bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive cornified envelope protein profile of odontogenic keratocysts clarifies the characteristics of non‐keratinized oral epithelium
Authors: Roy Rita R. , Ochiai Takanaga , Shimada Katsumitsu , Hasegawa Hiromasa
Published: July 2023

Background

Odontogenic keratocysts constitute 10%–20% of odontogenic cysts and exhibit a distinctive corrugated parakeratinized lining epithelium. Considering that cornified envelope formation is an important phenomenon during keratinocyte differentiation, this study aimed to clarify the characteristics of cornified envelope formation in odontogenic keratocysts.

Methods

We investigated the cellular distribution of cornified envelope‐related proteins (transglutaminases and their substrates), as well as the upstream regulatory protein c‐Fos, by immunohistochemical analysis of the lining epithelium of 20 odontogenic keratocysts. We examined the corresponding mRNA levels by quantitative polymerase chain reaction. Ten dentigerous cysts served as control non‐keratinized cysts.

Results

The distributions of transglutaminase and their substrates except loricrin and small protein‐rich protein 1a significantly differed between odontogenic keratocysts and dentigerous cysts. There was no significant difference in c‐Fos expression between odontogenic keratocysts and dentigerous cysts. The mRNA levels of transglutaminases and their substrates were significantly higher in odontogenic keratocysts than in dentigerous cysts. However, c‐Fos mRNA levels did not significantly differ between groups.

Conclusion

Surprisingly, the overall appearance of cornified envelope‐related proteins of odontogenic keratocysts was consistent with the characteristics of non‐keratinized oral mucosa identified in previous studies. These findings indicate that the contribution of cornified envelope‐related molecules in odontogenic keratocysts is similar to that in non‐keratinized oral epithelium, rather than keratinized oral epithelium, suggesting that odontogenic keratocysts are not genuine keratinized cysts. The upregulation of cornified envelope‐related genes in odontogenic epithelium could be an important pathognomonic event during odontogenic keratocyst development.
Burrell's Critical Thomism: Aquinas and Kant Revisited
Authors: Norman Jack E. V.
Published: July 2023

David Burrell's version of Aquinas was written with Kantian parallels in mind. This is the accusation of John Milbank that was questioned by Nicholas Lash and Paul DeHart in a series of articles. ‘Burrell's Critical Thomism’ shows beyond doubt that Milbank's claim is correct: Burrell cites Kant throughout his oeuvre and finds parallels between Aquinas and Kant's philosophies. However, this article also shows that the form of Kantianism promulgated by Burrell is not as dogmatic as Milbank argues, especially in Burrell's later writings. If Milbank's critique holds, it follows that a properly negative theology must be denied. Finally, the relationship between Milbank's participatory theology and Burrell's emphasis on divine simpleness is examined in order to critically evaluate the status of participation in God, arguing that, for Aquinas, it does not make sense to say we participate in the divine essence, only in its likeness. Direct participation in God's essence is rendered incoherent by divine simpleness.
Display optimization under the multinomial logit choice model: Balancing revenue and customer satisfaction
Authors: Feldman Jacob , Jiang Puping
Published: July 2023

In this paper, we consider an assortment optimization problem in which a platform must choose pairwise disjoint sets of assortments to offer across a series of T stages. Arriving customers begin their search process in the first stage, and progress sequentially through the stages until their patience expires, at which point they make a multinomial logit–based purchasing decision from among all products they have viewed throughout their search process. The goal is to choose the sequential displays of product offerings to maximize expected revenue. Additionally, we impose stage‐specific constraints that ensure that as each customer progresses farther and farther through the T stages, there is a minimum level of “desirability” met by the collections of displayed products. We consider two related measures of desirability: purchase likelihood and expected utility derived from the offered assortments. In this way, the offered sequence of assortments must be both high earning and well liked, which breaks from the traditional assortment setting, where customer‐centric considerations are generally not explicitly accounted for. We show that our assortment problem of interest is strongly NP‐Hard, thus ruling out the existence of a fully polynomial‐time approximation scheme (FPTAS). From an algorithmic standpoint, as a warm‐up, we develop a simple constant factor approximation scheme in which we carefully stitch together myopically selected assortments for each stage. Our main algorithmic result consists of a polynomial‐time approximation scheme (PTAS), which combines a handful of structural results related to the make‐up of the optimal assortment sequence within an approximate dynamic programming framework. We also provide an additional approximation scheme, which, under mild assumptions, can handle a cardinality constraint that enforces that an exact number of new products are introduced at each stage. Using an extensive set of numerical experiments, we demonstrate that both algorithms exhibit excellent practical performance, producing sequences of assortments that are, on average, always within 2% of optimal.
Lessons learned from a conservation translocation of a microendemic habitat specialist
Authors: Parker Mickey Ray , Hibbitts Toby J. , Ryberg Wade A. , Fitzgerald Lee A.
Published: July 2023

