bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonal plasticity and trait stability facilitate knotweed invasion in Europe
Authors: Cao Pei-Pei , Yin Wan-Dong , Bi Jing-Wen , Lin Tian-Tian , Wang Sheng-Yu , Zhou Hang , Liao Zhi-Yong , Zhang Lei , Parepa Madalin , Ju Rui-Ting , Ding Jian-Qing , Nie Ming , Bossdorf Oliver , Richards Christina L , Wu Ji-Hua , Li Bo
Published: July 2024

Invasive plant species pose significant ecological and economic threats due to their establishment and dominance in non-native ranges. Previous studies have yielded mixed results regarding the plants’ adaptive mechanisms for thriving in new environments, and particularly, little is known about how the phenotypic plasticity of growth and defense-related traits may facilitate plant invasion. This study addressed these uncertainties by employing the aggressive weed Reynoutria japonica as a study model. We examined the differences in growth, defense-related traits and biomass allocation between R. japonica populations from native and introduced ranges grown in two common gardens with distinct climate conditions. Our results demonstrated that while the introduced populations did not exhibit increases in height and total dry mass, nor reductions in leaf defense levels, their investment in leaf production was significantly higher compared to the native populations. Additionally, introduced populations displayed greater phenotypic plasticity in clonal ramet but less phenotypic plasticity in biomass production than native populations across varying environments. These findings highlight the roles of phenotypic plasticity and specific trait adaptations, such as clonality, in the successful invasion of R. japonica. This study has important implications for managing invasive plant species under changing environmental conditions.
Cross-effects of cultural and gay capitals in access to refugee status on the grounds of SOGI in France: Study of the formal and informal preparations of West African men for asylum trials
Authors: Bouchet-Mayer Cyriac , Ferez Sylvain
Published: July 2024

According to literature, ethnocentric representations of homosexuality structure the decision to grant asylum, or not, on the ground of sexual orientation. This ethnocentric criticism has recently led to a technicalization of evaluation practices by asylum judges, which are now based on a narrative and discursive mastery, a field in which respondents are unequal depending on their cultural and gay capitals. While the assessment as such appears to be more equitable, Western norms of gender and sexuality, and practicing self-narrative through their prism, continue to impose themselves in different ways, particularly in formal associative accompaniment or in informal preparation for the refugee status determination process. A 2-fold ethnographic approach, attentive to associative backing and the daily experience of exile as formal and informal spaces of asylum preparation and identity formation, is used to analyse the manner in which cultural and gay capitals influence identity formation, preparation for asylum trials, and chances of obtaining refugee status.
Prothrombin deficiency with recurrent subretinal hemorrhage
Authors: Qama Eros , Krishnamurthy Kritika , Mulvey Joseph J , Liu Kenneth G , Fernandes David L , Fang Yanan
Published: July 2024

Ocular hemorrhage has been recorded in congenital factor deficiencies like hemophilia A, but it has never been documented in prothrombin deficiency. Here, we describe an unusual case of sudden vision loss in the right eye caused by subretinal hemorrhage following a coughing episode in a 67-year-old woman. Notably, the patient underwent left eye enucleation 12 years previously under similar circumstances due to subretinal hemorrhage. During the interview, it was discovered that the patient had a history of prothrombin deficiency, which was subsequently confirmed through laboratory testing. Aside from recurrent ocular bleeding and 1 instance of bleeding following dental extraction in childhood, there is no other history of bleeding. Subsequent molecular studies revealed a homozygous missense mutation at G1499A (Arg500Gln), a variant previously identified as R457Q. Although the likelihood of prothrombin deficiency initiating subretinal hemorrhage is low, it is likely to worsen retinal hemorrhage and contribute to difficulty in controlling bleeding. A comprehensive coagulation workup is essential in patients with ocular hemorrhage. Determining factor II activity should be included in individuals exhibiting variably prolonged prothrombin time and activated partial thromboplastin time with correction in mixing studies. Additional investigations, such as genetic sequencing and family studies, are advised for those with isolated low prothrombin levels.
Spices and Herbs Increase Vegetable Palatability Among Military Service Members
Authors: D’Adamo Christopher R , Troncoso Melissa R , Piedrahita Gabriela , Messing Joshua , Scott Jonathan M
Published: July 2024

Introduction

Unhealthy eating behaviors are adversely impacting the health and performance of the U.S. armed forces. Vegetable intake, in particular, has been shown to be far below recommended levels in active duty military populations. Previous research in other populations has shown that the addition of spices and herbs can help overcome numerous barriers to vegetable intake. The goal of this study was to determine modifiable barriers to vegetable intake among a sample of active duty military service members at Naval Support Activity Bethesda and evaluate whether the addition of spices and herbs can help surmount these barriers.

