bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative distribution of HPV genotypes in histological cervical samples and associated grade lesion in a women population over the last 16 years in Burgundy, France
Authors: Auvray Christelle , Douvier Serge , Caritey Odile , Bour Jean-Baptiste , Manoha Catherine
Published: August 2023

Human papillomavirus is a predominant sexually transmitted viral pathogen. Our objective was to analyze the relative distribution of genotypes over time and to determine the genotypes associated with adverse clinical lesions. The study was based on data from adult women with cytological abnormalities from whom histological samples were obtained from 2005 to 2021. HPV genotyping was performed using PCR and INNO-LiPA assay (Fujirebio). Among the 1,017 HPV-positive biopsies, 732 (72%) were infected with a single HPV genotype and 285 (28%) were infected with several HPV genotypes. Most of the infections involved the high-risk genotypes 16, 31, and 52. Throughout the study period, HPV 16 was the most encountered genotype (541, 53.2%), while HPV 18 was rather under-represented (46, 4.5%), especially in invasive cervical carcinoma. HVP52 (165, 16.2%) was detected mainly from 2008 to 2014, and its distribution reached 19.7% in 2011. Such epidemiological data underlines the possibility of an emergence of a high-risk genotype. The most detected low-risk HPV in combination with high-risk HPV was HPV 54 in 6.5% of samples. Monoinfection by HPV 16 led statistically more often to severe lesions than multi-infection involving HPV 16 (p < 0.001), while for HPV 52, 31 or 33, multi-infections were significantly associated with severe lesions (p < 0.001 for each of these three genotypes). HPV 16 was involved in 55.2% of high-grade lesions and in situ carcinoma and 76.3% of invasive carcinomas. In severe lesions, HPV 16 participation was predominant, whereas diverse genotypes were seen in low-grade lesions. Importantly, we observed that high-risk genotypes, for example HPV 52, can emerge for a few years then decrease even without vaccine pressure.
Rhes depletion promotes striatal accumulation and aggregation of mutant huntingtin in a presymptomatic HD mouse model
Authors: Pan Yongcheng , Tang Beisha , Li Xiao-Jiang , Li Shihua , Liu Qiong
Published: August 2023

Introduction

Huntington’s disease (HD) is caused by CAG trinucleotide repeats in the HTT gene. Selective neurodegeneration in the striatum is prominent in HD, despite widespread expression of mutant HTT (mHTT). Ras homolog enriched in the striatum (Rhes) is a GTP-binding protein enriched in the striatum, involved in dopamine-related behaviors and autophagy regulation. Growing evidence suggests Rhes plays a critical role in the selective striatal degeneration in HD, but its specific function in this context remains complex and controversial.

Methods

In this study, we utilized CRISPR/Cas9 to knockdown Rhes at different disease stages through adeno-associated virus (AAV) transduction in HD knock-in (KI) mice. Immunoblotting and immunofluorescence were employed to assess the impact of Rhes depletion on mHTT levels, neuronal loss, astrogliosis and autophagy activity.

Results

Rhes depletion in 22-week-old HD KI mice (representing the presymptomatic stage) led to mHTT accumulation, reduced neuronal cell staining, and increased astrogliosis. However, no such effects were observed in 36-week-old HD KI mice (representing the symptomatic stage). Additionally, Rhes deletion in 22-week-old HD KI mice resulted in increased P62 levels, reduced LC3-II levels, and unchanged phosphorylation of mTOR and beclin-1, unchanged mTOR protein level, except for a decrease in beclin-1.

Discussion

Our findings suggest that knockdown Rhes promotes striatal aggregation of mutant huntingtin by reducing autophagy activity in a mTOR-independent manner. Rhes plays a protective role during the presymptomatic stage of HD KI mice.
Validity of the telematic Fugl Meyer assessment scale – upper extremity (TFMA-UE) Spanish version
Authors: Llamas-Ramos Rocío , Llamas-Ramos Inés , Pérez-Robledo Fátima , Sánchez-González Juan Luis , Bermejo-Gil Beatriz María , Frutos-Bernal Elisa , Martín-Nogueras Ana María
Published: August 2023

Background

Telematic assistance has become indispensable in recent years. The increased prevalence of Acquired brain injury and the sequels it causes, requires long–lasting multidisciplinary treatments. Validated tools to assess the evolution of the disabilities and limitations of this pathology are essential to individualize and prescribe adapted treatments. The aim has been to create the telematic version of the Fugl Meyer Assessment-Upper Extremity Motor Function (TFMA-UE) Spanish scale and its adaptation to the remote assessment of neurologic patients.

Methods

An adapted scale was designed based on the Fugl Meyer Assessment scale-telematic version (FMA-TV): TFMA-UE. This scale is composed by 21 items which evaluate the upper extremity motor function. Physiotherapists trained in this tool, evaluate the results obtained from applying the two versions (on-site and telematic) to compare the results.

