bluuebunny/crossref_metadata_2025 huggingface dataset:
Antarctic extreme events
Authors: Siegert Martin J. , Bentley Mike J. , Atkinson Angus , Bracegirdle Thomas J. , Convey Peter , Davies Bethan , Downie Rod , Hogg Anna E. , Holmes Caroline , Hughes Kevin A. , Meredith Michael P. , Ross Neil , Rumble Jane , Wilkinson Jeremy
Published: August 2023

There is increasing evidence that fossil-fuel burning, and consequential global heating of 1.1°C to date, has led to the increased occurrence and severity of extreme environmental events. It is well documented how such events have impacted society outside Antarctica through enhanced levels of rainfall and flooding, heatwaves and wildfires, drought and water/food shortages and episodes of intense cooling. Here, we briefly examine evidence for extreme events in Antarctica and the Southern Ocean across a variety of environments and timescales. We show how vulnerable natural Antarctic systems are to extreme events and highlight how governance and environmental protection of the continent must take them into account. Given future additional heating of at least 0.4°C is now unavoidable (to contain heating to the “Paris Agreement 1.5°C” scenario), and may indeed be higher unless drastic action is successfully taken on reducing greenhouse gas emissions to net zero by mid-Century, we explain it is virtually certain that future Antarctic extreme events will be more pronounced than those observed to date.
Soil carbon dynamics are linked to tree species growth strategy in a naturally regenerating tropical forest
Authors: Wallwork Abby , Castro-Trujillo Biancolino , Banin Lindsay F. , Dent Daisy H. , Skiba Ute , Kerdraon Deirdre , Sayer Emma J.
Published: August 2023

Secondary tropical forests are increasingly important for their role in the global carbon (C) balance as they can rapidly accumulate aboveground biomass C during regrowth. Substantial amounts of plant-derived carbon are also incorporated into the soil through decomposition processes, but our understanding of soil C dynamics during forest regrowth is limited. Secondary succession is characterised by a shift in tree functional groups from light-demanding to shade-tolerant species over time, which can influence rates of C turnover via differences in litter quality and by modifying the decomposition environment. Changes in decomposition processes in turn affect the amount of organic C stored in the soil or released to the atmosphere as CO2. Consequently, understanding how tree functional composition influences C turnover during decomposition could help us predict soil C storage during tropical forest regrowth. We experimentally explored the relationship between tree functional groups and soil C dynamics (decomposition and respiration) by conducting a litter decomposition experiment across a successional gradient of naturally regenerating tropical forest. We created litter mixtures representing tree communities differing in their shade tolerance, as well as a functionally diverse litter mixture, and observed litter mass loss and soil respiration as measures of C turnover over a 6 month period. Litter from light-demanding species decomposed faster than litter from shade-tolerant species, which was reflected in the pattern of soil respiration. There were no clear patterns of increasing or decreasing rates of litter decay or soil respiration with increasing forest age, but there was an interaction between stand age and litter type which influenced both decomposition and soil respiration rates. Interestingly, soil respiration from the functionally diverse litter mixture was significantly higher in the younger than older forest stands, and the functionally diverse litter mixture decayed more rapidly than expected in one of the younger stands. Our findings highlight the potential importance of functionally diverse plant inputs, as well as the interaction between local environmental attributes and litter type, for soil C dynamics in tropical forests.
Microbiota composition and its impact on DNA methylation in colorectal cancer
Authors: Gutierrez-Angulo Melva , Ayala-Madrigal Maria de la Luz , Moreno-Ortiz Jose Miguel , Peregrina-Sandoval Jorge , Garcia-Ayala Fernando Daniel
Published: August 2023

Colorectal cancer is a complex disease resulting from the interaction of genetics, epigenetics, and environmental factors. DNA methylation is frequently found in tumor suppressor genes to promote cancer development. Several factors are associated with changes in the DNA methylation pattern, and recently, the gastrointestinal microbiota could be associated with this epigenetic change. The predominant phyla in gut microbiota are Firmicutes and Bacteroidetes; however, an enrichment of Bacteroides fragilis, Fusobacterium nucleatum, and Streptococcus bovis, among others, has been reported in colorectal cancer, although the composition could be influenced by several factors, including diet, age, sex, and cancer stage. Fusobacterium nucleatum, a gram-negative anaerobic bacillus, is mainly associated with colorectal cancer patients positive for the CpG island methylator phenotype, although hypermethylation in genes such as MLH1, CDKN2A, MTSS1, RBM38, PKD1, PTPRT, and EYA4 has also been described. Moreover, Hungatella hathewayi, a gram-positive, rod-shaped bacterium, is related to hypermethylation in SOX11, THBD, SFRP2, GATA5, ESR1, EYA4, CDX2, and APC genes. The underlying epigenetic mechanism is unclear, although it could be implicated in the regulation of DNA methyltransferases, enzymes that catalyze the transfer of a methyl group on cytosine of CpG sites. Since DNA methylation is a reversible event, changes in gut microbiota could modulate the gene expression through DNA methylation and improve the colorectal cancer prognosis.
Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease
Authors: Mitchell Nadia L. , Murray Samantha J. , Wellby Martin P. , Barrell Graham K. , Russell Katharina N. , Deane Ashley R. , Wynyard John R. , Palmer Madeleine J. , Pulickan Anila , Prendergast Phillipa M. , Casy Widler , Gray Steven J. , Palmer David N.
Published: August 2023

