bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Covid-19 on the Greek Media
Authors: Papathanassopoulos Stylianos , Antoniades Euripides
Published: December 2023

It is widely recognized that Greece effectively managed the COVID-19 pandemic crisis through the early implementation of stringent measures and the imposition of lockdowns, similar to strategies adopted by other nations. Another noteworthy achievement was the rapid adaptation of the Greek populace to digital services. However, the situation differs in the realm of media, particularly in the context of traditional or "legacy" media. These media outlets, emerging from a decade-long financial crisis marked by significant declines in advertising revenues, confronted the adverse repercussions of the COVID-19 pandemic. While there was an increase in media consumption during this period, advertising revenue experienced a substantial decline. What remains unaltered, though, is the persistent "traditional dirigist role of the Greek state" in shaping the media landscape. Adversarial media or media supporting the “Opposition” political parties as well the major Opposition accused the government of discrimination regarding the allocation of the COVID-19 public communication campaign The pandemic has reaffirmed the inclination of the Greek media to endorse an interventionist state model, even in the digital age. Much of Greece's distinctive characteristics are attributed to the prominent role the state has assumed in promoting the country's economic development.This paper aims to highlight the side-effects of the COVID-19 crisis in the Greek media sector. It will also attempt to show that regardless of the changes caused due to the financial crisis and the fact that media outlets changed hands, the interplay between the Greek media and the political system still plays a pivotal role.
Effects of Water-to-Air Mass Ratio on Long-Term Washing Efficiency and Erosion Risk in an Axial Compressor Under Online Washing Conditions
Authors: Agati Giuliano , Venturini Paolo , Gabriele Serena , Rispoli Franco , Borello Domenico
Published: December 2023

One of the main reasons for gas turbines’ performance losses is the deposition of dirt on the compressor blades. Dirt deposit has to be periodically removed to keep the engine performance as high as possible. This is the reason motivating the presence of online water washing systems in most compressor gas turbines. Such systems aim at cleaning the compressor blades to recover efficiency; thus, the larger the water flow, the better it is assumed the compressor is cleaned (fixing all the other conditions). In the present work, we simulate the long-term behavior of a real axial compressor, from the inlet to the first-stage rotor, subject to online water washing with different water flowrates. The frozen rotor approach is adopted to solve the flow field in the rotor region. Simulations are performed by using the unsteady k-ɛ realizable model coupled with a Lagrangian tracking of the injected liquid phase. Water droplet erosion is handled by using a semi-empirical model developed by the authors. In each simulation, 504,000 parcels have been tracked, providing statistically reliable predictions. To simulate the long-term evolution of the washing process, a discrete mesh morphing technique coupled with the use of specific scale factors is adopted. Each of the tested configurations is composed of three successive erosive steps up to the blade compressor end-of-life. By varying the water-to-air mass fraction (WAMF*), six different injection configurations are assessed in terms of long-time average washing efficiency and erosion risk. The results predicted show the dependence of the considered washing indices on water mass flowrate and set the stage for the development of a washing optimization tool, which can help the design and management processes. In scenarios where washing indices are given minimal importance and the objective is to reduce the risk of erosion, the optimal injection configuration was shown to correspond to a WAMF* value of 0.250. Conversely, when washing efficiency is prioritized, the optimal injection configuration has been shown to correspond to the case where WAMF* = 0.750.
Exploring effects of social information on talker-independent accent adaptation
Authors: McLaughlin Drew J. , Van Engen Kristin J.
Published: December 2023

The present study examined whether race information about speakers can promote rapid and generalizable perceptual adaptation to second-language accent. First-language English listeners were presented with Cantonese-accented English sentences in speech-shaped noise during a training session with three intermixed talkers, followed by a test session with a novel (i.e., fourth) talker. Participants were assigned to view either three East Asian or three White faces during training, corresponding to each speaker. Results indicated no effect of the social priming manipulation on the training or test sessions, although both groups performed better at test than a control group.
The Evolution of Scholarship of Biomechanics and Motor Control Within the Academy: The Past, the Present, and the Future
Authors: Brink Kolby J. , Likens Aaron , Stergiou Nick
Published: December 2023

