bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of metabolism-related subtypes and feature genes in Alzheimer’s disease
Authors: Lian Piaopiao , Cai Xing , Wang Cailin , Liu Ke , Yang Xiaoman , Wu Yi , Zhang Zhaoyuan , Ma Zhuoran , Cao Xuebing , Xu Yan
Published: September 2023

Background

Owing to the heterogeneity of Alzheimer's disease (AD), its pathogenic mechanisms are yet to be fully elucidated. Evidence suggests an important role of metabolism in the pathophysiology of AD. Herein, we identified the metabolism-related AD subtypes and feature genes.

Methods

The AD datasets were obtained from the Gene Expression Omnibus database and the metabolism-relevant genes were downloaded from a previously published compilation. Consensus clustering was performed to identify the AD subclasses. The clinical characteristics, correlations with metabolic signatures, and immune infiltration of the AD subclasses were evaluated. Feature genes were screened using weighted correlation network analysis (WGCNA) and processed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, three machine-learning algorithms were used to narrow down the selection of the feature genes. Finally, we identified the diagnostic value and expression of the feature genes using the AD dataset and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.

Results

Three AD subclasses were identified, namely Metabolism Correlated (MC) A (MCA), MCB, and MCC subclasses. MCA contained signatures associated with high AD progression and may represent a high-risk subclass compared with the other two subclasses. MCA exhibited a high expression of genes related to glycolysis, fructose, and galactose metabolism, whereas genes associated with the citrate cycle and pyruvate metabolism were downregulated and associated with high immune infiltration. Conversely, MCB was associated with citrate cycle genes and exhibited elevated expression of immune checkpoint genes. Using WGCNA, 101 metabolic genes were identified to exhibit the strongest association with poor AD progression. Finally, the application of machine-learning algorithms enabled us to successfully identify eight feature genes, which were employed to develop a nomogram model that could bring distinct clinical benefits for patients with AD. As indicated by the AD datasets and qRT-PCR analysis, these genes were intimately associated with AD progression.

Conclusion

Metabolic dysfunction is associated with AD. Hypothetical molecular subclasses of AD based on metabolic genes may provide new insights for developing individualized therapy for AD. The feature genes highly correlated with AD progression included GFAP, CYB5R3, DARS, KIAA0513, EZR, KCNC1, COLEC12, and TST.
Predictive performance of triglyceride glucose index (TyG index) to identify glucose status conversion: a 5-year longitudinal cohort study in Chinese pre-diabetes people
Authors: Chen Xiaojie , Liu Danfeng , He Weiting , Hu Haofei , Wang Wenjian
Published: September 2023

Objective

Triglyceride glucose index (TyG index) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG and regression from prediabetes to normoglycemia remains to be elucidated.

Methods

This retrospective cohort study involved 25,248 subjects with prediabetes at baseline conducted from 2010 to 2016. A Cox proportional hazard regression model was designed to evaluate the role of TyG in identifying people at converting from prediabetes to normoglycemia. Cox proportional hazards regression with cubic spline functions and smooth curve fitting was used to dig out the nonlinear relationship between them. Detailed evaluations for TyG were also performed using sensitivity and subgroup analyse.

Results

Among the included prediabetes subjects (n = 25,248), the mean age was 49.27 ± 13.84 years old, and 16,701 (66.15%) were male. The mean TyG was 8.83 ± 0.60. The median follow-up time was 2.96 ± 0.90 years. 11,499 (45.54%) individuals had a final diagnosis of normoglycemia.

After adjusting for covariates, TyG was negatively affecting the results of glucose status conversion in prediabetes people (HR 0.895, 95% CI 0.863, 0.928). There was a nonlinear connection between TyG and normoglycemia in prediabetes people, and the inflection point was 8.88. The effect sizes (HR) on the left and right sides of the inflection point were 0.99 (0.93, 1.05) and 0.79 (0.74, 0.85), respectively. Sensitivity analysis confirmed the robustness of these results. Subgroup analysis showed that TyG was more strongly associated with incident glucose status conversion in male, BMI ≥ 25. In contrast, there was a weaker relationship in those with female, BMI < 25.

Conclusion

Based on sample of subjects evaluated between 2010 and 2016, TyG index appears to be a promising marker for predicting normoglycemic conversion among prediabetes people in China. This study demonstrates a negative and non-linear association between TyG and glucose status conversion from prediabetes to normoglycemia. TyG is strongly related to glucose status conversion when TyG is above 8.88. From a therapeutic point of view, it is meaningful to maintain TyG levels within the inflection point to 8.88.
Heterotopically-placed right ventricle-to-pulmonary artery conduit does not negatively affect outcomes
Authors: Kadeetham Khunthorn , Samankatiwat Piya
Published: September 2023

Objectives

Since the introduction of surgical implantation of conduit for right ventricle-to-pulmonary artery pathway reconstruction, there has been a number of studies on possible factors which might potentially affect conduit longevity, as well as patient’s reintervention-free and overall survival. Still, no definite consensual agreement could be made thus far. We aimed to compare conduit longevity, reintervention-free survival, and overall survival between patients with congenital heart diseases indicated for operations involving right ventricle-to-pulmonary artery pathway reconstruction whose conduits were placed heterotopically to those with orthotopically placed ones.

