bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing circulatory myokines and extracellular vesicle uptake with targeted exercise in patients with prostate cancer (the MYEX trial): a single-group crossover study
Authors: Kim Jin-Soo , Taaffe Dennis R. , Galvão Daniel A. , Clay Timothy D. , Redfern Andrew D. , Gray Elin S. , Newton Robert U.
Published: July 2024

Introduction

Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa.

Methods

A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients.

Discussion

If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community.

Trial registration

The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.
SARS-CoV-2 in Mozambican primary school-aged children at Maputo City and Province: a cross-sectional study from a low-income country
Authors: Bauhofer Adilson Fernando Loforte , Ussivane Édio , Chissaque Assucênio , Iahaia Fátima , Pololo Ramígio , Campos Fernanda , Miranda Emerson , António Luciana , Maholela Plácida , Gatambire Aline , Djedje Marlene , Ráice Fátima , Gonçalves Luzia , de Deus Nilsa , Inlamea Osvaldo
Published: July 2024

Background

Seroprevalence studies provide information on the true extent of infection and capture demographic and geographic differences, indicating the level of immunity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We sought to provide local evidence of SARS-CoV-2 exposure in school-aged children during in-class teaching in Maputo City and Province, Mozambique.

Methods

Between August and November 2022, we performed a cross-sectional study in school-aged children in four schools in rural, peri-urban, and urban areas of Maputo City and Province. A point-of-care test was used to evaluate SARS-CoV-2 antigens and anti-SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Descriptive statistics were used to estimate the prevalence of the antigens and antibodies. Multiple logistic regression models were used to estimate the adjusted odds ratio (AOR) for the factors associated with anti-SARS-CoV-2 antibodies.

Results

A total of 736 school-aged children were analyzed. The prevalence of the SARS-CoV-2 antigen was 0.5% (4/736). The prevalence of SARS-CoV-2 antigens was 0.0% (0/245), 0.8% (2/240) and 0.8% (2/251), in the rural, peri-urban and urban areas respectively. The overall seroprevalence of the anti-SARS-CoV-2 antibodies (IgG or IgM) was 80.7% (594/736). In rural area anti-SARS-CoV-2 IgG or IgM antibodies were detected in 76.7% (188/245), while in peri-urban area they were detected in 80.0% (192/240) and in urban area they were detected in 85.3% (214/251). In the adjusted logistic regression model, school-aged children from the urban area were more likely to have anti-SARS-CoV-2 IgG or IgM antibodies than were school-aged children from the rural area (adjusted odds ratio: 1.679; 95% CI: 1.060–2.684; p-value = 0.028).

Conclusions

During the in-class teaching period, active SARS-CoV-2 cases in school-aged children were observed. More than half of the school-aged children were exposed to SARS-CoV-2, and SARS-CoV-2 was significantly more common in the schools at the urban area than in the school in the rural area at Maputo City and Province.
Examining recovery and mental health service satisfaction among young immigrant Muslim women with mental distress in Quebec
Authors: Reich Malka , Jarvis G. Eric , Whitley Rob
Published: July 2024

Objective

The overall aim of this study was to understand the experiences and perspectives of immigrant Muslim women in Quebec living with mental illness, who have recently used formal mental health services such as an accredited therapist, psychologist, or clinician. Specific objectives included (i) eliciting and examining their self-identified barriers and facilitators to recovery; (ii) exploring links between religion and mental health; and (iii) self-reported satisfaction with mental health services received.

Methods

We adopted a qualitative approach, facilitating the prioritization of participant perspectives. This involved semi-structured interviews with 20 women who (i) identified as Muslim; (ii) had used mental health services in the last three years; and (iii) were 18 + years of age. Interviews were transcribed and analyzed using thematic analysis techniques.

Results

Three prominent themes emerged from the analysis. These themes were (i) stigma and misunderstandings in families (especially parents) and sometimes in the ethno-religious community, both acting as barriers to health service utilization and recovery; (ii) frustrating clinical experiences within formal mental health care settings, in particular a perceived lack of cultural and religious competence, which negatively affected service utilization and the development of a therapeutic alliance; and (iii) deeply-held religious beliefs, practices and trust in God imparting a rhythm, purpose and meaning, which were strong facilitators to recovery.

