bluuebunny/crossref_metadata_2025 huggingface dataset:
A synbiotic mixture of Bifidobacterium breve M16-V, oligosaccharides and pectin, enhances Short Chain Fatty Acid production and improves lung health in a preclinical model for pulmonary neutrophilia
Authors: Bezemer Gillina F. G. , Diks Mara A. P. , Mortaz Esmaeil , van Ark Ingrid , van Bergenhenegouwen Jeroen , Kraneveld Aletta D. , Folkerts Gert , Garssen Johan
Published: June 2024

Introduction

Pulmonary neutrophilia is a hallmark of numerous airway diseases including Chronic Obstructive Pulmonary Disease (COPD), Neutrophilic asthma, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS) and COVID-19. The aim of the current study was to investigate the effect of dietary interventions on lung health in context of pulmonary neutrophilia.

Methods

Male BALB/cByJ mice received 7 intra-nasal doses of either a vehicle or lipopolysaccharides (LPS). To study the effect of nutritional interventions they received 16 intra-gastric doses of either a vehicle (PBS) or the following supplements (1) probiotic Bifidobacterium breve (B. breve) M16-V; (2) a prebiotic fiber mixture of short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, and low-viscosity pectin in a 9:1:2 ratio (scGOS/lcFOS/lvPectin); and (3) A synbiotic combination B. breve M16-V and scGOS/lcFOS/lvPectin. Parameters for lung health included lung function, lung morphology and lung inflammation. Parameters for systemic immunomodulation included levels of fecal short chain fatty acids and regulatory T cells.

Results

The synbiotic supplement protected against the LPS induced decline in lung function (35% improved lung resistance at baseline p = 0.0002 and 25% at peak challenge, p = 0.0002), provided a significant relief from pulmonary neutrophilia (40.7% less neutrophils, p < 0.01) and improved the pulmonary neutrophil-to-lymphocyte ratio (NLR) by 55.3% (p = 0.0033). Supplements did not impact lung morphology in this specific experiment. LPS applied to the upper airways induced less fecal SCFAs production compared to mice that received PBS. The production of acetic acid between day −5 and day 16 was increased in all unchallenged mice (PBS-PBS p = 0.0003; PBS-Pro p < 0.0001; PBS-Pre, p = 0.0045; PBS-Syn, p = 0.0005) which upon LPS challenge was only observed in mice that received the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin (p = 0.0003). A moderate correlation was found for butyric acid and lung function parameters and a weak correlation was found between acetic acid, butyric acid and propionic acid concentrations and NLR.

Conclusion

This study suggests bidirectional gut lung cross-talk in a mouse model for pulmonary neutrophilia. Neutrophilic lung inflammation coexisted with attenuated levels of fecal SCFA. The beneficial effects of the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin on lung health associated with enhanced levels of SCFAs.
Development and validation of the BMQ-AIR©: a screening tool for assessing patients’ treatment beliefs about switching to anti-inflammatory reliever (AIR) therapy
Authors: Foot Holly , Chan Amy Hai Yan , Horne Rob
Published: June 2024

Introduction

Despite anti-inflammatory reliever (AIR) therapy now being the preferred treatment choice across all severities of asthma, many patients are still “attached” to their short-acting beta2-agonist (SABA) reliever, believing this to be the best way to control their asthma. To encourage individuals to switch to AIR, it is important to first identify the beliefs that patients hold about AIR.

Objective

The aim of this paper was to describe the initial development and validation of the BMQ-AIR©, a six-item screening tool which assesses and identifies patients’ treatment beliefs about switching to AIR therapy.

Methods

Statements were identified from the primary literature that assessed patients’ perceptions of AIR therapy and adapted from the Beliefs about Medicines Questionnaire (BMQ). Internal reliability was examined using Cronbach’s alpha coefficient. Construct validity was evaluated by comparing scores on BMQ-AIR© with a validated measure of medication adherence and SABA beliefs.

Results

A total of 446 participants completed the online survey. The BMQ-AIR© contained two subscales with three items each. Both the Necessity and Concerns subscales demonstrated good internal reliability, with Cronbach’s α-values of 0.70 and 0.69, respectively. Both subscales were negatively correlated with self-report inhaled corticosteroid adherence (Necessity: r = −0.28, p < 0.0001; Concerns: r = −0.28, p < 0.0001) and positively correlated with SRQ scores (Necessity: r = 0.51, p < 0.0001; Concerns: r = 0.44, p < 0.0001).