CLN5 neuronal ceroid lipofuscinosis (NCL, Batten disease) is a rare, inherited fatal neurodegenerative disorder caused by mutations in theCLN5gene. The disease is characterised by progressive neuronal loss, blindness, and premature death. There is no cure. This study evaluated the efficacy of intracerebroventricular (ICV) delivery of an adeno-associated viral vector encoding ovineCLN5(scAAV9/oCLN5) in a naturally occurring sheep model of CLN5 disease. CLN5 affected (CLN5−/−) sheep received low, moderate, or high doses of scAAV9/oCLN5 at three disease stages. The treatment delayed disease progression, extended survival and slowed stereotypical brain atrophy in most animals. Of note, one high dose treated animal only developed mild disease symptomology and survived to 60.1 months of age, triple the natural life expectancy of an untreated CLN5−/−sheep. Eyesight was not preserved at any administration age or dosage. Histopathologic examination revealed that greater transduction efficiency was achieved through higher ICV doses, and this resulted in greater amelioration of disease pathology. Together with other pre-clinical data from CLN5−/−sheep, the safety and efficacy data from these investigational new drug (IND)-enabling studies supported the initiation of the first in-human CLN5 gene therapy clinical study using the ICV delivery route for the treatment of CLN5 NCL.

Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT05228145
Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner
Authors: Wu Yang , Hu Qing , Wang Xiaoliang , Cheng Hongbo , Yu Jiegang , Li Yang , Luo Jianing , Zhang Qingjiu , Wu Jianliang , Zhang Gengshen
Published: August 2023

Microglial activation and subsequent inflammatory responses are critical processes in aggravating secondary brain injury after intracerebral hemorrhage (ICH). Pterostilbene (3’, 5’-dimethoxy-resveratrol) features antioxidant and anti-inflammation properties and has been proven neuroprotective. In this study, we aimed to explore whether Pterostilbene could attenuate neuroinflammation after experimental ICH, as well as underlying molecular mechanisms. Here, a collagenase-induced ICH in mice was followed by intraperitoneal injection of Pterostilbene (10 mg/kg) or vehicle once daily. PTE-treated mice performed significantly better than vehicle-treated controls in the neurological behavior test after ICH. Furthermore, our results showed that Pterostilbene reduced lesion volume and neural apoptosis, and alleviated blood-brain barrier (BBB) damage and brain edema. RNA sequencing and subsequent experiments showed that ICH-induced neuroinflammation and microglial proinflammatory activities were markedly suppressed by Pterostilbene treatment. With regard to the mechanisms, we identified that the anti-inflammatory effects of Pterostilbene relied on remodeling mitochondrial dynamics in microglia. Concretely, Pterostilbene reversed the downregulation of OPA1, promoted mitochondrial fusion, restored normal mitochondrial morphology, and reduced mitochondrial fragmentation and superoxide in microglia after OxyHb treatment. Moreover, conditionally deleting microglial OPA1 in mice largely countered the effects of Pterostilbene on alleviating microglial inflammation, BBB damage, brain edema and neurological impairment following ICH. In summary, we provided the first evidence that Pterostilbene is a promising agent for alleviating neuroinflammation and brain injury after ICH in mice, and uncovered a novel regulatory relationship between Pterostilbene and OPA1-mediated mitochondrial fusion.
Sulodexide improves vascular permeability via glycocalyx remodelling in endothelial cells during sepsis
Authors: Ying Jiayun , Zhang Caiyan , Wang Yaodong , Liu Tingyan , Yu Zhenhao , Wang Kexin , Chen Weiming , Zhou Yufeng , Lu Guoping
Published: August 2023

Background

Degradation of the endothelial glycocalyx is critical for sepsis-associated lung injury and pulmonary vascular permeability. We investigated whether sulodexide, a precursor for the synthesis of glycosaminoglycans, plays a biological role in glycocalyx remodeling and improves endothelial barrier dysfunction in sepsis.

Methods

The number of children with septic shock that were admitted to the PICU at Children’s Hospital of Fudan University who enrolled in the study was 28. On days one and three after enrollment, venous blood samples were collected, and heparan sulfate, and syndecan-1 (SDC1) were assayed in the plasma. We established a cell model of glycocalyx shedding by heparinase III and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Sulodexide was administrated to prevent endothelial glycocalyx damage. Endothelial barrier function and expression of endothelial-related proteins were determined using permeability, western blot and immunofluorescent staining. The survival rate, histopathology evaluation of lungs and wet-to-dry lung weight ratio were also evaluated.