Results

TFMA-UE was administered to 30 patients with acquired brain injury. It was applied on site and through the web platform selected by the patients in two different days. Patients completed all the scale in an easily way without help. The exploratory and confirmatory factor analysis confirmed a factorial structure with a factor (76.08% of the variance). The Cronbach’s internal consistency index obtained was 0.98 and the weight kappa index used to measure agreement between the two versions was 0.78 which represents substantial agreement.

Conclusion

The Telematic Fugl Meyer Assessment-Upper Extremity Motor Function (TFMA-UE) scale is a viable, useful and easy to apply tool that allows the upper extremity motor function assessment of Acquired Brain Injury patients.
How do patients with Parkinson’s disease and cerebellar ataxia read aloud? -Eye–voice coordination in text reading
Authors: Terao Yasuo , Tokushige Shin-ichi , Inomata-Terada Satomi , Miyazaki Tai , Kotsuki Naoki , Fisicaro Francesco , Ugawa Yoshikazu
Published: August 2023

Background

The coordination between gaze and voice is closely linked when reading text aloud, with the gaze leading the reading position by a certain eye–voice lead (EVL). How this coordination is affected is unknown in patients with cerebellar ataxia and parkinsonism, who show oculomotor deficits possibly impacting coordination between different effectors.

Objective

To elucidate the role of the cerebellum and basal ganglia in eye–voice coordination during reading aloud, by studying patients with Parkinson’s disease (PD) and spinocerebellar degeneration (SCD).

Methods

Participants were sixteen SCD patients, 18 PD patients, and 30 age-matched normal subjects, all native Japanese speakers without cognitive impairment. Subjects read aloud Japanese texts of varying readability displayed on a monitor in front of their eyes, consisting of Chinese characters and hiragana (Japanese phonograms). The gaze and voice reading the text was simultaneously recorded by video-oculography and a microphone. A custom program synchronized and aligned the gaze and audio data in time.

Results

Reading speed was significantly reduced in SCD patients (3.53 ± 1.81 letters/s), requiring frequent regressions to compensate for the slow reading speed. In contrast, PD patients read at a comparable speed to normal subjects (4.79 ± 3.13 letters/s vs. 4.71 ± 2.38 letters/s). The gaze scanning speed, excluding regressive saccades, was slower in PD patients (9.64 ± 4.26 letters/s) compared to both normal subjects (12.55 ± 5.42 letters/s) and SCD patients (10.81 ± 4.52 letters/s). PD patients’ gaze could not far exceed that of the reading speed, with smaller allowance for the gaze to proceed ahead of the reading position. Spatial EVL was similar across the three groups for all texts (normal: 2.95 ± 1.17 letters/s, PD: 2.95 ± 1.51 letters/s, SCD: 3.21 ± 1.35 letters/s). The ratio of gaze duration to temporal EVL was lowest for SCD patients (normal: 0.73 ± 0.50, PD: 0.70 ± 0.37, SCD: 0.40 ± 0.15).

Conclusion

Although coordination between voice and eye movements and normal eye-voice span was observed in both PD and SCD, SCD patients made frequent regressions to manage the slowed vocal output, restricting the ability for advance processing of text ahead of the gaze. In contrast, PD patients experience restricted reading speed primarily due to slowed scanning, limiting their maximum reading speed but effectively utilizing advance processing of upcoming text.
“Of mice and men”: the relevance of Cometin and Erythropoietin origin for its effects on murine spiral ganglion neuron survival and neurite outgrowth in vitro
Authors: Schwieger Jana , Gao Ziwen , Lenarz Thomas , Munro Gordon , Petersen Kenneth A. , Scheper Verena
Published: August 2023

Neurotrophic factors (NTF) play key roles in the survival of neurons, making them promising candidates for therapy of neurodegenerative diseases. In the case of the inner ear, sensorineural hearing loss (SNHL) is characterized over time by a degeneration of the primary auditory neurons, the spiral ganglion neurons (SGN). It is well known that selected NTF can protect SGN from degeneration, which positively influences the outcome of cochlear implants, the treatment of choice for patients with profound to severe SNHL. However, the outcome of studies investigating protective effects of NTF on auditory neurons are in some cases of high variability. We hypothesize that the factor origin may be one aspect that affects the neuroprotective potential. The aim of this study was to investigate the neuroprotective potential of human and mouse Erythropoietin (EPO) and Cometin on rat SGN. SGN were isolated from neonatal rats (P 2–5) and cultured in serum-free medium. EPO and Cometin of mouse and human origin were added in concentrations of 0.1, 1, and 10 ng/mL and 0.1, 1, and 10 μg/mL, respectively. The SGN survival rate and morphology, and the neurite outgrowth were determined and compared to negative (no additives) and positive (brain-derived neurotrophic factor, BDNF) controls. A neuroprotective effect of 10 μg/mL human Cometin comparable to that obtained with BDNF was observed in the SGN-culture. In contrast, mouse Cometin was ineffective. A similar influence of 10 μg/mL human and mouse and 1 μg/mL human Cometin on the length of regenerated neurites compared to BDNF was also detected. No other Cometin-conditions, and none of the EPO-conditions tested had neuroprotective or neuritogenic effects or influenced the neuronal morphology of the SGN. The neuroprotective effect of 10 μg/mL human Cometin on SGN indicates it is a potentially interesting protein for the supportive treatment of inner ear disorders. The finding that mouse Cometin had no effect on the SGN in the parallel-performed experiments underlines the importance of species origin of molecules being screened for therapeutic purpose.
From signals to music: a bottom-up approach to the structure of neuronal activity
Authors: Noel Gabriel D. , Mugno Lionel E. , Andres Daniela S.
Published: August 2023

