bluuebunny/crossref_metadata_2025 huggingface dataset:
Insular functional connectivity in migraine with aura
Authors: Gollion Cédric , Lerebours Fleur , Nemmi Federico , Arribarat Germain , Bonneville Fabrice , Larrue Vincent , Péran Patrice
Published: August 2022

Introduction

Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.

Methods

Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.

Results

Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.

Discussion

The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.

Conclusion

The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.

Trial registration

NCT02708797.
Length-Dependent Photoelectric Property of ZnO Nanowires
Authors: Ren Ren , Ren Xiaomin , Liu Hao , Huang Yongqing , Yuan Weifang
Published: August 2022

An interesting phenomenon that the photocurrent (the difference between illumination and dark current) of a ZnO nanowire (NW) under a specified voltage increased as its length increased in a certain range was observed previously and it was supposed to be mainly due to a special mean free path effect (MFPE) which caused a special distribution of dark electron density along the length with two higher electron density regions near the two ends of the NW, respectively, and the lower one in the middle part. However, such an explanation would be unreasonable and the true reasons should be the growing-process caused variation of the oxygen adsorption capacity along the NW length and the length-dependent lifetime of photogenerated carriers. Based on this understanding, a theoretical model to properly explain this phenomenon is proposed and the calculation results are in good agreement with the experimental data. This work has introduced an improved insight into the theory of the length-dependent photoelectric property of ZnO NWs.
RNAi-mediated knockdown of gut receptor-like genes prohibitin and α-amylase altered the susceptibility of Galleria mellonella to Cry1AcF toxin
Authors: Dutta Tushar K. , Mandal Abhishek , Kundu Artha , Phani Victor , Mathur Chetna , Veeresh Arudhimath , Sreevathsa Rohini
Published: August 2022

Background

Due to the prolonged usage of Bt-based biopesticides and Bt-transgenic crops worldwide, insects are continually developing resistance against Cry toxins. This resistance may occur if any mechanistic step in the insecticidal process is disrupted possibly because of the alteration in Cry-receptor binding affinity due to mutation in receptor genes. Compared to other lepidopteran insects, Cry receptor-related research has made asymmetric progress in the model insect Galleria mellonella.

Results

Present study describes the molecular characterization and functional analysis of five Cry toxin receptor-related genes (prohibitin, GLTP, α-amylase, ADAM and UDP-GT) and a gut repair gene (arylphorin) from the gut tissues of G. mellonella. Protein–protein docking analysis revealed that Cry1AcF putatively binds with all the five candidate proteins, suggesting their receptor-like function. These receptor-like genes were significantly overexpressed in the gut tissues of fourth-instar G. mellonella larvae upon early exposure to a sub-lethal dose of Cry1AcF toxin. However, targeted knockdown (by using bacterially-expressed dsRNAs) of these genes led to variable effect on insect susceptibility to Cry1AcF toxin. Insects pre-treated with prohibitin and α-amylase dsRNA exhibited significant reduction in Cry1AcF-induced mortality, suggesting their probable role as Cry receptor. By contrast, insects pre-treated with GLTP, ADAM and UDP-GT dsRNA exhibited no significant decline in mortality. This maybe explained by the possibility of RNAi feedback regulation (as few of the receptors belong to multigene family) or redundant role of GLTP, ADAM and UDP-GT in Cry intoxication process.

Conclusion

Since the laboratory culture of G. mellonella develop Bt resistance quite rapidly, findings of the current investigation may provide some useful information for future Cry receptor-related research in the model insect.
The insoluble excretion of multi-matrix system mesalazine preparations in patients with ulcerative colitis
Authors: Ohtaki Yuichiro , Uchiyama Kan , Kamiya Hirotaka , Moriizumi Eri , Yamada Moe , Aoki Yuma , Watanabe Toshimune , Kiryu Sachie , Suzuki Shizuka , Matsumoto Yoshihiro , Ito Zensho , Ohkusa Toshifumi , Koido Shigeo , Saruta Masayuki
Published: August 2022

Background

Multi-matrix mesalazine (MMX) is an important treatment for ulcerative colitis (UC); however, it is often excreted intact, which increases the risk of relapse. This study aimed to clarify the risk factors for insoluble MMX excretion.

Methods

The subjects were 102 UC patients who were newly prescribed MMX alone to induce remission. Their stools were evaluated on the Bristol Stool Form Scale (BSFS), the presence/absence of insoluble MMX excretion was investigated in interviews, and defecation frequency at the start of treatment and disease type were retrospectively investigated by examining their medical records.

Results

The insoluble excretion rate (IER) was 14.7%. It tended to be higher in the patients with left-sided colitis or extensive colitis, although the differences among the disease types were not significant (p = 0.053). The mean defecation frequency of the patients that reported insoluble MMX excretion was significantly higher than that of the patients that did not report it (6.27 ± 5.28 vs. 3.69 ± 3.17, p < 0.05). The IER tended to be higher among the patients with soft stools (4.5%, 21.9%, and 23.1% in those with BSFS scores of ≤ 4, 5, and ≥ 6, respectively). In ROC analysis of defecation frequency, ≥ 3.5 defecations was found to exhibit sensitivity and specificity of 66.7% and 65.5%, respectively, for predicting insoluble MMX excretion.

