bluuebunny/crossref_metadata_2025 huggingface dataset:
Características gerais dos patches e suas aplicações na indústria farmacêutica
Authors: Medeiros Beatriz Peroni , Oliveira Milena Dlugosz Dias , Silva Sofia Marques da , Hora Emily Soares da , Zanoni Guilherme de Almeida , Santos Jhennifer Soares , Giorgetti Leandro
Published: November 2023

Os adesivos transdérmicos são estruturas multilaminadas, flexíveis e medicamentosas que possuem propriedades bioadesivas, são formados, essencialmente, por um sistema de liberação de medicamentos e uma camada adesiva para fixação na pele, fornecendo uma absorção constante e prolongada. São exemplos de formulações tópicas sistêmicas que, devido as suas inovações em níveis promissoras, estão sendo cada vez mais estudadas na comunidade da indústria farmacêutica com o objetivo de obter inovação e novas tecnologias. Inovações essas que se baseiam na alteração dos sistemas de liberação transdérmicos possibilitando uma permeação de fármacos com variedades de propriedades físico-químicas. Tendo em vista o crescente interesse, ainda que exista um pequeno grupo de medicamentos sendo comercializados no Brasil, o objetivo principal deste estudo foi realizar uma revisão literária, para maior esclarecimento, ponderando a estrutura e constituição geral dos patches, as promissoras inovações de liberação, o atual controle de qualidade, suas aplicações e suas vantagens e desvantagens. Foi identificado que os adesivos transdérmicos dispõem de notáveis favorecimentos aos pacientes nos resultados terapêuticos esperados, devido principalmente à dispensação do fígado na filtragem do fármaco no efeito de primeira passagem hepática.
Effect of Selected Music Soundtracks on Cardiac Vagal Control and Complexity Assessed by Heart Rate Variability
Authors: PARIZEK D , VISNOVCOVA N , HAMZA SLADICEKOVA K , VETERNIK M , JAKUS J , JAKUSOVA J , VISNOVCOVA Z , FERENCOVA N , TONHAJZEROVA I
Published: November 2023

Listening to music is experimentally associated with positive stress reduction effect on human organisms. However, the opinions of therapists about this complementary non-invasive therapy are still different. Purpose: The aim of our study was to investigate the effect of selected passive music therapy frequencies without vocals on selected cardio-vagal and complexity indices of short-term heart rate variability (HRV) in healthy youth, in terms of calming the human. Main methods: 30 probands (15 male, averaged age: 19.7±1.4 years, BMI: 23.3±3.8 kg/m2) were examined during protocol (Silence baseline, Music 1 (20-1000 Hz), Silence 1, Music 2 (250-2000 Hz), Silence 2, Music 3 (1000-16000 Hz), and Silence 3). Evaluated HRV parameters in time, spectral, and geometrical domains represent indices of cardio-vagal and emotional regulation. Additionally, HRV complexity was calculated by approximate entropy and sample entropy (SampEn) and subjective characteristics of each phase by Likert scale. Results: the distance between subsequent R-waves in the electrocardiogram (RR intervals [ms]) and SampEn were significantly higher during Music 3 compared to Silence 3 (p=0.015, p=0.021, respectively). Geometrical cardio-vagal index was significantly higher during Music 2 than during Silence 2 (p=0.006). In the subjective perception of the healthy youths evaluated statistically through a Likert scale, the phases of music were perceived significantly more pleasant than the silent phases (p<0.001, p=0.008, p=0.003, respectively). Conclusions: Our findings revealed a rise of cardio-vagal modulation and higher complexity assessed by short-term HRV indices suggesting positive relaxing effect music especially of higher frequency on human organism.
ÖZEL YETENEKLİ ÖĞRENCİLER İÇİN HAZIRLANAN FİZİKSEL AKTİVİTE DESTEKLİ PSİKO EĞİTİM PROGRAMIYLA (FİZPEP) İLGİLİ ÖĞRENCİ GÖRÜŞLERİNİN İNCELENMESİ
Authors: KARABURÇAK Seyit , GÜNDÜZ Nevin , KARACA Raşit
Published: November 2023