Introduction

The search for the “neural code” has been a fundamental quest in neuroscience, concerned with the way neurons and neuronal systems process and transmit information. However, the term “code” has been mostly used as a metaphor, seldom acknowledging the formal definitions introduced by information theory, and the contributions of linguistics and semiotics not at all. The heuristic potential of the latter was suggested by structuralism, which turned the methods and findings of linguistics to other fields of knowledge. For the study of complex communication systems, such as human language and music, the necessity of an approach that considers multilayered, nested, structured organization of symbols becomes evident. We work under the hypothesis that the neural code might be as complex as these human-made codes. To test this, we propose a bottom-up approach, constructing a symbolic logic in order to translate neuronal signals into music scores.

Methods

We recorded single cells’ activity from the rat’s globus pallidus pars interna under conditions of full alertness, blindfoldedness and environmental silence. We analyzed the signals with statistical, spectral, and complex methods, including Fast Fourier Transform, Hurst exponent and recurrence plot analysis.

Results

The results indicated complex behavior and recurrence graphs consistent with fractality, and a Hurst exponent >0.5, evidencing temporal persistence. On the whole, these features point toward a complex behavior of the time series analyzed, also present in classical music, which upholds the hypothesis of structural similarities between music and neuronal activity. Furthermore, through our experiment we performed a comparison between music and raw neuronal activity. Our results point to the same conclusion, showing the structures of music and neuronal activity to be homologous. The scores were not only spontaneously tonal, but they exhibited structure and features normally present in human-made musical creations.

Discussion

The hypothesis of a structural homology between the neural code and the code of music holds, suggesting that some of the insights introduced by linguistic and semiotic theory might be a useful methodological resource to go beyond the limits set by metaphoric notions of “code.”
Neuroprotective and antioxidant activities of Colombian plants against paraquat and C2-ceramide exposure in SH-SY5Y cells
Authors: Bustos-Rangel Angie , Muñoz-Cabrera Jonathan , Cuca Luis , Arboleda Gonzalo , Ávila Murillo Mónica , Sandoval-Hernández Adrián G.
Published: August 2023

Abnormal production of reactive oxygen species (ROS) has been implicated in the physiopathology of neuronal cell death. Increased ROS levels are associated with exacerbated peptide aggregation, inflammation, and mitochondrial dysfunction, which facilitate the triggering of specific cell death pathways. Antioxidant molecules are potentially useful in the amelioration of neurodegeneration. In this regard, natural products are an invaluable source of antioxidants. Therefore, we investigate the antioxidant and neuroprotective activities of four Colombian angiosperm extracts. Antioxidant activity was evaluated by phytochemical assays using TLC techniques with Dragendorff reagent, ninhydrin, and chloranil in dioxane, NH3, Fast Blue, and FeCl3, together with bioautography using DPPH and β-carotene. In vitro neuroprotective activity, cell death, and ROS accumulation were evaluated by MTT and flow cytometry in the SH-SY5Y cell line exposed to paraquat and C2-ceramide. We found that Zanthoxylum rhoifolium Lam, Zanthoxylum martinicense, Nectandra membranacea, and Nectandra reticulata extracts have antioxidant activity higher than quercetin under a β-carotene bleaching assay and protect SH-SY5Y cells against paraquat and C2-ceramide associated with a reduction in ROS. In conclusion, these extracts have a strong neuroprotective potential, and the precise mechanism requires more evaluation.
LC-MS guided isolation of N,β-glucopyranosyl vincosamide and other compounds from the curare ingredient Strychnos peckii
Authors: Santos Carla L. G. , Neves Kidney O. G. , Silva-Filho Francinaldo A. , Lima Bruna R. , Costa Emmanoel V. , Souza Afonso D. L. de , Koolen Hector H. F. , Pinheiro Maria Lúcia B. , Silva Felipe M. A. da
Published: August 2023

