bluuebunny/crossref_metadata_2025 huggingface dataset:
Topical application of jojoba (Simmondsia chinensis L.) wax enhances the synthesis of pro-collagen III and hyaluronic acid and reduces inflammation in the ex-vivo human skin organ culture model
Authors: Tietel Zipora , Melamed Sarit , Ogen-Shtern Navit , Eretz-Kdosha Noy , Silberstein Eldad , Ayzenberg Tomer , Dag Arnon , Cohen Guy
Published: January 2024

Jojoba (Simmondsia chinensis L.) wax was previously reported to increase cutaneous wound healing, ameliorate acne and psoriasis manifestations, and reduce oxidative stress and inflammation. However, its potential cosmetic properties have not been fully investigated. Thus, the current study aimed to evaluate the anti-inflammatory activities of jojoba wax and its impact on the synthesis of extracellular components following topical application. The fatty acid and fatty alcohol profiles of two industrial and two lab-scale cold-press jojoba waxes were analyzed along with total tocopherol and phytosterol content. The dermo-cosmetic effect of all jojoba wax preparations was evaluated ex-vivo, using the human skin organ culture model, which emulates key features of intact tissue. The ability of jojoba wax to reduce secreted levels of key pro-inflammatory cytokines and the safety of the applications in the ex-vivo model were evaluated. In addition, the impact on the synthesis of pro-collagen and hyaluronic acid levels upon treatment was investigated. The results demonstrate that topically applied jojoba wax can reduce LPS-induced secretion of IL-6, IL-8, and TNFα by approx. 30% compared to untreated skin. This effect was enhanced when treatment was combined with low non-toxic levels of Triton X-100, and its efficacy was similar to the anti-inflammatory activity of dexamethasone used as a positive control. In addition, mRNA and protein levels of collagen III and synthesis of hyaluronic acid were markedly increased upon topical application of jojoba. Moreover, the enhanced content of extracellular matrix (ECM) components correlated with the enhanced expression of TGFβ1. Collectively, our results further demonstrate that jojoba can reduce local skin inflammation, and this effect may be increased by emulsifier which increases its bioavailability. In addition, the finding that topical application of jojoba wax enhances the synthesis of pro-collagen and hyaluronic acid and may be beneficial in the treatment of age-related manifestations.
Influence on the fermentation quality, microbial diversity, and metabolomics in the ensiling of sunflower stalks and alfalfa
Authors: Jiang Heng , Wang Si-Yi , Wang Hao-Ran , Jing Yuan-Yuan , Qu Hui , Sun Le , Wang Jiao , Liu Bin , Gao Feng-Qin
Published: January 2024

With the rapid development of the livestock industry, finding new sources of feed has become a critical issue that needs to be addressed urgently. China is one of the top five sunflower producers in the world and generates a massive amount of sunflower stalks annually, yet this resource has not been effectively utilized. Therefore, in order to tap into the potential of sunflower stalks for animal feed, it is essential to explore and develop efficient methods for their utilization.In this study, various proportions of alfalfa and sunflower straw were co-ensiled with the following mixing ratios: 0:10, 2:8, 4:6, 5:5, 6:4, and 8:2, denoted as A0S10, A2S8, A4S6, A5S5, A6S4, and A8S2, respectively. The nutrient composition, fermentation quality, microbial quantity, microbial diversity, and broad-spectrum metabolomics on the 60th day were assessed. The results showed that the treatment groups with more sunflower straw added (A2S8, A4S6) could start fermentation earlier. On the first day of fermentation, Weissella spp.dominated overwhelmingly in these two groups. At the same time, in the early stage of fermentation, the pH in these two groups dropped rapidly, which could effectively reduce the loss of nutrients in the early stage of fermentation.In the later fermentation period, a declining trend in acetic acid levels was observed in A0S10, A2S8, and A4S6, while no butyric acid production was detected in A0S10 and A2S8 throughout the process. In A4S6, butyric acid production was observed only after 30 days of fermentation. From the perspective of metabolites, compared with sunflower ensiling alone, many bioactive substances such as flavonoids, alkaloids, and terpenes are upregulated in mixed ensiling.
How to win in FIFA World Cup Qatar 2022? A study on the configurations of technical and tactical indicators based on fuzzy-set qualitative comparative analysis
Authors: Yan Weihua , Li Shiyue , Wang Di , Yuan Bo , Zeng Haocheng , Ren Dingmeng
Published: January 2024

