bluuebunny/crossref_metadata_2025 huggingface dataset:
Collective memories and previous experiences of older people in the face of disaster risk processes: lessons learned, implication, and social support
Authors: Sandoval-Díaz José , Navarrete-Valladares Camila , Suazo-Muñoz Consuelo , Martínez-Labrín Soledad
Published: November 2023

Introduction

Climate change amplifies the vulnerability of various groups, especially of older people. Though seen as highly vulnerable, studies reveal their remarkable resilience and that they experience less distress than the young population. Collective memory and experience thus act as coping devices, facilitating learning processes and adaptation when faced with natural risks.

Method

The objective was to characterize the lessons learned, implications and social support perceived by the older people in disaster risk situations. The study was conducted with six groups of older people in Ñuble (Chile) using the SWOT matrix (Strengths, Weaknesses, Opportunities, and Threats), life stories, focus groups, photo evocation, and other participatory techniques. Content analysis was based on a systematic coding of category quantifications.

Results

Negative impacts and positive learning processes were identified that prompted significant changes and made post-traumatic growth processes and capacity-building possible. The type of disaster, its frequency and stage in which it occurs influence the perception of risk and coping strategies, underscoring the importance of strengthening communication about natural risks that are often rendered invisible, such as heat waves. Social support is the main source of collective capacity and has been shown to reduce perceived vulnerability to disaster risk scenarios.

Conclusions

The collective memory and prior disaster experiences of the older people provide them with tools to reinterpret new risk scenarios, highlighting their abilities and promoting their empowerment. These resources are crucial for the development of intergenerational learning aimed at comprehensive risk management. However, facing recent disaster risk situations such as COVID-19 or heatwaves has posed a challenge due to a lack of prior experiences and knowledge on how to handle them. This underscores the importance of having continuous psychoeducation, tailored to the specific and territorial needs of the older people, especially in the context of climate change.
Ezetimibe and atherosclerotic cardiovascular disease: a systematic review and meta-analysis
Authors: Omidi Fatemeh , Rahmannia Maryam , Shahidi Bonjar Amir Hashem , Mohammadsharifi Parsa , Nasiri Mohammad Javad , Sarmastzadeh Tala
Published: November 2023

Introduction

Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.

Methods

We conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).

Results

We encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (−14.06 mg/dl; 95% CI −18.0 to −10.0; p = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.

Conclusions

Our study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.
Regional character of geomagnetic field directional circularity: Holocene Eastern North America
Authors: Lund Steven P.
Published: November 2023

This study characterizes the paleomagnetic secular variation (PSV) in five Holocene records from Eastern North America. We have determined equi-spaced (100-year) declination and inclination time series for the five sites and compared their directional variability. We note ten correlatable features in both inclination and declination, which indicate that these five PSV records all lie within the same PSV region. We focus on clockwise or counter-clockwise looping of paleomagnetic directions (termed circularity) in these PSV records. We have used two techniques to estimate the circularity. We have first calculated the rate and direction of motion in 200-year intervals for each record. We have also looked for discernable looping (full loops down to 1/2 loops) in individual records. We estimate the loop sizes, durations, and circularity direction. We note the same pattern of circularity in both methods. There are seven intervals of alternating circularity in all five sites. They normally agree in timing and direction of circularity. Both methods suggest an alternating, teeter-totter like, behavior to PSV circularity. This teeter-totter behavior is unbalanced with more time spent in counter-clockwise motion than in clockwise motion. The loops have a distribution of sizes and durations with smaller loops being shorter in duration (400–800 years) and bigger loops having longer durations (600–1,200 years). The teeter-totter alternation of clockwise versus counter-clockwise circularity is distinctive and may be a normal aspect of PSV. The alternation is not consistent with several traditional ideas about fluid flow (drift, whirling motion, simple convection) in the outer core. Recent studies have identified torsional oscillations as a source for both historical short-term (decadal) and millennial-scale (103) secular variation. Such a pattern of fluid flow might create the alternating teeter-totter-like behavior of circularity that we see. All five PSV records also display five short (<400 years) intervals of higher-amplitude acceleration and faster PSV rates. These features are analogous to geomagnetic jerks in that they are short intervals of anomalous acceleration. Previous studies showed evidence in PSV for similar anomalous acceleration intervals (∼102 yrs). We think our anomalous intervals are comparable to them.
Investigating trainee instrumental/vocal teachers’ perceptions of dialogic teaching: an exploratory study
Authors: Poole James , Norton Naomi
Published: November 2023