Conclusions and implications for practice

These findings suggest that recovery from mental illness can be advanced by a three-pronged approach in this population. First, anti-stigma mental health literacy interventions could be held in collaboration with Muslim community groups. Second, there is a need for further religious and cultural competence interventions, resources and trainings for mental health professionals working with Muslims. Third, self-care resources should be developed that harness aspects of religious practices that can give structure, meaning, purpose and hope. All this could ultimately foster recovery in this population.
Sex differences in physical functioning among older adults: cross-sectional results from the OUTDOOR ACTIVE study
Authors: Stalling Imke , Gruber Martin , Bammann Karin
Published: July 2024

Background

Maintaining good functional ability is a key component of healthy ageing and a basic requirement for carrying out activities of daily living, staying independent, and delaying admission to a nursing home. Even though women have a higher life expectancy and slower age-related muscle mass loss than men, they often show a higher prevalence of limitations in physical functioning. However, the reasons behind these sex differences are still unclear. Therefore, the aims of this study were to investigate sex differences among older adults regarding physical functioning and to study which factors are explaining these sex differences.

Methods

Cross-sectional data from participants of the OUTDOOR ACTIVE study residing in Bremen, Germany, aged 65 to 75 years, were included in the analyses. Physical functioning was assessed via a self-administered questionnaire using the SF-36 10-item Physical Functioning Scale. Social, lifestyle, and health-related factors were also assessed using the questionnaire. Physical activity was measured objectively using wrist-worn accelerometers over seven consecutive days. Descriptive analyses with absolute and relative frequencies, means and standard deviations, as well as T-tests and chi-square tests were carried out. To test for associations between sex, physical functioning, and several individual factors, linear regressions were performed.

Results

Data of 2 141 participants (52.1% female) were included in the study. Women and men showed statistically significant differences in physical functioning, with men perceiving fewer limitations than women. On average, women had a physical functioning score of 81.4 ± 19.3 and men 86.7 ± 17.0. Linear regression showed a statistically significant negative association between physical functioning score and sex (β: -0.15, 95% CL: -0.19, -0.10). The association remained statistically significant when adding individual factors to the model. All factors together were only able to explain 51% of the physical functioning-sex association with health indicators and the presence of chronic diseases being the most influential factors.

Conclusions

We found sex differences in physical functioning, with older women having more limitations than older men. The results showed that health-related factors and chronic diseases played the biggest roles in the different physical functioning scores of women and men. These findings contribute to future longitudinal, more in-depth research.

Trial registration

German Clinical Trials Register DRKS00015117 (Date of registration 17-07-2018).
Study on the relationship and related factors between physical fitness and health behavior of preschool children in southwest China
Authors: Zou Ruyun , Wang Kun , Li Dan , Liu Yongsen , Zhang Tingran , Wei Xiudong
Published: July 2024

Objective

To investigate the physical fitness level and health behavior status of preschool children in China, explore the relationship between physical fitness and health behavior, and further reveal the main factors affecting health behavior, to provide a reference for improving the physical fitness level of preschool children and maintaining healthy behavior.

Methods

A total of 755 preschool children (394 boys and 361 girls, aged 4.52 ± 1.11 years) were selected from Chongqing and Liupanshui in China by cluster random sampling method for questionnaire survey and physical monitoring, and SPSS21.0 software was used to process and analyze the data.

Results

(1) Heart rate (p = 0.015), protein content (p < 0.001), and time spent on the balance beam (p < 0.001) were significantly lower in boys than in girls, while BMI (p = 0.012), muscle mass (p < 0.001), and distance of standing long jump (p < 0.001) were significantly higher in boys than in girls. Meanwhile, systolic blood pressure (p = 0.004) and diastolic blood pressure (p = 0.001) of rural children were significantly higher than those of urban children, while BMI (p < 0.001) and sitting forward flexion (p = 0.019) were significantly lower than those of urban children. (2) The light-intensity physical activity (LPA) and moderate to vigorous physical activity (MVPA) of boys were significantly higher than that of girls (p < 0.001), and the MVPA of urban children was significantly higher than that of rural children (p = 0.001), and the former participated in sports classes more frequently (p < 0.001). (3) There was a significant correlation between physical activity (PA) and physical fitness indicators of preschoolers. Participating in sports interest classes was only significantly correlated with systolic blood pressure (r = 0.08) and sitting forward flexion (r = 0.09). (4) The PA level of preschool children was related to gender, household registration, kindergarten nature, age, residence environment, parental support, and participation degree. Participation in sports interest classes was related to gender, the nature of the kindergarten, household registration, age, and parent participation. Daily screen time was related to household registration, the nature of the kindergarten, the environment of residence, and the value perception of parents.

