bluuebunny/crossref_metadata_2025 huggingface dataset:
Allostatic load and chronic pain: a prospective finding from the national survey of midlife development in the United States, 2004–2014
Authors: Liang Yunlong , Booker Cara
Published: February 2024

Background

Previous research has demonstrated a correlation between chronic stress and chronic pain (CP). However, there have been few studies examining the prospective association of allostatic load (AL)—the biological processes related to stress—with CP.

Methods

We firstly conducted latent class analysis to identify phenotypes of AL using a community-dwelling sample, the Midlife in the United States. Multinomial logistic regression models were used to examine the prospective association between phenotypes of AL at MIDUS 2 biomarker project and the presence of CP, CP interference and the number of CP sites at MIDUS 3.

Results

Three phenotypes of AL, low biological dysregulation, parasympathetic dysregulation and metabolic dysregulation, were identified. Compared to low biological dysregulation group, participants experiencing metabolic dysregulation phenotype of AL at MIDUS 2 had higher risks of having high-interference CP (RRR = 2.00, 95% CI: 1.06, 3.79, P < 0.05) and 3 or more CP sites (RRR = 2.03, 95% CI: 1.08, 3.83, P < 0.05) at MIDUS 3.

Conclusion

The findings indicate that focusing on mitigating the metabolic dysfunction phenotype of AL has the potential to be an efficacious strategy for alleviating future CP bodily widespreadness and high CP interference.
Psychometric evaluation of the Chinese version of the stressors in breast cancer scale: a translation and validation study
Authors: Hu Wenqi , Bao Jiahui , Yang Xiaolin , Ye Mao
Published: February 2024

Objective

To translate the Stressors in Breast Cancer Scale (SBCS) from English to Chinese and assess its psychometric properties.

Methods

The Brislin’s translation model was applied to perform forward translation, back translation, cross-cultural adaptation, Whereas the Chinese version of the SBCS was formed by conducting pre-testing. A cohort of 878 breast cancer patients participated in this methodological study. Content validity, construct validity, convergent validity, discriminant validity, and criterion-related validity were used to establish validity. Internal consistency reliability, split-half reliability, and test-retest reliability were used to establish reliability.

Results

The final scale contained five dimensions and 24 items, including interpersonal relationship and healthcare strains, worries and concerns about the future, physical appearance and sex strains, daily difficulties and health. The average content validity index of the scale was 0.975. The goodness-of-fit index (χ2/DF = 2.416, RMSEA = 0.057, GFI = 0.896, CFI = 0.947, IFI = 0.947, and TLI = 0.939) indicated that the model was well-fitted. The composite reliability (CR) of the dimensions ranged from 0.825 to 0.934, the average variance extracted (AVE) ranged from 0.539 to 0.712, and the correlation coefficients of each dimension with the other dimensions were less than the square root of the AVE for that dimension. The Criterion-related validity was 0.511. The Cronbach’s alpha was 0.938, and the dimensions ranged from 0.779 to 0.900. Split-half reliability was 0.853, with dimensions ranging from 0.761 to 0.892. Test-retest reliability was 0.855.

Conclusions

The Chinese version of the SBCS has good reliability and validity, which can be applied to the assessment of stressors in breast cancer patients in China.
Detecting high-risk neighborhoods and socioeconomic determinants for common oral diseases in Germany
Authors: Völker Sebastian , van der Zee-Neuen Antje , Rinnert Alexander , Hanneken Jessica , Johansson Tim
Published: February 2024

Background

Ideally, health services and interventions to improve dental health should be tailored to local target populations. But this is not the standard. Little is known about risk clusters in dental health care and their evaluation based on small-scale, spatial data, particularly among under-represented groups in health surveys. Our study aims to investigate the incidence rates of major oral diseases among privately insured and self-paying individuals in Germany, explore the spatial clustering of these diseases, and evaluate the influence of social determinants on oral disease risk clusters using advanced data analysis techniques, i.e. machine learning.

Methods

A retrospective cohort study was performed to calculate the age- and sex-standardized incidence rate of oral diseases in a study population of privately insured and self-pay patients in Germany who received dental treatment between 2016 and 2021. This was based on anonymized claims data from BFS health finance, Bertelsmann, Dortmund, Germany. The disease history of individuals was recorded and aggregated at the ZIP code 5 level (n = 8871).

Results

Statistically significant, spatially compact clusters and relative risks (RR) of incidence rates were identified. By linking disease and socioeconomic databases on the ZIP-5 level, local risk models for each disease were estimated based on spatial-neighborhood variables using different machine learning models. We found that dental diseases were spatially clustered among privately insured and self-payer patients in Germany. Incidence rates within clusters were significantly elevated compared to incidence rates outside clusters. The relative risks (RR) for a new dental disease in primary risk clusters were min = 1.3 (irreversible pulpitis; 95%-CI = 1.3–1.3) and max = 2.7 (periodontitis; 95%-CI = 2.6–2.8), depending on the disease. Despite some similarity in the importance of variables from machine learning models across different clusters, each cluster is unique and must be treated as such when addressing oral public health threats.