Araştırmadaki amaç özel yetenekliler için hazırlanan fiziksel aktivite destekli psiko eğitim programına yönelik öğrenci görüşlerinin incelenmesidir. Program doktora çalışması kapsamında haftada 1 oturum, 2 etkinlik toplam beş hafta sürmüştür. Programının değişkenleri öz yeterlik, motivasyon, sosyal duygusal iyi oluş ve fiziksel aktivite düzeyidir. Araştırmada 6. Sınıftaki 28 özel yetenekli öğrencinin görüşlerini toplamak amacıyla 3 bölümden oluşan, 11 soru içeren yapılandırılmış açık uçlu soru formu hazırlanmıştır. Verilerin analizinde içerik analizi yöntemi kullanılmıştır. Toplanan veriler, önce kavramsallaştırılmış daha sonra mantıklı bir biçimde düzenlenmiş ve 5 tema, 9 kategori belirlenmiştir. Programın öğrenciler üzerine etkisi ile ilgili temanın sonuçlarına göre; özel yetenekli öğrenciler eğitimin çok etkili ve verimli geçtiğini, insanın kendine güven ve inancını arttırdığını, nasıl motive olduklarını öğrenip öncesine göre daha iyi motive olduklarını, hem eğlenip hem de öğrendiklerini belirtmişlerdir. FA’nin öğrenci üzerine etkileri temasında da dikkat, hız ve reaksiyon aktivitelerinin etkili ve verimli geçtiğini, neşeli bardakları çok eglenceli bulduklarını, dikkatlerini arttırdiğını belirtmişlerdir. Aerobik ve fitness aktiviteleriyle ilgili ise step aerobik aktivitelerini öğrendiklerini ve böylece ısnma amaçlı kullanabileceklerini ve sağlıklı olacaklarını belirtmişlerdir. FA nın öz yeterlikleri üzerine etkileri temasında öğrenciler kimseden çekinmediklerini kendilerine güvendiklerini, işleri başardıklarını belirtmiş, FA nın Motivasyonları üzerine etkileri ile ilgili temada çok faydalandıklarını mutlu ve motive olduklarını belirtmişlerdir. FA nın sosyal duygusal iyi oluşları üzerine etkileri ile ilgili görüşlerinde ise öğrenciler kendilerine güvendiklerini ve dersi verimli geçirdiklerini, kendilerini iyi hissettiklerini belirtmişlerdir. Sonuç olarak programın genelinin özel yetenekli öğrenciler tarafından olumlu değerlendirildiği bu kapsamda da yaygınlaştırılması için bu öğrencilerin eğitim aldığı BİLSEM’lerde, destek eğitim odalarında ve diğer eğitim kurumlarında uygulanması önerilebilir.
ELİT GENÇ ERKEK BASKETBOLCULARDA SİRKADİYEN RİTMİN MAÇ PERFORMANSINA ETKİSİ
Authors: ÖZDALYAN Fırat , MANCI Egemen , GÜMÜŞ Hikmet , AÇIKGÖZ Osman
Published: November 2023

Bir basketbol maçını kazanabilmek için fiziksel, fizyolojik, psikolojik, biyomotor, bilişsel, teknik ve taktik özelliklerin gelişmiş olması gerekmektedir. Bu özelliklerin sirkadiyen ritimden etkilendiği, bu nedenle günün farklı saatlerinde söz konusu performansların değişebildiği bilinmektedir. Bu araştırmada, sirkadiyen ritmin 18 Yaş Altı Erkekler Basketbol Türkiye Şampiyonasına katılan takımların performanslarına olan etkisi incelenmiştir. Türkiye Basketbol Federasyonu resmi sitesinde açık erişimli olarak paylaşılan beş turnuvadaki 208 maçın istatistik verisi toplanmıştır. Araştırmaya sadece uzatmaya giden ya da 10 sayıdan az farkla biten 97 maç dahil edilmiştir. Bu maçlarda takımların istatistik verileri toplanmış ve her maç için takım başı birer veri seti olmak üzere toplamda 194 farklı takım istatistik verisi incelenmiştir. Sirkadiyen ritmin performansa etkisini incelemek için maç istatistikleri ile maç başlama saati arasındaki ilişki test edilmiştir. Ayrıca sabah ve akşam saatlerindeki maçların istatistikleri de birbirileriyle karşılaştırılmıştır. Korelasyon analizi sonucu iki sayılık deneme ve asist istatistiklerinin maç saati ile negatif; üç sayılık deneme, serbest atış deneme, başarılı serbest atış ve faul istatistiklerinin ise maç saatiyle pozitif korelasyon gösterdiği belirlenmiştir (p<0.05). Sabah ve akşam maçlarının karşılaştırılması sonucu ise saha içi deneme, iki sayılık deneme ve asist istatistiklerinin sabah maçlarında; serbest atış yüzdesi, serbest atış deneme, başarılı serbest atış ve faul istatistiklerinin ise akşam maçlarında daha fazla olduğu tespit edilmiştir (p<0.05). Ulaşılan bulgular ışığında akşam maçlarında şutör oyunculara verilen sürenin artırılması ve takımın önemli uzun oyuncularının faul problemine girme ihtimali göz önünde tutularak stratejik planlanmaların yapılması önerilmektedir. Sabah maçlarında ise kolay penetre yememek ve yenilen penetreleri daha etkili savunabilmek için taktik hazırlıkların planlanmış ve çalışılmış olması oldukça önemlidir.
3D simulation model for IoD-to-vehicles communication in IoD-assisted VANET
Authors: Ahmed Gamil , Sheltami Tarek , Mahmoud Ashraf , Yasar Ansar
Published: November 2023

