bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development
Authors: Courreges Christina J. F. , Davenport Elizabeth C. M. , Bilanges Benoit , Rebollo-Gomez Elena , Hukelmann Jens , Schoenfelder Priya , Edgar James R. , Sansom David , Scudamore Cheryl L. , Roychoudhuri Rahul , Garden Oliver A. , Vanhaesebroeck Bart , Okkenhaug Klaus
Published: November 2024

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cells in vitro. Our data suggest that VPS34 is required for the maintaining normal numbers of mature Treg. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy may contribute to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells.
Checkpoint based immunotherapy in non-small cell lung cancer: a real-world retrospective study
Authors: Liguori Luigi , Giorgio Gabriele , Polcaro Giovanna , Pagliara Valentina , Malandrino Domenico , Perri Francesco , Cascella Marco , Ottaiano Alessandro , Conti Valeria , Servetto Alberto , Bianco Roberto , Pepe Stefano , Sabbatino Francesco
Published: November 2024

Introduction

Immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has radically changed the management of many types of solid tumors including non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated that ICIs improve the survival and the quality of life of patients with advanced non oncogene NSCLC as compared to standard therapies. However, not all patients achieve a clinical benefit from this immunotherapeutic approach. As a result, real-word validation of the efficacy and safety of ICIs can be useful for defining potential predictive biomarkers as well as for overcoming limitations linked to clinical trial restrictions.

Methods

We retrospectively retrieved the clinical data of patients with advanced non oncogene NSCLC treated with ICIs (anti-PD-1 or anti-PD-L1) as single agent or in combination with chemotherapy at “San Giovanni di Dio e Ruggi D’Aragona” University Hospital from January 2016 to December 2023. Potential correlations between clinical-pathological characteristics and safety or survival outcomes were investigated employing the Fisher’s exact test, Mann-Whitney U test, the Kruskal-Wallis method and log-rank test, as applicable. Multivariate survival analyses were performed using the Cox proportional hazards model.

Results

Clinical data of 129 patients were retrieved. At a median follow-up of 29.70 months, progression-free survival (PFS) and overall survival (OS) were 5.27 months and 8.43 months, respectively. At the multivariate analyses, smoking status, presence of bone metastases and the occurrence of immune-related adverse events (irAEs) were correlated with both PFS and OS. Moreover, patients treated with anti-PD-1-based therapy achieved an increased clinical benefit than those treated with anti-PD-L1.

Discussion

In this study we described our real-world experience of ICIs for the treatment of patients with advanced non oncogene NSCLC. A decreased OS in our study population was reported as compared to that of patients included in the clinical trials. Noteworthy, correlations between clinical-pathological characteristics and survival outcomes emerged. Nevertheless, the potential integration of clinical-pathological characteristics as predictive biomarkers in more accurate therapeutic algorithms as well as the underlying biological mechanisms should be further validated in ad hoc studies.
The circadian clock gene BMAL1 modulates autoimmunity features in lupus
Authors: Nakabo Shuichiro , Sandoval-Heglund Donavon , Hanata Norio , Brooks Stephen , Hoffmann Victoria , Zhang Mingzeng , Ambler William , Manna Zerai , Poncio Elaine , Hasni Sarfaraz , Islam Shamima , Dell’Orso Stefania , Kaplan Mariana J.
Published: November 2024

Objectives

An important pathogenic role for neutrophils in systemic lupus erythematosus (SLE) has been proposed. Neutrophils that lack brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1), one of the clock genes, are defective in aging and proinflammatory responses. We assessed the role of Bmal1 in clinical and immunologic manifestations of murine lupus and in human SLE neutrophils.

Methods

Myeloid-conditional Bmal1 knockout mice (Bmal1Mye−/−) and wild type (WT) were treated with epicutaneous TLR7/8 agonist (imiquimod; IMQ) for 6 weeks to induce a lupus phenotype. Upon euthanasia, immune responses, autoantibodies and renal manifestations were evaluated. NET formation and gene expression of bone marrow (BM)-derived murine neutrophils were evaluated. BMAL1 expression was quantified in SLE neutrophils and compared with clinical disease.

Results

IMQ-treated Bmal1Mye−/− and WT displayed comparable systemic inflammation. While renal function did not differ, serum anti-dsDNA levels and renal immune complex deposition were significantly increased in Bmal1Mye−/−. While no differences were observed in NET formation, expression levels of April in BM neutrophils were significantly higher in Bmal1Mye−/−. Bulk RNA-sequence data showed that BM neutrophils in IMQ-treated Bmal1Mye−/− were relatively immature when compared with IMQ-treated WT. BM showed an enhanced April protein expression in Bmal1Mye−/− mice. BMAL1 levels in human SLE peripheral blood neutrophils correlated positively with serum C3 and negatively with serum anti-dsDNA levels.

Conclusion

Bmal1 is associated with lower disease activity in SLE. These results indicate that perturbation in the circadian rhythm of neutrophils can have pathogenic consequences in SLE.
Acute hypoxia stress mediates HIF-1α-Yki-Cactus axis to facilitate the infection of Vibrio parahaemolyticus in Litopenaeus vannamei
Authors: He Honghui , Huang Shaoqing , Geng Ningze , Weng Shaoping , He Jianguo , Li Chaozheng
Published: November 2024

Introduction

Hypoxia stress renders aquatic animals more susceptible to bacterial disease, yet the underlying mechanism remains elusive.