Materials and methods

We retrospectively collected data from electronic medical records of Ramathibodi hospital from 1st January 2005 to 31st December 2022. Patients with congenital heart diseases whose operations involved reconstruction of right ventricle-to-pulmonary artery continuity were included. Patients whose medical record data were significantly missing were excluded. Demographic data, operative, and postoperative details were collected and reviewed.

Results

There were 67 patients included in our study, with 25 receiving orthotopic and the other 42 receiving heterotopic conduit implantation. Conduit dysfunction-free, reintervention-free, and overall survival were not statistically different between both groups. There was 1 early and no late death up to the end date of our study.

Conclusions

Conduits placed on a heterotopic position did not result in worse longevity, reintervention-free survival, as well as overall survival when compared to conduits placed on an orthotopic position. This suggested that the less technically demanding heterotopic conduit placement could be recommended as an operation of choice for right ventricular outflow tract reconstruction.
Nail psoriasis dynamics during biologic treatment and withdrawal in patients with psoriasis who may be at high risk of developing psoriatic arthritis: a post hoc analysis of the VOYAGE 2 randomized trial
Authors: Tillett William , Egeberg Alexander , Sonkoly Enikö , Gorecki Patricia , Tjärnlund Anna , Buyze Jozefien , Wegner Sven , McGonagle Dennis
Published: September 2023

Background

Nail psoriasis is a common, physiologically, and psychologically disruptive, and yet often under-treated manifestation of psoriasis. The objectives of this analysis were to investigate the trajectory of nail psoriasis, a risk factor for psoriatic arthritis (PsA), with guselkumab vs adalimumab treatment followed by withdrawal, and determine characteristics associated with nail response in patients treated with guselkumab.

Methods

This post hoc analysis of the phase III trial VOYAGE 2 included patients with moderate-to-severe plaque psoriasis and baseline nail involvement. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Area and Severity Index (PASI) were analyzed through week 48 in patients randomized to guselkumab or adalimumab. Multiple logistic regression analyzed factors associated with NAPSI 0/1 at week 24/week 48 following guselkumab treatment. In a separate analysis, patients were stratified by prior biologic experience.

Results

Overall, 272 vs 132 patients receiving guselkumab vs adalimumab had nail psoriasis at baseline. Lower baseline NAPSI and week 16 PASI were associated with achieving NAPSI 0/1 at week 24 (NAPSI, odds ratio 0.685 [95% confidence interval: 0.586, 0.802]; week 16 PASI, 0.469 [0.281, 0.782]) and week 48 (NAPSI, 0.784 [0.674, 0.914]; week 16 PASI, 0.557 [0.331, 0.937]) with guselkumab. Previous biologic experience did not impact NAPSI response. Following treatment withdrawal at week 28, mean NAPSI was maintained in the guselkumab arm (week 24 1.7, week 48 1.9) and increased slightly in the adalimumab arm (week 24 1.4, week 48 2.3). Mean PASI increased across both treatment arms.

Conclusions

Higher skin efficacy at week 16 was associated with better nail responses during guselkumab treatment. Nail psoriasis improvements reflected skin improvements. Following guselkumab withdrawal, nail response was maintained longer than skin response. Future studies should investigate whether such improvements in nail response reduce patients’ risk of later PsA development.

Trial registration

ClinicalTrials.gov, NCT02207244. Registered July 31, 2014.
Rotational stability can be enhanced in revision anterior cruciate ligament reconstruction using the over-the-top augmentation technique compared to single bundle technique
Authors: Lim Sumin , Park Ki-Hoon , Park Do Young , Kim Tae Hun , Koh Jeong-Hyun , Chung Jun Young
Published: September 2023

Purpose

Revision anterior cruciate ligament (ACL) reconstruction is technically challenging due to mispositioned tunnels, bone loss, and tunnel enlargement, which may compromise graft fixation and result in failure. To obtain firm graft fixation and strength in one stage, we utilized an over-the-top augmentation technique using an Achilles tendon allograft in revision ACL reconstruction (OA-ACLR). This study compared OA-ACLR with single-bundle ACL reconstruction (SB-ACLR). We hypothesized that OA-ACLR would enhance the postoperative knee joint rotational stability.

Methods

We retrospectively analyzed 47 patients who underwent revisional OA-ACLR and 48 who underwent primary SB-ACLR with minimum follow-up of 6 months. Knee instability was evaluated with the anterior drawer, Lachman, and pivot shift tests preoperatively and at the final follow-up. Side-to-side differences were compared with the non-affected side at the final follow-up. Function was evaluated using the IKDC subjective and Lysholm knee scores preoperatively and at the final follow-up.

Results

The groups did not differ in terms of sex, age, BMI, and etiology. There were no significant differences in concomitant surgical procedures, such as meniscectomy and meniscus repair, between the two groups (p = 0.335, > 0.99). Both groups significantly improved in the anterior drawer, Lachman, pivot shift tests, and IKDC and Lysholm knee scores after surgery (all p < 0.001). The OA-ACLR group showed significantly higher rotational stability in the pivot shift test than the SB-ACLR group (p = 0.017). The postoperative side-to-side difference, the IKDC and Lysholm scores showed no significant differences between the groups (p = 0.34, 0.301, 0.438).