Strychnos peckii (Loganiaceae) is an important active ingredient in curare poisons in the Amazon rainforest. Although previous studies have identified this species as a promising source of monoterpene indole alkaloids (MIAs), knowledge about other natural products is still scarce. Thus, to detect and guide the isolation of unprecedented bioactive compounds from the leaves of S. peckii, an untargeted high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis was performed with the leaf aqueous extract. The HPLC-MS analysis allowed the detection of eleven compounds, including the alkaloids harman-3-carboxylic acid (5) and N,β-glucopyranosyl vincosamide (6), and the flavonoids quercetin 3-O-rhamnopyranoside (9) and kaempferol 3-O-rhamnopyranoside (10), all not previously reported in the Loganiaceae family. These compounds, along with strictosidine (3), 5-carboxystrictosidine (7), and desoxycordifoline (8) were isolated through modern chromatographic techniques and determined by using NMR spectroscopy in combination with MS. Overall, the untargeted HPLC-MS analysis proved to be a simple and effective approach to guide the isolation of substances not yet identified from S. peckii.
Association of eating habits with health perception and diseases among Chinese physicians: a cross-sectional study
Authors: Chen Moxi , Xu Xuan , Liu Yinghua , Yao Ying , Zhang Pianhong , Liu Jingfang , Zhang Qian , Li Rongrong , Li Hailong , Liu Yan , Chen Wei
Published: August 2023

Background

Some eating habits may be related to the development of gastrointestinal diseases, obesity, and related metabolic dysfunctions. Because of long working hours, and shift schedules, physicians are more likely to form such eating habits and have a high risk of developing these diseases.

Objectives

We aimed to investigate the association between physicians’ eating habits and their health perception and diseases.

Methods

Between 24 June and 5 August 2020, we performed convenience sampling of in-service physicians in hospitals in mainland China. A questionnaire was administered to collect data pertaining to basic sociodemographic characteristics, eating habits, health-related information such as body mass index classification, and prevalence of common diseases. The associations among eating habits and perceived suboptimal health status, micronutrient deficiency-related diseases, obesity, and related metabolic diseases were analysed.

Results

The prevalence of unhealthy eating habits was high: more eating out-of-home (53.4% in hospital canteens, 23.0% in restaurants and takeaways), fewer meals at home, irregular meals (30.5%), and eating too fast (the duration <10 min, 34.6%). Among those with the above eating habits, the prevalence rates of sub-optimal health and disease were higher than among those without the above eating habits.

Conclusion

Eating habits such as frequent eating out-of-home, irregular meals, and eating too fast were common among physicians, and were significantly related to perceived sub-optimal health status and disease occurrence.
Exploring the potentials of sorghum genotypes: a comprehensive study on nutritional qualities, functional metabolites, and antioxidant capacities
Authors: Lee Sukyeung , Choi Yu-Mi , Shin Myoung-Jae , Yoon Hyemyeong , Wang Xiaohan , Lee Yoonjung , Yi Jungyoon , Jeon Young-ah , Desta Kebede Taye
Published: August 2023

Introduction

Sorghum, long regarded as one of the most underutilized crops, has received attention in recent years. As a result, conducting multidisciplinary studies on the potential and health benefits of sorghum resources is vital if they are to be fully exploited. In this study, the nutritional contents, functional metabolites, and antioxidant capacities of 23 sorghum breeding lines and three popular cultivars were assessed.

Materials and method

All of the sorghum genotypes were grown under the same conditions, and mature seeds were hand-harvested. The metabolite contents and antioxidant capacities of sorghum seeds were assessed using standard protocols. Fatty acids were quantified using a gas chromatography-flame ionization detector, whereas flavonoids and 3-deoxyanthocyanidins were analyzed using a liquid chromatography-tandem mass spectrometry method. The data were analyzed using both univariate and multivariate statistical approaches.

Results and discussion

Total protein (9.05–14.61%), total fat (2.99–6.91%), crude fiber (0.71–2.62%), dietary fiber (6.72–16.27%), total phenolic (0.92–10.38 mg GAE/g), and total tannin (0.68–434.22 mg CE/g) contents varied significantly across the sorghum genotypes (p < 0.05). Antioxidant capacity, measured using three assays, also differed significantly. Five fatty acids, including palmitic, stearic, oleic, linoleic, and linolenic acids, were found in all the sorghum genotypes with statistically different contents (p < 0.05). Furthermore, the majority of the sorghum genotypes contained four 3-deoxyanthocyanidins, including luteolinidin, apigeninidin, 5-methoxyluteolinidin, and 7-methoxyapigeninidin, as well as two dominant flavonoids, luteolin and apigenin. Compared to the cultivars, some breeding lines had significantly high levels of metabolites and antioxidant activities. On the other hand, statistical analysis showed that total tannin, total phenolic, and antioxidant capacities varied significantly across white, yellow, and orange genotypes. Principal component analysis was used to differentiate the sorghum genotypes based on seed color and antioxidant index levels. Pearson’s correlation analysis revealed strong links between biosynthetically related metabolites and those with synergistic antioxidant properties.

Conclusion

This research demonstrated the diversity of the sorghum resources investigated. Those genotypes with high levels of nutritional components, functional metabolites, and antioxidant activities could be used for consumption and breeding programs.
Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer
Authors: Jia Xiaolong , Zhang Dongxu , Zhou Cheng , Yan Zejun , Jiang Zhaohui , Xie Liping , Jiang Junhui
Published: August 2023

Background

The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known.

