bluuebunny/crossref_metadata_2025 huggingface dataset:
A rapid review of best practices in the development of risk registers for public health emergency management
Authors: Kostirko Danylo , Zhao Jiawei , Lavigne Melissa , Hermant Benoit , Totten Liam
Published: November 2023

Introduction

Public health organizations (PHO) must prepare to respond to a range of emergencies. This represents an ongoing challenge in an increasingly connected world, where the scope, complexity, and diversity of public health threats (PHT) have expanded, as exemplified by the COVID-19 pandemic. Risk registers (RR) offer a framework for identifying and managing threats, which can be employed by PHOs to better identify and characterize health threats. The aim of this review is to establish best practices (BP) for the development of RRs within Public Health Emergency Management (PHEM).

Methods

In partnership with a librarian from Health Canada (HC), and guided by the Cochrane Rapid Review Guideline, journal articles were retrieved through MEDLINE, and a comprehensive search strategy was applied to obtain grey literature through various databases. Articles were limited to those that met the following criteria: published on or after January 1, 2010, published in the English language and published within an Organisation for Economic Co-operation and Development setting.

Results

57 articles were included for synthesis. 41 papers specifically discussed the design of RRs. The review identified several guidelines to establish RRs in PHEM, including forward-looking, multidisciplinary, transparent, fit-for-purpose, and utilizing a systems approach to analyze and prioritize threats. Expert consultations, literature reviews, and prioritization methods such as multi-criteria-decision-analysis (MCDA) are often used to support the development of RRs. A minimum five-year-outlook is applied to assess PHTs, which are revisited yearly, and iteratively revised as new knowledge arises.

Discussion

Based upon this review, RRs offer a systems approach to PHEM that can be expanded to facilitate the analysis of disparate threats. These approaches should factor in the multidimensionality of threats, need for multi-sectoral inputs, and use of vulnerability analyses that consider inherent drivers. Further research is needed to understand how drivers modify threats. The BPs and recommendations highlighted in our research can be adopted in the practice of PHEM to characterize the public health (PH) risk environment at a given point in time and support PHOs policy and decision-making.
Bacillus subtilis engineered for aerospace medicine: a platform for on-demand production of pharmaceutical peptides
Authors: Vallota-Eastman Alec , Bui Cynthia , Williams Philip M. , Valentine David L. , Loftus David , Rothschild Lynn
Published: November 2023

Biologics, such as pharmaceutical peptides, have notoriously short shelf lives, insufficient for long-duration space flight missions to the Moon or Mars. To enable the sustainable presence of humans on the Moon or Mars, we must develop methods for on-site production of pharmaceutical peptides in space, a concept we call the Astropharmacy. Here, we present a proof-of-concept for the first step needed: a low-mass system for pharmaceutical production designed to be stable in space. To demonstrate feasibility, we engineered strains of the space-hardy spore-forming bacterium, Bacillus subtilis, to secrete two pharmaceutical peptides important for astronaut health: teriparatide (an anabolic agent for combating osteoporosis) and filgrastim (an effective countermeasure for radiation-induced neutropenia). We found that the secretion peptides from the walM and yoqH genes of B. subtilis worked well for secreting teriparatide and filgrastim, respectively. In consideration of the Translational Research Institute for Space Health (TRISH) challenge to produce a dose equivalent in 24 h, dried spores of our engineered strains were used to produce 1 dose equivalent of teriparatide from a 2 mL culture and 1 dose equivalent of filgrastim from 52 mL of culture in 24 h. Further optimization of strain growth conditions, expression conditions, and promoter sequences should allow for higher production rates to be achieved. These strains provide the template for future optimization efforts and address the first step in the Astropharmacy, capable of on-site production, purification, and processing of biopharmaceutical compounds in platforms amenable for use in space.
Why Do Some People Have Down Syndrome?
Authors: Osorio Celeste Gonzalez , Harirama Mithila , Tandon Jasmine , Osier Nico
Published: November 2023

Down syndrome is a health condition in which there is an extra copy of the genetic material found on chromosome number 21. This can cause unrelated people with Down syndrome to share certain features such as being shorter and having small ears. Kids with Down syndrome often need extra help with some things, and may learn better in special classrooms. In this article, we will tell you about DS, sharing its key features. Then, to explain how people get DS, we will describe what normally happens when cells divide, specifically what special structures called chromosomes are supposed to do. Next, we will discuss what can go wrong during cell division and how these mistakes can lead to DS. Finally, we will talk about how DS is diagnosed.
The prevalence and risk factors of dental disease found in 100 miniature horses
Authors: Tinsley Tracy , Fogle Callie , Means Elaine , Robertston James
Published: November 2023

Introduction

Dental disease is a common condition affecting horses. Its prevalence and characteristics among most of the common breeds of horses and donkeys have been investigated and described in the literature, but information about the prevalence and etiology of dental disease of miniature horses is sparse.