The FIFA World Cup, which represents the highest level in football, is regarded as a showcase to unfold the development trends of modern football, thus arousing great interest among researchers. However, most of the previous research designs studied the simple linear correlation between technical indicators and game outcomes, which may overlook the complex causalities in football performance. The aim of current study was to introduce a new method to examine winning patterns emerging from Qatar 2022 through a configurational lens. To this end, fuzzy-set qualitative comparative analysis (fsQCA) was conducted using 98 samples (n = 98) out of 49 Qatar 2022 matches discriminating winning and losing teams in regular time (group stage) and in 30 min of extra time (knockout stage). Then, we selected seven variables as our causal conditions, namely, shots on target, possession, defensive line breaks, crosses, receptions in the final third, forced turnovers, and direct pressures. Necessity analysis and sufficiency analysis of configurations were conducted according to fsQCA requirements. The fsQCA operation showed that no individual causal condition is necessary to winning a game and four configurations were derived from the QCA results and these combinations of conditions fall into three typologies of play style: a possession play style, direct play style, and all-round play style. The results confirmed the fact that football is a complex system and suggested that a winning outcome is often produced by combinations of multiple factors. The findings of the current study contribute to the literature by introducing the configurations of various technical and tactical indicators that could raise the possibility of winning and can be used by practitioners working within the fields of player development, coaching, and match preparation.
The effect of age on emotion processing in individuals with mood disorders and in healthy individuals
Authors: Gray Vanessa , Moot William , Frampton Christopher M. A. , Douglas Katie M. , Gallagher Peter , Jordan Jennifer , Carter Janet D. , Inder Maree , Crowe Marie , McIntosh Virginia V. W. , Porter Richard J.
Published: January 2024

Introduction

Emotion processing is an essential part of interpersonal relationships and social interactions. Changes in emotion processing have been found in both mood disorders and in aging, however, the interaction between such factors has yet to be examined in detail. This is of interest due to the contrary nature of the changes observed in existing research - a negativity bias in mood disorders versus a positivity effect with aging. It is also unclear how changes in non-emotional cognitive function with aging and in mood disorders, interact with these biases.

Methods and results

In individuals with mood disorders and in healthy control participants, we examined emotional processing and its relationship to age in detail. Data sets from two studies examining facial expression recognition were pooled. In one study, 98 currently depressed individuals (either unipolar or bipolar) were compared with 61 healthy control participants, and in the other, 100 people with bipolar disorder (in various mood states) were tested on the same facial expression recognition task. Repeated measures analysis of variance was used to examine the effects of age and mood disorder diagnosis alongside interactions between individual emotion, age, and mood disorder diagnosis. A positivity effect was associated with increasing age which was evident irrespective of the presence of mood disorder or current mood episode.

Discussion

Results suggest a positivity effect occurring at a relatively early age but with no evidence of a bias toward negative emotions in mood disorder or specifically, in depressed episodes. The positivity effect in emotional processing in aging appears to occur even within people with mood disorders. Further research is needed to understand how this fits with negative biases seen in previous studies in mood disorders.
The influence of gratitude on patriotism among college students: a cross-sectional and longitudinal study
Authors: Hu Yunjun , Zhang Huilin , Zhang Wei , Li Qian , Cui Guanyu
Published: January 2024

Introduction

Patriotism, a positive emotional attachment to one’s country, has been associated with prosocial behavior, social responsibility, and gratitude. It plays a crucial role in promoting social harmony and national development. However, the factors influencing patriotism and their mechanisms remain unclear. This research consists of two studies exploring the internal mechanisms that connect gratitude and patriotism.

Methods

Study 1 conducted a cross-sectional analysis among 3,826 college students to investigate the influence of gratitude on patriotism, emphasizing the mediating role of general life satisfaction and the moderating impact of socioeconomic status. This approach aimed to elucidate the complex relationships between these variables within college students. Study 2 adopted a longitudinal approach, surveying 905 college students across three-time points. This study was designed to explore the temporal mediation of general life satisfaction in the gratitude-patriotism relationship, offering insights into the evolution of these constructs over time. The sequential surveys aimed to capture the dynamic nature of gratitude’s impact on patriotism, considering the continuous interplay with general life satisfaction among college students.

Results

Study 1 reveals a noteworthy finding: Gratitude enables the direct prediction of patriotism, while additionally, general life satisfaction plays a role between them. Furthermore, the predictive effect of gratitude on patriotism is strengthened among individuals with higher levels of socioeconomic status. However, there is no significant moderating effect between general life satisfaction and patriotism by socioeconomic status. Study 2 demonstrates that general life satisfaction plays a significant mediating role in the relationship between gratitude and patriotism, over a period of three times. However, the moderating influence of socioeconomic status was not substantiated in the longitudinal mediation model.

