bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Utility of INSM1 in Medullary Thyroid Carcinoma
Authors: Seok Jae Yeon , Kang Myunghee , De Peralta-Venturina Mariza , Fan Xuemo
Published: March 2021

Insulinoma-associated protein 1 (INSM1) is shown to be an excellent marker for neuroendocrine differentiation. However, the diagnostic utility of INSM1 in medullary thyroid carcinoma (MTC) has not yet been extensively investigated. INSM1 staining was performed on 21 MTCs, 7 MTC mimickers (including 3 papillary carcinomas, 2 poorly differentiated carcinomas, 1 follicular adenoma, and 1 nodular plasma cell hyperplasia), and 3 cases of C-cell hyperplasia. INSM1 staining of these cases was compared with the traditional MTC markers including calcitonin (CT), monoclonal carcinoembryonic antigen (mCEA), chromogranin A (CgA), and synaptophysin (Syn). The H-score was generated using the QuPath program, an open-source image analysis software. All 21 MTC cases and 3 C-cell hyperplasia cases were positive for all markers. The MTC mimickers were entirely negative for INSM1. INSM1 and Syn displayed, more consistently, high expression with minimal variability than CgA that showed a wide range of expression with significant variability. mCEA and CT exhibited mostly a high expression with some variability. Being a nuclear stain, interpretation was easier with INSM1 compared to other cytoplasmic markers. INSM1 is an excellent marker for neuroendocrine differentiation, entirely applicable in the diagnosis of MTC and C-cell hyperplasia with high sensitivity and specificity. In comparison with the traditional MTC markers, INSM1 is unique in the crisp nuclear staining pattern with a consistent, diffuse, and strong expression. INSM1 can be potentially combined with CT or mCEA as a dual stain, especially when the lesional tissue is limited for a panel of immunostains.
Modelling flexural wave propagation by the nonlocal strain gradient elasticity with fractional derivatives
Authors: Huang Yishuang , Wei Peijun , Xu Yuqian , Li Yueqiu
Published: March 2021

The flexural wave propagation in a microbeam is studied based upon the nonlocal strain gradient model with the spatial and time fractional order differentials in the present work. To capture the dispersive behaviour induced by the inherent nanoscale heterogeneity, the stress gradient elasticity and the strain gradient elasticity are often used to model the mechanical behaviour. The present model incorporates the two models and introduces the fractional order derivatives which can be understood as a generalization of integral order nonlocal strain gradient model. The Laplacian operator in the constitutive equation is replaced with the symmetric Caputo fractional differential in the present model. To illustrate the flexibility of the present model, the flexural wave propagation in a microbeam is studied. The fractional order in the present model as a new material parameter can be adjusted appropriately to describe the dispersive properties of the flexural waves. The numerical results based on the new nonlocal strain gradient elasticity with fractional order derivatives are provided for both Euler–Bernoulli beam and Timoshenko beam. The comparisons with the integer order nonlocal strain gradient model and the molecular dynamic simulation are performed to validate the flexibility of the fractional order nonlocal strain gradient model.
Effect of advanced biofuels on WLTC emissions of a Euro 6 diesel vehicle with SCR under different climatic conditions
Authors: Calle-Asensio A , Hernández JJ , Rodríguez-Fernández J , Lapuerta M , Ramos A , Barba J
Published: March 2021

Hydrotreated vegetable oil (HVO), a glycerol-derived biofuel (blended with diesel fuel at 20% v/v, Mo·bio®) and biodiesel produced through the esterification of residual free fatty acids from the palm oil industry (pure and blended with diesel fuel at 20% v/v), all of them considered as advanced biofuels as defined in the Directive EU/2018/2001, were tested in a Euro 6 diesel vehicle equipped with ammonia-SCR. Tests were carried out in a chassis dyno at warm (24°C) and cold (−7°C) ambient conditions following the Worldwide harmonized Light-duty vehicles Test Cycle (WLTC). The efficiency of the SCR when changing the fuel was also analysed. Regarding vehicle performance, fuel properties were mainly relevant at warm conditions. Because of the lower EGR rate, NOx emissions upstream of the SCR were higher at cold temperature, mainly during the low and the extra-high speed phases of the WLTC. CO and THC emissions were only important at the beginning of the cycle and at −7°C. HVO presented advantages regarding these compounds, while the worse cloud point of biodiesel led to higher emissions. As expected, engine-out NOx emissions were very sensitive to the EGR rate, HVO showing a slightly better behaviour because of its high cetane number. The SCR efficiency was mainly affected by the exhaust gas temperature, although fuel-derived effects were also significant. In fact, a more appropriate NO2/NOx ratio at the catalyst inlet for HVO and a higher hydrocarbon concentration at the low-speed phase for B20 contributed to a lower tail-pipe NOx emissions at −7°C. The oxygen content of biodiesel-based fuels (B100 and B20) led to lower particle number with respect to diesel fuel. Despite its nil aromatic content, the higher EGR rate and the extremely superior autoignition trend of HVO led to higher particle number under high engine load and warm conditions.
Do We Report the Information That Is Necessary to Give Psychology Away? A Scoping Review of the Psychological Intervention Literature 2000–2018
Authors: Premachandra Bharathy , Lewis Neil A.
Published: March 2021