Methods

To determine the prevalence and characteristics of dental disease of miniature horses, we performed oral and dental radiographic examinations on 100 miniature horses. The findings of these examinations were analyzed to determine the prevalence of dental disease and its correlation to age, sex, weight, body condition score, height at the withers, head length and head width. Older horses had a higher prevalence of dental disease, diastemata and crown elongations.

Results

The most common dental diseases detected in this population were crown elongation, oral mucosal ulceration, diastemata, class 1 malocclusion and hypodontia. Horses with a high body condition score had an increased likelihood of having a class 1 malocclusion. Horses with wider heads had a higher prevalence of dental disease and class 1 malocclusions.

Conclusion

Frequent oral examinations, starting at an early age, should be prioritized as a part of miniature horse preventive health care to decrease morbidity and slow progression of dental disease.
Evaluation of in vitro intrinsic radiosensitivity and characterization of five canine high-grade glioma cell lines
Authors: Cartiaux Benjamin , Deviers Alexandra , Delmas Caroline , Abadie Jérôme , Pumarola Battle Martí , Cohen-Jonathan Moyal Elizabeth , Mogicato Giovanni
Published: November 2023

Glioma is the most common primary brain tumor in dogs and predominantly affects brachycephalic breeds. Diagnosis relies on CT or MRI imaging, and the proposed treatments include surgical resection, chemotherapy, and radiotherapy depending on the tumor’s location. Canine glioma from domestic dogs could be used as a more powerful model to study radiotherapy for human glioma than the murine model. Indeed, (i) contrary to mice, immunocompetent dogs develop spontaneous glioma, (ii) the canine brain structure is closer to human than mice, and (iii) domestic dogs are exposed to the same environmental factors than humans. Moreover, imaging techniques and radiation therapy used in human medicine can be applied to dogs, facilitating the direct transposition of results. The objective of this study is to fully characterize 5 canine glioma cell lines and to evaluate their intrinsic radiosensitivity. Canine cell lines present numerous analogies between the data obtained during this study on different glioma cell lines in dogs. Cell morphology is identical, such as doubling time, clonality test and karyotype. Immunohistochemical study of surface proteins, directly on cell lines and after stereotaxic injection in mice also reveals close similarity. Radiosensitivity profile of canine glial cells present high profile of radioresistance.
The Role of Agile Values in Enhancing Good Governance in Public Administration during the COVID-19 Crisis: An International Survey
Authors: Tomaževič Nina , Kovač Polonca , Ravšelj Dejan , Umek Lan , Babaoğlu Cenay , Bohatá Marie , Hirsch Bernhard , Kulaç Onur , Nurlybaeva Guliya K. , Schäfer Fabienne-Sophie , Aristovnik Aleksander
Published: November 2023

This study aimed to analyse the impact of digitalisation on good governance with respect to selected local public administrations during the COVID-19 lockdown in the spring of 2020. The overriding assumption made is that agile values mediate the relationship between digitalisation and good governance on this level of public administration. Data were obtained through a web-based survey conducted between June and August 2020. The empirical analysis was facilitated by applying partial least squares structural equation modelling (PLS-SEM) on a sample of 761 public managers from five Central European countries (Czech Republic, Germany, Poland, Romania, Slovenia). The results show that digitalisation acted as an essential driver of good governance during the COVID-19 pandemic. Three out of four agile values—“employees and internal relationships”, “working public services”, and “change management”—were also shown to help make digitalisation more effective and thereby facilitate good governance. Despite some limitations (e.g., respondents’ subjective evaluations, the study only being performed during the first wave of the COVID-19 pandemic in the observed countries with different situations and consequent measures in response, and differences in the broader environment and local administration systems in the studied countries), the findings of the study are important given the lack of similar empirical studies. Public administrations should be digitalised and reformed in a way that ensures that they effectively and efficiently design, implement, measure, and continuously improve their strategies, tactics, and services, which can all be accomplished by being agile. The paper offers insights into: (1) the lessons learnt about the nature of digitalised public services/processes and agile management approaches in response to the COVID-19 pandemic and their impact on good governance; and (2) proposals for policymakers and managers in public administrations with regard to operating in extreme VUCA circumstances in any next wave of COVID-19 pandemic or in a new pandemic/public health disaster.
Effects of Two Sowing Methods on the Growth, Yield, and Quality of Hybrid Rice under Mechanical Transplantation
Authors: Gao Pinglei , Xiao Jiahao , Deng Shiwen , Dai Qigen
Published: November 2023