Methods

We conducted an acute hypoxia stress experiment to investigate the impact of stress on the immune response of Litopenaeus vannamei via transcriptome analysis, RT-qPCR and Western blot.

Results

Our results showed that acute hypoxia stress disrupted the tissue architecture, and significantly changed the gene expression profiles in the hepatopancreas of shrimp. More importantly, acute hypoxia stress significantly changed the expression levels of immune-related genes. Ladderlectin, GBP 1, Caspase-1, CLEC4F, MR1 and GBP 2 were significantly down-regulated, but HIF-1α, Cactus, TIPE, Akirin-2, Ivns1abp and TLR3 were significantly up-regulated. We further demonstrated that acute hypoxia activated Yki via HIF-1α to enhance expression level of Cactus, and then Cactus inhibited the phosphorylation of Dorsal and its nuclear translocation, thereby suppressing antibacterial immunity. Subsequently, the challenge experiment following stress revealed that exposure to acute hypoxia stress amplified the infectivity and lethality of Vibrio parahaemolyticus to shrimp. The mechanism of HIF-1α-Yki-Cautus axis provided an explanation for this phenomenon.

Discussion

This study offered new insights into interactions among environmental hypoxia stress, host immunity and pathogens, thereby providing practical guidelines for optimizing shrimp culture practices.
Research status of cutting machining NiTi shape memory alloys: a comprehensive review
Authors: Wei Junying , Yang Lei , Wang Guijie , Gong Chengming , Yang Feiyang
Published: November 2024

NiTi shape memory alloys (SMA) have garnered significant interest owing to their shape memory effect, superior corosion resistance, and biocompatibility. This paper reviewed the current research status of cutting machining for NiTi SMA, focusing on turning, milling, and drilling processes, emphasizing the influence of various cutting parameters, tool materials, and cooling methods on machining performance. The optimal turning effect under dry cutting circumstances is achieved when the cutting speed surpasses 100 m/min. The application of Minimum Quantity Lubrication (MQL) in milling, alongside the use of cold air and the optimization of parameters such as feed rate and cutting depth, could diminish cutting force and temperature, thus reducing burr formation. Cemented carbide and high-speed steel covered with TiN are the ideal materials for drilling tools, and the use of substantial cutting fluid yields superior cutting performance compared to MQL. This review concludes that, despite advancements in the study of machining NiTi shape memory alloys, further research is necessary to enhance the efficiency and quality of NiTi SMA machining, particularly with tool material selection and cooling techniques. Finally, based on the current research results, this paper proposes possible future research directions, which provides valuable theoretical guidance for the processing research of NiTi SMA.
Different fungal signatures in ALD and MAFLD
Authors: Zhang Daya , Wang Qi , Li Da , Chen Chen , Lv Yanting , Huang Shimei , Zeng Fan , Huang Xianfeng , Mao Fengjiao , Bai Feihu
Published: November 2024

Objective

This study investigates the differential impact of fecal fungal microbiota on the pathogenesis of alcohol-associated liver disease (ALD) and metabolic-associated fatty liver disease (MAFLD). We aim to delineate distinct microbial patterns across various stages of each disease.

Methods

We conducted fungal internal transcribed spacer 2 (ITS2) sequencing analysis on fecal samples from 48 ALD patients, 55 MAFLD patients, and 64 healthy controls (HCs).

Results

Distinct fungal microbiota profiles were significantly identified between the ALD and MAFLD patients. In the ALD group, genera such as Trichosporon, Davidiella and Asterotremella along with species like Trichosporon unclassified and Davidiella unclassified were elevated compared to those in the MAFLD group. Conversely, Fungi unclassified, Rhizopus, Periconia, and Candida albicans were more prevalent in MAFLD patients. A specific fungal signature comprising Asterotremella_pseudolonga, Malassezia_restricta and Malassezia, was notably effective in differentiating ALD from MAFLD, achieving an area under the curve (AUC) of 0.94. Periconia and Periconia byssoides were more abundant in non-obese MAFLD patients compared to obese MAFLD and HCs. Rhizopus microsporus var. chinensis and var. rhizopodiformis, along with Pleosporales unclassified, were predominantly found in MAFLD patients with moderate to severe hepatic steatosis (HS). The genera Pleosporales_unclassified and the species Candida_albicans were markedly elevated in ALC patients when contrasted with AFL or HCs.

Conclusion

This investigation introduces a novel fungal signature that successfully differentiates between ALD and MAFLD, underscoring Pleosporales unclassified, as biomarkers for disease progression in ALD and MAFLD. The findings also suggest a significant role for Periconia in the progression of non-obese MAFLD.
The role of astrocytes in Alzheimer’s disease: a bibliometric analysis
Authors: An Xiaoqiong , He Jun , Bi Bin , Wu Gang , Xu Jianwei , Yu Wenfeng , Ren Zhenkui
Published: November 2024

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder marked by cognitive decline and memory loss. Recent research underscores the crucial role of astrocytes in AD. This study reviews research trends and contributions on astrocytes in AD from 2000 to 2024, shedding light on the evolving research landscape.