This essay delves into the intricate relationship between biomechanics and motor control, exploring their historical evolution and close interdependence. From the foundational works of Aristotle to the contemporary advancements achieved by esteemed members of the National Academy of Kinesiology, we describe the impactful contributions of both past and present National Academy of Kinesiology figures in the realms of motor control and biomechanics. A key theme throughout the essay is the recognition of the fundamental influence of natural laws on movement and the fundamental role of variability in unifying the realms of biomechanics and motor control. Looking ahead, we emphasize the transformative potential of strong inference as a guiding principle for substantive research in both fields, illustrating its application through our investigative endeavors. By uniting biomechanics and motor control through interdisciplinary collaboration, this pursuit of knowledge holds the promise of reshaping our comprehension of human movement and performance.
Large females connect Atlantic cod spawning sites
Authors: Olsen Esben Moland , Karlsen Ørjan , Skjæraasen Jon Egil
Published: December 2023

The Earth’s ecosystems are increasingly deprived of large animals. Global simulations suggest that this downsizing of nature has serious consequences for biosphere functioning. However, the historical loss of large animals means that it is now often impossible to secure empirical data revealing their true ecological importance. We tracked 465 mature Atlantic cod (
Gadus morhua
) during their winter spawning season and show that large females (up to 114 centimeters in length), which are still found in mid-Norway, were characterized by more complex movement networks compared with smaller females. Large males were sparse but displayed similar movement patterns. Our finding implies that management programs promoting large fish will have positive impacts on population resilience by facilitating the continued use of a diversity of spawning habitats and the connectivity between them.
Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules
Authors: Muir Kyle W. , Batters Christopher , Dendooven Tom , Yang Jing , Zhang Ziguo , Burt Alister , Barford David
Published: December 2023

Kinetochores couple chromosomes to the mitotic spindle to segregate the genome during cell division. An error correction mechanism drives the turnover of kinetochore-microtubule attachments until biorientation is achieved. The structural basis for how kinetochore-mediated chromosome segregation is accomplished and regulated remains an outstanding question. In this work, we describe the cryo–electron microscopy structure of the budding yeast outer kinetochore Ndc80 and Dam1 ring complexes assembled onto microtubules. Complex assembly occurs through multiple interfaces, and a staple within Dam1 aids ring assembly. Perturbation of key interfaces suppresses yeast viability. Force-rupture assays indicated that this is a consequence of impaired kinetochore-microtubule attachment. The presence of error correction phosphorylation sites at Ndc80-Dam1 ring complex interfaces and the Dam1 staple explains how kinetochore-microtubule attachments are destabilized and reset.
Sediment austerity is the new coastal norm
Authors: Larsen Laurel G. , Milligan Brett
Published: December 2023

Insufficient river-derived sediment for tidal marshes requires creative, local management
Cecal microbiota and mammary gland microRNA signatures are related and modifiable by dietary flaxseed with implications for breast cancer risk
Authors: Wu Diana , Thompson Lilian U. , Comelli Elena M.
Published: December 2023

The gut microbial ecosystem underlies physiological relationships between the gut and distal organs. Mechanisms remain elusive but rely at least partially on the production of a diverse set of absorbable metabolites and host gene expression regulation. Here we show that in female mice, gut cecal microbiota profiles are related to microRNAs (miRNAs) expressed in the mammary gland. A subset of these miRNAs were found to regulate genes involved in breast cancer-related processes, such as cell proliferation and migration. To determine if these relationships could be exploited toward the reduction of breast cancer risk, we studied if they are modifiable by dietary flaxseed (FS), a source of lignan secoisolariciresinol diglucoside (SDG) and alpha-linolenic acid (ALA)-rich oil (FSO), both with antitumor effects. Importantly, SDG, but not ALA, needs microbial processing to release bioactive metabolites. We found that the microbiota and mammary gland miRNA are related, and FS modifies these relationships toward an antioncogenic phenotype. FSO- and SDG-related miRNAs were found to be involved in different pathways and neither FSO nor SDG alone could recapitulate the effects of whole FS, affecting unique pathways related to extracellular matrix processing. These findings highlight the existence of inter-organ microbiota-miRNA relationships, show that dietary interventions interact to affect them, and suggest a novel route for breast cancer prevention.

