyroid carcinoma. Thus, we diagnosed her with spinal metastases from thyroid carcinoma. Conservative treatment was chosen with the hope of a significant neurologic recovery; however, 9 months after the primary surgery, she returned to our hospital with reprogressive paraplegia. In addition to progression of osteolytic changes to the T5-7 vertebrae, a coin lesion on the right side of the lung and elevation of CRP were observed. Finally, we diagnosed her with spinal tuberculosis based on the results of a CT-guided needle culture. Two-stage surgeries (posterior and anterior) were performed in addition to administering antituberculosis medications. At the 1-year postoperative follow-up evaluation, both neurologic function and laboratory data were improved with T5-9 complete fusion. It is difficult to determine based on imaging findings alone whether osteolytic vertebrae represent spinal metastases or tuberculosis. Even though inflammatory biomarkers, such as CRP, were not elevated, we should consider the possibility of not only spinal metastases but also tuberculosis when planning surgery involving osteolytic vertebrae. In addition, the combination of neurological, imaging, and pathological findings is important for the diagnosis of spinal tuberculosis.
Advances in the Study of Lens Refilling
Authors: Zhang Wen-Wen , Xie Zheng-Gao
Published: August 2020

The ultimate goal of cataract surgery is to restore the accommodation while restoring distance visual acuity. Different kinds of accommodative intraocular lens (IOLs) and surgical techniques have been suggested to apply during the surgery, but they showed poor postoperative accommodation. It is possible to achieve this goal by refilling the lens with an injectable polymer. We present a summary of the existing materials, methods, results, and some obstacles in clinical application that remain of lens refilling for restoration of accommodation. Two main problems have restricted the clinical application of this technique. One was the formation of postoperative secondary capsule opacification and the other was the different accommodative power after surgery.
Impact of Health Insurance on Health Care Utilisation and Out‐of‐Pocket Health Expenditure in Vietnam
Authors: Thuong Nguyen Thi Thu , Huy Tran Quang , Tai Do Anh , Kien Tran Nhuan
Published: August 2020

Background. In recent years, health insurance (HI) has been chosen by many low‐ and middle‐income countries to obtain an important health policy target—universal health coverage. Vietnam has recently introduced the Revised Health Insurance Law, and the effects of the voluntary health insurance (VHI) and heavily subsidised health insurance (HSHI) programmes have not yet been analysed. Therefore, this study is aimed at examining the impact of these HI programmes on the utilisation of health care services and out‐of‐pocket health expenditure (OOP) in general and across different health care providers in particular. Methods. Using the two waves of Vietnam Household Living Standard Surveys 2014 and 2016 and the difference‐in‐difference method, the impacts of VHI and HSHI on health care utilisation and OOP in Vietnam were estimated. Results. For both the VHI and HSHI groups, we found that HI increased the probability of seeking outpatient care, the mean number of outpatient visits, the total number of visits, and the mean number of visits at the district level of health care providers in the last 12 months. However, there was no evidence that the HSHI programmes increased the mean number of inpatient visits and the number of visits at the provincial hospital. We also found that while the VHI programme reduced OOP for both outpatient and inpatient care, the HSHI scheme did not result in a reduction in OOP for hospitalisation, although HI lowered the total OOP. Similarly, we found that for both groups, HI reduced OOP when the insured visited district and provincial hospitals. However, the statistically significant impact was not demonstrated when the enrolees of HSHI programmes visited provincial hospitals. Conclusion. The study offers evidence that the Vietnamese HI scheme increased health care service utilisation and decreased OOP for the participants of the VHI and HSHI programmes. Therefore, the government should continue to consider improving the HI system as a strategy to achieve universal health coverage.
Oncogenic TRIM37 Links Chemoresistance and Metastatic Fate in Triple-Negative Breast Cancer
Authors: Przanowski Piotr , Lou Song , Tihagam Rachisan Djiake , Mondal Tanmoy , Conlan Caroline , Shivange Gururaj , Saltani Ilyas , Singh Chandrajeet , Xing Kun , Morris Benjamin B. , Mayo Marty W. , Teixeira Luis , Lehmann-Che Jacqueline , Tushir-Singh Jogender , Bhatnagar Sanchita
Published: August 2020