Conclusion

These two studies shed light on the complex relationship between gratitude and patriotism. They emphasize the significance of gratitude, general life satisfaction, and socioeconomic status in shaping patriotism, offering potential avenues for understanding the internal mechanisms that influence patriotism.
Adaptive leadership and safety citizenship behaviors in Pakistan: the roles of readiness to change, psychosocial safety climate, and proactive personality
Authors: Khan Hira Salah ud din , Chughtai Muhmmmad Salman , Ma Zhiqiang , Li Mingxing , He Di
Published: January 2024

Challenging times have put organizations in a perilous and chaotic state that demands immediate resolution and calls for effective leadership to help navigate out of the crisis. In this context, we focused on psychosocial safety climate theory to investigate the influence of adaptive leadership on safety citizenship behaviors by looking at the mediating effect of readiness to change and the moderating impact of psychosocial safety climate and proactive personality, particularly in the Pakistani healthcare sector. To test the hypotheses, the data were collected from 397 employees working in the healthcare sector of Pakistan at two different times. The results of this study supported the model. The moderated path analysis revealed that psychosocial safety climate strengthens the direct effect of adaptive leadership on readiness to change, whereas the moderating impact of a proactive personality also strengthens the relationship between readiness to change and safety citizenship behaviors. Similarly, both moderators significantly moderated the indirect impact of adaptive leadership on safety citizenship behaviors via readiness to change. To conclude, the present study has significant implications for organizations and practitioners in both steady and uncertain environments.
Rapid initiation of antiretroviral therapy in Turkey: a modeling study
Authors: Yaylali Emine , Erdogan Zikriye Melisa , Calisir Fethi , Pullukcu Husnu , Yildirim Figen , Inan Asuman , Aydin Ozlem Altuntas , Tekin Suda , Sonmezer Meliha Cagla , Sahin Toros , Ozcagli Tahsin Gokcem , Ozelgun Berna
Published: January 2024

Background

To effectively control the HIV epidemic and meet global targets, policymakers recommend the rapid initiation of antiretroviral therapy (ART). Our study aims to investigate the effect of rapid ART programs on individuals diagnosed with HIV, considering varying coverage and initiation days after diagnosis, and compare it to standard-of-care ART treatment in Turkey.

Methods

We used a dynamic compartmental model to simulate the dynamics of HIV infection in Turkey. Rapid treatment, defined as initiation of ART within 7 days of diagnosis, was contrasted with standard-of-care treatment, which starts within 30 days of diagnosis. This study considered three coverage levels (10%, 50%, and 90%) and two rapid periods (7 and 14 days after diagnosis), comparing them to standard-of-care treatment in evaluating the number of HIV infections between 2020 and 2030.

Results

Annual HIV incidence and prevalence for a 10-year period were obtained from model projections. In the absence of a rapid ART program, the model projected approximately 444,000 new HIV cases while the number of cases were reduced to 345,000 (22% reduction) with 90% of diagnosed cases included in the rapid ART program. Similarly, 10% and 50% rapid ART coverage has resulted in 3% and 13% reduction in HIV prevalence over a 10-year period.

Conclusion

Rapid ART demonstrates the potential to mitigate the increasing HIV incidence in Turkey by reducing the number of infections. The benefit of the rapid ART program could be substantial when the coverage of the program reaches above a certain percentage of diagnosed population.
Research on the impact of China’s reform to delegate power, streamline administration, and optimize government services on the technology innovation efficiency of the pharmaceutical manufacturing industry
Authors: Gu Yang , Zhuang Qian
Published: January 2024

Objective

The government has recently implemented reforms aimed at delegating power, streamlining administration, and optimizing government services. This reform has eliminated barriers that impede the growth of various industries, thereby unleashing innovative potential. Additionally, there have been several medical policies, including changes to medical insurance and centralized volume-based procurement. China’s pharmaceutical market has undergone significant changes, leading to increased demands for innovation technology efficiency in pharmaceutical manufacturing.

Methods

The three-stage BCC theory was employed to assess the effectiveness of technology innovation in the industry under this reform. Calculate precise comprehensive technical efficiency values, pure technical efficiency values, and scale efficiency values for technological innovation in the pharmaceutical industry across 30 provinces from 2018 to 2020, after removing environmental factors.

Results

In 2020, Jiangsu and Shandong and nine other provinces reached the comprehensive technical efficiency frontier surface, joining Tianjin, Zhejiang, and Guangdong provinces. However, Gansu, Qinghai, Ningxia, and Xinjiang still need to catch up due to their smaller industrial scale and lack of technology.