Psychologists are spending a considerable amount of time researching and developing interventions in hopes that their efforts can help to tackle some of society’s pressing problems. Unfortunately, those hopes are often not realized—many interventions are developed and reported in journals but do not make their way into the broader world they were designed to change. One potential reason for this is that there may be a gap between the information reported in articles and the information others, such as practitioners, need to implement the findings. We explored this possibility in the current article. We conducted a scoping review to assess the extent to which the information needed for implementation is reported in psychological intervention articles. Results suggest psychological intervention articles report, at most, 64% of the information needed to implement interventions. We discuss the implications of this for both psychological theories and applying them in the world.
Anterior Plate-Screws and Lower Postoperative T1 Slope Affect Cervical Allospacer Failures in Multi-Level ACDF Surgery: Anterior Versus Posterior Fixation
Authors: Suk Kyung-Soo , Jimenez Kathryn Anne , Jo Je Hyung , Kim Hak-Sun , Lee Hwan-Mo , Moon Seong-Hwan , Lee Byung Ho
Published: March 2021

Study Design:

Prospective observational study.

Objective:

In ACDF, graft failure and subsidence are common complications of surgery. Depending on the cervical fixation, different biomechanical characteristics are applied on the grafts. This aims to describe the incidence of cervical spacer failure in patients with cervical degenerative condition according to the cervical fixation method and sagittal balance.

Method:

From November 2011 to December 2015, 262 patients who underwent cervical spine surgery were enrolled prospectively. Patients were divided into 3 groups based on fixation method: anterior plate/screw (APS), posterior lateral mass screw (LMS), pedicle screw (PPS) groups. Serial X-rays and CT scans were utilized to evaluate radiologic outcomes.

Results:

Mean patient ages were 56.1 years in the APS group, 61.5 years in the LMS group, and 57.6 years in the PPS group ( P = 0.002). Allospacer failure was most common in the APS group, compared to the LMS and PPS groups (chi-square, P = 0.038). Longer fusion level was associated with greater allospacer failure (Baseline 2 level surgery; Odds ratio (OR) 3.4 in 3 level, 15.2 in 4 level, P = 0.036,0.013). Higher T1 slope was correlated with less allospacer failure (OR 0.875, P = 0.001). ORs of allospacer failure in the LMS and PPS groups were 0.04 and 0.02, respectively, ( P = 0.01, 0.01), compared with the APS group.

Conclusion:

This study was able to show that allospacer failure in multi-level ACDF surgery is more common with a longer fusion length, less postoperative T1 slope, and an anterior plate-screws technique. Pedicle screws provided the best biomechanical stability among the 3 constructs.
End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA
Authors: Kostakoglu Lale , Martelli Maurizio , Sehn Laurie H. , Belada David , Carella Angelo-Michele , Chua Neil , Gonzalez-Barca Eva , Hong Xiaonan , Pinto Antonio , Shi Yuankai , Tatsumi Yoichi , Knapp Andrea , Mattiello Federico , Nielsen Tina , Sahin Deniz , Sellam Gila , Oestergaard Mikkel Z. , Vitolo Umberto , Trněný Marek
Published: March 2021

GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)–based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP. Patients received a mandatory fluoro-2-deoxy-d-glucose–PET/computed tomography scan at baseline and end of treatment. After a median follow-up of 29 months, the numbers of independent review committee–assessed PFS and OS events in the entire cohort were 416 (29.3%) and 252 (17.8%), respectively. End-of-treatment PET CR was highly prognostic for PFS and OS according to Lugano 2014 criteria (PFS: hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.19-0.38; P < .0001; OS: HR, 0.12; 95% CI, 0.08-0.17; P < .0001), irrespective of international prognostic index score and cell of origin. In conclusion, the results from this prospectively acquired large cohort corroborated previously published data from smaller sample sizes showing that end-of-treatment PET CR is an independent predictor of PFS and OS and a promising prognostic marker in DLBCL. Long-term survival analysis confirmed the robustness of these data over time. Additional meta-analyses including other prospective studies are necessary to support the substitution of PET CR for PFS as an effective and practical surrogate end point. This trial was registered at www.clinicaltrials.gov as #NCT01287741.
Disruption of CSF-1R signaling inhibits growth of AML with inv(16)
Authors: Simonis Alexander , Russkamp Norman F. , Mueller Jan , Wilk C. Matthias , Wildschut Mattheus H. E. , Myburgh Renier , Wildner-Verhey van Wijk Nicole , Mueller Rouven , Balabanov Stefan , Valk Peter J. M. , Theocharides Alexandre P. A. , Manz Markus G.
Published: March 2021

Key Points

Human inv(16) AML cells express CSF-1R and are exposed to CSF-1 in vivo. Inhibition of CSF-1R signaling reduces viability of inv(16) AML cells in vitro and in therapeutic settings in humanized mice in vivo.
A machine learning-based gene signature of response to the novel alkylating agent LP-184 distinguishes its potential tumor indications
Authors: Kathad Umesh , Kulkarni Aditya , McDermott Joseph Ryan , Wegner Jordan , Carr Peter , Biyani Neha , Modali Rama , Richard Jean-Philippe , Sharma Panna , Bhatia Kishor
Published: March 2021