Results

We found that circulating SDC1 levels were persistently upregulated in the non-alive group on days 1 and 3 and were positively correlated with IL-6 levels. Receiver operating characteristic curve analysis showed that SDC1 could distinguish patients with mortality. We showed that SDC1-shedding caused endothelial permeability in the presence of heparinase III and sepsis conditions. Mechanistically, sulodexide (30 LSU/mL) administration markedly inhibited SDC1 shedding and prevented endothelial permeability with zonula occludens-1 (ZO-1) upregulation via NF-κB/ZO-1 pathway. In mice with LPS and CLP-induced sepsis, sulodexide (40 mg/kg) administration decreased the plasma levels of SDC1 and increased survival rate. Additionally, sulodexide alleviated lung injury and restored endothelial glycocalyx damage.

Conlusions

In conclusion, our data suggest that SDC1 predicts prognosis in children with septic shock and sulodexide may have therapeutic potential for the treatment of sepsis-associated endothelial dysfunction.
Substrate-specific binding of 8-oxoguanine DNA glycosylase 1 (OGG1) reprograms mucosal adaptations to chronic airway injury
Authors: Pan Lang , Vlahopoulos Spiros , Tanner Lloyd , Bergwik Jesper , Bacsi Attila , Radak Zsolt , Egesten Arne , Ba Xueqing , Brasier Allan R. , Boldogh Istvan
Published: August 2023

Recent advances have uncovered the non-random distribution of 7, 8-dihydro-8-oxoguanine (8-oxoGua) induced by reactive oxygen species, which is believed to have epigenetic effects. Its cognate repair protein, 8-oxoguanine DNA glycosylase 1 (OGG1), reads oxidative substrates and participates in transcriptional initiation. When redox signaling is activated in small airway epithelial cells, the DNA repair function of OGG1 is repurposed to transmit acute inflammatory signals accompanied by cell state transitions and modification of the extracellular matrix. Epithelial-mesenchymal and epithelial-immune interactions act cooperatively to establish a local niche that instructs the mucosal immune landscape. If the transitional cell state governed by OGG1 remains responsive to inflammatory mediators instead of differentiation, the collateral damage provides positive feedback to inflammation, ascribing inflammatory remodeling to one of the drivers in chronic pathologies. In this review, we discuss the substrate-specific read through OGG1 has evolved in regulating the innate immune response, controlling adaptations of the airway to environmental and inflammatory injury, with a focus on the reader function of OGG1 in initiation and progression of epithelial to mesenchymal transitions in chronic pulmonary disease.
Delineating spatial use combined with threat assessment to aid critical recovery of northeast Australia’s endangered hawksbill turtle, one of western Pacific's last strongholds
Authors: Madden Hof Christine A. , Smith Caitlin , Miller Simon , Ashman Kita , Townsend Kathy A. , Meager Justin
Published: August 2023

The current rate of decline in the globally significant western Pacific hawksbill turtle nesting population on Milman Island on the northern Great Barrier Reef (neQLD) suggests that it could be functionally extinct within a decade. Yet a poor understanding of the relative importance and spatial distribution of threats to this population has been a major impediment to recovery actions. For the first time, we assess all threats to the neQLD stock using a combination of a post-hatchling dispersal model, new satellite tracking of post-nesting migrations and a comprehensive review of existing data. We overlay migration routes and foraging areas from the satellite tracking data with spatially referenced threat layers to analyse threat exposure. We found all tracked hawksbills remained in Australian waters, with migration to foraging areas in Queensland including western Cape York to western Torres Strait (n = 8), and eastern Cape York to eastern Torres Strait (n = 5). These results underscore the critical importance of foraging habitats in Queensland (particularly western Queensland) to the Millman Island nesting population. In contrast, the Lagrangian post-hatchling dispersal model predicted a concentration of turtles in the Torres Strait to Gulf of Papua region, with most final positions in Australian waters (63%), followed by Papua New Guinea (31%), Solomon Islands (3%), Indonesia (2%), Vanuatu (0.49%), New Caledonia (1%). Even though 37% of post-hatchling turtles were predicted to recruit to foraging areas outside of the Australian Exclusive Economic Zone (EEZ), none of the 25 turtles tracked left the Australian EEZ (13 in this study and 12 previously). This suggests that survival to breeding is low for turtles outside of the Australian EEZ, but other explanations are discussed. No single pervasive threat was identified in the threat risk assessment however, fisheries (bycatch/ghost gear) interactions, direct harvesting and climate change were considered to have the potential to impede recovery or result in further decline in the population. Fisheries and harvesting should be the priorities for immediate management actions. The lack of spatial protection in foraging habitats in western Queensland was identified as a major policy gap requiring immediate attention if this population’s trajectory is to be reversed and remain one of western Pacific’s strongholds.
Targeting type 2 inflammation in bullous pemphigoid: current and emerging therapeutic approaches
Authors: Toh Wu Han , Lee Hua-En , Chen Chun-Bing
Published: August 2023

Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases and mainly affects an elderly population with multi-morbidity. Due to the frailty of many BP patients, existing treatment options are limited. The blisters associated with BP result from IgG and IgE autoantibodies binding to the central components of hemidesmosome, BP180, and BP230, stimulating a destructive inflammatory process. The known characteristic features of BP, such as intense pruritus, urticarial prodrome, peripheral eosinophilia, elevated IgE, as well as recent expanding evidence from in vitro and in vivo studies implicate type 2 inflammation as an important driver of BP pathogenesis. Type 2 inflammation is an inflammatory pathway involving a subset of CD4+ T cells that secrete IL-4, IL-5, and IL-13, IgE-secreting B cells, and granulocytes, such as eosinophils, mast cells, and basophils. It is believed that effectors in type 2 inflammation may serve as novel and effective treatment targets for BP. This review focuses on recent understandings of BP pathogenesis with a particular emphasis on the role of type 2 inflammation. We summarize current clinical evidence of using rituximab (B-cell depletion), omalizumab (anti-IgE antibody), and dupilumab (anti-IL-4/13 antibody) in the treatment of BP. The latest advances in emerging targeted therapeutic approaches for BP treatment are also discussed.
Impact of the histologic grade of acute gastrointestinal graft-versus-host disease on outcomes in pediatric patients treated with allogeneic hematopoietic stem cell transplantation
Authors: Kim Eun Sil , Kwon Yiyoung , Choe Yon Ho , Kim Mi Jin , Yoo Keon Hee
Published: August 2023

Introduction

Acute gastrointestinal graft-versus-host disease (GVHD) is a common life-threatening complication after hematopoietic stem cell transplantation (HCT). We aimed to investigate outcomes according to the clinical, endoscopic, and histologic severity of gastrointestinal GVHD in pediatric patients treated with allogeneic HCT.

Methods

This retrospective cohort study included pediatric patients who underwent sufficient endoscopic and histopathologic evaluation for clinically suspected acute gastrointestinal GVHD between 2010 and 2020.

Results

Fifty-one patients were included (male proportion, 68.6% [35/51]; median age at HCT, 6.4 years). When the patients were classified according to the histologic severity of gastrointestinal GVHD, the severe group had an earlier onset of GVHD symptoms and a higher proportion of patients with severe clinical gastrointestinal GVHD than the mild-to-moderate and “absent” groups. In Cox proportional hazards regression analysis, the groups with more severe clinical and histologic gastrointestinal GVHD showed a higher risk of non-relapse mortality (NRM). The 5-year overall survival (OS) rates were 58.3 and 36.4% in the mild-to-moderate and histologic gastrointestinal GVHD groups, respectively (p = 0.0384). Patients with higher clinical and histologic grades of gastrointestinal GVHD showed higher cumulative incidence of NRM.

Discussion

Our results demonstrated that histologic severity of gastrointestinal GVHD is a relevant factor affecting OS and NRM, and patients with mild-to-moderate or severe histologic gastrointestinal GVHD have worse outcomes than patients without histologic GVHD. These findings support the importance of assessing the histologic grade in the diagnostic evaluation of patients with clinical gastrointestinal GVHD.
Tracking the evolution of the SARS-CoV-2 Delta variant of concern: analysis of genetic diversity and selection across the whole viral genome
Authors: Li Katherine , Melnychuk Stephanie , Sandstrom Paul , Ji Hezhao
Published: August 2023

Background

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has diversified extensively, producing five highly virulent lineages designated as variants of concern (VOCs). The Delta VOC emerged in India with increased transmission, immune evasion, and mortality, causing a massive global case surge in 2021. This study aims to understand how the Delta VOC evolved by characterizing mutation patterns in the viral population before and after its emergence. Furthermore, we aim to identify the influence of positive and negative selection on VOC evolution and understand the prevalence of different mutation types in the viral genome.

Methods

Three groups of whole viral genomes were retrieved from GISAID, sourced from India, with collection periods as follows: Group A—during the initial appearance of SARS-CoV-2; Group B—just before the emergence of the Delta variant; Group C—after the establishment of the Delta variant in India. Mutations in >1% of each group were identified with BioEdit to reveal differences in mutation quantity and type. Sites under positive or negative selection were identified with FUBAR. The results were compared to determine how mutations correspond with selective pressures and how viral mutation profiles changed to reflect genetic diversity before and after VOC emergence.

Results

The number of mutations increased progressively in Groups A–C, with Group C reporting a 2.2- and 1.9-fold increase from Groups A and B, respectively. Among all the observed mutations, Group C had the highest percentage of deletions (22.7%; vs. 4.2% and 2.6% in Groups A and B, respectively), and most mutations altered the final amino acid code, such as non-synonymous substitutions and deletions. Conversely, Group B had the most synonymous substitutions that are effectively silent. The number of sites experiencing positive selection increased in Groups A–C, but Group B had 2.4- and 2.6 times more sites under negative selection compared to Groups A and C, respectively.