Methods

We conducted a bibliometric analysis using data from the Web of Science Core Collection, covering publications from January 1, 2000, to July 6, 2024, on “Alzheimer’s disease” and “astrocytes.” We identified 5,252 relevant English articles and reviews. For data visualization and analysis, we used VOSviewer, CiteSpace, and the R package “bibliometrix,” examining collaboration networks, co-citation networks, keyword co-occurrence, and thematic evolution.

Results

Between 2000 and 2024, 5,252 publications were identified, including 4,125 original research articles and 1,127 review articles. Publications increased significantly after 2016. The United States had the most contributions (1,468), followed by China (836). Major institutions were the University of California system (517) and Harvard University (402). The Journal of Alzheimer’s Disease published the most articles (215). Verkhratsky A was the top author with 51 papers and 1,585 co-citations.

Conclusion

Our extensive bibliometric analysis indicates a significant increase in research on astrocytes in AD over the past 20 years. This study emphasizes the growing acknowledgment of astrocytes’ crucial role in AD pathogenesis and points to future research on their mechanisms and therapeutic potential.
The ligamentous cervical instability etiology of human disease from the forward head-facedown lifestyle: emphasis on obstruction of fluid flow into and out of the brain
Authors: Hauser R. A. , Matias D. , Rawlings B.
Published: November 2024

Ligamentous cervical instability, especially ligamentous upper cervical instability, can be the missing structural cause and/or co-morbidity for many chronic disabling brain and systemic body symptoms and diagnoses. Due to the forward head-facedown lifestyle from excessive computer and cell phone usage, the posterior ligament complex of the cervical spine undergoes a slow stretch termed “creep” which can, over time, lead to cervical instability and a breakdown of the cervical curve. As this degenerative process continues, the cervical curve straightens and ultimately becomes kyphotic, a process called cervical dysstructure; simultaneously, the atlas (C1) moves forward, both of which can lead to encroachment of the structures in the carotid sheath, especially the internal jugular veins and vagus nerves. This obstruction of fluid flow can account for many brain diseases, and compression and stretch of the vagus nerve for body diseases, including dysautonomia. This article describes the consequences of impaired fluid flow into and out of the brain, especially venous flow through the internal jugular veins, leading to intracranial hypertension (formerly called pseudotumor cerebri). Cervical structural, internal jugular vein, and optic nerve sheath measurements are presented from a retrospective chart review of 227 consecutive patients with no obvious cause for 1 of 8 specific brain or mental health symptoms—anxiety, brain fog, concentration difficulty, depression/hopelessness, headaches, obsessive thoughts, panic attacks, and rumination on traumatic events. A case example is given to demonstrate how cervical structural treatments can open up internal jugular veins and improve a patient’s chronic symptoms.
RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Cash Alan , Vernon Suzanne D. , Rond Candace , Bateman Lucinda , Abbaszadeh Saeed , Bell Jennifer , Yellman Brayden , Kaufman David L.
Published: November 2024

Background

The energy metabolite oxaloacetate is significantly lower in the blood plasma of ME/CFS subjects. A previous open-label trial with oxaloacetate supplementation demonstrated a significant reduction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-related fatigue.

Methods

In this follow-up trial, 82 ME/CFS subjects were enrolled in a 3-month randomized, double-blinded, controlled study, receiving either 2,000 mg of oxaloacetate or control per day. The primary endpoints were safety and reduction in fatigue from baseline. Secondary and exploratory endpoints included functional capacity and general health status.

Results

Anhydrous enol-oxaloacetate (oxaloacetate) was well tolerated at the tested doses. Oxaloacetate significantly reduced fatigue by more than 25% from baseline, while the control group showed a non-significant reduction of approximately 10%. Intergroup analysis showed a significant decrease in fatigue levels in the oxaloacetate group (p = 0.0039) with no notable change in the control group. A greater proportion of subjects in the oxaloacetate group achieved a reduction in fatigue greater than 25% compared to the control group (p < 0.05). Additionally, 40.5% of the oxaloacetate group were classified as “enhanced responders,” with an average fatigue reduction of 63%. Both physical and mental fatigue improved with oxaloacetate supplementation.

Conclusion

Oxaloacetate is well tolerated and effectively helps reduce fatigue in ME/CFS patients.

Clinical trial registration

https://clinicaltrials.gov/study/NCT05273372.
25-year neuroimaging research on spoken language processing: a bibliometric analysis
Authors: Zheng Yuxuan , Zhang Boning
Published: November 2024

Introduction

Spoken language processing is of huge interest to cognitive and neural scientists, as it is the dominant channel for everyday verbal communication. The aim of this study is to depict the dynamics of publications in the field of neuroimaging research on spoken language processing between 2000 and 2024.

Methods

A bibliometric analysis was conducted to probe this particular subject matter based on data retrieved from Web of Science. A total of 8,085 articles were found, which were analyzed together with their authors, journals of publication, citations and countries of origin.