Conclusions

Our study analyzed the incidence of major oral diseases in Germany and employed spatial methods to identify and characterize high-risk clusters for targeted interventions. We found that private claims data, combined with a network-based, data-driven approach, can effectively pinpoint areas and factors relevant to oral healthcare, including socioeconomic determinants like income and occupational status. The methodology presented here enables the identification of disease clusters of greatest demand, which would allow implementing more targeted approaches and improve access to quality care where they can have the most impact.
The experience of patients with hematological malignancy in their terminal stage: a phenomenological study from Jordan’s perspective
Authors: Alnaeem Mohammad M. , Shehadeh Anas , Nashwan Abdulqadir J.
Published: February 2024

Background

Patients diagnosed with hematological malignancies residing in low-middle-income countries undergo significant physical and psychological stressors. Despite this, only 16% of them receive proper care during the terminal stages. It is therefore crucial to gain insight into the unique experiences of this population.

Aim

To have a better understanding of the needs and experiences of adult patients with advanced hematological malignancy by exploring their perspectives.

Methods

A qualitative interpretive design was employed to collect and analyze data using a phenomenological approach. The study involved in-depth interviews with ten participants aged between 49 and 65 years, utilizing a semi-structured approach.

Results

Two primary themes emerged from the participants’ experiences of reaching the terminal stage of illness: “Pain, Suffering, and Distress” and “Spiritual Coping.” The first theme encompassed physical and emotional pain, suffering, and distress, while the second theme was centered on the participants’ spiritual coping mechanisms. These coping mechanisms included seeking comfort in religious practices, relying on spiritual support from family and friends, and finding solace in their beliefs and faith.

Conclusion

Patients with hematological malignancies in the terminal stages of their disease experience severe pain, considerable physical and psychosocial suffering, and spiritual distress. While they require support to cope with their daily struggles, their experiences often go unnoticed, leading to disappointment and loss of dignity. Patients mainly rely on their spirituality to cope with their situations. Healthcare providers must acknowledge these patients’ needs and provide more holistic and effective care.
Examining the pedagogical practices that support cultural proficiency development in graduate health science students
Authors: Speer Julie E. , Conley Quincy
Published: February 2024

Background

Health disparities are often a function of systemic discrimination and healthcare providers’ biases. In recognition of this, health science programs have begun to offer training to foster cultural proficiency (CP) in future professionals. However, there is not yet consensus about the best ways to integrate CP into didactic and clinical education, and little is known about the role of clinical rotations in fostering CP.

Methods

Here, a mixed-methods approach was used to survey students (n = 131) from a private all-graduate level osteopathic health sciences university to gain insight into the training approaches students encountered related to CP and how these may vary as a function of academic progression. The research survey included instruments designed to quantify students’ implicit associations, beliefs, and experiences related to the CP training they encountered through the use of validated instruments, including Implicit Association Tests and the Ethnocultural Empathy Inventory, and custom-designed questions.

Results

The data revealed that most students (73%) had received CP training during graduate school which primarily occurred via discussions, lectures, and readings; however, the duration and students’ perception of the training varied substantially (e.g., training range = 1–100 hours). In addition, while students largely indicated that they valued CP and sought to provide empathetic care to their patients, they also expressed personal understandings of CP that often fell short of advocacy and addressing personal and societal biases. The results further suggested that clinical rotations may help students attenuate implicit biases but did not appear to be synergistic with pre-clinical courses in fostering other CP knowledge, skills, and attitudes.

Conclusions

These findings highlight the need to utilize evidence-based pedagogical practices to design intentional, integrated, and holistic CP training throughout health science programs that employ an intersectional lens and empowers learners to serve as advocates for their patients and address systemic challenges.
Motivational drivers for health professionals in a large quality improvement collaborative project in Brazil: a qualitative study
Authors: da Silva Eliane Pereira , Saturno-Hernández Pedro Jesus , de Freitas Marise Reis , da Silva Gama Zenewton André
Published: February 2024

Background

The success of collaborative quality improvement (QI) projects in healthcare depends on the context and engagement of health teams; however, the factors that modulate teams’ motivation to participate in these projects are still unclear. The objective of the current study was to explore the barriers to and facilitators of motivation; the perspective was health professionals in a large project aiming to implement evidence-based infection prevention practices in intensive care units of Brazilian hospitals.