Conclusions

The likelihood of insoluble MMX excretion is influenced by defecation frequency and the extent of inflammation. It is important to keep the possibility of insoluble excretion in mind when prescribing MMX.
Perception of dignity in older men and women in the early stages of dementia: a cross-sectional study
Authors: Klůzová Kráčmarová Lucie , Tomanová Jitka , Černíková Kristýna A. , Tavel Peter , Langová Kateřina , Greaves Peta Jane , Kisvetrová Helena
Published: August 2022

Background

Dementia is a serious problem in old age, that impacts an individual’s ability to function and may threaten personal dignity. Given the variable features of the illness and the diversity of life experiences, many factors may contribute to the perception of dignity by men and women with dementia. The purpose of the study was to explore the factors that contribute to dignity and its domains in men and women with dementia.

Methods

This cross-sectional study involved 316 community-dwelling patients with early-stage dementia (aged ≥ 60) (PwD). We assessed the participants’ sociodemographic and social involvement characteristics, health-related variables (pain, depression, physical performance, visual and hearing impairments), attitude to aging, and self-sufficiency in the activities of daily living (ADL). These factors were investigated as independent variables for the perception of dignity and of its domains in men and women.

Results

Multivariate regression analysis showed that PwD experienced minor dignity problems in the early stages of dementia. In both men and women higher rates of depression, negative attitudes to aging, and pain were associated with reductions in the perception of dignity. In men, but not in women visual impairment had a negative effect on overall dignity, and on the associated domains of ‘Loss of Autonomy’ and ‘Loss of Confidence’. In women, lowered self-sufficiency in ADL contributed to reduced self-perception of dignity and in the associated domains of ‘Loss of Purpose of Life’, ‘Loss of Autonomy’, and ‘Loss of Confidence’. Sociodemographic and social involvement characteristics, hearing impairment, and physical performance did not influence the participants’ self-perception of dignity.

Conclusion

The results suggested that several common factors (depression, attitudes to aging, and pain) contribute to the perception of dignity in both men and women. Other factors, visual impairments in men, and self-sufficiency in ADL in women, appear to be more gender specific. These differences might relate to their specific gender roles and experiences. The self-perception of dignity in PwD can be helped by supporting the individual, to the extent that their illness allows, in maintaining activities that are important to their gender roles, and that preserve their gender identity.

Trial registration

NCT04443621.
Association between urinary sodium excretion and hard outcomes in non-dialysis chronic kidney disease patients
Authors: Cury Cecília Malheiro , Banin Vanessa Burgugi , dos Reis Pamela Falbo , Caramori Jacqueline Costa Teixeira , Barretti Pasqual , de Andrade Luís Gustavo Modelli , Martin Luis Cuadrado
Published: August 2022

Background

Restriction of sodium intake is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains uncertain. We evaluated the association between urinary sodium excretion (as a surrogate for sodium intake) with the occurrence of renal failure and mortality in patients with non-dialytic CKD.

Methods

We conducted a retrospective study of patients followed at a CKD clinic care hospital from October 2006 to March 2017. Adult patients with non-dialytic CKD were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a categorical variable (categorized as quintiles: 1st quintile: 0.54–2.51 g; 2nd quintile: 2.52–3.11 g, 3rd quintile: 3.12–3.97 g, 4th quintile: 3.98–5.24 g and 5th quintile: 5.26–13.80 g) and the outcomes of interest. The primary outcome was defined as progression to end-stage renal disease requiring any type of renal replacement therapy. The secondary outcome was mortality.

Results

Two hundred five patients were included in the study (mean follow up of 2.6 years) with a mean eGFR of 26 (19–41) ml/min/1.73m2. 37 patients (18%) required renal replacement therapy and 52 (25,3%) died. There was association between urinary sodium excretion and need for renal replacement therapy (adjusted HR 0.245; 95%CI 0.660–0.912). There was no association between urinary sodium excretion and mortality in adjusted models.

Conclusion

Moderate sodium intake was associated with a lower risk of renal failure.
CDC50A might be a novel biomarker of epithelial ovarian cancer-initiating cells
Authors: Yin Jie , Wen Yiping , Zeng Jing , Zhang Yanyan , Chen Jiayu , Zhang Yanmei , Han Tiantian , Li Xiaoying , Huang Hong , Cai Yan , Jin Ying , Li Yan , Guo Wei , Pan Lingya
Published: August 2022

Background

The aim of this work was to screen and validate biomarkers of ovarian cancer-initiating cells to detect the mechanisms of recurrence of epithelial ovarian cancer (EOC).

Methods

Stably labelled the amino acid in side population (SP) cells of epithelial ovarian cancer which were rich in cancer-initiating cells and non-SP cells with isotope in culture and differentially expressed cellular membrane proteins in SP cells were identified through proteomics technology. The new candidate biomarker was screened and validated through RT-PCR and western blot. Both in cell lines and primary EOC, cancer-initiating biofunctions of CDC50A positive cells were validated. Moreover, the characteristics of mesenchymal transition (EMT) was also detected and the correlation between the biomarker and clinical prognosis was observed.