Poor adaptability of hybrid-rice (Oryza sativa L.) mechanical transplanting is one of the main factors limiting hybrid-rice production. Mixed sowing ensured stronger seedlings and better mechanical transplanting quality than conventional sowing in mechanical transplanting hybrid rice. Field experiments were conducted to identify the effects of mixed and conventional sowing of hybrid rice on rice growth, yield, and quality under mechanical transplantation in Yangzhou City, Jiangsu Province, China in 2021 and 2022. Two hybrid-rice varieties, japonica rice Changyou 4 and indica rice Yuanliangyou, and two conventional rice varieties, japonica rice Nanjing 5055 and indica rice Yangdao 6 were included in this study. Both japonica and indica rice showed the following results. There were no significant differences in biomass and leaf-area index of rice under different sowing methods at the heading and maturity stages. The basic seedling and spike rate was 38.27% and 16.24% higher, respectively, in mixed sowing than those averages in conventional sowing. In addition, the spikelets per panicle of hybrid rice in mixed sowing was 10.88% greater than the average in conventional sowing, indicating better heterosis. Compared to conventional sowing, mixed sowing increased the average gel consistency and taste value by 15.86% and 28.21%, respectively, while chalkiness degree, amylose content, and protein content decreased by an average of 60.47%, 44.89%, and 36.63%, respectively. Our study showed that similar biomass and leaf-area index, large basal seedling and spike rate, and large spikelets per panicle of hybrid rice are the keys to ensuring high yield in mixed sowing. At the same time, mixed sowing improved the appearance, nutrition, and cooking/eating qualities of the rice.
Planting Year- and Climate-Controlled Soil Aggregate Stability and Soil Fertility in the Karst Region of Southwest China
Authors: Zhang Wei-Chun , Wu Wei , Liu Hong-Bin
Published: November 2023

The effects of long-term monocropping systems combined with climate on soil water aggregate stability (WSA) and soil fertility in the karst region of Southwest China (KRSWC) are unclear. Our research was conducted in the KRSWC, wherein tobacco (Nicotiana tabacum) production is characterized by heavy fertilization and continuous monocropping. The tobacco fields in the study area have similar soil types and fertilization and tillage practices and are spread over an area of 11,500 km2. A total of 568 topsoil samples were collected in 2021. Soil fertility was reflected using the soil fertility index (SFI), which was calculated using the minimum data set method with six soil fertility-related factors, namely, soil pH, soil organic matter, cation exchange capacity, available nitrogen, available phosphorus, and available potassium. Results showed that long-term planting generally promoted soil fertility levels and WSA content. WSA and SFI had inconsistent spatial distribution patterns likely due to different climate-driven effects. WSA variability was greatly controlled by precipitation (Spearman correlation coefficient [r] = −0.49, p < 0.01), whereas SFI variability was mostly dominated by temperature (r = −0.36, p < 0.01). The levels of SFI and WSA were optimal under conditions of low temperature and precipitation and poor under conditions of high temperature and precipitation. Moreover, long-term planting could alleviate the negative effects of climate on SFI and WSA in the KRSWC. The results of this study could provide valuable information on fertilization and climate-adapted strategies for tobacco fields in the KRSWC.
The Impact of Different Relative Humidity Levels on the Production Performance, Slaughter Performance, and Meat Quality of White Pekin Ducks Aged 4 to 42 Days
Authors: Sun Dongyue , Xu Congcong , Liu Yi , Dai Zichun , Pan Ziyi , Chen Rong , Guo Rihong , Chen Fang , Shi Zhendan , Ying Shijia
Published: November 2023

This study aimed to investigate the effects of different humidity levels on the growth performance, slaughter performance, and meat quality of Pekin ducks through the artificial control of humidity, and to identify the suitable environmental humidity for Pekin duck growth. A completely randomized single-factor design was employed, selecting 144 newly hatched male Pekin ducks with healthy and similar BW (body weight) (60.92 g ± 4.38). These ducks were randomly assigned to four groups (A (RH (relative humidity) = 60%), B (RH = 67%), C (RH = 74%), D (RH = 81%)), with 12 ducks and 3 replicates in each group. The ducks were raised in a climate-controlled room for 42 days with ad libitum access to feed and water. BW and feed intake were measured every 3 days, and slaughter performance and meat quality were assessed at 42 days. There was no significant difference in the ADG (average daily gain) from 1 to 21 days (p > 0.05). The ADFI (average daily feed intake) of Group D was significantly lower than that of Groups A, B, and C (p < 0.05), with no significant differences between Groups A, B, and C (p > 0.05). At 42 days, the BW, ADG, and ADFI of Groups A and C were significantly higher than those of Group D (p < 0.05), with no significant differences among Groups A, B, and C (p > 0.05). Group C had a significantly higher breast muscle weight, breast muscle ratio, liver weight, and liver index than Groups B and D (p < 0.05), with no significant differences between Groups A, B, and D (p > 0.05). The meat shear force in Group C was significantly lower than that in Groups A, B, and D (p < 0.05). The L* (brightness) of Group C was significantly lower than that of Group A (p < 0.05), and the a* (redness) value of Group C was significantly higher than that of Groups A and B (p < 0.05), with no significant difference compared to Group D (p > 0.05). Group B had a significantly higher cooking loss than Groups A, C, and D (p < 0.05), with no significant differences among Groups A, C, and D (p > 0.05). Under 26 °C conditions, Pekin ducks perform best in terms of the production performance and feed efficiency, with high-quality meat, especially when reared at 74% humidity.
Anthropic Settlements’ Impact on the Light-Absorbing Aerosol Concentrations and Heating Rate in the Arctic
Authors: Losi Niccolò , Markuszewski Piotr , Rigler Martin , Gregorič Asta , Močnik Griša , Drozdowska Violetta , Makuch Przemysław , Zielinski Tymon , Pakszys Paulina , Kitowska Małgorzata , Cefalì Amedeo Manuel , Gini Irene , Doldi Andrea , Cerri Sofia , Maroni Pietro , Bolzacchini Ezio , Ferrero Luca
Published: November 2023