Methods

A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs.

Results

The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed.

Conclusions

This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.
Dual-energy CT-based radiomics for predicting invasiveness of lung adenocarcinoma appearing as ground-glass nodules
Authors: Zheng Yuting , Han Xiaoyu , Jia Xi , Ding Chengyu , Zhang Kailu , Li Hanting , Cao Xuexiang , Zhang Xiaohui , Zhang Xin , Shi Heshui
Published: August 2023

Objectives

To explore the value of radiomics based on Dual-energy CT (DECT) for discriminating preinvasive or MIA from IA appearing as GGNs before surgery.

Methods

The retrospective study included 92 patients with lung adenocarcinoma comprising 30 IA and 62 preinvasive-MIA, which were further divided into a training (n=64) and a test set (n=28). Clinical and radiographic features along with quantitative parameters were recorded. Radiomics features were derived from virtual monoenergetic images (VMI), including 50kev and 150kev images. Intraclass correlation coefficients (ICCs), Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) penalized logistic regression were conducted to eliminate unstable and redundant features. The performance of the models was evaluated by area under the curve (AUC) and the clinical utility was assessed using decision curve analysis (DCA).

Results

The DECT-based radiomics model performed well with an AUC of 0.957 and 0.865 in the training and test set. The clinical-DECT model, comprising sex, age, tumor size, density, smoking, alcohol, effective atomic number, and normalized iodine concentration, had an AUC of 0.929 in the training and 0.719 in the test set. In addition, the radiomics model revealed a higher AUC value and a greater net benefit to patients than the clinical-DECT model.

Conclusion

DECT-based radiomics features were valuable in predicting the invasiveness of GGNs, yielding a better predictive performance than the clinical-DECT model.
Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations
Authors: Deboever Nathaniel , Zhou Nicolas , McGrail Daniel J. , Tomczak Katarzyna , Oliva Jacqueline L. , Feldman Hope A. , Parra Edwin , Zhang Jianjun , Lee Percy P. , Antonoff Mara B. , Hofstetter Wayne L. , Mehran Reza J. , Rajaram Ravi , Rice David C. , Roth Jack A. , Swisher Stephen S. , Vaporciyan Ara A. , Altan Mehmet , Weissferdt Annikka , Tsao Anne S. , Haymaker Cara L. , Sepesi Boris
Published: August 2023

Background

Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).

Methods

Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria.

Results

In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was –16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62–5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55–4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001).

Conclusion

Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.
Case Report: Giant paratesticular liposarcoma was resected and refused radical orchiectomy
Authors: Zou Qianming , Gan Shu , Li Yuan , Huang Qinzhan , Wang Shusheng , Li Siyi , Gu Chiming
Published: August 2023

Paratesticular liposarcoma (PLS) causes scrotal mass changes, rarely in the urinary system. Before surgery, PLS causes scrotal mass changes that are difficult to distinguish from other causes. There has been a report of a giant paratestis liposarcoma resection and refusal to undergo orchiectomy. A 65-year-old man presented with finding the left scrotal mass after 2 years. Physical examination showed that the left scrotal mass was obviously difficult to retract. Pelvic CT showed that the left scrotal mass and flaky fat density shadow accompanied with left inguinal hernia. During surgery, laparoscopic exploration was performed to rule out inguinal hernia, and a scrotal exploration was also performed concurrently. The intraoperative frozen pathology considered lipogenic tumor, and the patient’s wife refused to undergo simultaneous left radical orchiectomy. Later the mass was completely removed, and postoperative pathology confirmed paratestis liposarcoma. During a 15-month routine follow-up, the tumor did not recur locally or metastasize distantly. PLS should be focused on early diagnosis and treatment, preoperative examinations and postoperative pathology should be combined, and highly personalized treatment will be implemented.
Optimizing the synergy between stereotactic radiosurgery and immunotherapy for brain metastases
Authors: Yoo Kelly H. , Park David J. , Choi John H. , Marianayagam Neelan J. , Lim Michael , Meola Antonio , Chang Steven D.
Published: August 2023