Methods

This qualitative study was based on content analysis of semistructured in-depth interviews held with health professionals who participated in a collaborative QI project named “Improving patient safety on a large scale in Brazil”. In accordance with the principle of saturation, we selected a final sample of 12 hospitals located throughout the five regions of Brazil that have implemented QI; then, we conducted videoconference interviews with 28 health professionals from those hospitals. We encoded the interview data with NVivo software, and the interrelations among the data were assessed with the COM-B model.

Results

The key barriers identified were belief that improvement increases workload, lack of knowledge about quality improvement, resistance to change, minimal involvement of physicians, lack of supplies, lack support from senior managers and work overload. The primary driver of motivation was tangible outcomes, as evidenced by a decrease in infections. Additionally, factors such as the active participation of senior managers, teamwork, learning in practice and understanding the reason for changes played significant roles in fostering motivation.

Conclusion

The motivation of health professionals to participate in collaborative QI projects is driven by a variety of barriers and facilitators. The interactions between the senior manager, quality improvement teams, and healthcare professionals generate attitudes that modulate motivation. Thus, these aspects should be considered during the implementation of such projects. Future research could explore the cost-effectiveness of motivational approaches.
Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans
Authors: Lv Yunhui , Li Kai , Wang Shuo , Wang Xiaokang , Yue Guangxin , Zhang Yangyang , Lv Xin , Zhao Ping , Wang Shiping , Zhang Qi , Li Qiuju , Zhu Jinyan , Li Jubo , Peng Peng , Li Yue , Luo Jiafei , Zhang Xue , Yang Jianzhong , Zhang Baojie , Wang Xuemin , Zhang Min , Shen Chen , Wang Xin , Wang Miao , Ye Zhen , Cui Yongchun
Published: February 2024

Aim

Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury.

Methods and results

Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose.

Conclusions

AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.
M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy
Authors: Wang Xingxing , Xu Changlin , Bian Cunxin , Ge Pengfei , Lei Jie , Wang Jingfan , Xiao Tianhao , Fan Yuanyuan , Gu Qinyuan , Li Hong-Ying , Xu Jingyi , Hu Zizhong , Xie Ping
Published: February 2024

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

Graphical Abstract
Mitral valve repair for degenerative mitral regurgitation with Carpentier’s functional classification type II in elderly patients: a single center experience
Authors: Kawamura Masashi , Monta Osamu , Maeda Shusaku , Tsutsumi Yasushi
Published: February 2024

Objective

Mitral valve (MV) repair for Carpentier functional classification Type II (C-II) mitral regurgitation (MR) is widely accepted because of its efficacy. It is unclear whether MV repair has the same benefits in elderly patients as in younger patients because of their lower life expectancy. Herein, we examined the midterm results of MV repair for C-II mitral regurgitation, especially in patients aged ≧70 years.

Method

A retrospective review was performed on 176 patients who underwent MV repair for C-II mitral regurgitation with a median age of 65 years; 55 (31%) patients were ≧70 years, and 124 were male (71%). Lesions of the mitral valve were isolated from the anterior leaflet (48 patients), posterior leaflet (113 patients), and both leaflets (15 patients), and included seven patients with Barlow’s disease. We compared the outcomes between patients aged ≧70 years (≧70 years; median age, 76 years) and those aged < 70 years (median age, 60 years).

Results

In terms of the durability of MV repair in elderly patients, there were no significant differences in the rates of freedom from reoperation or MR recurrence at 5 years between patients aged < 70 years and those aged ≧70 years (reoperation:98% in < 70 years versus 89% in ≧70 years; P = 0.4053; MR recurrence:95% in < 70 years versus 81% in ≧70 years; P = 0.095). The mitral valve complexity was divided into two grades: Simple (isolated posterior mitral lesion) and Complex (isolated anterior lesion or both lesions). In patients aged < 70 years, there was no significant difference in the rate of freedom from MR recurrence at 5 years between the Simple and Complex groups (96% vs. 91%; P = 0.1029). In contrast, in patients aged ≧70 years, the MR recurrence rate at 3 years in Complex was significantly higher in the Complex group than in the Simple (100% vs. 80%; P = 0.0265).

Conclusions

We studied the outcomes of MV repair for C-II in MR. In elderly patients, MR recurrence was higher in complex lesions than in simple lesions. MV replacement may be considered for elderly patients with complex mitral valve lesions, if appropriately selected.
Risk factors associated with severe adverse events in patients with relapsing polychondritis undergoing flexible bronchoscopy
Authors: Wang Shao-Ting , Wang Jinglan , Gao Xiaoxing , Chen Keqi , Xu Kai-Feng , Tian Xinlun
Published: February 2024

Background

Patients with relapsing polychondritis (RP) sometimes experience upper airway collapse or lower airway stenosis, and bronchoscopy may provide a valuable typical image to confirm the diagnosis. This study aimed to identify potential risk factors associated with severe adverse effects during bronchoscopy.