Light-absorbing aerosols (LAA) impact the atmosphere by heating it. Their effect in the Arctic was investigated during two summer Arctic oceanographic campaigns (2018 and 2019) around the Svalbard Archipelago in order to unravel the differences between the Arctic background and the local anthropic settlements. Therefore, the LAA heating rate (HR) was experimentally determined. Both the chemical composition and high-resolution measurements highlighted substantial differences between the Arctic Ocean background (average eBC concentration of 11.7 ± 0.1 ng/m3) and the human settlements, among which the most impacting appeared to be Tromsø and Isfjorden (mean eBC of 99.4 ± 3.1 ng/m3). Consequently, the HR in Isfjorden (8.2 × 10−3 ± 0.3 × 10−3 K/day) was one order of magnitude higher than in the pristine background conditions (0.8 × 10−3 ± 0.9 × 10−5 K/day). Therefore, we conclude that the direct climate impact of local LAA sources on the Arctic atmosphere is not negligible and may rise in the future due to ice retreat and enhanced marine traffic.
Turbulence and Pollutant Statistics around a High-Rise Building with and without Overhangs
Authors: Jiang Guoyi , Wu Ming , Hu Tingting
Published: November 2023

Wind flow around an isolated building is highly turbulent. Facade appurtenances can further increase the complexity of the flow, which strongly affects the gas dispersion around the building. This study investigated the turbulence and pollutant statistics around a high-rise building with large-eddy simulations and determined the influence of overhangs on the local wind flow and dispersion. Large-scale periodic vortex motion was detected. The results indicated that both the oncoming flow and the flow around the building followed a standard Gaussian distribution, whereas the occurrence frequencies of pollutant concentrations were far from Gaussian for pollutants discharged from both the rooftop and the ground behind the building. Near the pollutant sources, the positive concentration fluctuations occurred more frequently; occasionally, positive and negative fluctuations occurred equally. For the majority of areas far from the source, negative fluctuations were more common, but the maximum positive fluctuations were much larger. Overhangs changed the local flow structures near the building facade. Both the maximum concentration fluctuation and the maximum occurrence frequency decreased in the region between overhangs because turbulence was restricted.
Decoding Chiari Malformation and Syringomyelia: From Epidemiology and Genetics to Advanced Diagnosis and Management Strategies
Authors: Toader Corneliu , Ples Horia , Covache-Busuioc Razvan-Adrian , Costin Horia Petre , Bratu Bogdan-Gabriel , Dumitrascu David-Ioan , Glavan Luca Andrei , Ciurea Alexandru Vlad
Published: November 2023

Chiari Malformation and Syringomyelia are neurosurgical entities that have been the subject of extensive research and clinical interest. Globally prevalent, these disorders vary demographically and have witnessed evolving temporal trends. Chiari Malformation impacts the normal cerebrospinal fluid flow, consequently affecting overall health. Key observations from canine studies offer pivotal insights into the pathogenesis of Syringomyelia and its extrapolation to human manifestations. Genetics plays a pivotal role; contemporary knowledge identifies specific genes, illuminating avenues for future exploration. Clinically, these disorders present distinct phenotypes. Diagnostically, while traditional methods have stood the test of time, innovative neurophysiological techniques are revolutionizing early detection and management. Neuroradiology, a cornerstone in diagnosis, follows defined criteria. Advanced imaging techniques are amplifying diagnostic precision. In therapeutic realms, surgery remains primary. For Chiari 1 Malformation, surgical outcomes vary based on the presence of Syringomyelia. Isolated Syringomyelia demands a unique surgical approach, the effectiveness of which is continually being optimized. Post-operative long-term prognosis and quality of life measures are crucial in assessing intervention success. In conclusion, this review amalgamates existing knowledge, paving the way for future research and enhanced clinical strategies in the management of Chiari Malformation and Syringomyelia.
Applying the Behaviour Change Wheel to UK Local Authority Policy Documents: A Content Analysis in the Context of Financial Behaviour
Authors: Mills Zach , Wright Katryn , D’Lima Danielle
Published: November 2023