The majority of clinical deaths in patients with triple-negative breast cancer (TNBC) are due to chemoresistance and aggressive metastases, with high prevalence in younger women of African ethnicity. Although tumorigenic drivers are numerous and varied, the drivers of metastatic transition remain largely unknown. Here, we uncovered a molecular dependence of TNBC tumors on the TRIM37 network, which enables tumor cells to resist chemotherapeutic as well as metastatic stress. TRIM37-directed histone H2A monoubiquitination enforces changes in DNA repair that rendered TP53-mutant TNBC cells resistant to chemotherapy. Chemotherapeutic drugs triggered a positive feedback loop via ATM/E2F1/STAT signaling, amplifying the TRIM37 network in chemoresistant cancer cells. High expression of TRIM37 induced transcriptomic changes characteristic of a metastatic phenotype, and inhibition of TRIM37 substantially reduced the in vivo propensity of TNBC cells. Selective delivery of TRIM37-specific antisense oligonucleotides using antifolate receptor 1–conjugated nanoparticles in combination with chemotherapy suppressed lung metastasis in spontaneous metastatic murine models. Collectively, these findings establish TRIM37 as a clinically relevant target with opportunities for therapeutic intervention.

Significance:

TRIM37 drives aggressive TNBC biology by promoting resistance to chemotherapy and inducing a prometastatic transcriptional program; inhibition of TRIM37 increases chemotherapy efficacy and reduces metastasis risk in patients with TNBC.
Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER+ Breast Cancer Growth In Vivo More Effectively than Tamoxifen
Authors: Abrahamsson Annelie , Rodriguez Gabriela Vazquez , Dabrosin Charlotta
Published: August 2020

Although blocking estrogen-dependent signaling is a cornerstone of adjuvant treatment for breast cancer, 25% of patients experience recurrent disease. Stroma events including innate immune responses are key in cancer progression. How different estrogen receptor (ER)–targeting therapies, including the partial agonist tamoxifen and the pure antagonist fulvestrant, affect the tumor stroma has not yet been elucidated. Fulvestrant is used in only postmenopausal patients, and its effects in the presence of estradiol remain undetermined. Here we observe that fulvestrant decreases ER+ breast cancer growth compared with tamoxifen in the presence of physiologic levels of estradiol in human breast cancer in nude mice and in murine breast cancer in immune-competent mice. Fulvestrant significantly inhibited macrophage and neutrophil infiltration in both models. These effects were corroborated in a zebrafish model where fulvestrant inhibited neutrophil- and macrophage-dependent cancer cell dissemination more effectively than tamoxifen. A comprehensive analysis of 234 human proteins released into the cancer microenvironment by the cancer cells sampled via microdialysis in vivo revealed that 38 proteins were altered following both treatments; 25 of these proteins were associated with immune response and were altered by fulvestrant only. Compared with tamoxifen, fulvestrant significantly affected inflammatory proteins released by murine stroma cells. Importantly, in vivo microdialysis of human ER+ breast cancer revealed that the majority of affected proteins in murine models were upregulated in patients. Together, these results suggest that fulvestrant targets ER+ breast cancer more effectively than tamoxifen even in the presence of estradiol, mainly by attenuation of the innate immune response.

Significance:

These findings demonstrate novel effects of the pure antiestrogen fulvestrant in ER+ breast cancer and evaluate its effects under physiologic levels of estradiol, representative of premenopausal patients.
Genetics of Smoking Behaviors in American Indians
Authors: Henderson Jeffrey A. , Buchwald Dedra S. , Howard Barbara V. , Henderson Patricia Nez , Li Yafang , Tyndale Rachel F. , Amos Christopher I. , Gorlova Olga Y.
Published: August 2020

Background:

The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

Methods:

We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in the Northern Plains (n = 323) and the other in the Southwest (n = 176). A total of 384 SNPs were genotyped using an Illumina custom GoldenGate platform. Samples were also assessed for cotinine and 3-hydroxycotinine as markers of nicotine intake and nicotine metabolite ratio.

Results:

Among 499 participants, we identified, in the Northern Plains sample only, a variant of the gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2) (rs2119767) on chromosome 4p that was associated with many of the intake biomarkers of smoking we examined, suggesting a role for this gene in modifying smoking behavior in this population. We also identified three SNPs, in the Southwest sample only, as significant correlates of only cigarettes per day: rs4274224, rs4245147 (both dopamine receptor D2 gene), and rs1386493 (tryptophan hydroxylase 2 gene).

Conclusions:

The contribution of many genes known to underlie smoking behaviors in NHWs may differ in AIs.