Results

Through proteomics technology, candidate protein CDC50A was screened, and its significantly differential expression in SP cells was validated. CDC50A-positive cells from cell lines and primary ovarian cancer tissues were validated to show characteristics of cancer-initiating cells both in vitro and in vivo, including sphere-forming, self-renewal, differentiation, tumor metastasis and tumorigenicity in mice. The relationship between CDC50A-positive cells from primary tissues and tumour metastasis was confirmed based on their mesenchymal transition characteristics. Among 16 high-grade ovarian serous cancer patients, a high ratio of CDC50A-positive cells in primary tumours was correlated with a shorter platinum-free interval (p = 0.031, HR 0.260, 95% CI 0.77 ~ 0.885).

Conclusion

CDC50A could be used to screen ovarian cancer-initiating cells and might be a new target to resolve tumour development in EOC patients.
Environmental health influences in pregnancy and risk of gestational diabetes mellitus: a systematic review
Authors: Eberle Claudia , Stichling Stefanie
Published: August 2022

Background

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications globally. Environmental risk factors may lead to increased glucose levels and GDM, which in turn may affect not only the health of the mother but assuming hypotheses of "fetal programming", also the health of the offspring. In addition to traditional GDM risk factors, the evidence is growing that environmental influences might affect the development of GDM. We conducted a systematic review analyzing the association between several environmental health risk factors in pregnancy, including climate factors, chemicals and metals, and GDM.

Methods

We performed a systematic literature search in Medline (PubMed), EMBASE, CINAHL, Cochrane Library and Web of Science Core Collection databases for research articles published until March 2021. Epidemiological human and animal model studies that examined GDM as an outcome and / or glycemic outcomes and at least one environmental risk factor for GDM were included.

Results

Of n = 91 studies, we classified n = 28 air pollution, n = 18 persistent organic pollutants (POP), n = 11 arsenic, n = 9 phthalate n = 8 bisphenol A (BPA), n = 8 seasonality, n = 6 cadmium and n = 5 ambient temperature studies. In total, we identified two animal model studies. Whilst we found clear evidence for an association between GDM and air pollution, ambient temperature, season, cadmium, arsenic, POPs and phthalates, the findings regarding phenols were rather inconsistent. There were clear associations between adverse glycemic outcomes and air pollution, ambient temperature, season, POPs, phenols, and phthalates. Findings regarding cadmium and arsenic were heterogeneous (n = 2 publications in each case).

Conclusions

Environmental risk factors are important to consider in the management and prevention of GDM. In view of mechanisms of fetal programming, the environmental risk factors investigated may impair the health of mother and offspring in the short and long term. Further research is needed.
Associations between consumption of three types of beverages and risk of cardiometabolic multimorbidity in UK Biobank participants: a prospective cohort study
Authors: Luo Yi , He Lingfang , Ma Tianqi , Li Jinchen , Bai Yongping , Cheng Xunjie , Zhang Guogang
Published: August 2022

Background

Although the association between beverages and a single cardiometabolic disease has been well studied, their role in disease progression from the single cardiometabolic disease state to cardiometabolic multimorbidity (CMM) state remains unclear. This study examined the associations between three types of beverages: sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and pure fruit/vegetable juices, and the incidence of CMM in patients with a single cardiometabolic disease.

Methods

Our analysis included 37,994 participants from the UK Biobank who completed at least one dietary questionnaire and were diagnosed with only one cardiometabolic disease at the time of recruitment. Competing risk models were used to examine the association between the three types of beverages and incidence of CMM. We conducted analysis both in patients with any single cardiometabolic disease and in patients with specific cardiometabolic disease.

Results

During a median follow-up of 9.1 years (interquartile range [IQR] 9.0–9.8), a total of 6399 participants developed CMM. The consumption of SSBs and ASBs (>1 serving per day) was associated with a higher risk of CMM (SSBs: hazard ratio [HR] 1.19, 95% confidence interval [95% CI] 1.08–1.31; ASBs: HR 1.15, 95% CI 1.04–1.27). Intake of pure fruit/vegetable juices was inversely associated with the incidence of CMM (0–1 serving per day: HR 0.90, 95% CI 0.85–0.94; >1 serving per day: HR 0.90, 95% CI 0.81–0.99). However, the association of the high-level consumption of pure fruit/vegetable juices (>1 serving per day) was not statistically significant after correcting for multiple testing. In the analysis of patients with specific cardiometabolic diseases, positive associations were observed in patients with hypertension for SSBs consumption, while inverse associations persisted in patients with cardiovascular disease (coronary heart disease or stroke) and in hypertensive patients for pure fruit/vegetable juice consumption.

Conclusions

Consuming >1 serving of SSBs and ASBs per day was associated with a higher risk of CMM in patients with a single cardiometabolic disease. In contrast, intake of pure fruit/vegetable juices was inversely associated with the risk of CMM. Our findings highlight the need to limit the use of SSBs and ASBs in patients with a single cardiometabolic disease.
Molecular effects of the consumption of margarine and butter varying in trans fat composition: a parallel human intervention study
Authors: Guggisberg Dominik , Burton-Pimentel Kathryn J. , Walther Barbara , Badertscher René , Blaser Carola , Portmann Reto , Schmid Alexandra , Radtke Thomas , Saner Hugo , Fournier Nadine , Bütikofer Ueli , Vergères Guy
Published: August 2022

Background

Whereas the dietary intake of industrialtransfatty acids (iTFA) has been specifically associated with inflammation, cardiovascular disease, and type 2 diabetes, understanding the impact of dietary fats on human health remains challenging owing to their complex composition and individual effects of their lipid components on metabolism. The aim of this study is to profile the composition of blood, measured by the fatty acid (FAs) profile and untargeted metabolome of serum and the transcriptome of blood cells, in order to identify molecular signatures that discriminate dietary fat intakes.