Results

Results showed a steady increase of publication volume and a relatively high academic visibility of this research field indexed by total citations in the first 25 years of the 21st century. Maps of frequent keywords, institutional collaboration network show that cooperations mainly happen between institutions in the United States, the United Kingdom and Germany. Future trends based on burst detection predict that classification, Alzheimer’s disease and oscillations are potential hot topics.

Discussion

Possible reasons for the result include the aging of the population in developed countries, and the rapid growth of artificial intelligence in the past decade. Finally, specific research avenues were proposed which might benefit future studies.
Mirrors and toothaches: commonplace manipulations of non-auditory feedback availability change perceived speech intelligibility
Authors: Casserly Elizabeth D. , Marino Francesca R.
Published: November 2024

This paper investigates the impact of two non-technical speech feedback perturbations outside the auditory modality: topical application of commercially-available benzocaine to reduce somatosensory feedback from speakers’ lips and tongue tip, and the presence of a mirror to provide fully-detailed visual self-feedback. In experiment 1, speakers were recorded under normal quiet conditions (i.e., baseline), then again with benzocaine application plus auditory degradation, and finally with the addition of mirror feedback. Speech produced under normal and both feedback-altered conditions was assessed via naïve listeners’ intelligibility discrimination judgments. Listeners judged speech produced under bisensory degradation to be less intelligible than speech from the un-degraded baseline, and with a greater degree of difference than previously observed with auditory-only degradation. The introduction of mirror feedback, however, did not result in relative improvements in intelligibility. Experiment 2, therefore, assessed the effect of a mirror on speech intelligibility in isolation with no other sensory feedback manipulations. Speech was recorded at baseline and then again in front of a mirror, and relative intelligibility was discriminated by naïve listeners. Speech produced with mirror feedback was judged as less intelligible than baseline tokens, indicating a negative impact of visual self-feedback in the absence of other sensory manipulations. The results of both experiments demonstrate that relatively accessible manipulations of non-auditory sensory feedback can produce speech-relevant effects, and that those effects are perceptible to naïve listeners.
Toll-like receptors as a missing link in Notch signaling cascade during neurodevelopment
Authors: Stojanovic Mario , Kalanj-Bognar Svjetlana
Published: November 2024

Neurodevelopment encompasses a complex series of molecular events occuring at defined time points distinguishable by the specific genetic readout and active protein machinery. Due to immense intricacy of intertwined molecular pathways, extracting and describing all the components of a single pathway is a demanding task. In other words, there is always a risk of leaving potential transient molecular partners unnoticed while investigating signaling cascades with core functions—and the very neglected ones could be the turning point in understanding the context and regulation of the signaling events. For example, signaling pathways of Notch and Toll-like receptors (TLRs) have been so far unrelated in the vast body of knowledge about neurodevelopment, however evidence from available literature points to their remarkable overlap in influence on identical molecular processes and reveals their potential functional links. Based on data demonstrating Notch and TLR structural engagement and functions during neurodevelopment, along with our description of novel molecular binding models, here we hypothesize that TLR proteins act as likely crucial components in the Notch signaling cascade. We advocate for the hypothesized role of TLRs in Notch signaling by: elaborating components and features of their pathways; reviewing their effects on fates of neural progenitor cells during neurodevelopment; proposing molecular and functional aspects of the hypothesis, along with venues for testing it. Finally, we discuss substantial indications of environmental influence on the proposed Notch-TLR system and its impact on neurodevelopmental outcomes.
Effect of synbiotic supplementation on obesity and gut microbiota in obese adults: a double-blind randomized controlled trial
Authors: Niu Xiaokang , Zhang Qi , Liu Julong , Zhao Yuyang , Shang Nan , Li Shusen , Liu Yinghua , Xiong Wei , Sun Erna , Zhang Yong , Zhao Hongfeng , Li Yixuan , Wang Pengjie , Fang Bing , Zhao Liang , Chen Juan , Wang Fuqing , Pang Guofang , Wang Chenyuan , He Jingjing , Wang Ran
Published: November 2024

Background

Synbiotics, combining specific probiotics and selected prebiotics, may benefit health issues like obesity, but evidence remains inconsistent.

Objective

This study aimed to verify the effect of a pre-screened synbiotics combination [containing Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup), galacto-oligosaccharides (GOS) and xylo-oligosaccharides (XOS)] on obesity in the population.

Methods

In a randomized, double-blind, placebo-controlled trial, 80 individuals with obesity consumed daily synbiotics (containing MN-Gup 1 × 1011 CFU/day, GOS 0.7 g/day, and XOS 0.7 g/day) or placebo for 12 weeks. Body composition, blood lipids, serum hormone, bile acids, and gut microbiota were measured pre-and post-intervention.

Results

Synbiotics supplementation significantly decreased body fat percentage, waist, and serum low-density lipoprotein cholesterol (LDL-C), increased peptide YY, cholecystokinin, oxyntomodulin, GSH (glutathione peroxidase) in individuals with obesity. Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria and bile acids chenodeoxycholic acid (CDCA). Bifidobacterium and Romboutsia were significantly positively correlated with CDCA. A more favorable effect was observed in individuals with obesity and abnormal LDL-C compared to those without dyslipidemia.