Translocations are often characterized as “successes” or “failures”. However, this dichotomy masks the challenges of successful translocations and ignores important lessons learned in cases where a population was not established in perpetuity. We translocated 76 individuals of an imperiled endemic lizard, the Dunes Sagebrush Lizard (Sceloporus arenicolus), to a locality where it had gone extinct. Translocated lizards survived and reproduced in small numbers. Based on intensive monitoring, we were able to conclude the incipient population declined to zero individuals after 4 years. It is possible that predation, Allee effects, or stochastic factors prevented the population from sustaining itself at this historically occupied site. Valuable lessons for conservation translocations can be taken from this case. We offer novel perspectives on the IUCN Guidelines for Reintroductions and Other Conservation Translocations regarding release site selection, propagule bias, behavioral monitoring, population monitoring, and issues of land tenure. We recommend pairing knowledge of habitat requirements with quantitative analyses to select suitable release sites, translocating gravid females to jump‐start population growth, coupling delayed releases with intensive behavioral monitoring, using Poisson‐based models to determine necessary intensity of monitoring, and recognizing how issues of land tenure may present pitfalls for conservation translocations in the long term.
The power of the Paris Agreement in international climate litigation
Authors: Voigt Christina
Published: July 2023

Climate litigation has reached the international level with several requests for advisory opinions from international courts and tribunals, and human rights treaty bodies addressing climate change‐related human rights violations. The Paris Agreement will likely be relevant in many of these and other cases to come, whether directly in disputes about its application or interpretation, or indirectly in informing the interpretation of other international agreements, such as the European Convention on Human Rights (ECHR) or the United Nations Convention on the Law of the Sea (UNCLOS). It could also inform the due diligence standard contained in customary international environmental law. This article first examines normative elements of the Paris Agreement that may become relevant in the interpretation of other international norms. It then identifies some potential entry points of legal influence of these elements in the interpretation and application of other international law, especially the ECHR and UNCLOS. The article argues that the legal influence of the Agreement goes above and beyond the ‘legal fold’ in which it was adopted and can inform the interpretation of other international treaties and norms. ‘Paris‐aligned’ interpretation, taking into account the diligence standards contained in the Agreement, could impact on the contemporary understanding of international law more generally. Such interpretation might be necessary to avoid undermining the relevance of the Agreement. Importantly, it suggests that Paris‐aligned interpretation of other international treaties can provide a positive feedback loop towards effective implementation of, and compliance with, the Paris Agreement. Eventually, such Paris alignment may enhance legal consistency between diverse parts of international law and break down fragmented silos.
A risk–risk trade‐off assessment of climate‐induced mortality risk changes
Authors: Mussio Irene , Chilton Susan , Duxbury Darren , Nielsen Jytte Seested
Published: July 2023

The impact of climate change on human health was identified as a priority for the UN COP26 conference. In this article, we consider climate‐induced changes to mortality risks and how to incorporate these formally in the policy appraisal process. In the United Kingdom (UK), the Value of Statistical Life (VSL) is used to monetarize the benefits of policies to reduce mortality risks but it remains an open, empirical question as to whether the current VSL (£2.14 million per fatality prevented, December 2021 values) for traffic accidents should be applied in other contexts without any modification and particularly for extreme weather event fatalities. Using a representative sample of the UK population, we aim to estimate and better understand the trade‐offs people make when comparing mortality risks, drawing on psychological insights from construal level and regulatory focus theories. We design a stated preference survey using a relative valuation framework with nonmonetary, risk–risk trade‐off questions between extreme weather event and traffic accident mortality risks. We find evidence of an extreme weather event risk premium of 1.2–1.6 (implying a climate‐related VSL of £2.52–£3.41 million). We also find that participants who are psychologically close to climate change (based on construal level theory), weigh reducing extreme weather event mortality risks almost two times that of reducing traffic accident mortality risks.
Latinoamérica, Abya-Yala, Améfrica, Ñamérica. ¿Desde dónde hablamos?
Authors: Duque Cardona Natalia , Wellington de Oliveira Silva Alderlan
Published: July 2023

El artículo presenta un ejercicio de reflexión, cuyo propósito es cuestionar, en términos políticos, éticos y epistémicos, el lugar de enunciación geográfico/territorial enmarcado en el Sur Global, planteado desde los estudios culturales a las ciencias sociales y humanas, en la última década, como eje conceptual para avanzar en la comprensión de los fenómenos sociales. Se realiza un recorrido por la noción de territorio, configurado como un espacio no limitado geográficamente, sino como un campo de disputas en torno al conocimiento científico y la configuración simbólica del mundo. De manera particular, se exploran las formas de nombrar lo que hoy conocemos como Latinoamérica: Indoamérica, Abya-Yala, Améfrica y Ñamérica, con la intención de explorar cómo estos modos de enunciación hacen visibles nuevas u otras formas de conocimiento invisibilizadas y la razón por la cual se distancian de Iberoamérica para ciencias como la bibliotecología y la Ciencia de la Información.
Controlled Bubble Formation From a Microelectrode Single Bubble Generator
Authors: Yang Bo , Jafarian Mehdi , Freidoonimehr Navid , Arjomandi Maziar
Published: July 2023