Materials and Methods

Monadic sensory testing was conducted that compared typical preparation (butter and salt) of 4 vegetables (broccoli, carrots, cauliflower, and kale) vs. otherwise identical preparation with the addition of spices and herbs. The Menu Item Survey, a 9-point hedonic scale utilized throughout the U.S. Military for recipe development, was the primary outcome of the vegetable sensory testing. Questionnaires were administered to assess barriers to military dining facility vegetable intake. Unpaired t-tests were utilized to compare Menu Item Survey ratings of typical vegetables vs. vegetables with spices and herbs. Descriptive statistics were computed to summarize the results of the barriers questionnaires, and qualitative analysis of open-ended questions was conducted to identify perceived areas of improved vegetable intake.

Results

A diverse sample of 70 active duty service members participated in the vegetable sensory testing and provided outcome data. The most common barriers to military dining facility vegetable intake were appearance (42.9%), preparation style (41.3%), and taste (39.7%). Sensory testing revealed that vegetables with spices and herbs were preferred over typical preparations in overall appeal, flavor, and aroma (P <.03).

Discussion

The addition of spices and herbs appears to help overcome key sensory-related barriers to military dining facility vegetable intake. Future comparison of vegetable intake with and without spices and herbs when included in a full meal in a military dining setting is warranted in order to better evaluate the effectiveness in increasing vegetable intake under typical dining conditions.
A normal broad line AGN SDSS J1617+0638 as the host galaxy of a central tidal disruption event
Authors: Zhang Xue-Guang
Published: July 2024

In this manuscript, strong clues are reported to support the normal broad line AGN SDSS J1617+0638 as the host galaxy harbouring a central tidal disruption event (TDE). Through the optical flare in the CSS 8.5yr-long light curve and the none-variability in the up-to-date ASAS-SN light curves, the theoretical TDE model described by the mosfit code can be applied in SDSS J1617+0638. Meanwhile, considering the assumed central TDE expected continuum emissions not strong enough to describe the continuum emissions in the SDSS spectrum of SDSS J1617+0638, an additional power-law component from pre-existing AGN activity should be necessary in SDSS J1617+0638. Furthermore, considering the short time duration to the observed date for the SDSS spectrum from the starting time of the assumed central TDE in SDSS J1617+0638, TDE model expected accreting mass only about 0.03 $\mathrm{ M}_\odot$ can lead to few effects of TDEs debris on the observed broad emission lines in the SDSS spectrum of SDSS J1617+0638, indicating the TDE model determined BH mass simply consistent with the virial BH mass by broad emission lines, as determined results in SDSS J1617+0638. Therefore, through both the photometric variability and the spectroscopic results, a central TDE can be preferred in the normal broad line AGN SDSS J1617+0638  with pre-existing central AGN activity and pre-existing broad emission line regions.
Fast and Accurate Estimation of Selection Coefficients and Allele Histories from Ancient and Modern DNA
Authors: Vaughn Andrew H , Nielsen Rasmus
Published: July 2024

We here present CLUES2, a full-likelihood method to infer natural selection from sequence data that is an extension of the method CLUES. We make several substantial improvements to the CLUES method that greatly increases both its applicability and its speed. We add the ability to use ancestral recombination graphs on ancient data as emissions to the underlying hidden Markov model, which enables CLUES2 to use both temporal and linkage information to make estimates of selection coefficients. We also fully implement the ability to estimate distinct selection coefficients in different epochs, which allows for the analysis of changes in selective pressures through time, as well as selection with dominance. In addition, we greatly increase the computational efficiency of CLUES2 over CLUES using several approximations to the forward–backward algorithms and develop a new way to reconstruct historic allele frequencies by integrating over the uncertainty in the estimation of the selection coefficients. We illustrate the accuracy of CLUES2 through extensive simulations and validate the importance sampling framework for integrating over the uncertainty in the inference of gene trees. We also show that CLUES2 is well-calibrated by showing that under the null hypothesis, the distribution of log-likelihood ratios follows a χ2 distribution with the appropriate degrees of freedom. We run CLUES2 on a set of recently published ancient human data from Western Eurasia and test for evidence of changing selection coefficients through time. We find significant evidence of changing selective pressures in several genes correlated with the introduction of agriculture to Europe and the ensuing dietary and demographic shifts of that time. In particular, our analysis supports previous hypotheses of strong selection on lactase persistence during periods of ancient famines and attenuated selection in more modern periods.
Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens
Authors: Yang Chao , Yao Longfeng , Chen Dan , Chen Changling , Li Wenbo , Tong Hua , Cheng Zihang , Yan Yanling , Lin Long , Zhang Jing , Shi Anbing
Published: July 2024