Methods

We performed a retrospective cohort study of 82 consecutive patients with RP hospitalized at Peking Union Medical College Hospital between January 1, 2012 and December 31, 2022. Clinical features and disease patterns were compared among patients with RP undergoing bronchoscopy with or without severe adverse effects. Binary logistic regression analysis was performed to identify the associated risk factors.

Results

For patients with RP undergoing bronchoscopy with severe adverse effects, the forced vital capacity (FVC), forced vital capacity percent predicted values (FVC%), and peak expiratory flow were significantly lower (P = 0.001, P = 0.001, and P = 0.021, respectively) than those in the non-severe adverse effect subgroup. Binary logistic regression analysis revealed that low FVC% (odds ratio, 0.930; 95% confidence interval, 0.880–0.982; P = 0.009) was an independent risk factor for severe adverse events in patients undergoing bronchoscopy.

Conclusions

Low FVC or FVC% suggests a high risk of severe adverse effects in patients with RP undergoing bronchoscopy. Patients with such risk factors should be carefully evaluated before bronchoscopy and adequately prepared for emergency tracheal intubation or tracheostomy.
IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts
Authors: Van den Eynde Astrid , Gehrcken Laura , Verhezen Tias , Lau Ho Wa , Hermans Christophe , Lambrechts Hilde , Flieswasser Tal , Quatannens Delphine , Roex Gils , Zwaenepoel Karen , Marcq Elly , Joye Philippe , Cardenas De La Hoz Edgar , Deben Christophe , Gasparini Alessia , Montay-Gruel Pierre , Le Compte Maxim , Lion Eva , Lardon Filip , Van Laere Steven , Siozopoulou Vasiliki , Campillo-Davo Diana , De Waele Jorrit , Pauwels Patrick , Jacobs Julie , Smits Evelien , Van Audenaerde Jonas R. M.
Published: February 2024

Background

It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies. Moreover, CD70 is also expressed on cancer-associated fibroblasts (CAFs), another roadblock for treatment efficacy in CRC and PDAC. We explored the therapeutic potential of CD70 as target for CAR natural killer (NK) cell therapy in CRC, PDAC, focusing on tumor cells and CAFs, and lymphoma.

Methods

RNA-seq data and immunohistochemical analysis of patient samples were used to explore CD70 expression in CRC and PDAC patients. In addition, CD70-targeting CAR NK cells were developed to assess cytotoxic activity against CD70+ tumor cells and CAFs, and the effect of cytokine stimulation on their efficacy was evaluated. The in vitro functionality of CD70-CAR NK cells was investigated against a panel of tumor and CAF cell lines with varying CD70 expression. Lymphoma-bearing mice were used to validate in vivo potency of CD70-CAR NK cells. Lastly, to consider patient variability, CD70-CAR NK cells were tested on patient-derived organoids containing CAFs.

Results

In this study, we identified CD70 as a target for tumor cells and CAFs in CRC and PDAC patients. Functional evaluation of CD70-directed CAR NK cells indicated that IL-15 stimulation is essential to obtain effective elimination of CD70+ tumor cells and CAFs, and to improve tumor burden and survival of mice bearing CD70+ tumors. Mechanistically, IL-15 stimulation resulted in improved potency of CD70-CAR NK cells by upregulating CAR expression and increasing secretion of pro-inflammatory cytokines, in a mainly autocrine or intracellular manner.

Conclusions

We disclose CD70 as an attractive target both in hematological and solid tumors. IL-15 armored CAR NK cells act as potent effectors to eliminate these CD70+ cells. They can target both tumor cells and CAFs in patients with CRC and PDAC, and potentially other desmoplastic solid tumors.
Calcium signaling positively regulates cellulase translation and secretion in a Clr-2-overexpressing, catabolically derepressed strain of Penicillium funiculosum
Authors: Randhawa Anmoldeep , A. Ogunyewo Olusola , Jawed Kamran , Yazdani Syed Shams
Published: February 2024

Background

Low-cost cellulase production is vital to sustainable second-generation biorefineries. The catabolically derepressed strain of Penicillium funiculosum NCIM1228 (PfMig188 or ∆Mig1) secretes a superior set of cellulolytic enzymes, that are most suitable for 2G biorefineries. At a 3% (w/w) load, the ∆Mig1 secretome can release > 80% of fermentable sugars from lignocellulose at a 15% (w/v) biomass load, irrespective of the type of biomass and pretreatment. The robustness of the secretome can be further increased by improving the cellulase production capacity of the fungal strain.