Conclusions

OA-ACLR showed enhanced rotational stability with pivot shift test compared to SB-ACLR. It may be considered a useful alternative for revision ACL reconstruction.
Transhepatic ultrasound guided embolization as a successful novel technique in treatment of pediatric complex intrahepatic arterioportal fistula: a case report and review of the literature
Authors: Taher Heba , Kidr ElSayed , Kamal Ahmed , ElGobashy Mohamed , Mashhour Shady , Nassef Amr , Tawfik Sherifa , El Tagy Gamal , Shaban Muayad , Eltantawi Haytham , Abdullateef Khaled S.
Published: September 2023

Introduction

Intrahepatic vascular shunts “IHVS” are abnormal communications between intra-hepatic vasculature involving the arterial, portal, or hepatic venous system. Arterio-portal fistula “APF” is an intrahepatic communication between the hepatic arterial system and the portal venous system without any communication with the systemic venous circulation. APF is considered a rare cause of portal hypertension and gastrointestinal bleeding in infancy.

Case presentation

A 3-month-old Mediterranean female with known cardiac congenital anomalies presented to us with abdominal distension and diarrhea. Ultrasonography revealed massive ascites and computerized tomography (CT) abdomen with intravenous (IV) contrast revealed a left hepatic lesion. On further evaluation, an intrahepatic arterio-portal vascular malformation was detected. Attempted trans arterial embolization failed and radiology team successfully carried out direct trans hepatic ultrasound guided coiling of the aneurysmal venous sac followed by successful resection of segment 4 of the liver with the vascular malformation avoiding life threatening intra operative bleeding.

Conclusion

Any child with recurrent gastrointestinal bleeding, failure to thrive, vomiting, diarrhea, steatorrhea, splenomegaly, or ascites should be investigated for intrahepatic arterio-portal fistula “IAPF”. Our novel technique of direct trans hepatic ultrasound guided coiling is an alternative method if trans arterial embolization “TAE” failed.
The fundamental solution and blow-up problem of an anisotropic parabolic equation
Authors: Zhan Huashui
Published: September 2023

This paper is devoted to the study of anisotropic parabolic equation related to the $p_{i}$

p
i

-Laplacian with a source term $f(u)$
f
(
u
)
. If $f(u)=0$
f
(
u
)
=
0
, then the fundamental solution of the equation is constructed. If there are some restrictions on the growth order of u in the source term, the initial energy $E(0)$
E
(
0
)
is positive and has a super boundedness, which depends on the Sobolev imbedding index, then the local solution may blow up in finite time.
Construction of a prediction model for rebleeding in patients with acute upper gastrointestinal bleeding
Authors: Zhuang Yangping , Xia Shaohuai , Chen Junwei , Ke Jun , Lin Shirong , Lin Qingming , Tang Xiahong , Huang Hanlin , Zheng Nan , Wang Yi , Chen Feng
Published: September 2023

Background

The incidence of rebleeding in patients with upper gastrointestinal bleeding (UGIB) remains despite advances in intervention approaches. Therefore, early prediction of the risk of rebleeding could help to greatly reduce the mortality rate in these patients. We aim to develop and validate a new prediction model to predict the probability of rebleeding in patients with AUGIB.

Methods

A total of 1170 AUGIB patients who completed the procedure of emergency gastroscopy within 48 h of admission were included. Logistic regression analyses were performed to construct a new prediction model. A receiver operating characteristic curve, a line graph, and a calibration and decision curve were used to assess the predictive performance of our new prediction model and compare its performance with that of the AIMS65 scoring system to determine the predictive value of our prediction model.

Results

A new prediction model was constructed based on Lactic acid (LAC), neutrophil percentage (NEUTP), platelet (PLT), albumin (ALB), and D-DIMER. The AUC values and their 95% confidence interval (CI) for the new prediction model and the AIMS65 score were 0.746 and 0.619, respectively, and 0.697–0.795 and 0.567–0.670, respectively. In the training group, the C index values based on the prediction model and the AIMS65 scoring system were 0.720 and 0.610, respectively. In the validation group, the C index values based on the prediction model and the AIMS65 scoring system were 0.828 and 0.667, respectively. The decision and calibration curve analysis also showed that the prediction model was superior to the AIMS65 scoring system in terms of accuracy of prediction, consistency, and net clinical benefit.

Conclusion

The prediction model can predict the probability of rebleeding in AUGIB patients after endoscopic hemostasis therapy.
Prenylated flavonoids isolated from the twigs of Artocarpus champeden as potential activators for tobacco powdery mildew and their mode of actions
Authors: Hu Qiu-Fen , Yao Sui , Ma Yue-Yu , Xiong Rui-Feng , Kong Guang-Hui , Wu Yu-Ping , Zhao Gao-Kun , Dong Miao , Wang Wei-Guang , Zhou Min , Li Yin-Ke
Published: September 2023

Background

Golovinomyces cichoracearum (DC.) is the main pathogen for tobacco powdery mildew fungus disease. Its outbreaks often result in severe harvest losses for the yield and quality of tobacco. Artocarpus champeden is rich in prenylated flavonoids, which are important for the plant’s defensive strategies. With the aim of continuously exploring bioactive natural metabolites for agricultural chemicals, the chemical investigations on the twigs of A. champeden were carried out.

