bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical analysis of smoke flow under the effect of longitudinal airflow in a tunnel fire
Authors: Kalech Brahim , Bouterra Mourad , ElCafsi Afif
Published: September 2020

This study investigated the influence of the longitudinal airflow on the smoke propagation in a tunnel by large‐eddy simulation, which is now widely applied to study the turbulent flow. The smoke movement characteristics were studied in detail, with varying the longitudinal airflow in the tunnel. Six fire scenarios have been simulated with Fire Dynamics Simulator (FDS) and the results of the longitudinal distribution of CO concentration, temperature distribution, interface height, stratification, and the efficiency of smoke extraction in the tunnel have been analyzed to evaluate the different fire cases. FDS predicted a CO concentration distribution compared to calculated values using the Hu model. Furthermore, the predicted maximum smoke temperatures are compared to those given by the Kurioka model. A reasonably good agreement has been obtained for both models. The obtained results showed that the increase of the forced airflow velocity has for results a loss of stratification and significant decrease in the efficiency of extraction.
Origin of Late Jurassic high‐K felsic volcanic rocks and related Au mineralization in the Dongyang deposit, central‐eastern Fujian, SE China, and its tectonic implications
Authors: Xu Zhi‐Tao , Yang Qing‐Fu , Sun Jing‐Gui , Lei Feng‐Zhi , Pan Xiao‐Dong , Li Zhong‐Wei
Published: September 2020

The newly discovered Dongyang low‐sulphidation epithermal Au deposit is located in central‐eastern Fujian Province, coastal SE China. Ore bodies occur in Late Jurassic rhyolite porphyry, rhyolite, and dacitic crystal tuff lava. In this study, rhyolite and dacitic crystal tuff lava are dated to 151.9 ± 0.4 Ma and 158.3 ± 0.4 Ma, respectively, and belong to the second member of the Nanyuan Formation. They are high in K2O (6.91–3.81 wt%) and Na2O/K2O (0.55–0.02), strongly peraluminous (A/CNK = 2.11–1.67) and high‐K calc‐alkaline or shoshonitic. They contain low ∑REEs (248–125 ppm), are enriched in Rb, K, Au, and depleted in Ba, Sr, P, Zr, Hf, and have slightly negative Eu anomalies (δEu = 0.94–0.56), suggesting that they are weakly fractionated felsic volcanic rocks. The zircon εHf(t) values (−11.2 to −5.4; two‐stage model ages = 2,650–2,128 Ma) suggest that they were mainly derived from Palaeoproterozoic crust. Lead isotope compositions also imply a dominantly lower crustal source. Detailed geological characteristics and elemental and isotopic data suggest that the oxidizing and weakly fractionated nature of the Dongyang high‐K felsic magma may have played a key role in Au mineralization. Integrating new and published data on the tectonic evolution, we suggest that the Late Jurassic Au mineralization and its causative magmatism actually extended to the SE China coastal area. The Dongyang rhyolite and dacitic crystal tuff lava may have been generated from partial melting of the crust caused by underplating of mantle‐derived magmas in an extensional environment. Regional extension may have been related to the NW‐directed roll‐back of the Palaeo‐Pacific Plate beneath the South China Block.
Patient income and health innovation
Authors: Moradpour Javad , Hollis Aidan
Published: September 2020

This study analyzes the relationship between the number of clinical trials in a disease area, the health losses from that disease, and the average income of people suffering from it. Average patient income appears strongly predictive of the number of clinical trials, whether funded by industry or not. We are able to precisely estimate the relationship between income and the number of trials and to identify both (a) the specific diseases that appear to be underfunded relative to their harm to human health and (b) the amount of additional funding required to bring innovation investment up to the present average.
Population‐based analysis on the effect of nodal and distant metastases in sinonasal adenocarcinoma
Authors: Chweya Cynthia M. , Low Christopher M. , Van Gompel Jamie J. , Van Abel Kathryn M. , Stokken Janalee K. , Choby Garret
Published: September 2020

Background

Minimal information has been reported on the effect of distant and nodal metastases at the time of diagnosis on survival in patients with sinonasal adenocarcinoma (SNAC).

Methods

The Surveillance, Epidemiology, and End Results database was utilized to compare overall survival (OS) and disease‐specific survival (DSS).

Results

Of the 325 patients with SNAC identified, 5‐year and 10‐year OS for all included patients was 64% and 58%, respectively. On multivariate analysis, the presence of distant metastases (P < .0001), maxillary and frontal sinus primary tumors (P = .0042, P = .0006), and increasing age (P = .007) were risk factors for worsened DSS. The presence of regional spread to multiple cervical nodal basins (OS RR 3.26, P = .002; DSS RR 2.51, P = .013) and a single nodal basin (DSS RR 2.19, P = .046) was associated with worsened survival compared to no regional spread.