Results

We began by identifying the transcription factor responsible for cellulase production in NCIM1228. An advanced RNA-seq screen identified three genes, clr-2, ctf1a and ctf1b; the genes were cloned under their native promoters and transformed into NCIM1228. Of the three, clr-2 overexpression led to twofold higher cellulase production than the parent strain and was thus identified as the transcriptional activator of cellulase in NCIM1228. Next, we overexpressed clr-2 in ∆Mig1 and expected an exponential increase in cellulolytic attributes accredited to the reinforced activation mechanisms, conjoint with diminished negative regulation. Although clr-2 overexpression increased the transcript levels of cellulase genes in ∆Mig1, there was no increase in cellulase yield. Even a further increase in the transcript levels of clr-2 via a stronger promoter was ineffective. However, when the CaCO3 concentration was increased to 5 g/l in the growth medium, we achieved a 1.5-fold higher activity of 6.4 FPU/ml in the ∆Mig1 strain with clr-2 overexpression. Enthused by the calcium effect, a transcriptomic screen for genes encoding Ca2+-activated kinase identified ssp1, whose overexpression could further increase cellulase yield to ~ 7.5 FPU/ml. Investigation of the mechanism revealed that calcium signaling exclusively enhances the translation and secretion of cellulase in Penicillium funiculosum.

Conclusions

Our study identifies for the first time that cellulose activates two discrete signaling events to govern cellulase transcription and posttranscriptional processes (translation, processing and secretion) in P. funiculosum NCIM1228. Whereas Clr-2, the transcriptional activator of cellulase, governs transcription, calcium signaling specifically activates cellulase translation and secretion.
Intestinal metabolites predict treatment resistance of patients with depression and anxiety
Authors: Matsuzaki Juntaro , Kurokawa Shunya , Iwamoto Chiaki , Miyaho Katsuma , Takamiya Akihiro , Ishii Chiharu , Hirayama Akiyoshi , Sanada Kenji , Fukuda Shinji , Mimura Masaru , Kishimoto Taishiro , Saito Yoshimasa
Published: February 2024

Background

The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance.

Results

We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69–1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment.

Conclusion

Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.
The impact of strategic napping on peak expiratory flow and respiratory function in young elite athletes
Authors: Kurtoğlu Ahmet , Eken Özgür , Aydın Engin , Çar Bekir , Nobari Hadi
Published: February 2024

Respiratory health is a critical determinant of athletic performance, and the utilization of restorative strategies, such as strategic napping, may offer a competitive edge to athletes. This study investigates the effects of nap duration on the respiratory function of young elite athletes who have achieved top rankings national competitions. Participants engage in three test sessions with varying nap durations: no nap (N0), a 25-minute nap (N25), and a 45-minute nap (N45), with a minimum 72-hour interval between sessions. Respiratory parameters including Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), FEV1/FVC ratio, Peak Expiratory Flow rate (PEF), Forced Expiratory Flow at 25–75% of FVC (FEF25-75%), and Forced Expiratory Time (FET) are assessed. Results reveal a significant enhancement in PEF values following a 45-minute nap (N45) compared to the no-nap control (N0) [F1 − 11=7.356, p =.004, ηp2 = 0.401, (95% CI for difference: -1.56 to − 0.056)], indicating a potential positive influence of napping on maximum expiratory flow rate and, consequently, athletes’ respiratory performance. While no significant changes are observed in other respiratory parameters across different nap durations, these findings underscore the potential benefits of strategic napping in optimizing respiratory health in young elite athletes.
Remembering the null hypothesis when searching for brain sex differences
Authors: Eliot Lise
Published: February 2024

Human brain sex differences have fascinated scholars for centuries and become a key focus of neuroscientists since the dawn of MRI. We recently published a major review in Neuroscience and Biobehavioral Reviews showing that most male–female brain differences in humans are small and few have been reliably replicated. Although widely cited, this work was the target of a critical Commentary by DeCasien et al. (Biol Sex Differ 13:43, 2022). In this response, I update our findings and confirm the small effect sizes and pronounced scatter across recent large neuroimaging studies of human sex/gender difference. Based on the sum of data, neuroscientists would be well-advised to take the null hypothesis seriously: that men and women’s brains are fundamentally similar, or “monomorphic”. This perspective has important implications for how we study the genesis of behavioral and neuropsychiatric gender disparities.
A novel nanobody-based immunocytokine of a mutant interleukin-2 as a potential cancer therapeutic
Authors: Beig Parikhani Arezoo , Dehghan Rada , Talebkhan Yeganeh , Bayat Elham , Biglari Alireza , Shokrgozar Mohammad Ali , Ahangari Cohan Reza , Mirabzadeh Esmat , Ajdary Soheila , Behdani Mahdi
Published: February 2024