Discussion

To ensure the effectiveness of reforms, it is crucial to fully consider provincial differences. Articulating national and provincial policies is necessary to allow efficient provinces to continue and allocate resources toward less efficient provinces to improve overall efficiency.
Occupational risk perception of construction workers: a cross sectional study
Authors: Mastrantonio Riccardo , Cofini Vincenza , Mastrangeli Giada , Pettinaro Mauro , Mastrodomenico Marianna , Fabiani Leila
Published: January 2024

Introduction

Construction workers are often exposed to significant injury risk. The aim of our study is to assess their occupational hazards and injury risk perception.

Methods

We administered 256 questionnaires to construction workers. The survey was aimed at collecting information regarding occupational risk and hazard exposure perception, risk control and behavioral self-assessment. We analyzed the data obtained in order to highlight any associations between injury risk perception and anamnestic, occupational, behavioral or perceptual factors.

Results

Participants were prevalently males (92.37%) aged 21–60 years (94%). They showed a job seniority level of 21.3 (11.51) on average and, ranging from a 1 to 10 score, a danger awareness of 6.8 (2.9), a lack of prevention measures 6.0 (3.3), an improper behavior of 7.3 (2.7), an unpredictable fate of 6.0 (2.9). These factors resulted significantly associated with the injury risk perception. Multivariable analysis highlighted that the injury risk perception was associated with the lack of prevention measure and unpredictable fate. On the other hand, we found a negative association with the workers’ improper behaviors.

Conclusion

Workers’ perception showed fairly uniform average values even when occupational risk was demonstrated. Our analysis suggests a positive correlation between injury risk perception and the idea that injuries are due both to fate and to chance; it also shows a negative correlation between injury risk perception and the idea that injuries are due to improper behavior. A lack of fully comparable studies confirms the need for further studies on the injury risk perception of construction workers.
How Games Help Us Research Age-Related Memory Changes
Authors: Ashton Charlotte , McNab Fiona
Published: January 2024

Working memory is the ability to hold information in our minds for a short time, often while we work on it. We need it for schoolwork, solving problems, and many aspects of life. Some people can hold more information in mind than others, and as we get older the amount we can hold tends to decline. If we understand what limits working memory and how working memory changes with age, we can figure out ways to improve it. A person’s ability to focus on relevant information and ignore distraction seems to be important. Our research group looked at how well people can ignore different types of distraction, which might limit their working memory. To sample a large number of people with a range of abilities, we used a game played by 29,631 people. The results gave us clues about how our ability to ignore distraction affects our working memory, and we identified a specific type of distraction that seems to particularly affect working memory in older adults.
Farmers’ willingness to accept compensation for ginkgo conservation: evidence from rural Taixing, China
Authors: Dai Xiaoqing , Pu Lijie , Jiang Debang , Zhang Ying , Rao Fangping
Published: January 2024

Numerous potential socioeconomic benefits provided by ginkgo resources have been identified but these have been threatened due to insufficient conservation over recent decades. Economic compensation is essential to induce enthusiasm for conservation. This paper examines the farmers’ willingness to accept ginkgo conservation compensation as well as other influencing factors based on survey data from 208 households. The results show that: first, the compensation amounts for the three different ginkgo conservation values are 820.86, 249.03, and 71.29 yuan per tree, respectively. Second, the overall compensation value is 388.17 yuan per tree with an average of 8430.83 yuan per household. Third, factors that influence the conservation compensation values are size-specific. Specifically, for large ginkgoes, a given respondent’s age, gender, job, household income, the number of large ginkgoes and arable land area are the most important factors. For medium ginkgoes, the area of arable land and farmers’ willingness to protect ginkgo trees are the key determining factors. By contrast, the requisite factors are different for small size ginkgo trees. A given respondent’s job, the arable land area and farmers’ perception of the importance of conducting conservation for local development are found to have significant impacts. These findings provide a useful base for assessing the conservation value for this endangered and valuable forest resource. Furthermore, the results also indicate that a size-based payment for farmers’ ginkgo conservation behaviors can be a useful economic tool to induce and deepen the latter’s conservation efforts.
Stream Life Cycle Assessment Model for Aircraft Preliminary Design
Authors: Vivalda Pietro , Fioriti Marco
Published: January 2024