Impact:

Once validated, these variants could be useful in developing more effective cessation strategies.
Circulating Levels of Inflammatory and Metabolic Biomarkers and Risk of Esophageal Adenocarcinoma and Barrett Esophagus: Systematic Review and Meta-analysis
Authors: Xie Shao-Hua , Rabbani Sirus , Ness-Jensen Eivind , Lagergren Jesper
Published: August 2020

Associations between circulating levels of obesity-related biomarkers and risk of esophageal adenocarcinoma and Barrett esophagus have been reported, but the results are inconsistent. A literature search until October 2018 in MEDLINE and EMBASE was performed. Pooled ORs with 95% confidence intervals (CI) were estimated for associations between 13 obesity-related inflammatory and metabolic biomarkers and risk of esophageal adenocarcinoma or Barrett esophagus using random effect meta-analyses. Among 7,641 studies, 19 were eligible for inclusion (12 cross-sectional, two nested case–control, and five cohort studies). Comparing the highest versus lowest categories of circulating biomarker levels, the pooled ORs were increased for leptin (OR, 1.68; 95% CI, 0.95–2.97 for Barrett esophagus), glucose (OR, 1.12; 95% CI, 1.03–1.22 for esophageal adenocarcinoma), insulin (OR, 1.47; 95% CI, 1.06–2.00 for Barrett esophagus), C-reactive protein (CRP; OR, 2.06; 95% CI, 1.28–3.31 for esophageal adenocarcinoma), IL6 (OR, 1.50; 95% CI, 1.03–2.19 for esophageal adenocarcinoma), and soluble TNF receptor 2 (sTNFR-2; OR, 3.16; 95% CI, 1.76–5.65 for esophageal adenocarcinoma). No associations were identified for adiponectin, ghrelin, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, triglycerides, IL8, or TNFα. Higher circulating levels of leptin, glucose, insulin, CRP, IL6, and sTNFR-2 may be associated with an increased risk of esophageal adenocarcinoma or Barrett esophagus. More prospective studies are required to identify biomarkers that can help select high-risk individuals for targeted prevention and early detection.
Association of Body Mass Index with Fecal Microbial Diversity and Metabolites in the Northern Finland Birth Cohort
Authors: Loftfield Erikka , Herzig Karl-Heinz , Caporaso J. Gregory , Derkach Andriy , Wan Yunhu , Byrd Doratha A. , Vogtmann Emily , Männikkö Minna , Karhunen Ville , Knight Rob , Gunter Marc J. , Järvelin Marjo-Riitta , Sinha Rashmi
Published: August 2020

Background:

Obesity is an established risk factor for multiple cancer types. Lower microbial richness has been linked to obesity, but human studies are inconsistent, and associations of early-life body mass index (BMI) with the fecal microbiome and metabolome are unknown.

Methods:

We characterized the fecal microbiome (n = 563) and metabolome (n = 340) in the Northern Finland Birth Cohort 1966 using 16S rRNA gene sequencing and untargeted metabolomics. We estimated associations of adult BMI and BMI history with microbial features and metabolites using linear regression and Spearman correlations (rs) and computed correlations between bacterial sequence variants and metabolites overall and by BMI category.

Results:

Microbial richness, including the number of sequence variants (rs = −0.21, P < 0.0001), decreased with increasing adult BMI but was not independently associated with BMI history. Adult BMI was associated with 56 metabolites but no bacterial genera. Significant correlations were observed between microbes in 5 bacterial phyla, including 18 bacterial genera, and metabolites in 49 of the 62 metabolic pathways evaluated. The genera with the strongest correlations with relative metabolite levels (positively and negatively) were Blautia, Oscillospira, and Ruminococcus in the Firmicutes phylum, but associations varied by adult BMI category.

Conclusions:

BMI is strongly related to fecal metabolite levels, and numerous associations between fecal microbial features and metabolite levels underscore the dynamic role of the gut microbiota in metabolism.

Impact:

Characterizing the associations between the fecal microbiome, the fecal metabolome, and BMI, both recent and early-life exposures, provides critical background information for future research on cancer prevention and etiology.
Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies
Authors: Lu Haihui , Molony Ryan D. , Chen Dongshu , Jang Sunyoung , Wolf Babette , Ewert Stefan , Flaherty Meghan , Xu Fangmin , Isim Sinan , Shim Yeonju , Dornelas Christina , Balke Nicole , Leber Xavier Charles , Scharenberg Meike , Koelln Johanna , Choi Eugene , Ward Rebecca , Johnson Jennifer , Calzascia Thomas , Isnardi Isabelle , Williams Juliet A. , Lindenbergh Pieter L. , van de Donk Niels W.C.J. , Mutis Tuna , Huet Heather , Lees Emma , Meyer Matthew J.
Published: August 2020

