bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractWomen 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.
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.