The growing environmental public awareness and the consequential pressure on every industrial field has made environmental impact assessment increasingly important in the last few years. In this scope, the most established tool used in the specialized literature is the life cycle assessment. Applying this method to the life cycle of an aircraft requires it to be broken down into at least four phases: production, operation, maintenance and disposal. In the assessment, the evaluation of the environmental impact of fuel consumption can be performed linearly and has already been studied over many years, while calculating the impact of other life phases is more complicated, and it is still under study. This paper describes a simple and effective method developed to assess the environmental impact of an aircraft at a preliminary design stage and the implemented model that resulted from it. A detailed consideration of all life cycle phases is essential to serve as a reference for the ecological assessment of novel aircraft concepts. Thereby, the developed method is based on some parametric equations that take into account preliminary information, such as the mass breakdown, the technology used and some program considerations. The results obtained have been compared with those of the literature for verification and validation and have proved to be quite reliable. In fact, the comparison with known analyses, conducted on individual aircraft in a very precise manner, has showed that the proposed model is capable of giving results that fell within ±10% of the reference values. This is due to the broad generality of the model, which does not require a large number of specific data as a starting point to obtain reasonably reliable results for use during project development. In the near future, the use of this model can assist the design of aircraft architectures that comply with the European Green Deal of reducing net greenhouse gas emissions by at least 55% by 2030 and of having no net emissions of greenhouse gases by 2050.
Elucidating Multimodal Imaging Patterns in Accelerated Brain Aging: Heterogeneity through a Discriminant Analysis Approach Using the UK Biobank Dataset
Authors: Liu Lingyu , Lin Lan , Sun Shen , Wu Shuicai
Published: January 2024

Accelerated brain aging (ABA) intricately links with age-associated neurodegenerative and neuropsychiatric diseases, emphasizing the critical need for a nuanced exploration of heterogeneous ABA patterns. This investigation leveraged data from the UK Biobank (UKB) for a comprehensive analysis, utilizing structural magnetic resonance imaging (sMRI), diffusion magnetic resonance imaging (dMRI), and resting-state functional magnetic resonance imaging (rsfMRI) from 31,621 participants. Pre-processing employed tools from the FMRIB Software Library (FSL, version 5.0.10), FreeSurfer, DTIFIT, and MELODIC, seamlessly integrated into the UKB imaging processing pipeline. The Lasso algorithm was employed for brain-age prediction, utilizing derived phenotypes obtained from brain imaging data. Subpopulations of accelerated brain aging (ABA) and resilient brain aging (RBA) were delineated based on the error between actual age and predicted brain age. The ABA subgroup comprised 1949 subjects (experimental group), while the RBA subgroup comprised 3203 subjects (control group). Semi-supervised heterogeneity through discriminant analysis (HYDRA) refined and characterized the ABA subgroups based on distinctive neuroimaging features. HYDRA systematically stratified ABA subjects into three subtypes: SubGroup 2 exhibited extensive gray-matter atrophy, distinctive white-matter patterns, and unique connectivity features, displaying lower cognitive performance; SubGroup 3 demonstrated minimal atrophy, superior cognitive performance, and higher physical activity; and SubGroup 1 occupied an intermediate position. This investigation underscores pronounced structural and functional heterogeneity in ABA, revealing three subtypes and paving the way for personalized neuroprotective treatments for age-related neurological, neuropsychiatric, and neurodegenerative diseases.
Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache
Authors: Viganò Alessandro , Sasso D’Elia Tullia , Sava Simona Liliana , Colosimo Alfredo , Di Piero Vittorio , Magis Delphine , Schoenen Jean
Published: January 2024

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.
Development of a Cell Culture Chamber for Investigating the Therapeutic Effects of Electrical Stimulation on Neural Growth
Authors: Huynh Quy-Susan , Holsinger R. M. Damian
Published: January 2024

Natural electric fields exist throughout the body during development and following injury, and, as such, EFs have the potential to be utilized to guide cell growth and regeneration. Electrical stimulation (ES) can also affect gene expression and other cellular behaviors, including cell migration and proliferation. To investigate the effects of electric fields on cells in vitro, a sterile chamber that delivers electrical stimuli is required. Here, we describe the construction of an ES chamber through the modification of an existing lid of a 6-well cell culture plate. Using human SH-SY5Y neuroblastoma cells, we tested the biocompatibility of materials, such as Araldite®, Tefgel™ and superglue, that were used to secure and maintain platinum electrodes to the cell culture plate lid, and we validated the electrical properties of the constructed ES chamber by calculating the comparable electrical conductivities of phosphate-buffered saline (PBS) and cell culture media from voltage and current measurements obtained from the ES chamber. Various electrical signals and durations of stimulation were tested on SH-SY5Y cells. Although none of the signals caused significant cell death, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed that shorter stimulation times and lower currents minimized negative effects. This design can be easily replicated and can be used to further investigate the therapeutic effects of electrical stimulation on neural cells.
Dose Calculation Accuracy of Beam Models in RadCalc for a 1.5 T MR-Linac
Authors: Sung Jiwon , Choi Yeonho , Kim Jun Won , Lee Ho
Published: January 2024

