bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-RA33 Antibodies Are Present in Patients With Lyme Disease
Authors: Miller John B. , Yang Ting , Rebman Alison W. , Cappelli Laura , Bingham Clifton O. , Villegas de Flores Marcia Daniela , Darrah Erika , Aucott John N. 
Published: November 2024

Background/Objective
To determine if anti-RA33 antibodies, which can be seen in early forms of inflammatory arthritis, are present in patients with Lyme arthritis (LA).

Methods
Anti-RA33 antibodies were tested using a commercially available assay in patients with LA (n = 47) and compared with patients with erythema migrans who returned to health (EM RTH, n = 20) and those with post-treatment Lyme disease (PTLD) (n = 50), characterized by noninflammatory arthralgia, as an observational comparative study utilizing Lyme-exposed patients from various original cohorts.

Results
We found that anti-RA33 was present in higher proportions of patients with LA (23.4% vs. 0%, p = 0.001) and PTLD (12.0% vs. 0%, p = 0.040) than healthy controls. There was also a trend toward a higher percentage of anti-RA33 positivity in patients with EM RTH versus controls (10.0% vs. 0%, p = 0.080). There were no statistically significant differences among groups of patients with LA, PTLD, and EM RTH (p ≥ 0.567). There was also no difference in the proportion of patients with antibiotic-responsive LA compared with those with persistent synovitis after antibiotics, termed post-infectious LA, and there were no differences in clinical manifestations, musculoskeletal ultrasound evaluation (synovial hypertrophy, power Doppler, tendinopathy), or patient-reported outcomes based on anti-RA33 status.

Conclusions
This is the first study to identify anti-RA33 antibodies in patients with LA, though these antibodies did not identify a unique clinical subset of patients in this cohort. Unexpectedly, we found anti-RA33 antibodies at similar levels in patients with PTLD and EM RTH; further study is needed to determine the relevance of this finding.
First Successful In-Human Application of 225Ac-DOTA-LM3 Mono-PRRT for the Treatment of an Otherwise Therapy-Resistant Neuroendocrine Tumor (NET G3)
Authors: Speicher Tilman , Burgard Caroline , Bastian Moritz , Rosar Florian , Bartholomä Mark , Maus Stephan , Ezziddin Samer 
Published: November 2024

Abstract
We present a case of a 60-year-old woman diagnosed with metastasized small bowl NET G3 with high hepatic tumor burden and highly glucometabolic (FDG-avid) disease. In the postchemotherapy setting with progressive disease, the patient underwent PRRT with 177Lu-DOTA-octreotate and 225Ac-DOTA-octreotate initially resulting in stable disease. In a novel approach, 225Ac-DOTA-LM3 (somatostatin receptor antagonist) was administered, leading to a favorable treatment response in the 18F-FDG PET/CT scan. This interesting image illustrates the promising antitumor potential of alpha-sst2 antagonist PRRT with 225Ac-DOTA-LM3, and to the best of our knowledge, it is the first documented evidence of superiority over standard alpha-PRRT from intraindividual comparison.
HER2-Targeted Affibody Molecule 99mTc-ABH2 for Imaging HER2 Expression in Breast Cancer
Authors: Jin Xiaona , Zhang Yuwei , Cao Xi , Wang Peipei , Ren Chao , Cai Jiong , Wang Xuefei , Jing Hongli , Sun Qiang , Li Fang 
Published: November 2024

Purpose
Accuracy in in vivo assessment of human epidermal growth factor receptor type 2 (HER2) status is crucial for predicting the response to HER2-targeted therapies in breast cancer. This study assessed the safety, feasibility, and diagnostic accuracy of 99mTc-ABH2, a reengineered affibody molecule with radionuclide labeling, for HER2 expression in breast cancer using SPECT/CT imaging, compared with 18F-FDG PET/CT.

Patients and Methods
Thirty-six patients suspected of primary breast cancer were enrolled in this prospective, single-center study from March to July in 2023. Each participant underwent SPECT/CT imaging with 99mTc-ABH2 SPECT/CT and 18F-FDG PET/CT. The imaging results were validated against immunohistochemistry and fluorescence in situ hybridization, employing visual scores and quantitative values for analysis.

