bluuebunny/crossref_metadata_2025 huggingface dataset:
NF2 loss-of-function and hypoxia drive radiation resistance in grade 2 meningiomas
Authors: Patel Bhuvic , Pugazenthi Sangami , English Collin W , Nitturi Vijay , Pari Shree S , Mahlokozera Tatenda , Leidig William A , Lu Hsiang-Chih , Yang Alicia , Roberts Kaleigh , DeSouza Patrick , McGeehan Kyle P , Mao Diane D , Sinha Namita , Ippolito Joseph E , Dahiya Sonika , Petti Allegra , Yano Hiroko , Klisch Tiemo J , Harmanci Akdes S , Patel Akash J , Kim Albert H
Published: January 2025

Background

World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. G2Ms with histopathological necrosis have been associated with worse local control (LC) following radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods

We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival following ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as eight G2Ms by single nuclei RNA sequencing.

Results

NF2 loss-of-function (LOF) mutations were associated with necrosis in G2Ms (p = .0127). Tumors with NF2 mutation and necrosis had worse post-radiation LC compared to NF2 wildtype tumors without necrosis (p = .035). Under hypoxic conditions, NF2 knockdown increased radiation resistance in vitro (p < .001). Bulk RNA sequencing revealed NF2- and hypoxia-specific changes and a 50-gene set signature specific to radiation resistant, NF2 knockdown and hypoxic cells, which distinguished NF2 mutant/necrotic patient G2Ms by unsupervised clustering. Enrichment analysis revealed downregulation of apoptosis pathway genes and upregulation of proliferation-associated genes and genes normally downregulated after UV radiation exposure in NF2-mutant/necrotic tumor cells, which were validated with functional assays.

Conclusions

NF2 LOF in the setting of hypoxia confers radiation resistance through transcriptional programs that reduce apoptosis and promote proliferation. These pathways may identify tumors resistant to radiation and represent therapeutic targets that in the future could improve LC in patients with radiation resistant G2Ms.
Size matters: early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors
Authors: Derks S H A E , Ho L S , Koene S R , Starmans M P A , Oomen-de Hoop E , Joosse A , de Jonge M J A , Naipal K A T , Jongen J L M , van den Bent M J , Smits M , van der Veldt A A M
Published: January 2025

Background

Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within six months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM.

Methods

In this single-centre cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (i.e. within six months after start of ICIs) and intracranial progression-free survival (PFS), respectively.

Results

A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥4 BMs and 53.7% of patients had at least one BM with a diameter ≥10mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (Odds ratio 1.10, 95%CI 1.05-1.15, p<0.001). On the patient level, having at least one BM ≥10mm was associated with shorter intracranial PFS (Hazard ratio 2.08, 95%CI 1.64-5.56, p<0.001).

Conclusions

Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥10mm.
HIV-related differences in placental immunology: Data from the PRACHITi cohort in Pune, India
Authors: Mathad Jyoti S , Alexander Mallika , Bhosale Ramesh , Naik Shilpa , Cranmer Lisa Marie , Kulkarni Vandana , Busch Sydney , Chalem Andrea , Gitlin Emily , Lei Jun , Liu Anguo , Liu Jin , Liu Yang , Shivakoti Rupak , Gupta Amita , Burd Irina
Published: January 2025

Background

Maternal HIV infection can affect placental immunology and expression of the neonatal crystallizable fragment receptor (FcRn), which allows transplacental antibody transfer. This study delineated differences in placental FcRn and T-cell expression by HIV status, with or without viral suppression.

Methods

This observational cohort study in Pune, India, followed pregnant women with and without HIV through one year postpartum; 42 had placenta collected, stratified by HIV status. FcRn expression was analyzed by Western blot (normalized by GADPH) and compared using ImageJ. Placental CD4/CD8 abundance was assessed by immunofluorescent counting per high powered field.

Results

The median gestational age at delivery was 38.3 weeks (IQR: 37.5-39.1). Of 18 women living with HIV, all were on combined antiretroviral therapy with a median CD4 of 455 cells/mm3 (IQR 281-640) at entry and 429 cells/mm3 (IQR 317-686) at delivery. Ten had undetectable virus (£40 copies/mL); of those with detectable virus, the median viral load was 151 copies/mL (IQR: 118.15-539334). Relative placental FcRn expression was lower in women living with HIV compared to without (median 0.54 vs. 0.84, p=0.01) and not associated with CD4 or viral load. Women living with HIV had significantly higher abundance of placental CD8+ T-cells, regardless of viral suppression, compared to women without.

Conclusions

Maternal HIV, even with viral suppression, is associated with lower placental FcRn expression and increased placental CD8+ T-cells. These results suggest that dysregulation may not be completely reversed by antiretroviral therapy and could contribute to poorer infant outcomes, even in the absence of mother-to-child HIV transmission.
Proteomic Analyses in COVID-19-Associated Secondary Hemophagocytic Lymphohistiocytosis
Authors: Canny Susan P. , Stanaway Ian B. , Holton Sarah E. , Mitchem Mallorie , O’Rourke Allison R. , Pribitzer Stephan , Baxter Sarah K. , Wurfel Mark M. , Malhotra Uma , Buckner Jane H. , Bhatraju Pavan K. , Morrell Eric D. , Speake Cate , Mikacenic Carmen , Hamerman Jessica A.
Published: January 2025

CONTEXT:

COVID-19 has been associated with features of a cytokine storm syndrome with some patients sharing features with the hyperinflammatory disorder, secondary hemophagocytic lymphohistiocytosis (sHLH).