Conclusion

Our findings demonstrated that viral genetic diversity continuously increased during and after the emergence of the Delta VOC. Despite this, Group B reports heightened negative selection, which potentially preserves important gene regions during evolution. Group C contains an unprecedented quantity of mutations and positively selected sites, providing strong evidence of active viral adaptation in the population.
Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings
Authors: Lopez Francesca V. , O’Shea Andrew , Rosenberg Jens T. , Leeuwenburgh Christiaan , Anton Stephen , Bowers Dawn , Woods Adam J.
Published: August 2023

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (31P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using 31P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.
Aerobic exercise, an effective prevention and treatment for mild cognitive impairment
Authors: Huang Baiqing , Chen Kang , Li Ying
Published: August 2023

Aerobic exercise has emerged as a promising intervention for mild cognitive impairment (MCI), a precursor to dementia. The therapeutic benefits of aerobic exercise are multifaceted, encompassing both clinical and molecular domains. Clinically, aerobic exercise has been shown to mitigate hypertension and type 2 diabetes mellitus, conditions that significantly elevate the risk of MCI. Moreover, it stimulates the release of nitric oxide, enhancing arterial elasticity and reducing blood pressure. At a molecular level, it is hypothesized that aerobic exercise modulates the activation of microglia and astrocytes, cells crucial to brain inflammation and neurogenesis, respectively. It has also been suggested that aerobic exercise promotes the release of exercise factors such as irisin, cathepsin B, CLU, and GPLD1, which could enhance synaptic plasticity and neuroprotection. Consequently, regular aerobic exercise could potentially prevent or reduce the likelihood of MCI development in elderly individuals. These molecular mechanisms, however, are hypotheses that require further validation. The mechanisms of action are intricate, and further research is needed to elucidate the precise molecular underpinnings and to develop targeted therapeutics for MCI.
Distinct amyloid-dependent patterns of nigra dopamine depletion in Lewy body diseases
Authors: Baik Kyoungwon , Cha Jungho , Park Mincheol , Lee Younggun , Chung Seok Jong , Yoo Han Soo , Sohn Young H. , Lee Phil Hyu
Published: August 2023

Introduction

Concomitant amyloid pathology is not uncommon and contributes to the clinical characteristics of Lewy body disease (LBD). We investigated the effect of amyloid on striatal18F-FP-CIT uptake patterns in LBD, including Parkinson's disease (PD) and dementia with Lewy bodies.

Methods

We enrolled 125 patients with LBD who underwent18F-florbetaben positron emission tomography (PET) and18F-FP-CIT PET. Patients were divided into amyloid-positive and amyloid-negative groups. We investigated the effect of amyloid on striatal dopamine transporter (DAT) availability, depending on the type of LBD, using general linear models with interaction analysis after controlling for age, sex, education, deep white matter hyperintensity (WMH), periventricular WMH, and cognitive status.

Results

There was a significant interaction effect between the disease group and the presence of amyloid on DAT availability in the anterior putamen, posterior putamen, caudate, and ventral striatum. In the presence of amyloid, only the PD group exhibited decreased DAT availability in the anterior and posterior putamen. In both groups, the presence of amyloid was not associated with DAT availability in the caudate and ventral striatum. The presence of amyloid was not directly related to the worse parkinsonian motor symptoms in both groups. However, there was a significant indirect effect of amyloid on parkinsonian motor symptoms, which was mediated by anterior and posterior putaminal DAT availability in the PD group alone.

Discussion

This study demonstrates different amyloid-dependent or amyloid-independent18F-FP-CIT PET patterns in patients with LBD, suggesting distinctive interactions between α-synuclein and amyloid pathology based on the type of LBD.
The effect of hearing impairment and social participation on depressive symptoms in older adults: a cross-lagged analysis
Authors: Zhao Hejun , Wang Xinying , Shi Yuhao
Published: August 2023

Objective

This study aimed to investigate the relationship between hearing impairment, depressive symptoms, and social participation in older adults.

Methods

The study used data from the China Health and Retirement Longitudinal Study (CHARLS) in 2013 and 2018, which included 3,980 samples. The analysis was conducted using cross-lagged structural equation modeling with SPSS 23.0 and Mplus 7.4.

Results

The findings show that from 2013 to 2018, older people had significantly more hearing impairment and depressive symptoms and significantly less social participation. Hearing impairment was a significant negative predictor of social participation, and older adults with hearing impairment were less likely to participate in social activities. In addition, there may be a bidirectional relationship between hearing impairment and depressive symptoms, with both being positive predictors of each other. Finally, the study found that social participation played an important mediating role in the relationship between hearing impairment and depressive symptoms.