Vehicle ad hoc networks (VANETs) have gradually emerged to enhance transportation information, entertainment, safety, and other services. However, such infrastructures have certain limitations, causing intermittent network disconnection. Further, in urban areas, terrain heights act as obstacles and hinder or attenuate transmitted signals. In this study, we propose a dynamic 3D internet of drones collaborative communication approach for efficient VANET-assistance (3DIoDAV) by integrating the IoD network and VANET to support terrestrial communication. We model IoD locations as an optimization problem to optimize the IoD nodes in three-dimensional terrain. Improved particle swarm optimization is used to optimally deploy IoD nodes in 3D terrain for minimizing the number of isolated vehicles. The proposed approach considers the terrain profile influence on communication. Therefore, we propose a 3D propagation model for efficient IoD-to-vehicle (IoD2V) communication in 3D space. Experiments are performed based on the received signal from ground vehicles to examine the performance of the proposed model and the 3DIoDAV approach. Simulation results show different behaviors of IoD nodes in two-dimensional (2D) and 3D scenarios. Comparison with 2D VANET-assisted and IoDAV approaches demonstrates the proposed 3DIoDAV approach’s ability to detect terrain obstacles, which guarantees the dispatching of IoD nodes into the most appropriate locations in 3D space, thereby minimizing the impact of terrain obstacles on communication.
Towards sustainable electrochemistry: green synthesis and sintering aid modulations in the development of BaZr0.87Y0.1M0.03O3−δ (M = Mn, Co, and Fe) IT-SOFC electrolytes
Authors: Ain Qurat ul , Irshad Muneeb , Butt Muhammad Salim , Tabish Asif Nadeem , Hanif Muhammad Bilal , Khalid Muhammad Ali , Ghaffar Rabia , Rafique Muhammad , Shawar Kazmi Syeda Dur E. , Siraj Khurram , Hafez Amal A. Abdel , Abd-Rabboh Hisham S. M. , Zmrhalova Zuzana , Filonova Elena A. , Medvedev Dmitry A. , Motola Martin
Published: November 2023

In this study, BaZr0.87Y0.1M0.03O3−δ perovskite electrolytes with sintering aids (M = Mn, Co, and Fe) were synthesized by a sustainable approach using spinach powder as a chelating agent and then compared with chemically synthesized BaZr0.87Y0.1M0.03O3−δ (M = Mn, Co, and Fe) electrolytes for intermediate temperature SOFCs. This is the first example of such a sustainable synthesis of perovskite materials with sintering aids. Structural analysis revealed the presence of a cubic perovskite structure in BaZr0.87Y0.1M0.03O3−δ (M = Mn, Co, and Fe) samples synthesized by both green and conventional chemical methods. No significant secondary phases were observed in the samples synthesized by a sustainable approach. The observed phenomena of plane shift were because of the disparities between ionic radii of the dopants, impurities, and host materials. The surface morphology analysis revealed a denser microstructure for the electrolytes synthesized via green routes due to metallic impurities in the organic chelating agent. The absence of significant impurities was also observed by compositional analysis, while functional groups were identified through Fourier-transform infrared spectroscopy. Conductivity measurements showed that BaZr0.87Y0.1M0.03O3−δ (M = Mn, Co, and Fe) electrolytes synthesized by oxalic acid have higher conductivities compared to BaZr0.87Y0.1M0.03O3−δ (M = Mn, Co, and Fe) electrolytes synthesized by the green approach. The button cells employing BaZr0.87Y0.1Co0.03O3−δ electrolytes synthesized by the chemical and green routes achieved peak power densities 344 and 271 mW·cm−2 respectively, suggesting that the novel green route can be applied to synthesize SOFC perovskite materials with minimal environmental impact and without significantly compromising cell performance.
Exercise during chemotherapy to prevent breast cancer-related cognitive decline: protocol for a pilot randomized controlled trial
Authors: Salerno Elizabeth A. , Harriss Courtney , Andrade D. Carolina , Peterson Lindsay L. , Duncan Ryan P. , Kepper Maura M. , Luo Jingqin , Creel Patricia , Colditz Graham A.
Published: November 2023

Background

Cancer-related cognitive decline (CRCD) is one of the most reported and debilitating symptoms associated with breast cancer treatment with no currently accepted treatment. Physical activity has emerged as a promising solution for maintaining cognitive health after cancer, with research suggesting that earlier intervention may be important for preventing or mitigating CRCD. There is a clear need to pilot the feasibility and efficacy of pragmatic physical activity interventions to promote cognitive health during active breast cancer treatment. The purpose of this study is to pilot test a home-based prehabilitation physical activity intervention aimed at preventing cognitive decline during chemotherapy, as well as assess the feasibility, acceptability and appropriateness of the intervention among patients.

Methods

This study is a two-arm, pilot randomized controlled trial in 40 adult patients newly diagnosed with breast cancer stages I-III who are scheduled to receive curative intent neo-adjuvant chemotherapy. Participants will be randomized 1:1 to a usual care waitlist control group or a home-based prehabilitation physical activity intervention delivered by a licensed physical therapist. The exercise group will receive an individualized, tapered exercise program comprised of home exercise sessions and virtual coaching calls. Both groups will receive activity monitors and be encouraged to maintain a healthy lifestyle during treatment. Participant adherence and adverse events will be assessed throughout the study.

Results

This research was supported by the Alvin J. Siteman Cancer Center through The Foundation for Barnes-Jewish Hospital (award No. 6257). The protocol was approved by Washington University's Protocol Review and Monitoring Committee and Institutional Review Board. Enrollment began in May 2023 and is anticipated to continue through July 2024.

Conclusions

This study will provide the necessary preliminary data to support larger trials investigating if and how physical activity can be incorporated into early rehabilitation strategies to prevent chemotherapy-related sequelae.