Solid tumors metastasizing to the brain are a frequent occurrence with an estimated incidence of approximately 30% of all cases. The longstanding conventional standard of care comprises surgical resection and whole-brain radiotherapy (WBRT); however, this approach is associated with limited long-term survival and local control outcomes. Consequently, stereotactic radiosurgery (SRS) has emerged as a potential alternative approach. The primary aim of SRS has been to improve long-term control rates. Nevertheless, rare observations of abscopal or out-of-field effects have sparked interest in the potential to elicit antitumor immunity via the administration of high-dose radiation. The blood-brain barrier (BBB) has traditionally posed a significant challenge to the efficacy of systemic therapy in managing intracranial metastasis. However, recent insights into the immune-brain interface and the development of immunotherapeutic agents have shown promise in preclinical and early-phase clinical trials. Researchers have investigated combining immunotherapy with SRS to enhance treatment outcomes in patients with brain metastasis. The combination approach aims to optimize long-term control and overall survival (OS) outcomes by leveraging the synergistic effects of both therapies. Initial findings have been encouraging in the management of various intracranial metastases, while further studies are required to determine the optimal order of administration, radiation doses, and fractionation regimens that have the potential for the best tumor response. Currently, several clinical trials are underway to assess the safety and efficacy of administering immunotherapeutic agents concurrently or consecutively with SRS. In this review, we conduct a comprehensive analysis of the advantages and drawbacks of integrating immunotherapy into conventional SRS protocols for the treatment of intracranial metastasis.
Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis
Authors: Nipp Grace E. , Lee Terry , Sarici Kubra , Malek Goldis , Hadziahmetovic Majda
Published: August 2023

Adult-onset foveomacular dystrophy (AOFVD) is a retinal pattern dystrophy that may affect up to 1 in 7,400 individuals. There is much that is unknown regarding this disease’s epidemiology, risk factors for development, and rate of progression through its four stages. Advancements in retinal imaging over the past 15 years have enabled improved characterization of the different stages of AOFVD. These imaging advancements also offer new ways of differentiating AOFVD from phenotypically similar retinal diseases like age-related macular degeneration and Best disease. This review synthesizes the most recent discoveries regarding imaging correlates within AOFVD as well as risk factors for the development of AOFVD, complications of AOFVD, and treatment options. Our aim is to provide ophthalmologists a succinct resource so that they may offer clarity, guidance, and appropriate monitoring and treatments for their patients with suspected AOFVD.
β-hydroxybutyrate impairs bovine oocyte maturation via pyruvate dehydrogenase (PDH) associated energy metabolism abnormality
Authors: Zhang Kai-Yan , Guo Jing , Zhan Cheng-Lin , Yuan Chong-Shan , Min Chang-Guo , Li Zhi-Qiang , Liu Hong-Yu , Wang Jun , Zhao Jing , Lu Wen-Fa , Ma Xin
Published: August 2023

Background: Ketosis is one of the most frequent and costly metabolic disorders in high-producing dairy cows, and negatively associated with the health and reproductive performance of bovine. Ketosis is mainly caused by the accumulation of ketone body β-hydroxybutyric acid and its diagnosis is based on β-hydroxybutyrate (βHB) concentration in blood.

Methods: In this study, we investigated the effects of βHB on bovine oocyte maturation in the concentration of subclinical (1.2 mM) βHB and clinical (3.6 mM).

Results: The results showed βHB disrupted bovine oocyte maturation and development capacity. Further analysis showed that βHB induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species (ROS), disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, oxidative stress triggered early apoptosis, as shown by the enhanced levels of Caspase-3 and Annexin-V. Moreover, 3.6 mM βHB induced the disruption of the pyruvate dehydrogenase (PDH) activity, showing with the decrease of the global acetylation modification and the increase of the abnormal spindle rate.

Conclusion: Our study showed that βHB in subclinical/clinical concentration had toxic effects on mitochondrial function and PDH activity, which might affect energy metabolism and epigenetic modification of bovine oocytes and embryos.
Pharmacogenomic implications of the differential distribution of CYP2C9 metabolic phenotypes among Latin American populations
Authors: Suarez-Kurtz Guilherme
Published: August 2023

The CYP2C9 gene encodes the major drug metabolism enzyme CYP2C9. This gene is highly polymorphic, and no-function (CYP2C9*3) plus decreased function (CYP2C9*2, *5, *8 and *11) star alleles (haplotypes) are commonly used to predict CYP2C9 metabolic phenotypes. This study explores the pharmacogenomic implications of the differential distribution of genotype-predicted CYP2C9 phenotypes across Latin American populations. Data from 1,404 individuals from the South American countries Brazil, Colombia and Peru, from Puerto Rico in the Caribbean and from persons with Mexican ancestry living in North America were analysed. The results showed that the distribution of CYP2C9 alleles and diplotypes, and diplotype-predicted CYP2C9 phenotypes vary significantly across the distinct country cohorts, as well as among self-identified White, Brown and Black Brazilians. Differences in average proportions of biogeographical ancestry across the study groups, especially Native American and African ancestry, are the likely explanation for these results. The differential distribution of genotype-predicted CYP2C9 phenotypes has potentially clinically-relevant pharmacogenomic implications, through its influence on the proportion of individuals at high risk for adverse response to medications that are CYP2C9 substrates, the proportion on individuals with CPIC therapeutic recommendations for dosing and choice of nonsteroidal antinflammatory drugs (NSAIDs) and the number of individuals that need to be genotyped in order to prevent adverse effects of NSAIDs. Collectively, these findings are likely to impact the perceived benefits, cost-effectiveness and clinical adoption of pharmacogenomic screening for drugs that are predominantly metabolized by CYP2C9.
Deficits in neuromuscular control of increasing force in patients with chronic lateral epicondylitis
Authors: Chen Yueh , Hu Chia-Ling , Hong Chih-Kai , Hsu Kai-Lan , Kuan Fa-Chuan , Chen Wei-Li , Su Wei-Ren , Chen Yi-Ching , Hwang Ing-Shiou
Published: August 2023

Objective: This study investigated the neuromuscular control of increasing and releasing force in patients with chronic lateral epicondylitis (CLE).