Conclusion

Survival in SNAC was significantly worsened with increasing age, tumor site of origin, and distant metastatic disease.
Age and risk of recurrence in oral tongue squamous cell carcinoma: Systematic review
Authors: Lenze Nicholas R. , Farquhar Douglas R. , Dorismond Christina , Sheth Siddharth , Zevallos Jose P. , Blumberg Jeffrey , Lumley Catherine , Patel Samip , Hackman Trevor , Weissler Mark C. , Yarbrough Wendell G. , Olshan Andrew F. , Zanation Adam M.
Published: September 2020

The incidence of oral tongue squamous cell carcinoma has been increasing in young patients (≤45 years) without a clear etiologic driver. It is unknown if younger patients have an increased risk of recurrence compared to older patients. A literature search was conducted through January 2020 using PubMed/MEDLINE, Embase, Cochrane, Scopus, Science Direct, and clinicaltrials.gov. This review was registered with PROSPERO (ID: CRD42020167498) and the PRISMA statement was followed. Studies were eligible for inclusion if they assessed risk of recurrence by age using a time‐to‐event analysis, used an age cutoff of ≤45 years or less for the younger cohort, and limited the analysis to the oral tongue subsite. Data were extracted independently by two reviewers using a form with a prespecified list of variables. There were 13 articles that met criteria for the qualitative synthesis (n = 1763 patients). The reported 5‐year rates of disease‐free survival ranged from 30% to 72% for the younger cohorts and 42% to 81% for the older cohorts. Three studies reported a statistically significant increased risk of recurrence in younger patients, three studies reported a nonsignificant increased risk in younger patients, and seven studies reported a similar risk in younger patients based on the time‐to‐event analyses. There may be an increased risk of recurrence for younger patients with oral tongue cancer. A definitive conclusion is precluded by limitations among individual studies, and additional research is warranted to examine this question.
Human papillomavirus oropharynx carcinoma: Aggressive de‐escalation of adjuvant therapy
Authors: Moore Eric J. , Van Abel Kathryn M. , Routman David M. , Lohse Christine M. , Price Katharine A. R. , Neben‐Wittich Michelle , Chintakuntlawar Ashish V. , Price Daniel L. , Kasperbauer Jan L. , Garcia Joaquin J. , Hinni Michael L. , Patel Samir H. , Janus Jeffrey R. , Foote Robert L. , Ma Dan J.
Published: September 2020

Background

Aggressive dose de‐escalated adjuvant radiation therapy (RT) in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC).

Methods

Patients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de‐escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence‐free, regional recurrence‐free, distant metastases‐free survival, and progression‐free survival (PFS) were assessed.

Results

Of 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range [IQR] 0.7‐2.0; range 0.3‐5.4); 10 patients in the de‐escalated cohort and 13 patients in the standard cohort. The 3‐year PFS rate for the de‐escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio [HR] 1.18, 95% confidence interval (CI) [0.50‐2.75]).

Conclusion

Patients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de‐escalation of RT without increasing risk of progression locally, regionally or at distant sites.
Prospective Multicenter Study of Early Antiviral Therapy in Liver and Kidney Transplant Recipients of HCV‐Viremic Donors
Authors: Terrault Norah A. , Burton James , Ghobrial Mark , Verna Elizabeth , Bayer Johanna , Klein Christina , Victor David , Mohan Sumit , Trotter James , Dodge Jennifer , Niemann Claus U. , Rubin Raymond A.
Published: September 2020

Background and Aims

Organs from hepatitis C virus (HCV)‐viremic donors have been used in HCV‐uninfected recipients (D+/R‐), but the optimal treatment approach has not been defined. We evaluated the kinetics of HCV infection following transplant in D+/R‐ kidney‐transplant (KT) and liver‐transplant (LT) recipients when a preemptive antiviral strategy was used.

Approach and Results

Six US transplant programs prospectively treated D+/R‐ primary LT and KT recipients with sofosbuvir‐velpastasvir for 12 weeks starting once viremia was confirmed following transplant and the patients were judged to be clinically stable, including estimated glomerular filtration rate >30 mL/min. Primary endpoints were sustained virologic response at 12 weeks following transplant and safety (assessed by proportion of treatment‐related adverse and serious adverse events). Of the 24 patients transplanted (13 liver, of whom 2 had prior‐treated HCV infection; 11 kidney), 23 became viremic after transplant. The median (interquartile range) time from transplant to start of antiviral therapy was 7.0 (6.0, 12.0) versus 16.5 (9.8, 24.5) days, and the median (interquartile range) HCV‐RNA level 3 days after transplant was 6.5 (3.9, 7.1) versus 3.6 (2.9, 4.0) log10 IU/mL in LT versus KT recipients, respectively. By week 4 of treatment, 10 of 13 (77%) LT, but only 2 of 10 (20%) KT, had undetectable HCV RNA (P = 0.01). At the end of treatment, all LT recipients were HCV RNA–undetectable, whereas 3 (30%) of the kidney recipients still had detectable, but not quantifiable, viremia. All achieved sustained virologic response at 12 weeks following transplant (lower 95% confidence interval bound: 85%). Serious adverse events considered possibly related to treatment were antibody‐mediated rejection, biliary sclerosis, cardiomyopathy, and graft‐versus‐host disease, with the latter associated with multiorgan failure, premature treatment discontinuation, and death.