Results

Six new (1–6) and five known (7–11) prenylated flavonoids were isolated. Compound 1 is the first example of flavone whose prenylated side-chain is converted into an unusual 1H-pyrrol-2-yl functional group. Compounds 2 and 3 are rare flavones bearing a 4-methylfuran-2-yl moiety. The frameworks of the above three flavones are reported in natural products for the first time. Interestingly, compound 1 showed high anti-G. cichoracearum activity with an inhibition rate of 88.3% ± 6.2. This rate is higher than that of the positive control (with an inhibition rate of 81.5% ± 6.3) compared to the negative control, compounds 2–11 also showed potential activities with inhibition rates in the range of 50.9%–72.0%. In addition, the mechanistic studies on 1 revealed that it has a potent direct effect on conidiospores of G. cichoracearum and induces systemic acquired resistance for tobacco plants, which may be the reasons for its significant effects against G. cichoracearum.

Conclusions

Powdery mildew is a fungal disease harmful to tobacco. Flavonoids have been identified as the sources of promising antifungal agents. For prenylated flavonoids, the combination of a flavonoid skeleton with prenylated side-chain can give the resultant more potential for biological activities. The successful isolation and structure identification of the above prenylated flavonoids provide new materials for the screening of powdery mildew inhibitors, and also contribute to the improved utilization of A. champeden.

Graphical Abstract
Adoption of artificial intelligence in science teaching: From the vantage point of the African science teachers
Authors: Nja Cecilia Obi , Idiege Kimson Joseph , Uwe Uduak Edet , Meremikwu Anne Ndidi , Ekon Esther Etop , Erim Costly Manyo , Ukah Julius Ukah , Eyo Eneyo Okon , Anari Mary Ideba , Cornelius-Ukpepi Bernedette Umalili
Published: September 2023

This study investigated the factors influencing science teachers' 'Artificial Intelligence' (AI) utilization by using the 'Technology Acceptance Model' (TAM). The factors investigated alongside TAM variables were teachers' data like; age, sex, and residence type. TAM items that were correlated in this study included; self-esteem, stress and anxiousness, ease of utilization, behavioural intention, attitude towards AI usage, and expected benefits. The population of this study comprised all science teachers (170) in the Calabar Education Zone of Cross River State, Nigeria. The sample was made up of 79 science teachers comprising (58.22%) 46 females and (41.77%) 33 males. The descriptive and analytical research design was used in this study. A questionnaire named ' Approval of Artificial Intelligence: The Teachers' Eye' Questionnaire (AAITEQ) was used for the study. This study raised 3 research questions. The reliability for AAITEQ was from 0.72 to 0.81 using Cronbach's alpha. Findings indicated that the approval for the utilization of AI was high with an overall mean score of 3.00. The highest predicting value for behaviour intent using TAM variables was the ease of usage r = .789. Science teachers' sex (t, 77 = 1.988; p = .060, (p ˃ .05), age F (2, 76) = .547; p = .581 (p ˃ .05) and teachers' residence location (t, .77 = .533; p = − .062 (p ˃ .05) did not influence the behaviour of science teachers' intention of the utilization of AI. It was recommended that both in-service and pre-service teachers be trained on the utilization of AI.
Secondary instability generated on the equatorial plasma bubbles wall due to an interaction with midnight brightness wave
Authors: Figueiredo Cosme Alexandre Oliveira Barros , Miranda Rodrigo A. , Wrasse Cristiano Max , Takahashi Hisao , Barros Diego , Egito Fábio , Rosa Geângelo de Matos , Sampaio Antonio Hélder Rodrigues
Published: September 2023

Interaction between Equatorial Plasma Bubbles (EPBs) and midnight Brightness wave (MBW) was observed over Bom Jesus da Lapa (13.3° S, 43.5° W; Quasi-Dipole geomagnetic latitude of 14.1° S), using OI 630 nm all-sky images. On the night of December 22nd, 2019, an EPB was seen propagating eastward in its fossil stage until it interacted with an MBW. After the interaction, the west walls of EPBs generated secondary instabilities that can be associated with gradient drift instability (GDI) and/or Kelvin–Helmholtz instabilities (KHI). We suggest that the MBW contributed to generate a shear in the EPBs walls due to changes in the thermospheric dynamics, such as neutral wind in the F layer height. Furthermore, spectral analysis of the all-sky images suggests that GDI and/or KHI generated turbulence and helped to dissipate the EPBs.

Graphical Abstract
High levels of maternally derived antibodies do not significantly interfere with the development of humoral and cell-mediated responses to Porcine circovirus 2 after intradermal vaccination
Authors: Martin-Valls Gerard E. , Cortey Martí , Swam Hanny , Jiménez Marta , Mateu Enric
Published: September 2023

Background

Vaccination of pigs against PCV2 is usually performed around weaning when animals still have maternally derived antibodies (MDA). The present study aimed to assess the possible interference of MDA in the development of the PCV2-specific immune response after vaccination of commercial weaners. For this purpose, a PRRS-negative 600-sow farrow-to-finish farm was selected. Half of the sows were vaccinated and revaccinated with Porcilis® PCV ID against PCV2 7 and 3 weeks before farrowing. After farrowing, piglets were tested by AlphaLisa to select 72 animals with high and low levels of MDA. Groups were further subdivided and vaccinated intradermally with Porcilis® PCV ID at 21 or 28 days of age. Unvaccinated controls were also included. Animals were followed afterward for 42 days to examine the development of PCV2-specific antibodies and interferon-γ secreting cells (IFN-γ SC).