Methods: Fifteen patients with CLE (10 males, 5 females, 46.5 ± 6.3 years) and fifteen healthy participants (9 males, 6 females, 45.3 ± 2.5 years) participated in this study. In addition to power grip and maximal voluntary contraction (MVC) of wrist extension, force fluctuation dynamics and characteristics of inter-spike intervals (ISI) of motor units (MUs) with various recruitment thresholds in the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) during a designated force-tracking task with a trapezoidal target (0%–75%–0% MVC) were assessed.

Results: Besides a smaller MVC of wrist extension, the patients exhibited significantly greater task errors (p = 0.007) and force fluctuations (p = 0.001) during force increment than the healthy counterparts. Nevertheless, no force variables significantly differed between groups during force release (p > 0.05). During force increment, the amplitudes of the motor unit action potential of the ECRB and ECRL muscles of the patients were smaller than those of the heathy counterparts (p < 0.001). The patient group also exhibited a higher percentage of motor units (MU) with lower recruitment threshold (<5% MVC) in the ECRL/ECRB muscles and a lower percentage of MU with higher recruitment threshold (>40% MVC) in the ECRB muscle, compared to the healthy group. During force increment, the patient group exhibited a higher rate of decrease in inter-spike intervals (ISIs) of motor units with lower recruitment thresholds (<10% MVC) in the ECRB and ECRL muscles, compared to the control group (p < 0.005).

Conclusion: The patients with CLE exhibited more pronounced impairment in increasing force than in releasing force. This impairment in increasing force is attributed to deficits in tendon structure and degenerative changes in the larger motor units of the wrist extensors. To compensate for the neuromuscular deficits, the rate of progressive increase in discharge rate of the remaining smaller motor units (MUs) is enhanced to generate force.

Significance: The deficits in neuromuscular control observed in CLE with degenerative changes cannot be fully explained by the experimental pain model, which predicts pain-related inhibition on low-threshold motor units.
Baroreflex activity through the analysis of the cardio-respiratory variability influence over blood pressure in cardiomyopathy patients
Authors: Rodriguez Javier , Schulz Steffen , Voss Andreas , Herrera Sergio , Benito Salvador , Giraldo Beatriz F.
Published: August 2023

A large portion of the elderly population are affected by cardiovascular diseases. Early prognosis of cardiomyopathies remains a challenge. The aim of this study was to classify cardiomyopathy patients by their etiology based on significant indexes extracted from the characterization of the baroreflex mechanism in function of the influence of the cardio-respiratory activity over the blood pressure. Forty-one cardiomyopathy patients (CMP) classified as ischemic (ICM—24 patients) and dilated (DCM—17 patients) were considered. In addition, thirty-nine control (CON) subjects were used as reference. The beat-to-beat (BBI) time series, from the electrocardiographic (ECG) signal, the systolic (SBP), and diastolic (DBP) time series, from the blood pressure signal (BP), and the respiratory time (TT), from the respiratory flow (RF) signal, were extracted. The three-dimensional representation of the cardiorespiratory and vascular activities was characterized geometrically, by fitting a polygon that contains 95% of data, and by statistical descriptive indices. DCM patients presented specific patterns in the respiratory response to decreasing blood pressure activity. ICM patients presented more stable cardiorespiratory activity in comparison with DCM patients. In general, CMP shown limited ability to regulate changes in blood pressure. In addition, patients also shown a limited ability of their cardiac and respiratory systems response to regulate incremental changes of the vascular variability and a lower heart rate variability. The best classifiers were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 92.7% accuracy, 94.1% sensitivity, and 91.7% specificity. When comparing CMP patients and CON subjects, the best model achieved 86.2% accuracy, 82.9% sensitivity, and 89.7% specificity. When comparing ICM patients and CON subjects, the best model achieved 88.9% accuracy, 87.5% sensitivity, and 89.7% specificity. When comparing DCM patients and CON subjects, the best model achieved 87.5% accuracy, 76.5% sensitivity, and 92.3% specificity. In conclusion, this study introduced a new method for the classification of patients by their etiology based on new indices from the analysis of the baroreflex mechanism.
Advancing physiology education by understanding the multiple dimensions of homeostasis
Authors: Kuang Serena Y.
Published: August 2023