Conclusions

Despite differing kinetics of early HCV infection in liver versus non‐liver recipients, a preemptive antiviral strategy is effective. Vigilance for adverse immunologic events is warranted.
Analysis on chronic pain management: Focus on the Italian network
Authors: Amato Francesco , Ceniti Silvia , Laurita Sara , Pasceri Erika , Guarasci Roberto , Parisi Francesca , Parrilla Luciano , Panizzoli Giuseppina , Perri Anna
Published: September 2020

The Italian Law 38/2010, ‘Dispositions to guarantee access to Palliative Care and Pain Management’ orders that the health care systems of Italian regions create dedicated structures for palliative care and pain therapies, according to a specific organizational model called ‘Hub‐Spoke’, to ensure the diagnostic‐therapeutic continuity of patients affected by chronic pain (CP). The aim of our study was to investigate the Italian pain therapy network, 8 years following the approval of the Law. We sent a questionnaire to the national health representatives operating in CP management. The main result emerging from the analysis concerns the management of mini‐invasive procedures, showing that 93.2% of the responding facilities carry out invasive procedures, 6.8% do not perform them and that 100% of the facilities belonging to 12 regions provided these procedures, while in eight regions more than 80%. Finally, only 38.5% of facilities declared to have a shared protocol with the relevant territorial facilities in order to guarantee the process of care and assistance of patients affected by CP. In conclusion, our study demonstrated the efficacy of the organizational model in most of the responding facilities, although the territorial management of patients after their hospital discharge should be strengthened.
Advocating the use of threshold effects estimation: An illustration using the gender wage gap
Authors: Yerger David B. , Stephenson Amber L.
Published: September 2020

While linear models remain the backbone of human resource development (HRD) as well as broader social science research, they are limited by their inability to detect curvilinearity or changes in direction and, therefore, may not accurately represent the nature of relationships between variables. This paper advocates the utility of the Andrews' (1993) threshold effect technique in the HRD, work, organization, and employment study literatures and does so using the gender wage gap as an illustration. The analysis compares traditional linear regression, a curvilinear quadratic model, and the threshold effect technique using publicly available wage data. This article demonstrates how the threshold method permits the data to organically determine the location of a critical break point, should one exist, and how it addresses the problem of overlooked relationships due to traditional linear assumptions. An overview of the technique and related coding is provided for researchers interested in broadening their analytical arsenal to enhance the study of the gender wage gap as well as other human‐resource‐related phenomena.
Opium use and the risk of head and neck squamous cell carcinoma
Authors: Mohebbi Elham , Hadji Maryam , Rashidian Hamideh , Rezaianzadeh Abass , Marzban Maryam , Haghdoost Ali Akbar , Naghibzadeh Tahami Ahmad , Moradi Abdolvahab , Gholipour Mahin , Najafi Farid , Safari‐Faramani Roya , Alizadeh‐Navaei Reza , Ansari‐Moghaddam Alireza , Bakhshi Mahdieh , Nejatizadeh Azim , Mahmoudi Masumeh , Shahidsales Soodabeh , Ahmadi‐Simab Saeideh , Arabi Mianroodi Ali Asghar , Seyyedsalehi Monireh Sadat , Hosseini Bayan , Peyghambari Vahideh , Shirkhoda Mohammad , Shirkoohi Reza , Ebrahimi Elmira , Manifar Soheila , Mohagheghi Mohammad Ali , Rozek Laura , Brennan Paul , Poustchi Hossein , Etemadi Arash , Pukkala Eero , Schüz Joachim , Malekzadeh Reza , Weiderpass Elisabete , Rahimi‐Movaghar Afarin , Boffetta Paolo , Kamanagar Farin , Zendehdel Kazem
Published: September 2020

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case‐control study—Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency‐matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed‐effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96‐4.79) for all HNSCC combined. Strong dose‐response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40‐6.02), 6.55 (4.69‐9.13) and 5.95 (2.41‐14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water‐pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20‐10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.
Leukemia inhibitory factor is a novel biomarker to predict lymph node and distant metastasis in pancreatic cancer
Authors: Jiang Wenna , Bai Weiwei , Li Jianhua , Liu Jing , Zhao Kaili , Ren Li
Published: September 2020