HYPOTHESIS:

We hypothesized that proteins associated with sHLH from other causes will be associated with COVID-sHLH and that subjects with fatal COVID-sHLH would have defects in immune-related pathways.

METHODS AND MODELS:

We identified two cohorts of adult patients presenting with COVID-19 at two tertiary care hospitals in Seattle, Washington in 2020 and 2021. In this observational study, we assessed clinical laboratory values and plasma proteomics. Subjects identified as having sHLH (ferritin > 1000 plus cytopenias in two or more lineages [WBC < 5000 odds ratio [OR] ANC (absolute neutrophil count) < 1000, hemoglobin < 9 or hematocrit < 27, platelets < 100,000], and elevated transaminases [either AST (aspartate aminotransferase) or ALT (alanine aminotransferase) > 30] OR subjects with a ferritin > 3000) were compared with those with COVID-19 without sHLH. We identified 264 patients with COVID-19 of whom 24 met our sHLH definition. Eight patients who died of COVID-sHLH underwent genomic sequencing to identify variants in immune-related genes.

RESULTS:

Nine percent of enrolled COVID-19 subjects met our defined criteria for sHLH (n = 24/264). Using broad serum proteomic approaches (O-link and SomaScan), we identified three proteins increased in subjects with COVID-19-associated sHLH (soluble PD-L1 [sPD-L1], tumor necrosis factor-R1, and interleukin [IL]-18BP, p < 0.05 for O-link and false discovery rate < 0.05 for SomaScan), supporting a role for proteins previously associated with other forms of sHLH (IL-18BP and soluble tumor necrosis factor receptor 1). We also identified candidate proteins and pathways associated with COVID-sHLH, including sPD-L1 and the syntaxin pathway. We detected pathogenic variants in DOCK8 and TMPRSS15 in deceased individuals with COVID-sHLH, further suggesting that alterations in immune-related processes may contribute to hyperinflammation and fatal outcomes in COVID-19.

INTERPRETATIONS AND CONCLUSIONS:

Proteins increased in COVID-19-associated sHLH, such as sPD-L1, and pathways, such as the syntaxin pathway, suggest important roles for the immune response in driving sHLH in the context of COVID-19.
Effectiveness of a Pharmacist-Led Intervention to Reduce Acid Suppression Therapy for Stress Ulcer Prophylaxis in ICUs in China: A Multicenter, Stepped-Wedge, Cluster-Randomized Controlled Trial
Authors: Li Hailong , Zeng Linan , Xu Peipei , Olsen Keith , Granholm Anders , Jin Xiaodong , Zhang Lingli , Guyatt Gordon
Published: January 2025

Objectives:

This study aimed to evaluate the effectiveness of a pharmacist-led intervention in decreasing the overuse of stress ulcer prophylaxis (SUP) compared with the usual care for adult patients in Chinese ICUs.

Design:

Pragmatic, multicenter, stepped-wedge, cluster-randomized controlled trial.

Setting:

Twenty-six ICUs in China from October 2022 to March 2023.

Patients:

We enrolled 2199 patients 18 years old or older who were newly admitted to the participating ICUs.

Interventions:

Using the Medical Research Council framework for developing and evaluating complex intervention measures, a multidisciplinary team (Scenarios, Improving and Refining Interventions, Constructing, Refining and Testing Research Theories, Incorporating Stakeholders, Identifying Important Uncertainties, and Economics Considerations) designed a multifaceted intervention.

Measurements and Main Results:

The primary outcomes were the proportion of patients receiving SUP and that with overt gastrointestinal bleeding. We conducted intention-to-treat analyses using generalized linear mixed models to adjust for potential confounders (age, sex, and acute physiology and chronic health evaluation II score) with random effects for the site. The proportion of patients receiving SUP in the intervention group was lower than that in the control group (45.5% vs. 49.5%; odds ratio [OR], 0.81; 95% CI, 0.68–0.96; p = 0.017). The proportion of patients with overt gastrointestinal bleeding was similar (3.7% vs. 4.0%; OR, 1.05; 95% CI, 0.65–2.85; p = 0.81).

Conclusions:

The pharmacist-led intervention reduced the proportion of patients receiving SUP in the ICUs, without significantly affecting the proportion of patients with overt gastrointestinal bleeding. These findings will help guide ICU medical decision-making.
Phosphoproteomics delineates hepatocellular carcinoma subtypes and pinpoints therapeutic targets
Authors: Zhang Ze , Zhang Zhenpeng , Zhang Yao , Li Yuan , Li Kaixuan , Liu Shu , Cao Junning , Li Yanchang , Peng Xuehui , Li Suzhen , Yin Yanan , Jiang Songhao , Zuo Tao , Chang Lei , Xu Zhongwei , Li Chonghui , Ding Jin , Wu Jushan , Zhang Wenwen , Wang Xinxin , Xia Guimin , Lu Shichun , Xu Ping
Published: January 2025

Background & Aims:

Only a minority of patients could benefit from systemic therapy owing to the high heterogeneity of HCC. Therefore, a deeper understanding of the pathogenesis of HCC is essential for precision therapy. Genomic and proteomic studies of HCC have enhanced our understanding of HCC. However, phosphoproteomic characterization of HCC remains poorly understood.