In this work, a new micro-electrode bubble generator is presented that employs a micro-electrode installed inside a small nozzle enabling the production of bubbles with controllable size and frequency. This bubble generator can be employed as a simple and potentially cheap method for the generation of single bubbles in a liquid, as long as it enables ion exchange, as an alternative to more complicated methods such as timely injection of a gas through a nozzle, which requires sophisticated nozzle design, manufacturing, and monitoring of the injected gas flow rate. A systematic investigation was conducted to assess the effect of the bubble generator dimensions, applied voltage, and electrolyte flow conditions on the size and frequency of the generated bubbles. It was shown that when the micro-electrode is thinly concealed within the nozzle, this bubble generator can successfully produce bubbles covering a wide range of diameters from 0.4 to 1.4 mm with a size distribution standard deviation of about 25%. The mechanism of single and continuous bubbles formation from the proposed bubble generator is also discussed. While this paper introduces this new micro-electrode bubble generator, further work is required to optimize it, enabling more accurate control over bubble size and frequency.
Coaches’ Use of Remote Coaching: Experiences From Paralympic Sport
Authors: Taylor Sarah , Renshaw Ian , Pinder Ross , Polman Remco , Russell Scott
Published: July 2023

Remote coaching via the use of digital technologies has been utilized within Paralympic Sports since 2015 to address challenges experienced by coaches. These technologies have connected coaches and athletes in real time, alleviating time and travel costs. However, very little is known about the experience of coaching in these environments. Therefore, the aim of this study was to explore the experiences of coaches’ use of remote coaching technologies. Seven coaches from five Paralympic Sports were recruited for this study and participated in semistructured interviews. Additionally, observations were conducted of remote coaching sessions that were part of their regular training schedules. Coaches’ insights highlight that remote technologies created opportunities to increase coach–athlete interactions and positively impact the development of interpersonal relationships. This allowed coaches to explore and exploit newly discovered information from within training environments to aid athletes in skill development. Additionally, remote coaching provided unexpected opportunities for coach development. However, coaches also reported new environmental and logistical challenges which disrupted their usual coaching approach. Overall, remote coaching technologies were perceived as being beneficial despite the challenges experienced. However, future research that looks to understand how to impact coach and athlete development through the online environment is encouraged.
New options for patenting in Europe
Authors: Veugelers Reinhilde , Harhoff Dietmar
Published: July 2023

Inventors seeking to protect their intellectual property in Europe now have an important choice to make. More than a decade after its approval, a new patent system came into effect last month, which some European Union (EU) countries already have signed on to. Inventors in these countries can use either the new unitary patent (UP) system or the previously existing route of European patents. A balance between the two paths is hoped to spur a more robust pan-European patent landscape. However, the new system must be widely adopted first.
Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management
Authors: Thompson George R. , Jenks Jeffrey D. , Baddley John W. , Lewis James S. , Egger Matthias , Schwartz Ilan S. , Boyer Johannes , Patterson Thomas F. , Chen Sharon C.-A. , Pappas Peter G. , Hoenigl Martin
Published: July 2023

Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (>70%), and presents numerous challenges during clinical care.Candidaspp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed byAspergillusandHistoplasmaspp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use.
Chromatin control of human cytomegalovirus infection
Authors: Matthews Stephen M. , Groves Ian J. , O'Connor Christine M.
Published: July 2023

Human cytomegalovirus (HCMV) is a betaherpesvirus that establishes lifelong infection in its host and can cause severe comorbidities in individuals with suppressed or compromised immune systems. The lifecycle of HCMV consists of lytic and latent phases, largely dependent upon the cell type infected and whether transcription from the major immediate early locus can ensue. Control of this locus, which acts as a critical “switch” region from where the lytic gene expression cascade originates, as well as regulation of the additional ~235 kilobases of virus genome, occurs through chromatinization with cellular histone proteins after infection. Upon infection of a host cell, an initial intrinsic antiviral response represses gene expression from the incoming genome, which is relieved in permissive cells by viral and host factors in concert. Latency is established in a subset of hematopoietic cells, during which viral transcription is largely repressed while the genome is maintained. As these latently infected cells differentiate, the cellular milieu and epigenetic modifications change, giving rise to the initial stages of virus reactivation from latency. Thus, throughout the cycle of infection, chromatinization, chromatin modifiers, and the recruitment of specific transcription factors influence the expression of genes from the HCMV genome. In this review, we discuss epigenetic regulation of the HCMV genome during the different phases of infection, with an emphasis on recent reports that add to our current perspective.
Intensive care unit sinks are persistently colonized with multidrug resistant bacteria and mobilizable, resistance-conferring plasmids
Authors: Diorio-Toth Luke , Wallace Meghan A. , Farnsworth Christopher W. , Wang Bin , Gul Danish , Kwon Jennie H. , Andleeb Saadia , Burnham Carey-Ann D. , Dantas Gautam
Published: July 2023

Contamination of hospital sinks with microbial pathogens presents a serious potential threat to patients, but our understanding of sink colonization dynamics is largely based on infection outbreaks. Here, we investigate the colonization patterns of multidrug-resistant organisms (MDROs) in intensive care unit sinks and water from two hospitals in the USA and Pakistan collected over 27 months of prospective sampling. Using culture-based methods, we recovered 822 bacterial isolates representing 104 unique species and genomospecies. Genomic analyses revealed long-term colonization by
Pseudomonas
spp. and
Serratia marcescens
strains across multiple rooms. Nanopore sequencing uncovered examples of long-term persistence of resistance-conferring plasmids in unrelated hosts. These data indicate that antibiotic resistance (AR) in
Pseudomonas
spp. is maintained both by strain colonization and horizontal gene transfer (HGT), while HGT maintains AR within
Acinetobacter
spp. and Enterobacterales, independent of colonization. These results emphasize the importance of proactive, genomic-focused surveillance of built environments to mitigate MDRO spread.