Conclusion

Preliminary findings indicate that BMQ-AIR© demonstrates satisfactory reliability and validity. BMQ-AIR© is a promising tool that may help tailor interventions to an individual’s specific beliefs and barriers to switching to better support individuals in stopping SABA and initiating AIR therapy.
Clinical efficacy of Osteoking in knee osteoarthritis therapy: a prospective, multicenter, non-randomized controlled study in China
Authors: Zhou Jun , Zheng Zelu , Luo Yuxin , Dong Yawei , Yan Yan , Zhang Yi , Tang Kaiqiang , Quan Rui , Lin Jiaming , Zhang Kuayue , Dong Pengxuan , Wang Rongtian , He Haijun , Lin Na , Weng Xisheng , Mi Baohong , Zhang Yanqiong , Chen Weiheng
Published: June 2024

Background

Osteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs).

Aims

To evaluate the efficacy and safety of Osteoking in treating KOA.

Methods

In the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc.

Results

After 8 weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8 weeks more effectively than that by the treatment of NSAIDs. After 8 weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8 weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2 weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65 years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65 years old and with VAS 8–10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs.

Conclusion

Osteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4–7 scores.

Clinical Trial Registration:

https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR2000034475
Effects of structured and unstructured interventions on fundamental motor skills in preschool children: a meta-analysis
Authors: Chen Delong , Zhao Guanggao , Fu Jinmei , Shun Sunli , Su Liqiang , He Zihao , Chen Ruiming , Jiang Tianle , Hu Xuewen , Li Yunong , Shen Fanchao
Published: June 2024

Background

It has been suggested that higher levels of fundamental motor skills (FMS) promote the physical health of preschool-aged children. The impacts of structured and unstructured interventions on FMS in children aged 10–16 years have been widely acknowledged in previous studies. However, there is a lack of relevant studies in preschool-aged children.

Objective

This meta-analysis aimed to compare the effects of structured and unstructured interventions on FMS in preschool-aged children.

Methods

The PubMed, Web of Science, and Google Scholar databases were searched from inception to 1 November 2023 to identify experiments describing structured and unstructured interventions for FMS in preschool-aged children. The Downs and Black Checklist was used to assess the risk of bias. A random effects model was used for the meta-analysis to evaluate the pooled effects of interventions on FMS. Subgroup analyses based on the duration and characteristics of the intervention were conducted to identify sources of heterogeneity.

Results

A total of 23 studies with 4,068 participants were included. There were 12 studies examining structured interventions, 9 studies examining unstructured interventions, and 6 studies comparing structured vs. unstructured interventions. The risk of bias in the included studies was generally low. All interventions significantly improved FMS in preschool-aged children compared to control treatments (p < 0.05). Structured interventions had more significant effects on locomotor skills (LMSs) in preschool-aged children than unstructured interventions (Hedges’ g = 0.44, p = 0.04). The effects of structured interventions were strongly influenced by the total intervention duration, such that long-term interventions were more effective (Hedge’s g = 1.29, p < 0.001).

Conclusion

Structured interventions play a crucial role in enhancing FMS among young children, especially when considering LMSs. These interventions require consistent and repeated practice over time to reach proficiency.

Systematic review registration:

PROSPERO, identifier number CRD42023475088, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023475088.
TLtrack: Combining Transformers and a Linear Model for Robust Multi-Object Tracking
Authors: He Zuojie , Zhao Kai , Zeng Dan
Published: June 2024

Multi-object tracking (MOT) aims at estimating locations and identities of objects in videos. Many modern multiple-object tracking systems follow the tracking-by-detection paradigm, consisting of a detector followed by a method for associating detections into tracks. Tracking by associating detections through motion-based similarity heuristics is the basic way. Motion models aim at utilizing motion information to estimate future locations, playing an important role in enhancing the performance of association. Recently, a large-scale dataset, DanceTrack, where objects have uniform appearance and diverse motion patterns, was proposed. With existing hand-crafted motion models, it is hard to achieve decent results on DanceTrack because of the lack of prior knowledge. In this work, we present a motion-based algorithm named TLtrack, which adopts a hybrid strategy to make motion estimates based on confidence scores. For high confidence score detections, TLtrack employs transformers to predict its locations. For low confidence score detections, a simple linear model that estimates locations through trajectory historical information is used. TLtrack can not only consider the historical information of the trajectory, but also analyze the latest movements. Our experimental results on the DanceTrack dataset show that our method achieves the best performance compared with other motion models.
Association of Bovine Respiratory Disease during the Pre-Weaning Period with Blood Cell Counts and Circulating Concentration of Metabolites, Minerals, and Acute Phase Proteins in Dairy Calves Transported to a Calf Raising Facility
Authors: Bielamowicz Lauren Paige , Celestino Maria Luiza , Menta Paulo R. , Fernandes Leticia , Ballou Michael , Neves Rafael C. , Machado Vinicius S.
Published: June 2024