Results

The average titres of antibodies of the groups vaccinated in the presence of low or high MDA levels were similar at 28 and 42 days post-vaccination while in the controls the titres declined throughout the observation period. Results of vaccinating at 21 or 28 days of age were equivalent with regard to antibody development. Regarding the IFN-γ SC, vaccinated animals produced significant frequencies of IFN-γ SC by day 28. Again, no differences were observed between the groups with high or low antibody levels.

Conclusion

High levels of MDA did not interfere with the development of humoral and cell-mediated responses to Porcine circovirus 2 after intradermal vaccination at 21 or 28 days of age.
Temporal and spatial patterns of seed dispersal of four shrubs in a Cistus-Erica shrubland from central Spain
Authors: Moreno José M. , Zuazua Eva , Torres Iván , Parra Antonio , Moreno-Fenoll Clara
Published: September 2023

Background

Mediterranean shrublands are composed of species that have different regeneration strategies after fire and soil seed bank types. However, differences over the years in seed dispersal temporal and spatial patterns of the various plants composing a community have been little investigated. Here, we studied the temporal and spatial patterns of seed dispersal in four shrubs of an old (> 40 years) shrubland in central Spain. Three of them are seeders (Cistus ladanifer, Erica umbellata, and Salvia rosmarinus), and one is a resprouter (Erica arborea); the first two have persistent soil seed banks, and the latter two, transient. A 15 × 10 m plot was chosen and divided into a 0.5 × 0.5 m grid, where plant cover and density were measured. At 106 quadrats, seed traps were set and periodically (1–2 monthly) monitored for 3 years.

Results

S. rosmarinus dispersed in late spring-early summer, E. arborea dispersed during the summer, and C. ladanifer and E. umbellata dispersed from early summer to nearly late spring of the next year. Globally, seeds were being dispersed all year round. The seed crop size of a given species varied between years, although species differed in the year their seed crop was largest, despite large differences in climate. Seed rain and plant cover of each species were poorly related in terms of the variance explained by the models. Semivariogram analysis showed that seed dispersal expanded beyond that of the plant cover of each species by a few meters. No association between seed crop size and spatial dependence was ascertained. While species dispersal in space tended to be negatively related to one another, E. arborea seeds tended to dominate underneath the majority of the other species.

Conclusions

S. rosmarinus dispersed before the fire season, which is consistent with seeds avoiding fire while on the plant; C. ladanifer and E. umbellata dispersed mostly after the fire season, which is coherent with a bet-hedging strategy against seed predators; E. arborea dispersed before the rainy season, which is expected for a plant that germinates readily after imbibition. Seed dispersal in time was compatible with the type of soil seed bank and post-fire regeneration of the species. The evidence of such a relationship with spatial patterns was weak. The dominance of E. arborea seeds underneath most of the other species suggests that this mid-successional species might dominate when openings form due to the deaths of standing plants of the seeders between two fires, given their lower longevity.
Evidence that the domesticated fungus Leucoagaricus gongylophorus recycles its cytoplasmic contents as nutritional rewards to feed its leafcutter ant farmers
Authors: Leal-Dutra Caio Ambrosio , Yuen Lok Man , Guedes Bruno Augusto Maciel , Contreras-Serrano Marta , Marques Pedro Elias , Shik Jonathan Zvi
Published: September 2023

Leafcutter ants farm a fungal cultivar (Leucoagaricus gongylophorus) that converts inedible vegetation into food that sustains colonies with up to millions of workers. Analogous to edible fruits of crops domesticated by humans, L. gongylophorus has evolved specialized nutritional rewards—swollen hyphal cells called gongylidia that package metabolites and are consumed by ant farmers. Yet, little is known about how gongylidia form, and thus how fungal physiology and ant provisioning collectively govern farming performance. We explored the process of gongylidium formation using advanced microscopy to image the cultivar at scales of nanometers, and both in vitro experiments and in silico analyses to examine the mechanisms of gongylidia formation when isolated from ant farmers. We first used transmission electron, fluorescence, and confocal microscopy imaging to see inside hyphal cells. This imaging showed that the cultivar uses a process called autophagy to recycle its own cellular material (e.g. cytosol, mitochondria) and then shuttles the resulting metabolites into a vacuole whose continual expansion displaces other organelles and causes the gongylidium cell’s bulging bulb-like appearance. We next used scanning electron microscopy and light microscopy to link this intracellular rearrangement to the external branching patterns of gongylidium cells as they clump together into edible bundles called staphyla. We next confirmed that autophagy plays a critical role in gongylidium formation both: (1) in vitro as gongylidium suppression occurred when isolated fungal cultures were grown on media with autophagy inhibitors, and (2) in silico as differential transcript expression (RNA-seq) analyses showed upregulation of multiple autophagy gene isoforms in gongylidia relative to undifferentiated hyphae. While autophagy is a ubiquitous and often highly derived process across the tree of life, our study reveals a new role for autophagy as a mechanism of functional integration between ant farmers and their fungal crop, and potentially as a signifier of higher-level homeostasis between uniquely life-time committed ectosymbionts.
Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649
Authors: Moehler Markus , Xiao Hong , Blum Steven I. , Elimova Elena , Cella David , Shitara Kohei , Ajani Jaffer A. , Janjigian Yelena Y. , Garrido Marcelo , Shen Lin , Yamaguchi Kensei , Liu Tianshu , Schenker Michael , Kowalyszyn Ruben , Bragagnoli Arinilda Campos , Bruges Ricardo , Montesarchio Vincenzo , Pazo-Cid Roberto , Hunter Shannon , Davenport Eric , Wang Jinyi , Kondo Kaoru , Li Mingshun , Wyrwicz Lucjan
Published: September 2023