Background

Non-targeted cytotoxics with anticancer activity are often developed through preclinical stages using response criteria observed in cell lines and xenografts. A panel of the NCI-60 cell lines is frequently the first line to define tumor types that are optimally responsive. Open data on the gene expression of the NCI-60 cell lines, provides a unique opportunity to add another dimension to the preclinical development of such drugs by interrogating correlations with gene expression patterns. Machine learning can be used to reduce the complexity of whole genome gene expression patterns to derive manageable signatures of response. Application of machine learning in early phases of preclinical development is likely to allow a better positioning and ultimate clinical success of molecules. LP-184 is a highly potent novel alkylating agent where the preclinical development is being guided by a dedicated machine learning-derived response signature. We show the feasibility and the accuracy of such a signature of response by accurately predicting the response to LP-184 validated using wet lab derived IC50s on a panel of cell lines.

Results

We applied our proprietary RADR® platform to an NCI-60 discovery dataset encompassing LP-184 IC50s and publicly available gene expression data. We used multiple feature selection layers followed by the XGBoost regression model and reduced the complexity of 20,000 gene expression values to generate a 16-gene signature leading to the identification of a set of predictive candidate biomarkers which form an LP-184 response gene signature. We further validated this signature and predicted response to an additional panel of cell lines. Considering fold change differences and correlation between actual and predicted LP-184 IC50 values as validation performance measures, we obtained 86% accuracy at four-fold cut-off, and a strong (r = 0.70) and significant (p value 1.36e−06) correlation between actual and predicted LP-184 sensitivity. In agreement with the perceived mechanism of action of LP-184, PTGR1 emerged as the top weighted gene.

Conclusion

Integration of a machine learning-derived signature of response with in vitro assessment of LP-184 efficacy facilitated the derivation of manageable yet robust biomarkers which can be used to predict drug sensitivity with high accuracy and clinical value.
Women’s perception of continuity of team midwifery care in Iran: a qualitative content analysis
Authors: Shahinfar Sholeh , Abedi Parvin , Najafian Mahin , Abbaspoor Zahra , Mohammadi Eesa , Alianmoghaddam Narges
Published: March 2021

Background

Understanding the pregnant women’s perception of continuity of team midwifery care is necessary for introducing and implementing this model of midwife-led care in the Iranian maternity services. This qualitative study aims to explore women’s perception of continuity of team midwifery care in Iran.

Methods

This research is a qualitative study conducted in Iran to explore women’s perception of continuity of team midwifery care during pregnancy, birth and postpartum from October 2019 to August 2020. Fifteen semi-structured interviews were conducted with women individually in private midwifery clinic through a purposive sampling method. Interviews were digitally recorded and transcribed verbatim in Persian and analyzed using conventional content analysis.

Results

From the data analysis, two themes, four main categories, and nine subcategories emerged. The themes were “Maternal empowerment” and “Mother’s satisfaction during the transition from pregnancy to motherhood”. The first theme included two categories of improving self-efficacy during antenatal education classes and the effective midwife-mother interaction. The second theme composed of two categories of satisfaction with the process of pregnancy, childbirth and postpartum as well as satisfaction with motherhood.

Conclusion

Findings of this qualitative study highlight the effectiveness of continuity of team midwifery model of care for promoting empowerment and satisfaction in women during pregnancy, birth and postpartum. The results of this study could pave the way for developing, introducing and implementing the midwife-led continuity models of care in Iran.
Short-term outcomes and safety of radiotherapy for immediate breast reconstruction with autologous flap transfer following breast-conserving surgery
Authors: Zhang Shu-Ling , Song Jun , Wang Yan-Ru , Guo Yi-Jia , Zhao Jian-Zhu , Sun Li , Huang Le-Tian , Ma Jie-Tao , Han Cheng-Bo
Published: March 2021

Background

The outcomes of immediate autologous breast reconstruction (IABR) after partial mastectomy followed by postoperative radiotherapy (RT) in terms of aesthetics, treatment-related complications, and local control are unclear. In this study, we evaluated the efficacy of IABR after partial mastectomy with or without breast RT, and thus the impact of radiation on autologous flap transfer.

Method

A retrospective cohort study involving consecutive breast cancer patients who underwent IABR after partial mastectomy between July 2011 and December 2017 at Shengjing Hospital was performed. Patients were divided into two groups based on whether or not they received RT after IABR. We compared aesthetic outcomes and changes in the flap size over the three-dimensional coordinates at various timepoints (pre-RT, 1, 6, and 12 months post-RT), as well as postoperative complications, survival, and recurrence rates between the two groups.