This research explores perceptions of dialogic teaching amongst trainee instrumental/vocal teachers enrolled on the MA Music Education: Instrumental and Vocal Teaching programme at the University of York. Thirty students from three different cohorts responded to an online questionnaire. Findings indicate that respondents were aware of a broader range of advantages of using dialogic teaching than disadvantages. Despite this, 59% of respondents reported that they inconsistently use dialogic teaching. Respondents also reported that they learn to use dialogic teaching through observation of fellow teachers, practical teaching experience, and peer-to-peer discussion. Some respondents viewed dialogic teaching primarily as a process of teacher-led questioning, rather than questioning and discussion, which suggests that trainee teachers may benefit from a more in-depth understanding of dialogic teaching within the context of instrumental/vocal lessons. The results of this research are of relevance to teachers, teacher educators, and providers of pedagogical resources.
Enhanced trimethylamine metabolism and gut dysbiosis in type 2 diabetes mellitus with microalbumin
Authors: Huo Lixia , Li Hui , Zhu Ming , Liu Yang , Ren Lingyan , Hu Jia , Wang Xiaoyi
Published: November 2023

Background

Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic nephropathy. This study aimed to investigate the gut microbiota profiles and a group of targeted urine metabolic characteristics in T2DM patients with or without microalbuminuria, to determine the correlation between the gut microbiota composition, trimethylamine (TMA) metabolism, and the clinical features during progression of diabetic kidney disease (DKD)

Methods

This study included 26 T2DM patients with microalbuminuria (Micro), 26 T2DM patients with normoalbuminuria (Normo), and 15 healthy controls (HC). Urine and Fecal samples were detected using ultra performance liquid chromatography tandem mass spectrometry and 16S ribosomal DNA gene sequencing, respectively.

Results

The TMAO/TMA ratio decreased gradually during the HC-Normo-Micro transition. The levels of TMA, choline and betaine were significantly different between the HC group and the T2DM patients belonging to both Normo and Micro groups. At the operational taxonomic unit (OTU) level, the gut microflora diversity was significantly reduced in the Micro groups compared to the HC groups and the Normo groups. Taxonomic analyses revealed significant consumption in the relative abundances of eight bacterial genera and significant enrichment of two bacterial genera during the HC-Normo-Micro transition. Furthermore, the relative abundances of six bacterial genera, namely, Ruminococcus_1, [Eubacterium]_ruminantium_group, Roseburia, Faecalibacterium, Fusicatenibacter and Coprococcus_3 exhibited significant differences, and were associated with elevated urinary albumin creatinine ratio (UACR), TMAO/TMA, TMA and its precursors in the Micro group compared with the other groups.

Conclusion

The imbalance of gut microbiota has occurred in patients with early-stage DKD, and the consumption of short-chain fatty acid-producing bacteria were associated with the accumulation of TMA and UACR.
Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis
Authors: Zhou Zheng , Liu Jinjin , Chen Yun , Ren Bingxuan , Wan Siyuan , Chen Yao , He Yanhong , Wei Qiuyang , Gao Haiyan , Liu Lixiang , Shen Hongmei
Published: November 2023

Background

Hashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from patients suffering from HT.

Method

Using the Illumina 850K BeadChip, we conducted a genome-wide DNAm assessment on 10 matched pairs of HT sufferers and healthy individuals. Genes with differential methylation (DMGs) were identified and underwent functional annotation via the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The transcriptional significance of potential epigenetic biomarker genes was corroborated through qRT-PCR.

Results

The DNAm profiling across the genome indicated an overall reduction in methylation in HT subjects in comparison with their healthy counterparts. We detected 283 DMPs (adjusted P < 0.05 and |Δβ| > 0.1), among which 152 exhibited hypomethylation and 131 demonstrated hypermethylation. Further analysis exposed a noteworthy concentration of hypermethylated DMPs in the 3´UTR, North Shore, and CpG islands, while there was a significant decrease in the Open Sea (all P < 0.001). The 283 DMPs were broadly distributed from chromosome 1 to 22, with chromosome 6 harboring the most DMPs (n = 51) and chromosome 12 carrying the most DMGs (n = 15). The SLFN12 gene, which presented with extreme hypomethylation in its promoter DMPs among HT patients, was identified as the epigenetic marker gene. Consequently, the SLFN12 mRNA expression was markedly upregulated in HT, displaying a negative relationship with its methylation levels. The area under curve (AUC) value for the SLFN12 gene among HT patients was 0.85 (sensitivity: 0.7, specificity: 0.7), a significant difference compared with healthy controls. The methylation levels of all DMPs in SLFN12 gene were negatively correlated with TSH and one CpG site (cg24470734) was positively assocciated with FT4.