Methods

In a parallel study, the molecular effects of consuming dairy fat containing ruminant TFA (rTFA) or margarine containing iTFA were investigated. Healthy volunteers (n = 42; 45–69 y) were randomly assigned to diets containing margarine without TFA as major source of fat (wTFA control group with 0.4 g TFA per 100 g margarine), margarine with iTFA (iTFA group with 4.1 g TFA per 100 g margarine), or butter with rTFA (rTFA group with 6.3 g TFA per 100 g butter) for 4 weeks. The amounts of test products were individually selected so that fat intake contributed to 30–33% of energy requirements and TFA in the rTFA and iTFA groups contributed to up to 2% of energy intake. Changes in fasting blood values of lipid profiles (GC with flame-ionization detection), metabolome profiles (LC-MS, GC-MS), and gene expression (microarray) were measured.

Results

Eighteen FAs, as well as 242 additional features measured by LC-MS (185) and GC-MS (54) showed significantly different responses to the diets (PFDR-adjusted < 0.05), mainly distinguishing butter from the margarine diets while gene expression was not differentially affected. The most abundant TFA in the butter, i.e. TFA containing (E)-octadec-11-enoic acid (C18:1 t11;transvaccenic acid), and margarines, i.e. TFA containing (E)-octadec-9-enoic acid (C18:1 t9; elaidic acid) were reflected in the significantly different serum levels of TFAs measured after the dietary interventions.

Conclusions

The untargeted serum metabolome differentiates margarine from butter intake although the identification of the discriminating features remains a bottleneck. The targeted serum FA profile provides detailed information on specific molecules differentiating not only butter from margarine intake but also diets with different content of iTFAs in margarine.

Trial registration

ClinicalTrials.gov NCT00933322.
Syntaxin interacts with arachidonic acid to prevent diabetes mellitus
Authors: Das Undurti N.
Published: August 2022

Syntaxin regulates pancreatic β cell mass and participates in insulin secretion by regulating insulin exocytosis. In addition, syntaxin 4 reduces IFNγ and TNF-α signaling via NF-ĸB in islet β-cells that facilitates plasma glucose sensing and appropriate insulin secretion. Arachidonic acid (AA) has potent anti-inflammatory actions and prevents the cytotoxic actions of alloxan and streptozotocin (STZ) against pancreatic β cells and thus, prevents the development of type 1 diabetes mellitus (induced by alloxan and STZ) and by virtue of its anti-inflammatory actions protects against the development of type 2 diabetes mellitus (DM) induced by STZ in experimental animals that are models of type 1 and type 2 DM in humans. AA has been shown to interact with syntaxin and thus, potentiate exocytosis. AA enhances cell membrane fluidity, increases the expression of GLUT and insulin receptors, and brings about its anti-inflammatory actions at least in part by enhancing the formation of its metabolite lipoxin A4 (LXA4). Prostaglandin E2 (PGE2), the pro-inflammatory metabolite of AA, activates ventromedial hypothalamus (VMH) neurons of the hypothalamus and inhibits insulin secretion leading to reduced glucose tolerance and decreases insulin sensitivity in the skeletal muscle and liver. This adverse action of PGE2 on insulin release and action can be attributed to its (PGE2) pro-inflammatory action and inhibitory action on vagal tone (vagus nerve and its principal neurotransmitter acetylcholine has potent anti-inflammatory actions). High fat diet fed animals have hypothalamic inflammation due to chronic elevation of PGE2. Patients with type 2 DM show low plasma concentrations of AA and LXA4 and elevated levels of PGE2. Administration of AA enhances LXA4 formation without altering or reducing PGE2 levels and thus, tilts the balance more towards anti-inflammatory events. These results suggest that administration of AA is useful in the prevention and management of DM by enhancing the action of syntaxin, increasing cell membrane fluidity, and reducing VMH inflammation. Docosahexaenoic acid (DHA) has actions like AA: it increases cell membrane fluidity; has anti-inflammatory actions by enhancing the formation of its anti-inflammatory metabolites resolvins, protectins and maresins; interacts with syntaxin and enhance exocytosis in general and of insulin. But the DHA content of cell membrane is lower compared to AA and its content in brain is significant. Hence, it is likely DHA is important in neurotransmitters secretion and regulating hypothalamic inflammation. It is likely that a combination of AA and DHA can prevent DM.
Pregnancy loss and subsequent risk of prediabetes, diabetes and metabolic syndrome in couples: Tehran lipid and glucose study
Authors: Rahmati Maryam , Saei Ghare Naz Marzieh , Azizi Fereidoun , Ramezani Tehrani Fahimeh
Published: August 2022

Background

There is limited evidence regarding the impact of pregnancy loss on the subsequent risk of metabolic disorders. We aimed to investigate whether history of pregnancy loss is associated with the subsequent risk of prediabetes (pre-DM), diabetes (DM), and metabolic syndrome (METs) among couples.