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10’s involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal’s response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
The Importance of Emotional Intelligence in Social Work Students and Its Relation to Perceived Efficacy
Authors: Chinchilla Francisco Lucas , Fernández Natalia Beni , Queiruga Dolores Alicia , Montañés Muro Pilar
Published: July 2024

Social workers have a greater than average risk of suffering burnout syndrome. In the same way as the professionals, students too can suffer academic burnout. However, few empirical studies have studied burnout and protective factors in social work students exclusively. Emotional intelligence (EI) has been described as a protective factor for burnout both in the professional and the academic context. The present study aims to explore which components of EI predict the burnout domains in students studying a degree in social work, in Spain. To this end, 87 social work students completed a questionnaire in which information was gathered on EI, burnout, average grade in the degree, and sociodemographic variables. The regression analysis results indicate that the students with poorer academic success and from higher years reported greater symptoms of burnout. Regarding the components of EI, emotional clarity and emotional repair predict the academic efficacy perceived by the students. These results highlight the importance of including EI in academic policies to promote the design of EI training programs aimed at developing EI skills, particularly emotional clarity and emotional repair, as a way of improving the perception of efficacy in social work students.
In Vitro Efficacy of Various Fungicides Against Fungi Associated with Leaf, Stem, and Soilborne Diseases of Proteaceae in Hawai‘i, U.S.A.
Authors: Luiz Blaine C. , Sugiyama Lionel S. , Bushe Brian C. , Lutgen Hannah , Keith Lisa M.
Published: July 2024

Species in the Proteaceae have been important ornamental plants cultivated for both cut flowers and foliage in Hawaiian agriculture since the 1960s. Symptoms ranging from spots on leaves and flowers to branch lesions and cankers, as well as dieback, have been reported on various Proteaceae in Hawai‘i and attributed to various fungi. Nurseries can experience significant economic losses if symptoms are not controlled. Few studies are available regarding the effectiveness of chemical treatments to reduce disease incidence and severity. The efficacy of six ornamental fungicides from various Fungicide Resistance Action Committee (FRAC) groups were evaluated in vitro for their ability to inhibit the mycelial growth of nine fungal isolates of six known or suspected protea pathogen genera ( Diaporthe, Alternaria, Neofusicoccum, Neopestalotiopsis, Phomopsis, and Calonectria). Isolates were recovered from symptomatic stems and leaves, as well as soil surrounding diseased Proteaceae grown at the Maui Agricultural Research Center (MARC), Kula, HI, and from 10 commercial farms on Maui. All fungicides evaluated in the study inhibited the in vitro growth of some, if not all, of the nine isolates to some capacity. Tebuconazole was the most effective fungicide, reducing mycelial growth of all isolates by ≥85% or more compared with the nonamended control plates. Rotation of these fungicides could potentially be used for disease management against a broad range of pathogens infecting Proteaceae in Hawai‘i.
Greater molecular potential for glucose metabolism in adipose tissue and skeletal muscle of women compared with men
Authors: Nicolaisen Trine S. , Sjøberg Kim A. , Carl Christian S. , Richter Erik A. , Kiens Bente , Fritzen Andreas M. , Lundsgaard Anne‐Marie
Published: July 2024

Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole‐body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic–euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose‐stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2‐fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men.
Mapping High-Risk Arteries Using Doppler Ultrasound for Forehead Contouring in Korean Patients
Authors: Lee Won , Kim Tae-Ho , Yang Eun-Jung
Published: July 2024

BACKGROUND

Forehead flatness is common in Korean populations, and one of the most straightforward techniques for adding volume and achieving a concave forehead is injecting hyaluronic acid (HA) filler. However, definitive guidelines for this procedure are lacking, and careful attention to the arterial anatomy is required to avoid vascular complications.

OBJECTIVE

The authors aimed to establish guidelines for performing forehead augmentation using Doppler ultrasound to identify vasculature before HA injection.

METHODS AND MATERIALS

Arterial mapping of the faces of 34 patients was performed using Doppler ultrasound. Each anatomic layer (skin, subcutaneous fat, and galea aponeurotica) of the forehead with blood vessels was identified. An average volume of 2.85 mL of HA filler was injected. Postoperative complications, such as infection, hematoma, bruising, nodules, skin necrosis, and blindness, were evaluated.

RESULTS

Using Doppler ultrasound, the authors successfully traced all 3 blood vessels (supraorbital, supratrochlear, and frontal branch of the superficial temporal arteries) and avoided them during HA injection. None of the patients experienced arterial complications.