Pancreatic cancer has a low survival rate, and most patients have lymph node metastasis and distant metastasis at the time of diagnosis. Despite efforts to improve overall survival (OS) and recurrence free survival (RFS), the prognosis of pancreatic cancer remains poor, underscoring the importance of identifying new biomarkers to predict metastasis in patients with pancreatic cancer. Leukemia inhibitory factor (LIF) is overexpressed in many types of cancer and is involved in the development of various malignancies including pancreatic cancer. However, the role of LIF as a biomarker to predict metastasis in pancreatic cancer remains unclear. In this study, univariate and multivariate Cox regression analyses identified LIF expression in pancreatic tumor tissues as an independent risk factor related to worse OS and RFS. LIF overexpression was related to poor clinicopathological features such as lymph node metastasis and Pathological stage (pTNM) stage. Serum LIF levels were higher in pancreatic cancer patients than in healthy controls. The area under the receiver operating characteristic curve indicated that serum LIF is more effective than other biomarkers (CA199 and CEA) for predicting lymph node and distant metastasis.
Examining the use of the FIGO Nutrition Checklist in routine antenatal practice: multistakeholder feedback to implementation
Authors: Killeen Sarah Louise , Callaghan Shauna L. , Jacob Chandni Maria , Hanson Mark A. , McAuliffe Fionnuala M.
Published: September 2020

Objective

To gain insights from pregnant women and obstetricians on the utility of the FIGO Nutrition Checklist in antenatal practice.

Methods

Women were recruited from the antenatal department of a large tertiary‐level university maternity hospital in Dublin, Ireland, between October and December 2019. Participants completed the FIGO Nutrition Checklist before their routine antenatal appointment. Obstetricians and women were encouraged to discuss the FIGO Nutrition Checklist during the clinical visit. Completed FIGO Nutrition Checklists were collected after appointments. Acceptability was assessed through questionnaires.

Results

The majority (80.0%) of women answered “No” to at least one diet quality question, indicating a potential nutritional risk. While none of the participating obstetricians routinely discussed nutrition with women, all agreed that using the Checklist encouraged them to address nutrition with pregnant women. Nearly every woman (99.0%) found the Checklist quick to complete; however, all participating obstetricians felt there was not enough time to discuss it in routine practice. Despite this, most obstetricians and pregnant women recommended the FIGO Nutrition Checklist for use.

Conclusion

The FIGO Nutrition Checklist is acceptable for use in routine antenatal practice in tertiary care settings. It helped identify potentially at‐risk women during early pregnancy and facilitated conversations related to optimum diet.
Performance evaluation of participatory irrigation management as an alternative to a state‐managed irrigation system*
Authors: Hussain Sabir , Khan Mudasser Muneer , Shoaib Muhammad , Raza Ali , Shah Syyed Adnan Raheel , Khan Tanveer Ahmed , Khan Sher
Published: September 2020

The Lower Bari Doab Canal (LBDC) system is one of the large old irrigation systems in Punjab, Pakistan. To overcome problems of water distribution and management in conventional state‐managed irrigation, a participatory irrigation management (PIM) system was introduced in the LBDC command area in 2012. From the very large system of the LBDC, 20 different kinds of distributaries were selected in this study as representatives for evaluating performance of the new system. The primary data were gathered through questionnaires and by interviewing farmers, whereas the secondary data were gathered from the related offices of the Punjab Irrigation Department. The analysis of collected data illustrates that water service deliveries (WSDs) were poor even after implementation of PIM. The research shows that under administration of both systems, efficiency regarding provision of water seemed to be poor. The outcomes show that with the passage of time, recovery (abiana) decreased after implementation of the PIM system but the financial sustainability of PIM has improved compared to state administration. Finally, the current study recommends institutional reforms in PIM and comprehensive work on educating the farmers about their role in PIM as a mandatory component for improving efficiency of the PIM system.
A new look at 9‐substituted acridines with various biological activities
Authors: Kozurkova Maria , Sabolova Danica , Kristian Pavol
Published: September 2020

Heterocycles have long been the focus of intensive study in attempts to develop novel therapeutic compounds, and acridine, a polynuclear nitrogen molecule containing a heterocycle, has attracted a considerable amount of scientific attention. Acridine derivatives have been studied in detail and have been found to possess multitarget properties, which inhibit topoisomerase enzymes that regulate topological changes in DNA and interfere with the essential biological function of DNA. This article describes some recent advancements in the field of new 9‐substituted acridine heterocyclic agents and describes both the structure and the structure–activity relationship of the most promising molecules. The article will also present the IC50 values of the novel derivatives against various human cancer cell lines. The mini review also investigates the topoisomerase inhibition and antibacterial and antimalarial activity of these polycyclic aromatic derivatives.
Regeneration enhanced in critical‐sized bone defects using bone‐specific extracellular matrix protein
Authors: Miar Solaleh , Pearson Joseph , Montelongo Sergio , Zamilpa Rogelio , Betancourt Alejandro M. , Ram Bharath , Navara Christopher , Appleford Mark R. , Ong Joo L. , Griffey Sy , Guda Teja
Published: September 2020

Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue‐specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM‐MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence‐activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM‐MSC response to bone marrow specific ECM (BM‐ECM). BM‐ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM‐ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical‐sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM‐ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM‐ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM‐ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm4 with BM‐ECM supplementation compared to 48 ± 0.2 mm4 in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM‐ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.
Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus
Authors: Hunt Heather B , Miller Nicholas A , Hemmerling Kimberly J , Koga Maho , Lopez Kelsie A , Taylor Erik A , Sellmeyer Deborah E , Moseley Kendall F , Donnelly Eve
Published: September 2020

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).
6‐Gingerol suppresses tumor cell metastasis by increasing YAPser127 phosphorylation in renal cell carcinoma
Authors: Xu Shan , Zhang Haibao , Liu Tianjie , Wang Zixi , Yang Wenjie , Hou Tao , Wang Xinyang , He Dalin , Zheng Pengsheng
Published: September 2020

According to the World Health Organization, the incidence and mortality rates of renal cell carcinoma (RCC) are rapidly increasing worldwide. Serious side effects caused by immune therapy and resistance to targeted drug therapy are urgent clinical problems facing kidney treatment. There is increasing global interest in developing natural products with a reduced number of side effects as adjunctive therapeutic options for RCC. Ginger is a spice and herbal remedy used worldwide, and 6‐gingerol is a major pharmacologically active ingredient in ginger. In our study, we found that 6‐gingerol suppressed RCC cell migration and metastasis in vitro and in vivo. Moreover, reduction in MMP2, Slug, and Vimentin protein levels was observed following 6‐gingerol treatment of 786‐O and ACHN cells. Furthermore, we revealed the mechanisms underlying the ability of 6‐gingerol to inhibit RCC cell migration and metastasis. 6‐Gingerol increased yes‐associated protein (YAP)ser127 phosphorylation and reduced YAP levels in cell nuclei. We also used a series of loss‐of‐function and gain‐of‐function experiments to support our results. Western blot results showed that MMP2, Slug, and Vimentin protein expression was downregulated in YAP‐silenced cells and upregulated in YAP‐overexpressing cells. Transwell data demonstrated that YAP suppressed RCC migration ability. Immunofluorescence images showed that 6‐gingerol decreased YAP levels, leading to disordered F‐actin and a reduction in cell lamellipodia. Overall, our results indicated that 6‐gingerol is a potential antimetastatic compound for use in kidney therapy.
A comparative study of five plateletpheresis machines in a tertiary care center of India: AmiCORE vs COM.TEC vs Haemonetics MCS+ vs Spectra Optia vs Trima Accel
Authors: Arcot Priyadarsini Jayachandran , Kumar Karan , Coshic Poonam , Andriyas Vijay , Mehta Vikas
Published: September 2020

Background

Single donor apheresis platelets are superior in quality, but their usage is limited in a developing country due to cost and time constraints. Hence the product obtained must exceed in terms of yield, donor safety and technical convenience. Previous literature available on cell separators is on older versions.

Aims

Prospective comparison of 5 latest cell separators (AmiCORE, COM.TEC, Haemonetics MCS+, SpectraOptia and TrimaAccel) for product yield, performance variables and donor adverse effects.

Material & Methods

From October 2019 ‐ March 2020, 1108 donors were randomly allotted to a cell separator. Post‐donation sample was taken from the donor 15‐20 minutes after procedure completion. The platelet yield from the product collected was measured twice (day 0 and day 1). Donor demography, pre‐and post‐procedural donor peripheral blood values, performance and product variables were statistically analyzed.

Results

AmiCORE had an optimal collection efficacy (44.6%) and collection rate (0.037 x 1011/minute). Haemonetics MCS+ had a better collection efficacy (48.4%) and rate (0.038 x 1011/minute). Spectra Optia achieved least procedural time (59.5 minutes), donor adverse effects (6.3%); highest collection efficacy (52.8%) and rate (0.056 x 1011/minute). Trima Accel achieved highest collection rate (0.056 x 1011/minute) and the least product volume (228 ml).