Approach & Results:

We conducted an in-depth analysis of a clinical cohort of HCC using high-coverage phosphoproteomic. Effective therapeutic targets were validated using liver cancer cell lines and HCC patient-derived xenograft (PDX) mouse models that correspond to the phosphoproteomic subtypes of HCC. Phosphoproteomic analysis classified HCC into three subtypes, A, B, and C, with increasing malignancy and correlation with clinical features, including patient prognosis, tumor staging, serum alpha fetoprotein (AFP) levels, tumor thrombus, and tumor size. Phosphoproteomic subtyping deeply reflected the biological characteristics and clinical features of HCC patients. The profiles of HCC dysregulated kinase activities inferred from the different phosphoproteomic subtypes, consistently identifying increased kinase activity related to cell proliferation. Subtype-C HCC patients showed the most significant dysregulation, indicating a potential therapeutic target. The corresponding drug, bosutinib, demonstrated efficacy in inhibiting the growth of subtype C tumors in liver cancer cell lines and HCC patient-derived xenograft (PDX) mouse models representative of the phosphoproteomic HCC subtypes.

Conclusions:

Our study provides a comprehensive exploration of the phosphoproteomic landscape of HCC, establishing new subtypes that match clinical features and identifying potential therapeutic targets for the most malignant C subtype.
Assessing chatbots ability to produce leaflets on cataract surgery: Bing AI, chatGPT 3.5, chatGPT 4o, ChatSonic, Google Bard, Perplexity and Pi
Authors: Thompson Dr Polly , Thornton Dr Richard , Ramsden Mr Conor
Published: January 2025

Purpose:

This study aimed to evaluate leaflets on cataract surgery produced by seven common free chatbots.

Setting:

Usage of conversational artificial intelligence services (chatbots) is becoming more prevalent in all aspects of life, including healthcare. Cataract surgery is the most commonly performed operation in the world, with numbers set to increase. Possible applications for chatbots include information giving and education, allowing clinicians to allocate their time more efficiently.

Design:

Analysis of answers given by seven chatbots (Bing AI, chatGPT 3.5, chatGPT 4o, ChatSonic, Google Bard, Perplexity and Pi) were prompted to “make a patient information leaflet on cataract surgery”.

Methods:

Answers were evaluated using the DISCERN instrument, Patient Education Materials Assessment Tool (PEMAT), presence of misinformation, the Flesch-Kincaid Grade Level readability score and material reliability.

Results:

The highest overall scored response was from ChatSonic, followed by Bing AI and then Perplexity. The lowest scoring was ChatGPT 3.5.

ChatSonic achieved the highest DISCERN and PEMAT scores, and had the highest Flesch-Kincaid Grade level. The lowest DISCERN and PEMAT scores were for Pi. Only ChatGPT 3.5 included some misinformation in its response. Bing AI, ChatSonic and Perplexity included reliable references; the other chatbots provided no references.

Conclusions:

This study demonstrates a range of answers given by chatbots creating a cataract surgery leaflet, suggesting variation in their development and reliability. ChatGPT 3.5 scored the most poorly. However, ChatSonic indicated promise in how technology may be used to assist information giving in ophthalmology.
Focused Recommendations for the Management of Metabolic Dysfunction-Associated Steatohepatitis (MASH) by Advanced Practice Providers in the United States
Authors: Lam Brian P. , Bartholomew Jessica , Bau Sherona , Gilles HoChong , Keller Andrea , Moore Ann , Nader Khalil , Richards Lisa , Henry Linda , Younossi Zobair M.
Published: January 2025

Metabolic dysfunction-associated steatohepatitis (MASH) has become the dominant cause of liver disease in the United States. With the growing burden of this disease in gastroenterology practices, the identification and treatment of those at risk of developing adverse outcomes (cirrhosis, hepatocellular carcinoma, or liver-related death) has become urgent. In recent years, the development of noninvasive tests (NITs) to identify “at-risk MASH” patients have provided cost-effective algorithms to identify these patients. Although treatment has historically been limited to lifestyle modification, recent FDA approval of resmetirom for noncirrhosis MASH with stages 2 and 3 fibrosis has provided a new ﻿ opportunity in the United States to provide these patients with novel﻿ treatment options. Other n﻿ew effective treatment regimens are on the horizon. Given that gastroenterology and hepatology practices in the United States heavily rely on advanced practice providers (APPs)﻿ to manage patients with MASLD, the APP Committee of the Global NASH/MASH Council has curated the essentials of day-to-day MASH management for our busy gastrohepatology providers and their APP colleagues. The goal of this document is to equip and mobilize more GI providers with the requisite competencies for the management of at-risk MASH, given the rapidly evolving MASH treatment landscape.
Two case reports of rare Down’s syndrome during in vitro fertilization and embryo transfer (IVF-ET)
Authors: Taherzadeh Boroujen Parisa , Nemati Mitra , Naderipour Fatemeh
Published: January 2025

Rationale:

Despite the potential risks, assisted reproductive technology has provided hope and opportunities for individuals and couples struggling with infertility to conceive and have children. This study presents a case report that describes an occurrence where a pregnancy achieved through in vitro fertilization (IVF) and embryo transfer had to be ended because of the presence of trisomy 21 syndrome.