Conclusions

There were different degrees of correlation between preschool children’s physical fitness and health behaviors, and children’s health behaviors were closely related to gender, environment, parents, and other factors. Therefore, how to increase the protective factors of children’s health behaviors and controlling the risk factors may be crucial to promoting the development of good health behaviors and improving the physical fitness of preschool children.
Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis
Authors: Fang Yiqiao , Liu Fen , Zhang Xinyue , Chen Lei , Liu Yang , Yang Lin , Zheng Xiaofeng , Liu Jiaye , Li Kewei , Li Zhihui
Published: July 2024

Background

Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis.

Methods

Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis.

Results

A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51–68.29) and lowest of formication (20.5%, 95% CI 13.44–28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems.

Conclusion

The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.
A patient with AL amyloidosis presenting with refractory tuberculosis, chest tightness and hypotension: case report
Authors: Yang Jun , Farhath Mohamed Fahim Fathima , Tian Huohuan , Yang Linhui , Liu Dan
Published: July 2024

Introduction

Immunoglobulin light chain (AL) amyloidosis presents a clinical spectrum characterized by diverse manifestations and involvement of multiple organs, posing a significant diagnostic challenge for physicians.

Methods and results

We present a case of a patient admitted to our hospital due to recurrent cough and sputum, which was initially diagnosed as refractory tuberculosis. Throughout his hospitalization, the patient experienced distressing symptoms, including uncontrollable chest tightness, hypotension, and fever. Noteworthy observations included a persistent elevation in cardiac biomarkers, indicative of cardiac damage. Bronchoalveolar lavage revealed the presence of various pathogenic microorganisms, while bone marrow flow cytometry demonstrated the existence of clonal plasma cells. Additionally, the urine free light chain assay detected the presence of M protein, and the positive congo red staining of the abdominal wall fat biopsy confirmed amyloid deposition in the tissues. Taking into account the patient’s clinical presentation and the examination findings, we reached a conclusive diagnosis of immunoglobulin light chain (AL) amyloidosis.

Conclusion

This case serves as a reminder for physicians to consider rare diseases like AL amyloidosis when patients present with symptoms involving multiple organ systems such as heart, lung and kidney that are unresponsive to conventional treatment options.
Relationship between prostate-specific antigen, alkaline phosphatase levels, and time-to-tumor shrinkage: understanding the progression of prostate cancer in a longitudinal study
Authors: Liaqat Madiha , Khan Rehan Ahmad , Fischer Florian , Kamal Shahid
Published: July 2024

Background

This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer .

Methods

A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model’s utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients’ baseline characteristics ($$Age$$

Age

, body mass index ($$BMI$$

BMI

), $$Gleason Score$$

GleasonScore

, $$Grade$$

Grade

, and $$Drug$$

Drug

) and two longitudinal endogenous covariates ($$Platelets$$

Platelets

and $$Bilirubin$$

Bilirubin

).

Results

The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression.

Conclusions

The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.
Use of ultrasound imaging Omics in predicting molecular typing and assessing the risk of postoperative recurrence in breast cancer
Authors: Song Xinyu , Xu Haoyi , Wang Xiaoli , Liu Wen , Leng Xiaoling , Hu Yue , Luo Zhimin , Chen Yanyan , Dong Chao , Ma Binlin
Published: July 2024

Background

The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer.

Methods

A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves.

Results

In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability.

Conclusion

The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.
Mortality in sea lions is associated with the introduction of the H5N1 clade 2.3.4.4b virus in Brazil October 2023: whole genome sequencing and phylogenetic analysis
Authors: de Carvalho Araujo Andreina , Cho Andrew Yong , Silva Laura Morais Nascimento , Corrêa Thais Camilo , de Souza Gabriela Cristini , Albuquerque Adriana Silva , Macagnan Eduardo , Kolesnikvoas Cristiane K. M. , Meurer Rafael , Vieira Jenyffer Vierheller , Lemos Giulia Gaglianone , Barreto André Silva , Dick Jeferson Luis , Groch Karina Rejane , de Castilho Pedro Volkmer , Amgarten Deyvid , Malta Fernanda , Miller Michael , Dorlass Erick G. , Palameta Soledad , Lee Sun-Hak , Arns Clarice Weis , Durigon Edison L. , Pinho João Renato R. , Lee Dong-Hun , Ferreira Helena Lage
Published: July 2024

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.
Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia
Authors: Nouri Zahra , Sarmadi Akram , Narrei Sina , Kianersi Hamidreza , Kianersi Farzan , Tabatabaiefar Mohammad Amin
Published: July 2024

Background

Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals.