Conclusion

Highest collection efficacy was achieved by Trima Accel, highest collection rate by Trima Accel and Spectra Optia, lowest donor adverse effects by Spectra Optia and least number of procedural troubleshooting by COM.TEC. Apart from this, fiscal factors and service availability also need to be considered before choosing a cell separator.
Synthesis, characterization, and antioxidant activity of heterocyclic Schiff bases
Authors: Kizilkaya Hakan , Dag Beşir , Aral Tarik , Genc Nusret , Erenler Ramazan
Published: September 2020

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one (1) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, 1H‐NMR, 13C‐NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1‐diphenyl‐2‐picryl‐hydrazyl free radical (DPPH•) scavenging, 2,2′‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)‐4‐((1H‐indol‐3‐yl)methyleneamino)‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one (3), (E)‐1,5‐dimethyl‐4‐((2‐methyl‐1H‐indol‐3‐yl)methyleneamino)‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one (5), (E)‐1,5‐dimethyl‐2‐phenyl‐4‐(thiophen‐2‐ylmethyleneamino)‐1H‐pyrazol‐3(2H)‐one (7), (E)‐1,5‐dimethyl‐2‐phenyl‐4‐(quinolin‐2‐ylmethyleneamino)‐1H‐pyrazol‐3(2H)‐one (9), (1S,2S,N1,N2)‐N1,N2‐bis((1H‐indol‐3‐yl)methylene)cyclohexane‐1,2‐diamine (11), and (1S,2S,N1,N2)‐N1,N2‐bis((2‐methyl‐1H‐indol‐3‐yl)methylene)cyclohexane‐1,2‐diamine (12) were synthesized in high yields. Compound 5 displayed a good ABTS•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best‐reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds (3, 5, 7) have the potential to be used as synthetic antioxidant agents.
Intergenerational effects of maternal separation on cognitive abilities of adolescent rats
Authors: Joushi Sara , Esmaeilpour Khadijeh , Taherizadeh Zahra , Taheri Farahnaz , Sheibani Vahid
Published: September 2020

Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother–infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA‐induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (postnatal day (PND) 1‐21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother‐MS group of both sexes showed normal cognitive behavior, father‐MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father‐MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS‐induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex‐dependent manner.
Group connectivity under 3‐edge‐connectivity
Authors: Han Miaomiao , Li Jiaao , Li Xueliang , Wang Meiling
Published: September 2020

Let be two distinct finite Abelian groups with . A fundamental theorem of Tutte shows that a graph admits a nowhere‐zero ‐flow if and only if it admits a nowhere‐zero ‐flow. Jaeger et al in 1992 introduced group connectivity as an extension of flow theory, and they asked whether such a relation holds for group connectivity analogy. It was negatively answered by Hušek et al in 2017 for graphs with edge‐connectivity 2 for the groups and . In this paper, we extend their results to 3‐edge‐connected graphs (including both cubic and general graphs), which answers open problems proposed by Hušek et al and Lai et al. Combining some previous results, this characterizes all the equivalence of group connectivity under 3‐edge‐connectivity, showing that every 3‐edge‐connected ‐connected graph is ‐connected if and only if .
Economic evaluation of facility‐based HIV self‐testing among adult outpatients in Malawi
Authors: Nichols Brooke E , Offorjebe O Agatha , Cele Refiloe , Shaba Frackson , Balakasi Kelvin , Chivwara Mackenzie , Hoffman Risa M , Long Lawrence C , Rosen Sydney , Dovel Kathryn
Published: September 2020

Introduction

HIV self‐testing (HIVST) in outpatient departments (OPD) is a promising strategy for HIV testing in Malawi, given high OPD patient volumes and substantial wait times. To evaluate the relative cost and expected impact of facility‐based HIVST (FB‐HIVST) at OPDs in Malawi for increasing HIV status awareness, we conducted an economic evaluation of an HIVST cluster‐randomized controlled trial.

Methods

A cluster‐randomized trial was conducted at 15 sites in Malawi from September 2017 to February 2018 with three arms: 1) Standard provider‐initiated‐testing‐and‐counselling (PITC); 2) Optimized PITC (additional provider training and job‐aids) and 3) FB‐HIVST (HIVST demonstration, distribution and kit use in OPD, private kit interpretation and optional HIV counselling). The total production cost per newly identified positive and per person newly initiated on ART were calculated by study arm. These were calculated as the total cost of testing everyone divided by the number of newly identified positives; and the total cost of testing everyone divided by the number of those initiated on ART. Cost‐outcomes were calculated under three cost scenarios: (1) full study costs, (2) routine implementation costs and (3) routine implementation + reduced cost for HIVST kits.

Results

The average cost per person newly diagnosed in the full study cost scenario was $101, $156 and $189, and cost per person initiated on ART was $121, $156 and $279 for Standard PITC, Optimized PITC and FB‐HIVST respectively. In the routine implementation cost scenario, the average cost per person newly diagnosed was reduced to $83, and $93, and cost per person initiated on ART to $83, and $137 for Optimized PITC and FB‐HIVST respectively. In the negotiated HIVST cost scenario, the average cost per person newly diagnosed was reduced to $55 and cost per person newly initiated on ART reduced to $81 in the FB‐HIVST arm.

