bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of amalgam contamination and different surface modifications on microleakage of dentin bonded to bulk fill composite when using different adhesive protocols
Authors: Alshehri Nojoud , Aljamhan Abdullah , Bin-Shuwaish Mohammed 
Published: May 2022

Abstract
Background
To evaluate the effect of amalgam contamination, different surface treatments, and adhesive protocols on dentin microleakage to bulk-fill composite resin material.

Methods
Forty teeth were fixed in (polyvinyl siloxane) PVS molds, and the Class II cavities were placed on mesial and distal aspects. Thirty teeth were restored by amalgam and thermocycled to 10,000 cycles (5 and 55 °C, 30-s dwell time). The rest were restored with Filtek one Bulk Fill composite without amalgam predecessor. Samples were divided into: G1 (dentin pretreated with 2% chlorhexidine gluconate), G2 (0.5 mm of dentin was removed), G3 (no surface modification), and G4 (control, where composite was bonded to sound dentin without amalgam predecessor.). Single Bond Universal Adhesive system was used to bond the composite material, by using the etch-and-rinse protocol in the mesial cavity preparation and self-etch protocol in the distal. Specimens underwent thermocycling for 5000 cycles, then embedded in silver nitrate and sectioned for stereomicroscope examination. Descriptive statistics, Mann–Whitney U test, and Kruskal–Wallis test were used to analyze the results at p < 0.05.

Results
The highest microleakage score values (4.00) were found in the G2, and G4 in etch-and-rinse protocol. While the lowest scores were found in G2 when using self-etching protocol (1.5). Lower microleakage values were associated with the chlorhexidine treatment group for both adhesive protocols. No significant differences were found between amalgam contaminated and non-contaminated groups.

Conclusions
Amalgam contamination did not affect microleakage. Self-etching adhesive protocol significantly reduced microleakage for all groups irrespective of the surface treatment. Chlorhexidine pretreatment improved microleakage for both adhesive protocols but had no significant effect.
Knowledge on risk factors and practice of early detection methods of breast cancer among graduating students of Debre Tabor University, Northcentral Ethiopia
Authors: Mehiret Gashaw , Molla Amsalu , Tesfaw Aragaw 
Published: May 2022

AbstractBackgroundBreast cancer is the greatest common cancer in women worldwide, with approximately 1.7 million new cases diagnosed each year in the world which accounts for 12% of all new cancer cases and 25% of all cancers in women. Even though the higher mortality rate of breast cancer in low and middle-income countries, the practice of early detection methods is low and the majority of the patients who appeared at an advanced stage of the disease need palliative care with little survival rates. However, evidence is scarce on the knowledge and practice of breast cancer early detection methods among women of reproductive age in Ethiopia. Therefore we aimed to assess the knowledge on risk factors and practice of early detection methods of breast cancer among female graduating students of Debre Tabor University.MethodsInstitution-based cross-sectional study was conducted. A stratified random sampling technique was used. Data were collected with a self-administer questionnaire. The collected data were processed and analyzed with the computer using SPSS version 25 software. Descriptive statistics were used to describe the socio-demographic information of participants. Binary and multivariable logistic regression with an adjusted odds ratio (AOR) and 95% confidence interval (CI) was used to identify factors associated with the outcome variable. Statistical significance was stated at p < 0.05.ResultA total of 270 female students participated in the study. The median age (± SD) was 24.63 years (± 1.26). All of the students heard about breast cancer and early detection methods. About 206 (76.67%) of the participants had good knowledge of breast self-examination. Mass media, health professionals, and friends in combination were the main source of information 172 (63.77%), only 110 (40.70%) of students performed a breast-self-examination and the rest did not perform it due to forgetting fullness and lack of knowledge. About 208 (77.1%) of the respondents respond family history is a risk factor for breast cancer. Being a health science student (AOR = 2.32; 95% CI: 2.12, 3.52), family history of breast problems (AOR = 3.41; 95% CI: 3.22, 8.33), and having a good level of knowledge (AOR = 1.83; 95% CI: 1.01, 5.68) were the factors associated with the practice of breast self-examination.ConclusionMost of the participants were unaware of the benefits, appropriate timing, and techniques of doing a breast self-examination. Health science students had better awareness & practice of breast self-examination than non-health science students. Trained health professionals must give focus on giving health information regarding risk factors of breast cancer and methods of early detection of breast cancer to the public & their clients.
Applying spectral fractal dimension index to predict the SPAD value of rice leaves under bacterial blight disease stress
Authors: Cao YiFei , Xu Huanliang , Song Jin , Yang Yao , Hu Xiaohui , Wiyao Korohou Tchalla , Zhai Zhaoyu 
Published: May 2022