CONCLUSION

Doppler ultrasound proves to be an effective technique for arterial mapping, enabling the identification and avoidance of the major blood vessels of the forehead before HA filler injection.
Lack of Interchangeability Between 3 Different Methods for Quantification of Everolimus in Blood: ACMIA, LTIA, and UHPLC-MS/MS
Authors: Miyagi Chika , Tanaka Ryota , Shiraiwa Ken , Tatsuta Ryosuke , Itoh Hiroki
Published: July 2024

Background:

Affinity chrome-mediated immunoassays (ACMIA) do not require pretreatment and have a wide calibration range and good analytical performance. To date, no studies have compared ACMIA and latex agglutination turbidimetry immunoassays (LTIA). The objective of this study was to evaluate the interchangeability of ACMIA, LTIA, and the previously developed ultra–high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS).

Methods:

A total of 111 whole blood samples were collected from 25 patients undergoing routine everolimus therapeutic drug monitoring. The interchangeability between the 3 methods was assessed using robust Passing–Bablok regression analysis and Bland–Altman plots.

Results:

All samples were quantifiable by UHPLC-MS/MS, whereas 56 and 1 samples were below the lower limits of quantification by LTIA and ACMIA, respectively. In the robust Passing–Bablok regression plots, the slopes of the regression equations between ACMIA and UHPLC-MS/MS, LTIA and UHPLC-MS/MS, and ACMIA and LTIA were 1.23 (95% [confidence interval] CI, 1.13–1.33), 0.67 (95% CI, 0.57–0.77), and 1.71 (95% CI, 1.43–2.33), respectively, with significant proportional biases indicating no interchangeability among all 3 methods. Bland–Altman plots also revealed statistically significant proportional biases between ACMIA and UHPLC-MS/MS (P = 0.012), LTIA and UHPLC-MS/MS (P < 0.001), and ACMIA and LTIA (P < 0.001).

Conclusions:

Statistically significant proportional biases were observed among the 3 methods. Blood everolimus concentration measurements should be interpreted with caution when switching the quantification methods for therapeutic drug monitoring.
B cells expressing mutated IGHV1-69–encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection
Authors: Schultheiß Christoph , Willscher Edith , Paschold Lisa , Ackermann Christin , Escher Moritz , Scholz Rebekka , Knapp Maximilian , Lützkendorf Jana , Müller Lutz P. , Schulze zur Wiesch Julian , Binder Mascha
Published: July 2024

Background:

Chronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear.

Methods:

We sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors.

Results:

We identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT.

Conclusions:

We provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination.
Long-term HBV infection of engineered cultures of induced pluripotent stem cell-derived hepatocytes
Authors: Yuan Yang , Bodke Vedant V. , Lin Christine , Gao Shang , Rehman Jalees , Li Jisu , Khetani Salman R.
Published: July 2024

Background:

HBV infects ~257 million people and can cause hepatocellular carcinoma. Since current drugs are not curative, novel therapies are needed. HBV infects chimpanzee and human livers. However, chimpanzee studies are severely restricted and cost-prohibitive, while transgenic/chimeric mouse models that circumvent the species barrier lack natural HBV infection and disease progression. Thus, in vitro human models of HBV infection are useful in addressing the above limitations. Induced pluripotent stem cell-derived hepatocyte-like cells mitigate the supply limitations of primary human hepatocytes and the abnormal proliferation/functions of hepatoma cell lines. However, variable infection across donors, deficient drug metabolism capacity, and/or low throughput limit iHep utility for drug development.

Methods:

We developed an optimal pipeline using combinations of small molecules, Janus kinase inhibitor, and 3’,5’-cAMP to infect iHep-containing micropatterned co-cultures (iMPCC) with stromal fibroblasts within 96-well plates with serum-derived HBV and cell culture-derived HBV (cHBV). Polyethylene glycol was necessary for cell-derived HBV but not for serum-derived HBV infection.

Results:

Unlike iHep monocultures, iMPCCs created from 3 iHep donors could sustain HBV infection for 2+ weeks. Infected iMPCCs maintained high levels of differentiated functions, including drug metabolism capacity. HBV antigen secretion and gene expression patterns in infected iMPCCs in pathways such as fatty acid metabolism and cholesterol biosynthesis were comparable to primary human hepatocyte-MPCCs. Furthermore, iMPCCs could help elucidate the effects of interferons and direct-acting antiviral drugs on the HBV lifecycle and any hepatotoxicity; iMPCC response to compounds was similar to primary human hepatocyte-MPCCs.