Conclusion

Twelve-week synbiotics intervention reduced body fat percentage, waist, and serum LDL-C, especially in individuals with obesity and abnormal LDL-C. The possible mechanisms may be related to changes in gut microbiota, bile acids and gut hormones.

Clinical trial registration

Chictr.org.cn, identifier ChiCTR2200064156.
A critical review of the progress in prevention and treatment of radiation-induced skin damage
Authors: Kemin Li , Rutie Yin
Published: November 2024

Radiation therapy was initially used in dermatology to treat various skin diseases, including acne vulgaris, keloids, plantar warts, tinea capitis and hirsutism. Although it is no longer used in the treatment of many of these diseases, radiation therapy still plays a crucial role in the treatment of keloids, skin cancer and solid organ malignancies. In the past 20 years, the widespread use of intensity-modulated radiation therapy has significantly increased in the management of tumor growth in multiple cancer sites and reduced the incidence of complications in normal organs. However, the occurrence and severity of radiation-induced organ complications still significantly affects the quality of life of patients and remains a research hotspot. Skin tissue is the largest area in the human body, serving as both a barrier and a defender. In patients undergoing radiation therapy, skin is often the first tissue that gets damaged. Especially, when the tumor involves the skin or is close to the skin (i.e., skin cancer, head and neck cancer, breast cancer, vulvar cancer), the treatment targets the superficial tissues, and may have inherent adverse effects on the skin. With the increasing incidence of cancer and the widespread use of radiation therapy in cancer treatment, the radiation-induced skin damage has become a serious problem. In this pursuit, the present study provides a review of the progress in the prevention and treatment of radiation-induced skin damage, thereby providing a reference for the prevention and treatment of radiation-induced skin damage.
Case report: Prolonged benefit of ESG401, a Trop2 antibody-drug conjugate, in endocrine-refractory hormone receptor-positive, HER-2 negative metastatic breast cancer
Authors: Zhao Jing , Huang Fengbo , Xu Xia , Zhang Yan , Xing Xiaoyan , Huang Jian , Qiu Fuming
Published: November 2024

Breast cancer (BC) remains a leading cause of cancer-related mortality in women, with hormone receptor-positive (HR+) tumors accounting for a significant proportion of cases. Despite advancements in endocrine therapy (ET), resistance remains a challenge in metastatic settings. The use of cyclin-dependent kinases 4/6 (CDK4/6) inhibitors in combination with endocrine therapy has notably improved survival. In China, when patients develop resistance to CDK4/6 inhibitors (CDK4/6i) or face financial constraints that prevent their use, chemotherapy becomes the standard treatment approach. This highlights an urgent need for effective treatments following CDK4/6i therapy. ESG401 is a novel trophoblast cell-surface antigen 2 (Trop2) directed antibody-drug conjugate (ADC) with promising preclinical and early clinical efficacy and safety data. We report a case of a 61-year-old female with HR+HER2- metastatic breast cancer (MBC) who developed resistance to fulvestrant and subsequent chemotherapy but achieved a durable partial response (PR) lasting more than 22.5 months following ESG401 treatment. This case underscores the potential role of Trop2-directed ADCs, such as ESG401, in overcoming endocrine resistance and providing meaningful clinical benefit in heavily pretreated patients with HR+/HER2- MBC. Furthermore, the patient’s exceptionally long clinical benefit distinguishes her from other patients receiving ESG401 treatment. Further exploration of the use of ESG401 in HR+HER2- MBC patients, as well as a deeper understanding of the characteristics of patients that may impact sustained efficacy, in expanded clinical trials is warranted.
Alteration of phycobilisome excitation energy transfer properties in response to attenuations in peripheral electron flow
Authors: Guo Zhanjun , Smolinski Sharon L. , King Paul W. , Lubner Carolyn E.
Published: November 2024

In Synechocystis sp. PCC 6803 (S. 6803), two types of phycobilisome (PBS) complexes, CpcG-PBS and CpcL-PBS, function to harvest light energy for photosynthetic reaction centers (RCs), photosystem I (PSI) and photosystem II (PSII). The compositional differences between these two forms of PBS and their specificity for RCs have led to suggestions that they may differ in function. To address this question, we examined how PBS-RC interactions, and the transfer of excitation energy from PBS to RCs, might be adjusted under conditions where electron demand and photon availability are modulated. The CpcG-PBS, CpcL-PBS, and RC complexes were isolated from a S. 6803 strain defective in expression of flavodiiron 1 (oxygen reduction reaction 1, ORR1) grown under varied light regimes. The energy transfer preference from CpcL-PBS to either PSI or PSII was investigated by in vitro crosslinking and 77 K fluorescence emission spectroscopy to assess energy transfer efficiency under photoexcitation. While the results demonstrate that the transfer of excitation energy from CpcL-PBS favors PSI over PSII in WT strains as previously shown, the preference of CpcL-PBS switches from PSI to PSII in ORR1 strains. Surprisingly, this change in preference was reproduced when ORR1 CpcL-PBS was crosslinked with WT RCs, or when WT CpcL-PBS was cross-crosslinked with ORR1 RCs, indicating there are physical modifications to both PBS and RCs that mediate the preference switch. In contrast, the analysis with ORR1 CpcG-PBS shows similar preferences to WT. Additionally, PBS populations in ORR1 shifted to a greater proportion of CpcL-PBS relative to CpcG-PBS. These results demonstrate that under conditions where electron utilization changes, there is a tuning of the excitation energy allocation from CpcL-PBS to RCs to manage the energy distribution for photosynthesis under dynamic flux conditions.
Negative pressure breathing: the response of human respiration and circulation to different levels of rarefaction during inspiration
Authors: Semenov Yury S. , Popova Julia A. , Luzhnov Petr V. , Demin Artem V. , Moreva Tatiana I. , Kriushev Evgeny S. , Nichiporuk Igor A. , Dyachenko Alexander I.
Published: November 2024