Our objective was to investigate the association of bovine respiratory disease (BRD) occurring within the first 56 days of life with blood cell counts and the circulating concentration of metabolites, minerals, and acute phase proteins throughout the pre-weaning period in dairy calves transported to a heifer raising facility within their first week of life. Data from 305 calves transported from dairies in Minnesota to a calf raising facility in New Mexico within their first four days of life were used in this retrospective cohort study. Blood samples were collected at 7, 17, 34, and 56 days of life for the analysis of blood cell counts, biochemistry, and the concentration of acute phase proteins. Blood urea nitrogen, albumin, GLDH, CK, P, Na, K, Cl, Zn, Hp, SAA, and monocyte counts were associated with BRD status throughout or at least at one of the time points evaluated in this study. In conclusion, several hematological variables were associated with BRD status in dairy calves that underwent transportation stress in early life.
The Mechanics Underpinning Non-Deterministic Computation in Cortical Neural Networks
Authors: Stoll Elizabeth A.
Published: June 2024

Cortical neurons integrate upstream signals and random electrical noise to gate signaling outcomes, leading to statistically random patterns of activity. Yet classically, the neuron is modeled as a binary computational unit, encoding Shannon entropy. Here, the neuronal membrane potential is modeled as a function of inherently probabilistic ion behavior. In this new model, each neuron computes the probability of transitioning from an off-state to an on-state, thereby encoding von Neumann entropy. Component pure states are integrated into a physical quantity of information, and the derivative of this high-dimensional probability distribution yields eigenvalues across the multi-scale quantum system. In accordance with the Hellman–Feynman theorem, the resolution of the system state is paired with a spontaneous shift in charge distribution, so this defined system state instantly becomes the past as a new probability distribution emerges. This mechanistic model produces testable predictions regarding the wavelength of free energy released upon information compression and the temporal relationship of these events to physiological outcomes. Overall, this model demonstrates how cortical neurons might achieve non-deterministic signaling outcomes through a computational process of noisy coincidence detection.
CT-Guided Percutaneous Cryoablation of Breast Cancer: A Single-Center Experience
Authors: Vogl Thomas J. , Bielfeldt John , Kübler Ulrich , Adwan Hamzah
Published: June 2024

This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation as an outpatient procedure. We used a liquid-nitrogen based system with a single cryoprobe and performed two freeze cycles with an intermediate thawing. The mean tumor diameter was 1.6 ± 0.7 cm. Follow-up was conducted via contrast-enhanced MR images of the breast. No complications were observed in all 56 ablations. Initial complete ablation was achieved in 100% of cases. Four cases of local tumor progression were reported, resulting in a rate of 8.9%, and 6 cases of intramammary distant recurrence at a rate of 13.3%. The extramammary tumor progression was observed in 7 patients at a rate of 15.6%. The mean overall survival was 4.13 years (95% CI: 3.7–4.5). The mean overall progression-free survival was 2.5 years (95% CI: 1.8–3.2) and the mean local progression-free survival was 2.9 years (95% CI: 2.3–3.6). Cryoablation is a safe and effective treatment for primary breast cancer tumors, which can be performed in analgosedation and as an outpatient procedure. However, potential for improvement exists and further evidence is necessary.
The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Jingbo , Moon Ji Eun , Guo Xin , Yu Jiaqi , Yi Junlin , Bae Sun Hyun
Published: June 2024

Background: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. Results: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56–66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0–100%), 40% (0–77%), and 31% (0–75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89–94%), 89% (95% CI, 86–93%), and 84% (95% CI, 73–92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70–83%), 67% (95% CI, 60–74%), and 61% (95% CI, 55–67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79–88%), 75% (95% CI, 72–79%), and 68% (95% CI, 62–74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3–14%). Conclusion: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.
Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study
Authors: Tabernacki Tomasz , Wang Lindsey , Kaelber David C. , Xu Rong , Berger Nathan A.
Published: June 2024

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.
Dose Contribution to the Regional Lymph-Node Metastases and Point B from Intracavity and Interstitial Hybrid Brachytherapy in Locally Advanced Cervical Cancer
Authors: Muramoto Yoichi , Murakami Naoya , Okonogi Noriyuki , Takatsu Jun , Iijima Kotaro , Inoue Tatsuya , Kato Kanade , Karino Tatsuki , Kojima Kanako , Oshima Masaki , Kosugi Yasuo , Kawamoto Terufumi , Hirayama Takashi , Fujino Kazunari , Terao Yasuhisa , Shikama Naoto
Published: June 2024