The immunotherapeutic application of interleukin-2 (IL-2) in cancer treatment is limited by its off-target effects on different cell populations and insufficient activation of anti-tumor effector cells at the site of the tumor upon tolerated doses. Targeting IL-2 to the tumor microenvironment by generating antibody-cytokine fusion proteins (immunocytokine) would be a promising approach to increase efficacy without associated toxicity. In this study, a novel nanobody-based immunocytokine is developed by the fusion of a mutant (m) IL-2 with a decreased affinity toward CD25 to an anti-vascular endothelial growth factor receptor-2 (VEGFR2) specific nanobody, denoted as VGRmIL2-IC. The antigen binding, cell proliferation, IFN-γ-secretion, and cytotoxicity of this new immunocytokine are evaluated and compared to mIL-2 alone. Furthermore, the pharmacokinetic properties are analyzed. Flow cytometry analysis shows that the VGRmIL2-IC molecule can selectively target VEGFR2-positive cells. The results reveal that the immunocytokine is comparable to mIL-2 alone in the stimulation of Primary Peripheral Blood Mononuclear Cells (PBMCs) and cytotoxicity in in vitro conditions. In vivo studies demonstrate improved pharmacokinetic properties of VGRmIL2-IC in comparison to the wild or mutant IL-2 proteins. The results presented here suggest VGRmIL2-IC could be considered a candidate for the treatment of VEGFR2-positive tumors.
Downregulation of salusins alleviates hypertrophic cardiomyopathy via attenuating oxidative stress and autophagy
Authors: Dang Jing-Yi , Zhang Wei , Chu Yi , Chen Jiang-Hong , Ji Zhao-Le , Feng Pin
Published: February 2024

Introduction

Salusins, which are translated from the alternatively spliced mRNA of torsin family 2 member A (TOR2A), play a vital role in regulation of various cardiovascular diseases. However, it remains unclear precisely regarding their roles in hypertrophic cardiomyopathy (HCM). Therefore, this study was conducted to explore therapeutic effect and the underlying mechanisms of salusins on HCM.

Material and methods

In vivo experiments, Sprague–Dawley rats were used to induce HCM model by angiotensin (Ang) II infusion for 4 weeks. The rats were randomly divided into four groups, namely, Saline + Control shRNA (n = 7), Ang II + Control shRNA (n = 8), Saline + TOR2A shRNA (n = 7), and Ang II + TOR2A shRNA groups (n = 8). After HCM induction, doppler echocardiography is recommended to evaluate heart function. In vitro experiments, primary neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (NRCFs) were obtained from newborn rats, and were treated with Ang II (10–6 M) for 24 h.

Results

After treatment with Ang II, levels of salusin-α and salusin-β were elevated in serum and cardiac tissues of rats and in the neonatal rat cardiomyocytes and cardiac fibroblasts. Downregulation of salusins alleviated the Ang II-induced cardiac hypertrophy by suppressing the increased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (β-MHC) and cardiac fibrosis by blocking collagen I, collagen III and transforming growth factor-beta (TGF-β), and it also attenuated oxidative stress by suppressing the increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels and reversing the decreased superoxide dismutase (SOD) activity and autophagy by inhibiting the increased microtubule-associated protein light chain 3B (LC3B), Beclin1, autophagy related gene (Atg) 3 and Atg5 in the cardiac tissues of Ang II-infused rats and in the Ang II-treated NRCMs.

Conclusions

All these findings suggest that the levels of salusins were elevated in the HCM, and targeting of salusins contributes to alleviation of cardiac hypertrophy and fibrosis probably via attenuating oxidative stress and autophagy. Accordingly, targeting of salusins may be a strategy for HCM therapy.
Detection of skin α-synuclein using RT-QuIC as a diagnostic biomarker for Parkinson’s disease in the Chinese population
Authors: Li Jiaqi , Duan Suying , Yang Jing , Zheng Honglin , Yuan Yanpeng , Tang Mibo , Wang Yanlin , Liu Yutao , Xia Zongping , Luo Haiyang , Xu Yuming
Published: February 2024

Background

Several studies have indicated that skin holds promise as a potential sample for detecting pathological α-Syn and serving as a diagnostic biomarker for α-synucleinopathies. Despite reports in Chinese PD patients, comprehensive research on skin α-Syn detection using RT-QuIC is lacking.

Objective

This study aimed to evaluate the diagnostic performance of skin samples using RT-QuIC from PD patients in the Chinese population.

Methods

Patients with sporadic PD and controls were included according to the British PD Association Brain Bank diagnostic criteria. The seeding activity of misfolded α-Syn in these skin samples was detected using the RT-QuIC assay after protein extraction. Biochemical and morphological analyses of RT-QuIC products were conducted by atomic force microscopy, transmission electron microscopy, Congo red staining, and dot blot analysis.

Result

30 patients clinically diagnosed with PD and 28 controls with non-α-synucleinopathies were included in this study. 28 of 30 PD patients demonstrated positive α-Syn seeding activity by RT-QuIC assay. In contrast, no α-Syn seeding activity was detected in the 28 control samples, with an overall sensitivity and specificity of 93.3% and 100%, respectively (P < 0.001). Biochemical characterization of the RT-QuIC product indicated fibrillary α-Syn species in PD-seeded reactions, while control samples failed in the conversion of recombinant α-Syn substrate.