Local authorities in the UK often try to improve their residents’ financial well-being by promoting changes in behaviour. The extent to which these behaviour change activities are based on relevant theory or evidence is unknown. This research aims to retrospectively analyse the content of local authorities’ policies to identify opportunities for improvement. The Action, Actor, Context, Target, Time (AACTT) framework was used to assess the specification of target behaviours. The Behaviour Change Wheel (BCW) process was used to assess intervention content. Within the policy documents, target behaviours were not consistently specified in terms of the AACTT criteria. Descriptions of interventions lacked detail with 28% unable to be categorised and there was a reliance on Education (46%) to change financial behaviour. The designing and reporting of interventions to change residents’ financial behaviour were not always aligned with behavioural science evidence and utilising systematic frameworks could help local authorities achieve policy objectives.
Effective Factors for Implementing Building Information Modeling Using Fuzzy Method to Manage Buildings on Mars
Authors: Javaherikhah Amirhossein , Valiente Lopez Mercedes
Published: November 2023

Ever since mankind has known the world around him and space, he has been trying to find a suitable alternative for his current residence, the Earth. In this research, two main criteria for buildings on Mars and their information management were extracted by checking the library of studies on Mars. These two main criteria are the components of the building and the internal components of the building. The criteria for building components include the health of walls, the health of roofs, meteor protection, the health of facilities, and the health of windows (air exchange), and the internal components of the building, including air temperature, air pressure, ambient oxygen, ambient carbon dioxide, humidity, and the amount of light. These criteria, which were extracted from the library materials, were screened using the fuzzy Delphi method, which is one of the most accurate criteria screening methods and is completed by experts. After the opinions of experts, the criteria of health of walls, health of roofs, health of facilities, rejection, air exchange, ambient temperature, and oxygen content were extracted as final criteria. The results of the experts’ paired questionnaire were analyzed using the fuzzy AHP method, and the health criteria of the walls, the health of the ceilings, and air exchange have the first priority; the criteria of the ambient temperature and oxygen level are the second priority; and the criteria of the facilities are the last priority. These were placed as a suggestion, and it can be stated to the researchers that these priorities should be implemented in the blockchain platform so that the building information management system (BIM) works well in buildings on Mars and against any intrusion or damage. Being resistant, but it seems that the experts considered the components of the building separately from its protective components and put components such as the health of the window as a guarantee of the architecture of Martian buildings and did not include them as part of the main criteria of the research. Also, this research can be used as background for other research in this field.
Quantifying Energy Savings from Optimal Selection of HVAC Temperature Setpoints and Setbacks across Diverse Occupancy Rates and Patterns
Authors: Talami Riccardo , Dawoodjee Ilyas , Ghahramani Ali
Published: November 2023

With the advent of flexible working arrangements, we are observing a dramatic shift in how buildings are occupied today, which presents an opportunity to optimize Heating, Ventilation, and Air Conditioning system temperature setpoints based on variations in occupancy. Guidelines often suggest the adoption of the highest or lowest setpoint or setback to minimize energy consumption in hot or cold climates, respectively. However, at outdoor temperatures where variations in occupancy heat loads prompt buildings to fluctuate across cooling, free-running, and heating mode, optimal setpoints and setbacks are not always the lowest or highest. In addition, the perturbations caused by rapid switching between setpoint and setback could diminish energy savings due to system destabilization. This paper aims to systematically compare the potential energy savings from fixed and optimal setpoints and setbacks across wide-ranging occupancy scenarios (four occupancy rates and 14 patterns). Energy simulations were conducted using the Department of Energy reference models for small, medium, and large office buildings to enable an exhaustive search of optimal setpoint/setbacks in 17 climate zones. Explored setpoints were 19.5 °C to 25.5 °C with intervals of 1 °C, and setbacks were 17 °C/19 °C for heating and 26 °C/28 °C for cooling. The findings indicate that, on average, while lower occupancy heat loads results in 5.48% energy reduction, a conventional fixed setpoint and setback strategy provides an additional 11.80%, and optimal selection of setpoints and setbacks could provide an additional 34.36–38.08%, emphasizing the untapped potential energy saving. To facilitate practical applications, this paper presents an interactive graphical interface: Optimal Temperature Setpoint Tool.
Hypofractionation in Glioblastoma: An Overview of Palliative, Definitive, and Exploratory Uses
Authors: Jiang Cecilia , Mogilevsky Casey , Belal Zayne , Kurtz Goldie , Alonso-Basanta Michelle
Published: November 2023