Results
Optimal imaging contrast was observed around 2 hours postinjection of 99mTc-ABH2. Among the evaluated 27 patients with immunohistochemistry and fluorescence in situ hybridization findings, the 99mTc-ABH2 SPECT/CT visual evaluation displayed a sensitivity of 71.4%, specificity of 72.2%, and accuracy of 71.9%. Using an SUVmax cutoff of 2.32, the sensitivity, specificity, and accuracy for detecting HER2 status were 92.86%, 72.22%, and 81.25%, respectively. Notably, 99mTc-ABH2 precisely identified all immunohistochemistry (3+) tumors and showed increased uptake in bone and lymph node metastases. Meanwhile, 18F-FDG PET/CT showed no significant difference in uptake between HER2 (2+/3+) and HER2 (0/1+) tumors (P = 0.81).

Conclusions
This study validated 99mTc-ABH2 SPECT/CT as a promising diagnostic tool for precise HER2 assessment. The robust sensitivity for immunohistochemistry (3+) tumors and the visualization of metastases highlight its diagnostic significance, potentially impacting patient outcomes positively.
A Case Report
Authors: Al Sawafi Fatema Mohd , Hasan Olfat Kamel , Bonert Michael , Haider Ehsan , Shayegan Bobby 
Published: November 2024

Abstract
Prostate-specific membrane antigen (PSMA) PET/CT scan has significantly improved the detection and staging of prostate cancer. We report a rare case of a 72-year-old man with a history of Gleason score 7 (3 + 4) prostate adenocarcinoma, status post radical prostatectomy, referred for restaging PSMA PET/CT scan due to rising PSA (0.12 μg/L). The scan revealed a PSMA-avid lesion in the retroperitoneum, later confirmed via further investigations and histopathological analysis to be a retroperitoneal hemangioma. This case emphasizes the challenges in interpreting PSMA PET/CT scan in prostate cancer and highlights the significance of thorough consideration in forming a comprehensive differential diagnosis.
Head-to-Head Comparison of 68Ga-FAPI-04 and 68Ga-DOTA-TATE PET/CT in Recurrent Medullary Thyroid Cancer
Authors: Isik Emine Goknur , Has Simsek Duygu , Gul Nurdan , Erturk Sukru Mehmet , Buyukkaya Fikret , Soyluk Selcukbiricik Ozlem , Iscan Ahmet Yalin , Özkan Zeynep Gözde , Sanli Yasemin , Mudun Ayse , Kuyumcu Serkan 
Published: November 2024

Purpose
We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC).

Patients and Methods
Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated.

Results
The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas.

Conclusions
FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases.
Efficacy and Safety of 177Lu-DOTA-IBA in Tumor Bone Metastasis Treatment
Authors: Xu Tingting , Wang Yudi , Liu Guangfu , Li Hongmei , Qu Gengcuo , Zhang Xiaoling , Wang Wei , Xing Naiguo , Hua Qingchu , Chen Yue 
Published: November 2024

Purpose
The aim of this study was to evaluate the efficacy and safety of 177Lu-DOTA-IBA for pain palliation in participants with bone metastases and confirm its potential for treating bone metastasis.

Patients and Methods
Overall, 69 participants with bone metastases were included. 68Ga-DOTA-IBA PET/CT was performed within 1 week before treatment. Vital signs, blood markers, electrocardiogram, Karnofsky Performance Status (KPS), and pain scores were evaluated within 7 days before treatment. Postadministration of 177Lu-DOTA-IBA, participants’ vital signs and general conditions were monitored. Follow-up evaluations of KPS, pain scores, and blood biomarkers were performed within 8 weeks. 68Ga-DOTA-IBA PET/CT was repeated to evaluate imaging responses at 8 weeks. Imaging responses were defined as complete response, partial response, stable disease, and disease progression. Subsequent treatments were administered based on participants’ agreement and clinical conditions.

Results
Sixty-nine participants received at least 1 dose of 177Lu-DOTA-IBA treatment; 22 received 38 reinjected doses, totaling 107 treatments. The median injection dose of 177Lu-DOTA-IBA was 1110 MBq. The pain remission rates after first treatment, retreatment, and total treatment were 82.5%, 72.4%, and 79.3%, respectively. The improvement rates in KPS for first treatment, retreatment, and total treatment were 81.3%, 60.6%, and 74.2%, respectively. The total incidence of the pain flare reaction (temporary aggravation of pain intensity after treatment) was 16.8%. Comparative analysis of 68Ga-DOTA-IBA PET/CT showed a 27.1% rate of partial response imaging response. The total incidence of adverse hematological events was 15%.