Purpose: Analyzing dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS). Methods: Dose distributions of eleven LACC patients with 38 RLNMs, and who received 38 IC/IS sessions were analyzed in EQD2, considering RLNM positions and ipsilateral interstitial needles; these RLNMs, excepting the para-aortic region, were classified into four groups. Results: RLNMs had a median of two ipsilateral interstitial needles per session. Significant differences were observed in total RLNM D90, depending on whether the position was cranial or caudal of the uterine base (85.5 vs. 378.9 cGy, p < 0.0001), and whether the RLNM D90 was associated with a number of ipsilateral interstitial needles between 0–1 or 2 or more (68.4 vs. 112.2 cGy, p = 0.006) per session. At each session, Group 1 RLNMs (cranial of the uterine base, 0–1 ipsilateral interstitial needle) had a mean D90 of 21.1 cGy; Group 2 (cranial, 2 or more), 73.8; Group 3 (caudal, 0–1), 94.7; and Group 4 (caudal, 2 or more), 136.1. Conclusion: RLNMs located caudal of the uterine base associated with two or more ipsilateral interstitial needles in IC/IS had a higher dose contribution, which should be considered when calculating the RLNMs’ dose of external beam boost irradiation.
Exploring the Biosafety Potential of Haberlea rhodopensis Friv. In Vitro Culture Total Ethanol Extract: A Comprehensive Assessment of Genotoxicity, Mitotoxicity, and Cytotoxicity for Therapeutic Applications
Authors: Vasileva Bela , Krasteva Natalia , Hristova-Panusheva Kamelia , Ivanov Penyo , Miloshev George , Pavlov Atanas , Georgiev Vasil , Georgieva Milena
Published: June 2024

The escalating elderly population worldwide has prompted a surge of interest in longevity medicine. Its goal is to interfere with the speed of ageing by slowing it down or even reversing its accompanying effects. As a field, it is rapidly growing and spreading into different branches. One of these is the use of nutraceuticals as anti-ageing drugs. This field is gaining massive popularity nowadays, as people are shifting towards a more natural approach to life and seeking to use natural products as a source of medicine. The present article focuses on the cellular effect of Haberlea rhodopensis Friv. in vitro culture total ethanol extract (HRT), produced by a sustainable biotechnological approach. The extract showed a similar phytochemical profile to plant leaf extract and was rich in primary bioactive ingredients—caffeoyl phenylethanoid glycosides, myconoside, and paucifloside. This study examined the biosafety potential, cytotoxicity, genotoxicity, and mitochondrial activity of the extract using in vitro cultures. The results showed high cell survival rates and minimal cytotoxic effects on Lep3 cells, with no induction of reactive oxygen species nor genotoxicity. Additionally, the extract positively influenced mitochondrial activity, indicating potential benefits for cellular health. The results are promising and show the beneficial effect of HRT without the observation of any adverse effects, which sets the foundation for its further testing and potential therapeutic applications.
The Antioxidant Potential of Commercial Manuka Honey from New Zealand—Biochemical and Cellular Studies
Authors: Kaźmierczak-Barańska Julia , Karwowski Bolesław T.
Published: June 2024

Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive and antioxidant substances such as polyphenols that contribute to its protective effects against oxidative stress. In this study, commercially available Manuka honey was tested for its total polyphenol content and DPPH radical scavenging ability. It was then tested in vitro on human fibroblast cells exposed to UV radiation to assess its potential to protect cells against oxidative stress. The results showed that the honey itself significantly interfered with cell metabolism, and its presence only slightly alleviated the effects of UV exposure. This study also suggested that the MGO content has a minor impact on reducing oxidative stress in UV-irradiated cells and efficiency in scavenging the DPPH radical.
Structural Variations of Prions and Prion-like Proteins Associated with Neurodegeneration
Authors: Christensen Carter Sky , Wang Sean , Li Wenshu , Yu Danyang , Li Henry James
Published: June 2024

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Both amyloid-β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to those of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms largely focus on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and this knowledge could contribute to diagnoses and treatments for the given NDs.
An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer
Authors: Schelz Zsuzsanna , Muddather Hiba F. , Jaski Fatemeh Sheihaki , Bózsity Noémi , Zupkó István
Published: June 2024