The purpose of this study is to evaluate RadCalc, an independent dose verification software, for patient-specific quality assurance (PSQA) in online adaptive planning with a magnetic resonance linear accelerator (MR-linac) of a 1.5 T. Version 7.1.4 of RadCalc to introduce the capability to establish a beam model that incorporates MR field characteristics. A total of six models were established, with one using manufacturer-provided data and the others differing in percentage depth dose (PDD) data sources. Overall, two models utilized PDD data from the treatment planning system (TPS), and three used commissioned PDD data from gantry angles of 0° and 270°. Simple tests on a virtual water phantom assessed dose-calculation accuracy, revealing percentage differences ranging from −0.5% to −20.6%. Excluding models with significant differences, clinical tests on 575 adaptive plans (prostate, liver, and breast) showed percentage differences of −0.51%, 1.12%, and 4.10%, respectively. The doses calculated using RadCalc demonstrated similar trends to those of the PSQA-based measurements. The newly released version of RadCalc enables beam modeling that considers the characteristics of the 1.5 T magnetic field. The accuracy of the software in calculating doses at 1.5 T magnetic fields has been verified, thereby making it a reliable and effective tool for PSQA in adaptive plans.
Smart Conditioning with Venetoclax-Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies
Authors: Schulz Felicitas , Jäger Paul , Tischer Johanna , Fraccaroli Alessia , Bug Gesine , Hausmann Andreas , Baermann Ben-Niklas , Tressin Patrick , Hoelscher Alexander , Kasprzak Annika , Nachtkamp Kathrin , Schetelig Johannes , Hilgendorf Inken , Germing Ulrich , Dietrich Sascha , Kobbe Guido
Published: January 2024

Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA-based sequential conditioning with venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related, or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to venetoclax was observed. On day +30, 55 patients (90%) were in complete remission. Acute GvHD II°–IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The off-label combination of sequential FLAMSA-RIC with venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial was initiated in July 2023.
Genetic Impact of HOTAIR, LINC00951, POLR2E and HULC Polymorphisms in Histopathological and Laboratory Prognostic Factors in Esophageal Cancer in the West: A Case-Control Study
Authors: Baili Efstratia , Gazouli Maria , Lazaris Andreas C. , Kanavidis Prodromos , Boura Maria , Michalinos Adamantios , Charalabopoulos Alexandros , Liakakos Theodore , Alexandrou Andreas
Published: January 2024

Long non-coding RNAs’ HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016, and HULC rs7763881 are progressively reported having a close genetic affinity with esophageal carcinogenesis in the East. Nonetheless, their correlation with variables already endorsed as significant prognostic factors in terms of staging, guiding treatment and predicting recurrence, metastasis, and survival have yet to be explored. Herein, we investigated their prognostic value by correlating them with clinicopathological and laboratory prognostic markers in esophageal cancer in the West. Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated on for esophageal cancer between 2014 and 2018 were compared with 121 healthy community controls. HULC was not detected differently in any of the cancer prognostic subgroups. LINC00951 was underrepresented in Ca19.9 elevated subgroup. HOTAIR was more frequent in both worse differentiation grade and positive Signet-Ring-Cell and Ca19.9 subgroups. POLR2E was identified less frequently in Adenocarcinoma, Signet-Ring-Cell, and Diffuse histologies, as well as in Perineural, Lymphovascular, and Perivascular Invasion positive, while it was overrepresented in CEA positive subgroup. These lncRNAs polymorphisms may hold great potential not only as future therapeutic agents but also as novel markers for predictive analysis of esophageal cancer risk, clinical outcome, and survival. Clinical implications of these findings need to be validated with prospective larger sample-size studies.
Optimizing Clinical Implementation of Hypofractionation: Comprehensive Evidence Synthesis and Practical Guidelines for Low- and Middle-Income Settings
Authors: Starling Maria Thereza Mansur , Thibodeau Stephane , de Sousa Cecília Félix Penido Mendes , Restini Felipe Cicci Farinha , Viani Gustavo A. , Gouveia Andre G. , Mendez Lucas C. , Marta Gustavo Nader , Moraes Fabio Ynoe
Published: January 2024