IMPORTANCE

Hospital sinks are frequently linked to outbreaks of antibiotic-resistant bacteria. Here, we used whole-genome sequencing to track the long-term colonization patterns in intensive care unit (ICU) sinks and water from two hospitals in the USA and Pakistan collected over 27 months of prospective sampling. We analyzed 822 bacterial genomes, representing over 100 different species. We identified long-term contamination by opportunistic pathogens, as well as transient appearance of other common pathogens. We found that bacteria recovered from the ICU had more antibiotic resistance genes (ARGs) in their genomes compared to matched community spaces. We also found that many of these ARGs are harbored on mobilizable plasmids, which were found shared in the genomes of unrelated bacteria. Overall, this study provides an in-depth view of contamination patterns for common nosocomial pathogens and identifies specific targets for surveillance.
Medically assisted dying in Canada and unjust social conditions: a response to Wiebe and Mullin
Authors: Christie Timothy , Li Madeline
Published: July 2023

In the paper, titled ‘Choosing death in unjust conditions: hope, autonomy and harm reduction,’ Wiebe and Mullin argue that people living in unjust social conditions are sufficiently autonomous to request medical assistance in dying (MAiD). The ethical issue is that some people may request MAiD primarily because of unjust social conditions, not their illness, disease, disability or decline in capability. It is easily agreed that people living in unjust social conditions can be autonomous. Nevertheless, Wiebe and Mullin fail to appreciate that autonomy is only a necessary condition for MAiD. In addition to autonomy, one must decide that providing assisted dying to a patient because they are living in unjust social conditions is ethical. Central to making this ethical decision is the principle of non-maleficence, famously articulated as ‘do no harm.’ The authors admit that performing MAiD in response to unjust social circumstances is harmful, but they justify this harmful action by appealing to the principle of harm reduction. A fundamental flaw of their approach is that it relies on the legislative definition of intolerable suffering, which is based on circular reasoning and given that 99.2% of patients that have applied for MAiD satisfied this criterion, it is essentially equivalent to no standard/criterion. Canadian society is struggling with the ethical implications of its permissive MAiD programme, and, fundamental to this debate, will be determining the proper balance between autonomy and non-maleficence for people living in unjust social conditions.
Listening campaigns: engaging clinicians to assess system factors contributing to burnout
Authors: Richards Sarah E , Kennel Victoria , Wardian Jana , Carlson Kristy , Lowndes Bethany
Published: July 2023

Background

Even prior to the pandemic, many US physicians experienced burnout affecting patient care quality, safety and experience. Institutions often focus on personal resilience instead of system-level issues. Our leaders developed a novel process to identify and prioritise key system-related solutions and work to mitigate factors that negatively impact clinician well-being through a structured listening campaign.

Methods

The listening campaign consists of meeting with each clinician group leader, a group listening session, a follow-up meeting with the leader, a final report and a follow-up session. During the listening session, clinicians engage in open discussion about what is going well, complete individual reflection worksheets and identify one ‘wish’ to improve their professional satisfaction. Participants rate these wishes to assist with prioritisation.

Results

As of January 2020, over 200 clinicians participated in 20 listening sessions. One hundred and twenty-two participants completed a survey; 80% stated they benefited from participation and 83% would recommend it to others.

Conclusion

Collecting feedback from clinicians on their experience provides guidance for leaders in prioritising initiatives and opportunities to connect clinicians to organisational resources. A listening campaign is a tool recommended for healthcare systems to elicit clinician perspectives and communicate efforts to address systemic factors.
Comparing landscape partitioning approaches to protect wildlife habitat in managed forests
Authors: Yemshanov Denys , Hart Triin , Cameron Jeff , Liu Ning , Koch Frank H. , Leblond Mathieu
Published: July 2023

Industrial forestry activities can increase landscape fragmentation, impacting wildlife populations, particularly Canada’s woodland caribou, Rangifer tarandus caribou. To protect caribou in areas with forestry activities, the province of Ontario, Canada, implemented a Dynamic Caribou Harvest Schedule (DCHS). The DCHS spatially aggregates harvest disturbance into regions and distributes them across the landscape to maintain forest patch size–age distributions consistent with a natural variation range. However, the DCHS may negatively impact the cost of timber supply. We compared the DCHS with an alternative zoning approach that assigned the harvest deferral and operational management zones within a large forest area. We compared these approaches using an optimization model that combined harvest scheduling, access road construction, and caribou protection sub-problems. We formulated the protection of caribou habitat and road construction as network flow problems, while the harvesting problem incorporated the ecological constraints prescribed by the forest management plan. We compared the DCHS and zoning approaches in the Wabadowgang Noopming Forest of Ontario, a boreal area within the caribou distribution zone. For the same volume of sustainable harvest, the zoning approach protected less total area but more habitat and old-growth stands over the long term, and yielded lower timber costs by 1.2–2.2 $·m−3 than the DCHS.
Research on the Turning of Graphic Design Information Communication from Static Presentation to Interactive
Authors: Zhang Huiling
Published: July 2023