The sole inhibitory Fcγ receptor CD32b (FcγRIIb) is expressed throughout B and plasma cell development and on their malignant counterparts. CD32b expression on malignant B cells is known to provide a mechanism of resistance to rituximab that can be ameliorated with a CD32b-blocking antibody. CD32b, therefore, represents an attractive tumor antigen for targeting with a monoclonal antibody (mAb). To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. Their complementarity-determining regions (CDR) bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcγRIIIa on immune effector cells. The NVS32b mAbs selectively target CD32b+ malignant cells and healthy B cells but not myeloid cells. They mediate potent killing of opsonized CD32b+ cells via antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) as well as complement-dependent cytotoxicity (CDC). In addition, NVS32b CDRs block the CD32b Fc–binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b+ xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor and enhancement of dendritic cell maturation in response to immune complexes. Finally, the activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed using samples from patients with B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32b+ malignant cells.
Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD
Authors: Zhao Liang , Chen Haojun , Guo Zhide , Fu Kaili , Yao Lanling , Fu Li , Guo Weixi , Wen Xuejun , Jacobson Orit , Zhang Xianzhong , Sun Long , Wu Hua , Lin Qin , Chen Xiaoyuan
Published: August 2020

Currently, most patients with non–small cell lung cancer (NSCLC) are diagnosed in advanced stages with a poor five-year survival rate. Therefore, intensive research aimed at finding novel therapeutic strategies has been ongoing; experimental models that reliably emulate NSCLC disease are greatly needed to predict responses to novel therapeutics. Therefore, we developed patient-derived xenograft (PDX) models of NSCLC, which we then used to evaluate the therapeutic efficacy of 177Lu-EB-RGD, a peptide-based radiopharmaceutical with improved pharmacokinetics that targets integrin αvβ3. In this study, three different groups of NSCLC-PDXs were successfully established, all of which maintained the same IHC and genetic characteristics of the human primary tumor. The two NSCLC-PDX groups with intense and low expression of integrin αvβ3 (denoted as PDXαvβ3+ and PDXαvβ3-) were chosen as the experimental models to evaluate the in vivo biological behavior of 177Lu-EB-RGD. In SPECT imaging and biodistribution studies, 177Lu-EB-RGD showed significantly higher accumulation in PDXαvβ3+ and PDXαvβ3- models than its corresponding monomer 177Lu-RGD. A single dose of 18.5 MBq 177Lu-EB-RGD was enough to completely eradicate the tumors in PDXαvβ3+, with no sign of tumor recurrence during the observation period. Such treatment was also efficacious in PDXαvβ3-: a single dose of 29.6 MBq 177Lu-EB-RGD led to a significant delay in tumor growth as compared with that in the control or 177Lu-RGD group. The preclinical data from the use of this model suggest that 177Lu-EB-RGD may be an effective treatment option for NSCLC and should be further evaluated in human trials.
Antihistamine Drug Ebastine Inhibits Cancer Growth by Targeting Polycomb Group Protein EZH2
Authors: Li Qiaqia , Liu Kilia Y. , Liu Qipeng , Wang Guangyu , Jiang Weihua , Meng Qingshu , Yi Yang , Yang Yongyong , Wang Rui , Zhu Sen , Li Chao , Wu Longxiang , Zhao Dongyu , Yan Lin , Zhang Lili , Kim Jung-Sun , Zu Xiongbing , Kozielski Anthony J. , Qian Wei , Chang Jenny C. , Patnaik Akash , Chen Kaifu , Cao Qi
Published: August 2020

Enhancer of zester homolog 2 (EZH2), a histone lysine methyltransferase and the catalytic component of polycomb repressive complex 2, has been extensively investigated as a chromatin regulator and a transcriptional suppressor by methylating H3 at lysine 27 (H3K27). EZH2 is upregulated or mutated in most cancers, and its expression levels are negatively associated with clinical outcomes. However, the current developed small-molecule inhibitors targeting EZH2 enzymatic activities could not inhibit the growth and progression of solid tumors. Here, we discovered an antihistamine drug, ebastine, as a novel EZH2 inhibitor by targeting EZH2 transcription and subsequently downregulating EZH2 protein level and H3K27 trimethylation in multiple cancer cell lines at concentrations below 10 μmol/L. The inhibition of EZH2 by ebastine further impaired the progression, migration, and invasiveness of these cancer cells. Overexpression of Ezh2 wild-type and its mutant, H689A (lacking methyltransferase activity), rescued the neoplastic properties of these cancer cells after ebastine treatment, suggesting that EZH2 targeted by ebastine is independent of its enzymatic function. Next-generation RNA-sequencing analysis also revealed that C4-2 cells treated with 8 μmol/L ebastine showed a gene profiling pattern similar to EZH2-knockdown C4-2 cells, which was distinctively different from cells treated with GSK126, an EZH2 enzyme inhibitor. In addition, ebastine treatment effectively reduced tumor growth and progression, and enhanced progression-free survival in triple-negative breast cancer and drug-resistant castration-resistant prostate cancer patient-derived xenograft mice. Our data demonstrated that ebastine is a novel, safe, and potent anticancer agent for patients with advanced cancer by targeting the oncoprotein EZH2.
Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology—Gynecologic Oncology Group Study 240 (NCT 00803062)
Authors: Tewari Krishnansu S. , Sill Michael W. , Monk Bradley J. , Penson Richard T. , Moore David H. , Lankes Heather A. , Ramondetta Lois M. , Landrum Lisa M. , Randall Leslie M. , Oaknin Ana , Leitao Mario M. , Eisenhauer Eric L. , DiSilvestro Paul , Van Le Linda , Pearl Michael L. , Burke James J. , Salani Ritu , Richardson Debra L. , Michael Helen E. , Kindelberger David W. , Birrer Michael J.
Published: August 2020