Conclusions:

The iMPCC platform can enable the development of safe and efficacious drugs against HBV and ultimately help elucidate genotype-phenotype relationships in HBV pathogenesis.
Reversal of hepatic accumulation of nordeoxycholic acid underlines the beneficial effects of cholestyramine on alcohol-associated liver disease in mice
Authors: Guo Wei , Zhong Wei , He Liqing , Wei Xiaoyuan , Hao Liuyi , Dong Haibo , Yue Ruichao , Sun Xinguo , Yin Xinmin , Zhao Jiangchao , Zhang Xiang , Zhou Zhanxiang
Published: July 2024

Background:

Dysregulation of bile acids (BAs) has been reported in alcohol-associated liver disease. However, the causal relationship between BA dyshomeostasis and alcohol-associated liver disease remains unclear. The study aimed to determine whether correcting BA perturbation protects against alcohol-associated liver disease and elucidate the underlying mechanism.

Methods:

BA sequestrant cholestyramine (CTM) was administered to C57BL/6J mice fed alcohol for 8 weeks to assess its protective effect and explore potential BA targets. The causal relationship between identified BA metabolite and cellular damage was examined in hepatocytes, with further manipulation of the detoxifying enzyme cytochrome p450 3A11. The toxicity of the BA metabolite was further validated in mice in an acute study.

Results:

We found that CTM effectively reversed hepatic BA accumulation, leading to a reversal of alcohol-induced hepatic inflammation, cell death, endoplasmic reticulum stress, and autophagy dysfunction. Specifically, nordeoxycholic acid (NorDCA), a hydrophobic BA metabolite, was identified as predominantly upregulated by alcohol and reduced by CTM. Hepatic cytochrome p450 3A11 expression was in parallel with NorDCA levels, being upregulated by alcohol and reduced by CTM. Moreover, CTM reversed alcohol-induced gut barrier disruption and endotoxin translocation. Mechanistically, NorDCA was implicated in causing endoplasmic reticulum stress, suppressing autophagy flux, and inducing cell injury, and such deleterious effects could be mitigated by cytochrome p450 3A11 overexpression. Acute NorDCA administration in mice significantly induced hepatic inflammation and injury along with disrupting gut barrier integrity, leading to subsequent endotoxemia.

Conclusions:

Our study demonstrated that CTM treatment effectively reversed alcohol-induced liver injury in mice. The beneficial effects of BA sequestrant involve lowering toxic NorDCA levels. NorDCA not only worsens hepatic endoplasmic reticulum stress and inhibits autophagy but also mediates gut barrier disruption and systemic translocation of pathogen-associated molecular patterns in mice.
Immuno-targeting the ectopic phosphorylation sites of PDGFRA generated by MAN2A1-FER fusion in HCC
Authors: Kader Muhamuda , Yu Yan-Ping , Liu Silvia , Luo Jian-Hua
Published: July 2024

Background:

HCC is one of the most lethal cancers for humans. Mannosidase alpha class 2A member 1 (MAN2A1)-FER is one of the most frequent oncogenic fusion genes in HCC. In this report, we showed that MAN2A1-FER ectopically phosphorylated the extracellular domains of PDGFRA, MET, AXL, and N-cadherin. The ectopic phosphorylation of these transmembrane proteins led to the activation of their kinase activities and initiated the activation cascades of their downstream signaling molecules.

Methods:

A panel of mouse monoclonal antibodies was developed to recognize the ectopic phosphorylation sites of PDGFRA.

Results and conclusions:

The analyses showed that these antibodies bound to the specific phosphotyrosine epitopes in the extracellular domain of PDGFRA with high affinity and specificity. The treatment of MAN2A1-FER–positive cancer HUH7 with one of the antibodies called 2-3B-G8 led to the deactivation of cell growth signaling pathways and cell growth arrest while having minimal impact on HUH7ko cells where MAN2A1-FER expression was disrupted. The treatment of 2-3B-G8 antibody also led to a large number of cell deaths of MAN2A1-FER–positive cancer cells such as HUH7, HEPG2, SNU449, etc., while the same treatment had no impact on HUH7ko cells. When severe combined immunodeficiency mice xenografted with HEPG2 or HUH7 were treated with monomethyl auristatin E-conjugated 2-3B-G8 antibody, it slowed the progression of tumor growth, eliminated the metastasis, and reduced the mortality, in comparison with the controls. Targeting the cancer-specific ectopic phosphorylation sites of PDGFRA induced by MAN2A1-FER may hold promise as an effective treatment for liver cancer.
Knowledge of Glaucoma Among New Patients to a Tertiary Eye Care Center in China
Authors: Li Ningfeng , Yang Yu , Ye Dan , Wu Ethan , Cheng Lu , Jin Ling , Ling Yunlan , Huang Jingjing
Published: July 2024

Précis:

Patients with glaucoma who had previously been evaluated by eye care professionals at lower-level facilities possessed limited awareness and knowledge about their condition upon presentation to a tertiary-care ophthalmic hospital, highlighting the need for improved patient education throughout the healthcare system.