AbstractBackgroundThe chlorophyll content is a vital indicator for reflecting the photosynthesis ability of plants and it plays a significant role in monitoring the general health of plants. Since the chlorophyll content and the soil–plant analysis development (SPAD) value are positively correlated, it is feasible to predict the SPAD value by calculating the vegetation indices (VIs) through hyperspectral images, thereby evaluating the severity of plant diseases. However, current indices simply adopt few wavelengths of the hyperspectral information, which may decrease the prediction accuracy. Besides, few researches explored the applicability of VIs over rice under the bacterial blight disease stress.MethodsIn this study, the SPAD value was predicted by calculating the spectral fractal dimension index (SFDI) from a hyperspectral curve (420 to 950 nm). The correlation between the SPAD value and hyperspectral information was further analyzed for determining the sensitive bands that correspond to different disease levels. In addition, a SPAD prediction model was built upon the combination of selected indices and four machine learning methods.ResultsThe results suggested that the SPAD value of rice leaves under different disease levels are sensitive to different wavelengths. Compared with current VIs, a stronger positive correlation was detected between the SPAD value and the SFDI, reaching an average correlation coefficient of 0.8263. For the prediction model, the one built with support vector regression and SFDI achieved the best performance, reaching R2, RMSE, and RE at 0.8752, 3.7715, and 7.8614%, respectively.ConclusionsThis work provides an in-depth insight for accurately and robustly predicting the SPAD value of rice leaves under the bacterial blight disease stress, and the SFDI is of great significance for monitoring the chlorophyll content in large-scale fields non-destructively.
Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets
Authors: Tie Yan , Tang Fan , Wei Yu-quan , Wei Xia-wei 
Published: May 2022

AbstractImmunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients are refractory or resistant to these therapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. Immunosuppressive cells such as myeloid-derived suppressive cells, tumor-associated macrophages, tumor-associated neutrophils, regulatory T cells (Tregs), and tumor-associated dendritic cells are critical factors correlated with immune resistance. In addition, cytokines and factors secreted by tumor cells or these immunosuppressive cells also mediate the tumor progression and immune escape of cancers. Thus, targeting these immunosuppressive cells and the related signals is the promising therapy to improve the efficacy of immunotherapies and reverse the immune resistance. However, even with certain success in preclinical studies or in some specific types of cancer, large perspectives are unknown for these immunosuppressive cells, and the related therapies have undesirable outcomes for clinical patients. In this review, we comprehensively summarized the phenotype, function, and potential therapeutic targets of these immunosuppressive cells in the tumor microenvironment.
Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients
Authors: Zhou Zhen , Ding Zhengping , Yuan Jie , Shen Shengping , Jian Hong , Tan Qiang , Yang Yunhai , Chen Zhiwei , Luo Qingquan , Cheng Xinghua , Yu Yongfeng , Niu Xiaomin , Qian Liqiang , Chen Xiaoke , Gu Linping , Liu Ruijun , Ma Shenglin , Huang Jia , Chen Tianxiang , Li Ziming , Ji Wenxiang , Song Liwei , Shen Lan , Jiang Long , Yu Zicheng , Zhang Chao , Tai Zaixian , Wang Changxi , Chen Rongrong , Carbone David P. , Xia Xuefeng , Lu Shun 
Published: May 2022

Abstract
Background
Neoadjuvant immunotherapy is emerging as novel effective intervention in lung cancer, but study to unearth effective surrogates indicating its therapeutic outcomes is limited. We investigated the genetic changes between non-small cell lung cancer (NSCLC) patients with varied response to neoadjuvant immunotherapy and discovered highly potential biomarkers with indicative capability in predicting outcomes.

Methods
In this study, 3 adenocarcinoma and 11 squamous cell carcinoma NSCLC patients were treated by neoadjuvant immunotherapy with variated regimens followed by surgical resection. Treatment-naive FFPE or fresh tissues and blood samples were subjected to whole-exome sequencing (WES). Genetic alternations were compared between differently-responded patients. Findings were further validated in multiple public cohorts.