Glioblastoma (GBM) is the most common primary brain malignancy in adults, and its incidence is increasing worldwide. Its prognosis remains limited despite recent imaging and therapeutic advances. The current standard of care is maximal safe resection followed by conventionally fractionated radiotherapy with concurrent and adjuvant temozolomide (TMZ), with or without tumor-treating fields (TTF). However, hypofractionated radiotherapy (HFRT) has also been utilized for a variety of reasons. It is an established treatment option in the palliative setting, where shortened treatment duration can positively impact the overall quality of life for older patients or those with additional health or socioeconomic considerations. HFRT, and in particular stereotactic radiosurgery (SRS), has also been explored in both the pre- and post-operative setting for newly diagnosed and recurrent diseases. In this review, we summarize the ways in which HFRT has been utilized in the GBM patient population and its evolving role in the experimental space. We also provide commentary on scenarios in which HFRT may be indicated, as well as guidance on dose and fractionation regimens informed by our institutional experience.
Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma
Authors: Ma Kun , Hu Ping
Published: November 2023

Glioblastoma (GBM), the most common primary brain tumor in adults, is characterized by low survival rates and a grim prognosis. Current treatment modalities, including extensive surgical resection, chemotherapy, and radiation therapy, often yield limited success due to the brain’s sensitivity, leading to significant side effects. Exciting advancements in immunotherapy have recently shown promise in treating various types of tumors, raising hopes for improved outcomes in brain tumor patients. One promising immunotherapy approach is chimeric antigen receptor (CAR) T-cell therapy, which recognizes surface proteins on targeted tumor cells and redirects cytotoxicity towards specific targets. This review aims to discuss the existing research and future prospects for CAR T-cell immunotherapy in treating glioblastoma.
High-Pressure Delivery of Oncolytic Viruses via Needle-Free Injection Preserves Therapeutic Activity
Authors: Said Aida , Hoang Huy-Dung , Earl Nathalie , Xiang Xiao , Siddiqui Nadeem , Côté Marceline , Alain Tommy
Published: November 2023

Intratumoural delivery of oncolytic viruses (OVs) to solid tumours is currently performed via multiple percutaneous methods of needle injections (NI). In this study, we investigated the potential use of a novel delivery approach, needle-free injection (NFI), to administer OVs to subcutaneous tumours. The stability and genetic integrity of several RNA and DNA viruses exposed to high-pressure jet injectors were first evaluated in vitro. We demonstrate that replication competence and infectivity of the viruses remained unchanged after NFI, as compared to traditional NI. Using the oncolytic Vesicular Stomatitis Virus expressing luciferase (VSVΔ51-Luc) in the syngeneic CT26 subcutaneous tumour model, we show that NFI administration not only successfully delivers infectious particles but also increases the dissemination of the virus within the tumour tissues when compared to NI. Furthermore, mice treated with VSVΔ51-Luc by NFI delivery showed similar reduction in tumour growth and survival compared to those with needle-administered virus. These results indicate that NFI represents a novel approach to administer and potentially increase the spread of OVs within accessible solid tumours, highlighting its usefulness in virotherapy.
Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Patients Using Harmonized Radiomics of Multcenter 18F-FDG-PET Image
Authors: Ju Hye-Min , Yang Jingyu , Park Jung-Mi , Choi Joon-Ho , Song Hyejin , Kim Byung-Il , Shin Ui-Sup , Moon Sun Mi , Cho Sangsik , Woo Sang-Keun
Published: November 2023

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.
POLD1 DEDD Motif Mutation Confers Hypermutation in Endometrial Cancer and Durable Response to Pembrolizumab
Authors: Wei Christina Hsiao , Wang Edward Wenge , Ma Lingzi , Zhou Yajing , Zheng Li , Hampel Heather , Shehayeb Susan , Lee Stephen , Cohen Joshua , Kohut Adrian , Fan Fang , Rosen Steven , Wu Xiwei , Shen Binghui , Zhao Yuqi
Published: November 2023

Background: Mutations in the DNA polymerase delta 1 (POLD1) exonuclease domain cause DNA proofreading defects, hypermutation, hereditary colorectal and endometrial cancer, and are predictive of immunotherapy response. Exonuclease activity is carried out by two magnesium cations, bound to four highly conserved, negatively charged amino acids (AA) consisting of aspartic acid at amino acid position 316 (p.D316), glutamic acid at position 318 (p.E318), p.D402, and p.D515 (termed DEDD motif). Germline polymorphisms resulting in charge-discordant AA substitutions in the DEDD motif are classified as variants of uncertain significance (VUSs) by laboratories and thus would be considered clinically inactionable. We hypothesize this mutation class is clinically pathogenic. Methods: A review of clinical presentation was performed in our index patient with a POLD1(p.D402N) heterozygous proband with endometrial cancer. Implications of this mutation class were evaluated by a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review, in silico analysis with orthogonal biochemical confirmation, and whole-exome and RNA sequencing analysis of the patient’s tumor and engineered cell lines. Results: Our systematic review favored a Mendelian disease mutation class associated with endometrial and colorectal cancers. In silico analysis predicted defective protein function, confirmed by biochemical assay demonstrating loss of nuclease activity. A POLD1-specific mutational signature was found in both the patient’s tumor and POLD1(p.D402N) overexpressing cell. Furthermore, paired whole-exome/transcriptome analysis of endometrial tumor demonstrated hypermutation and T cell-inflamed gene expression profile (GEP), which are joint predictive biomarkers for pembrolizumab. Our patient showed a deep, durable response to immune checkpoint inhibitor (ICI). Conclusion: Charge-discordant AA substitution in the DEDD motif of POLD1 is detrimental to DNA proofreading and should be reclassified as likely pathogenic and possibly predictive of ICI sensitivity.
Optimization of the Green Fibre Paper Film Preparation Process Based on Box–Behnken Response Surface Methodology
Authors: Cao Xiaoqing , Li Lu , Zhang Fengwei , Shi Linxiong , Zhang Fangyuan , Song Xuefeng , Zhao Wuyun , Dai Fei
Published: November 2023