IMPORTANCE

Breast cancer is a leading cause of cancer mortality worldwide. There is a growing interest in using dietary approaches, including flaxseed (FS) and its oil and lignan components, to mitigate breast cancer risk. Importantly, there is recognition that pubertal processes and lifestyle, including diet, are important for breast health throughout life. Mechanisms remain incompletely understood. Our research uncovers a link between mammary gland miRNA expression and the gut microbiota in young female mice. We found that this relationship is modifiable via a dietary intervention. Using data from The Cancer Genome Atlas, we also show that the expression of miRNAs involved in these relationships is altered in breast cancer in humans. These findings highlight a role for the gut microbiome as a modulator, and thus a target, of interventions aiming at reducing breast cancer risk. They also provide foundational knowledge to explore the effects of early life interventions and mechanisms programming breast health.
Kinetic Assessment of the Biodegradability of Gel-Forming Soil Conditioners in Incubation Experiments with Instrumental Monitoring of Carbon Dioxide
Authors: Smagin A. V. , Sadovnikova N. B. , Belyaeva E. A. , Korchagina K. V. , Kokoreva A. A. , Krivtsova V. N.
Published: December 2023

A quantitative study of the biodegradability of polymer soil conditioners is necessary for a reasonable prediction of their stability and functioning in soils. For this purpose, a new methodological approach based on PASCO (USA) equipment was proposed. This approach allows recording continuous kinetic curves of CO2 emission in laboratory experiments based on incubation of composite gel-forming soil conditioners. Several characteristic types of respiration curves have been identified, and new physically based models have been proposed for their description with subsequent calculation of the half-lives of composite hydrogels. For the traditionally considered non-biodegradable acrylic superabsorbents of soil water, the possibility of rapid biodegradation was shown for the first time in the case of the addition of a biologically active compost extract into their liquid phase. With this treatment, which brings laboratory experiments closer to real soil conditions, the half-lives of both the well-known European Aquasorb and Zeba superabsorbents and the Russian Aquapastus hydrogel decreased by an order of magnitude from the initial values of 2–6 years to 0.1–0.3 years. In practice, this can negatively affect the profitability of using such materials for soil conditioning due to their rapid destruction and loss of functionality. The addition of silver ions into innovative Aquapastus composite superabsorbents at a dose of 0.1% or 10 ppm in swollen gel structures effectively reduces their biodegradability, prolonging the half-life to 10 years or more, which is twice the German standard DüMV 05.12.12 of the stability of polymer ameliorants.
Elemental Phosphorus in the Synthesis of Organophosphorus Compounds: The Recent Advances (A Review)
Authors: Malysheva S. F. , Kuimov V. A. , Arbuzova S. N.
Published: December 2023

Recent publications on direct reactions of elemental phosphorus with organic halides (alkyl bromides, aryl (and hetaryl) halides, and aryl (and hetaryl) methyl halides) in the presence of superbasic and micellar catalysts are considered. The development of effective, technologically and environmentally acceptable methods for obtaining alkyl(and benzyl)-H-phosphinic and alkylphosphonic acids, triaryl(and hetaryl)phosphines and hetarylmethylphosphine oxides based on the above reactions is analyzed.
Non-pharmacological pain relief interventions in preterm neonates undergoing screening for retinopathy of prematurity: a systematic review
Authors: Fajolu Iretiola Bamikeolu , Dedeke Iyabode Olabisi Florence , Ezenwa Beatrice Nkolika , Ezeaka Veronica Chinyere
Published: December 2023

Objective

The objective of this review was to determine the efficacy of non-pharmacological interventions for pain management during retinopathy of prematurity (ROP) screening.

Methods and analysis

Electronic search of Ovid MEDLINE, PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Google Scholar and ClinicalTrials.gov (USA) was conducted. Search terms from the research question and inclusion criteria were used to select randomised control trials (RCT) published from January 2000 to May 2023. Relevant data were extracted, and risk of bias was assessed using the Cochrane Risk of Bias tool V.2. Critical appraisal and grading of the quality of evidence were done using the Critical Appraisal Skills Programme tool for RCTs and the Grading of Recommendations Assessment, Development and Evaluation, respectively.

Results

Twenty-one RCTs were included; 14 used sweet taste, while 7 used modified developmental care, touch or positioning, multisensory stimulation, non-nutritive sucking or music. Six studies on sweet taste and all seven latter studies showed a difference in the pain scores in favour of the interventions. The quality of evidence was however judged low and moderate due to some concerns in the randomisation process, measurement of outcome assessment and selection of reported results domains.