Purpose:

To investigate the depth of knowledge about glaucoma among patients who were referred to a tertiary eye hospital for their first visit.

Material and Methods:

An internally designed questionnaire (scored 0–15) assessing patients’ knowledge about glaucoma was administered at a glaucoma outpatient service. Patients were divided into normal, high-risk, and glaucoma groups based on comprehensive eye evaluation. Scores were analyzed by regression models. The relationship between glaucoma awareness and the stage of disease at presentation was explored.

Results:

One hundred thirty patients were enrolled and divided into 3 groups. The group with definitive diagnosis of glaucoma had the most prior medical visits but scored the lowest, with the primary source of information being previous healthcare providers. The high-risk group possessed more knowledge about glaucoma than the other groups and tended to acquire knowledge from the media and sought tertiary care earlier. Significant differences were observed between the glaucoma and the high-risk groups in all aspects of glaucoma knowledge (P < 0.05). In addition, the average scores of all participants who had visited lower-level facilities were low. Education, economic status, presence of risk factors for glaucoma positively correlated with awareness and knowledge, whereas age had an inverse relationship (all P < 0.05). Ophthalmic visit frequency had no impact (P > 0.05). Doctors were the primary source of information for all groups, but social media users were better informed.

Conclusions:

Patients at tertiary eye care centers lack glaucoma knowledge, despite experience with eye care providers previously. Implementing health education at all levels is crucial in preventing glaucoma-related visual impairment.
Evaluation of the Variability of Ambient Interactive Zippy Estimation of Sequential Rapid Tests on the “imo” Perimeter in Patients With Stable Glaucoma
Authors: Kitagawa Atsuko , Horiguchi Go , Nomoto Hiroki , Shimizu Michiko , Hironobu Mayumi , Ue Akemi , Teramukai Satoshi , Matsumoto Chota
Published: July 2024

Précis:

Analysis of Ambient Interactive Zippy Estimation of Sequential Testing (AIZE) Rapid test variability in patients with stable glaucoma showed that the 95% prediction interval of the mean deviation (MD) value, potentially an index for judging progression, was ±1.63 to ±1.78 dB in early-to-moderate-stage patients.

Objective:

To explore the 95% prediction interval of the MD value using the AIZE Rapid test strategy for glaucoma observation.

Patients and Methods:

This study included 72 patients with stable or suspected glaucoma who underwent the imo AIZE Rapid test 3 times or more within 2 years. Both eyes from each patient were classified as better or worse eyes. They were divided based on baseline MD values into the following 4 groups: MD > −3 dB, −6 dB < MD ≤ −3 dB, −12 dB < MD ≤ −6 dB, and MD ≤ −12 dB. The variability of MD during the observation period and the 95% prediction intervals were analyzed. Pointwise variability of limits at each test location was also calculated.

Results:

The numbers of better and worse eyes included in the study were 46 and 33. The median follow-up period was 1.3 years (range: 0.5 to 1.9 y). The 95% prediction intervals for MD values were ±1.41 dB for better eyes (n = 46) and ±1.47 dB for worse eyes (n = 33). The 95% prediction intervals in the MD > −3 dB, −6 dB < MD ≤ −3 dB, −12 dB < MD ≤ −6 dB, and MD ≤ −12 dB groups were ±1.63 dB, ±1.34 dB, ±1.78 dB, and ±1.33 dB, respectively. Pointwise variability of worse eyes was larger than that of better eyes, especially between 10 to 15 dB.

Conclusion:

In the case of a difference in MD greater than the 95% prediction intervals when compared with the previous visual field result, we should pay much attention to the possibility of progression of the glaucomatous visual field in patients with stable glaucoma.
Pneumonia With Empyema: A Rare Clinical Presentation of Bartonella henselae Infection in a 10-Year-old Boy
Authors: Topalušić Iva , Pejić Josip , Grmoja Tonći , Butić Iva , Pavić Ivan
Published: July 2024

Background:

Cat-scratch disease is a common zoonosis in children. However, atypical clinical presentation of cat-scratch disease is less common, and lung involvement is particularly rare. The usual presentation of lung disease in bartonellosis includes other organ involvement and is more common in immunocompromised patients.