Cervical cancer presents a significant challenge to the global health of women. Despite substantial advances in human papillomavirus (HPV)-related cervical cancer vaccines, non-HPV-related cervical cancer is still waiting novel therapeutic options. Drug repurposing has provided a promising approach to improve cancer therapy in recent years. Our study aimed to explore the potential in vitro antineoplastic effects of levosimendan on cervical cancer cells. The antiproliferative effects of levosimendan were investigated on cervical cancer cells using a standard MTT assay. Fluorescent double staining was performed to identify its ability to induce apoptosis and necrosis. The possible mechanism of action of levosimendan was explored using cell-cycle analysis. Furthermore, antimetastatic effects were investigated using a wound-healing assay and a Boyden chamber assay. Our results revealed that levosimendan exhibited the highest growth-inhibitory effect in the HPV-negative C33A cell line. However, the effects were modest compared to the standard agent, cisplatin. Cell-cycle analysis detected that levosimendan can induce cell-cycle arrest in C33A cells by increasing the G1 and G2/M phases, decreasing the S phase, and enhancing the hypodiploid subG1 population. Levosimendan inhibited cell migration and invasion in a concentration-dependent manner. As levosimendan showed antimetastatic efficacy, it could be considered for repurposing to contribute to overcoming resistance to therapy in cervical cancer.
The Autophagic and Apoptotic Death of Forebrain Neurons of Rats with Global Brain Ischemia Is Diminished by the Intranasal Administration of Insulin: Possible Mechanism of Its Action
Authors: Zakharova Irina O. , Bayunova Liubov V. , Avrova Daria K. , Tretyakova Alina D. , Shpakov Alexander O. , Avrova Natalia F.
Published: June 2024

Insulin is a promising neuroprotector. To better understand the mechanism of insulin action, it was important to show its ability to diminish autophagic neuronal death in animals with brain ischemic and reperfusion injury. In forebrain ischemia and reperfusion, the number of live neurons in the hippocampal CA1 region and frontal cortex of rats decreased to a large extent. Intracerebroventricular administration of the autophagy and apoptosis inhibitors to ischemic rats significantly increased the number of live neurons and showed that the main part of neurons died from autophagy and apoptosis. Intranasal administration of 0.5 IU of insulin per rat (before ischemia and daily during reperfusion) increased the number of live neurons in the hippocampal CA1 region and frontal brain cortex. In addition, insulin significantly diminished the level of autophagic marker LC3B-II in these forebrain regions, which markedly increased during ischemia and reperfusion. Our studies demonstrated for the first time the ability of insulin to decrease autophagic neuronal death, caused by brain ischemia and reperfusion. Insulin administered intranasally activated the Akt-kinase (activating the mTORC1 complex, which inhibits autophagy) and inhibited the AMP-activated protein kinase (which activates autophagy) in the hippocampus and frontal cortex of rats with brain ischemia and reperfusion.
Potential Protective Factors for Allergic Rhinitis Patients Infected with COVID-19
Authors: Dong Jiaoyue , Su Dingyuan , Zhao Binbin , Han Jiayang , Tu Mengjie , Zhang Kaifeng , Wang Fengling , An Yang
Published: June 2024

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway allergic disease may not be a high-risk factor, but may be a protective factor for COVID-19 infection, which is closely related to its low-level expression of the ACE2 receptor and the complex cytokines network as underlying molecular regulatory mechanisms. In addition, steroid hormones and age factors could not be ignored. In this review, we have summarized some current evidence on the relationship between COVID-19 and allergic rhinitis to highlight the underlying mechanisms of COVID-19 infection and provide novel insights for its prevention and treatment. The key findings show that allergic rhinitis and its related molecular mechanisms may have a protective effect against COVID-19 infection.
Sustainable and Innovative Self-Healing Concrete Technologies to Mitigate Environmental Impacts in Construction
Authors: Kaushal Vinayak , Saeed Elayna
Published: June 2024

The production of concrete and the manufacturing process of cement result in a significant carbon footprint, contributing to a large portion of global emissions in structures such as buildings, bridges, roads, and tunnels. Although concrete is an ideal building material that is durable and long-lasting, it can be susceptible to micro-cracks. These micro-cracks in concrete can allow water and chlorine ions to penetrate the structure, leading to the degradation of the concrete and corrosion of the reinforcement, posing an unacceptable level of structural risk. Self-healing concrete is not a new material in the construction industry but can be characterized by the capability of concrete to repair its cracks autogenously or autonomously. Recent advancements in concrete research and technology have given us a better understanding of concrete’s healing properties. Self-healing concrete combines durability with sustainability while offsetting the high carbon output of concrete manufacturing and production and associated life-cycle costs. Technologies such as microbially induced calcite (calcium carbonate) precipitation, shape-memory polymers, encapsulation methods, hydration, and swelling agents can potentially reduce carbon emissions while enhancing resilience and longevity. This paper examines these technologies and their applications in the construction industry by comprehensively reviewing the literature and available case studies. This study concluded that there are promising advancements and innovations in concrete, particularly when improving upon its autogenous healing properties. The recommendations for future research include exploring more ways to bring the concrete industry and cement manufacturing toward net-zero carbon emissions.
Surface Quality of High-Concentration SiC/Al Grinding with Electroassisted Biolubricant MQL
Authors: Zhang Weidong , Jia Dongzhou , Yang Min , Gao Qi , Gao Teng , Duan Zhenjing , Qu Da
Published: June 2024