To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45− cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0–18) and, at 36 days posttreatment, was 4 (range, 0–17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79–0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32–1.03) and PFS (HR, 0.59; 95% CI, 0.36–0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.
How to Intervene in the Caries Process: Dentin Caries in Primary Teeth
Authors: Santamaría Ruth M. , Abudrya Mohamed Hassan , Gül Gülsün , Mourad MHD Said , Gomez Grace Felix , Zandona Andrea G. Ferreira
Published: August 2020

For an ORCA/EFCD consensus, this review systematically assessed available evidence regarding interventions performed and materials used to manage dentin carious lesions in primary teeth. A search for systematic reviews (SRs) and randomized clinical trials (RCTs) with a follow-up of at least 12 months after intervention was performed in PubMed, LILACS, BBO, and the Cochrane Library. The risk of bias tool from the Cochrane Collaboration and the PRISMA Statement were used for assessment of the included studies. From 101 screened articles, 2 SRs and 5 RCTs, which assessed the effectiveness of interventions in terms of pulp vitality and success of restoration, and 10 SRs and 1 RCT assessing the success of restorative materials were included. For treatments involving no carious tissue removal, the Hall technique showed lower treatment failure for approximal carious lesions compared to complete caries removal (CCR) and filling. For the treatment of deep carious lesions, techniques involving selective caries removal (SCR) showed a reduction in the incidence of pulp exposure. However, the benefit of SCR over CCR in terms of pulp symptoms or restoration success/failure was not confirmed. Regarding restorative materials, preformed metal crowns (PMCs) used to restore multisurface lesions showed the highest success rates compared to other restorative materials (amalgam, composite resin, glass ionomer cement, and compomer), and in the long term (12–48 months) these were also less likely to fail. There is limited evidence supporting the use of PMCs to restore carious lesions with single cavities. Among nonrestorative options, silver diammine fluoride was significantly more effective in arresting caries than other treatments for treating active carious lesions of different depths. Considerable heterogeneity and bias risk were observed in the included studies. Although heterogeneity observed among the studies was substantial, the trends were similar. In conclusion, less invasive caries approaches involving selective or no caries removal seem advantageous in comparison to CCR for patients presenting with vital, symptomless, carious dentin lesions in primary teeth. There is evidence in favor of PMCs for restoring multisurface carious lesions in primary molars.
One-Year Course of Periprocedural Anticoagulation in Atrial Fibrillation Ablation: Results of a German Nationwide Survey
Authors: Bejinariu Alexandru Gabriel , Makimoto Hisaki , Wakili Reza , Mathew Shibu , Kosiuk Jedrzej , Linz Dominik , Steinfurt Johannes , Dechering Dirk G. , Meyer Christian , Veltmann Christian , Kelm Malte , Frommeyer Gerrit , Eckardt Lars , Deneke Thomas , Duncker David , Müller Patrick
Published: August 2020