PURPOSE

In CheckMate 649, first-line nivolumab plus chemotherapy prolonged overall survival versus chemotherapy in patients with advanced/metastatic non–human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC). We present exploratory patient-reported outcomes (PROs).

METHODS

In patients (N = 1,581) concurrently randomly assigned 1:1 to nivolumab plus chemotherapy or chemotherapy and in those with tumor PD-L1 expression at a combined positive score (CPS) of ≥5, health-related quality of life (HRQoL) was assessed using the EQ-5D and Functional Assessment of Cancer Therapy-Gastric (FACT-Ga), which included the FACT-General (FACT-G) and Gastric Cancer subscale (GaCS). The FACT-G GP5 item assessed treatment-related symptom burden. Longitudinal changes in HRQoL were assessed using mixed models for repeated measures in the PRO analysis population (randomly assigned patients with baseline and ≥1 postbaseline assessments). Time to symptom or definitive deterioration analyses were also conducted.

RESULTS

In the PRO analysis population (n = 1,360), PRO questionnaire completion rates were mostly >80% during treatment. Patient-reported symptom burden was not increased with nivolumab plus chemotherapy versus chemotherapy. Mean improved changes from baseline were greater with nivolumab plus chemotherapy versus chemotherapy for FACT-Ga total, GaCS, and EQ-5D visual analog scale in patients with a CPS of ≥5; results were similar for the overall PRO analysis population. In CPS ≥5 and all randomly assigned populations, nivolumab plus chemotherapy reduced the risk of symptom deterioration versus chemotherapy, on the basis of FACT-Ga total score and GaCS; time to definitive deterioration was longer, and the risk of definitive deterioration in HRQoL was reduced with nivolumab plus chemotherapy across EQ-5D and most FACT-Ga measures (hazard ratio [95% CI] <1).

CONCLUSION

Compared with chemotherapy alone, first-line nivolumab plus chemotherapy showed stable or better on-treatment HRQoL in patients with advanced/metastatic non–HER2-positive GC/GEJC/EAC and also showed decreased risk of definitive HRQoL deterioration.
Circulating miRNAs Detect High vs Low Visceral Adipose Tissue Inflammation in Patients Living With Obesity
Authors: Makarenkov Nataly , Haim Yulia , Yoel Uri , Pincu Yair , Tarnovscki Tanya , Liberty Idit F , Kukeev Ivan , Baraf Lior , Dukhno Oleg , Zilber Oleg , Blüher Matthias , Rudich Assaf , Veksler-Lublinsky Isana
Published: September 2023

Context

The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity subphenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the nonsurgical patient.

Objective

We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT inflammation.

Methods

Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n = 35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the messenger RNA levels of TNFA, IL6, and CCL2 (determined by reverse transcription polymerase chain reaction). Differentially expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by receiver operating characteristic–area under the curve (ROC-AUC) analysis.

Results

Fifty three out of 263 circ-miRs (20%) were associated with high-VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53 = 23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high- and low-VAT inflammation with ROC-AUC greater than 0.8. Of the resulting 5 circ-miRs that were differentially abundant in all 3 statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with homeostatic model assessment of insulin resistance (HOMA-IR) exhibited ROC-AUC of 0.951 (95% CI, 0.865-1) and 0.808 (95% CI, 0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low- vs high-VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence.

Conclusion

Circ-miRs that identify patients with low- vs high-VAT inflammation constitute a putative tool to improve personalized care of patients with obesity.
Sex-Specific Associations Between Preoperative Hemoglobin and Outcomes After Major Noncardiac Surgery: A Retrospective Cohort Study
Authors: Zhao Bing-Cheng , Lei Shao-Hui , Liu Jia-Ming , Qiu Shi-Da , Yao Zhi-Wen , Liu Jian , Deng Fan , Li Zhi-Hao , Liu Ke-Xuan
Published: September 2023

BACKGROUND:

Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies

METHODS:

This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test.

RESULTS:

We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women (P = .539) or men (P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87–0.98; P = .013) for women and 0.94 (95% CI, 0.90–0.97; P < .001) for men, with no interaction by sex (P
interaction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly.