SiC/Al composites are widely used in aerospace and other fields due to their excellent mechanical properties. For large-concentration composites, due to the extremely high proportion of SiC and the unstable interface between the two phases, the SiC particles are broken and detached during the processing, which makes the surface quality of the workpiece insufficient to meet the service requirements. Electrically assisted cutting technology is expected to break through this technical bottleneck. This paper investigates the surface quality of high-concentration SiC/Al grinding with electroassisted biolubricant MQL. The surface morphology after processing is observed. Firstly, by comparing the traditional grinding and electrically assisted grinding conditions, it is found that the fundamental reason for the improvement in the grinding surface quality using a pulse current is the improvement in the Al plasticity. Secondly, based on the thermal effect and non-thermal effect of the pulse current, the influence of the electrical parameters (current, duty cycle and frequency) on the machining indication quality is discussed. It is found that when the current and duty cycle increase, the machining surface quality will also increase, while the frequency change has little effect on the surface quality. Finally, friction and wear experiments are carried out on the grinding surface under different working conditions to explore the friction and wear characteristics of the surface of the workpiece. The results show that the pulse current can significantly improve the wear resistance of the grinding surface.
Emotional Regulation, Adult Attachment Orientations, and Risk of COVID-19 Infection: Virtual Reality Simulation
Authors: Pinto Ricardo J. , Albuquerque Sara , Vieira de Castro Maria , Gamito Pedro , Jongenelen Inês , Levendosky Alytia
Published: June 2024

(1) Background: To mitigate COVID-19 transmission, global public health interventions were swiftly implemented. However, a comprehensive understanding of individual variations in adhering to these recommendations remains elusive. Addressing this gap is crucial for effectively managing future epidemic and pandemic scenarios. This study aims to explore individual differences in attachment, emotion regulation, and risk for COVID-19 infection using virtual reality (VR). (2) Methods: The sample included 73 (88%) university students and 10 (12%) university staff. Participants completed questionnaires on sociodemographic information, the Difficulties in Emotion Regulation Scale, the Experiences in Close Relationships—Relationship Structures Questionnaire, and the fear of COVID-19 Scale. Additionally, each participant engaged in five daily situations using a VR simulator to assess the risk of COVID-19 infection. (3) Results: Our study revealed that high levels of attachment anxiety, difficulties controlling impulsive behaviors, and limited access to emotion regulation strategies were strong predictors of elevated risk of COVID-19 infection. Conversely, high levels of fear of COVID-19 and attachment avoidance were associated with lower risk of COVID-19 infection. (4) Conclusions: We discuss the importance of policymakers and health professionals being aware of some psychological characteristics that make it difficult for some individuals to adhere to public health measures involving social distancing.
A Paradigm Shift: The Reclassification of SARS-CoV-2 and Longitudinal Immune Responses in Japanese Healthcare Workers
Authors: Chano Tokuhiro , Kita Hiroko , Yamashita Tomoko , Fujimura Hirokazu , Ikemoto Toshiyuki
Published: June 2024

Under the aegis of the National Infectious Diseases Act, the virus transitioned from a category 2 menace to category 5, analogous to seasonal influenza. For this classification to be appropriate, a comprehensive assessment of the immune status of the Japanese population must be conducted to ensure adequacy. The current study has investigated the protracted immune responses of healthcare workers (HCWs) to SARS-CoV-2 in Japan. One year subsequent to the systematically implemented SARS-CoV-2 vaccination campaign among HCWs, humoral and cellular immune responses were sustained at levels as high as or higher than those immediately following the third booster vaccination. Persisting immunity has highlighted the resilience and lasting memory exhibited in HCW defense against the virus, suggesting that the classification of SARS-CoV-2 infection as a category 5 in Japan has appeared judicious.
Quantifying the Dosimetric Impact of Proton Range Uncertainties on RBE-Weighted Dose Distributions in Intensity-Modulated Proton Therapy for Bilateral Head and Neck Cancer
Authors: Rana Suresh , Manthala Padannayil Noufal , Tran Linh , Rosenfeld Anatoly B. , Saeed Hina , Kasper Michael
Published: June 2024