Method

In this population-based cohort study, 2765 couples with and without history of pregnancy loss and free of DM, pre-DM, and METs at baseline were included and followed for incidents of DM, pre-DM, and METs by 3-year intervals visits from 1999 to 2018. Detailed data of variables was collected using standard questionnaires, interviews, clinical and laboratory assessments. A modified Poisson regression for binary outcome data with a log link function and robust error variance was used to estimate relative risks (RRs) in couples with and without history of pregnancy loss. Both unadjusted and adjusted models were fitted, and effect measures were calculated.

Result

During a median follow-up of 15 years, females with history of pregnancy loss were experienced more pre-DM (50% vs. 45.5%), DM (28.9% vs. 21.3%), and METs (70% vs. 60.1%) than females without such history. Moreover, history of pregnancy loss increased the risk of METs by 8% among females. The incidence of DM in males with history of pregnancy loss in their spouses was higher than in males without it (28.8% vs. 23.5%). Among males, having a spouse with history of pregnancy loss was positively associated with the risk of pre-DM (RR = 1.12; 95%CI: 1.02, 1.23, p = 0.02); furthermore, they were more prone to the risk of METs than females with a history of pregnancy loss (RR = 1.13; 95%CI: 1.07, 1.20, p < 0.001).

Conclusion

Although pregnancy loss is a female-specific factor, may foreshadow the subsequent METs, our study identified a higher risk of subsequent pre-DM and METs in males with history of pregnancy loss in their spouses. Pregnancy loss could be considered a possible future risk factor for metabolic disorders in couples.
Super-enhancer hijacking LINC01977 promotes malignancy of early-stage lung adenocarcinoma addicted to the canonical TGF-β/SMAD3 pathway
Authors: Zhang Te , Xia Wenjie , Song Xuming , Mao Qixing , Huang Xing , Chen Bing , Liang Yingkuan , Wang Hui , Chen Yuzhong , Yu Xinnian , Zhang Zeyu , Yang Wenmin , Xu Lin , Dong Gaochao , Jiang Feng
Published: August 2022

Background

Lung adenocarcinoma (LUAD) is the leading cause of death worldwide. However, the roles of long noncoding RNAs (lncRNAs) hijacked by super-enhancers (SEs), vital regulatory elements of the epigenome, remain elusive in the progression of LUAD metastasis.

Methods

SE-associated lncRNA microarrays were used to identify the dysregulated lncRNAs in LUAD. ChIP-seq, Hi-C data analysis, and luciferase reporter assays were utilized to confirm the hijacking of LINC01977 by SE. The functions and mechanisms of LINC01977 in LUAD were explored by a series of in vitro and in vivo assays.

Results

We found that LINC01977, a cancer-testis lncRNA, was hijacked by SE, which promoted proliferation and invasion both in vitro and in vivo. LINC01977 interacted with SMAD3 to induce its nuclear transport, which facilitated the interaction between SMAD3 and CBP/P300, thereby regulating the downstream target gene ZEB1. Additionally, SMAD3 up-regulated LINC09177 transcription by simultaneously binding the promoter and SE, which was induced by the infiltration of M2-like tumor-associated macrophages (TAM2), subsequently activating the TGF-β/SMAD3 pathway. Moreover, LINC01977 expression was positively correlated with TAM2 infiltration and SMAD3 expression, especially in early-stage LUAD. Higher chromatin accessibility in the SE region of LINC01977 was observed with high expression of TGF-β. Early-stage LUAD patients with high LIN01977 expression had a shorter disease-free survival.

Conclusions

TAM2 infiltration induced a rich TGF-β microenvironment, activating SMAD3 to bind the promoter and the SE of LINC01977, which up-regulated LINC01977 expression. LINC01977 also promoted malignancy via the canonical TGF-β/SMAD3 pathway. LINC01977 hijacked by SE could be a valuable therapeutic target, especially for the treatment of early-stage LUAD.
The central and biodynamic role of gut microbiota in critically ill patients
Authors: Wozniak Hannah , Beckmann Tal Sarah , Fröhlich Lorin , Soccorsi Tania , Le Terrier Christophe , de Watteville Aude , Schrenzel Jacques , Heidegger Claudia-Paula
Published: August 2022

Gut microbiota plays an essential role in health and disease. It is constantly evolving and in permanent communication with its host. The gut microbiota is increasingly seen as an organ, and its failure, reflected by dysbiosis, is seen as an organ failure associated with poor outcomes. Critically ill patients may have an altered gut microbiota, namely dysbiosis, with a severe reduction in “health-promoting” commensal intestinal bacteria (such as Firmicutes or Bacteroidetes) and an increase in potentially pathogenic bacteria (e.g. Proteobacteria). Many factors that occur in critically ill patients favour dysbiosis, such as medications or changes in nutrition patterns. Dysbiosis leads to several important effects, including changes in gut integrity and in the production of metabolites such as short-chain fatty acids and trimethylamine N-oxide. There is increasing evidence that gut microbiota and its alteration interact with other organs, highlighting the concept of the gut–organ axis. Thus, dysbiosis will affect other organs and could have an impact on the progression of critical diseases. Current knowledge is only a small part of what remains to be discovered. The precise role and contribution of the gut microbiota and its interactions with various organs is an intense and challenging research area that offers exciting opportunities for disease prevention, management and therapy, particularly in critical care where multi-organ failure is often the focus. This narrative review provides an overview of the normal composition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlights the concept of the gut–organ axis.
uSing rolE-substitutioN In care homes to improve ORal health (SENIOR): a study protocol
Authors: McKenna Gerald , Tsakos Georgios , Watson Sinead , Jenkins Alison , Algar Patricia Masterson , Evans Rachel , Baker Sarah R. , Chestnutt Ivor G. , Smith Craig J. , O’Neill Ciaran , Hoare Zoe , Williams Lynne , Jones Vicki , Donaldson Michael , Karki Anup , Lappin Caroline , Moons Kirstie , Sandom Fiona , Wimbury Mary , Morgan Lorraine , Shepherd Karen , Brocklehurst Paul
Published: August 2022