Results

In total, 84 breast cancer patients were enrolled, with 32 patients in the RT group and 52 in the non-RT group. At a median follow-up time of 33.3 months, no significant difference was found in the rate of regional recurrence between the two groups (3.13% vs. 3.85%, P = 1.00), and no local recurrences occurred in either group. At the timepoints pre-RT, 1, and 6 months post-RT (approximately 4, 7, and 12 months after IABR, respectively), 77 (91.7%), 70 (83.3%), and 83 (98.8%) patients, respectively, had achieved very good or good cosmetic outcomes, and only changes in breast skin color at 1 month after RT significantly differed between the RT and non-RT groups, with very good or good cosmetic result rates of 62.5% vs. 96.2%, respectively (P < 0.001). No significant difference in the reduction of flap size was observed at any timepoint between the two groups. There were no significant differences between the two groups in the rates of postoperative complications including necrosis of the flap, infection, hematoma, or seroma (all P > 0.05). Additionally, no grade 3 or greater RT-associated adverse events occurred during or after RT.

Conclusion

RT following IABR provides aesthetically satisfactory results without intolerable adverse complications and may safely be performed in patients who underwent IABR after partial mastectomy.
IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
Authors: Shahangian Kimia , Ngan David A. , Chen H. H. Rachel , Oh Yeni , Tam Anthony , Wen Jing , Cheung Chung , Knight Darryl A. , Dorscheid Delbert R. , Hackett Tillie L. , Hughes Michael R. , McNagny Kelly M. , Hirota Jeremy A. , Niikura Masahiro , Man S. F. Paul , Sin Don D.
Published: March 2021

Background

Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of Th2 signalling, improved their outcomes.

Methods

Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy.

Results

Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p < .05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection.

Conclusion

Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease.
Time-dependent efficacy of combination of silver-containing hydroxyapatite coating and vancomycin on methicillin-resistant Staphylococcus aureus biofilm formation in vitro
Authors: Hashimoto Akira , Miyamoto Hiroshi , Kii Sakumo , Kobatake Tomoki , Shobuike Takeo , Noda Iwao , Sonohata Motoki , Mawatari Masaaki
Published: March 2021

Objective

We developed a silver-containing hydroxyapatite (Ag-HA) coating to prevent periprosthetic joint infection (PJI). Methicillin-resistantStaphylococcus aureus(MRSA) is the main PJI-causing bacteria. Previously, we had reported the combined effect of Ag-HA coating and vancomycin (VCM) on MRSA biofilm formation 24 h after MRSA inoculation. In this study, we investigated the time-dependent efficacy of Ag-HA coating and VCM on MRSA biofilm formation on Ti discs in vitro by three-dimensional confocal laser scanning microscopic analysis.

Results

For the Ti VCM and HA VCM groups, the total biofilm volumes per area at 96 h after MRSA inoculation were significantly larger than those at 48 h after MRSA inoculation, respectively (p < 0.001). In contrast, for the Ag-HA VCM group, the total biofilm volume per area at 96 h was significantly smaller than that at 48 h (p < 0.0001). Moreover, 96 h after MRSA inoculation, the total biofilm volume per area of the Ag-HA VCM groups was significantly smaller than those of the Ti VCM and HA VCM groups (p < 0.0001). Thus, the combination of Ag-HA and VCM might be useful for the prevention of MRSA-associated PJI.
Weight management intervention identifies association of decreased DNA methylation age with improved functional age measures in older adults with obesity
Authors: Petersen Curtis L. , Christensen Brock C. , Batsis John A.
Published: March 2021

Background

Assessing functional ability is an important component of understanding healthy aging. Objective measures of functional ability include grip strength, gait speed, sit-to-stand time, and 6-min walk distance. Using samples from a weight loss clinical trial in older adults with obesity, we examined the association between changes in physical function and DNA-methylation-based biological age at baseline and 12 weeks in 16 individuals. Peripheral blood DNA methylation was measured (pre/post) with the Illumina HumanMethylationEPIC array and the Hannum, Horvath, and PhenoAge DNA methylation age clocks were used. Linear regression models adjusted for chronological age and sex tested the relationship between DNA methylation age and grip strength, gait speed, sit-to-stand, and 6-min walk.

Results

Participant mean weight loss was 4.6 kg, and DNA methylation age decreased 0.8, 1.1, and 0.5 years using the Hannum, Horvath, and PhenoAge DNA methylation clocks respectively. Mean grip strength increased 3.2 kg. Decreased Hannum methylation age was significantly associated with increased grip strength (β = −0.30, p = 0.04), and increased gait speed (β = 0.02, p = 0.05), in adjusted models. Similarly, decreased methylation age using the PhenoAge clock was associated with significantly increased gait speed (β = 0.02, p = 0.04). A decrease in Horvath DNA methylation age and increase in physical functional ability did not demonstrate a significant association.

Conclusions

The observed relationship between increased physical functional ability and decreased biological age using DNA methylation clocks demonstrate the potential utility of DNA methylation clocks to assess interventional approaches to improve health in older obese adults.