Background: In current clinical practice, intensity-modulated proton therapy (IMPT) head and neck cancer (HNC) plans are generated using a constant relative biological effectiveness (cRBE) of 1.1. The primary goal of this study was to explore the dosimetric impact of proton range uncertainties on RBE-weighted dose (RWD) distributions using a variable RBE (vRBE) model in the context of bilateral HNC IMPT plans. Methods: The current study included the computed tomography (CT) datasets of ten bilateral HNC patients who had undergone photon therapy. Each patient’s plan was generated using three IMPT beams to deliver doses to the CTV_High and CTV_Low for doses of 70 Gy(RBE) and 54 Gy(RBE), respectively, in 35 fractions through a simultaneous integrated boost (SIB) technique. Each nominal plan calculated with a cRBE of 1.1 was subjected to the range uncertainties of ±3%. The McNamara vRBE model was used for RWD calculations. For each patient, the differences in dosimetric metrices between the RWD and nominal dose distributions were compared. Results: The constrictor muscles, oral cavity, parotids, larynx, thyroid, and esophagus showed average differences in mean dose (Dmean) values up to 6.91 Gy(RBE), indicating the impact of proton range uncertainties on RWD distributions. Similarly, the brachial plexus, brain, brainstem, spinal cord, and mandible showed varying degrees of the average differences in maximum dose (Dmax) values (2.78–10.75 Gy(RBE)). The Dmean and Dmax to the CTV from RWD distributions were within ±2% of the dosimetric results in nominal plans. Conclusion: The consistent trend of higher mean and maximum doses to the OARs with the McNamara vRBE model compared to cRBE model highlighted the need for consideration of proton range uncertainties while evaluating OAR doses in bilateral HNC IMPT plans.
Navigation-Based Telehealth Informed Decision-Making for Prostate Cancer Screening in Black Men
Authors: Ba Djibril M. , Kayembe Chrispin , Littlejohn Joe , Van Scoy Lauren J. , VanDyke Erika , Williams James , Katoch Avnish , Shook Neil C. , Zhang Yue , Livelsberger Craig , McDonald Alicia C. , Muscat Joshua E.
Published: June 2024

The rapid increase in telehealth has the potential to bring informed decision-making for prostate cancer screening (PCS) at the population level to high-risk individuals. We utilized a global technology platform of electronic health records data repositories (TriNetX) to determine its utility for Navigator-guided decision-making aid for PCS in Black men ages 45–79 years with no history of prostate cancer and PSA testing. Patients from Pennsylvania were invited to participate in a telehealth-delivered informed decision-making session for PCS. Focus groups, social learning theory, visual diagrams, and quantitative data on PCS risks and benefits were used to develop the content of the sessions, which included numerical discussions of risks vs. benefits in Black men. Participants completed several surveys, including baseline demographic and numeracy questionnaires, a one-on-one telehealth session with a trained Navigator, post-Navigation surveys, and an optional follow-up session with a urologist. Eighty-seven participants were consented and recruited. Although the mean numeracy score was only 1.9 out of 6, more than 90% rated as good or excellent that the sessions aided their PCS decision-making skills. This study indicates that Navigation by telehealth offers the ability to assist in informed decision-making for PCS at the population level.
To Reconstruct or Not to Reconstruct: Piloting a Vietnamese and Arabic Breast Reconstruction Decision Aid in Australia
Authors: Soon Patsy S. , Kamalmaz Khouloud , Wu Verena S. , Karimi Neda , Gerges Martha , Sherman Kerry A. , Girgis Afaf
Published: June 2024

Currently, there are no resources to support culturally and linguistically diverse (CALD) women with breast cancer to make decisions about undergoing breast reconstruction (BR). This study evaluated the usability and acceptability of decision aids (DAs) for Vietnamese- and Arabic-speaking women. This two-phase qualitative recruited Vietnamese- (Phase 1) and Arabic-speaking (Phase 2) adult (age ≥ 18 years) women who were diagnosed with breast cancer and could read Vietnamese/Arabic. Women participated in either think-aloud telephone interviews (Phase 1) or semi-structured telephone interviews (Phase 2) and provided feedback on the DA. Interviews were audio-recorded, translated, and transcribed from Vietnamese/Arabic to English, and inductive thematic analysis was undertaken. Additionally, Arabic-speaking women completed the Preparation for Decision Making (PrepDM) scale in Round 2. Twenty-five women were recruited in two phases (Phase 1: Vietnamese-speaking women, n = 14; Phase 2: Arabic-speaking, n = 11). Three themes were developed in Phase 1: (1) DA content and reception; (2) linguistic attributes and cultural appropriateness; and (3) factors that improve the DAs’ impact. Three themes were developed in Phase 2: (1) varying perceptions of DA content; (2) linguistic and cultural suitability of information; and (3) impact of DA on decision making. Women from both phases identified areas for improvement: minimising the use of medical terminology, considering the cultural taboos associated with the word ‘breast’, and addressing remaining information gaps. Both language DAs were generally perceived as acceptable and useful in providing information about BR options and prompting women’s reflections about the suitability of BR as part of their treatment. The mean PrepDM score for Arabic-speaking women in Round 2 was 4.8/5 (SD = 0.3). Further work is needed to ensure that culturally adapted DAs take into account the myriad of information needs and health literacy levels. The key role of healthcare professionals in shared decision making among CALD populations should also be considered.
Digital Papillary Adenocarcinoma: The Detection of Low-Risk Human Papillomaviruses and the BRAF p.V600E Mutation in a Subset of Cases
Authors: Chen Feifan , Nagarajan Priyadharsini , Aung Phyu P.
Published: June 2024