Introduction: Periprocedural oral anticoagulation (OAC) strategies for atrial fibrillation (AF) ablation procedures are changing rapidly. Objective: To assess the management and course of periprocedural OAC for AF ablation procedures in experienced electrophysiology (EP) centers in Germany over the last 12 months. Methods: The data are based on an electronic questionnaire, which was sent to 35 experienced EP centers in September 2018 and then exactly 1 year later. Participants provided information on their periprocedural OAC management, the handling with dual therapy (OAC plus single antiplatelet therapy), the availability of specific antidotes, the transseptal puncture approach, and noteworthy complications. Results: Responses were received from all 35 centers and represent 10,010 AF ablation procedures annually. In 2018, the administration of vitamin K antagonist (VKA) was continued throughout the procedure at all centers (100%). In contrast, the majority of centers used minimally interrupted periprocedural non-vitamin K antagonist oral anticoagulants (NOAC) (54.3%), 13 centers (37.2%) completely interrupted NOAC, and only 3 centers (8.5%) continued NOAC throughout the procedure. At the 1-year follow-up survey, 32 centers were found to have continued their previous strategy of periprocedural OAC and 3 changed from a minimally interrupted to a continued NOAC strategy. Of note, 30 centers (85.7%) performed transseptal puncture fluoroscopically without additional cardiac imaging. In the setting of uninterrupted periprocedural OAC management, no relevant complications were noted. Conclusion: Our survey shows marked heterogeneous periprocedural OAC management at experienced EP centers in Germany. Whereas continuation of VKA has already been integrated into clinical practice, the majority of centers still use a minimally interrupted NOAC strategy.
Dyslipidemia and Associated Risk Factors among Nigerians with Hypertension
Authors: Ayoade Olufisayo Gabriel , Umoh Idongesit , Amadi Collins
Published: August 2020

Background: Abnormalities in serum lipids and lipoprotein levels with essential hypertension are vital independent causal factors for atherosclerotic cardiovascular disease (ASCVD). The coexistence of these factors has a synergistic effect in heightening the risk of cardiovascular events. The aim of the study was to evaluate the pattern of dyslipidemia among hypertensives and to determine some of its correlations in patients attending a tertiary hospital in South South Nigeria. Methods: This was a cross-sectional study conducted on 544 eligible hypertensive patients attending the Cardiology Clinic, University of Uyo Teaching Hospital (UUTH), Uyo, Nigeria, over a period of 6 months. Fasting lipids, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were evaluated. Results: Overall, 60.0% of the hypertensive patients had dyslipidemia, with 43.4.0% having high TC, 30.3% high LDL-C, 20.8% elevated TG, and 12.9% low HDL-C, respectively. There was a significant relationship between gender and lipoproteins, with women having significantly higher lipoproteins (TC, HDL-C, LDL-C, and non-HDL-C) than men. Women also had more measures of obesity with a higher body mass index and waist circumference. TC and non-HDL had a significant association with both systolic and diastolic blood pressure (BP). Altogether, 43.4% of the hypertensives had poorly controlled BP and significantly higher atherogenic lipoproteins (TC, LDL-C, and non-HDL-C). Conclusion: This study has demonstrated the relatively high prevalence of dyslipidemia among hypertensive patient in this population. High plasma TC is the most dominant pattern of dyslipidemia. Hypertensive patients with poorly controlled BP have worse atherogenic lipoprotein values and are more likely predisposed to ASCVD.
When Actin is Not Actin’ Like It Should: A New Category of Distinct Primary Immunodeficiency Disorders
Authors: Sprenkeler Evelien G.G. , Webbers Steven D.S. , Kuijpers Taco W.
Published: August 2020

An increasing number of primary immunodeficiencies (PIDs) have been identified over the last decade, which are caused by deleterious mutations in genes encoding for proteins involved in actin cytoskeleton regulation. These mutations primarily affect hematopoietic cells and lead to defective function of immune cells, such as impaired motility, signaling, proliferative capacity, and defective antimicrobial host defense. Here, we review several of these immunological “actinopathies” and cover both clinical aspects, as well as cellular mechanisms of these PIDs. We focus in particular on the effect of these mutations on human neutrophil function.
Sleep Breathing Disorders in the COVID-19 Era: Italian Thoracic Society Organizational Models for a Correct Approach to Diagnosis and Treatment
Authors: Insalaco Giuseppe , Dal Farra Fabrizio , Braghiroli Alberto ,   Sacco, Salvaggio Adriana ,   on behalf of the Italian Thoracic Society (ITS-AIPO)
Published: August 2020