Conclusion

The use of gentle touch, nesting, positioning, music, multisensory stimulation and developmental care in reducing pain during ROP screening is promising, however, larger studies designed to eliminate the identified concerns are needed. More evidence is also needed before sweet taste interventions can be recommended in routine practice.
First law of black hole thermodynamics and the weak cosmic censorship conjecture for Kerr–Newman Taub–NUT black holes
Authors: Yang Si-Jiang , Guo Wen-Di , Wei Shao-Wen , Liu Yu-Xiao
Published: December 2023

Stimulated by the recent researches of black hole thermodynamics for black hole with Newman–Unti–Tamburino (NUT) parameter, we investigate the thermodynamics and weak cosmic censorship conjecture for a Kerr–Newman Taub–NUT black hole. By defining the electric charge as a Komar integral over the event horizon, we construct a consistent first law of black hole thermodynamics for a Kerr–Newman Taub–NUT black hole through Euclidean action. Having the first law of black hole thermodynamics, we investigate the weak cosmic censorship conjecture for the black hole with a charged test particle and a complex scalar field. We find that an extremal black hole cannot be destroyed by a charged test particle and a complex scalar field. For a near-extremal black hole with small NUT parameter, it can be destroyed by a charged test particle but cannot be destroyed by a complex scalar field.
Digital Ethics for Biometric Applications in a Smart City
Authors: Ng Lynnette H. X. , Lim Abigail C. M. , Lim Adrian X. W. , Taeihagh Araz
Published: December 2023

From border control using fingerprints to law enforcement with video surveillance to self-activating devices via voice identification, biometric data is used in many applications in the contemporary context of a Smart City. Biometric data consists of human characteristics that can identify one person from others. Given the advent of big data and the ability to collect large amounts of data about people, data sources ranging from fingerprints to typing patterns can build an identifying profile of a person. In this article, we examine different types of biometric data used in a smart city based on a framework that differentiates between profile initialization and identification processes. Then, we discuss digital ethics within the usage of biometric data along the lines of data permissibility and renewability. Finally, we provide suggestions for improving biometric data collection and processing in the modern smart city.
TikTok’s Project Texas - Social Media Data Governance Across Geopolitical Lines
Authors: Lee Roy Ka-Wei , Ng Lynnette Hui Xian
Published: December 2023

TikTok, a video sharing social media platform, is a subsidiary of ByteDance, a Chinese-owned company, with its headquarters in Singapore. There’s an ongoing concern in the United States Congress that American users’ data may be exposed to unauthorized access or manipulated by foreign entities. In an effort to alleviate these concerns and retain user trust, TikTok launched Project Texas, aimed at safeguarding American users’ data. This commentary examines the broader implications of Project Texas on data governance, particularly in the context of geopolitical boundaries. It delves into the geopolitics of social media and the autonomy of data governance in the digital age, offering advice for all social media platforms regarding these issues.
RF-TESI: Radio Frequency Fingerprint-based Smartphone Identification under Temperature Variation
Authors: Gu Xiaolin , Wu Wenjia , Song Aibo , Yang Ming , Ling Zhen , Luo Junzhou
Published: December 2023

Radio frequency fingerprint identification (RFFI) is a promising technique for smartphone identification. However, we find that the temperature of the RF front end in smartphones can significantly impact the RF features, including the carrier frequency offset (CFO) and statistical RF features. The unstable RF features caused by temperature changes can negatively affect the performance of state-of-the-art RFFI approaches. To this end, we propose the RF-TESI solution for smartphone identification under temperature variation. First, we construct a dataset by extracting temperature and RF features. In the dataset, the extracted temperature values constitute a set of temperature values and each registered temperature value corresponds to a group of RF features. Next, we evaluate the distinctiveness of RF features across smartphones to select the most suitable RF fingerprint. Then, we train multiple random forest models, each tagged with a registered temperature. In addition, because there are still many temperatures out of the temperature set, we design an RF fingerprint estimation method to estimate RF fingerprints at unregistered temperatures. Finally, the experiments show RF-TESI demonstrates satisfactory performance under different scenarios, taking into account variations in temperature, time and position. Besides, our proposed approach is better than all state-of-the-art approaches in smartphone identification.
T Follicular Helper Cell Heterogeneity
Authors: Song Wenzhi , Craft Joe
Published: December 2023

T follicular helper (Tfh) cells specialize in helping B cells and are therefore critical contributors to the generation of humoral immunity. Tfh cells aid immunoglobulin class-switch recombination and support the germinal center response, thereby promoting immunoglobulin affinity maturation and the generation of humoral immune memory. Although their primary function is to promote B cell responses, Tfh cells also display phenotypic and functional diversity determined by the immunological and spatial contexts from which they emerge. We review recent advances in understanding the heterogeneity within Tfh cell subsets along with their differentiation and migratory trajectory, the phenotypes they adopt, their ontological relationships with one another, and their function in their respective environments.
A low-cost 2-D sarcomere model to demonstrate titin-related mechanisms for force production
Authors: Baptista de Oliveira Medeiros Heron , de Brito Fontana Heiliane , Herzog Walter
Published: December 2023