Background

Dental service provision in the care home sector is poor, with little emphasis on prevention. Emerging evidence suggests that the use of Dental Care Professionals (dental therapists and dental nurses) as an alternative to dentists has the potential to improve preventive advice, the provision of care and access to services within care homes. However, robust empirical evidence from definitive trials on how to successfully implement and sustain these interventions within care homes is currently lacking. The aim of the study is to determine whether Dental Care Professionals could reduce plaque levels of dentate older adults (65 + years) residing in care homes.

Methods

This protocol describes a two-arm cluster-randomised controlled trial that will be undertaken in care homes across Wales, Northern Ireland and England. In the intervention arm, the dental therapists will visit the care homes every 6 months to assess and then treat eligible residents, where necessary. All treatment will be conducted within their Scope of Practice. Dental nurses will visit the care homes every month for the first 3 months and then three-monthly afterwards to promulgate advice to improve the day-to-day prevention offered to residents by carers. The control arm will be ‘treatment as usual’.

Eligible care homes (n = 40) will be randomised based on a 1:1 ratio (20 intervention and 20 control), with an average of seven residents recruited in each home resulting in an estimated sample of 280. Assessments will be undertaken at baseline, 6 months and 12 months and will include a dental examination and quality of life questionnaires. Care home staff will collect weekly information on the residents’ oral health (e.g. episodes of pain and unscheduled care). The primary outcome will be a binary classification of the mean reduction in Silness-Löe Plaque Index at 6 months. A parallel process evaluation will be undertaken to explore the intervention’s acceptability and how it could be embedded in standard practice (described in a separate paper), whilst a cost-effectiveness analysis will examine the potential long-term costs and benefits of the intervention.

Discussion

This trial will provide evidence on how to successfully implement and sustain a Dental Care Professional-led intervention within care homes to promote access and prevention.

Trial registration

ISRCTN16332897. Registered on 3 December 2021.
Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data
Authors: Conca Francesca , Esposito Valentina , Rundo Francesco , Quaranta Davide , Muscio Cristina , Manenti Rosa , Caruso Giulia , Lucca Ugo , Galbussera Alessia Antonella , Di Tella Sonia , Baglio Francesca , L’Abbate Federica , Canu Elisa , Catania Valentina , Filippi Massimo , Mattavelli Giulia , Poletti Barbara , Silani Vincenzo , Lodi Raffaele , De Matteis Maddalena , Stanzani Maserati Michelangelo , Arighi Andrea , Rotondo Emanuela , Tanzilli Antonio , Pace Andrea , Garramone Federica , Cavaliere Carlo , Pardini Matteo , Rizzetto Cristiano , Sorbi Sandro , Perri Roberta , Tiraboschi Pietro , Canessa Nicola , Cotelli Maria , Ferri Raffaele , Weintraub Sandra , Marra Camillo , Tagliavini Fabrizio , Catricalà Eleonora , Cappa Stefano Francesco
Published: August 2022

Background

Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer’s disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue.

Methods

Following the initiative of the University of Washington’s National Alzheimer’s Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms.

Results

Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward.

Conclusions

The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings.
Exploring awareness of obstetric fistula in Eastern and Northern Nigeria: perceived causes, symptoms, and availability of treatment services
Authors: Nwala Emmanuel Kelechi , Nwaigwe Charles , Sripad Pooja , Warren Charlotte E. , Ishaku Salisu , Kongyamba Solomon
Published: August 2022

Background

Evidence suggests that there are approximately two female genital fistula cases per 1000 women of reproductive age in sub-Saharan Africa. It is estimated that more than 200,000 women are affected by fistula in Nigeria, primarily due to obstetric causes. Awareness has been indicated as a risk factor for the development of obstetric fistula. This study explored the awareness of obstetric fistula such as causes, symptoms, and availability of and access to treatment services in southeastern and northwestern Nigeria.

Methods

An exploratory qualitative study design was used to conduct this research in Kano and Ebonyi states in northern and eastern Nigeria, respectively. A total of six (6) focus group discussions were conducted with three categories of participants: women who were successfully repaired and discharged (n = 2), community-married men (n = 2), and women (n = 2). Forty-four (44) In-depth interviews were conducted three categories of participants: 18 with women with fistula who were either awaiting repair or had been repaired; 6 family member caregivers accompanying fistula patients, and 20 health service providers at fistula repair centers. We developed a data analysis plan based on the emerging themes. The transcripts and field notes were imported into QSR Nvivo version 11 and coded accordingly. Content and thematic analysis was run by inductively drawing themes based on the elicited information from participants.