Trial registration

ClinicalTrials.gov, NCT05716542.
Elevating community voices through inclusive science communication: a case study of the We are Water program in the Southwestern United States
Authors: Marsh Casey L. , Gold Anne U. , Rongstad Strong Brigitta
Published: November 2023

Science communication plays a pivotal role in cultural engagement and life-long science learning. However, historically marginalized communities remain undervalued in these efforts due to practices that prioritize specific individuals, such as those who are affluent, college-educated, able-bodied, and already scientifically engaged. Science communicators can avoid these practices by acknowledging the intersecting historical and cultural dimensions surrounding science beyond those of the majority culture and practicing inclusive science communication efforts. Here, we define and describe the importance of inclusive science communication and outline how we use an asset-based community engagement framework in a place-based education program's communication practices with rural communities in the Southwestern United States. We describe how we designed our communication spaces, found our voice, and effectively communicate with non-English speaking and bilingual communities. We provide examples from the We are Water program, demonstrating how we utilize inclusive science communication practices to engage more widely with diverse communities and create space for community voices to be heard and shared. We conclude that the use of inclusive science communication strategies and an asset-based community engagement framework has allowed the We are Water program to connect with rural communities while communicating in a way that elevates historically marginalized voices, creates space for communities to share their own experiences through memories and stories, and honors diverse perspectives and ways of knowing.
Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction
Authors: Gou Qiling , Zhao Qianqian , Dong Mengya , Liang Lei , You Hongjun
Published: November 2023

Background

Heart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF.

Methods

The HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers.

Results

We selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation.

Conclusion

Our study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.
Robust model predictive control of wind turbines based on Bayesian parameter self-optimization
Authors: Tang Minan , Wang Wenjuan , Yan Yaguang , Zhang Yaqi , An Bo
Published: November 2023

This paper studies the effect of different turbulent wind speeds on the operation of wind turbines. The proportion of wind power in the field of new energy generation has increased massively and has gained wide application and attention. However, the smooth operation and the stability of the output power of the wind power generation system are susceptible to wind speed fluctuations. To tackle this problem, this paper takes a 5 MW horizontal axis wind turbine as the research object that proposes a parameter adaptive robust control method to achieve self-optimization of controller parameters by means of Bayesian optimization. The 5 MW wind turbine model is utilized to verify the feasibility of the algorithm by combining the wind speed types commonly found in a high-altitude region in northwestern. The simulation results validate the effectiveness of the proposed scheme. The outcomes demonstrate that Bayesian optimization can significantly decrease the effects of wind speed instability. The output power increases by 1.9% on average at low wind speed and stabilizes on 5 MW at high wind speed. Therefore, the stable controller for wind power output is the robust model predictive controller with parameter improvement.
Germline ablation achieved via CRISPR/Cas9 targeting of NANOS3 in bovine zygotes
Authors: Mueller Maci L. , McNabb Bret R. , Owen Joseph R. , Hennig Sadie L. , Ledesma Alba V. , Angove Mitchell L. , Conley Alan J. , Ross Pablo J. , Van Eenennaam Alison L.
Published: November 2023

NANOS3 is expressed in migrating primordial germ cells (PGCs) to protect them from apoptosis, and it is known to be a critical factor for germline development of both sexes in several organisms. However, to date, live NANOS3 knockout (KO) cattle have not been reported, and the specific role of NANOS3 in male cattle, or bulls, remains unexplored. This study generated NANOS3 KO cattle via cytoplasmic microinjection of the CRISPR/Cas9 system in vitro produced bovine zygotes and evaluated the effect of NANOS3 elimination on bovine germline development, from fetal development through reproductive age. The co-injection of two selected guide RNA (gRNA)/Cas9 ribonucleoprotein complexes (i.e., dual gRNA approach) at 6 h post fertilization achieved a high NANOS3 KO rate in developing embryos. Subsequent embryo transfers resulted in a 31% (n = 8/26) pregnancy rate. A 75% (n = 6/8) total KO rate (i.e., 100% of alleles present contained complete loss-of-function mutations) was achieved with the dual gRNA editing approach. In NANOS3 KO fetal testes, PGCs were found to be completely eliminated by 41-day of fetal age. Importantly, despite the absence of germ cells, seminiferous tubule development was not impaired in NANOS3 KO bovine testes during fetal, perinatal, and adult stages. Moreover, a live, NANOS3 KO, germline-ablated bull was produced and at sexual maturity he exhibited normal libido, an anatomically normal reproductive tract, and intact somatic gonadal development and structure. Additionally, a live, NANOS3 KO, germline-ablated heifer was produced. However, it was evident that the absence of germ cells in NANOS3 KO cattle compromised the normalcy of ovarian development to a greater extent than it did testes development. The meat composition of NANOS3 KO cattle was unremarkable. Overall, this study demonstrated that the absence of NANOS3 in cattle leads to the specific deficiency of both male and female germ cells, suggesting the potential of NANOS3 KO cattle to act as hosts for donor-derived exogenous germ cell production in both sexes. These findings contribute to the understanding of NANOS3 function in cattle and have valuable implications for the development of novel breeding technologies using germline complementation in NANOS3 KO germline-ablated hosts.
Broadening the horizon: potential applications of CAR-T cells beyond current indications
Authors: Karsten Hendrik , Matrisch Ludwig , Cichutek Sophia , Fiedler Walter , Alsdorf Winfried , Block Andreas
Published: November 2023

Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes of CAR-T-cell therapies in B-ALL. Several diseases can now be treated in highly therapy-refractory or relapsed conditions. Currently, a number of CD19- or BCMA-specific CAR-T-cell therapies are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma (MM), and follicular lymphoma (FL). The implementation of these therapies has significantly improved patient outcome and survival even in cases with previously very poor prognosis. In this comprehensive review, we present the current state of research, recent innovations, and the applications of CAR-T-cell therapy in a selected group of hematologic malignancies. We focus on B- and T-cell malignancies, including the entities of cutaneous and peripheral T-cell lymphoma (T-ALL, PTCL, CTCL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy cell leukemia (HCL), and Waldenström’s macroglobulinemia (WM). While these diseases are highly heterogenous, we highlight several similarly used approaches (combination with established therapeutics, target depletion on healthy cells), targets used in multiple diseases (CD30, CD38, TRBC1/2), and unique features that require individualized approaches. Furthermore, we focus on current limitations of CAR-T-cell therapy in individual diseases and entities such as immunocompromising tumor microenvironment (TME), risk of on-target-off-tumor effects, and differences in the occurrence of adverse events. Finally, we present an outlook into novel innovations in CAR-T-cell engineering like the use of artificial intelligence and the future role of CAR-T cells in therapy regimens in everyday clinical practice.
Induction chemoimmunotherapy may improve outcomes of chemoradiotherapy in patients with unresectable stage III NSCLC
Authors: Guan Song , Zhang Shufeng , Ren Kai , Li Xingyue , Li Xue , Zhao Lujun
Published: November 2023

Background

Currently, the value of induction chemoimmunotherapy before chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer (NSCLC) has not been explored. This study was designed to explore the efficacy and safety of induction chemoimmunotherapy in patients with unresectable stage III NSCLC.

Methods

Unresectable stage III NSCLC patients who received CRT with or without induction chemoimmunotherapy between August 2014 and December 2021 were retrospectively enrolled. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and estimated by the Kaplan-Meier method. The potential factors affecting PFS and OS were analyzed by univariate and multivariate Cox regression models. One-to-one propensity score matching (PSM) was used to further minimize confounding.

Results

A total of 279 consecutive patients were enrolled, with 53 (19.0%) receiving induction chemoimmunotherapy followed by CRT (I-CRT group), and the remaining 226 (81.0%) receiving CRT alone (CRT group). After PSM, the median PFS was 24.8 months in the I-CRT group vs. 13.3 months in the CRT group (P=0.035). The median OS was not reached (NR) vs. 36.6 months ((P=0.142). The incidence of treatment-related adverse events (TRAEs) was similar in both groups, except that the incidence of hematological toxicity was higher in the I-CRT group (77.1% vs. 58.3%, P=0.049). Compared to induction chemotherapy, induction chemoimmunotherapy demonstrated a superior objective response rate (60.4% vs. 22.2%, P<0.001) and further prolonged PFS (median NR vs. 13.2 months, P=0.009) and OS (median NR vs. 25.9 months, P=0.106) without increasing the incidence of TRAEs in patients receiving concurrent chemoradiotherapy.

Conclusion

Induction chemoimmunotherapy is safe and may improve outcomes of CRT in patients with unresectable stage III NSCLC. Moreover, induction chemoimmunotherapy may further improve treatment response and survival outcomes compared to induction chemotherapy before cCRT.
Fine-tuning the antigen sensitivity of CAR T cells: emerging strategies and current challenges
Authors: Harrer Dennis Christoph , Li Sin-Syue , Kaljanac Marcell , Barden Markus , Pan Hong , Abken Hinrich
Published: November 2023

Chimeric antigen receptor (CAR) T cells are “living drugs” that specifically recognize their target antigen through an antibody-derived binding domain resulting in T cell activation, expansion, and destruction of cognate target cells. The FDA/EMA approval of CAR T cells for the treatment of B cell malignancies established CAR T cell therapy as an emerging pillar of modern immunotherapy. However, nearly every second patient undergoing CAR T cell therapy is suffering from disease relapse within the first two years which is thought to be due to downregulation or loss of the CAR target antigen on cancer cells, along with decreased functional capacities known as T cell exhaustion. Antigen downregulation below CAR activation threshold leaves the T cell silent, rendering CAR T cell therapy ineffective. With the application of CAR T cells for the treatment of a growing number of malignant diseases, particularly solid tumors, there is a need for augmenting CAR sensitivity to target antigen present at low densities on cancer cells. Here, we discuss upcoming strategies and current challenges in designing CARs for recognition of antigen low cancer cells, aiming at augmenting sensitivity and finally therapeutic efficacy while reducing the risk of tumor relapse.
Lipid metabolism-related gene expression in the immune microenvironment predicts prognostic outcomes in renal cell carcinoma
Authors: Zhang Qian , Lin Bingbiao , Chen Huikun , Ye Yinyan , Huang Yijie , Chen Zhen , Li Jun
Published: November 2023

Background

Rates of renal cell carcinoma (RCC) occurrence and mortality are steadily rising. In an effort to address this issue, the present bioinformatics study was developed with the goal of identifying major lipid metabolism biomarkers and immune infiltration characteristics associated with RCC cases.