Aiming at the problem that the static presentation of graphic design information cannot meet the needs of current designers, a curve fitting algorithm based on inflection point detection is proposed. Combine it with the electronic whiteboard system to build an interactive whiteboard system for railway graphic design, and realize the transformation of graphic design information from static to dynamic in this way. The performance comparison experiment of the curve fitting algorithm proposed in the research shows that the accuracy rate of the algorithm is 88.2%, which is higher than that of similar comparison algorithms. The results show that the proposed curve fitting algorithm has better fitting performance. In the empirical analysis of the interactive electronic whiteboard system of railway plane information, it is found that the happy and excited emotional scores of users using the system are increased by 1.8 and 1.3 points respectively. In addition, the Timeliness and Convenience index scores of the transformed graphic design information transmission mode have increased by 1.7 and 1.3 points respectively. The result shows that the transformation of graphic design information transmission mode into dynamic interactive mode through the curve fitting algorithm can effectively improve its user experience, thus improving the designer's graphic design efficiency.
Selective Query Processing: A Risk-Sensitive Selection of Search Configurations
Authors: Mothe Josiane , Ullah Md. Zia
Published: July 2023

In information retrieval systems, search parameters are optimized to ensure high effectiveness based on a set of past searches, and these optimized parameters are then used as the search configuration for all subsequent queries. A better approach, however, would be to adapt the parameters to fit the query at hand. Selective query expansion is one such an approach, in which the system decides automatically whether or not to expand the query, resulting in two possible search configurations. This approach was extended recently to include many other parameters, leading to many possible search configurations where the system automatically selects the best configuration on a per-query basis. One problem with this approach is the system training, which requires evaluation of each training query with every possible configuration. In real-world systems, so many parameters and possible values must be evaluated that this approach is impractical, especially when the system must be updated frequently, as is the case for commercial search engines. In general, the more configurations, the greater the effectiveness when configuration selection is appropriate but also the greater the risk of decreasing effectiveness in the case of an inappropriate configuration selection. To determine the ideal configurations to be used for each query in real-world systems, we have developed a method in which a limited number of possible configurations are pre-selected, then used in a meta-search engine that decides the best search configuration for each query. We define a risk-sensitive approach for configuration pre-selection that considers the risk-reward tradeoff between the number of configurations kept and system effectiveness. We define two alternative risk functions to apply to different goals. For final configuration selection, the decision is based on query feature similarities. We compare two alternative risk functions on two query types (ad hoc and diversity) and compare these to more sophisticated machine learning based methods. We find that a relatively small number of configurations (20) selected by our risk-sensitive model is sufficient to obtain results close to the best achievable results for each query. Effectiveness is increased by about 15% according to the P@10 and nDCG@10 evaluation metrics when compared to traditional grid search using a single configuration and by about 20% when compared to learning to rank documents. Our risk-sensitive approach works for both diversity- and ad hoc oriented searches. Moreover, the similarity-based selection method outperforms the more sophisticated approaches. Thus, we demonstrate the feasibility of developing per-query information retrieval systems, which will guide future research in this direction.
The Exercise Preconditioning Effect on Cardiac Tissue Injury following Induction of Myocardial Infarction in Male Rats
Authors: Heiat Fatemeh , Ahmadi Azam , Shojaeifard Manzarbanoo
Published: July 2023

Background and Objective. Studies have shown that physical activity not only reduces cardiovascular risk factors but also improves cardiac protection against ischemia‐reperfusion. One of the protective pathways of the heart against ischemia is mitochondrial function protection, and the role of exercise preconditioning in this mechanism is important. We investigated the exercise pretraining on mitochondrial biogenesis effect, angiogenesis, and cardiac tissue injury in male rats following stroke. Materials and Methods. Twenty‐four male rats were divided into 4 groups including MI, Sham, HIIT, and HIIT+MI (N = 6). HIIT and HIIT+MI which underwent high‐intensity interval training (HIIT) for 4 weeks (5 days a week). The training protocol included 10 intervals of 1‐minute running, with 2 minutes rest between each interval. The training intensity was different every week according to the peak treadmill running speed (v peak) percentage of each rat. Isoproterenol injection was used to induce myocardial infarction (MI). Expressions of creatine kinase‐MB (CK‐MB), PGC‐1α troponin‐I, mitochondrial transcription factor A (TFAM), vascular endothelial growth factor (VEGF), and microRNA 126 (miR‐126) genes were measured. The variables were measured using biochemical and RT‐PCR methods. The significance level (P value≤0.05) was analyzed using ANOVA test. Results. The results showed that 4 weeks of HIIT training led to a significant increase in PGC‐1α, TFAm, and VEGF levels in the MI, HIIT, and HIIT+MI groups compared to the sham group (P = 0.001). HIIT exercises increased miR‐126 in the different groups compared to the sham group; however, it was not significant. Conclusion. The results obtained showed that HIIT exercise exerts cardio‐protective effects to reduce cardiac tissue injury and necrosis against MI. These effects increase mitochondrial biogenesis and angiogenesis by inducing the increased expression of VEGF, TFAM, PGC‐1α, and miR‐126 genes in the heart tissue. Therefore, HIIT training, as a preconditioning program, was able to protect the cardiac tissue against MI.
Metabolomics and Lipidomics Studies in Pediatric Type 1 Diabetes: Biomarker Discovery for the Early Diagnosis and Prognosis
Authors: Liu Yaru , Dong Guanping , Huang Ke , Hong Ye , Chen Xuefeng , Zhu Mingqiang , Hao Xiaoqiang , Ni Yan , Fu Junfen
Published: July 2023