Conclusion

This investigation presents an initial comprehensive DNAm blueprint for individuals with HT, which permits clear differentiation between HT subjects and normal controls through an epigenetic lens. The SLFN12 gene plays a pivotal role in the onset of HT, suggesting that the methylation status of this gene could serve as a potential epigenetic indicator for HT.
Untargeted metabolomics reveals dynamic changes in metabolic profiles of rat supraspinatus tendon at three different time points after diabetes induction
Authors: Xu Kuishuai , Zhang Liang , Wang Tianrui , Ren Zhongkai , Yu Tengbo , Zhang Yingze , Zhao Xia
Published: November 2023

Objective

To investigate the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes by untargeted metabolomics analysis.

Methods

A total of 80 Sprague–Dawley rats were randomly divided into normal (NG, n = 20) and type 2 diabetes mellitus groups (T2DM, n = 60) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-12w, and T2DM-24w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group. The metabolite profiles of supraspinatus tendon were obtained using tandem mass spectrometry. Metabolomics multivariate statistics were used for metabolic data analysis and differential metabolite (DEM) determination. The intersection of the three comparison groups’ DEMs was defined as key metabolites that changed consistently in the supraspinatus tendon after diabetes induction; then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed.

Results

T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group detected 94 (86 up-regulated and 8 down-regulated), 36 (13 up-regulated and 23 down-regulated) and 86 (24 up-regulated and 62 down-regulated) DEMs, respectively. Seven key metabolites of sustained changes in the supraspinatus tendon following induction of diabetes include D-Lactic acid, xanthine, O-acetyl-L-carnitine, isoleucylproline, propoxycarbazone, uric acid, and cytidine, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes. The results of KEGG pathway enrichment analysis showed that the main pathway of supraspinatus metabolism affected by diabetes (p < 0.05) was purine metabolism. The results of the KEGG metabolic pathway vs. DEMs correlation network graph revealed that uric acid and xanthine play a role in more metabolic pathways.

Conclusion

Untargeted metabolomics revealed the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes, and the newly discovered seven metabolites, especially uric acid and xanthine, may provide novel research to elucidate the mechanism of diabetes-induced tendinopathy.
Harmonic state estimation and localization based on broad-band measurement
Authors: Wu Wei , Zeng Dehui , Li Jianghui , Lu Jiajun , Li Chaojie , Liu Shenquan
Published: November 2023

Harmonic and power quality issues brought by the high power electronics penetration level have become a rising threat to power grids. To achieve accurate measurement of the broadband harmonics caused by the power electronic devices, the broadband phasor measurement unit has been developed and installed. However, due to its high cost, it is less practical to install bPMU on each node, and therefore, how to obtain the global harmonic state in the power grid with minimum bPMUs is a crucial issue. This paper is focused on the harmonic state estimation method based on bPMU data. The mathematical model for harmonic state estimation is first derived based on circuit principles. Then, the weighted least squares method is then utilized to solve the established measurement equations for harmonic state estimation to obtain the harmonic state across the grid. Furthermore, the 0–1 integer programming approach is employed to optimize the installation locations of the bPMUs to reduce the overall cost while maintaining full observability. Subsequently, the harmonic sources are localized by analyzing the injected harmonic power on each node. Finally, the validity and effectiveness of the proposed method are proved by matching results between the proposed methods and the simulation model based on the IEEE 14-node system.
Prediction of natural fracture distribution characteristics in tight oil and gas reservoirs based on paleotectonic stress field
Authors: Lin Lifei , Wang Mingwei , Wang Yanwei , Gao Yi , Li Song
Published: November 2023

The production of fractured oil and gas reservoirs in the world accounts for more than half of total oil and gas production and is one of the important fields for increasing oil and gas storage and production in the 21st century. The key to characterizing fractured oil and gas reservoirs is the distribution pattern of natural fractures. The distribution of natural fractures is dominated by structural deformations and fractures. Therefore, analytical and structural simulations of the tectonic stress field in geological structural systems play a crucial role in obtaining fracture distribution patterns. In this paper we have developed a description of the distribution of natural fractures based on finite element numerical simulations of the paleotectonic stress field. The study focused on the Chang 7 and Huangjialing Chang 8 reservoirs in the underground Siwan region of the Ordos Basin in China. First, an experimental assessment of the rock mechanics of the reservoir was completed, and the values of the paleotectonic stresses obtained from the tests were used as inversion criteria for the stress field simulations. Based on the geology, a refined geological model has been developed to study the structure of the Chang 7 and Chang 8 oil reservoirs in the block. The simulated paleotectonic stress fields for natural fractures in the Indosinian period are as follows: maximum principal stress of 94.67 MPa, minimum principal stress of 21.58 MPa, and vertical stress of 28.07 MPa. The direction of maximum principal stress remains essentially in the NE-SW direction, with the largest differential stress occurring in the Chang 8 oil layer group in Huangjialing, while the differential stress is relatively uniform in the Chang 7 oil layer group in Xiasiwan. It predicts the relative density of natural fractures in the Chang 7 and Chang 8 reservoirs, and finds high-to-low plane heterogeneity in the Huangjialing Chang 8 reservoir group and the Xiasiwan Chang 7 reservoir group, respectively. The paper reveals the pattern of development of reservoir fractures in both vertical and horizontal directions, providing an important geological basis for efficient and rational exploitation of oil and gas resources in the study area and improving oil recovery.
A facultative mutualism between habitat-forming species enhances the resistance of rocky shore communities to heat waves
Authors: Gutiérrez Jorge L. , Bagur María , Lorenzo Rodrigo A. , Palomo Maria Gabriela
Published: November 2023