Homeostasis of the internal environment has been considered the central organizing concept of physiology. However, current definitions of it in textbooks and online teaching sources do not sufficiently reflect how homeostasis serves its central unifying role. Meanwhile, scientific understanding of the functions of the body’s structures at multiple levels (molecular, cell, tissue, organ, organ system, and organism) has advanced significantly, but the understanding of homeostasis is still in the same place. In this article, the author describes some issues and insufficiencies in teaching about homeostasis in physiology education and proposes that homeostasis needs to be understood in terms of four dimensions rather than a simple definition: internal, functional organization; functional manifestation; mechanism; and effect or consequence. Each dimension has two subdimensions or sides. Throughout the elucidation of these dimensions and subdimensions, the original meaning of homeostasis is reinforced, what is lost in current understanding of homeostasis becomes clear, some insufficiencies mentioned above are supplemented, new insights into homeostasis develop, and how the four dimensions of homeostasis can be applied to physiology education is exampled. This new, comprehensive conceptualization advances the understanding of homeostasis and can facilitate teaching and learning about homeostasis and physiology.
De novo transcriptome analysis of Dysoxylum binectariferum to unravel the biosynthesis of pharmaceutically relevant specialized metabolites
Authors: Kumara Patel Mohana , Varun Eranna , Sanjay Joshi Renuka , Madhushree Anchedoddi Hanumegowda , Thimmappa Ramesha
Published: August 2023

The tropical tree, D. binectariferum, is a prominent source of chromone alkaloid rohitukine, which is used in the semi-syntheses of anticancer molecules such as flavopiridol and P-276-00. The biosynthetic pathway of rohitukine or its derivatives is currently unknown in plants. Here, we explored chromone alkaloid biosynthesis in D. binectariferum through targeted transcriptome sequencing. Illumina sequencing of leaves and roots of a year-old D. binectariferum seedling generated, 42.43 and 38.74 million paired-end short reads, respectively. Quality filtering and de novo assembly of the transcriptome generated 274,970 contigs and 126,788 unigenes with an N50 contig length of 1560 bp. The assembly generated 117,619 translated unigene protein sequences and 51,598 non-redundant sequences. Nearly 80% of these non-redundant sequences were annotated to publicly available protein and nucleotide databases, suggesting the completeness and effectiveness of the transcriptome assembly. Using the assembly, we identified a chalcone synthase (CHS) and three type III polyketide synthases (PKS-III; non-CHS type) that are likely to be involved in the biosynthesis of chromone ring/noreugenin moiety of rohitukine. We also identified key enzymes like lysine decarboxylase in the piperidine pathway that make the piperidine moiety of rohitukine. Besides these, the upstream enzymes in flavonoid biosynthesis like phenylalanine ammonia-lyase (PAL), trans-cinnamate 4-hydroxylase (C4H),4-coumarate-CoA ligase (4CL), and chalcone isomerase (CHI) have also been identified. Also, terpene synthases that are likely to be involved in the biosynthesis of various terpenoid scaffolds have been identified. Together, the D. binectariferum transcriptome resource forms a basis for further exploration of biosynthetic pathways of these valuable compounds through functional validation of the candidate genes and metabolic engineering in heterologous hosts. Additionally, the transcriptome dataset generated will serve as an important resource for research on functional genomics and enzyme discovery in D. binectariferum and comparative analysis with other Meliaceae family members.
Community-based mechanisms underlying the root cadmium uptake regulated by Cd-tolerant strains in rice (Oryza sativa. L)
Authors: Li Peng , Xiong Ziqin , Tian Yunhe , Zheng Zhongyi , Liu Zhixuan , Hu Ruiwen , Wang Qiming , Ao Hejun , Yi Zhenxie , Li Juan
Published: August 2023

In recent years, the problem of Cd pollution in paddy fields has become more and more serious, which seriously threatens the safe production of food crops and human health. Using microorganisms to reduce cadmium pollution in rice fields is a green, safe and efficient method, the complicated interactions between the microbes in rice roots throughout the process of cadmium absorption by rice roots are poorly understood. In this investigation, a hydroponic pot experiment was used to examine the effects of bacteria R3 (Herbaspirillum sp) and T4 (Bacillus cereus) on cadmium uptake and the endophytic bacterial community in rice roots. The results showed that compared with CK (Uninoculated bacterial liquid), the two strains had significant inhibitory or promotive effects on cadmium uptake in rice plant, respectively. Among them, the decrease of cadmium content in rice plants by R3 strain reached 78.57-79.39%, and the increase of cadmium content in rice plants by T4 strain reached 140.49-158.19%. Further investigation showed that the cadmium content and root cadmium enrichment coefficient of rice plants were significantly negatively correlated with the relative abundances of Burkholderia and Acidovorax, and significantly positively correlated with the relative abundances of Achromobacter, Agromyces and Acidocella. Moreover, a more complex network of microbes in rice roots inhibited rice plants from absorbing cadmium. These results suggest that cadmium uptake by rice plants is closely related to the endophytic bacterial community of roots. This study provides a reference scheme for the safe production of crops in cadmium contaminated paddies and lays a solid theoretical foundation for subsequent field applications.