Aim. Type 1 diabetes (T1D) is an autoimmune disease with heterogeneous risk factors. Metabolic perturbations in the pathogenesis of the disease are remarkable to illuminate the interaction between genetic and environmental factors and how islet immunity and overt diabetes develop. This review aimed to integrate the metabolic changes of T1D to identify potential biomarkers for predicting disease progression based on recent metabolomics and lipidomics studies with parallel methodologies. Methods. A total of 18 metabolomics and lipidomics studies of childhood T1D during the last 15 years were reviewed. The metabolic fingerprints consisting of 41 lipids and/or metabolite classes of subjects with islet autoantibodies, progressors of T1D, and T1D children were mapped in four-time dimensions based on a tentative effect-score rule. Results. From birth, high-risk T1D subjects had decreased unsaturated triacylglycerols, unsaturated phosphatidylcholines (PCs), sphingomyelins (SMs), amino acids, and metabolites in the tricarboxylic acid (TCA) cycle. On the contrary, lysophosphatidylcholines (LPCs) and monosaccharides increased. And LPCs and branched-chain amino acids (BCAAs) were elevated before the appearance of islet autoantibodies but were lowered after seroconversion. Choline-related lipids (including PCs, SMs, and LPCs), BCAAs, and metabolites involved in the TCA cycle were identified as consensus biomarkers potentially predicting the development of islet autoimmunity and T1D. Decreased LPCs and amino acids indicated poor glycemic control of T1D, while elevated lysophosphatidylethanolamines and saturated PCs implied good glycemic control. Further pathway analysis revealed that biosynthesis of aminoacyl-tRNA, BCAAs, and alanine, aspartate, and glutamate metabolism were significantly enriched. Moreover, established cohort studies and predictive statistical models of pediatric T1D were also summarized. Conclusion. The metabolic profile of high-risk T1D subjects and patients demonstrated significant changes compared with healthy controls. This integrated analysis provides a comprehensive overview of metabolic features and potential biomarkers in the pathogenesis and progression of T1D.
Multiple Levels of Influence on Lifestyle Behaviors among Cancer Survivors in Racial and Ethnic Minority Groups: A Systematic Review
Authors: Cho Dalnim , Kim Seokhun , Mama Scherezade K. , Swartz Maria C. , Geng Yimin , Lu Qian
Published: July 2023

Objective. This systematic review aimed to provide a critical summary of studies of physical activity (PA) and diet among racial/ethnic minority cancer survivors. Guided by the socio-ecological model, we identified factors across multiple levels—individual, family/social support, provider/team, and organization/local community/policy environment—that affect PA and diet among racial/ethnic minority survivors. Methods. We searched the Ovid MEDLINE, EBSCO CINAHL, Ovid PsycInfo, and PubMed databases. We extracted the behavior of focus (i.e., PA and diet), cancer type, race/ethnicity, and the level(s) of influence (and the corresponding factor(s)), and each eligible study investigated individual (e.g., demographic characteristics, psychological factors), family/social support, provider/team (e.g., healthcare provider recommendations), and organization/local community/policy environment (e.g., neighborhood/social environment). Results. Of 1,603 studies identified, 23 unique studies were eligible. Most studies included breast cancer survivors (n = 19) and Black survivors (n = 13). Seventeen studies assessed associations between PA and factors at the level of the individual (16 studies), family/social support (two studies), provider/team (one study), or organization/local community/policy environment (four studies). Eleven studies assessed associations between diet and factors at the level of the individual (11 studies), family/social support (two studies), provider/team (one study), or organization/local community/policy environment (two studies). Only five studies simultaneously investigated factors across multiple levels. Most demographic and cancer-related factors were not associated with PA or diet. Overall, factors from social-cognitive theories (e.g., self-efficacy) were positively associated with PA. Less consensus was found regarding diet because fewer studies existed, and they also investigated a diverse range of eating behaviors. Conclusions. There is a critical need for studies of PA and diet that investigate multiple levels of influence particularly for Asian American survivors, male survivors, and cancers other than breast cancer. Social-cognitive theories may help guide the designing of multilevel PA interventions for racial/ethnic minority survivors. Studies assessing overall eating quality or adherence to dietary guidelines are needed.
Biochemical Analysis and Human Aldose Reductase Inhibition Activity of Selected Medicinal Plants of Nepal
Authors: Upadhyaya Siddha Raj , Magar Lila Bahadur , Thapa Ranjita , Joshi Soniya , Khadayat Karan , Marasini Bishnu P. , Parajuli Niranjan
Published: July 2023