Results
DNA damage repair (DDR)-related InDel signatures and DDR-related gene mutations were enriched in better-responded patients, i.e., major pathological response (MPR) group. Besides, MPR patients exhibited provoked genome instability and unique homologous recombination deficiency (HRD) events. By further inspecting alternation status of homology-dependent recombination (HR) pathway genes, the clonal alternations were exclusively enriched in MPR group. Additionally, associations between HR gene alternations, percentage of viable tumor cells and HRD event were identified, which orchestrated tumor mutational burden (TMB), mutational intratumor heterogeneity (ITH), somatic copy number alteration (SCNA) ITH and clonal neoantigen load in patients. Validations in public cohorts further supported the generality of our findings.

Conclusions
We reported for the first time the association between HRD event and enhanced neoadjuvant immunotherapy response in lung cancer. The power of HRD event in patient therapeutic stratification persisted in multifaceted public cohorts. We propose that HR pathway gene status could serve as novel and additional indicators guiding immune-neoadjuvant and immunotherapy treatment decisions for NSCLC patients.
Efficacy and safety of Lenzumestrocel (Neuronata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial
Authors: Nam Jae-Yong , Lee Tae Yong , Kim Kwijoo , Chun Sehwan , Kim Min Sung , Shin Jin-Hong , Sung Jung-Joon , Kim Byoung Joon , Kim Byung-Jo , Oh Ki-Wook , Kim Kyung Suk , Kim Seung Hyun 
Published: May 2022

Abstract
Background
A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS.

Methods
ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months.

Discussion
Lenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group.

Trial registration
ClinicalTrials.govNCT04745299. Registered on Feb 9, 2021.
Clinical Research Information Service (CRIS) KCT0005954. Registered on Mar 4, 2021.
Synthesis, molecular docking, and cytotoxicity of quinazolinone and dihydroquinazolinone derivatives as cytotoxic agents
Authors: Taayoshi Fahimeh , Iraji Aida , Moazzam Ali , Soleimani Meysam , Asadi Mehdi , Pedrood Keyvan , Akbari Mosayeb , Salehabadi Hafezeh , Larijani Bagher , Adibpour Neda , Mahdavi Mohammad 
Published: May 2022

Abstract
Background
Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a–e and dihydroquinazolinone 10a–f compounds were designed, synthesized as cytotoxic agents.

Methodology
All derivatives (5a–e and 10a–f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software.

Results and discussion
Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87–205.9 μM against HCT-116 cell line and 14.70–98.45 μM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 μM after 72 h, respectively, indicated the plausible activities of the synthesized compounds.

Conclusion
The compounds quinazolinone 5a–e and dihydroquinazolinone 10a–f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.
Current challenges of high-solid anaerobic digestion and possible measures for its effective applications: a review
Authors: Akinbomi Julius G. , Patinvoh Regina J. , Taherzadeh Mohammad J. 
Published: May 2022

AbstractThe attention that high solids anaerobic digestion process (HS-AD) has received over the years, as a waste management and energy recovery process when compared to low solids anaerobic digestion process, can be attributed to its associated benefits including water conservation and smaller digester foot print. However, high solid content of the feedstock involved in the digestion process poses a barrier to the process stability and performance if it is not well managed. In this review, various limitations to effective performance of the HS-AD process, as well as, the possible measures highlighted in various research studies were garnered to serve as a guide for effective industrial application of this technology. A proposed design concept for overcoming substrate and product inhibition thereby improving methane yield and process stability was recommended for optimum performance of the HS-AD process.
Evaluating standards for ‘serious’ disease for preimplantation genetic testing: a multi-case study on regulatory frameworks in Japan, the UK, and Western Australia
Authors: Nakasato Kate , Yamamoto Beverley Anne , Kato Kazuto 
Published: May 2022

Abstract
Background
A number of countries are leading the way in creating regulatory frameworks for preimplantation genetic testing (PGT). Among these countries, a point of consensus is that PGT may be used to avoid the birth of a child with a serious genetic disease. However, standards for evaluating disease severity in this context are not always clear. Considering the numerous medical and social implications of defining a standard for serious disease, our study sought out to better understand how disease severity for PGT is being defined by analyzing and comparing the regulatory landscapes for PGT in various countries.