Methods

The Cancer Genome Atlas (TCGA) and E-MTAB-1980 were used to obtain matched clinical and RNA expression data from patients diagnosed with RCC. A LASSO algorithm and multivariate Cox regression analyses were employed to design a prognostic risk model for these patients. The tumor immune microenvironment (TIME) in RCC patients was further interrogated through ESTIMATE, TIMER, and single-cell gene set enrichment analysis (ssGSEA) analyses. Gene Ontology (GO), KEGG, and GSEA enrichment approaches were further employed to gauge the mechanistic basis for the observed results. Differences in gene expression and associated functional changes were then validated through appropriate molecular biology assays.

Results

Through the approach detailed above, a risk model based on 8 genes associated with RCC patient overall survival and lipid metabolism was ultimately identified that was capable of aiding in the diagnosis of this cancer type. Poorer prognostic outcomes in the analyzed RCC patients were associated with higher immune scores, lower levels of tumor purity, greater immune cell infiltration, and higher relative immune status. In GO and KEGG enrichment analyses, genes that were differentially expressed between risk groups were primarily related to the immune response and substance metabolism. GSEA analyses additionally revealed that the most enriched factors in the high-risk group included the stable internal environment, peroxisomes, and fatty acid metabolism. Subsequent experimental validation in vitro and in vivo revealed that the most significantly differentially expressed gene identified herein, ALOX5, was capable of suppressing RCC tumor cell proliferation, invasivity, and migration.

Conclusion

In summary, a risk model was successfully established that was significantly related to RCC patient prognosis and TIME composition, offering a robust foundation for the development of novel targeted therapeutic agents and individualized treatment regimens. In both immunoassays and functional analyses, dysregulated lipid metabolism was associated with aberrant immunological activity and the reprogramming of fatty acid metabolic activity, contributing to poorer outcomes.
The use of phase change material as an actuator in linkage fabric structures
Authors: Partik Christian , Porte Elze , Purkiss Danielle , Michalska Martyna , Miodownik Mark
Published: November 2023

Linkage fabric structures show potential as assistive technology that can provide support and assistance for individuals with specific mobility and disability needs. The core functionality of these fabrics is the ability to passively and actively control the mechanics of each link producing a structure with variable and adjustable stiffness. Current actuators have shown limited ability to produce active stiffening within a fabric structure without the addition of a continuous energy supply to the structure, therefore, limiting its use as wearable assistive technology. Here, we address the energy supply problem and show the novel use of sodium acetate trihydrate (SAT) in the linkage structures to induce mechanical stiffening through a phase change induced by an electric impulse. We find that a SAT aqueous concentration of 55 wt% is optimum to achieve a stable supercooled liquid (to ambient temperature) and effective electrical nucleation from liquid to solid, which provides robust locking mechanism of individual linkages able to withstand mechanical torsion up to 200 mNm. We demonstrate proof of principle through the integration of SAT into one- and two-dimensional linkage structures and their nearly instantaneous stiffening within each link by enabling electrically controlled actuation.
Inspiratory muscle training in patients with obesity: a systematic review and meta-analysis
Authors: Caicedo-Trujillo Saúl , Torres-Castro Rodrigo , Vasconcello-Castillo Luis , Solis-Navarro Lilian , Sanchez-Ramirez Diana , Núñez-Cortés Rodrigo , Vera-Uribe Roberto , Muñoz-Muñoz Isabel , Barros-Poblete Marisol , Romero Juan Eduardo , Vilaró Jordi
Published: November 2023

Introduction

Obesity is a chronic medical condition that affects, among others, the cardiovascular and respiratory systems. Interventions for its treatment focus on sustained weight reduction and general health improvement, leaving respiratory management aside. Our objective was to determine the effects of inspiratory muscle training (IMT) in patients with obesity.

Methods

A systematic review was performed in Embase, Cochrane Library (CENTRAL), CINAHL, Web of Science, and PubMed/MEDLINE on June 26, 2023. Randomized clinical trials (RCTs), and quasi-randomized clinical trials investigating the effects of IMT in people with obesity were included. Selected studies were screened by two independent reviewers who extracted data and assessed the quality of the evidence.

Results

The initial search returned 705 potential studies were included. Ultimately, eight studies met the criteria for eligibility and were included in the review. IMT improves physical capacity [6-minute walk test (6MWT): 44.5 m, 95% CI: 30.5 to 58.5; p < 0.0001] and the strength of the inspiratory muscles [maximal inspiratory pressure (MIP): −28.4 cm H2O, 95% CI: −41.9 to −14.8; p < 0.0001] compared to the controls, without differences in the pulmonary function, body mass index (BMI) and metabolic parameters.

Conclusion

Inspiratory muscle training improves physical capacity and inspiratory muscle strength without significant changes in lung function, BMI, and metabolic parameters.