Our physical sarcomere model illustrates not only the classic view of muscle contraction, the sliding filament and cross-bridge theories, but also the newly discovered role of titin in force regulation, called the three-filament theory. The model allows for easy visualization of the role of titin in muscle contraction and aids in explaining complex muscle properties that are not captured by the traditional cross-bridge theory.
Creating your own line: reflections from early career scientists
Authors: Bruce Christina D. , DuBose Lyndsey E. , Tremblay Joshua C. , Oliveira Barbara , Islam Hashim , Teixeira André L. , Brewster L. Madden , Meah Victoria L. , Tymko Michael M.
Published: December 2023

This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees that is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.
“CARBGAME” (CARd & Board GAmes in Medical Education): a gamification innovation to foster active learning in biochemistry for medical students
Authors: Surapaneni Krishna Mohan
Published: December 2023

“CARBGAME” (CARd & Board GAmes in Medical Education) creates a unique and fun-filled educational environment where students learn complex but essential medical chapters in a gamified manner using cards and boards. This customizable innovation is strengthened with fundamental educational principles to promote engaging and meaningful learning experiences for students.
Angiotensin II acts through Rac1 to upregulate pendrin: role of NADPH oxidase
Authors: Pham Truyen D. , Verlander Jill W. , Chen Chao , Pech Vladimir , Kim Hailey I. , Kim Young Hee , Weiner I. David , Milne Ginger L. , Zent Roy , Bock Fabian , Brown Dennis , Eaton Amity , Wall Susan M.
Published: December 2023

This study defines a new signaling mechanism by which angiotensin II modulates oxidative stress and blood pressure.
Brain and muscle activity during fatiguing maximum-speed knee movement
Authors: Correia José Pedro , Domingos Christophe , Witvrouw Erik , Luís Pedro , Rosa Agostinho , Vaz João R. , Freitas Sandro R.
Published: December 2023

The loss of knee movement rate with acute fatigue induced by high-speed movement is associated with both central and peripheral electrophysiological changes, such as a decrease in EEG power, increased agonist-antagonist cocontraction, and impaired brain-muscle coupling. These findings had not previously been reported for the knee joint, which shows functional and physiological differences compared with the existing findings for smaller upper limb joints.
The effects of 6 wk of resistance training on the gut microbiome and cardiometabolic health in young adults with overweight and obesity
Authors: Cullen John M. A. , Shahzad Shahim , Kanaley Jill A. , Ericsson Aaron C. , Dhillon Jaapna
Published: December 2023

Resistance training induces mixed changes in the gut microbiome, including an increase in the abundances of the Roseburia genus and minor alterations in microbial pathways. However, it is vital to interpret these changes in light of the broader context, where we observe stability in the overall microbiome composition. This stability may be attributed to the microbiome’s resilience, demonstrating its capacity to withstand short-term physiological stressors.
A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive–Compulsive Disorder
Authors: Jiang Jin , Wan Ke , Liu Yueling , Tang Yan , Tang Wenxin , Liu Jian , Ma Jiehua , Xue Chuang , Chen Lu , Qian Huichang , Liu Dandan , Shen Xinxin , Fan Ruijuan , Wang Yongguang , Wang Kai , Ji Gongjun , Zhu Chunyan
Published: December 2023

Background. Obsessive–compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method. Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS). Results. After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups (

p
<
0.001

), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90,

p
=
0.18

). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion. Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.
Reemerging of Encephalomyocarditis Virus in Pigs in Brazil: Pathological and Viral Characterization
Authors: Gris Anderson H. , Alves Raquel S. , Camargo Laura J. , Baumbach Letícia F. , Menegatt Jean C. O. , Silva Emanoelly M. S. , Perosa Fernanda F. , Lima Rafael P. , Bertolini Marianna , Fiúza Aparecida T. L. , Watanabe Tatiane T. N. , Canal Cláudio W. , Driemeier David
Published: December 2023