Conclusion

The study’s findings highlight the complex interplay between hearing impairment, social participation, and depressive symptoms in older adults. Therefore, it is important to intervene promptly when hearing impairment is detected in the elderly; pay attention to patient guidance and comfort for the elderly with hearing impairment, give them positive psychological support, encourage them to get out of the house and participate in more social activities to avoid depressive symptoms. The study’s results may inform the development of targeted interventions to address the mental health needs of older adults with hearing impairment.
Impact of respect, equity, and leadership in brain health
Authors: Arshad Faheem , Zegarra-Valdivia Jonathan Adrian , Prioleau Caroline , Valcour Victor , Miller Bruce L.
Published: August 2023

Respect is a feeling of admiration for someone. It forms one of the core values of the Global Brain Health Institute (GBHI), which strives to protect the world’s aging populations from threats to brain health. These values guide us as we advocate for reducing the global impact of dementia. By taking a values-based approach to brain health, we can drive global changes for millions of people. Respect fortifies gratitude and embraces diversity. Philosophical discussions of the ideas support the assertion that respect is crucial in everyday conversations and actions as well as in personal, social, political, and moral spheres. No one can become a leader unless they genuinely respect and care about the success of each team member. Diversity, equity, and inclusivity form the fundamental cornerstones of respect. Understanding this core value of respect will ensure altruistic behavior among the leaders that may help mitigate racism, cultural insults, gender discrimination, stigmatization, religious hatred, and, worst of all, poor leadership abilities that have been the disconcerting examples of disrespect in recent years. We present the underlying neurobiology of respect and its impact on equity and leadership.
Lacunes are associated with late-stage multiple sclerosis comorbidities
Authors: Zhang Lijie , Yu Xintong , Zheng Yexiang , Lin Aiyu , Zhang Zaiqiang , Li Shaowu , Wang Ning , Fu Ying
Published: August 2023

Multiple sclerosis (MS) is a condition that affects the veins and small blood vessels. Previous research suggests that individuals with MS have an increased risk of vascular events and higher mortality rates. However, the relationship between MS and cerebral small vessel disease (CSVD) remains uncertain. This study aims to investigate the association between MS and lacunes. A prospective observational study was conducted, including a total of 112 participants, of which 46 had MS and 66 had CSVD. All participants underwent an MRI scan and a battery of neurological functional assessments. The presence of definite lacunes and black holes was determined through the analysis of T2-weighted, T1-weighted, and FLAIR images. The occurrence of lacunes in MS patients was found to be 19.6%. Notably, the duration of MS was identified as the sole risk factor for the development of lacune lesions in MS patients [odds ratio (OR) = 1.3, 95% confidence interval (CI) = 1.1–1.6, p = 0.008]. Comparatively, MS patients with lacunes exhibited a higher frequency of attacks and larger volumes of T2 lesions compared to MS patients without lacunes. Further analysis using receiver operating characteristic (ROC) curves showed that lacune lesions had limited ability to discriminate between MS and CSVD when disease duration exceeded 6 years. The presence of small arterial lesions in the brain of individuals with MS, along with the duration of the disease, contributes to the development of lacunes in MS patients.
Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls
Authors: Ising Erik , Åhrman Emma , Thomsen Niels O. B. , Åkesson Anna , Malmström Johan , Dahlin Lars B.
Published: August 2023

Introduction

Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 (T1D) and type 2 diabetes (T2D). No cure for DPN is available, but several potential targets have been proposed for treatment. Heat shock proteins (HSPs) are known to respond to both hyper- and hypoglycemia. DPN can be diagnosed using electrophysiology and studied using peripheral nerve biopsies.

Aim

This study aimed to analyze the presence and patterns of HSPs in peripheral nerve biopsies from subjects with T1D, T2D, and healthy controls.

Methods

Posterior interosseous nerves (PIN) from a total of 56 subjects with T1D (n = 9), with T2D (n = 24), and without diabetes (i.e., healthy controls, n = 23) were harvested under local anesthesia and prepared for quantitative mass spectrometry analysis. Protein intensities were associated with electrophysiology data of the ulnar nerve and morphometry of the same PIN, and differences in protein intensities between groups were analyzed.

Results

In total, 32 different HSPs were identified and quantified in the nerve specimens. No statistically significant differences were observed regarding protein intensities between groups. Furthermore, protein intensities did not correlate with amplitude or conduction velocity in the ulnar nerve or with the myelinated nerve fiber density of PIN.

Conclusion

Quantitative proteomics can be used to study HSPs in nerve biopsies, but no clear differences in protein quantities were observed between groups in this cohort.
Role of nutrition in patients with coexisting chronic obstructive pulmonary disease and sarcopenia
Authors: Nan Yayun , Zhou Yuting , Dai Ziyu , Yan Ting , Zhong Pingping , Zhang Fufeng , Chen Qiong , Peng Linlin
Published: August 2023