Systematic review registration: PROSPERO, identifier CRD42023439625, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439625.
Defining medical liability when artificial intelligence is applied on diagnostic algorithms: a systematic review
Authors: Cestonaro Clara , Delicati Arianna , Marcante Beatrice , Caenazzo Luciana , Tozzo Pamela
Published: November 2023

Artificial intelligence (AI) in medicine is an increasingly studied and widespread phenomenon, applied in multiple clinical settings. Alongside its many potential advantages, such as easing clinicians’ workload and improving diagnostic accuracy, the use of AI raises ethical and legal concerns, to which there is still no unanimous response. A systematic literature review on medical professional liability related to the use of AI-based diagnostic algorithms was conducted using the public electronic database PubMed selecting studies published from 2020 to 2023. The systematic review was performed according to 2020 PRISMA guidelines. The literature review highlights how the issue of liability in case of AI-related error and patient’s damage has received growing attention in recent years. The application of AI and diagnostic algorithm moreover raises questions about the risks of using unrepresentative populations during the development and about the completeness of information given to the patient. Concerns about the impact on the fiduciary relationship between physician and patient and on the subject of empathy have also been raised. The use of AI in medical field and the application of diagnostic algorithms introduced a revolution in the doctor–patient relationship resulting in multiple possible medico-legal consequences. The regulatory framework on medical liability when AI is applied is therefore inadequate and requires urgent intervention, as there is no single and specific regulation governing the liability of various parties involved in the AI supply chain, nor on end-users. Greater attention should be paid to inherent risk in AI and the consequent need for regulations regarding product safety as well as the maintenance of minimum safety standards through appropriate updates.
Bibliometric analysis of global research trends between gut microbiota and pancreatic cancer: from 2004 to 2023
Authors: Wu Shuang , Wen Su , An Kangli , Xiong Liping , Zeng Hao , Niu Yueyue , Yin Tiejun
Published: November 2023

Background

Pancreatic cancer (PC) is one of the most lethal malignancies of the digestive system and is expected to be the second leading cause of cancer-related death in the United States by 2030. A growing body of evidence suggests that the gut microbiota (GM) is intimately involved in the clinical diagnosis, oncogenic mechanism and treatment of PC. However, no bibliometric analysis of PC and GM has been reported.

Methods

The literature on PC and GM was retrieved from the Web of Science Core Collection (WoSCC) database for the period from January 1, 2004 to April 25, 2023. Microsoft Excel 2021, CiteSpace, VOSviewer, Scimago Graphica, Graphpad Prism, Origin, the R package “bibliometrics” and the bibliometric online analysis program were used to visualize the publishing trends and hot spots in this field.

Results

A total of 1,449 articles were included, including 918 articles and 531 reviews. Publishing had grown rapidly since 2017, with the 2023 expected to publish 268 articles. Unsurprisingly, the United States ranked highest in terms of number of literatures, H index and average citations. The University of California System was the most active institution, but Harvard University tended to be cited the most on average. The three most influential researchers were Robert M. Hoffman, Zhao Minglei, and Zhang Yong. Cancers had published the most papers, while Nature was the most cited journal. Keyword analysis and theme analysis indicated that “tumor microenvironment,” “gemcitabine-resistance,” “ductal adenocarcinoma,” “gut microbiota” and “diagnosis” will be the hotspots and frontiers of research in the future.

Conclusion

In summary, the field is receiving increasing attention. We found that future hotspots of PC/GM research may focus on the mechanism of oncogenesis, flora combination therapy and the exploitation of new predictive biomarkers, which provides effective suggestions and new insights for scholars.
Chronotypes and their relationship with depression, anxiety, and fatigue among patients with multiple sclerosis in Vilnius, Lithuania
Authors: Jonušaitė Ieva , Sakalauskaitė-Juodeikienė Eglė , Kizlaitienė Rasa , Giedraitienė Nataša , Sereikė Ieva , Liutkienė Justina , Kaubrys Gintaras , Jatužis Dalius
Published: November 2023

Background

Approximately half of patients with multiple sclerosis (PWMS) experience sleep disorders or changes in the circadian rhythm, that may further promote the pathogenesis of multiple sclerosis. As the prevalence of chronotypes among PWMS remains unclear, we aimed to evaluate the prevalence of chronotypes among Lithuanian PWMS; to assess the relationship of chronotypes with depression, anxiety, and fatigue symptoms; and to compare these results with those of healthy controls.

Methods

We enrolled 101 PWMS and 100 healthy controls. We included 130 (64.7%) and 71 (35.3%) women and men, respectively. The median age of all respondents was 39 [interquartile range (IQR) 20.75] years. Participants were assessed using general questionnaire, Horne-Östberg Morningness-Eveningness Questionnaire (MEQ), Hospital Anxiety and Depression Scale (HADS), and Shortened Fatigue Questionnaire (SFQ). Chronotypes were identified based on the total MEQ score.

Results

The average MEQ scores of the PWMS and control groups were 54 (IQR 15.0) and 53.5 (IQR 13), respectively, which indicated the intermediate chronotype. There was no significant between-group difference in the prevalence of chronotypes (p = 0.893). In both groups, individuals with moderate evening and intermediate chronotypes showed higher average HADS depression scores (p = 0.022). Further, in both groups, the individuals with the evening chronotype showed the highest average HADS anxiety scores (p = 0.001). The PWMS group had a higher average SFQ score than the control group (p < 0.001). High SFQ scores were more common among PWMS who had the intermediate (p < 0.001) and morning chronotypes (p = 0.011). The fatigue level was higher among healthy individuals with the evening chronotype (p < 0.001).