Patient concerns:

Two 26-year-old women who were diagnosed with primary infertility due to polycystic ovary syndrome manifested with overweight and hirsutism.

Diagnosis:

These 2 cases were regarded as a diagnosis of Down syndrome, which resulted in the decision to legally terminate the pregnancy when the mother was, in her 12th week and 4 days of gestation. Upon examining the makeup of the cells in the chorionic villi it was discovered that all cells had a chromosomal composition of 47, XX.

Interventions:

In these case reports, 2 26-year-old woman with polycystic ovary syndrome underwent assisted reproductive technology and IVF to conceive. The first IVF transfer was unsuccessful, but the second attempt resulted in a successful transfer in both cases. However, a positive screening for Down syndrome led to a legal abortion at 12 + 4 weeks gestation.

Outcomes:

Genetic counseling revealed no family history of genetic diseases, and the couple opted for IVF without preimplantation genetic testing. During the trimester of their pregnancies the expectant mothers were initially screened at 12 + 4 weeks after conception. Nuchal translucency examination showed thickening of the fluid at the back of the fetal neck. Moreover, there was an increase in the levels of pregnancy related plasma protein and β human chorionic gonadotropin.

Lessons:

These 2 cases underscore the significance of genetic counseling and prenatal screening for couples who are undergoing assisted reproductive technologies, with the purpose of detecting and effectively addressing any possible genetic abnormalities that may arise in their progeny.
Identification of potential biomarkers associated with cuproptosis and immune microenvironment analysis in acute myocardial infarction: A diagnostic accuracy study
Authors: Zhang Jing , Yue Zhijie , Zhu Na , Zhao Na
Published: January 2025

Acute myocardial infarction (AMI), a critical cardiovascular condition, is often associated with serious health risks. Recent studies suggest a link between copper-induced apoptosis and immune cell infiltration. Specifically, abnormal accumulation of copper ions can lead to intracellular oxidative stress and apoptosis, while also affecting immune cell function and infiltration. Nevertheless, studies exploring this relationship in the context of AMI are notably scarce, underscoring the necessity of identifying biomarkers associated with cuproptosis in AMI. Consensus clustering analysis was employed to classify distinct subtypes of AMI in the GSE66360 dataset. Concurrently, differential expression analysis was performed to identify differentially expressed genes (DEGs) across subtypes and between AMI and control samples. We employed Venn diagrams to validate the selection of cuproptosis-related DEGs in patients with AMI. A protein–protein interaction network was constructed to pinpoint potential candidate genes. Receiver operating characteristic curves were generated to identify promising biomarkers. The immune infiltration milieu was analyzed using CIBERSORT algorithms. Finally, the expression levels of identified cuproptosis-related biomarkers were validated at the transcriptional level. We classified AMI into 2 distinct cuproptosis-related subtypes, leading to the identification of 157 cuproptosis-related DEGs. Further analysis refined this list to 10 potential candidate genes. Among these, 5 emerged as significant biomarkers for AMI: granzyme A (GZMA), GTPase immunity-associated proteins (GIMPAs) GIMAP7, GIMAP5, GIMAP6, and TRAF3 interacting protein 3 (TRAF3IP3). A comprehensive examination of immune infiltration in AMI samples revealed significant differences in the levels of 11 types of immune cells, with GZMA displaying the highest correlation with activated mast cells and CD8 + T cells. We observed markedly lower expression levels of GZMA, GIMAP6, and TRAF3IP3 in the AMI group compared to controls. This study identified 5 cuproptosis-related biomarkers (GZMA, GIMAP7, GIMAP5, GIMAP6, and TRAF3IP3) associated with AMI, laying a theoretical foundation for the treatment of AMI.
Clinical value analysis of integrated care model in reducing bleeding and complications during Da Vinci robot-assisted urology
Authors: Wang Ting , Hu Yu , Zhang Youqun
Published: January 2025

This study aims to explore the effect of integrated care mode on patients in Da Vinci robot-assisted urology surgery and provide a new nursing scheme for clinic. A total of 93 patients from August 2022 to March 2024 were selected and divided into intervention group (43 cases) and control group (50 cases). The operation time, blood loss, first postoperative exhaust time, time to get out of bed, pain score (visual analog scale), psychological status (self-rating anxiety scale and self-rating depression scale), quality of life score (36-Item Short Form Survey), catheter retention time, patient satisfaction, incision healing, incidence of urinary system infection, nutritional status, and complication rate were compared between the 2 groups. There were no significant differences in baseline data and operative time between the 2 groups (P > .05), but the amount of intraoperative blood loss in the intervention group (250.32 ± 50.23) mL was less than that in the control group (320.56 ± 65.34) mL (P < .05). The first postoperative exhaust time and getting out of bed time in the intervention group were shorter than those in the control group (P < .05), and the pain visual analog scale score was lower than that in the control group (P < .05). The scores of self-rating anxiety scale and self-rating depression scale of mental state were better than those of the control group (P < .05), and the scores of quality of life were higher (P < .05). The retention time of catheter was shorter than that of the control group (P < .05), the patient satisfaction was 93.02% higher than that of the control group 78.00% (P < .05), and the grade A incision healing rate was 90.70% higher than that of the control group 76.00% (P < .05). The incidence of urinary system infection (4.65%) was lower than that of the control group (16.00%) (P < .05), the changes of serum albumin level and body weight were lower than that of the control group (P < .05), and the complication rate of 6.98% was lower than that of the control group (22.00%) (P < .05). Although the integrated medical care model did not significantly shorten the operation time, it was beneficial to the postoperative recovery of patients in many aspects.
Organized chronic subdural hematoma with cognitive impairment: A case report and literature review
Authors: He Sen , Xue Fang , Li Jing , Hao Jianqiang , Zhang Wenyan , Xie Fei
Published: January 2025

Rationale:

Organic chronic subdural hematoma is extremely rare in clinical practice, with unclear etiology and pathogenesis. Its clinical manifestations and treatment approaches are diverse, making diagnosis challenging and prone to misdiagnosis or mistreatment, adversely affecting patient care and quality of life.