Encephalomyocarditis virus (EMCV) is a zoonotic disease caused by a highly pathogenic virus that affects wild and domestic animal species, with rodents as its reservoir. Most recently, in South America, this virus was detected in an outbreak affecting humans in Peru. In Brazil, EMCV infection was described in some wild species, in horses, and once in farrowing pigs. The aim of this study is to report the reemergence of EMCV in commercial growing–finishing pigs from two different farms that experienced sudden pig death in midwest Brazil. This aim was achieved through gross pathology, histologic examination, RT‒PCR analysis, and genetic characterization of the virus. Clinical signs, such as trembling, dyspnea, and squealing sounds shortly before death, were only occasionally observed and were nonspecific. On gross examination, cardiomegaly was observed, along with multifocal pale tan foci in the epicardium extending to the myocardium on the cut surface. Microscopically, there was severe myocardial necrosis, dystrophic mineralization, fibrosis, and lymphoplasmacytic and histiocytic myocarditis. Gross and microscopic examinations of the rats were unremarkable. The RT‒PCR analyses of the pig and rat organs were positive for EMCV, and the phylogenetic analysis of the VP1 gene showed that the samples from pigs and rats contained similar strains that had their closest relatives identified in humans in Peru. This is the first genetic characterization of EMCV in Brazil, and the other findings confirm the reemergence of the disease that was transmitted from rats to pigs.
First Clinical Case of Ilizarov Femur Lengthening over a Bioactive and Degradable Intramedullary Implant
Authors: Popkov Arnold , Tverdokhlebov Sergei , Muradisinov Sergei , Popkov Dmitry
Published: December 2023

Introduction. The Ilizarov distraction osteogenesis is a recognized method of limb lengthening in orthopaedic practice. Its most challenging problems are long duration of external fixation and related pin-tract infection and joint contractures. The solution might be the use of a bioactive degradable intramedullary implant stimulating bone healing. Case Presentation. We present a case of a 14-year-old boy with 6 cm posttraumatic shortening of the femur and associated varus deformity of 20 degrees. He was treated with the Ilizarov technique of femur lengthening over an intramedullary degradable polycaprolactone (PCL) implant with hydroxyapatite (HA) filling. We faced no complications within the lengthening process. Shortening and deformity of the femur were corrected in 90 days. The index of external fixation was 15 days/cm. External fixation time was reduced almost twice comparing to the conventional method. Degradable intramedullary nails ensured the advantage of avoidance of the removal procedure. Radiography and CT confirmed faster new bone healing and remodeling. Conclusion. The combined lengthening technique over a PCL/HA implant might be used to shorten external fixation time and to stimulate bone healing especially in patients with compromised bone. Using a bioabsorbable material presents the benefit of eliminating the need for a second surgery to remove the nail, thereby reducing soft tissue damage.
Genetic and Environmental Causes of Variation in an Automated Breast Cancer Risk Factor Based on Mammographic Textures
Authors: Ye Zhoufeng , Dite Gillian S. , Nguyen Tuong L. , MacInnis Robert J. , Schmidt Daniel F. , Makalic Enes , Al-Qershi Osamah M. , Nguyen-Dumont Tu , Goudey Benjamin , Stone Jennifer , Dowty James G. , Giles Graham G. , Southey Melissa C. , Hopper John L. , Li Shuai
Published: December 2023

Background:

Cirrus is an automated risk predictor for breast cancer that comprises texture-based mammographic features and is mostly independent of mammographic density. We investigated genetic and environmental variance of variation in Cirrus.

Methods:

We measured Cirrus for 3,195 breast cancer–free participants, including 527 pairs of monozygotic (MZ) twins, 271 pairs of dizygotic (DZ) twins, and 1,599 siblings of twins. Multivariate normal models were used to estimate the variance and familial correlations of age-adjusted Cirrus as a function of age. The classic twin model was expanded to allow the shared environment effects to differ by zygosity. The SNP-based heritability was estimated for a subset of 2,356 participants.

Results:

There was no evidence that the variance or familial correlations depended on age. The familial correlations were 0.52 (SE, 0.03) for MZ pairs and 0.16(SE, 0.03) for DZ and non-twin sister pairs combined. Shared environmental factors specific to MZ pairs accounted for 20% of the variance. Additive genetic factors accounted for 32% (SE = 5%) of the variance, consistent with the SNP-based heritability of 36% (SE = 16%).

Conclusion:

Cirrus is substantially familial due to genetic factors and an influence of shared environmental factors that was evident for MZ twin pairs only. The latter could be due to nongenetic factors operating in utero or in early life that are shared by MZ twins.