Digital papillary adenocarcinoma (DPA) is a rare malignant neoplasm which arises from the sweat glands and has metastatic potential. DPA exhibits a wide range of architectural features and exhibits low-grade to high-grade features, so distinguishing DPA from benign skin neoplasms, including acral hidradenoma, poses significant diagnostic challenges. The recent literature suggests a strong association between DPA and human papillomavirus (HPV) 42, a low-risk HPV (LR-HPV) subtype, and a possible association between DPA and BRAF p.V600E. To explore these associations, we assessed the utility of in situ hybridization (ISH) for LR-HPV (types 6, 11, 40, 42, 43, 44) and immunohistochemistry (IHC) for BRAF p.V600E in diagnosing DPA and distinguishing DPA from acral hidradenoma. With institutional review board approval, we retrospectively identified 15 specimens of DPA (from 13 patients) and 3 cases of acral hidradenoma. Of the 13 DPA cases, 6 were negative for LR-HPV and BRAF p.V600E; 6 were positive for only LR-HPV; and 1 was positive for only BRAF p.V600E but negative for LR-HPV. All three cases of acral hidradenoma were negative for LR-HPV and BRAF p.V600E. As our sample size is limited, larger studies are needed to assess the value of detecting LR-HPV and BRAF p.V600E in the distinction of DPA and acral hidradenoma. However, our findings indicate a stronger association of DPA with LR-HPV than with BRAF p.V600E.
Rise and Fall of Anderson Localization by Lattice Vibrations: A Time-Dependent Machine Learning Approach
Authors: Zimmermann Yoel , Keski-Rahkonen Joonas , Graf Anton M. , Heller Eric J.
Published: June 2024

The intricate relationship between electrons and the crystal lattice is a linchpin in condensed matter, traditionally described by the Fröhlich model encompassing the lowest-order lattice-electron coupling. Recently developed quantum acoustics, emphasizing the wave nature of lattice vibrations, has enabled the exploration of previously uncharted territories of electron–lattice interaction not accessible with conventional tools such as perturbation theory. In this context, our agenda here is two-fold. First, we showcase the application of machine learning methods to categorize various interaction regimes within the subtle interplay of electrons and the dynamical lattice landscape. Second, we shed light on a nebulous region of electron dynamics identified by the machine learning approach and then attribute it to transient localization, where strong lattice vibrations result in a momentary Anderson prison for electronic wavepackets, which are later released by the evolution of the lattice. Overall, our research illuminates the spectrum of dynamics within the Fröhlich model, such as transient localization, which has been suggested as a pivotal factor contributing to the mysteries surrounding strange metals. Furthermore, this paves the way for utilizing time-dependent perspectives in machine learning techniques for designing materials with tailored electron–lattice properties.
Development and Preliminary Validation of a Scale to Measure Perceived Therapist’s Knowledge about Gender Identity Diversity among Trans and Non-Binary Individuals in Puerto Rico
Authors: Esteban Caleb , Hernández-López Eddiel , Francia-Martínez Margarita , Ramos-Pibernus Alixida
Published: June 2024

This study aimed to describe the development of the Perceived Therapist’s Knowledge about Gender Identity Diversity Scale and to preliminarily validate this scale by describing its psychometric properties. This research instrument was constructed based on the existing literature and recommendations for instrument development. Initially, a 36-item scale was devised to assess perceived openness and knowledge about gender identity diversity in therapy. The content validation process involved 12 expert judges, leading to a refined 25-item scale. Participants consisting of 57 trans and non-binary Puerto Rican individuals completed the scale. Exploratory factor analysis revealed a unidimensional structure, supporting a single factor named “perceived knowledge about gender identity diversity in therapy.” The final scale demonstrated excellent reliability (α = 0.978; Sα = 0.980; ω = 0.979), indicating strong internal consistency. This validated scale contributes to assessing primarily Hispanic trans and non-binary individuals’ perceptions of their therapists’ knowledge about gender identity diversity.