Patient concerns:

The 58-year-old male patient exhibited cognitive impairment, characterized by memory deficits and delayed responses, over 1 month in the absence of notable medical comorbidities.

Diagnoses:

Initial neurological assessment upon admission showed cognitive deficits, with a Mini-Mental State Examination score of 18 and a Montreal Cognitive Assessment Scale score of 22. Imaging with a computed tomography scan revealed a subdural mass with low density. The preoperative diagnosis indicated a chronic subdural hematoma (may combined with intracranial hypertension) located at the apex of the right frontotemporal region, potentially with septation.

Interventions:

A bone flap craniotomy was proceeded under microscopic guidance for lesion resection. Postoperatively, the patient received targeted interventions, including fluid replacement, to promote brain tissue recovery and functional rehabilitation.

Outcomes:

After treatment, the patient demonstrated improvement and was discharged from the hospital. Over the 1-year postoperative period, he reported mild recent memory decline but remained asymptomatic, continued his usual activities, and demonstrated improved cognitive function, as evidenced by Mini-Mental State Examination and Montreal Cognitive Assessment Scale scores of 28 and 29, respectively, along with normal muscle strength in all limbs.

Lessons:

Patients with mild or no significant symptoms, such as headaches and dizziness, are advised to undergo regular imaging follow-ups. Surgical intervention is recommended for patients presenting with intracranial hypertension and neurological impairment, with bone flap craniotomy and lesion resection under microscopic guidance being the preferred approach. It is imperative to conduct regular postoperative monitoring to promptly detect potential complications, such as hematoma recurrence.
Prediction potential of serum sulfatide levels at diagnosis for end-stage kidney disease progression in ANCA-associated vasculitis
Authors: Do Hyunsue , Yoon Taejun , Park Yong-Beom , Ha Jang Woo , Ahn Sung Soo , Lee Sang-Won
Published: January 2025

The aim was to investigate the ability of serum sulfatide levels at diagnosis to reflect the cross-sectional activity and further longitudinally predict the occurrence of end-stage kidney disease (ESKD) during the follow-up period in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), regardless of kidney involvement at diagnosis. This study included 67 patients first diagnosed with AAV with available clinical data, including Birmingham Vasculitis Activity Score (BVAS), erythrocyte sedimentation rate, C-reactive protein, and blood samples at diagnosis. Serum sulfatide levels were assessed using stored serum samples at the time of diagnosis. The median age of the 67 patients (40.3% men and 59.7% women) was 61.0 years. During follow-up, 10 (14.9%) patients progressed to ESKD, and 4 (6.0%) died. Serum sulfatide levels significantly correlated with Five-Factor Score (r = −0.242), erythrocyte sedimentation rate (r = −0.315), and renal manifestation of the BVAS items (r = −0.296), but not BVAS at diagnosis. The cutoff of serum sulfatide levels at diagnosis for ESKD progression was 332.5 pg/mL. However, no significant cutoff of serum sulfatide levels for all-cause mortality was obtained. Patients with serum sulfatide levels ≤ 332.5 pg/mL at diagnosis exhibited both significantly higher frequency of ESKD progression (22.7% vs 0%, P = .012) and lower ESKD-free survival rate than those without (P = .011). This study highlighted the clinical usefulness of measuring serum sulfatide levels at the time of diagnosis as a biomarker to predict ESKD progression in patients with AAV regardless of kidney involvement at diagnosis.
Network pharmacology predicts targets and pathways of herbal components for the treatment of pneumonia: A review
Authors: Yang Dongxin , Chen Cuilian , Zhang Qingshang , Gong Jun
Published: January 2025

Pneumonia is a respiratory disease with high pathogenicity and mortality. Traditional Chinese medicine (TCM) is a natural therapy that has proven effectiveness and safety. Although TCM has been found to be effective in treating pneumonia, further research is needed to determine the specific mechanism of action. This paper presents a literature search conducted in PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases using the keywords “pneumonia” and “network pharmacology.” After screening, we retained the literature related to TCM. The study found that, according to network pharmacology prediction, 4 types of TCMs–natural active compounds, single herb medicine, Chinese patent medicines, and multi-component herbal formulations–were effective in treating pneumonia. TCM components demonstrated a multi-target and multi-pathway approach to treat the disease. The diversity of targets and signaling pathways not only facilitates the investigation of TCM’s mechanism of action of TCM in pneumonia treatment but also offers novel insights and perspectives for innovative drug research and development.
Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review
Authors: Liang Changming , Wang Song , Wu Chengwei , Wang Jiawei , Xu Lishuai , Wan Senlin , Zhang Xu , Hou Yinfen , Xia Yabin , Xu Li , Huang Xiaoxu , Xie Hao
Published: January 2025