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care.
Pancreatic Tumor Organoid-Derived Factors from Cachectic Patients Disrupt Contractile Smooth Muscle Cells
Authors: Vaes Rianne D. W. , van Bijnen Annemarie A. , Damink Steven W. M. Olde , Rensen Sander S.
Published: January 2024

Patients with pancreatic cancer often suffer from cachexia and experience gastrointestinal symptoms that may be related to intestinal smooth muscle cell (SMC) dysfunction. We hypothesized that pancreatic tumor organoids from cachectic patients release factors that perturb the SMC’s contractile characteristics. Human visceral SMCs were exposed to conditioned medium (CM) from the pancreatic tumor organoid cultures of cachectic (n = 2) and non-cachectic (n = 2) patients. Contractile proteins and markers of inflammation, muscle atrophy, and proliferation were evaluated by qPCR and Western blot. SMC proliferation and migration were monitored by live cell imaging. The Ki-67-positive cell fraction was determined in the intestinal smooth musculature of pancreatic cancer patients. CM from the pancreatic tumor organoids of cachectic patients did not affect IL-1β, IL-6, IL-8, MCP-1, or Atrogin-1 expression. However, CM reduced the α-SMA, γ-SMA, and SM22-α levels, which was accompanied by a reduced SMC doubling time and increased expression of S100A4, a Ca2+-binding protein associated with the synthetic SMC phenotype. In line with this, Ki-67-positive nuclei were increased in the intestinal smooth musculature of patients with a low versus high L3-SMI. In conclusion, patient-derived pancreatic tumor organoids release factors that compromise the contractile SMC phenotype and increase SMC proliferation. This may contribute to the frequently observed gastrointestinal motility problems in these patients.
Rictor—A Mediator of Progression and Metastasis in Lung Cancer
Authors: Szalai Fatime , Sztankovics Dániel , Krencz Ildikó , Moldvai Dorottya , Pápay Judit , Sebestyén Anna , Khoor Andras
Published: January 2024

Lung carcinoma is one of the most common cancer types for both men and women. Despite recent breakthroughs in targeted therapy and immunotherapy, it is characterized by a high metastatic rate, which can significantly affect quality of life and prognosis. Rictor (encoded by the RICTOR gene) is known as a scaffold protein for the multiprotein complex mTORC2. Among its diverse roles in regulating essential cellular functions, mTORC2 also facilitates epithelial–mesenchymal transition and metastasis formation. Amplification of the RICTOR gene and subsequent overexpression of the Rictor protein can result in the activation of mTORC2, which promotes cell survival and migration. Based on recent studies, RICTOR amplification or Rictor overexpression can serve as a marker for mTORC2 activation, which in turn provides a promising druggable target. Although selective inhibitors of Rictor and the Rictor-mTOR association are only in a preclinical phase, they seem to be potent novel approaches to reduce tumor cell migration and metastasis formation. Here, we summarize recent advances that support an important role for Rictor and mTORC2 as potential therapeutic targets in the treatment of lung cancer. This is a traditional (narrative) review based on Pubmed and Google Scholar searches for the following keywords: Rictor, RICTOR amplification, mTORC2, Rictor complexes, lung cancer, metastasis, progression, mTOR inhibitors.
Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects
Authors: Makimoto Atsushi , Fujisaki Hiroyuki , Matsumoto Kimikazu , Takahashi Yoshiyuki , Cho Yuko , Morikawa Yoshihiko , Yuza Yuki , Tajiri Tatsuro , Iehara Tomoko
Published: January 2024

Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is isotretinoin, which can contribute to improving event-free survival in patients with high-risk neuroblastoma by approximately 10% when administered over six months as maintenance therapy. Although isotretinoin is regarded as an essential component in the standard clinical management of high-risk neuroblastoma, its use for this purpose in the US and EU is off-label. To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy.
Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study
Authors: Kruiswijk Anouk A. , van de Sande Michiel A. J. , Verhoef Cornelis , Schrage Yvonne M. , Haas Rick L. , Bemelmans Marc H. A. , van Ginkel Robert J. , Bonenkamp Johannes J. , Witkamp Arjen J. , van den Akker-van Marle M. Elske , Marang-van de Mheen Perla J. , van Bodegom-Vos Leti
Published: January 2024

Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18–65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. Methods: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.
Posterior Vertebral Body Tethering: A Preliminary Study of a New Technique to Correct Lenke 5C Lumbar Curves in Adolescent Idiopathic Scoliosis
Authors: Metaizeau Jean-Damien , Denis Delphy
Published: January 2024