Methods

Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022.

Results

All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis.

Conclusions

Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.
Amino acids regulating skeletal muscle metabolism: mechanisms of action, physical training dosage recommendations and adverse effects
Authors: Li Guangqi , Li Zhaojun , Liu Junyi
Published: July 2024

Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research.
Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus
Authors: Mayo Francisco , González-Vinceiro Lourdes , Hiraldo-González Laura , Rodríguez-Gómez Francisco D. , Calle-Castillejo Claudia , Mayo Manuel , Netti Vanina , Ramírez-Lorca Reposo , Echevarría Miriam
Published: July 2024

AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4−/− mice (KO) due to stenosis of Silvio’s aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4−/− mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.
A high-efficiency transient expression system mediated by Agrobacterium tumefaciens in Spinacia oleracea leaves
Authors: Zhang Yumeng , Qiu Liuliu , Zhang Yongxue , Wang Yiran , Fu Chunxiang , Dai Shaojun , Sun Meihong
Published: July 2024

Background

Optimization of a highly efficient transient expression system is critical for the study of gene function, particularly in those plants in which stable transformation methods are not widely available. Agrobacterium tumefaciens‑mediated transient transformation is a simple and low-cost method that has been developed and applied to a wide variety of plant species. However, the transient expression in spinach (Spinacia oleracea L.) is still not reported.

Results

We developed a transient expression system in spinach leaves of the Sp75 and Sp73 varieties. Several factors influencing the transformation efficiency were optimized such as Agrobacterium strain, spinach seedling stage, leaf position, and the expression time after injection. Agrobacterium strain GV3101 (pSoup-p19) was more efficient than AGL1 in expressing recombinant protein in spinach leaves. In general, Sp75 leaves were more suitable than Sp73 leaves, regardless of grow stage. At four-leaf stage, higher intensity and efficiency of transient expression were observed in group 1 (G1) of Sp75 at 53 h after injection (HAI) and in G1 of Sp73 at 64 HAI. At six-leaf stage of Sp75, group 3 (G3) at 72 HAI were the most effective condition for transient expression. Using the optimized expression system, we detected the subcellular localization of a transcriptional co-activator SoMBF1c and a NADPH oxidase SoRbohF. We also detected the interaction of the protein kinase SoCRK10 and the NADPH oxidase SoRbohB.

Conclusion

This study established a method of highly efficient transient expression mediated by Agrobacterium in spinach leaves. The transient expression system will facilitate the analysis of gene function and lay a solid foundation for molecular design breeding of spinach.
MicroRNAs as the pivotal regulators of Temozolomide resistance in glioblastoma
Authors: Palizkaran Yazdi Mahsa , Barjasteh Amirhosein , Moghbeli Meysam
Published: July 2024

Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.
Addressing bioreactor hiPSC aggregate stability, maintenance and scaleup challenges using a design of experiment approach
Authors: Yehya Haneen , Raudins Sofija , Padmanabhan Roshan , Jensen Jan , Bukys Michael A.
Published: July 2024

Background

Stem cell-derived therapies hold the potential for treatment of regenerative clinical indications. Static culture has a limited ability to scale up thus restricting its use. Suspension culturing can be used to produce target cells in large quantities, but also presents challenges related to stress and aggregation stability.

Methods

Utilizing a design of experiments (DoE) approach in vertical wheel bioreactors, we evaluated media additives that have versatile properties. The additives evaluated are Heparin sodium salt (HS), polyethylene glycol (PEG), poly (vinyl alcohol) (PVA), Pluronic F68 and dextran sulfate (DS). Multiple response variables were chosen to assess cell growth, pluripotency maintenance and aggregate stability in response to the additive inputs, and mathematical models were generated and tuned for maximal predictive power.