Introduction

Negative pressure breathing is breathing with decreased pressure in the respiratory tract without lowering pressure acting on the torso. We lowered pressure only during inspiration (NPBin). NPBin is used to increase venous return to the heart and is considered as a countermeasure against redistribution of body fluids toward the head during spaceflight. Aims of our study were: to obtain quantitative information on NPBin-induced changes in parameters of circulation and respiration in healthy human at various rarefactions; to identify main processes involved in cardiorespiratory response to NPBin.

Methods

Cardiorespiratory response to 25 min of NPBin were studied, rarefaction ranged from −10 to −25 cmH2O. Parameters of systemic, cerebral, and peripheral hemodynamics, as well as respiratory and gas exchange parameters, were measured with non-invasive methods (Finometer, impedance cardiography, rheoencephalography, transcranial Doppler ultrasonography, laser Doppler flowmetry, capillaroscopy). Concentrations of endothelin-1, atrial and brain natriuretic peptides precursors in venous blood, O2 and CO2 tensions in arterialized capillary blood were measured.

Results

Tidal volume increased, respiratory rate decreased under NPBin with no significant changes in minute ventilation. Group averaged, respiratory rate and tidal volume changed approximately twice relative to their values observed under normal breathing. Despite the decrease in respiratory rate (up to 2-3 breaths/min), the results indicate CO2 wash-out. Changes in respiratory and gas exchange parameters were virtually independent of rarefaction level. Synchronous with breathing oscillations of circulatory parameters increased in amplitude under NPBin, while values of the parameters averaged over NPBin period changed little. Amplitude of oscillations in parameters associated with arteries virtually did not change with increasing rarefaction. Inspiration under NPBin reduced left ventricle stroke volume and arterial blood pressure, increased heart rate. Head blood filling decreased during inspiration under NPBin, the decrease increased almost linearly with increasing rarefaction. Parameters returned to their initial values after the end of inspiration. Peak-to-peak amplitude of oscillations under NPBin ranged: stroke volume 17–25 mL, mean arterial pressure 7–9 mmHg, heart rate 14–18 bpm. Peripheral hemodynamics responded to NPBin little.

Conclusion

Changes in stroke volume and central venous pressure during inspiration under NPBin appear to be the major phenomena mediating the effects of NPBin on the cardiorespiratory system.
A short review of application of near-infrared spectroscopy (NIRS) for the assessment of microvascular post-occlusive reactive hyperaemia (PORH) in skeletal muscle
Authors: Hendrick Elizabeth , Jamieson Alexandra , Chiesa Scott T. , Hughes Alun D. , Jones Siana
Published: November 2024

Near-infrared spectroscopy (NIRS) is an optical technique that can be used to non-invasively interrogate haemodynamic changes within skeletal muscle. It can be combined with a short (3–5 min) arterial cuff-occlusion to quantify post-occlusive reactive hyperaemia (PORH). This technique has utility in tracking changes in vascular health in relation to exercise, disease progression or treatment efficacy. However, methods for assessing PORH vary widely and there is little consensus on methodological approaches such as sampling frequency, correction for adipose tissue or the analysis endpoints. The purpose of this review was to: (1) summarise recent advances; (2) compare different methodological approaches and (3) identify current knowledge gaps and future objectives for use of NIRS for vascular assessment. We propose key areas for future work, including optimising occlusion duration and comparing methods of correction for the ischemic stimulus, standardising methods for adjustment of adipose tissue thickness, cross-device comparisons and establishing a standard for minimum sampling rate. Comparisons with alternative methods of capturing PORH or upstream vasodilatory responses would be valuable. Addressing these methodological considerations will aid our understanding of this useful, non-invasive tool for characterising PORH within skeletal muscle and facilitate interpretation of results across studies.
Association of grip strength, sleep duration, and comorbidities with depressive symptoms in middle-aged and older patients with chronic lung diseases: a cross-sectional network analysis based on CHARLS data
Authors: Li Lu , Meng Jiaqi , Wu Yinxiang , Bu Xiaoyuan , Gao Liping , Xiao Zhiwei , Chen Jiquan
Published: November 2024

Background

Depressive symptoms are prevalent among patients with chronic lung diseases (CLDs) and adversely impact their quality of life. This study aims to explore the association of grip strength (GS), sleep duration, and comorbidities with depressive symptoms in patients with CLDs, with an in-depth analysis of the underlying mechanisms.