Conclusions

While the cost per new ART initiation through FB‐HIVST was higher than Standard PITC, FB‐HIVST could become cost‐saving compared to PITC if the cost of kits is reduced or if treatment linkage rate were increased in the FB‐HIVST arm. For high volume OPDs, HIVST may increase facility capacity and increase the number of newly diagnosed positives.
Successes and gaps in the HIV cascade of care of a high HIV prevalence setting in Zimbabwe: a population‐based survey
Authors: Conan Nolwenn , Coulborn Rebecca M , Simons Erica , Mapfumo Abraham , Apollo Tsitsi , Garone Daniela B , Casas Esther C , Puren Adrian J , Chihana Menard L , Maman David
Published: September 2020

Introduction

Gutu, a rural district in Zimbabwe, has been implementing comprehensive HIV care with the support of Médecins Sans Frontières (MSF) since 2011, decentralizing testing and treatment services to all rural healthcare facilities. We evaluated HIV prevalence, incidence and the cascade of care, in Gutu District five years after MSF began its activities.

Methods

A cross‐sectional study was implemented between September and December 2016. Using multistage cluster sampling, individuals aged ≥15 years living in the selected households were eligible. Individuals who agreed to participate were interviewed and tested for HIV at home. All participants who tested HIV‐positive had their HIV‐RNA viral load (VL) measured, regardless of their antiretroviral therapy (ART) status, and those not on ART with HIV‐RNA VL ≥ 1000 copies/mL had Limiting‐Antigen‐Avidity EIA Assay for cross‐sectional estimation of population‐level HIV incidence.

Results

Among 5439 eligible adults ≥15 years old, 89.0% of adults were included in the study and accepted an HIV test. The overall prevalence was 13.6% (95%: Confidence Interval (CI): 12.6 to 14.5). Overall HIV‐positive status awareness was 87.4% (95% CI: 84.7 to 89.8), linkage to care 85.5% (95% CI: 82.5 to 88.0) and participants in care 83.8% (95% CI: 80.7 to 86.4). ART coverage among HIV‐positive participants was 83.0% (95% CI: 80.0 to 85.7). Overall, 71.6% (95% CI 68.0 to 75.0) of HIV‐infected participants had a HIV‐RNA VL < 1000 copies/mL. Women achieved higher outcomes than men in the five stages of the cascade of care. Viral Load Suppression (VLS) among participants on ART was 83.2% (95% CI: 79.7 to 86.2) and was not statistically different between women and men (p = 0.98). The overall HIV incidence was estimated at 0.35% (95% CI 0.00 to 0.70) equivalent to 35 new cases/10,000 person‐years.

Conclusions

Our study provides population‐level evidence that achievement of HIV cascade of care coverage overall and among women is feasible in a context with broad access to services and implementation of a decentralized model of care. However, the VLS was relatively low even among participants on ART. Quality care remains the most critical gap in the cascade of care to further reduce mortality and HIV transmission.
Escape of tumor cells from the NK cell cytotoxic activity
Authors: Cantoni Claudia , Wurzer Hannah , Thomas Clément , Vitale Massimo
Published: September 2020

In recent years, NK cells, initially identified as potent cytotoxic effector cells, have revealed an unexpected complexity, both at phenotypic and functional levels. The discovery of different NK cell subsets, characterized by distinct gene expression and phenotypes, was combined with the characterization of the diverse functions NK cells can exert, not only as circulating cells, but also as cells localized or recruited in lymphoid organs and in multiple tissues. Besides the elimination of tumor and virus-infected cells, these functions include the production of cytokines and chemokines, the regulation of innate and adaptive immune cells, the influence on tissue homeostasis. In addition, NK cells display a remarkable functional plasticity, being able to adapt to the environment and to develop a kind of memory. Nevertheless, the powerful cytotoxic activity of NK cells remains one of their most relevant properties, particularly in the antitumor response. In this review, the process of tumor cell recognition and killing mediated by NK cells, starting from the generation of cytolytic granules and recognition of target cell, to the establishment of the NK cell immunological synapse, the release of cytotoxic molecules, and consequent tumor cell death is described. Next, the review focuses on the heterogeneous mechanisms, either intrinsic to tumors or induced by the tumor microenvironment, by which cancer cells can escape the NK cell-mediated attack.
Brief review on the roles of neutrophils in cancer development
Authors: Long Wang , Chen Jingjing , Gao Chen , Lin Zhi , Xie Xubiao , Dai Helong
Published: September 2020