Tumor-associated macrophages (TAMs) are present in and are important components of the tumor microenvironment (TME). TAMs differentiate into 2 functionally distinct morphologies, classically activated (M1)-type TAMs and alternatively activated (M2)-type TAMs, when stimulated by different cytokines. The 2 types of TAMs exhibit distinct properties and functions. M1 TAMs secrete high levels of pro-inflammatory and chemotactic factors, exerting proinflammatory, antitumor effects. Conversely, M2 TAMs alter the extracellular matrix, facilitate cellular immune escape, and stimulate tumor angiogenesis, thereby promoting anti-inflammatory responses and tumor growth. The ratio of M1 TAMs to M2 TAMs in the TME is closely related to the prognosis of the tumor. Tumor cells and other cells in the TME can regulate the polarization of TAMs and thus promote tumor progression through the secretion of various substances; however, polarized TAMs can also act on various cells in the TME through the secretion of exosomes, thus forming a positive feedback loop. Therefore, modulating the phenotype of TAMs in the TME or blocking the polarization of M2 TAMs might be a new approach for cancer treatment. However, the intracellular signaling pathways involved in the polarization of TAMs are poorly understood. The AKT signaling pathway is an important signaling pathway involved in the polarization, growth, proliferation, recruitment, and apoptosis of TAMs, as well as the action of TAMs on other cells within the TME. This paper reviews the AKT signaling pathway in the polarization of TAMs and the regulation of the TME and provides new ideas for tumor immunotherapy.
Ultrasound-guided versus blind arthrocentesis in knee osteoarthritis: A systematic review and meta-analysis
Authors: Deng Xiaoyan , Li Yamei , Li Daishun
Published: January 2025

Background:

To summarize the current evidence about effectiveness and accuracy of using ultrasound-guided compared to blind arthrocentesis in the treatment of knee osteoarthritis.

Methods:

Web of Science, the Cochrane Central Register of Controlled Trials, EMBASE, Scopus, PubMed, ClinicalTrials.gov, Wangfang Database, and SinoMed were conducted from their inception to February 2024. Eligible studies included Randomized controlled trials (RCTs) and non-RCTs that compared the ultrasound-guided and blind arthrocentesis in knee osteoarthritis, with outcomes assessed base on pain, function, accuracy, and additional factors such as satisfaction, cost-effectiveness, fluid yield, and synovial membrane thickness.

Results:

Twenty-one studies that met the inclusion criteria (1924 patients) were identified. The results indicated that ultrasound-guided arthrocentesis was superior to blind arthrocentesis (10 trials; MD = −0.37; 95% CI = −0.55 to −0.19; P = .000). However, no significant difference was found in function improvement (7 trials; SMD = −0.60; 95% CI = −1.31 to 0.12; P = .101). Ultrasound-guided arthrocentesis also demonstrated better accuracy compared to blind arthrocentesis (RR = 1.26, 95% CI: 1.09–1.46, P = .001). For satisfaction, the result reported ultrasound was better than the blind group (MD = 1.11; 95% CI = 0.67–1.54; P = .000) at immediate post-procedure, and at the 4 to 6 weeks (MD = 0.98; 95% CI = 0.56–1.41; P = .000).

Conclusion:

In the comprehensive systematic review and meta-analysis of knee osteoarthritis, ultrasound-guided arthrocentesis is superior to anatomic landmark–guided arthrocentesis in terms of pain reduction and accuracy.
Association of antibiotic use with rheumatoid arthritis: A Mendelian randomization study
Authors: Liu Chang , Ma Zhijun , Zhao Xin , Luo Fang , Li Huinan , Shen Dingkun , Zhou Wei , Cao Puhua , Su Chengguo , Zhu Jun
Published: January 2025

Previous observational studies have suggested an association between antibiotic use and rheumatoid arthritis (RA), though the causal relationship remains unclear. This study aimed to investigate the causal link between antibiotic use and RA in a European population using Mendelian randomization (MR). We utilized pooled genome-wide association study (GWAS) data on 12 antibiotics and RA from European populations, extracted from the GWAS Catalog. Both univariate MR and multivariate MR were employed to examine the causal relationship. Three analysis methods were applied: inverse variance weighting, MR-Egger, and weighted median, with inverse variance weighting as the primary method. Sensitivity analyses were conducted using Cochran Q statistics, MR-PRESSO, the MR-Egger intercept, and the leave-one-out test. Univariate MR revealed that tetracycline use was positively associated with RA (odds ratio = 1.013, 95% confidence interval = 1.001–1.024, P = .028), while none of the other 11 antibiotics exhibited a causal relationship with RA. However, further multivariate MR analysis found no causal association between tetracycline use and RA. Our results do not support a direct causal relationship between RA and antibiotic use, which may help alleviate some concerns among clinicians. Further MR studies are needed to validate these findings as additional datasets from other cohorts and GWASs with more detailed information become available.
Neoadjuvant chemoradiation therapy application in radical esophagectomy surgery: Safety and feasibility: A descriptive study in Vietnam
Authors: Nguyen An Thi Thoai , Dang Thang Huy Quoc , Dang Son Ngoc , Tran Thanh Chi , Doan Nghia Trong , Nguyen Vinh Quoc , Pham Cuong Hung
Published: January 2025