Trial registration: National Institute on Aging (NIA), NCT03104192. Posted April 7, 2017, https://clinicaltrials.gov/ct2/show/NCT03104192
The angiogenic potential of CD271+ human adipose tissue-derived mesenchymal stem cells
Authors: Smith Richard J. P. , Faroni Alessandro , Barrow James R. , Soul Jamie , Reid Adam J.
Published: March 2021

Background

Autologous fat grafting is often a crucial aspect of reconstructive and aesthetic surgeries, yet poor graft retention is a major issue with this technique. Enriching fat grafts with adipose tissue-derived mesenchymal stem cells (AD-MSCs) improves graft survival—however, AD-MSCs represent a heterogeneous population. Selection of subpopulations of AD-MSCs would allow the targeting of specific AD-MSCs that may benefit fat graft survival more than the general AD-MSC population.

Methods

Human AD-MSCs were selected for the surface marker CD271 using magnetic-activated cell sorting and compared to the CD271 negative phenotype.  These subpopulations were analysed for gene expression using Real-Time qPCR and RNA sequencing; surface marker characteristics using immunostaining; ability to form tubules when cultured with endothelial cells; and gene and protein expression of key angiogenic mediators when cultured with ex-vivo adipose tissue.

Results

Human AD-MSCs with the surface marker CD271 express angiogenic genes at higher levels, and inflammatory genes at lower levels, than the CD271− AD-MSC population. A greater proportion of CD271+ AD-MSCs also possess the typical complement of stem cell surface markers and are more likely to promote effective neoangiogenesis, compared to CD271− AD-MSCs.

Conclusion

Enriching grafts with the CD271+ AD-MSC subpopulation holds potential for the improvement of reconstructive and aesthetic surgeries involving adipose tissue.
Identification of a potent antagonist of smoothened in hedgehog signaling
Authors: Fan Junwan , Li Haowen , Kuang Lun , Zhao Zichen , He Wenyan , Liu Chen , Wang Yongjun , Cheng Steven Y. , Chen Wei
Published: March 2021

Background

Hedgehog signaling is essential to the regulation of embryonic development, tissue homeostasis, and stem cell self-renewal, making it a prime target for developing cancer therapeutics. Given the close link between aberrant Hedgehog signaling and cancers, many small molecular compounds have been developed to inhibit Smoothened, a key signal transducer of this pathway, for treating cancer and several such compounds have been approved by the United States Food and Drug Administration (GDC-0449 and LDE-225). However, acquired drug resistance has emerged as an important obstacle to the effective use of these first generation Hedgehog pathway blockers. Thus, new Smoothened inhibitors that can overcome such resistance is an urgent need going forward.

Results

We established the Smoothened/βarrestin2-GFP high-throughput screening platform based on the mechanistic discovery of Hedgehog signaling pathway, and discovered several active small molecules targeting Smoothened including 0025A. Here we show that 0025A can block the translocation of βarrestin2-GFP to Smoothened, displace Bodipy-cyclopamine binding to wild-type Smoothened or mutant Smoothened-D473H, reduce the accumulation of Smo on primary cilia and the expression of Gli upon Hedgehog stimulation. In addition, we show that 0025A can effectively suppress hair follicle morphogenesis and hair growth in mice.

Conclusions

Our results demonstrate that 0025A is a potent antagonist targeting Smoothened wild-type and mutant receptors in the Hedgehog signaling pathway and may provide a new therapy for refractory cancers.
In respond to commensal bacteria: γδT cells play a pleiotropic role in tumor immunity
Authors: Liu Yongting , Han Ying , Zeng Shan , Shen Hong
Published: March 2021

γδT cells are a mixture of innate programming and acquired adaptability that bridge the adaptive and innate immune systems. γδT cells are mainly classified as tissue-resident Vδ1 or circulating Vδ2 γδT cells. In the tumor microenvironment, tumor immunity is influenced by the increased quantity and phenotype plasticity of γδT cells. Commensal bacteria are ubiquitous in the human body, and they have been confirmed to exist in various tumor tissues. With the participation of commensal bacteria, γδT cells maintain homeostasis and are activated to affect the development and progression of tumors. Here, we summarize the relationship between γδT cells and commensal bacteria, the potential protumor and antitumor effects underlying γδT cells, and the new developments in γδT cell-based tumor therapy which is expected to open new opportunities for tumor immunotherapy.
Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside
Authors: Carteaux Guillaume , Pons Manuella , Morin François , Tuffet Samuel , Lesimple Arnaud , Badat Bilal , Haudebourg Anne-Fleur , Perier François , Deplante Yvon , Guillaud Constance , Schlemmer Frédéric , Fois Elena , Mongardon Nicolas , Khellaf Mehdi , Jaffal Karim , Deguillard Camille , Grimbert Philippe , Huguet Raphaëlle , Razazi Keyvan , de Prost Nicolas , Templier François , Beloncle François , Mercat Alain , Brochard Laurent , Audard Vincent , Lim Pascal , Richard Jean-Christophe , Savary Dominique , Mekontso Dessap Armand
Published: March 2021

Background

We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter (“Filter Frugal CPAP”, FF-CPAP) in and out the ICU.

Methods

(1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak.

Results

Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient’s work of breathing (6–34%) needed to sustain the tidal volume, depending on the filter’s resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test).