Neutrophils, which are traditionally regarded as a hallmark of inflammation, are also a member of the intratumoral immune cells. The roles of neutrophils in cancer development are diverse and undefined. So far, they are known to be involved in tumor initiation and tumor cell proliferation and metastasis. They show heterogeneity in both phenotypes and functions during early versus late stage of cancer development. Because they are also associated with the clinical outcomes of various types of solid tumors, cancer treatments that target neutrophils might be highly effective. In this review, we briefly cover the latest findings on the multiple roles of neutrophils in cancer development and point out the future directions as well.
Feasibility of weight loss in obese atrial fibrillation patients attending a specialist arrhythmia clinic and its impact on ablation outcomes
Authors: Ding Wern Yew , Kozhuharov Nikola , Chin Shui Hao , Shaw Matthew , Snowdon Richard , Lip Gregory Y. H. , Gupta Dhiraj
Published: September 2020

Background

The feasibility of significant weight reduction in a specialist arrhythmia service, and its impact on atrial fibrillation (AF) ablation outcomes are unclear. We aimed to assess these factors in a real‐world cohort in the United Kingdom.

Methods

Patients from one specialized arrhythmia clinic were instructed to follow the “Intermittent Fasting 5:2 diet” (“diet group”, n = 50), and their outcomes were compared to a propensity matched cohort who received no specific dietary advice (“control group”, n = 42). The primary outcome was recurrence of AF or atrial tachycardia (AT) at 12 months postablation, with or without drugs.

Results

Body weight and body mass index (BMI) at baseline were 105.0 (±15.3) kgs and 36.0 (±4.0), respectively. Baseline characteristics between the two groups were comparable. Patients in diet group experienced a mean weight loss of 8.2 (±7.1) kgs prior to AF ablation (P < .01 for comparison to baseline and control group). About 14 (28%) patients in the diet group lost >10% of their body weight. Overall, 11 (22%) patients in the diet group and five (12%) in the control group had AF recurrence at 1 year, P = .21. AF recurrence was similar in patients with BMI ≥ 35 (15%) as compared to BMI < 35 (19%), P = .60. There was one procedural complication (pulmonary edema) in the diet group.

Conclusion

It is feasible to achieve significant weight reduction in obese AF patients in a specialist arrhythmia clinic setting with unsupervised dietary advice. Low rates of procedural complications and excellent medium‐term success rates were observed in this traditionally challenging population. Additional improvements in outcomes were not demonstrable in patients who exhibited significant weight loss.
Rainfall extremes and drought in Northeast Brazil and its relationship with El Niño–Southern Oscillation
Authors: Costa Micejane da Silva , Oliveira‐Júnior José Francisco de , Santos Paulo José dos , Correia Filho Washington Luiz Félix , Gois Givanildo de , Blanco Cláudio José Cavalcante , Teodoro Paulo Eduardo , Silva Junior Carlos Antonio da , Santiago Dimas de Barros , Souza Edson de Oliveira , Jardim Alexandre Maniçoba da Rosa Ferraz
Published: September 2020

The objective of this study was to evaluate the annual standardized precipitation index (SPI) obtained from the DrinC software based on multivariate analysis in the identification of rainfall and drought extremes in the State of Alagoas and its relationship with El Niño–Southern Oscillation. Monthly rainfall data from 1960 to 2016 from National Water Agency were analysed. Annual SPI (SPI‐12) has been designed for comparison with ENSO phases via Oceanic Niño Index for 3.4 region and in identifying climate extremes in the State of Alagoas. The principal component analysis and cluster analysis techniques were applied to the rainfall series of SPI‐12. Extreme events were identified in both rainy and drought periods according to SPI‐12, and were associated with the ENSO phases (El Niño, La Niña, and Neutral). The first four principal components explained 46.68% of the variance. Our findings are crucial for agriculture and civil defence since northeastern Brazil has several areas of risk and social vulnerability.
Resiliency, Self‐Regulation, and Reemployment After Job Loss
Authors: McLarnon Matthew J. W. , Rothstein Mitchell G. , King Gillian A.
Published: September 2020

This study investigated self‐regulation and resiliency in one's search for reemployment. Although trait‐based approaches are central to many resiliency conceptualizations, recent research has found that self‐regulation (affective, behavioral, and cognitive) contributes to predicting resiliency‐related outcomes. We hypothesized that self‐regulation would incrementally predict reemployment process outcomes, specifically the job search outcomes of psychological well‐being, job search self‐efficacy, and job search clarity. Results indicated that, over and above resiliency traits, behavioral and cognitive self‐regulation incrementally predicted well‐being and job search clarity, and cognitive self‐regulation incrementally predicted job search self‐efficacy. Implications for theory and continued research on resiliency in reemployment are discussed.