Heat waves have increased in frequency, duration, and magnitude in recent decades, causing mass mortality events in terrestrial and aquatic ecosystems. Arguably, mass mortalities of habitat-forming organisms – i.e., dominant sessile organisms that define habitats via their own physical structure – would be amongst the most dramatic impact of heat waves because of their negative, cascading consequences on their associated biodiversity. However, the resistance of habitat-forming organisms to heat waves can be enhanced if they associate with secondary habitat formers able to tolerate and modulate extreme heat levels. Here we show that a seaweed of the Porphyra/Pyropia (P/P) clade can shield primary habitat-forming mussels, Brachidontes rodriguezii, from the impacts of extreme temperatures in a southwestern Atlantic rocky intertidal shore. By means of P/P removal experiments and surveys, we illustrate that P/P cover (a) buffers temperatures in the understory mussel beds during daytime air exposure periods in the summer, (b) reduces mussel mortality and leads to increased mussel body condition during warm summer periods, and (c) can prevent mass mortality of mussels during the course of a heat wave. Additionally, by means of a mussel removal experiment we illustrate that mussel cover is critical for P/P establishment, which is in consonance with the remarkably higher P/P densities and cover observed in mussel beds relative to exposed rock surfaces across a ~70 km coastal range. Collectively, these findings reveal a facultative mutualism where mussels provide a favorable substrate for P/P colonization and P/P attenuates heat mediated mortality on mussels. The ability of P/P to enhance the resistance of mussel beds to extreme heat events and the occurrence of similar P/P-mussel associations during spring-summer at globally dispersed sites suggests a widespread importance of P/P for the stability of mussel beds and their associated communities under warming climates.
Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing
Authors: Wang You , Li Ru , Fu Fang , Huang Ruibin , Li Dongzhi , Liao Can
Published: November 2023

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.

Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.

Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.

Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.
Genome-wide association study (GWAS) with high-throughput SNP chip DNA markers identified novel genetic factors for mesocotyl elongation and seedling emergence in rice (Oryza sativa L.) using multiple GAPIT models
Authors: Kabange Nkulu Rolly , Alibu Simon , Kwon Youngho , Lee So-Myeong , Oh Ki-Won , Lee Jong-Hee
Published: November 2023

This study employed a joint strategy high-density SNP Chip DNA markers and multiple Genome Association and Prediction Integrated Tool (GAPIT) models [(Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK), Fixed and random model Circulating Probability Uniform (FarmCPU), General Linear Model (GLM), and Settlement of Mixed Linear Model (MLM) Under Progressively Exclusive Relationship (SUPER)], to investigate novel genetic factors controlling mesocotyl elongation and seedling emergence for direct-seeded rice. Genotype data (230,526 SNP Chip DNA makers) of 117 doubled haploid lines (derived from a cross between 93–11 (Oryza sativa L. ssp. indica) and Milyang352 (O. sativa L. ssp. japonica) were used to perform a Genome-Wide Association Study (GWAS). Results revealed the association between five (5) topmost significant SNP markers, of which number two [AX-155741269, Chr2: 15422406 bp, and AX-155200917, Chr7: 23814085 bp, explaining 37.5% and 13.8% of the phenotypic variance explained (PVE)] are linked to the mesocotyl elongation loci, while three (AX-282097034 and AX-283652873, Chr9: 9882817 bp and 1023383 bp, PVE 64.5%, and 20.2%, respectively, and AX-154356231, Chr1: 17413989 bp, PVE 21.1%) are tightly linked to the loci controlling seedling emergence. The qMEL2-1 and qSEM9-1 are identified as major QTLs explaining 37.5% and 64.5% of the PVE for mesocotyl elongation and seedling emergence, respectively. The AX-282097034 (Chr9: 9882817 bp) was co-detected by four GAPIT models (BLINK, FarmCPU, SUPER, and GLM), while AX-155741269 was co-detected by BLINK and SUPER. Furthermore, a high estimated heritability (Mesocotyl elongation: h2 = 0.955; seedling emergence: h2 = 0.863; shoot length: h2 = 0.707) was observed. Genes harbored by qMEL2-1 and qSEM9-1 have interesting annotated molecular functions that could be investigated through functional studies to uncover their roles during mesocotyl elongation and seedling emergence events in rice. Furthermore, the presence of genes encoding transcription factors, growth- and stress response, or signaling-related genes would suggest that mesocotyl elongation and seedling emergence from deep direct-seeded rice might involve an active signaling cascade and transport of molecules, which could be elucidated through functional analysis. Likewise, genomic selection analysis suggested markers useful for downstream marker-assisted selection (MAS).
Immune checkpoints in rheumatoid arthritis: progress and promise
Authors: Small Annabelle , Lowe Katie , Wechalekar Mihir D.
Published: November 2023