Results

Expansion of iPSCs using 100 ml vertical wheel bioreactor assay for 4 days on 19 different media combinations resulted in models that can optimize pluripotency, stability, and expansion. The expansion optimization resulted in the combination of PA, PVA and PEG with E8. This mixture resulted in an expansion doubling time that was 40% shorter than that of E8 alone. Pluripotency optimizer highlighted the importance of adding 1% PEG to the E8 medium. Aggregate stability optimization that minimizes aggregate fusion in 3D culture indicated that the interaction of both Heparin and PEG can limit aggregation as well as increase the maintenance capacity and expansion of hiPSCs, suggesting that controlling fusion is a critical parameter for expansion and maintenance. Validation of optimized solution on two cell lines in bioreactors with decreased speed of 40 RPM, showed consistency and prolonged control over aggregates that have high frequency of pluripotency markers of OCT4 and SOX2 (> 90%). A doubling time of around 1–1.4 days was maintained after passaging as clumps in the optimized medium. Controlling aggregate fusion allowed for a decrease in bioreactor speed and therefore shear stress exerted on the cells in a large-scale expansion.

Conclusion

This study resulted in a control of aggregate size within suspension cultures, while informing about concomitant state control of the iPSC state. Wider application of this approach can address media optimization complexity and bioreactor scale-up challenges.
Sex-related differences in left atrial substrate among patients with atrial fibrillation: evidence from high-density voltage mapping
Authors: Huang Wenchao , Sun Huaxin , Xiong Shiqiang , Luo Yan , Tang Yan , Zhang Zhen , Liu Hanxiong
Published: July 2024

Background

There is sufficient evidence that women with atrial fibrillation (AF) have a greater symptom burden than men with AF and are more likely to experience recurrence after catheter ablation. However, the mechanisms underlying these sex differences are unclear.

Methods

We prospectively enrolled 125 consecutive patients, including 40 non-AF patients and 85 AF patients, who underwent high-density voltage mapping during sinus rhythm and AF patients who underwent first ablation.

Results

Overall, 37 (44%) female patients with AF and 24 (60%) female non-AF patients with a mean age of 61.7 ± 11.6 years and 53.6 ± 16.7 years, respectively, were enrolled in this study. The results showed that the atrial voltage of female AF patients was significantly lower than that of male AF patients (1.11 ± 0.58 mV vs. 1.53 ± 0.65 mV; P = 0.003), while there were no significant sex differences in non-AF patients (3.02 ± 0.86 mV vs. 3.21 ± 0.84 mV; P = 0.498). Multiple linear regression analysis revealed that female sex (− 0.29, 95% confidence interval [CI] − 0.64 to − 0.13, P = 0.004) and AF type (− 0.32, 95% CI − 0.69 to − 0.13, P = 0.004) were the only factors independently associated with voltage. Compared with men, women in the paroxysmal AF group had a 3.5-fold greater incidence of recurrence (adjusted hazard ratio 4.49; 95% CI 1.101–18.332, P = 0.036). Both globally and regionally, the results showed that sex-related differences in voltage values occurred prominently in paroxysmal AF patients but not in nonparoxysmal AF patients.

Conclusion

Sex-related differences in atrial substrates and arrhythmia-free survival were found in paroxysmal AF patients, suggesting the existence of sex-related pathophysiological factors.
Centering and flourishing: an online intervention study assessing the effects of a Christian contemplative practice on stress-reduction and human flourishing
Authors: Rohde Julia S. , Goldy Sean , Graziosi Marianna , Ferguson Michael A. , Thrul Johannes , Yaden David B.
Published: July 2024

Despite widespread engagement in contemplative religious practices, comparatively little research has been conducted on their potential effects on well-being. Furthermore, few studies have focused on how an explicitly religious framing may impact the outcomes of such practices. In this online randomized controlled trial (N = 702), we tested the well-being effects of a contemplative prayer practice called Centering Prayer on self-identifying Christians. We compared 1) presenting the practice with an explicitly religious framing (experimental condition), 2) presenting the practice without an explicitly religious framing (active control), and 3) presenting simple instructions to reflect on the day, without any instructions regarding a meditation-like practice (passive control). After randomization into one of these three conditions, participants were asked to complete their assigned practice daily for 28 days. We hypothesized that the religious framing version of the practice would increase well-being over the active and passive control conditions. Well-being was assessed at three follow-up time points: one day, one week, and one month after the practice period. We found no group differences between the conditions on our primary outcome measure of well-being at one-week post-intervention. Each group increased in well-being from baseline to follow-up. We found significant group differences on acute measures of spiritual experience, the Mystical Experience Questionnaire (MEQ-30) and Daily Spiritual Experience Questionnaire (DSES). These results suggest that a religious framing may not enhance well-being effects but may alter spiritual outcomes related to contemplative practices.
Habitat and movement selection processes of American lobster/jakej within a restricted bay in the Bras d’Or Lake/Pitu’paq, Nova Scotia, Canada
Authors: Landovskis Shannon , Bailey Megan , Iverson Sara , Jeddore Skyler , Lennox Robert J. , Murray Caelin , Whoriskey Fred
Published: July 2024