Conclusions

177Lu-DOTA-IBA is a promising bone-seeking radiopharmaceutical with a considerable pain relief rate and safety. It also can benefit some participants with bone metastases in imaging response.
Uncovering Hidden Metastases at Unusual Site
Authors: Mahdi Raza Abbas , Saraswat Dhananjaya , Aggarwal Piyush , Sood Ashwani , Kumar Munish , Mittal Bhagwant Rai 
Published: November 2024

Abstract
Prostate cancer frequently metastasizes to bones; however, the detection of metastases can be challenging in rare locations. We present the case of a 76-year-old man with metastatic castration-resistant prostate cancer with lymph nodal and skeletal metastases who underwent 177Lu–prostate-specific membrane antigen (PSMA) therapy. Initial 18F-PSMA PET/CT scan acquired until the midthigh failed to identify metastases in the foot, but posttherapy 177Lu-PSMA scan revealed the presence of metastases in the navicular and cuboid bones of the right foot, which is a very rare finding. This case highlights the limitations of standard PSMA PET/CT acquisition protocol and incremental value of whole-body posttherapy scan.
Single-dock Robotic Bilateral Transversus Abdominis Release: Technique Description and Preliminary Outcomes
Authors: Estrada Arturo , Rodriguez-Quintero Jorge Humberto , Arias-Espinosa Luis , Sreeramoju Prashanth , Cheema Fareed , Pereira Xavier , Malcher Flavio 
Published: November 2024

Background:
Posterior component separation with transversus abdominis release (TAR) is a valuable adjunct to address incisional hernia defects. Currently, bilateral docking is a standard technique for robotic TAR. The aim of this study is to describe our technique for extended totally extraperitoneal (eTEP) repair with bilateral TAR through a bottom single-dock robotic approach for hernias at the level of the umbilicus or higher.

Materials and Methods:
We retrospectively reviewed a case series of patients who underwent robotic eTEP repair with bilateral TAR using a single bottom docking between November 2021 and November 2023. A comprehensive description of our patient selection, surgical technique, and short-term clinical outcomes is reported.

Results:
Ten patients with incisional hernias were included. Their median age was 55 years (IQR: 49.5 to 61.25), 70% were male, the median BMI was 27.25 kg/m (IQR: 22.95 to 33.53), and ASA class was ≥2 in 80%. Median hernia width was 10 cm (IQR: 6.75 to 12.25) and length 11 cm (IQR: 9.25 to 16.25). The median operative time was 178.5 minutes (IQR: 153.75 to 222), and the length of stay was 1 day (IQR: 0.75 to 1.75). At a median follow-up of 5 months (IQR: 2.6 to 9.7), 20% of patients developed a surgical site occurrence requiring procedural intervention.

Conclusion:
Bilateral TAR using a single bottom dock is a feasible and safe adjunct to robotic eTEP ventral hernia repair in appropriately selected patients.
Protein profile of the Escherichia coli strain, BW25113, exposed to two novel iron-halide compounds: Fe(Hampy)2Cl4 and Fe(Hampy)2Br4.
Authors: Abedin Nusrat , Wagner Sarah , Khalkar Yukta Sanjay , Johnson Zulekha , Egbowon Biola F. , Hargreaves Alan J. , Fitzpatrick Anthony J. , Miles Amanda K. , Dafhnis-Calas Felix 
Published: November 2024

The mortality rate and economic burden of infections caused by antimicrobial resistant pathogens are increasingly higher. This frustrating scenario emphasizes the urgent need for developing new antimicrobial drugs. We have previously addressed this problem by studying the antimicrobial activity of two novel iron-halide complexes, Fe(Hampy)2Cl4 (iron-tetrachloride) and Fe(Hampy)2Br4 (iron-tetrabromide). Both compounds showed bactericidal and antibiofilm activities against bacteria with an antimicrobial resistance phenotype. Herein, we used a proteomics approach to investigate the protein-expression profile of bacterial cells previously exposed to both iron-halide complexes. For this study, the Escherichia coli strain, BW25113, was used as a model to facilitate the rapid identification of deregulated proteins. Heat map analysis of the common deregulated proteins highlighted that both complexes caused downregulation of proteins associated with key metabolic pathways, biofilm formation, cell-envelope biogenesis, and iron ion binding. In addition, network study suggested that the most influential proteins of the tetrachloride activity were those involved in TCA cycle, oxidative phosphorylation, iron ion homeostasis and carbon/secondary metabolism. This protein-protein interaction analysis also hinted that the main drivers of the tetrabromide activity were proteins involved in translation, ribosomal biogenesis, and cell motility. The above results strongly suggested how the presence of different halide ligands could be used to generate compounds with potentially different molecular mechanisms. Importantly, the findings of this study can also be used as a reference to compare with the protein profile of a bacteria exposed to future variants of the iron-halide complexes.
Characterizing the Solution Space of Migration Histories of Metastatic Cancers with MACH2
Authors: Roddur Mrinmoy S. , Ramavarapu Vikram , Bunkum Abigail , Huebner Ariana , Mineyev Roman , McGranahan Nicholas , Zaccaria Simone , El-Kebir Mohammed 
Published: November 2024