Conclusion

Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.
Policing and public health calls for service in Philadelphia
Authors: Ratcliffe Jerry H.
Published: March 2021

This contribution outlines various spatial and temporal aspects of medical or public-health related calls for service from the public to police in Philadelphia in 2019. These incidents comprise about 8% of the police department’s workload that originates from the public. Calls appear to be highly concentrated in a few areas, and specifically the Center City and Kensington neighborhoods. They are also more likely to occur late afternoon and evening. The article shows that some medical or public health activity initially masquerades as crime or other policing work and some events eventually determined to be police/crime activity can initially appear to be public health related. About 20% of activity in this area does not appear predictable from the initial call type as handled by police dispatch.
An online survey to explore the awareness and acceptance of geothermal energy among an educated segment of the population in five European and American countries
Authors: Balzan-Alzate D. , López-Sánchez J. , Blessent D. , Raymond J. , Dezayes C. , Portela J. P. , Restrepo E. Ramírez , Rendón D. Moreno , Malo M. , Goderniaux P. , Daniele L. , Le Borgne T.
Published: March 2021

Advances in new technologies and the desire to achieve a sustainable and safe energy supply, enable communities to transition from conventional to renewable resources, such as geothermal energy. Perception and acceptance amongst different audiences have a high impact on the feasibility of energy projects, which is an important aspect to analyze. For this reason, this study focuses on describing the level of awareness and acceptance of deep geothermal energy within an educated segment of the population in five European and American countries (Canada, Colombia, Chile, Belgium, and France) at different stages of geothermal development. This study was conducted through an online survey, which was targeted to post-secondary students and professionals. Some of the most significant conclusions are: (1) there is a high degree of awareness of geothermal energy among the respondents in Chile and Canada, a medium level in Belgium and France, and a low one in Colombia; (2) there is a favorable acceptance of a geothermal project in each country, even when hydraulic stimulation is considered; (3) environmental aspects and community safety are the most important issues that must be addressed to support a pilot geothermal project.
Healing the next generation: an adaptive agent model for the effects of parental narcissism
Authors: Jabeen Fakhra , Gerritsen Charlotte , Treur Jan
Published: March 2021

Parents play an important role in the mental development of a child. In our previous work, we addressed how a narcissistic parent influences a child (online/offline) when (s)he is happy and admires the child. Now, we address the influence of a parent who is not so much pleased, and may curse the child for being the reason for his or her unhappiness. An abusive relationship with a parent can also cause trauma and poor mental health of the child. We also address how certain coping behaviors can help the child cope with such a situation. Therefore, the aim of the study is threefold. We present an adaptive agent model of a child, while incorporating the concept of mirroring through social contagion, the avoidance behaviors from a child, and the effects of regulation strategies to cope with stressful situations.
Negative-pressure wound therapy in combination with bronchial occlusion to treat bronchopleural fistula: a case report
Authors: Iwasaki Masashi , Shimomura Masanori , Ii Tsunehiro
Published: March 2021

Background

Bronchopleural fistula, which usually accompanies bronchial fistula and empyema, is a severe complication of lung cancer surgery. Negative-pressure wound therapy can enhance drainage and reduce the empyema cavity, potentially leading to early recovery. This therapy is not currently indicated for bronchopleural fistulas because of the risk of insufficient respiration due to air loss from the fistula.

Case presentation

A 73-year-old man, who was malnourished because of peritoneal dialysis, was referred to our hospital for the treatment of lung cancer. Right lower lobectomy with mediastinal lymph node dissection was performed via posterolateral thoracotomy, and the bronchial stump was covered with the intercostal muscle flap. His postoperative course was uneventful and he was discharged. However, he was readmitted to our hospital because of respiratory failure and diagnosed as having bronchopleural fistula on the basis of the bronchoscopic finding of a 10-mm hole at the membranous portion of the inlet of the remnant lower lobe bronchus. Thus, thoracotomy debridement and open window thoracostomy were immediately performed. After achieving infection control, bronchial occlusion was performed using fibrin glue and a polyglycolic acid sheet was inserted through a fenestrated wound. Bronchial fistula closure was observed on bronchoscopy; therefore, a negative-pressure wound therapy system was applied to close the fenestrated wound. The collapsed lung was re-expanded and the granulation tissue around the wound increased; therefore, thoracic cavity size decreased and thoracoplasty using the latissimus dorsi was performed.

Conclusions

This bronchopleural fistula was treated successfully after a right lower lobectomy using an extra-pleural bronchial occlusion and negative-pressure wound therapy.
Correction to: The effect of glucocorticoid therapy on mortality in patients with rheumatoid arthritis and concomitant type II diabetes: a retrospective cohort study
Authors: Costello Ruth E. , Marsden Antonia , Movahedi Mohammad , Lunt Mark , Humphreys Jenny H. , Emsley Richard , Dixon William G.
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Investigation of bioactivities of endophytes of Ficus carica L. Fam Moraceae
Authors: Abdou Randa , Mojally Mariam , Attia Gouda H.
Published: March 2021

Background

The medicinal plant Ficus carica L., inhabiting southwest regions of Asia, is known for its wide ethnopharmacological applications. In traditional medicine, it has been applied as a treatment of respiratory, gastrointestinal and cardiovascular disorders, among others. Recent studies confirmed antimicrobial and anticancer activities for the plant extract. To find out whether endophytes of F. carica contribute to its biological activities, endophytes of the aerial parts of the plant were isolated and examined for anticancer and antimicrobial effects.