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases in the elderly population and is characterized by persistent respiratory symptoms and airflow obstruction. During COPD progression, a variety of pulmonary and extrapulmonary complications develop, with sarcopenia being one of the most common extrapulmonary complications. Factors that contribute to the pathogenesis of coexisting COPD and sarcopenia include systemic inflammation, hypoxia, hypercapnia, oxidative stress, protein metabolic imbalance, and myocyte mitochondrial dysfunction. These factors, individually or in concert, affect muscle function, resulting in decreased muscle mass and strength. The occurrence of sarcopenia severely affects the quality of life of patients with COPD, resulting in increased readmission rates, longer hospital admission, and higher mortality. In recent years, studies have found that oral supplementation with protein, micronutrients, fat, or a combination of nutritional supplements can improve the muscle strength and physical performance of these patients; some studies have also elucidated the possible underlying mechanisms. This review aimed to elucidate the role of nutrition among patients with coexisting COPD and sarcopenia.
Case Report: Long-term remission of malignant pleural and peritoneal effusion in a case of advanced lung adenocarcinoma treated with combined crizotinib and anlotinib therapy
Authors: Tian Jin , Long Lin , Zang Jianhua , Liu Peng , Zhao Lili , Zhang Hongtao , Xiao Jun
Published: August 2023

Malignant pleural and peritoneal effusion are common clinical manifestations in advanced malignant tumors, associated with a poor prognosis. This article presents a case of advanced lung adenocarcinoma with ROS1 rearrangement, characterized by persistent malignant pleural and peritoneal effusion. The patient received combined therapy of Crizotinib and Anlotinib, resulting in a significant reduction and even disappearance of the malignant effusion. Exploratory use of this treatment approach improved the patient’s quality of life and holds potential for extending overall survival. However, given the single case report nature, the efficacy of this regimen in treating advanced ROS1-rearranged lung adenocarcinoma should be considered as a supplementary strategy, warranting further validation through multicenter clinical data.
Acupuncture for tumor-related depression: a systematic review and meta-analysis
Authors: Li Xiaoyi , Wang Yang , Wu Liu , Zhao Xinyu , Zhu Tianmin
Published: August 2023

Introduction

Tumor-related depression is a series of symptoms or states triggered by a tumor as the basic disease. It does not belong to psychiatric depression but dramatically affects individuals’ quality of life. Acupuncture is extensively used to treat tumor-related depression, but the effect of body acupuncture on tumor-related depression is still unsubstantiated. This work, therefore, set out to assess the effect of acupuncture on tumor-related depression.

Methods

Eight databases were searched from inception to October 2022 for randomized controlled trials (RCTs). Two researchers separately implemented the database search, study selection, data extraction, and quality assessment. All analyses were performed by using Review Manager 5.3.

Results

A total of 10 studies, including 725 participants, were included. A majority of studies recruited patients diagnosed with various tumor types and statuses. Meta-analysis revealed that acupuncture had a beneficial effect compared with usual care on the Hamilton depression scale (HAMD) (mean difference (MD) = −2.23, 95% CI [−4.43, −0.03], p = 0.05), self-rating depression scale (SDS) (MD= −6.22, 95% CI [−10.67, −1.78], p = 0.006), effective rate (RR = 1.23, 95% CI [1.06, 1.43], p = 0.006), and quality-of-life questionnaire (QLQ-C30) (MD = 6.08, 95% CI [3.72, 8.43], p<0.0001). In the dimension of the HAMD (MD = −4.41, 95% CI [−6.77, −2.05], p = 0.0002) and SDS (MD = −9.19, 95% CI [−13.14, −5.24], p <0.00001), subgroup analysis also highlighted that acupuncture combined with usual care had an advantage over usual care. However, there was no superiority in acupuncture itself compared to usual care on the HAMD (MD = −1.25, 95% CI [−4.34, −1.84], p = 0.43) and SDS (MD = −3.08, 95% CI [−11.14, 4.98], p = 0.45). Acupuncture also reduced the incidence of adverse effects (RR=0.43, 95% CI [0.23, 0.80], p = 0.008).

Conclusion

Acupuncture is a safe and effective complementary therapy for tumor-related depression. This technique can provide clinical references for the medical field.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022372513.
Hypoxia-induced cancer cell reprogramming: a review on how cancer stem cells arise
Authors: Abd Genevieve M. , Laird Madison C. , Ku Jennifer C. , Li Yong
Published: August 2023

Cancer stem cells are a subset of cells within the tumor that possess the ability to self-renew as well as differentiate into different cancer cell lineages. The exact mechanisms by which cancer stem cells arise is still not completely understood. However, current research suggests that cancer stem cells may originate from normal stem cells that have undergone genetic mutations or epigenetic changes. A more recent discovery is the dedifferentiation of cancer cells to stem-like cells. These stem-like cells have been found to express and even upregulate induced pluripotent stem cell markers known as Yamanaka factors. Here we discuss developments in how cancer stem cells arise and consider how environmental factors, such as hypoxia, plays a key role in promoting the progression of cancer stem cells and metastasis. Understanding the mechanisms that give rise to these cells could have important implications for the development of new strategies in cancer treatments and therapies.
Exploring autonomic modulation: day-to-day recovery after exercise sessions in breast cancer survivors
Authors: Lavín-Pérez Ana Myriam , Collado-Mateo Daniel , Hinojo González Carmen , de Juan Ferré Ana , Ruisánchez Villar Cristina , Mayo Xián , Jiménez Alfonso
Published: August 2023

Purpose

The current study aimed to analyze the changes in heart rate variability (HRV) 24h, 48h and 72h after exercise sessions in breast cancer survivors.