Methods

Based on data from the China Health and Retirement Longitudinal Study (CHARLS), this study included participants aged 45 and above with diagnosed CLDs. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Binary logistic regression, subgroup analysis, and network analysis were conducted to examine the intricate relationships between GS, sleep duration, comorbidities, and specific depressive symptoms.

Results

Among the 1,427 participants, 39.8% exhibited depressive symptoms. Adjusted analyses revealed that GS (OR = 0.964, p < 0.001) and sleep duration (OR = 0.808, p < 0.001) were negatively associated with depressive symptoms, whereas the number of comorbid chronic diseases (OR = 1.189, p < 0.001) showed a significant positive correlation with depressive symptoms. Subgroup analyses demonstrated variations in these relationships across different demographic characteristics and lifestyle factors. Network analysis pinpointed “depressed” as the core symptom, with “annoyed,” “exhausted,” and “lonely” as secondary core symptoms. The robust associations between specific factors and depressive symptoms (GS with “annoyed,” sleep and comorbid chronic diseases with “depressed”) suggested potential targets for interventions.

Conclusion

This study underscores the complex interplay of GS, sleep duration, and comorbidities with depressive symptoms in patients with CLDs. These findings offer new perspectives for improving the mental health of this vulnerable population.
Flashbulb memories in the context of group hierarchies: effects of gender, system justification, and social dominance orientation on negative private and public flashbulb memories
Authors: Çavuşoğlu Merve , Kuşdil Muharrem Ersin
Published: November 2024

Research on flashbulb memories (FBMs) has primarily focused on cognitive aspects. However, recent studies indicate that FBMs are closely associated with social and cultural dynamics. This descriptive study explored the structural aspects and psychosocial functions of negative FBMs within the context of intergroup theories, mainly focusing on negative public (coup attempt in Türkiye on July 15, 2016) and private (bad news of a loved one) FBMs. Participants in the main study (N = 233) were selected and grouped based on their social dominance orientations (SDO; high and low groups) and system justification tendencies (SJT; high and low groups), using data from a preliminary survey (N = 1,113). In the main study, participants’ responses to items on canonical categories, phenomenological aspects, and psychosocial functions of FBMs and their involvement in different protest actions against the coup attempt were compared considering SDO, SJT, and gender. The results show that private FBMs were generally rated higher by participants than public FBMs in all aspects. Although the canonical quality of private FBM did not differ between gender groups, public FBM quality was better in men. Participants in the high-SJT group had higher-quality public FBMs and rated these memories as more functional than participants in the low-SJT group, along with their high levels of protest participation. No differences were observed between the SDO groups for either type of FBM. The findings are discussed in terms of their relevance to group hierarchies and system justification motives. As the first attempt to place the FBM phenomenon in the context of SDO and SJT at the individual level, this study is intended to encourage others to adopt multi-level intergroup theories for integrating bottom-up and top-down processes.
A blended group intervention to promote social connectedness and wellbeing among international university students: an exploratory study
Authors: Cipolletta Sabrina , Tedoldi Ilaria , Tomaino Silvia Caterina Maria
Published: November 2024

Introduction

Loneliness is a prevalent issue among international university students, often exacerbated by cultural and linguistic barriers. This pilot study aims to assess the feasibility, acceptability and impact of a blended intervention to promote international students’ social connectedness and well-being.

Methods

A sample of 49 international students from the University of Padua (Italy) was recruited. The study followed the methodology of a non-randomized controlled trial comparing a blended intervention (comprising group activities and online self-help materials) with two other active conditions (self-help only and peer-to-peer interventions) and a control condition at two times (baseline and at 8 weeks). Participants completed a survey to assess their satisfaction with the interventions, changes in their interactions and wellbeing. They also filled in some questionnaires to measure anxiety, depression, perceived social support, loneliness and satisfaction with life. A mixed-method analysis was conducted.

Results

Results showed that interventions involving in-person activities had significant advantages over self-help intervention in terms of interaction improvement and a higher number of relationships. Participants perceived self-help materials as more relevant, satisfactory, and functional within the blended group compared to the self-help group. Contrary to the control group, the blended and peer-to-peer groups reported lower scores on the standardized measures of loneliness, anxiety, and depression, and higher scores on satisfaction with life, collected pre- and post-intervention. The thematic analysis of the answers to the open-ended questions showed that in-person group activities provided the opportunity to compare themselves with peers and have a direct experience of new social connections.