To improve the utilization rate of flax straw and the clean treatment of livestock manure, an experimental study was conducted on the process and performance of making fibre paper films by mixing cow dung and flax straw fibre. Cow dung and flax straw were used as the main raw materials, and functional additives were not added. The whole technological process of the pretreatment, the beating process, the determination of the beating degree, the basis weight of the paper, papermaking, drying, sample cutting, and the determination and analysis of the related mechanical properties of the film-making materials were studied. In this study, the Box–Behnken experimental design principle in the response surface methodology was adopted, and the effect of each factor on the tensile strength and tear strength of fibre paper film made of mixed fibres was determined using the combined experimental design comprising four factors and three levels centres. The results showed that the optimum technological parameters were as follows: the beating degree of the cow dung fibre was 37 °SR, the beating degree of the flax straw fibre was 85 °SR, the paper basis weight was 80 g/m2, and the addition of flax straw fibre was 65%. At a drying temperature of 80 °C and a drying time of 8 min, under the conditions of the hybrid fibre paper film placed in the laboratory environment (humidity of 30%~40%, temperature of 18 °C) for 24 h, the measured tensile strength was about 8.26 MPa, and the tear strength was about 19.91 N/mm. This study provides a reference that can be used for the further study of fibre paper film.
Perovskite/Pyrochlore Composite Mineral-like Ceramic Fabrication for 90Sr/90Y Immobilization Using SPS-RS Technique
Authors: Papynov Evgeniy K. , Shichalin Oleg O. , Belov Anton A. , Buravlev Igor Yu. , Zavjalov Alexey , Azon S. A. , Fedorets Alexander N. , Kornakova Zlata E. , Lembikov Aleksey O. , Gridasova E. A. , Ivanets Andrei , Tananaev Ivan G.
Published: November 2023

A novel solid-phase synthetic approach was developed to produce a mineral-like composite ceramic based on strontium titanate (SrTiO3) and yttrium titanate (Y2Ti2O7) matrices for immobilizing radionuclides such as 90Sr and its daughter product 90Y, as well as lanthanides and actinides, via reactive spark plasma sintering technology (SPS-RS). Using XRD, SEM, and EDS analyses, the sintering kinetics of the initial mixed oxide reactants of composition YxSr1–1.5xTiO3 (x = 0.2, 0.4, 0.6 and 1) and structure-phase changes in the ceramics under SPS-RS conditions were investigated as a function of Y3+ content. In addition, a detailed study of phase transformation kinetics over time as a function of the heating temperature of the initial components (SrCO3, TiO2, and Y2O3) was conducted via in situ synchrotron XRD heating experiments. The composite ceramic achieved relatively high physicomechanical properties, including relative density between 4.92–4.64 g/cm3, Vickers microhardness of 500–800 HV, and compressive strength ranging from 95.5–272.4 MPa. An evaluation of hydrolytic stability and leaching rates of Sr2+ and Y3+ from the matrices was performed, demonstrating rates did not exceed 10−5–10−6 g·cm−2·day−1 in compliance with GOST R 50926-96 and ANSI/ANS 16.1 standards. The leaching mechanism of these components was studied, including the calculation of solution penetration depth in the ceramic bulk and ion diffusion coefficients in the solution. These findings show great promise for radioactive waste conditioning technologies and the manufacturing of radioisotope products.
Effect of Electrical Resistance Heating on Recrystallization of Cold-Rolled Low-Carbon Steel
Authors: Van Iderstine Dawn , Mujahid Shiraz , Paudel YubRaj , Rhee Hongjoo
Published: November 2023

The “electron wind effect” has long been cited as a potential catalyst of solid-state transformations in metals, particularly when high current densities are involved. However, the literature exploring similar effects at lower current densities, such as those occurring during Gleeble thermomechanical simulation, remains scarce. The present work compares recrystallization activity in cold-rolled low-carbon steel during heat treatment by conventional furnace versus direct resistance heating (Gleeble). Multiple levels of cold work, annealing durations, and soak temperatures were examined, allowing for an in-depth comparison of recrystallization rates and activation energies between samples subjected to identical time–temperature profiles in the furnace and Gleeble. In addition to the expected increase in recrystallization behavior with the increases in temperature and cold-reduction levels, the use of the Gleeble system as the heating method resulted in faster initial microstructural transformation than a conventional furnace. The variability in recrystallized fractions persisted until the microstructures had saturated to their nearly fully recrystallized levels, at which point the microhardness and electron backscatter diffraction (EBSD) revealed convergence to equivalent behavior irrespective of the heating method. Analysis of the recrystallization kinetics by fitting to a JMAK relationship reflected the increased transformation activity during Gleeble treatment, with the value of the kinetic exponent also indicating greater grain growth activity at higher temperature.
Synthesis and Crystallization of N-Rich Triazole Compounds
Authors: Parisi Emmanuele , Centore Roberto
Published: November 2023