The attenuation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, at least in Italy, allows a gradual resumption of diagnostic and therapeutic activities for sleep respiratory disorders. The knowledge on this new disorder is growing fast, but our experience is still limited and when a physician cannot rely on evidence-based medicine, the experience of his peers can support the decision-making and operational process of reopening sleep laboratories. The aim of this paper is to focus on the safety of patients and operators accessing hospitals and the practice of diagnosing and treating sleep-related respiratory disorders. The whole process requires a careful plan, starting with a triage preceding the access to the facility, to minimize the risk of infection. Preparation of the medical record can be performed through standard questionnaires administered over the phone or by e-mail, including an assessment of the COVID-19 risk. The home sleep test should include single-patient sensors or easy-to-sanitize material. The use of nasal cannulas is discouraged in view of the risk of the virus colonizing the internal reading chamber, since no filter has been tested and certified to be used extensively for coronavirus due to its small size. The adaptation to positive airway pressure (PAP) treatment can also be performed mainly using telemedicine procedures. In the adaptation session, the mask should be new or correctly sanitized and the PAP device, without a humidifier, should be protected by an antibacterial/antiviral filter, then sanitized and reassigned after at least 4 days since SARS-CoV-2 was detected on some surfaces up to 72 h after. Identification of pressure should preferably be performed by telemedicine. The patient should be informed of the risk of spreading the disease in the family environment through droplets and how to reduce this risk. The follow-up phase can again be performed mainly by telemedicine both for problem solving and the collection of data. Public access to hospital should be minimized and granted to patients only. Constant monitoring of institutional communications will help in implementing the necessary recommendations.
LIMITED SEED DISPERSAL MAY SHAPE GENETIC STRUCTURE OF Hydnophytum formicarum JACK. POPULATIONS IN MANGROVE ECOSYSTEM
Authors: Yusoff Abdul Shukor , Wan Omar Wan Bayani , Rohani Shahrudin
Published: August 2020

Hydnophytum formicarum is an epiphytic plant, commonly distributed throughout Southeast Asia. However, its distribution is currently declining due to forest fragmentation and the subsequent habitat changes which may have also consequently affected the genetic structure of H. formicarum populations. Hence, this study aimed to understand the genetic variation and differentiation within and among populations of this species. Using Random Amplified Polymorphic DNA (RAPD) markers, the genetic variation and genetic differentiation among three populations were assessed in order to identify potential conservation management strategies for this species in the mangrove ecosystem in Malaysia. Ten highly reproducible primers were used in the population analysis, resulting in a total of 221 discernible fragments. Genetic variation among populations was high at 98% identified polymorphic fragments. AMOVA showed significant genetic differentiation among the populations (Î¦PT = 0.554, p â‰¤ 0.001), with pairwise genetic distances between the populations ranging from 0.495 - 0.589. PCoA clustering analysis separated the populations according to their geographical locations. The high genetic variation within a population, high genetic differentiation between populations and clear separation in the cluster analysis indicated a restricted seed dispersal of the species.
O conceito de Bildung na Formação da literatura brasileira de Antonio Candido: intersecções
Authors: Couto Elvis Paulo
Published: August 2020

Pretende-se refletir sobre o conceito de Bildung, não do ponto de vista de uma determinada personagem romanesca, mas como projeto coletivo de construção de uma personalidade literária autêntica e autônoma e como Leitmotiv da história do Romantismo brasileiro escrita por Antonio Candido na Formação da literatura brasileira. Esquematicamente, nossa análise da Bildung concentra-se em: 1) formação do caráter nacional representada na literatura romântica brasileira; 2) historiografia crítica do período romântico brasileiro norteada pelo objetivo de esclarecimento dos elementos formativos; 3) impulso de formação de uma crítica literária moderna no Brasil.
Série estudo para mãe
Authors: Hortides Ana Lúcia
Published: August 2020

Estudo para mãe é uma série de fichas escritas uma a uma onde é catalogada às avessas, a mãe da artista.
Persistência do não lugar literário: algumas questões com Juliano Garcia Pessanha
Authors: Fernandes Thiago H.
Published: August 2020

Entrevista com o autor Juliano Garcia Pessanha.
Editorial
Authors: Fernandes Thiago H. , Caldas Juliana
Published: August 2020

Apresentação do número 16 da Opiniães - Revista dos alunos de literatura brasileira.
Reinstatement of Pimpinella katrajensis R.S.Rao & Hemadri (Apiaceae), an endemic species to Maharashtra with notes on its taxonomy and distribution
Authors: S.M. Deshpande  , S.D. Kulkarni  , R.B. More  , K.V.C. Gosavi
Published: August 2020

Pimpinella katrajensis Rolla Rao & Hemadri (Apiaceae) is an endemic and less known species, reported from a few localities of Maharashtra.  Mukherjee & Constance subsumed P. katrajensis in P. wallichiana Gandhi although both species are very distinct.  Thus, the present investigation provides detailed morphological description, distribution, distinguishing characters and images of P. katrajensis for correct identification.
HDL (High-Density Lipoprotein) Remodeling and Magnetic Resonance Imaging–Assessed Atherosclerotic Plaque Burden
Authors: Ben-Aicha Soumaya , Casaní Laura , Muñoz-García Natàlia , Joan-Babot Oriol , Peña Esther , Aržanauskaitė Monika , Gutierrez Manuel , Mendieta Guiomar , Padró Teresa , Badimon Lina , Vilahur Gemma
Published: August 2020

Objective:

HDL (high-density lipoprotein) role in atherosclerosis is controversial. Clinical trials with CETP (cholesterylester transfer protein)-inhibitors have not provided benefit. We have shown that HDL remodeling in hypercholesterolemia reduces HDL cardioprotective potential. We aimed to assess whether hypercholesterolemia affects HDL-induced atherosclerotic plaque regression.