Vertebral body tethering has been approved for adolescent scoliosis correction. The usual approach is anterior, which is relatively easy for the thoracic spine, but becomes much more challenging for the lumbar curves, with a higher rate of complications. The purpose of this study was to describe and evaluate the first results of a new posterior vertebral body tethering (PVBT) technique using pedicle screws through a posterolateral Wiltse approach. Twenty-two patients with 5C idiopathic scoliosis (Lenke classification) were included in this retrospective study, with a follow up of 2 years after surgery. The lumbar and thoracic curves were measured pre-operatively (POS), at first standing (FS) and at 2 years (2Y). Complications were also analysed. A significant improvement of 30.7° was observed for lumbar curve magnitude between POS and 2Y. Both the thoracic kyphosis and the lumbar lordosis remained stable. Thirteen complications were noted: three led to posterior arthrodesis, three needed a revision with a good outcome, and the seven others (overcorrections, screw breakage or pull-out) achieved a good result. PVBT seems an effective technique for the management of type 5 C adolescent idiopathic scoliosis. The complication rate seems high but is probably secondary to the learning curve of this new technic as it concerns only the first half of the patients.
Supportive Relationships Mitigate the Effect of Cumulative Exposure to Adverse Childhood Experiences on Depression, Anxiety, Stress, and Suicide Considerations—The Arizona Youth Risk Behavior Survey
Authors: Suh Bin C. , Gallaway M. Shayne , Celaya Martin F.
Published: January 2024

Declining adolescent mental health is a significant public health concern during the COVID-19 pandemic. Social distancing and stay-at-home orders have led to missed social connections with peers and adults outside households, and this has increased the risk of mental health problems in children and adolescents, particularly those with adverse childhood experiences (ACEs). Studies have shown that strong interpersonal support improves adolescent mental health. We examined the association between ACEs and poor mental health (including stress, anxiety, and depression) and how the presence of interpersonal support from caring adults and friends and school connectedness can mitigate this relationship among adolescents in Arizona. This study analyzed data from the 2021 Arizona Youth Risk Behavior Survey (YRBS; n = 1181), a population-based survey conducted biennially across the United States. The Arizona sample included high school students in grades 9–12 who were enrolled in public and charter schools. This study revealed that nearly three of four adolescents experienced an ACE, and one of five experienced ≥4 ACEs. Compared with adolescents who experienced zero ACEs, those with ≥4 ACEs experienced less interpersonal support from caring adults, friends, and school and more frequently reported poor mental health and suicidal thoughts. However, adolescents with interpersonal support consistently reported lower rates of mental health issues, even with exposure to multiple ACEs. Post-pandemic programs to improve social relationships with adults, peers, and schools are critical, especially for adolescents with multiple adversities.
Comprehensive Dataset on Pre-SARS-CoV-2 Infection Sports-Related Physical Activity Levels, Disease Severity, and Treatment Outcomes: Insights and Implications for COVID-19 Management
Authors: Bourdas Dimitrios I. , Bakirtzoglou Panteleimon , Travlos Antonios K. , Andrianopoulos Vasileios , Zacharakis Emmanouil
Published: January 2024

This dataset aimed to explore associations between pre-SARS-CoV-2 infection exercise and sports-related physical activity (PA) levels and disease severity, along with treatments administered following the most recent SARS-CoV-2 infection. A comprehensive analysis investigated the relationships between PA categories (“Inactive”, “Low PA”, “Moderate PA”, “High PA”), disease severity (“Sporadic”, “Episodic”, “Recurrent”, “Frequent”, “Persistent”), and treatments post-SARS-CoV-2 infection (“No treatment”, “Home remedies”, “Prescribed medication”, “Hospital admission”, “Intensive care unit admission”) within a sample population (n = 5829) from the Hellenic territory. Utilizing the Active-Q questionnaire, data were collected from February to March 2023, capturing PA habits, participant characteristics, medical history, vaccination status, and illness experiences. Findings revealed an independent relationship between preinfection PA levels and disease severity (χ2 = 9.097, df = 12, p = 0.695). Additionally, a statistical dependency emerged between PA levels and illness treatment categories (χ2 = 39.362, df = 12, p < 0.001), particularly linking inactive PA with home remedies treatment. These results highlight the potential influence of preinfection PA on disease severity and treatment choices following SARS-CoV-2 infection. The dataset offers valuable insights into the interplay between PA, disease outcomes, and treatment decisions, aiding future research in shaping targeted interventions and public health strategies related to COVID-19 management.