Aldose reductase has received extensive research as a key enzyme in the development of long-term problems linked to diabetes mellitus. Overexpression of this enzyme or with exceeded glucose concentration in the blood increases sorbitol on the retina leading to retinopathy, which is the adverse effect of type II diabetes. Approximately 100 million people are suffering from diabetic retinopathy globally. This research is focused on studying the total phenolic content (TPC), total flavonoid content (TFC), antioxidant potential, and aldose reductase inhibiting properties of selected medicinal plants such as Anacyclus pyrethrum, Bergenia ciliata, Rhododendron arboreum, and Swertia chirayita. In addition, ADMET analysis and molecular docking of seven previously identified compounds from the chosen medicinal plants were carried out against human aldose reductase (PDB ID: 4JIR). The ethanol extract of S. chirayita exhibited the highest TPC (4.63 ± 0.16 mg GAE/g) and TFC (0.90 ± 0.06 mg QE/g). Analysis of 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based antioxidant assay showed that IC50 of the ethanolic extract of B. cilata and R. arboreum showed a significant antioxidant activity with IC50 value of 0.05 mg/mL. The percentage inhibition of AR by extract of B. ciliata (94.74 ± 0.01%) was higher than other plant extracts. A molecular docking study showed that morin isolated from B. ciliata showed a good binding interaction with AR. This study showed that the extracts of A. pyrethrum, B. ciliata, and R. arboreum could be potential sources of inhibitors against AR to treat retinopathy.
Supplementary Figure S3 from Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer
Authors: Williams Christopher J.M. , Elliott Faye , Sapanara Nancy , Aghaei Faranak , Zhang Liping , Muranyi Andrea , Yan Dongyao , Bai Isaac , Zhao Zuo , Shires Michael , Wood Henry M. , Richman Susan D. , Hemmings Gemma , Hale Michael , Bottomley Daniel , Galvin Leanne , Cartlidge Caroline , Dance Sarah , Bacon Chris M. , Mansfield Laura , Young-Zvandasara Kathe , Sudan Ajay , Lambert Katy , Bibby Irena , Coupland Sarah E. , Montazeri Amir , Kipling Natalie , Hughes Kathryn , Cross Simon S. , Dewdney Alice , Pheasey Leanne , Leng Cathryn , Gochera Tatenda , Mangham D. Chas , Saunders Mark , Pritchard Martin , Stott Helen , Mukherjee Abhik , Ilyas Mohammad , Silverman Rafael , Hyland Georgina , Sculthorpe Declan , Thornton Kirsty , Gould Imogen , O'Callaghan Ann , Brown Nicholas , Turnbull Samantha , Shaw Lisa , Seymour Matthew T. , West Nicholas P. , Seligmann Jenny F. , Singh Shalini , Shanmugam Kandavel , Quirke Philip
Published: July 2023

Scatterplot: AREG vs EREG
Supplementary Tables S1-S5 from The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas
Authors: Heinze Karolin , Cairns Evan S. , Thornton Shelby , Harris Bronwyn , Milne Katy , Grube Marcel , Meyer Charlotte , Karnezis Anthony N. , Fereday Sian , Garsed Dale W. , Leung Samuel C.Y. , Chiu Derek S. , Moubarak Malak , Harter Philipp , Heitz Florian , McAlpine Jessica N. , DeFazio Anna , Bowtell David D.L. , Goode Ellen L. , Pike Malcolm , Ramus Susan J. , Pearce C. Leigh , Staebler Annette , Köbel Martin , Kommoss Stefan , Talhouk Aline , Nelson Brad H. , Anglesio Michael S.
Published: July 2023

Supplementary Tables S1-S5
Supplementary Table S3 from B-cell Receptor Pathway Mutations Are Infrequent in Patients with Chronic Lymphocytic Leukemia on Continuous Ibrutinib Therapy
Authors: Woyach Jennifer A. , Ghia Paolo , Byrd John C. , Ahn Inhye E. , Moreno Carol , O'Brien Susan M. , Jones Daniel , Cheung Leo W.K. , Chong Elizabeth , Kwei Kevin , Dean James P. , James Danelle F. , Wiestner Adrian
Published: July 2023

Supplemental Table 3. Frequency of BTK and PLCG2 mutations in previously untreated patients or those with relapsed/refractory disease who experienced Richter's transformation
Data from The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas
Authors: Heinze Karolin , Cairns Evan S. , Thornton Shelby , Harris Bronwyn , Milne Katy , Grube Marcel , Meyer Charlotte , Karnezis Anthony N. , Fereday Sian , Garsed Dale W. , Leung Samuel C.Y. , Chiu Derek S. , Moubarak Malak , Harter Philipp , Heitz Florian , McAlpine Jessica N. , DeFazio Anna , Bowtell David D.L. , Goode Ellen L. , Pike Malcolm , Ramus Susan J. , Pearce C. Leigh , Staebler Annette , Köbel Martin , Kommoss Stefan , Talhouk Aline , Nelson Brad H. , Anglesio Michael S.
Published: July 2023