AbstractUnderstanding the migration history of cancer cells is essential for advancing metastasis research and developing therapies. Existing migration history inference methods often rely on parsimony criteria such as minimizing migrations, comigrations, and seeding locations. Importantly, existing methods either yield a single optimal solution or are probabilistic algorithms without guarantees on optimality nor comprehensiveness of the returned solution space. As such, current methods are unable to capture the full extent of uncertainty inherent to the data. To address these limitations, we introduce MACH2, a method that systematically enumerates all plausible migration histories by exactly solving the ParsimoniousMigrationHistory withTreeRefinement(PMH-TR). In addition to the migration and comigration criteria, MACH2 employs a novel parsimony criterion that minimizes the number of clones unobserved in their inferred location of origin. MACH2 allows one to specify both the order and the set of criteria to include during optimization, allowing users to adapt the model to specific analysis needs. MACH2 also includes a summary graph to identify high-confidence migrations. Finally, we introduce MACH2-viz, an interactive webtool for visualizing and exploring MACH2 solution spaces. Using simulated tumors with known ground truth, we show that MACH2, especially the version that prioritizes the new unobserved clone criterion, outperforms existing methods. On real data, MACH2 detects extensive uncertainty in non-small cell lung, ovarian, and prostate cancers, and infers migration histories consistent with orthogonal experimental data.
Barley resistance and susceptibility to fungal cell entry involve the interplay of ROP signaling with phosphatidylinositol-monophosphates
Authors: Weiß Lukas Sebastian , Bartram Christoph , Bradai Mariem , Heilmann Mareike , Mergner Julia , Kuster Bernhard , Hensel Götz , Kumlehn Jochen , Engelhardt Stefan , Heilmann Ingo , Hückelhoven Ralph 
Published: November 2024