Conclusion

The most common chronotype for PWMS and healthy controls was the intermediate chronotype. Further, in both groups, higher HADS depression and anxiety scores were associated with the evening chronotype. Fatigue was more commonly found in healthy controls with the evening, and in PWMS - with intermediate and morning chronotypes.
Overall survival in advanced hepatocellular carcinoma treated with concomitant systemic therapy and stereotactic body radiation therapy or systemic therapy alone
Authors: Piening Alexander , Swaminath Anand , Dombrowski John , Teague Ryan M. , Al-Hammadi Noor , Shahi Jeevin
Published: November 2023

Introduction

First-line systemic therapy (ST) options for advanced hepatocellular carcinoma (HCC) include tyrosine kinase inhibitors and immunotherapy (IO). Evolving data suggest prolonged overall survival (OS) when ST is combined with stereotactic body radiation therapy (SBRT), although evidence is significantly limited in HCC populations. We hypothesized that advanced HCC patients in the National Cancer Database (NCDB) would have improved OS when receiving ST+SBRT vs ST alone.

Methods

Stage III/IV HCC patients diagnosed from 2010-2020 and treated with first-line ST±SBRT were identified from the NCDB. The primary endpoint was OS from date of diagnosis stratified by the receipt of SBRT (ST+SBRT vs ST alone). Survival was estimated using Kaplan-Meier methodology and compared via log-rank. Multivariate analysis (MVA) was performed by Cox regression.

Results

Of 10,505 eligible patients with stage III disease, 115 (1.1%) received ST+SBRT and 10,390 (98.9%) received ST alone. Of 9,617 eligible patients with stage IV disease, 127 (1.3%) received ST+SBRT and 9,490 (98.7%) received ST alone. Median follow-up time was 6.8 months. Baseline characteristics were similar between cohorts. Patients with stage III disease receiving ST+SBRT had improved median OS (12.62 months vs 8.38 months) and higher rates of survival at 1-year (53.0% vs 38.7%) and 2-years (27.0% vs 20.7%) compared to those receiving ST alone (log-rank P=0.0054). Similarly, patients with stage IV disease receiving ST+SBRT had improved median OS (11.79 months vs 5.72 months) and higher rates of survival at 1-year (49.6% vs 26.2%) and 2-years (23.6% vs 12.0%) (log-rank P<0.0001). On MVA, receipt of SBRT predicted improved OS (HR=0.748, 95%CI 0.588-0.951; P=0.0178) and receipt of IO trended towards improved OS (HR=0.859, 95%CI 0.735-1.003; P=0.0538).

Conclusion

In advanced HCC, patients receiving ST+SBRT had improved OS compared to those receiving ST alone. Prospective clinical trials are warranted to better identify HCC populations which may benefit from combined modality therapy.
Flavonol and A-type procyanidin-rich extracts of Prunus spinosa L. flower exhibit anticoagulant activity through direct thrombin inhibition, but do not affect platelet aggregation in vitro
Authors: Marchelak Anna , Kolodziejczyk-Czepas Joanna , Ponczek Michał B. , Liudvytska Oleksandra , Markowicz-Piasecka Magdalena , Bielska Beata , Miłowska Katarzyna , Olszewska Monika A.
Published: November 2023

Background: Blackthorn flower (Prunus spinosa L.) is a traditional herbal remedy recommended for treating cardiovascular diseases (CVDs).

Aim: This in vitro study investigates the effects of flavonol and A-type procyanidin-rich blackthorn flower extracts on the hemostatic system, including the blood plasma coagulation cascade and platelet aggregation.

Methods: Six distinct extracts, characterized through various techniques, including LC-MS/MS, were assessed at in vivo-relevant levels (1–50 μg/mL) for their antithrombotic activity. The thrombin, prothrombin, and activated partial thromboplastin times were measured. Additionally, the thrombin enzymatic activity was tested using the chromogenic substrate S-2238 and fibrinogen as the physiological substrate of the enzyme. To gain insights into the mechanism of action, the interactions between the primary extracts’ constituents, their potential metabolites, and thrombin were examined in silico. The computational analyses were complemented by in vitro experiments and circular dichroism spectroscopy. The platelet aggregation in human platelet-rich plasma was assessed after ADP or collagen stimulation. Furthermore, the extracts’ biocompatibility was tested on human peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs).

Results: The extracts slightly prolonged the prothrombin and thrombin times and effectively inhibited the thrombin’s enzymatic activity, reducing its amidolytic and proteolytic functions at 50 μg/mL by 91.2% and 74.8%, respectively. In silico molecular docking demonstrated a strong binding affinity of the examined polyphenols and their metabolites to thrombin. Most analytes bound exclusively within the enzyme active site; however, afzelin, kaempferitrin, and procyanidin A2 revealed the affinity to additional binding sites, including exosite I. The structure-activity relationship of flavonols as thrombin inhibitors was studied in vitro. Circular dichroism spectroscopy confirmed that the interactions between thrombin and the compounds (even at 1 μg/mL) induce alterations within the α-helices’ secondary structure, resulting in noticeable changes in the enzyme’s CD spectrum. On the other hand, the extracts did not influence platelet aggregation. Eventually, their cellular biocompatibility with PBMCs and RBCs was confirmed.

Conclusion: The extracts directly inhibit thrombin, a critical serine protease in hemostasis and a prime anticoagulant drug target, and do not exhibit antiplatelet effects. This study enhances the knowledge of the biological activity of blackthorn flowers and supports their traditional use in CVDs.