CONCLUSIONS:

Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.
Narrating the Future: A World-Literary Take on the Crisis of Imagination and the Novel
Authors: Bekhta Natalya
Published: September 2023

This article intervenes in the current debates that revolve around the possibility of imagining and narrating utopian projects and alternative futures. Very often these debates culminate in the diagnosis that the future is too complex to be adequately represented in narrative form and that the imagination more generally is in crisis. To move beyond what increasingly seems like an impasse in this theoretical discourse, the author suggests that the inquiry should take into account the heterogeneity of futural visions across the world-literary field by shifting the focus from its core regions to the semi-periphery. Reframing the problem of the future as that of collective action rather than of complexity, the author proposes that the perceived failure of narrative imagination is, in fact, an expression of the generic limits of the novel, limits that are particularly visible on the world-literary semi-periphery. To illustrate these points, the author offers an analysis of Taras Antypovych's Khronos (2011) and discusses how the pervasive concern with the future structurally manifests itself in the contemporary Ukrainian novel as a lack of transformative collective agency.
Controlled Chemical Construction in Nature: Unified Biogenesis Accounting for Synthesis of Fungal Dimeric Anhydrides
Authors: Minami Atsushi
Published: September 2023

Controlled chemical construction is a characteristic feature of enzymes in the synthesis of structurally complicated natural products. One of the most representative examples of such a construction is dimerization for the synthesis of fungal dimeric anhydrides (FDAs). The initial biosynthetic proposal for the synthesis of FDAs was reported in 1965. Subsequently, nearly half a century later, unified biogenesis for the synthesis of structurally diverse FDAs was proposed through the identification and mechanistic analysis of the dimerization enzyme. This review presents an overview of the dimerization mechanism and discusses the structural diversification strategy of nature.
Οι συνέπειες του Γ' ψηφίσματος στην Αθήνα την περίοδο του εμφυλίου (1946-1949)
Authors: Ραζάκος Θεοχάρης
Published: September 2023

Η παρούσα μελέτη διερευνά την εφαρμογή του Γ’ Ψηφίσματος «Περί εκτάκτων μέτρων αφορώντων την Δημόσιαν τάξιν και ασφάλειαν» στην περιοχή της Αθήνας, κατά την περίοδο του Εμφυλίου πολέμου (1946-1949).Εξετάζει το ζήτημα της γενίκευσης του καθεστώτος «έκτακτης ανάγκης» στην περιοχή της πρωτεύουσας, τα μέσα και τα ιδιαίτερα χαρακτηριστικά επιβολής του, όσο γενικεύεται και βαθαίνει η ένοπλη σύγκρουση. Μελετά τις συνέπειες που είχε στην πολιτική και κοινωνική ζωή της Αθήνας η ένταση της κρατικής καταστολής εναντίον των «υπονομευτών» του Κράτους, στα πλαίσια ενός ευρύτερου καθεστώτος ελέγχου του συνόλου της κοινωνίας των αστικών κέντρων και της επιχείρησης «εκκαθάρισης» των «μετόπισθεν» του πολεμικού μετώπου από τα δυνάμει στηρίγματα της «κομμουνιστικής ανταρσίας». Μέσα από την μελέτη της διευρυμένης έννοιας του «αντεθνικού» εγκλήματος, όπως αυτή πραγματώνεται με τη θέσπιση του Γ’ Ψηφίσματος και την κλιμακούμενη ενίσχυση του νομικού πλαισίου του εμφυλιακού Κράτους, εξετάζονται οι μέθοδοι αντιμετώπισης του κύριου πολιτικού του αντιπάλου, των Οργανώσεων του ΚΚΕ (ΚΟΑ) και του ΕΑΜ της πρωτεύουσας.Ταυτόχρονα, γίνεται προσπάθεια να μελετηθεί η δράση της ΚΟΑ ενάντια στις κρατικές μεθοδεύσεις και την καταστολή, μέσα στα πλαίσια της ολοένα και επιδεινούμενης κατάστασης «πολιτικής ασφυξίας», η οποία διαμορφώνεται στην Αθήνα του Εμφυλίου πολέμου.
Μελέτη ασφάλειας της προδιάτασης με μπαλόνι μεταξύ αυτό-εκπτυσσόμενων βαλβίδων σε ασθενείς που υποβάλλονται σε TAVI
Authors: Κολιαστάσης Λεωνίδας
Published: September 2023