AbstractRho-of-plant small GTPases (ROPs) are regulators of plant polar growth and of plant- pathogen interactions. The barley ROP, RACB, is involved in susceptibility towards infection by the barley powdery mildew fungusBlumeria hordei(Bh), but little is known about the cellular pathways that connect RACB-signaling to disease susceptibility. Here we identify novel RACB interaction partners of plant or fungal origin by untargeted co-immunoprecipitation of constitutively active (CA) RACB tagged by green-fluorescent protein fromBh-infected barley epidermal layers expressing and subsequent analysis by liquid chromatography-coupled mass spectrometry. Three of immunoprecipitated proteins, a plant phosphoinositide phosphatase, a plant phosphoinositide phospholipase and a putativeBh-effector protein are involved in the barley-Bh-pathosystem and mediate disease resistance or susceptibility, respectively. RACB and its plant interactors bind to overlapping anionic phospholipid speciesin vitro, and in case of RACB, this lipid-interaction is mediated by its carboxy-terminal polybasic region (PBR). Fluorescent markers for anionic phospholipids show altered subcellular distribution in barley cells duringBh-attack. Phosphatidylinositol 4-phosphate and phosphatidylserine show a distinct enrichment at the haustorial neck region, suggesting a connection to subcellular targeting of RACB at this site. The interplay of ROPs with anionic phospholipids and phospholipid–metabolizing enzymes may, thus, enable the subcellular enrichment of components pivotal for success or failure of fungal penetration.
Tetanus Toxoid Utilizes Dual-Faceted Anticancer Mechanism Through Targeting Tumoral Sialic Acids and Enhancing Cytotoxic CD4+ T cell Responses Against Pancreatic Cancer
Authors: Giurini Eileena F , Pappas Sam G , Gupta Kajal H 
Published: November 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) remains profoundly resistant to conventional chemotherapy and immunotherapeutic interventions. Innovative therapeutic modalities, particularly microbe-derived immunotherapies, have demonstrated durable anti-tumor efficacy in preclinical PDAC models. This study elucidates that administration of the FDA-approved Haemophilus influenzae type b (H Flu - Hiberix) vaccine attenuates tumor progression and enhances survival outcomes in murine PDAC. H Flu treatment significantly augmented CD4+ T cell, CD8+ T cell, and natural killer (NK) cell infiltration within the tumor microenvironment, concurrently inducing a cytotoxic T cell phenotype, evidenced by upregulation of CD69, granzyme B, and perforin. Additionally, H Flu therapy promoted the accumulation of CD44+ CD62L-memory T cells within tumors of pre-immunized mice. Mechanistic investigations revealed that depletion of CD4+ T cells or NK cells, but not CD8+ T cells, negated the anti-tumor efficacy of H Flu, suggesting that CD4+ T cells and NK cells are critical mediators of H Flu-induced anti-tumor immunity. To further elucidate the mechanistic basis of H Flu’s anti-tumor activity, we assessed the individual constituents of the H Flu vaccine: tetanus toxoid (TT) and polyrobosyl ribitol phosphate (PRP). Notably, TT administration achieved superior tumor growth suppression, characterized by enhanced CD4+ T cell cytotoxicity and increased NK cell infiltration, relative to PRP or PBS-treated controls. Furthermore, TT induced apoptosis in PDAC cells and reduced their proliferation, potentially by targeting tumor-associated sialic acids. This disruption might interfere with the interaction between sialic acids and siglec receptors, thereby impairing mechanisms of immune evasion.TT-mediated modulation of sialic acid expression in cancer cells underscores its potential to augment immunotherapeutic efficacy in PDAC. Collectively, these findings reveal a novel anti-cancer mechanism for TT, leveraging both immunostimulatory and sialic acid-targeting pathways to suppress PDAC progression.Graphical Abstract
An immunomechanical checkpoint PYK2 governs monocyte-to-macrophage differentiation in pancreatic cancer
Authors: Xie Wenyan , Yu Xin , Yang Qingxin , Ke Nengwen , Wang Ping , Kong Hao , Wu Xiangji , Ma Panpan , Chen Lang , Yang Jie , Feng Xiuqing , Wang Yuan , Shi Hubing , Chen Lu , Liu Yun-Hua , Ding Bi-Sen , Wei Qiang , Jiang Hong 
Published: November 2024

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is a highly fibrotic and stiff tumor, and tumor-associated macrophages (TAMs) are pivotal in driving ECM remodeling, PDAC progression and immune evasion. The contribution of mechanical cues to monocyte differentiation into TAMs remains largely unexplored. Here we show that mechanical force is required for monocyte-to-macrophage differentiation. PYK2, as an innovative immunomechanical checkpoint, de facto governs this differentiation process. We demonstrated that PYK2 responds to mechanical signals within the tumor microenvironment (TME) via Piezo1 and integrins, leading to its activation and subsequent F-actin polymerization. Activated PYK2 then translocates to the nucleus, where it engages with promoters of genes governing mechanotransduction and differentiation, includingACTR3andRELA. Targeted deletion of PYK2 impairs the differentiation and polarization of monocyte-derived macrophages, reshapes the PDAC microenvironment, and enhances the efficacy of anti-PD-1 immunotherapy. These findings underscore the critical role of mechanical cues in monocyte differentiation and suggest that targeting PYK2 is a promising strategy to modulate TAM function and improve immunotherapy outcomes in patients with PDAC.
Beta-DIA: Integrating learning-based and function-based feature scores to optimize the proteome profiling of single-shot diaPASEF mass spectrometry data
Authors: Song Jian , Liu Hebin , Shen Chengpin , Wu Xiaohui 
Published: November 2024

AbstractWe present a freely available diaPASEF data analysis software, Beta-DIA, that utilizes deep learning methods to score coelution consistency in retention time-ion mobility dimensions and spectrum similarity. Beta-DIA integrates these learning-based scores with traditional function-based scores, enhancing the qualitative analysis performance. In some low detection datasets, Beta-DIA identifies twice as many protein groups as DIA-NN. The success of Beta-DIA has paved another way for the application of deep learning in fundamental proteome profiling.