Case Report:

We present a 10-year-old immunocompetent patient with pneumonia and inoculated empyema caused by Bartonella henselae, without any other organ involvement, which occurred 2 weeks after lymphadenopathy. The definite diagnosis was established using the polymerase chain reaction of the empyema obtained from thoracocentesis. The boy was treated with several antibiotics (ceftriaxone, azithromycin, amoxicillin with clavulanic acid, meropenem and vancomycin) and completely recovered after the 3-month follow-up period.

Conclusions:

This is a unique case of the difficult-to-treat pneumonia with inoculated empyema, caused by B. henselae, in an immunocompetent child, without any other organ involvement. The clinical course was favorable. A high level of clinical suspicion is mandatory for the diagnosis.
Lateral Temporal Bone Resection With a High-Riding Jugular Bulb
Authors: Page Joshua Cody , Nader Marc-Elie , Gidley Paul W.
Published: July 2024

A high-riding jugular bulb can complicate standard otologic and neurotologic approaches and must be taken into account during surgical planning.
Distal versus traditional radial access in patients undergoing emergency coronary angiography or percutaneous coronary intervention: a systematic review and meta-analysis
Authors: Bittar Vinicius , Trevisan Thierry , Clemente Mariana R. C. , Pontes Guilherme , Felix Nicole , Gomes Wilton F.
Published: July 2024

Background

Distal radial access (DRA) is a well-tolerated and effective alternative to traditional radial access (TRA) for coronary procedures. However, the comparative value of these modalities remains unknown in the emergency setting, particularly in patients with ST-elevation myocardial infarction (STEMI).

Objective

To compare DRA versus TRA for emergency coronary procedures through a meta-analysis

Methods

We systematically searched PubMed, Embase, and Cochrane databases to identify studies comparing DRA versus TRA in patients undergoing emergency coronary angiography (CAG) or percutaneous coronary intervention (PCI). All statistical analyses were performed using R software version 4.3.1 with a random-effects model.

Results

We included four studies comprising 543 patients undergoing emergency CAG or PCI, of whom 447 (82.3%) had STEMI. As compared with TRA, DRA was associated with lower radial artery occlusion rates (RR, 0.21; 95% CI, 0.06–0.72) and shorter hemostasis time (MD, −4.23 h; 95% CI, −6.23 to 2.13). There was no significant difference between modalities in terms of puncture failure (RR, 1.38; 95% CI, 0.31–6.19), crossover access (RR, 1.37; 95% CI, 0.42–4.44), puncture time (SMD, 0.33; 95% CI, −0.16 to 0.81), procedure time (MD, 0.97 min; 95% CI, −5.19 to 7.13), or rates of cannulation success (RR, 0.94; 95% CI, 0.83–1.06). In terms of other periprocedural complications, there were no differences between both groups. These findings remained consistent in a subgroup analysis of patients with STEMI.

Conclusion

In this meta-analysis, DRA was superior to TRA in terms of radial artery occlusion and hemostasis time, with similar rates of periprocedural complications.
Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis
Authors: Fang Yingying , Lou Dandi , Zhou Jie , Zhang Qiufeng , Dai Youran , Ren Wei
Published: July 2024

Objective:

This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE).

Methods:

PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence.

Results:

Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups.

Conclusions:

P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.
Diagnostic Performance of Stool-based Testing for Colorectal Lesions Among Average-risk Individuals
Authors: Cheney Catherine , Parish Alice , Niedzwiecki Donna , Oko Chukwuemeka , Walters Christy , Sullivan Brian A.
Published: July 2024

Objective:

We assessed the real-world performance of stool-based tests (SBTs) for colorectal cancer screening.

Materials and Methods:

Retrospective review of average-risk individuals with positive SBT for advanced neoplasia (adenocarcinoma, advanced adenoma, and/or advanced serrated lesions) detection at follow-up colonoscopy.

Results:

There was no statistical difference in the detection of advanced neoplasia (P= 0.16) between SBTs [30.7% for multitargeted stool DNA (mt-sDNA) vs 22.8% for fecal immunochemical test]. However, there was a significant difference in the detection of advanced serrated lesions (11.3% for mt-sDNA vs 1.8% for fecal immunochemical test, P< 0.001).

Conclusion:

There was no difference between SBTs for advanced neoplasia detection, though mt-sDNA detected significantly more advanced serrated lesions.
Elexacaftor–tezacaftor–ivacaftor use after solid organ transplant
Authors: Kapnadak Siddhartha G. , Ramos Kathleen J.
Published: July 2024

Purpose of review

In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor–tezacaftor–ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients.

Recent findings

Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI.

Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.
Association of early doses of diuretics and nitrates in acute heart failure with 30 days outcomes: ancillary analysis of ELISABETH study
Authors: Gorlicki Judith , Nekrouf Célia , Miró Òscar , Cotter Gad , Davison Beth , Mebazaa Alexandre , Simon Tabassome , Freund Yonathan
Published: July 2024

Aims

The optimal dose of diuretics and nitrates for acute heart failure treatment remains uncertain. This study aimed to assess the association between intravenous nitrates and loop diuretics doses within the initial 4 h of emergency department presentation and the number of days alive and out of hospital (NDAOH) through 30 days.

Methods

This was an ancillary study of the ELISABETH stepped-wedge cluster randomized trial that included 502 acute heart failure patients 75 years or older in 15 French emergency departments. The primary endpoint was the NDAOH at 30 days. The total dose of intravenous nitrates and loop diuretics administered in the initial 4 h were each categorized into three classes: ‘no nitrate’, ‘> 0–16’, and ‘> 16 mg’ for nitrates and ‘< 60’, ‘60’, and ‘> 60 mg’ for diuretics. Secondary endpoints included 30-day mortality, 30-day hospital readmission, and hospital length of stay in patients alive at 30 days. Generalized linear mixed models were used to examine associations with the endpoints.

Results

Of 502 patients, the median age was 87 years, with 59% women. The median administered dose within the initial 4 h was 16 mg (5.0; 40.0) for nitrates and 40 mg (40.0; 80.0) for diuretics. The median NDAOH at 30 days was 19 (0.0–24.0). The adjusted ratios of the NDAOH were 0.88 [95% confidence interval (CI): 0.63–1.23] and 0.76 (95% CI: 0.58–1.00) for patients that received 60 and > 60 mg, respectively, compared with patients that received 40 mg or less of diuretics. Compared with patients who did not receive nitrates, the adjusted ratios of the NDAOH were 1.17 (95% CI: 0.82–1.67) and 1.45 (95% CI: 0.90–2.33) for patients who received 1–16 and > 16 mg, respectively. There was no significant association with any of the secondary endpoints.

Conclusion

In this ancillary analysis, there was no significant association between different doses of diuretics and nitrates with the NDAOH at 30 days. Point estimates and CIs may suggest that the optimal doses are less than 60 mg of diuretics, and more than 16 mg of nitrates in the first 4 h.
Correlation of PSA blood levels with standard uptake value maximum (SUVmax) and total metabolic tumor volume (TMTV) in 18F-PSMA-1007 and 18F-choline PET/CT in patients with biochemically recurrent prostate cancer
Authors: Fragkiadaki Vasiliki , Panagiotidis Emmanouil , Vlontzou Evaggelia , Kalathas Theodoros , Paschali Anna , Kypraios Charalampos , Chatzipavlidou Vasiliki , Datseris Ioannis
Published: July 2024

Objectives

In this prospective study, we investigated the correlation between prostate-specific antigen (PSA) levels in the blood of patients with prostate cancer in biochemical recurrence after radical treatment with the semiquantitative parameters standard uptake value maximum (SUVmax) and the total metabolic tumor volume (TMTV) in the metastatic foci depicted in 18F-prostate-specific membrane antigen (PSMA)-1007 and 18F-choline PET/computed tomography (CT) imaging.

Methods

We prospectively examined 104 patients with biochemical relapse of prostate cancer after primary definitive treatment. All patients underwent one 18F-PSMA-1007 and one 18F-choline PET/CT examination in randomized order within a time frame of 10 days and were followed for at least 6 months (182 ± 10 days). The semiquantitative parameters of SUVmax and metabolic tumor volume (MTV) of each neoplastic lesion in PET/CT imaging were calculated, and further summation of each MTV value was done to calculate the TMTV.

Results

According to the Spearman correlation analysis, a positive correlation was found between PSA levels and SUVmax and TMTV scores in the metastatic foci of 18F-PSMA-1007 PET/CT (r = 0.24 and 0.35, respectively; P < 0.05) and SUVmax in the lesions of 18F-choline PET/CT (r = 0.28; P < 0.0239). However, a positive but NS correlation was demonstrated between values of PSA and TMTV for each lesion in the 18F-choline PET/CT study (r = 0.22; P = 0.0795). The detection rate of the different PSA levels with a cutoff of 1 ng/ml was higher for 18F-PSMA-1007 than 18F-choline.

Conclusion

In biochemical relapse patients there is a positive correlation between PSA levels in the blood and the semiquantitative parameters SUVmax and TMTV of the metastatic foci in the 18F-PSMA-1007 and 18F-Choline PET/CT imaging.