Εισαγωγή: Η βαλβιδοπλαστική με μπαλόνι πριν από την διακαθετηριακή εμφύτευση αορτικής βαλβίδας (ΔΕΑΒ) είναι αμφισβητούμενη σημασίας αν και αρχικά θεωρούταν απαραίτητο βήμα. Η μελέτη DIRECT κατέληξε σε μη κατωτερότητα της απευθείας εμφύτευσης βαλβίδων CoreValve/Evolut σε σχέση με την εμφύτευση μετά από προδιάταση με μπαλόνι. Η βαλβίδα ACURATE neo είναι μια αυτοεκπτυσσόμενη συσκευή και η κατασκευή της προσφέρει χαμηλά ποσοστά διαταραχών αγωγιμότητας και νέας εμφύτευσης βηματοδότη, ενώ έχει συσχετιστεί με αυξημένα ποσοστά παραβαλβιδικής ανεπάρκειας. Στόχοι: Η κλινική μελέτη έχει ως στόχο την αξιολόγηση των κλινικών και υπερηχογραφικών αποτελεσμάτων ασφάλειας και αποδοτικότητας στις 30 ημέρες σε ασθενείς που υποβάλλονται σε ΔΕΑΒ με αυτοεκπτυσσόμενες βαλβίδες γενιάς σε σχέση με την προδιάταση με μπαλόνι. Υλικό και μέθοδος: Η μελέτη είναι προοπτική, πολυκεντρική, μη-τυχαιοποιημένη. 78 ασθενείς με σοβαρή στένωση αορτικής βαλβίδας υποβλήθηκαν σε TAVI με τη βαλβίδα ACURATE neo με σε κέντρα Ελλάδας και Πολωνίας. Όλοι οι ασθενείς υποβλήθηκαν σε προδιάταση με μπαλόνι. Η ομάδα αυτή συγκρίθηκε με τις τους ασθενείς της μελέτης DIRECT (85 ασθενείς με CoreValve/Evolut χωρίς προδιάταση με μπαλόνι και 86 με προδιάταση). Το πρωτογενές καταληκτικό σημείο είναι η επιτυχία συσκευής όπως ορίζεται από τα κριτήρια VARC-2 και συγκρίθηκε με τα αντίστοιχα ποσοστά βάσει ορισμών VARC και VARC-3. Τα δευτερογενή καταληκτικά σημεία ασφάλειας υπολογίστηκαν βάσει των ορισμών κατά VARC-2. Αποτελέσματα: Η επιτυχία συσκευής κατά VARC-2 υπολογίστηκε σε 87,2% για την ACURATE neo, 76,5% για τις CoreValve/Evolut χωρίς προδιάταση και 74,4% για τις CoreValve/Evolut με προδιάταση. Τα αντίστοιχα ποσοστά σε VARC-1 oορισμούς ήταν 91% έναντι 88.2% έναντι 87.2% (p=0.73) και σε VARC-3 87.2 έναντι 92.9% έναντι 91.9% (p=0.41) αντίστοιχα. 1 θάνατος συνέβη στην ομάδα ACURATE και κανένας στις άλλες 2 (p=0,31). Τα ποσοστά εμφύτευσης βηματοδότη (3.8 έναντι 22.4% έναντι 25.9%, p<0.001) και αναντιστοιχίας βαλβίδας-ασθενή (3.8 έναντι 21.2 έναντι 20.9, p=0.002) ήταν υπέρ της ACURATE neo. Η μεταδιάταση ήταν συχνότερη στην ομάδα της ACURATE (33.3 έναντι 29.4 έναντι 5.1%, p=0.018). Συμπεράσματα: H βαλβίδα ACURATE neo συνδυάζει υψηλά ποσοστά επιτυχημένης εμφύτευσης με ευνοϊκό προφίλ ασφαλείας και χαμηλό ποσοστό νέας εμφύτευσης μόνιμου βηματοδότη όταν εμφυτεύεται με προδιάταση. Η μεταδιάταση, ωστόσο, είναι συχνότερη, ενώ είναι σημαντικά χαμηλότερη στις βαλβίδες CoreValve/Evolut όταν εμφυτεύονται μετά από προδιάταση.
Correlations of betanodavirus load in the brain of experimentally infected sea bass (Dicentrarchus labrax, L.) with varying levels of resistance to viral nervous necrosis
Authors: BAKOPOULOS VASILEIOS , PANAGIOTAKI ANASTASIA , VALSAMIDIS MICHAIL-AGGELOS , WHITE DANIELLA-MARI , PAPAHARISIS LEONIDAS , DIMITROGLOU ARKADIOS , KAKAVA ELLI
Published: September 2023

The red-spotted grouper nervous necrosis virus (RGNNV) genotype of Betanodavirus causes significant losses to the European sea bass aquaculture industry. The lack of widely available vaccines against this genotype has led researchers and the industry to investigate other avenues for reducing mortality caused by the disease, such as the selection of resistant stocks. The objectives of this study were: a) to assess the presence of natural resistance in sea bass families propagated in the genetic improvement program of Nireus S.A., Greece and, b) to test an ELISA method able to detect viral coat antigen and measure viral load in the brain of tested fish. The second objective was to investigate virus antigen fluctuations during the course of the infection and its correlation with disease development, mortality and resistance. Further aspects of disease pathogenesis were investigated. A population of sea bass consisting of 89 families was experimentally infected with an RGNNV genotype of Betanodavirus; mortalities were recorded and brain samples from dead and survived fish were collected. Experimental infection of fish resulted in a typical pattern of mortality development that reached 56%. Different levels of natural resistance between families were found with cumulative mortality ranging from 20% to 86.2%. There was no statistical difference between the weight of dead fish and the resistant and susceptible families, except when extreme phenotypes were tested, indicating that the weight of fish that died was not a significant factor of final mortality. Brain virus load in the population as a whole increased sharply until D6 post-infection and then gradually dropped until the end of the experiment. When the viral load in the population (dead and survived fish) was tested against time of death, no correlation was found. In fish that survived the infection, the virus load remained high. The viral load per mg of brain tissue in samples taken from dead fish was not a factor that influenced family cumulative % mortality. Brain samples from survived fish reproduced the disease after infection of healthy fish. This study revealed a natural resistance of sea bass to Betanodavirus infection. This important finding can be used as an additional tool in reducing the mortality of cultured stocks. Additionally, there was clear evidence that fish surviving infection become subclinical carriers of the pathogen. Apparently, survival may not be associated with mechanisms of viral clearance but to other mechanisms that may suspend viral replication or aid infected cell endurance. These findings may assist in developing future vaccines and stock selection. A combination of effective vaccination and resistant stocks could be the way ahead.