Results

The isolated species were identified as Chaetomium globosum, Penicillium oxalicum, Alternaria alternata, Fusarium proliferatum and Aspergillus neoniger. An anticancer assay was carried out on the extracts of fungal strains against human umbilical vein endothelial cells (HUVEC), human immortalized myelogenous leukemia cell line (K-562) and human immortal cervical cancer cell line (HeLa). Results revealed antiproliferative effects for all endophytic strains against HUVEC and K-562 with GI50 values ranging from 4.75 to 13.75 µg mL−1 as well as cytotoxicity against HeLa with CC50 ranging from 8.25 to 18.75 µg mL−1. The antimicrobial activity of the extracts was tested against several test strains in agar diffusion assay, and MIC values were determined by the broth microdilution method. All strain extracts exerted antibacterial and antifungal activities with highest antifungal effect observed for A. neoniger extract (MIC = 3.75 µg mL−1).

Conclusions

These results support the assumption that endophytes of F. carica contribute to the plant’s reported antimicrobial and anticancer activities and its corresponding applications in traditional medicine.
An efficient hybrid system for anomaly detection in social networks
Authors: Rahman Md. Shafiur , Halder Sajal , Uddin Md. Ashraf , Acharjee Uzzal Kumar
Published: March 2021

Anomaly detection has been an essential and dynamic research area in the data mining. A wide range of applications including different social medias have adopted different state-of-the-art methods to identify anomaly for ensuring user’s security and privacy. The social network refers to a forum used by different groups of people to express their thoughts, communicate with each other, and share the content needed. This social networks also facilitate abnormal activities, spread fake news, rumours, misinformation, unsolicited messages, and propaganda post malicious links. Therefore, detection of abnormalities is one of the important data analysis activities for the identification of normal or abnormal users on the social networks. In this paper, we have developed a hybrid anomaly detection method named DT-SVMNB that cascades several machine learning algorithms including decision tree (C5.0), Support Vector Machine (SVM) and Naïve Bayesian classifier (NBC) for classifying normal and abnormal users in social networks. We have extracted a list of unique features derived from users’ profile and contents. Using two kinds of dataset with the selected features, the proposed machine learning model called DT-SVMNB is trained. Our model classifies users as depressed one or suicidal one in the social network. We have conducted an experiment of our model using synthetic and real datasets from social network. The performance analysis demonstrates around 98% accuracy which proves the effectiveness and efficiency of our proposed system.
Variability of computed tomography angiography coverage of lung parenchyma in acute stroke
Authors: Pfaff Johannes A. R. , Füssel Bianka , Harlan Marcial E. , Hubert Alexander , Bendszus Martin
Published: March 2021

Background

Computed tomography angiography (CTA) of the head and neck during acute ischemic stroke (AIS) usually includes visualization of lung apices. The possibility to evaluate for pulmonary changes, e.g. peripheral ground-glass and consolidative opacities suggestive of coronavirus disease 2019 (COVID-19)–related pneumonia, depends on the area of the lung covered by CTA.

Methods

We performed an analysis of a real-world scenario assessing the variability of lung coverage on CTA in patients presenting with AIS to a comprehensive stroke center (CSC) or to one of eight primary stroke centers (PSC) within a teleradiological network covered by the comprehensive stroke center in 2019.

Results

Our final analysis included n = 940 CTA, and in n = 573 (61%) merely lung apices were covered. In 19/940 (2%) of patients no lung tissue was covered by CTA. CTA scanning protocols in the CSC began significantly more frequently at the level of the ascending aorta (CSC: n = 180 (38.2%), PSC: n = 127 (27.1%), p-value < 0.001) and the aortic arch (CSC: n = 140 (29.7%), PSC: n = 83 (17.7%), p-value < 0.001), and by this covered less frequently the lower lobes compared to CTA acquired in one of the PSC.

Conclusions

In our pre-COVID-19 pandemic representative stroke patient cohort, CTA for AIS covered most often only lung apices. In 37% of the patients CTA visualized at least parts of the lower lobes, the lingula or the middle lobe allowing for a more extensive assessment of the lungs.
Network meta-analysis (NMA) comparing the efficacy of enzalutamide versus apalutamide, darolutamide, and bicalutamide for treatment of nonmetastatic (nm) castration-resistant prostate cancer (CRPC).
Authors: Beer Tomasz M. , Saad Fred , Sternberg Cora N. , Hussain Maha H. A. , Ganguli Arijit , Bhadauria Hemant Singh , Oh Mok , Skaltsa Konstantina , Tombal Bertrand
Published: March 2021