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune inflammatory conditions, and while the mechanisms driving pathogenesis are yet to be completely elucidated, self-reactive T cells and immune checkpoint pathways have a clear role. In this review, we provide an overview of the importance of checkpoint pathways in the T cell response and describe the involvement of these in RA development and progression. We discuss the relationship between immune checkpoint therapy in cancer and autoimmune adverse events, draw parallels with the involvement of immune checkpoints in RA pathobiology, summarise emerging research into some of the lesser-known pathways, and the potential of targeting checkpoint-related pathways in future treatment approaches to RA management.
The capability of heterogeneous γδ T cells in cancer treatment
Authors: Yan Wenyi , Dunmall Louisa S. Chard , Lemoine Nicholas R. , Wang Yaohe , Wang Yafeng , Wang Pengju
Published: November 2023

γδ T cells, a specialized subset of T lymphocytes, have garnered significant attention within the realm of cancer immunotherapy. Operating at the nexus between adaptive and innate immunological paradigms, these cells showcase a profound tumor discernment repertoire, hinting at novel immunotherapeutic strategies. Significantly, these cells possess the capability to directly identify and eliminate tumor cells without reliance on HLA-antigen presentation. Furthermore, γδ T cells have the faculty to present tumor antigens to αβ T cells, amplifying their anti-tumoral efficacy.Within the diverse and heterogeneous subpopulations of γδ T cells, distinct immune functionalities emerge, manifesting either anti-tumor or pro-tumor roles within the tumor microenvironment. Grasping and strategically harnessing these heterogeneous γδ T cell cohorts is pivotal to their integration in tumor-specific immunotherapeutic modalities. The aim of this review is to describe the heterogeneity of the γδ T cell lineage and the functional plasticity it generates in the treatment of malignant tumors. This review endeavors to elucidate the intricate heterogeneity inherent to the γδ T cell lineage, the consequential functional dynamics in combating malignancies, the latest advancements from clinical trials, and the evolving landscape of γδ T cell-based oncological interventions, while addressing the challenges impeding the field.
Regulated necrosis role in inflammation and repair in acute kidney injury
Authors: Guerrero-Mauvecin Juan , Villar-Gómez Natalia , Rayego-Mateos Sandra , Ramos Adrian M. , Ruiz-Ortega Marta , Ortiz Alberto , Sanz Ana B.
Published: November 2023

Acute kidney injury (AKI) frequently occurs in patients with chronic kidney disease (CKD) and in turn, may cause or accelerate CKD. Therapeutic options in AKI are limited and mostly relate to replacement of kidney function until the kidneys recover spontaneously. Furthermore, there is no treatment that prevents the AKI-to-CKD transition. Regulated necrosis has recently emerged as key player in kidney injury. Specifically, there is functional evidence for a role of necroptosis, ferroptosis or pyroptosis in AKI and the AKI-to-CKD progression. Regulated necrosis may be proinflammatory and immunogenic, triggering subsequent waves of regulated necrosis. In a paradigmatic murine nephrotoxic AKI model, a first wave of ferroptosis was followed by recruitment of inflammatory cytokines such as TWEAK that, in turn, triggered a secondary wave of necroptosis which led to persistent kidney injury and decreased kidney function. A correct understanding of the specific forms of regulated necrosis, their timing and intracellular molecular pathways may help design novel therapeutic strategies to prevent or treat AKI at different stages of the condition, thus improving patient survival and the AKI-to-CKD transition. We now review key regulated necrosis pathways and their role in AKI and the AKI-to-CKD transition both at the time of the initial insult and during the repair phase following AKI.
Hippocampal microstructure, but not macrostructure, mediates age differences in episodic memory
Authors: Ibrahim Kirolos , Bennett Ilana J.
Published: November 2023