Conclusion

This study applied RT-QuIC technology to identify misfolded α-Syn seeding activity in skin samples from Chinese PD patients, demonstrating high specificity and sensitivity. Skin α-Syn RT-QuIC is expected to be a reliable approach for the diagnosis of PD.
Counteracting mental fatigue for athletes: a systematic review of the interventions
Authors: Sun He , Soh Kim Geok , Mohammadi Alireza , Toumi Zakaria , Zhang Lingling , Ding Cong , Gao Xiaojuan , Tian Jian
Published: February 2024

The deleterious effects of mental fatigue (MF) on athletes have been carefully studied in various sports, such as soccer, badminton, and swimming. Even though many researchers have sought ways to ameliorate the negative impact of MF, there is still a lack of studies that review the interventions used to counteract MF among athletes. This review aims to report the current evidence exploring the effects of interventions on MF and sport-specific performance, including sport-specific motor performance and perceptual-cognitive skills. Web of Science, Scopus, PubMed, and SPORTDicus (EBSCOhost) were combed through to find relevant publications. Additionally, the references and Google Scholar were searched for any grey literature. For the current review, we included only randomized controlled trials that involved athletes, a primary task to induce MF, interventions to counter MF with comparable protocols, and the outcomes of sport-specific motor performance and perceptual-cognitive skill. The selection criteria resulted in the inclusion of 10 articles. The manipulations of autonomous self-control exertion, person-fit, nature exposure, mindfulness, and transactional direct current stimulation showed that positive interventions counteract MF and improve sport-specific performance in different domains, including strength, speed, skill, stamina, and perceptual-cognitive skills. The selected interventions could significantly counteract MF and improve subsequent sport-specific performance. Moreover, self-regulation and attention resources showed the importance of the potential mechanisms behind the relevant interventions.
Impact of APOE on amyloid and tau accumulation in argyrophilic grain disease and Alzheimer’s disease
Authors: Raulin Ana-Caroline , Doss Sydney V. , Heckman Michael G. , Craver Emily C. , Li Zonghua , Ikezu Tadafumi C. , Sekiya Hiroaki , Liu Chia-Chen , Martens Yuka A. , Rosenberg Cassandra L. , Kuchenbecker Lindsey A. , DeTure Michael , Reichard R. Ross , Nguyen Aivi T. , Constantopoulos Eleni , Larsen Rachel A. , Kounaves Emmaline K. , Murray Melissa E. , Dickson Dennis W. , Petersen Ronald C. , Bu Guojun , Kanekiyo Takahisa
Published: February 2024

Alzheimer’s disease (AD), characterized by the deposition of amyloid-β (Aβ) in senile plaques and neurofibrillary tangles of phosphorylated tau (pTau), is increasingly recognized as a complex disease with multiple pathologies. AD sometimes pathologically overlaps with age-related tauopathies such as four repeat (4R)-tau predominant argyrophilic grain disease (AGD). While AGD is often detected with AD pathology, the contribution of APOE4 to AGD risk is not clear despite its robust effects on AD pathogenesis. Specifically, how APOE genotype influences Aβ and tau pathology in co-occurring AGD and AD has not been fully understood. Using postmortem brain samples (N = 353) from a neuropathologically defined cohort comprising of cases with AD and/or AGD pathology built to best represent different APOE genotypes, we measured the amounts of major AD-related molecules, including Aβ40, Aβ42, apolipoprotein E (apoE), total tau (tTau), and pTau181, in the temporal cortex. The presence of tau lesions characteristic of AD (AD-tau) was correlated with cognitive decline based on Mini-Mental State Examination (MMSE) scores, while the presence of AGD tau lesions (AGD-tau) was not. Interestingly, while APOE4 increased the risk of AD-tau pathology, it did not increase the risk of AGD-tau pathology. Although APOE4 was significantly associated with higher levels of insoluble Aβ40, Aβ42, apoE, and pTau181, the APOE4 effect was no longer detected in the presence of AGD-tau. We also found that co-occurrence of AGD with AD was associated with lower insoluble Aβ42 and pTau181 levels. Overall, our findings suggest that different patterns of Aβ, tau, and apoE accumulation mediate the development of AD-tau and AGD-tau pathology, which is affected by APOE genotype.
Artificial intelligence and quantum cryptography
Authors: Radanliev Petar
Published: February 2024