Discussion

The findings highlight the importance of translating insights from self-help materials into active and direct social experiences, to reduce loneliness through the emergence of new perspectives and shared meaning making.
Physicians’ ethical concerns about artificial intelligence in medicine: a qualitative study: “The final decision should rest with a human”
Authors: Kahraman Fatma , Aktas Aysenur , Bayrakceken Serra , Çakar Tuna , Tarcan Hande Serim , Bayram Bugrahan , Durak Berk , Ulman Yesim Isil
Published: November 2024

Background/aim

Artificial Intelligence (AI) is the capability of computational systems to perform tasks that require human-like cognitive functions, such as reasoning, learning, and decision-making. Unlike human intelligence, AI does not involve sentience or consciousness but focuses on data processing, pattern recognition, and prediction through algorithms and learned experiences. In healthcare including neuroscience, AI is valuable for improving prevention, diagnosis, prognosis, and surveillance.

Methods

This qualitative study aimed to investigate the acceptability of AI in Medicine (AIIM) and to elucidate any technical and scientific, as well as social and ethical issues involved. Twenty-five doctors from various specialties were carefully interviewed regarding their views, experience, knowledge, and attitude toward AI in healthcare.

Results

Content analysis confirmed the key ethical principles involved: confidentiality, beneficence, and non-maleficence. Honesty was the least invoked principle. A thematic analysis established four salient topic areas, i.e., advantages, risks, restrictions, and precautions. Alongside the advantages, there were many limitations and risks. The study revealed a perceived need for precautions to be embedded in healthcare policies to counter the risks discussed. These precautions need to be multi-dimensional.

Conclusion

The authors conclude that AI should be rationally guided, function transparently, and produce impartial results. It should assist human healthcare professionals collaboratively. This kind of AI will permit fairer, more innovative healthcare which benefits patients and society whilst preserving human dignity. It can foster accuracy and precision in medical practice and reduce the workload by assisting physicians during clinical tasks. AIIM that functions transparently and respects the public interest can be an inspiring scientific innovation for humanity.
Exploring the structural validity and reliability of the swimming competence assessment scale in college students
Authors: Zhao Miao , Chen Cheng , Ning Peng , Zhang Bo Wei , Shen Yupeng
Published: November 2024

Purpose

As a globally popular physical activity, swimming also presents challenges due to its inherent aquatic risks. Therefore, the cultivation of swimming competence emerges as a crucial strategy in preventing drowning incidents. This study aimed to develop and validate the Swimming Competence Assessment Scale in College Students (SCAS) to address the gap in structured swimming proficiency evaluation, essential for drowning prevention and water safety education.

Methods

The research involved 160 full-time second-year college students, including 92 males (age:20.48±0.51) and 68 females (age:20.65±0.70), who underwent two swimming ability assessments. The evaluation covered fundamental swimming skills, including entry, submersion, rotation, prone and supine swimming, floating, and exiting the water.

Results

Exploratory Factor Analysis revealed goodness-of-fit for a two-factor model swimming coherent motion and swimming stable posture, which supported the construct validity. The inter-factor construct reliability (CR = 0.866, CR = 0.835) and the square root of Average Variance Extracted (AVE1 = 0.754, AVE1 = 0.848) exceeded the standards for supporting convergent and discriminant validity. The inter-rater reliability (IRR = 0.542) and Cronbach’s alpha (α = 0.840, α = 0.827) coefficient results have demonstrated the internal reliability of the SACS. Positive correlation between SCAS scores at pre-test and post-test provided evidence for SCAS’s test–retest reliability (TRR = 0.825, TRR = 0.758).

Conclusion

SCAS is a valid and reliable assessment scale. It assesses college students’ swimming competence through two aspects: Swimming Coherent Motion and Swimming Stable Posture.
Associations between ethylene oxide exposure and biological age acceleration: evidence from NHANES 2013–2016
Authors: Chen Xinyun , Shi Fangyu , Yu Wenhui , He Chunying , Gou Shenju , Fu Ping
Published: November 2024

Introduction

Population aging is a global concern, with the World Health Organization predicting that by 2030, one in six individuals worldwide will be 60 years or older. Ethylene oxide (EO) is a widely used industrial chemical with potential health risks, including associations with age-related diseases. This study investigates the relationship between EO exposure and biological age acceleration.

Method

Data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 were analyzed, including 3,155 participants after exclusions. Blood EO levels were measured using hemoglobin adducts (HbEO). Biological age acceleration was assessed using two methods: Phenotypic Age Acceleration (PhenoAgeAccel) and Klemera-Doubal Method Age Acceleration (KDM-AA). Linear and logistic regression models were applied, adjusting for various covariates, and restricted cubic spline (RCS) regression was used to explore non-linear associations.

Results

Higher EO exposure was significantly associated with increased PhenoAgeAccel and KDM-AA across all models. In the continuous model, substantial positive associations were observed (PhenoAgeAccel: β = 0.73, p < 0.001; KDM-AA: β = 0.66, p < 0.001) in Model 3. Quintile analysis indicated a trend of increasing biological age acceleration with higher EO exposure. RCS regression demonstrated a significant linear relationship between EO exposure and PhenoAgeAccel (p for non-linearity = 0.067), as well as with KDM-AA (p for non-linearity = 0.083). Subgroup and interaction analyses revealed significant modifying effects by factors such as body mass index, gender, diabetes status, and physical activity level.

Conclusion

Our study demonstrates a significant association between EO exposure and accelerated biological aging. These findings highlight the need for further prospective and mechanistic studies to validate and explore this phenomenon.