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Background: Enzalutamide is a potent androgen receptor (AR) inhibitor, targeting multiple steps in AR signaling. In recent years, the EMA and FDA approved enzalutamide for the management of adults with CRPC, irrespective of metastatic status, based on the Phase 3 PROSPER clinical trial results. To provide indirect evidence on the relative efficacy of enzalutamide vs bicalutamide or the second-generation AR antagonists apalutamide and darolutamide for the management of nmCRPC, a NMA was performed using published data from their Phase 3 clinical trials. Methods: NMA enables indirect comparison of ≥3 interventions across a network of studies, identified by systematic literature review and based on a common comparator, to estimate relative effects between interventions. This NMA compared data from PROSPER (enzalutamide vs placebo [PBO]), SPARTAN (apalutamide vs PBO), ARAMIS (darolutamide vs PBO), and STRIVE (enzalutamide vs bicalutamide) studies, following NICE technical support document 2. Four key endpoints (metastasis-free survival [MFS], overall survival [OS], time to prostate-specific antigen progression [TTPP], and time to first use of cytotoxic chemotherapy [TTCH]) were assessed. It was assumed that there was no variation between studies that could influence the size of treatment effect. Fixed-effect models were developed and implemented under a Bayesian framework. Results: MFS, OS, and TTCH outcomes of PROSPER, SPARTAN, and ARAMIS were compared between androgen deprivation treatment alone and in combination with enzalutamide/apalutamide/darolutamide. TTPP of PROSPER, SPARTAN, ARAMIS, and STRIVE was compared between enzalutamide, apalutamide, darolutamide, bicalutamide, and PBO. Enzalutamide showed significant benefit vs PBO for all endpoints measured (median hazard ratio [HR] 0.29, 0.73, 0.54, 0.07 for MFS, OS, TTCH, TTPP respectively, Table), vs darolutamide for MFS HR 0.71, and vs darolutamide HR 0.51 and bicalutamide HR 0.18 for TTPP. OS for enzalutamide vs apalutamide was not statistically different HR 0.94. Conclusions: Enzalutamide showed significant therapeutic benefit; MFS, OS, TTCH, and TTPP were better vs PBO and MFS and/or TTPP were longer compared to darolutamide and bicalutamide. No statistically significant differences were observed between enzalutamide and apalutamide. This NMA may facilitate the development and testing of treatment strategies for nmCRPC. [Table: see text]
Final results of a phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and NOX66 in men with end-stage metastatic castration-resistant prostate cancer (LuPIN trial).
Authors: Pathmanandavel Sarennya , Crumbaker Megan , Yam Andrew On Wah , Rofe Christopher , Ho Bao , Chan Wai Ling , Sharma Shikha , Hickey Adam James , Kongrak Kamonwan , Ratnayake Lalith , Kwan Edmond Michael , Azad Arun , Eu Peter , Nguyen Andrew , Joshua Anthony M. , Emmett Louise
Published: March 2021

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Background: 177LuPSMA – 617 is a promising therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently and synergistic combination therapy may improve outcomes. We combined 177LuPSMA – 617 with idronoxil (NOX66), an inhibitor of external NADH oxidase type 2 with radio-sensitizing properties. We present the final safety and efficacy results. Methods: Men with progressive mCRPC after androgen signalling inhibition (ASI) and taxane chemotherapy were enrolled. Key inclusion criteria were: PSMA PET/CT intensity SUV max > 15 with no discordant disease on FDG PET/CT, haemoglobin > 100g/L, platelets > 100x109/L and eGFR > 40mls/min. Enrolled patients received up to six doses of 177 Lu-PSMA 617 (7.5Gbq) day 1 every 6 weeks in combination with NOX66 days 1-10 each cycle. Cohort 1 (n = 8) received 400mg NOX66. Following safety reviews the doses were escalated in cohorts 2 (n = 24) and 3 (n = 24) to 800mg and 1200mg of NOX66, respectively. Blood samples were prospectively collected for androgen receptor splice variant 7 (ARV7) expression. PSMA and FDG PET/CT were performed at study entry and on progression. The primary outcomes were safety and tolerability; the secondary outcomes evaluated were efficacy, pain scores, and quality of life. Results: Of the 56 men enrolled, all had received prior treatment with ASI and docetaxel, and 95% (53/56) had prior cabazitaxel. 96% (54/56) patients received ≥2 cycles and 46% (26/56) completed six cycles of treatment. Adverse events are summarized in the table below. PSA responses were as follows: 86% (48/56) had any PSA reduction and 61% (34/56) had > 50% PSA reduction. 84% (47/56) have had PSA progression to date with median follow up 18.9 months (95% CI 11.9-25.8). Median PSA PFS was 7.5 months (95% CI 6.0-9.0). 55% (31/56) have died and median overall survival was 19.7 months (95% CI 10.7-28.7). 34/56 men had baseline pain scores ≥3, of whom 53% (18/34) had significant reduction in pain indicators. There was no correlation between quantitative PET results and either PSA > 50% response, PSA PFS or OS. Conclusions: The combination of 177 Lu-PSMA 617 + NOX66 appears safe and efficacious in men with heavily pre-treated mCRPC. Exploratory analysis of ARV7 expression and quantitative PET imaging markers of treatment response and resistance is in progress. Clinical trial information: ACTRN12618001073291. [Table: see text]