Approach and Results:

Atherosclerosis was induced in New Zealand White rabbits for 3-months by combining a high-fat-diet and double-balloon aortic denudation. Then, animals underwent magnetic resonance imaging (basal plaque) and randomized to receive 4 IV infusions (1 infusion/wk) of HDL isolated from normocholesterolemic (NC-HDL; 75 mg/kg; n=10), hypercholesterolemic (HC-HDL; 75 mg/Kg; n=10), or vehicle (n=10) rabbits. Then, animals underwent a second magnetic resonance imaging (end plaque). Blood, aorta, and liver samples were obtained for analyses. Follow-up magnetic resonance imaging revealed that NC-HDL administration regressed atherosclerotic lesions by 4.3%, whereas, conversely, the administration of HC-HDLs induced a further 6.5% progression (
P
<0.05 versus basal). Plaque characterization showed that HC-HDL administered animals had a 2-fold higher lipid and cholesterol content versus those infused NC-HDL and vehicle (
P
<0.05). No differences were observed among groups in CD31 levels, nor in infiltrated macrophages or smooth muscle cells. Plaques from HC-HDL administered animals exhibited higher Casp3 (caspase 3) content (
P
<0.05 versus vehicle and NC-HDL) whereas plaques from NC-HDL infused animals showed lower expression of Casp3, Cox1 (cyclooxygenase 1), inducible nitric oxide synthase, and MMP (metalloproteinase) activity (
P
<0.05 versus HC-HDL and vehicle). HDLs isolated from animals administered HC-HDL displayed lower antioxidant potential and cholesterol efflux capacity as compared with HDLs isolated from NC-HDL-infused animal and vehicle or donor HDL (
P
<0.05). There were no differences in HDL-ApoA1 content, ABCA1 (ATP-binding cassette transporter A1) vascular expression, and SRB1 (scavenger receptor B1) and ABCA1 liver expression.

Conclusions:

HDL particles isolated from a hypercholesterolemic milieu lose their ability to regress and stabilize atherosclerotic lesions. Our data suggest that HDL remodeling in patients with co-morbidities may lead to the loss of HDL atheroprotective functions.
Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm
Authors: Flahault Adrien , Oliveira Fernandes Rafael , De Meulemeester Julie , Ravizzoni Dartora Daniela , Cloutier Anik , Gyger Geneviève , El-Jalbout Ramy , Bigras Jean-Luc , Luu Thuy Mai , Nuyt Anne Monique
Published: August 2020

Objective:

Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown.

Approach and Results:

We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility.

Conclusions:

Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.
Patterns of Postpartum Ambulatory Care Follow‐up Care Among Women With Hypertensive Disorders of Pregnancy
Authors: Lewey Jennifer , Levine Lisa D. , Yang Lin , Triebwasser Jourdan E. , Groeneveld Peter W.
Published: August 2020

Background

Preeclampsia and gestational hypertension are hypertensive disorders of pregnancy (HDP) that identify an increased risk of developing chronic hypertension and cardiovascular disease later in life. Postpartum follow‐up may facilitate early screening and treatment of cardiovascular risk factors. Our objective is to describe patterns of postpartum visits with primary care and women's health providers (eg, family medicine and obstetrics) among women with and without HDP in a nationally representative sample of commercially insured women.

Methods and Results

We conducted a retrospective cohort study using insurance claims from a US health insurance database to describe patterns in office visits in the 6 months after delivery. We identified 566 059 women with completed pregnancies between 2005 and 2014. At 6 months, 13% of women with normotensive pregnancies, 18% with HDP, and 23% with chronic hypertension had primary care visits (
P
<0.0001 for comparing HDP and chronic hypertension groups with control participants). Only 58% of women with HDP had 6‐month follow‐up with any continuity provider compared with 47% of women without hypertension (
P
<0.0001). In multivariable analysis, women with severe preeclampsia were 16% more likely to have postpartum continuity follow‐up (adjusted odds ratio, 1.16; 95% CI, 1.2–1.21). Factors associated with a lower likelihood of any follow‐up included age ≥30 years, Black race, Hispanic ethnicity, and having multiple gestations.

Conclusions

Rates of continuity care follow‐up after a pregnancy complicated by hypertension were low. This represents a substantial missed opportunity to provide cardiovascular risk screening and management to women at increased risk of future cardiovascular disease.