Among N-rich heterocycle backbone compounds, the triazoles building block received a lot of interest in several different academic and industrial studies and applications. This article outlines the process of synthesizing three different 1,2,4-triazole-based systems, commencing with 1,3-diaminoguanidine hydrochloride monohydrate as the starting material. The five novel crystal structures, Triaz1, Triaz2, Triaz3, Triaz4, and Triaz5, were characterized by NMR spectroscopy and single-crystal X-ray diffraction analysis. Hirshfeld surface analysis was employed to explore the intermolecular interactions that are responsible for quantitative crystal packing. The synthesized compounds, with their elevated nitrogen content, serve as potential components for High-Energy-Density material science applications.
Patient Adherence to Oral Anticancer Agents: A Mapping Review of Supportive Interventions
Authors: Ahmed Saima , Loiselle Carmen G.
Published: November 2023

The development and use of oral anticancer agents (OAAs) continue to grow, and supporting individuals on OAAs is now a priority as they find themselves taking these drugs at home with little professional guidance. This mapping review provides an overview of the current evidence concerning OAA-supportive adherence interventions, identifying potential gaps, and making recommendations to guide future work. Four large databases and the grey literature were searched for publications from 2010 to 2022. Quantitative, qualitative, mixed-method, theses/dissertations, reports, and abstracts were included, whereas protocols and reviews were excluded. Duplicates were removed, and the remaining publications were screened by title and abstract. Full-text publications were assessed and those meeting the inclusion criteria were retained. Data extracted included the year of publication, theoretical underpinnings, study design, targeted patients, sample size, intervention type, and primary outcome(s). 3175 publications were screened, with 435 fully read. Of these, 314 were excluded with 120 retained. Of the 120 publications, 39.2% (n = 47) were observational studies, 38.3% (n = 46) were quasi-experimental, and 16.7% (n = 20) were experimental. Only 17.5% (n = 21) were theory-based. Despite the known efficacy of multi-modal interventions, 63.7% (n = 76) contained one or two modalities, 33.3% (n = 40) included 3, and 3.3% (n = 4) contained four types of modalities. Medication adherence was measured primarily through self-report (n = 31) or chart review/pharmacy refills (n = 28). Given the importance of patient tailored interventions, future work should test whether having four intervention modalities (behavioral, educational, medical, and technological) guided by theory can optimize OAA-related outcomes.
Simultaneous Occurrence of Medullary Thyroid Carcinoma and Papillary Thyroid Carcinoma: A Case Series with Literature Review
Authors: Fallahi Poupak , Patrizio Armando , Stoppini Giulio , Elia Giusy , Ragusa Francesca , Paparo Sabrina Rosaria , Balestri Eugenia , Mazzi Valeria , Botrini Chiara , Varricchi Gilda , Ulisse Salvatore , Ghionzoli Marco , Antonelli Alessandro , Ferrari Silvia Martina
Published: November 2023

Background: Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. Methods: This is a retrospective, single-center observational study conducted over 16 years (2001–2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy. Results: Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases. Conclusions: The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin.
Phase-Specific Damage Tolerance of a Eutectic High Entropy Alloy
Authors: Jha Shristy , Mishra Rajiv S. , Mukherjee Sundeep
Published: November 2023

Phase-specific damage tolerance was investigated for the AlCoCrFeNi2.1 high entropy alloy with a lamellar microstructure of L12 and B2 phases. A microcantilever bending technique was utilized with notches milled in each of the two phases as well as at the phase boundary. The L12 phase exhibited superior bending strength, strain hardening, and plastic deformation, while the B2 phase showed limited damage tolerance during bending due to micro-crack formation. The dimensionalized stiffness (DS) of the L12 phase cantilevers were relatively constant, indicating strain hardening followed by increase in stiffness at the later stages and, therefore, indicating plastic failure. In contrast, the B2 phase cantilevers showed a continuous drop in stiffness, indicating crack propagation. Distinct differences in micro-scale deformation mechanisms were reflected in post-compression fractography, with L12-phase cantilevers showing typical characteristics of ductile failure, including the activation of multiple slip planes, shear lips at the notch edge, and tearing inside the notch versus quasi-cleavage fracture with cleavage facets and a river pattern on the fracture surface for the B2-phase cantilevers.