American lobster inhabit the unique, brackish Bras d’Or Lake system, although densities are low compared to areas with similar habitats in the Atlantic Ocean. Nevertheless, lobsters are an important part of local First Nation (Mi’kmaq) food and culture. We used acoustic telemetry and habitat mapping, combined with local Mi’kmaw knowledge, to document the movements and habitat use of adult lobsters within a section of the Lake. Movement patterns of acoustically tagged individual lobsters were analyzed with both resource selection functions and integrated step selection functions using data obtained from a high-resolution VEMCO Positioning System within a restricted bay in the Bras d’Or Lake. The resource selection function suggested stronger selections of substrates that contained a combination of soft and hard sediments. While the integrated step selection functions found substantial individual variability in habitat selections, there was a trend for lobsters to exhibit more resident behaviour on the combined soft/hard substrates despite the fact these sediments provided little in the way of obvious shelters for the animals. Adult lobsters at this site have very little risk of predation, which presumably allows them to freely exhibit exploratory behaviours and reduce their association with substrates that provide shelters.
Single-nucleus multi-omics of Parkinson’s disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks
Authors: Shwab E. Keats , Gingerich Daniel C. , Man Zhaohui , Gamache Julia , Garrett Melanie E. , Crawford Gregory E. , Ashley-Koch Allison E. , Serrano Geidy E. , Beach Thomas G. , Lutz Michael W. , Chiba-Falek Ornit
Published: July 2024

The genetic architecture of Parkinson’s disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.
Random forest-based prediction of intracranial hypertension in patients with traumatic brain injury
Authors: Zhu Jun , Shan Yingchi , Li Yihua , Xu Xuxu , Wu Xiang , Xue Yajun , Gao Guoyi
Published: July 2024

Background

Treatment and prevention of intracranial hypertension (IH) to minimize secondary brain injury are central to the neurocritical care management of traumatic brain injury (TBI). Predicting the onset of IH in advance allows for a more aggressive prophylactic treatment. This study aimed to develop random forest (RF) models for predicting IH events in TBI patients.

Methods

We analyzed prospectively collected data from patients admitted to the intensive care unit with invasive intracranial pressure (ICP) monitoring. Patients with persistent ICP > 22 mmHg in the early postoperative period (first 6 h) were excluded to focus on IH events that had not yet occurred. ICP-related data from the initial 6 h were used to extract linear (ICP, cerebral perfusion pressure, pressure reactivity index, and cerebrospinal fluid compensatory reserve index) and nonlinear features (complexity of ICP and cerebral perfusion pressure). IH was defined as ICP > 22 mmHg for > 5 min, and severe IH (SIH) as ICP > 22 mmHg for > 1 h during the subsequent ICP monitoring period. RF models were then developed using baseline characteristics (age, sex, and initial Glasgow Coma Scale score) along with linear and nonlinear features. Fivefold cross-validation was performed to avoid overfitting.

Results

The study included 69 patients. Forty-three patients (62.3%) experienced an IH event, of whom 30 (43%) progressed to SIH. The median time to IH events was 9.83 h, and to SIH events, it was 11.22 h. The RF model showed acceptable performance in predicting IH with an area under the curve (AUC) of 0.76 and excellent performance in predicting SIH (AUC = 0.84). Cross-validation analysis confirmed the stability of the results.

Conclusions

The presented RF model can forecast subsequent IH events, particularly severe ones, in TBI patients using ICP data from the early postoperative period. It provides researchers and clinicians with a potentially predictive pathway and framework that could help triage patients requiring more intensive neurological treatment at an early stage.
Regioselective and enantioselective propargylic hydroxylations catalyzed by P450tol monooxygenases
Authors: Deng Xu , Song Cheng-Cheng , Gu Wen-Jing , Wang Yu-Jie , Feng Lu , Zhou Xiao-Jian , Zhou Ming-Qiang , Yuan Wei-Cheng , Chen Yong-Zheng
Published: July 2024

Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C–H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which’s an important synthetic intermediate of antifungal drug Ravuconazole.

Graphical Abstract