Introduction

Separate unimodal magnetic resonance imaging (MRI) literatures have shown that hippocampal gray matter macrostructure (volume) and microstructure (diffusion) decline with age and relate to episodic memory performance, with multimodal MRI studies reporting that episodic memory may be better explained by a combination of these metrics. However, these effects are often assessed independent of age or only within older adults and therefore do not address whether these distinct modalities explain variance in (i.e, mediate) the effect of age on episodic memory.

Methods

Here, we simultaneously examined the unique and joint contribution of hippocampal volume and diffusion to age-related differences in episodic memory in 83 younger and 61 older adults who underwent a T1- and diffusion-weighted MRI and completed the Rey Auditory Verbal Learning Test.

Results

As expected, older age was significantly related to smaller volume and higher diffusion (intracellular, dispersion, and free) in bilateral hippocampus and to worse episodic memory performance (immediate and delayed free recall, recognition). Structural equation modelling revealed that the age-memory relationship was significantly mediated by hippocampal diffusion, but not volume. A non-significant influential indirect effect further revealed that the structural metrics did not jointly mediate the age-memory relationship.

Discussion

Together, these findings indicate that hippocampal microstructure uniquely contributes to age-related differences in episodic memory and suggest that volume and diffusion capture distinct neurobiological properties of hippocampal gray matter.
Case report: Dopamine Dysregulation Syndrome, mania, and compulsive buying in a patient with Parkinson's disease
Authors: Silva Carlos , Rebelo Marta , Chendo Inês
Published: November 2023

Neuropsychiatric symptoms and syndromes are among the most common non-motor symptoms of Parkinson's Disease but they are frequently unrecognized and untreated. Dopamine Dysregulation Syndrome is an uncommon complication of the treatment of Parkinson's disease, characterized by an addictive use of dopamine far more than the dosage required for treatment of objective motor impairment, leading to severe dyskinesia, euphoria, aggressivity, or psychosis. We present a paradigmatic case of Dopamine Dysregulation Syndrome, Mania, and Compulsive Buying in a 55-year-old male with Parkinson's Disease. We also reviewed the risk factors and the therapeutic management of Dopamine Dysregulation Syndrome in Parkinson's Disease.
Short-term effects of etifoxine on human gut microbiome in healthy men
Authors: Manook André , Baghai Thomas C. , Riebel Marco , Nothdurfter Caroline , Schwarzbach Jens Volkmar , Gessner André , Rupprecht Rainer , Hiergeist Andreas
Published: November 2023

Background

Neurosteroids have recently gained in interest as a treatment strategy for affective disorders. Etifoxine is known for its dual mode of action, one of which is to stimulate endogenous neurosteroid synthesis. The gut microbiome has been studied in affective disorders, but it has not been investigated in the context of human etifoxine or neurosteroid interventions.

Methods

We performed a crossover study with 36 healthy male volunteers who received etifoxine versus alprazolam and placebo in a balanced Williams design. Participants were randomized into six sequences and went through three 5-day treatments followed by wash-out phases of 9 days. Bacterial compositions in stool samples were determined by high-throughput 16S rRNA amplicon sequencing.

Results

Gut microbiome analyses revealed no relevant effects between treatments with respect to alpha and beta diversity. Differential abundance analyses yielded etifoxine treatment as the only effect related to changes in microbial features with reductions of Faecalibacterium duncaniae, Roseburia hominis and Lactobacillus rogosae (i.e., Bacteroides galacturonicus).

Conclusion

Here we report on the first human investigation of the gut microbiome with short-term etifoxine intervention. Differences in diversity and compositional structure of the microbiome were more likely due to between- subject effects rather than medication. However, five-day treatment with etifoxine reduced the abundance of a few bacterial species. These species are currently seen as beneficial components of a healthy intestinal microbiome. This reduction in abundances may be related to elevated endogenous neurosteroids.
Machine-learning assisted swallowing assessment: a deep learning-based quality improvement tool to screen for post-stroke dysphagia
Authors: Saab Rami , Balachandar Arjun , Mahdi Hamza , Nashnoush Eptehal , Perri Lucas X. , Waldron Ashley L. , Sadeghian Alireza , Rubenfeld Gordon , Crowley Mark , Boulos Mark I. , Murray Brian J. , Khosravani Houman
Published: November 2023

Introduction

Post-stroke dysphagia is common and associated with significant morbidity and mortality, rendering bedside screening of significant clinical importance. Using voice as a biomarker coupled with deep learning has the potential to improve patient access to screening and mitigate the subjectivity associated with detecting voice change, a component of several validated screening protocols.