Results

There was lack of knowledge of obstetric fistula and its causes among married men and women in the community, caregivers, and some patients were unaware of what caused their fistula for years. In this study, none of the community men and women nor caregivers correctly identified the causes and symptoms of a fistula or knew where to seek treatment. Knowledge about fistula was more common among women who had undergone repairs. Some repaired women attributed the cause of fistula to the providers who attended to them during delivery.

Conclusions

Findings reveal a widespread lack of awareness of obstetric fistula onset and awareness of the availability of repair services at the community level. There is an urgent need to explore multi-pronged strategies for increasing awareness of obstetric fistula and available treatment services among women and other community members.
Improvement plans on the operation of the Institutional Animal Care and Use Committee: focusing on the case of Seoul National University
Authors: Ahn Na , Park Jaehak , Ihm Jungjoon , Roh Sangho
Published: August 2022

Background

The Institutional Animal Care and Use Committee (IACUC) became compulsory in 2008 by the Animal Protection Act in Korea. Seoul National University (SNU), which conducts 5% of Korea’s total animal protocol reviews and uses 10% of national laboratory animal usage, has been influential in the review of animal protocols and management of animal facilities. This study was undertaken to suggest the operational improvement of the IACUC. It focused on the case of SNU.

Results

The methodological framework consists of a qualitative approach. In particular, this study is focused on the grounded theory approach and sixty people were surveyed through purposeful sampling. Through this study, we found that various practical educations are necessary such as: (1) education for researchers on how to write a protocol, (2) standardization of screening criteria for various animal experiments by presenting various cases, (3) training on a detailed understanding of relevant laws and policies. In particular, an integrated management system, making it possible to share information among the related committees, would be essential for smoother operation of the IACUC.

Conclusions

If various levels of education and the integrated management system are established, it will be possible to enhance the excellence of researchers and to better manage the operation of the IACUC.
Effect of doping concentration of tunnel junction on I-V characteristics of photovoltaic power converter
Authors: Huo Wenxue , Zhou Hang , Du Chunhua
Published: August 2022

Tunnel junction is the crucial part for photovoltaic power converters, especially for those with the multi-junction structure. In this research, through changing growing temperature and the ratio of V-III precursor, four single-junction photovoltaic power converters with tunnel junction of different doping concentrations are fabricated. The I-V characteristics of four samples are measured, and also their power conversion efficiency and fill factors are calculated. It was found that the I-V curves of the samples exhibited significant differences as the doping concentration increased. Within an appropriate range, the photovoltaic power converter with higher doping concentration exhibits higher power conversion efficiency. However, when the doping concentration is too high, a reverse barrier appears inside the tunnel junction, manifesting as a “stair” I-V curve. This barrier will result in a reduction in device efficiency. This work provides important guidance for designing the doping concentration of tunnel junctions and fabricating high-performance photovoltaic power converters.
The centriolar satellite protein Cfap53 facilitates formation of the zygotic microtubule organizing center in the zebrafish embryo
Authors: Willekers Sven , Tessadori Federico , van der Vaart Babet , Henning Heiko H. , Stucchi Riccardo , Altelaar Maarten , Roelen Bernard A. J. , Akhmanova Anna , Bakkers Jeroen
Published: August 2022

In embryos of most animal species, the zygotic centrosome is assembled by the centriole derived from the sperm cell and pericentriolar proteins present in the oocyte. This zygotic centrosome acts as a microtubule organizing center (MTOC) to assemble the sperm aster and mitotic spindle. As MTOC formation has been studied mainly in adult cells, very little is known about the formation of the zygotic MTOC. Here, we show that zebrafish (Danio rerio) embryos lacking either maternal or paternal Cfap53, a centriolar satellite protein, arrest during the first cell cycle. Although Cfap53 is dispensable for sperm aster function, it aids proper formation of the mitotic spindle. During cell division, Cfap53 colocalizes with γ-tubulin and with other centrosomal and centriolar satellite proteins at the MTOC. Furthermore, we find that γ-tubulin localization at the MTOC is impaired in the absence of Cfap53. Based on these results, we propose a model in which Cfap53 deposited in the oocyte and the sperm participates in the organization of the zygotic MTOC to allow mitotic spindle formation.
Assessment of endocytic traffic and Ocrl function in the developing zebrafish neuroepithelium
Authors: Williams Daniel M. , Gungordu Lale , Jackson-Crawford Anthony , Lowe Martin
Published: August 2022

Endocytosis allows cells to internalise a wide range of molecules from their environment and to maintain their plasma membrane composition. It is vital during development and for maintenance of tissue homeostasis. The ability to visualise endocytosis in vivo requires suitable assays to monitor the process. Here, we describe imaging-based assays to visualise endocytosis in the neuroepithelium of living zebrafish embryos. Injection of fluorescent tracers into the brain ventricles followed by live imaging was used to study fluid-phase or receptor-mediated endocytosis, for which we used receptor-associated protein (RAP, encoded by Lrpap1) as a ligand for low-density lipoprotein receptor-related protein (LRP) receptors. Using dual-colour imaging combined with expression of endocytic markers, it is possible to track the progression of endocytosed tracers and to monitor trafficking dynamics. Using these assays, we reveal a role for the Lowe syndrome protein Ocrl in endocytic trafficking within the neuroepithelium. We also found that the RAP-binding receptor Lrp2 (encoded by lrp2a) appears to contribute only partially to neuroepithelial RAP endocytosis. Altogether, our results provide a basis to track endocytosis within the neuroepithelium in vivo and support a role for Ocrl in this process.