Methods
We carried out a multi-case study analysis using policy documents from the UK, Western Australia, and Japan. Documentary analysis was used to analyze and compare these documents in terms of medical indications for PGT, evaluation methods of applications for PGT, and review frameworks used during the evaluation process, which includes the specific medical and social factors that are considered.

Results
Within our three case studies, medical indications for PGT are based on an estimated risk of the woman giving birth to a child with a genetic abnormality with known clinical deficits. Evaluation methods for approving applications for PGT include reference to a pre-approved list of genetic conditions (the UK) and case-by-case reviews (all case studies). Review frameworks for case-by-case reviews include reference to a list of considered factors (the UK and Western Australia) and a definition statement of disease severity (Japan), which provide insight into interpretations of disease severity in each context.

Conclusions
The results of this study point to the possible medical and social impacts of PGT regulatory frameworks on multiple stakeholders. Furthermore, it suggests that impacts in this case are not only caused by whether PGT is permitted or not, but also by the circumstances under which it is allowed and how decisions regarding its approval are made. Our results may serve as valuable insights for countries that already have established policy for PGT but are considering revision, countries that are without policy, and for discussions on related genetic and reproductive technologies.
Ex vivo permeation parameters and skin deposition of melatonin-loaded microemulsion for treatment of alopecia
Authors: Elshall Asmaa A. , Ghoneim Amira M. , Abdel-Mageed Heidi M. , Osman Rihab , Shaker Dalia S. 
Published: May 2022

Abstract
Background
Melatonin (MEL) is a powerful antioxidant molecule with anti-androgenic property. A microemulsion (ME) system loaded with MEL was designed for treatment of androgenic alopecia. Pseudo-ternary phase diagram was constructed, and ME formulae were developed using coconut oil, Tween 80 and PEG 400. In the present study, MEL ME was characterized and evaluated for droplet size, polydispersity index, zeta potential, morphology using TEM imaging. MEL ex vivo permeation study through rat skin followed by tape stripping for stratum corneum (SC) was performed for different ME formulae, to determine skin permeation parameters and detect SC-MEL deposition.

Results
Spherical and uniform particles of MEL-loaded microemulsion were formulated with high stability. In ex vivo permeation study, MEL ME exhibited low steady-state skin flux along with pronounced SC deposition which prevailed a controlled release manner.

Conclusion
The results suggested that MEL ME could be a promising candidate for further permeation and in vivo studies for androgenic alopecia treatment.
Hematopoietic Stem-Cell Transplant Utilization in Relapsed/Refractory Hodgkin Lymphoma: A Population-Level Analysis of Statewide Claims Data
Authors: Waheed Anem , Rodday Angie Mae , Kumar Anita J. , Miller Kenneth B. , Parsons Susan K. 
Published: May 2022

PURPOSE Although hematologic malignancies affect adults of all ages, few data exist on the real-world patterns of care for patients younger than 65 years in the United States. Understanding patterns of care from diagnosis through relapsed disease may provide insight about care across community and academic centers. We used a large statewide claims database to describe the path of Hodgkin lymphoma (HL) treatment among adults age < 65 years at diagnosis. METHODS We defined a cohort of commercially insured patients with HL who underwent hematopoietic stem-cell transplantation (HSCT) from 2009 to 2013 in the Massachusetts All-Payer Claims Database (APCD). The primary goals of our study were to accurately identify patients and their treatment patterns who had relapsed/refractory HL and underwent HSCT. We also characterized time to treatment failure and overall survival. RESULTS A total of 7,613 patients had International Classification of Diseases, Ninth Revision, diagnostic codes for HL. From our algorithm, we identified 117 patients as part of the final cohort who underwent autologous and/or allogeneic HSCT. Median age was 39.0 years and 50.4% were female. Initial therapy was identified for 68 of the 117 patients (58.1%). Most (> 74.4%) of the identified transplants were autologous, and 19 patients (16.2%) underwent allogeneic transplant, with or without prior autologous transplant. Of the 68 patients with initial therapy data, the median time to HSCT after completion of initial treatment was 223.5 days (Q1 = 151.5, Q3 = 414.5). CONCLUSION We used the Massachusetts APCD to create a cohort of patients age < 65 years with relapsed/refractory HL. Our findings support the use of APCD for the large-scale analysis of patient characteristics, treatment patterns, and outcomes for young adult patients with hematologic malignancies.