Esophageal cancer (EC) ranks as the 7th most prevalent form of cancer and the 6th leading cause of cancer-related mortality globally. Neoadjuvant therapy, encompassing neoadjuvant chemotherapy or chemoradiotherapy, has shown promise in reducing the staging of EC and mitigating the risk of early systemic spread. This study seeks to assess the safety and viability of implementing neoadjuvant chemoradiotherapy (nCRT) in conjunction with radical esophagectomy surgery for Vietnamese patients diagnosed with locally advanced EC. Safety was evaluated based on the incidence of grade ≥3 treatment-related adverse events, while feasibility was assessed through indicators such as pathological complete response, major pathological response, and R0 resection rates. The study analyzed data from 30 patients, following specific inclusion criteria. Baseline characteristics analysis revealed a participant cohort entirely composed of males, wherein 83.3% were identified as smokers, with tumors predominantly located in the middle (46.7%) and lower (53.3%) regions of the thoracic esophagus. The predominance of clinical stages II and III was observed. The nCRT protocol resulted in a substantial reduction in dysphagia score, with a statistically significant P < .001. The median duration from the conclusion of radiation treatment to surgery was 62 days, with a median operative time of 302 minutes and a median estimated blood loss of 189 mL. Surgical complications primarily included anastomotic leakage and pneumonia, occurring in 23.3% and 16.7% of cases, respectively. R0 resection was achieved in 29 (96.7%) patients, with 43.4% attaining pathological complete response and 56.7% demonstrating tumor complete response. The study’s outcomes emphasize the safety and feasibility of employing esophagectomy subsequent to nCRT in Vietnamese patients, as evidenced by the absence of mortality, low complication rates, and favorable surgical results. It also suggests the potential advantages of utilizing a lower daily Gy dose for enhanced safety and considering squamous cell carcinoma as a specific criterion for nCRT.
Antegrade horizontal stenting for endovascular coiling of wide-neck aneurysms in the basilar tip: Two case reports
Authors: Baek Byung Hyun , Yoon Woong , Kim You Sub , Kim Tae Sun , Kim Seul Kee , Lee Yun Young , Lee Byung Chan , Park Chan
Published: January 2025

Rationale:

Endovascular coil embolization for wide-neck intracranial aneurysms is technically challenging and requires supporting devices. Intracranial stents are widely used as a buttress for compact coil filling and preventing coil protrusion into the parent artery. Horizontal stenting has been developed to maximize coil insertion and reduce the risk of thromboembolism. An anterograde route for horizontal stenting could be attempted for basilar tip aneurysms if the posterior communicating artery is not accessible. Here, we report 2 cases of antegrade horizontal stenting (AHS) for wide-neck aneurysm (WNA) in the basilar tip. This approach aims to maximize coil insertion and achieve complete aneurysm occlusion.

Patient concerns:

Both patients were admitted for the treatment of cerebral aneurysms, which were incidentally detected during routine health checkups.

Diagnoses:

Both patients were diagnosed with WNAs at the basilar tip and hypoplastic communicating arteries.

Interventions:

The patients underwent stent-assisted coil embolization for WNA in the basilar tip using the catheter jailing technique. After positioning a pre-jailed microcatheter within a basilar aneurysm, AHS was performed using the Neuroform Atlas stent, with the proximal part of the stent deployed across the neck of the basilar tip aneurysm. In both cases, the preselected microcatheter tip shifted either to the anterior or posterior side of the aneurysm immediately after AHS using the pushing technique. The coils inserted into the aneurysm did not reach the opposite side of the microcatheter placement, necessitating additional catheterization.

Outcomes:

Complete occlusion was achieved by inserting additional coils through the repositioned microcatheter.

Lessons:

Horizontal stenting via an antegrade route may be an effective strategy for achieving compact coil embolization in selected patients with WNAs at the basilar tip. The Neuroform Atlas stent appears to be a promising tool for AHS owing to its hybrid-cell design. However, the shifting phenomenon of a jailed microcatheter after AHS warrants attention, as it may present potential challenges that require further catheterization.
Can brain network analyses guide epilepsy surgery?
Authors: Makhoul Ghassan S. , Doss Derek J. , Englot Dario J.
Published: January 2025

Purpose of review

Epilepsy surgery is a potentially curative intervention for medically refractory epilepsy. In the last several decades, epilepsy has been studied as a network disorder. How has this disease model influenced surgical interventions?

Recent findings

Surgical outcomes for resection are increasingly being tied to network features, such as node hubness score. These findings imply that measuring network features may augment epileptologist seizure onset zone designation for surgical planning. Network models are also leveraged for neuromodulation, specifically in studies with thalamic targets. Recent findings suggest that the thalamus may function as a reasonable target for neuromodulation because of its role in the seizure propagation networks.

In this review, we discuss the degree these models of epilepsy are influencing surgery today and barriers for the widespread adoption of network models when planning epilepsy surgery.
Autoimmune dementia
Authors: Dinoto Alessandro , Flanagan Eoin P.
Published: January 2025

Purpose of review

The aim of this review is to summarize clinical, radiological and laboratory findings in autoimmune dementia, to help clinicians in promptly identify this elusive condition.