AbstractPurpose:
Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%–20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited.
Experimental Design:
We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC.
Results:
Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (POLEmut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival P > 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the no specific molecular profile (NSMP) subtype, where immune infiltrates lacking B cells (TILB minus) had inferior outcome (disease-specific survival: HR, 4.0; 95% confidence interval, 1.1–14.7; P < 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes.
Conclusions:
Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study.
Supplementary Table S5B from Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study
Authors: Koyama Takafumi , Shimizu Toshio , Kojima Yuki , Sudo Kazuki , Okuma Hitomi Sumiyoshi , Shimoi Tatsunori , Ichikawa Hitoshi , Kohsaka Shinji , Sadachi Ryo , Hirakawa Akihiro , Yoshida Akihiko , Ando Reiko Makihara , Ueno Toshihide , Yanagaki Mitsuru , Matsui Naoko , Nakamura Kenichi , Yamamoto Noboru , Yonemori Kan
Published: July 2023

Whole-exome sequencing and RNA sequencing analyses oftumor tissue samples at pre-and post-treatment
Supplementary Table S4 from Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study
Authors: Koyama Takafumi , Shimizu Toshio , Kojima Yuki , Sudo Kazuki , Okuma Hitomi Sumiyoshi , Shimoi Tatsunori , Ichikawa Hitoshi , Kohsaka Shinji , Sadachi Ryo , Hirakawa Akihiro , Yoshida Akihiko , Ando Reiko Makihara , Ueno Toshihide , Yanagaki Mitsuru , Matsui Naoko , Nakamura Kenichi , Yamamoto Noboru , Yonemori Kan
Published: July 2023

Progression-free survival ratio
Supplementary Figure S6 from Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study
Authors: Koyama Takafumi , Shimizu Toshio , Kojima Yuki , Sudo Kazuki , Okuma Hitomi Sumiyoshi , Shimoi Tatsunori , Ichikawa Hitoshi , Kohsaka Shinji , Sadachi Ryo , Hirakawa Akihiro , Yoshida Akihiko , Ando Reiko Makihara , Ueno Toshihide , Yanagaki Mitsuru , Matsui Naoko , Nakamura Kenichi , Yamamoto Noboru , Yonemori Kan
Published: July 2023

Study design
Figure S4 from Synergism between IL21 and anti-PD-1 combination therapy is underpinned by coordinated reprogramming of the immune cellular network in the tumor microenvironment
Authors: Wu Shaoxian , Huang Hao , Sun Runzi , Gao David Shihong , Ye Fan , Huang Jianing , Li Ella , Ni Andrew , Lu Kevin GuoKai , Chen Kong , Jiang Jingting , Morel Penelope A. , Zhong Ziyang , Lu Binfeng
Published: July 2023

Supplementary Figure 4. IL21-anti-HSA and PD-1 mAbs synergy at the proliferation is due to upregulation of IL21R by PD-1 mAbs treatment and IL21 directly promotes proliferation on IL21R+ CD8+ T cells.
Figure S3 from Synergism between IL21 and anti-PD-1 combination therapy is underpinned by coordinated reprogramming of the immune cellular network in the tumor microenvironment
Authors: Wu Shaoxian , Huang Hao , Sun Runzi , Gao David Shihong , Ye Fan , Huang Jianing , Li Ella , Ni Andrew , Lu Kevin GuoKai , Chen Kong , Jiang Jingting , Morel Penelope A. , Zhong Ziyang , Lu Binfeng
Published: July 2023

Supplementary Figure 3. IL21-anti-HSA/anti-PD-1 leads to altered immune cell populations in the tumor microenvironment.
Figure S2 from Synergism between IL21 and anti-PD-1 combination therapy is underpinned by coordinated reprogramming of the immune cellular network in the tumor microenvironment
Authors: Wu Shaoxian , Huang Hao , Sun Runzi , Gao David Shihong , Ye Fan , Huang Jianing , Li Ella , Ni Andrew , Lu Kevin GuoKai , Chen Kong , Jiang Jingting , Morel Penelope A. , Zhong Ziyang , Lu Binfeng
Published: July 2023

Supplementary Figure 2. FTY720 injection did not affect on anti-PD-1 anti-tumor effect.
Supplementary Table 5 from Exploring the onset and progression of prostate cancer through a multicellular agent-based model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M , Bergman Andries M , Zwart Wilbert , Eduati Federica
Published: July 2023

Patient markers distinguishing the eight different patient classes
Figure S3 from Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Anti-Tumor Activity Against Prostaglandin-Expressing Tumors
Authors: Francica Brian J. , Holtz Anja , Lopez Justine M , Freund David , Chen Austin , Wang Dingzhi , Powell David , Kipper Franciele C , Panigrahy Dipak , DuBois Raymond N , Whiting Chan C. , Prasit Peppi , Dubensky Thomas W
Published: July 2023

Combination of Single EP2 and EP4 antagonism mirrors dual antagonism by TPST-1495