Methods

In this single-center study, we developed a proof-of-concept model for automated dysphagia screening and evaluated the performance of this model on training and testing cohorts. Patients were admitted to a comprehensive stroke center, where primary English speakers could follow commands without significant aphasia and participated on a rolling basis. The primary outcome was classification either as a pass or fail equivalent using a dysphagia screening test as a label. Voice data was recorded from patients who spoke a standardized set of vowels, words, and sentences from the National Institute of Health Stroke Scale. Seventy patients were recruited and 68 were included in the analysis, with 40 in training and 28 in testing cohorts, respectively. Speech from patients was segmented into 1,579 audio clips, from which 6,655 Mel-spectrogram images were computed and used as inputs for deep-learning models (DenseNet and ConvNext, separately and together). Clip-level and participant-level swallowing status predictions were obtained through a voting method.

Results

The models demonstrated clip-level dysphagia screening sensitivity of 71% and specificity of 77% (F1 = 0.73, AUC = 0.80 [95% CI: 0.78–0.82]). At the participant level, the sensitivity and specificity were 89 and 79%, respectively (F1 = 0.81, AUC = 0.91 [95% CI: 0.77–1.05]).

Discussion

This study is the first to demonstrate the feasibility of applying deep learning to classify vocalizations to detect post-stroke dysphagia. Our findings suggest potential for enhancing dysphagia screening in clinical settings. https://github.com/UofTNeurology/masa-open-source.
Association of dietary live microbe intake with abdominal aortic calcification in US adults: a cross-sectional study of NHANES 2013–2014
Authors: Huo Xingwei , Jia Shanshan , Zhang Xin , Sun Lirong , Liu Xueting , Liu Lu , Zuo Xianghao , Chen Xiaoping
Published: November 2023

Object

To explore the potential association between dietary live microbe intake and abdominal aortic calcification (AAC).

Methods

We conducted a cross-section study based on the National Health and Nutrition Examination Survey (NHANES). We categorized the participants into three groups (low, medium, and high dietary intake of live microbes) according to Sanders’s dietary live microbe classification system and participants’ 24-h dietary recall data. AAC was quantified by using dual-energy X-ray absorptiometry (DXA) and diagnosed by using the Kauppila AAC-24 score system. The analyses utilized weighted logistic regression and weighted linear regression.

Results

A total of 2,586 participants were included. After the full adjustment for covariates, compared to participants with a low dietary live microbe intake, participants with a high dietary live microbe intake had a significantly lower risk of severe AAC (OR: 0.39, 95% CI: 0.22, 0.68, p = 0.003), and the AAC score was also significantly decreased (β:−0.53, 95% CI: −0.83, −0.23, p = 0.002).

Conclusion

In this study, more dietary live microbial intake was associated with lower AAC scores and a lower risk of severe AAC. However, more research is needed to verify this.
Diet-driven microbiome changes and physical activity in cancer patients
Authors: Ciernikova Sona , Sevcikova Aneta , Stevurkova Viola , Mego Michal
Published: November 2023

Exploring the role of the gut microbiome in oncology is gaining more attention, mainly due to its ability to shape the immune system in cancer patients. A well-balanced microbial composition forms a symbiotic relationship with the host organism. Mounting evidence supports the potential of modifiable lifestyle factors, such as diet and physical activity, in restoring intestinal dysbiosis related to cancer development and treatment. In this Minireview, we describe the host-microbiome interplay following different dietary patterns, including a high-fat diet, fiber-rich diet, diet rich in rice and beans, Mediterranean diet, ketogenic diet, and physical activity in preclinical findings and clinical settings. According to the results, nutrition is a critical factor influencing the composition of gut microbial communities. Therefore, knowledge about the patient’s nutritional status in pre-treatment and treatment becomes crucial for further management. A combination of individualized dietary habits and professional training plans might help to maintain gut homeostasis, potentially improving the response to anti-cancer therapy and the quality of life in cancer survivors. However, a deep understanding of underlying mechanisms and large clinical trials are needed to uncover clinically relevant correlations for personalized treatment approaches leading to better outcomes for cancer patients.
High resting energy expenditure in women with episodic migraine: exploring the use of predictive formulas
Authors: Martins Laís Bhering , Ribeiro Jéssica Sales , Rodrigues Ana Maria dos Santos , Santos Luana Caroline dos , Teixeira Antonio Lúcio , Ferreira Adaliene Versiani Matos
Published: November 2023

Introduction

Migraine is a common and disabling primary headache, and its pathophysiology is not fully understood. Previous studies have suggested that pain can increase humans’ Resting Energy Expenditure (REE). However, no previous study has investigated whether the REE of individuals with migraine differs from the general population. Therefore, this study aims to assess whether the REE of women with migraine differs from that of women without headaches. We also tested the accuracy of REE predictive formulas in the migraine patients.