This article has an associated First Person interview with the first author of the paper.
Μελέτη ορθοκολικού καρκίνου με μικροδορυφορική αστάθεια
Authors: Ζούκη Διονυσία
Published: August 2022

Ο ορθοκολικός καρκίνος αποτελεί την τρίτη σε συχνότητα κακοήθεια παγκοσμίως. Παρόλο που αποτελεσματικές μέθοδοι προσυμπτωματικού ελέγχου έχουν μειώσει σημαντικά τα ποσοστά επίπτωσης και θνητότητας, εξακολουθεί να συγκαταλέγεται στις κυριότερες αιτίες θανάτου που σχετίζονται με τον καρκίνο. Στην παθογένεση της νόσου εμπλέκονται πολύπλοκοι μοριακοί μηχανισμοί. Η οδός μεταγωγής σήματος PI3k/Akt/mTOR αποτελεί έναν από αυτούς και εμφανίζει υψηλή ενεργότητα στον συγκεκριμένο τύπο κακοήθειας, προσφέροντας ένα εξαίρετο πεδίο επιστημονικής έρευνας και πιθανής στόχευσης. Παρόλα αυτά η συσχέτισή του με την κατάσταση της μικροδορυφορικής αστάθειας σε ορθοκολικά καρκινώματα δεν έχει ακόμη διερευνηθεί. Η κινάση mTOR και ο καταληκτικός της στόχος, η πρωτεΐνη 4EBP1, αποτελούν μόρια-κλειδιά της συγκεκριμένης οδού με καίριο ρόλο. Στην παρούσα εργασία επικεντρώνουμε τη μελέτη μας σε 108 δείγματα ορθοκολικών καρκινωμάτων με ακέραιο ή ελλιπές σύστημα επιδιόρθωσης αταίριαστων ζευγών βάσεων ή αλλιώς μικροδορυφορικά σταθερούς ή ασταθείς όγκους αντίστοιχα (proficient ΜΜR/ pMMR και deficient MMR/ dMMR αντιστοίχως) με παράλληλη ανοσοϊστοχημική εκτίμηση της έκφρασης των φωσφορυλιωμένων πρωτεϊνών mTOR (pmTOR) και 4EBP1 (p4EBP1). Επιπρόσθετα, εξετάζουμε εκτενώς τις πιθανές συσχετίσεις που προκύπτουν μεταξύ τους καθώς και με διάφορα κλινικά και παθολογοανατομικά δεδομένα, με το μοριακό προφίλ των όγκων αλλά και την επίπτωσή τους στη συνολική επιβίωση των ασθενών. Τα αποτελέσματα που προέκυψαν ανέδειξαν την πιθανή συνεχή αλληλεπίδραση μεταξύ των σηματοδοτικών οδών MAPK και PI3k/Akt, καθώς οι ανιχνευόμενες μεταλλάξεις στο γονίδιο KRAS φάνηκαν να συσχετίζονται σημαντικά με την έκφραση της πρωτεΐνης pmTOR (p=0.004). Επίσης η έκφραση της p4EBP1 δεν φάνηκε να συσχετίζεται με την pmTOR (p=0.206), υποδεικνύοντας ότι στον ορθοκολικό καρκίνο ενδεχομένως να υποκρύπτονται και άλλοι τρόποι ρύθμισης της συγκεκριμένης πρωτεΐνης, οι οποίοι είναι ανεξάρτητοι από την mTOR. Από την πολυπαραγοντική ανάλυση επιβίωσης, μόνο η έκφραση της p4EBP1 αναδείχθηκε ως ανεξάρτητος αρνητικός προγνωστικός παράγοντας για τη συνολική επιβίωση (HR: 3.322, 95% CI: 1.110-9.945, p=0.032). Παράλληλα, μια ενδιαφέρουσα συσχέτιση αποδείχθηκε μεταξύ της κατάστασης της μικροδορυφορικής αστάθειας και της έκφρασης της p4EBP1, με την έννοια ότι τα dMMR καρκινώματα εμφάνιζαν συνηθέστερα χαμηλή έκφραση της πρωτεΐνης αυτής (p=0.002). Καταλήγοντας, προτείνουμε την συνδυαστική στόχευση των MAPK και PI3k/Akt μονοπατιών ως θεραπευτική στρατηγική σε ασθενείς με ανιχνευόμενες μεταλλαγές στα γονίδια RAS ή και BRAF. Επισημαίνουμε επίσης την πιθανή προγνωστική αξία της p4EBP1 στον συγκεκριμένο τύπο καρκίνου, ενώ παράλληλα, για πρώτη φορά στη διεθνή βιβλιογραφία, προσπαθούμε να δώσουμε απάντηση στο αναδυόμενο ερώτημα αν η παρουσία ή η απουσία μικροδορυφορικής αστάθειας μπορεί να κατευθύνει τη θεραπευτική στόχευση της mTOR σε ασθενείς με καρκίνο παχέος εντέρου.