Recent findings

The rapid advances in the field of autoimmune neurology have led to the discovery of novel antibodies and associated disorders, which are more frequent than previously hypothesized. The correct and prompt identification of cognitive decline of autoimmune origin is vital to ensure early treatment and better outcomes. The diagnosis of autoimmune dementia relies on specific clinical and radiological features and on the detection of specific autoantibodies. Autoantibody specificities predict response to treatment and the occurrence of cancer. In recent years, the differential diagnosis of autoimmune dementia has become more relevant, as the overinterpretation of antibody results, clinical and radiological findings may lead to an erroneous diagnosis of autoimmune dementia, with potential harm to patients due to inappropriate exposure to immunosuppressants.

Autoimmune dementia is a potentially treatable condition and should not be missed in clinical practice given the potential for reversibility with immunotherapy. The diagnosis of autoimmune dementia relies on a comprehensive review of clinical, radiological and laboratory data, and exclusion of other causes of dementia.
The allosteric mechanism of G-protein-coupled receptors is induced fit, not conformational selection
Authors: Asadollahi Kazem , Gooley Paul R. , Weikl Thomas R.
Published: January 2025

The allosteric mechanism of G-protein-coupled receptors (GPCRs) involves a population shift from inactive to active receptor conformations in response to the binding of ligand agonists. Two possible kinetic mechanisms for this population shift are induced fit and conformational selection. The two mechanisms differ in the temporal sequence of binding events and conformational changes: Ligand bindings occurs prior to the change from the inactive to the active receptor conformation in the induced-fit mechanism, and after the conformational change in the conformational-selection mechanism. In this article, we discuss the current evidence from experiments that probe the binding kinetics of GPCRs to identify the allosteric mechanism. For the peptide-activated neurotensin receptor 1, the modeling of kinetic data from stopped-flow mixing experiments indicates an induced-fit mechanism1. The conformational exchange rates of the induced-fit mechanism obtained from this modeling agree with rates measured by saturation transfer difference NMR experiments of the peptide-receptor complex, which corroborates the mechanism. For the small-molecule-activated β2-andrenergic receptor, an induced-fit mechanism has been inferred from a comparison of ligand-association rates for the inactive and the active receptor conformation2. A stabilization of the active receptor conformation by G proteins or nanobodies leads to a decrease of ligand association rates, which indicates that ligand binding occurs in the inactive conformation and, thus, prior to the change from the inactive to the active conformation as in the induced-fit mechanism. A structural explanation for the induced-fit mechanism of the β2-andrenergic receptor is a closed lid over the binding site that blocks ligand entry in the active conformation. Since constriction and closing of the ligand-binding site in the active conformation is rather common for small-molecule-activated and peptide-activated GPCRs, induced fit likely is shared as allosteric mechanism by these GPCRs.
Sulfuriferulaspp. from sulfide mineral weathering environments have diverse sulfur- and iron-cycling capabilities
Authors: Hobart Kathryn K , Walker Gabriel M , Feinberg Joshua M , Bailey Jake V , Jones Daniel S
Published: January 2025

Microorganisms are important catalysts for the oxidation of reduced inorganic sulfur compounds. One environmentally important source of reduced sulfur is metal sulfide minerals that occur in economic mineral deposits and mine waste. Previous research found thatSulfuriferulaspp. were abundant and active in long-term weathering experiments with simulated waste rock and tailings from the Duluth Complex, Northern Minnesota. We therefore isolated several strains ofSulfuriferulaspp. from these long-term experiments and characterized their metabolic and genomic properties to provide insight into microbe-mineral interactions and the microbial biogeochemistry in these and other moderately acidic to circumneutral environments. TheSulfuriferulastrains are all obligate chemolithoautotrophs capable of oxidizing inorganic sulfur compounds and ferrous iron. The strains grew over different pH ranges, but all grew between pH 4.5-7, matching the weathering conditions of the Duluth Complex rocks. All strains grew on the iron-sulfide mineral pyrrhotite (Fe1-xS, 0 < x < 0.125) as the sole energy source, as well as hydrogen sulfide and thiosulfate, which are products of sulfide mineral breakdown. Despite their metabolic similarities, each strain encodes a distinct pathway for the oxidation of reduced inorganic sulfur compounds as well as differences in nitrogen metabolism that reveal diverse genomic capabilities among the group. Our results show thatSulfuriferulaspp. are primary producers that likely play a role in sulfide mineral breakdown in moderately acidic to circumneutral mine waste, and the metabolic diversity within the genus likely explains their success in sulfide mineral-rich and other sulfidic environments.
Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains
Authors: Radford Caelan E , Bloom Jesse D
Published: January 2025

Antibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimentally define the escape mutations from specific antibodies in specific viral strains, but it remains unclear how much the effects of mutations on neutralization differ among HIV strains. Here, we use pseudovirus deep mutational scanning to comprehensively map escape mutations from the V3 loop targeting antibody 10-1074 and the CD4-binding site targeting antibody 3BNC117 for both a clade A (BF520) and a clade B (TRO.11) HIV Envelope (Env). Mutations that escape neutralization by antibody 10-1074 are largely similar for the two Envs, but mutations that escape 3BNC117 differ greatly between Envs. Some differences in the effects of mutations on escape between Envs can be explained by strain-to-strain variation in mutational tolerance or glycosylation patterns, but other mutations have different effects on escape for unclear reasons. Overall, the extent that measurements of mutational effects on antibody neutralization can be generalized across HIV strain differs among antibodies.