Methods

This cross-sectional study involves 131 adult women aged between 18 and 65 years, 83 with migraine and 48 without (controls). We collected clinical, demographic, and anthropometric data. Migraine severity was measured using the Migraine Disability Test and Headache Impact Test, version 6. The REE was measured by indirect calorimetry, and it was compared with the predicted REE calculated by formulas.

Results

Patients with migraine had higher REE when compared to controls (p < 0.01). There was a positive correlation between REE and the patient-reported number of migraine attacks per month (Rho = 0.226; p = 0.044). Mifflin-St Jeor and Henry and Rees were the predictive formulas that have more accuracy in predicting REE in women with migraine.

Discussion

Considering the benefits of nutritional interventions on treating migraines, accurately measuring REE can positively impact migraine patient care. This study enhances our understanding of the relationship between pain and energy expenditure. Our results also provide valuable insights for healthcare professionals in selecting the most effective predictive formula to calculate energy expenditure in patients with migraine.
TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial
Authors: Wan Juefeng , Wu Ruiyan , Fu Miaomiao , Shen Lijun , Zhang Hui , Wang Yan , Wang Yaqi , Zhou Shujuan , Chen Yajie , Xia Fan , Zhang Zhen
Published: November 2023

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%–50%. Additionally, only approximately 40%–50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25–40 Gy/5 Fx irradiation or 15–30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients.

Clinical trial registration

https://clinicaltrials.gov/study/NCT05628038, identifier NCT05628038.
The systematic review and meta-analysis evaluated the efficacy and safety of nefopam for catheter-related bladder discomfort based on randomized controlled trials
Authors: Chi Junpeng , Wu Jinhui , Lou Keyuan , Ma Jian , Wu Jitao , Cui Yuanshan
Published: November 2023

Background: Catheter-related bladder discomfort (CRBD) is a frequent occurrence following urinary catheterization during surgical procedures, as well as a commonly experienced bladder pain syndrome after surgery. There have been various studies on drugs and interventions to manage CRBD, but their comparative efficacy and safety are still a topic of debate. We conducted a meta-analysis to assess the efficacy and safety of nefopam for managing postoperative CRBD.

Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to find randomized controlled trials (RCTs) on using nefopam in postoperative CRBD. The study employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data analysis was performed using RevMan version 5.4.1.

Results: Five RCTs with 405 patients were analyzed to evaluate the efficacy of nefopam on postoperative CRBD. Short-term and long-term periods were defined as within 6 h and longer than 12 h after surgery, respectively. The incidence and severity of CRBD were compared between the two groups during these time periods. The analysis proved that nefopam reduced the short-term incidence of postoperative CRBD (RR 0.36; 95% CI, 0.18–0.70; p = 0.003, I2 = 78%) and the long-term incidence (RR 0.49; 95% CI, 0.32–0.74; p = 0.0007, I2 = 0%) significantly. We compared the incidence of moderate-to-severe CRBD between groups based on the scaling system (none, mild, moderate, and severe). This was used to assess the severity of postoperative CRBD. The results showed that patients in the nefopam group had a significantly lower incidence of moderate-to-severe CRBD compared to those in the placebo group in the short-term (RR 0.19; 95% CI, 0.10–0.34; p < 0.00001; I2 = 0%). However, there were no significant differences between the two groups in the incidence of moderate-to-severe CRBD in the long-term (RR 0.61; 95% CI, 0.21–1.76; p = 0.36; I2 = 0%). There were no significant variations in the occurrence of adverse events between the nefopam and control groups, mainly including postoperative nausea and vomiting (PONV) (RR 1.14; 95% CI, 0.40–3.21; p = 0.81), and tachycardia (RR 0.25; 95% CI, 0.03–2.11, p = 0.20).

Conclusion: The findings of this meta-analysis indicate that nefopam significantly reduced the incidence of short or long-term postoperative CRBD. Nefopam decreased the severity of postoperative CRBD, particularly significantly reducing the occurrence of moderate to severe CRBD in the short-term. Overall, patients have good tolerance and no apparent side effects.

Systematic Review Registration: identifier PROSPERO (CRD42023475012)