The technological advancements made in recent times, particularly in artificial intelligence (AI) and quantum computing, have brought about significant changes in technology. These advancements have profoundly impacted quantum cryptography, a field where AI methodologies hold tremendous potential to enhance the efficiency and robustness of cryptographic systems. However, the emergence of quantum computers has created a new challenge for existing security algorithms, commonly called the ‘quantum threat’. Despite these challenges, there are promising avenues for integrating neural network-based AI in cryptography, which has significant implications for future digital security paradigms. This summary highlights the key themes in the intersection of AI and quantum cryptography, including the potential benefits of AI-driven cryptography, the challenges that need to be addressed, and the prospects of this interdisciplinary research area.
Seascape connectivity: ontogenetic migration for Haemulon flavolineatum
Authors: Rodriguez-Torres Diana Carolina , Acosta Alberto
Published: February 2024

In the seascape, species migrate between ecosystems to complete their life cycles, and such ontogenetic migrations create functional connections between ecosystems. Nevertheless, the scarcity of information on patch distribution, species life history and ecology limits its application in Marine Protected Areas (MPA) management. We use a potential connectivity network approach to analyze how Haemulon flavolineatum might move through a complex and diverse seascape by simulating part of its life cycle migrations among three ecosystems (reef, mangrove, and seagrass) in the MPA of Bahía Portete-Kaurrele (BPK), Colombia. We used available ecosystem cover maps to conduct habitat fragmentation analyses and evaluate structural connectivity in BPK using eight indices that describe ecosystem patches and how they are related. With published information on the H. flavolineatum home range and its ontogenetic migration distances, we estimated the potential functional connectivity (CONNECT and migration distances) between ecosystems by building bipartite graphs. The benthic habitat configuration of the BPK could allow Haemulon flavolineatum to complete at least two stages of its life cycle (stage 5 mangroves to reefs being more likely than stage 4 seagrass to mangroves). Ontogenetic migrations is possible since, patches of different ecosystems were highly intermixed (76%) rather than grouped (58%); reefs showed higher values of structural indices (patch area, largest patch, shape complexity, functional links) than mangrove (shortest distance to the nearest neighbor) and seagrass (representativeness); and juveniles migrate from mangroves to reef patches along the bay, but they could be isolated by distance when moving from particular seagrass to mangrove patches. Our methodological approach, which integrates ecological information (evidence-based ranges of species migration distances between habitat patches) and the seascape (spatial configuration of habitat patches and fragmentation) is novel for a marine fish species with ontogenetic migration to search for the likelihood of completing its life cycle stages. We discuss the need for ecological information on French grunts and the need to validate future models and scenarios.
Translation and psychometric assessment of the mastectomy module of the BREAST-Q questionnaire for use in Nigeria
Authors: Olasehinde Olalekan , Lynch Kathleen A. , Goldman Debra A. , Agodirin Olaide , Okereke Chukwuma , Wuraola Funmilola O. , Owoade Israel Adeyemi , Akinmaye Promise Rebecca , Ajibade Olusola , Barber Karin , Ogunwale Joshua , Alatise Olusegun , Kingham T. Peter , Pusic Andrea , Romanoff Anya
Published: February 2024

Background

The majority of non-metastatic breast cancer patients in sub-Saharan Africa are recommended to have mastectomy. The impact of mastectomy on a predominantly young African patient population requires evaluation. The BREAST-Q is a validated patient-reported outcome measure of quality-of-life following breast surgery that has been translated into 30 languages-none in Africa. This study aimed to translate and assess the psychometric properties of the mastectomy module of the BREAST-Q for use in Nigeria.

Methods

The BREAST-Q mastectomy module was translated from English to Yoruba and its psychometric properties assessed using best practice guidelines. Translation was performed in 4 steps: forward translation (x2), back translation, back translation review, and cognitive interviews with post-mastectomy patients. The translated BREAST-Q instrument was administered to post-mastectomy patients (n = 21) alongside the EORTC-QLQ BR23 to evaluate construct validity. Test-retest reliability was evaluated using intraclass correlation coefficients (ICC); surveys were re-administered 4 weeks apart.

Results

The translation process identified English phrases not amenable to direct translation, including “emotionally healthy” and descriptions of pain (“nagging,” “throbbing,” “sharp”). Translations were amended to reflect local context and question intent. During cognitive interviews, patients provided suggestions to simplify complex phrases, e.g. “discomfort in your breast area.”. Internal consistency within scales was over 0.70 for psychosocial wellbeing (α = 0.84–0.87), sexual wellbeing (α = 0.98–0.99), physical wellbeing in chest (α = 0.84–0.86), and satisfaction with care (α = 0.89–0.93). ICC for test-retest reliability was moderate (0.46–0.63).

Conclusions

The Yoruba version of the BREAST-Q mastectomy module presents a unique opportunity to adequately capture the experiences of Nigerian women post mastectomy. This instrument is being used in a pilot study of Nigerian patients to identify targets for intervention to improve the patient experience and compliance with breast cancer surgery.