Impact:

Early-life factors, shared more by MZ pairs than DZ/non-twin sister pairs, could play a role in the variation in Cirrus, consistent with early life being recognized as a critical window of vulnerability to breast carcinogens.
First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results
Authors: Schmid Peter , Turner Nicholas C. , Barrios Carlos H. , Isakoff Steven J. , Kim Sung-Bae , Sablin Marie-Paule , Saji Shigehira , Savas Peter , Vidal Gregory A. , Oliveira Mafalda , O'Shaughnessy Joyce , Italiano Antoine , Espinosa Enrique , Boni Valentina , White Shane , Rojas Beatriz , Freitas-Junior Ruffo , Chae Yeesoo , Bondarenko Igor , Lee Jieun , Torres Mattos Cesar , Martinez Rodriguez Jorge Luis , Lam Lisa H. , Jones Surai , Reilly Sarah-Jayne , Huang Xiayu , Shah Kalpit , Dent Rebecca
Published: December 2023

Purpose:

To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC).

Patients and Methods:

The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1–21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance.

Results:

Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels.

Conclusions:

In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts.
Supplementary Table 4 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Supplemental Table 4. Significance measures for correlation matrix between intracellular cytokine FSIs and phosphoprotein FSIs with the CD4 compartment, stimulated conditions. p values for each Pearson’s correlation shown in Supplemental Figure 11B are shown, with statistically significant values highlighted in red.
Supplementary Table 3 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Supplemental Table 3. Significance measures for correlation matrix between intracellular cytokine FSIs and phosphoprotein FSIs with the CD4 compartment, tonic conditions. p values for each Pearson’s correlation shown in Supplemental Figure 11A are shown, with statistically significant values highlighted in red.
Supplemental Figure 9 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Association between CD8 p-NF-kB p65 FSI and intracellular IFN-γ FSI and clinical response to transgenic TCR T cell therapy. Tonic p-NF-kB p65 FSI associations between peak change in tumor burden (A) and overall survival (B). Tonic intracellular IFN-γ FSI associations between peak change in tumor burden (C) and overall survival (D).
Supplemental Figure 5 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Contribution of all assayed secreted cytokines to CD4 cytokine functional strength indices (FSI). Groups are divided by clinical response and tonic vs stimulated culture conditions. Error bars represent +/- standard error of the mean (SEM).
Supplemental Figure 4 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Contribution of all assayed secreted cytokines to CD8 cytokine polyfunctionality strength indices (PSI). Groups are divided by clinical response and tonic vs stimulated culture conditions. Error bars represent +/- standard error of the mean (SEM).
Supplemental Figure 17 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

No association between CD4 Th1 cytokine polyfunctionality and patient survival or change in tumor burden in response to transgenic TCR T cell therapy. CD4 Th1 PSI showed no significant correlations with patient overall survival (A) or peak change in tumor burden (B).
Supplemental Figure 16 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

CD4 Th2 cytokine polyfunctionality is not associated with patient survival. CD4 PSI scores showed no significant correlation with patient overall survival (OS), as measured by Pearson’s r.
Supplemental Figure 14 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Acellular CD4 secretion levels of IL-4 and IL-5 are associated with inferior clinical response to transgenic TCR-T cell therapy. Association of acellular CD4 secretion levels of IL-4 with clinical response (A) and percent change in tumor burden per RECIST 1.1 criteria (B). Association of bulk CD4 secretion levels of IL-5 with clinical response (C) and percent change in tumor burden per RECIST 1.1 criteria (D). * p<0.05, **p<0.01, unpaired t-test.
Supplemental Figure 11 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Correlation matrix between intracellular cytokine FSIs and phosphoprotein FSIs with the CD8 compartment. Values for the tonic conditions (A) and stimulated conditions (B) are shown. Heatmap and numerical values for the corresponding Pearson’s r for each correlation condition are shown.
Data from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Abstract
Transgenic T-cell receptor (TCR) T cell–based adoptive cell therapies for solid tumors are associated with dramatic initial response rates, but there remain many instances of treatment failure and disease relapse. The association of infusion product cytokine profiles with clinical response has not been explored in the context of TCR T-cell therapy products. Single-cell antigen-dependent secretomic and proteomic analysis of preinfusion clinical TCR T-cell therapy products revealed that TNFα cytokine functionality of CD8+ T cells and phospho-STAT3 signaling in these cells were both associated with superior clinical responsiveness to therapy. By contrast, CD4+ T-helper 2 cell cytokine profiles were associated with inferior clinical responses. In parallel, preinfusion levels of IL15, Flt3-L, and CX3CL1 were all found to be associated with clinical response to therapy. These results have implications for the development of therapeutic biomarkers and identify potential targets for enrichment in the design of transgenic TCR T-cell therapies for solid tumors.
Figure S6 from Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance
Authors: Echavidre William , Durivault Jérôme , Gotorbe Célia , Blanchard Thays , Pagnuzzi Marina , Vial Valérie , Raes Florian , Broisat Alexis , Villeneuve Rémy , Amblard Régis , Garnier Nicolas , Ortholan Cécile , Faraggi Marc , Serrano Benjamin , Picco Vincent , Montemagno Christopher
Published: December 2023