Methods

Sixteen survivors who had undergone chemotherapy and radiotherapy were included. Participants trained resistance and cardiovascular components 3 times per week. The intervention was supervised and delivered online for 4 weeks. In this period, patients measured their HRV daily obtaining the lnrMSSD and lnSDNN values of: day 0 (the morning of the training sessions), 24h, 48h and 72h after exercise.

Results

Significant changes in lnrMSSD (p=0.015) and lnSDNN (p=0.031) during recovery times and lnSDNN during the weeks were found (p=0.015). The most prominent differences were identified between the baseline measurement taken on day 0 and 24h after exercise (p=0.007 and p=0.048, respectively) and between measurements obtained 24h and 48h after the training session (p=0.019 and p=0.026, respectively).

Conclusion

Our study suggests that patients may decrease their lnrMSSD and lnSDNN values 24h after exercise and they were close to recover 48h after the sessions. In this regard, HRV may be an useful tool to monitor their recovery and exercise tolerance.
Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis
Authors: Thewamit Rapeepat , Khongkhatithum Chaiyos , Thampratankul Lunliya , Kamolvisit Wuttichart , Khongkrapan Arthaporn , Wattanasirichaigoon Duangrurdee
Published: August 2023

Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the GLDC gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1–2 deletion in the GLDC gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate–related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the PROC gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause.
Progress of research on molecular targeted therapies for colorectal cancer
Authors: Huang Shilin , Ye Jiazhou , Gao Xing , Huang Xi , Huang Julu , Lu Lu , Lu Cheng , Li Yongqiang , Luo Min , Xie Mingzhi , Lin Yan , Liang Rong
Published: August 2023

Colorectal cancer (CRC) is one of the most common malignancies, accounting for approximately 10% of global cancer incidence and mortality. Approximately 20% of patients with CRC present metastatic disease (mCRC) at the time of diagnosis. Moreover, up to 50% of patients with localized disease eventually metastasize. mCRC encompasses a complex cascade of reactions involving multiple factors and processes, leading to a diverse array of molecular mechanisms. Improved comprehension of the pathways underlying cancer cell development and proliferation, coupled with the accessibility of relevant targeted agents, has propelled advancements in CRC treatment, ultimately leading to enhanced survival rates. Mutations in various pathways and location of the primary tumor in CRC influences the efficacy of targeted agents. This review summarizes available targeted agents for different CRC pathways, with a focus on recent advances in anti-angiogenic and anti-epidermal growth factor receptor agents, BRAF mutations, and human epidermal growth factor receptor 2-associated targeted agents.
Intertrack interaction at ultra-high dose rates and its role in the FLASH effect
Authors: Baikalov Alexander , Abolfath Ramin , Schüler Emil , Mohan Radhe , Wilkens Jan J. , Bartzsch Stefan
Published: August 2023

Background: The mechanism responsible for the FLASH effect remains undetermined yet critical to the clinical translation of FLASH radiotherapy. The potential role of intertrack interactions in the FLASH effect, arising from the high spatio-temporal concentrations of particle tracks at UHDRs, has been widely discussed but its influence is unknown.

Methods: We construct an analytical model of the distribution, diffusive evolution, and chemical interaction of particle tracks in an irradiated target. We fit parameters of the model to Monte Carlo (MC) simulations of electron tracks, and include the effects of scavenging capacities of different target media. We compare the model’s predictions to MC simulations of many interacting electron tracks, and use the comparison to predict the prevalence of intertrack interactions in the parameter space where the FLASH effect is observed in vivo, and where differential reactive species (RS) yields have been observed in aqua.

Results: MC simulations of interacting electron tracks demonstrate negligible changes in RS yields at 12 Gy both in oxygenated water and in cellular scavenging conditions, but significant changes at 58 Gy in oxygenated water. The model fits well to the simulation data, and predicts that pulse doses >90Gy delivered in 0.5 μs would be necessary for intertrack interactions to affect RS yields in cellular scavenging conditions, and >13Gy in 0.5 μs for water at 4% O2. The model defines optimal beam parameters (e.g., dose, pulse width, LET) to maximize intertrack interactions, and indicates that decreasing the pulse width of electron pulses further below ≈0.5 μs has no effect on intertrack interactions.

Conclusion: The results of the MC simulations indicate that intertrack interactions do not play a role in the parameters space where the FLASH effect is observed. However, potentially critical limitations in the simulations performed provide the possibility that intertrack interactions occur much more readily than predicted. More accurate simulations, as well as experimental characterization of RS yields across the pulse parameter space, are necessary to more confidently confirm or deny the role of intertrack interactions in the FLASH effect.