Proliferation of DAOY_ KO#22 cells treated with LM609 (1 or 10 μg/mL) for 96 h. The proliferation rates are expressed as the percentage of day 0.
Figure S3 from Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance
Authors: Echavidre William , Durivault Jérôme , Gotorbe Célia , Blanchard Thays , Pagnuzzi Marina , Vial Valérie , Raes Florian , Broisat Alexis , Villeneuve Rémy , Amblard Régis , Garnier Nicolas , Ortholan Cécile , Faraggi Marc , Serrano Benjamin , Picco Vincent , Montemagno Christopher
Published: December 2023

Western-blot analysis of integrin-αvβ3-downstream pathways. Relative protein contents of pFAK/FAK, pAkt/Akt and pERK1/2/ERK were determined in DAOY-derived and HD-MB03-derived cells. Actin acted as a protein-loading control and blots are representative of three independent experiments.
FIGURE 5 from Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance
Authors: Echavidre William , Durivault Jérôme , Gotorbe Célia , Blanchard Thays , Pagnuzzi Marina , Vial Valérie , Raes Florian , Broisat Alexis , Villeneuve Rémy , Amblard Régis , Garnier Nicolas , Ortholan Cécile , Faraggi Marc , Serrano Benjamin , Picco Vincent , Montemagno Christopher
Published: December 2023

In vivo measurement of integrin-αvβ3 expression using SPECT/MRI dual-modality. A, Representative coronal views of MRI (bottom), SPECT (center), and fused SPECT/CT/MRI of HD-MB03 (left) and DAOY (right) tumors at 1 hour postinjection of 99mTc-RAFT-RGD. B,In vivo quantification of 99mTc-RAFT-RGD tumor uptake from SPECT images. Results are expressed as tumor-to-cerebellum ratios. C, Autoradiography on 20 µm tumor-containing cerebellum slices (top) and staining of adjacent slices by Crystal Violet. D, Autoradiographic image quantification of 99mTc-RAFT-RGD uptake in HD-MB03 and DAOY tumor lesions. Results are expressed as tumor-to-cerebellum ratios. Key: *, P < 0.05; **, P < 0.01 versus HD-MB03.
FIGURE 3 from Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance
Authors: Echavidre William , Durivault Jérôme , Gotorbe Célia , Blanchard Thays , Pagnuzzi Marina , Vial Valérie , Raes Florian , Broisat Alexis , Villeneuve Rémy , Amblard Régis , Garnier Nicolas , Ortholan Cécile , Faraggi Marc , Serrano Benjamin , Picco Vincent , Montemagno Christopher
Published: December 2023

Pharmacologic disruption of integrin-αvβ3 impairs downstream signaling, decreasing cell proliferation, migration, and invasion of DAOY. Representative Western blots depicting FAK, Akt, and ERK1/2 activation in DAOY cells following treatment with cilengitide (1 hour of treatment with 1, 5, or 25 µmol/L cilengitide) in A or LM609 (30, 60, or 90 minutes of treatment with 10 µg/mL LM609) in B. Three independent experiments were conducted. Evaluation of DAOY cell proliferation after treatment with cilengitide (0.5 or 2.5 µmol/L) in C or LM609 (1 and 10 µg/mL) in D for 96 hours. Proliferation rates are expressed as a percentage of day 0. Three independent experiments were performed, and data are presented as mean ± SEM. Invasion assays for DAOY cells treated with cilengitide (E) or LM609 (F) for 12 hours. Serum-starved cells were exposed to cilengitide (0.5 or 2.5 µmol/L) in E or LM609 (1 and 10 µg/mL) in F and allowed to invade for 12 hours. Invasion assays were conducted using Matrigel-coated Boyden chamber assays, and the results are expressed as a percentage relative to control cells. Three independent experiments were carried out, and data are presented as mean ± SEM. Key: *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus indicated conditions.