bluuebunny/crossref_metadata_2025_split huggingface dataset:
The systematic role of pancreatic cancer exosomes: distant communication, liquid biopsy and future therapy
Authors: Qin Cheng , Li Tianyu , Lin Chen , Zhao Bangbo , Li Zeru , Zhao Yutong , Wang Weibin 
Published: July 2024

AbstractPancreatic cancer remains one of the most lethal diseases worldwide. Cancer-derived exosomes, benefiting from the protective role of the lipid membrane, exhibit remarkable stability in the circulatory system. These exosomes, released by tumor microenvironment, contain various biomolecules such as proteins, RNAs, and lipids that plays a pivotal role in mediating distant communication between the local pancreatic tumor and other organs or tissues. They facilitate the transfer of oncogenic factors to distant sites, contributing to the compromised body immune system, distant metastasis, diabetes, cachexia, and promoting a microenvironment conducive to tumor growth and metastasis in pancreatic cancer patients. Beyond their intrinsic roles, circulating exosomes in peripheral blood can be detected to facilitate accurate liquid biopsy. This approach offers a novel and promising method for the diagnosis and management of pancreatic cancer. Consequently, circulating exosomes are not only crucial mediators of systemic cell-cell communication during pancreatic cancer progression but also hold great potential as precise tools for pancreatic cancer management and treatment. Exosome-based liquid biopsy and therapy represent promising advancements in the diagnosis and treatment of pancreatic cancer. Exosomes can serve as drug delivery vehicles, enhancing the targeting and efficacy of anticancer treatments, modulating the immune system, and facilitating gene editing to suppress tumor growth. Ongoing research focuses on biomarker identification, drug delivery systems, and clinical trials to validate the safety and efficacy of exosome-based therapies, offering new possibilities for early diagnosis and precision treatment in pancreatic cancer. Leveraging the therapeutic potential of exosomes, including their ability to deliver targeted drugs and modulate immune responses, opens new avenues for innovative treatment strategies.
Development of a humanized anti-FABP4 monoclonal antibody for potential treatment of breast cancer
Authors: Hao Jiaqing , Jin Rong , Yi Yanmei , Jiang Xingshan , Yu Jianyu , Xu Zhen , Schnicker Nicholas J. , Chimenti Michael S. , Sugg Sonia L. , Li Bing 
Published: July 2024

Abstract
Background
Breast cancer is the most common cancer in women diagnosed in the U.S. and worldwide. Obesity increases breast cancer risk without clear underlying molecular mechanisms. Our studies demonstrate that circulating adipose fatty acid binding protein (A-FABP, or FABP4) links obesity-induced dysregulated lipid metabolism and breast cancer risk, thus potentially offering a new target for breast cancer treatment.

Methods
We immunized FABP4 knockout mice with recombinant human FABP4 and screened hybridoma clones with specific binding to FABP4. The potential effects of antibodies on breast cancer cells in vitro were evaluated using migration, invasion, and limiting dilution assays. Tumor progression in vivo was evaluated in various types of tumorigenesis models including C57BL/6 mice, Balb/c mice, and SCID mice. The phenotype and function of immune cells in tumor microenvironment were characterized with multi-color flow cytometry. Tumor stemness was detected by ALDH assays. To characterize antigen-antibody binding capacity, we determined the dissociation constant of selected anti-FABP4 antibodies via surface plasmon resonance. Further analyses in tumor tissue were performed using 10X Genomics Visium spatial single cell technology.

Results
Herein, we report the generation of humanized monoclonal antibodies blocking FABP4 activity for breast cancer treatment in mouse models. One clone, named 12G2, which significantly reduced circulating levels of FABP4 and inhibited mammary tumor growth, was selected for further characterization. After confirming the therapeutic efficacy of the chimeric 12G2 monoclonal antibody consisting of mouse variable regions and human IgG1 constant regions, 16 humanized 12G2 monoclonal antibody variants were generated by grafting its complementary determining regions to selected human germline sequences. Humanized V9 monoclonal antibody showed consistent results in inhibiting mammary tumor growth and metastasis by affecting tumor cell mitochondrial metabolism.

Conclusions
Our current evidence suggests that targeting FABP4 with humanized monoclonal antibodies may represent a novel strategy for the treatment of breast cancer and possibly other obesity- associated diseases.
SonicParanoid2: fast, accurate, and comprehensive orthology inference with machine learning and language models
Authors: Cosentino Salvatore , Sriswasdi Sira , Iwasaki Wataru 
Published: July 2024

AbstractAccurate inference of orthologous genes constitutes a prerequisite for comparative and evolutionary genomics. SonicParanoid is one of the fastest tools for orthology inference; however, its scalability and accuracy have been hampered by time-consuming all-versus-all alignments and the existence of proteins with complex domain architectures. Here, we present a substantial update of SonicParanoid, where a gradient boosting predictor halves the execution time and a language model doubles the recall. Application to empirical large-scale and standardized benchmark datasets shows that SonicParanoid2 is much faster than comparable methods and also the most accurate. SonicParanoid2 is available at https://gitlab.com/salvo981/sonicparanoid2 and https://zenodo.org/doi/10.5281/zenodo.11371108.
“Adjusting internal organs and dredging channelon” electroacupuncture glycolipid metabolism disorders in NAFLD mice by mediating the AMPK/ACC signaling pathway
Authors: Jia Xinyu , Li Mengyuan , Zhang Wen , Guo Yihui , Xue Fuyu , Ma Shiqi , Yu Shuo , Zhong Zhen , Huang Haipeng 
Published: July 2024

AbstractTo investigate the effect mechanism of electroacupuncture based on the AMP-activated protein kinase (AMPK) /acetyl-CoA carboxylase (ACC) signaling pathway to improve glycolipid metabolism disorders in db/db mice. 10 db/m mice with normal genotype were used as the normal control group without diabetes (Con), and 30 db/db mice were divided randomly into three groups: Pathological model mice (Mod), Acupuncture + ACC antagonist group (Acu + ACC), and Acupuncture + AMPK antagonist group (Acu + AMPK). Con and Mod did not receive any special treatment, only as a control observation. The latter two groups of mice received electroacupuncture treatment for 4 weeks. Mouse triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C), and cholesterin(CHO) levels were detected by colorimetric assay. Enzyme-linked immunoassay (ELISA) was used to detect insulin(INS) levels. Liver histopathologic changes and hepatic glycogen synthesis were observed by HE and PAS staining. The mRNA and protein expression of insulin receptor substrate-1(IRS1), Phosphatidylinositol 3-kinase(PI3K), protein kinase B (AKT), AMPK, and ACC were detected by Western blot and qRT-PCR.The results show that compared with Mod, TG, LDL, CHO, and INS levels of Acu + AMPK and Acu + ACC mice were significantly reduced (P < 0.05), and the HDL levels were significantly increased (P < 0.05), the steatotic degeneration of mice hepatocytes was reduced to different degrees, and the hepatocyte glycogen particles were increased, and the latter two groups had a decrease in AKT, ACC mRNA expression was reduced (P < 0.05), PI3K protein expression was increased, and AKT and ACC protein expression was reduced (P < 0.05), in addition, protein expression of AMPK was increased and IRS1 protein expression was reduced in Acu + ACC (P < 0.05). The study showed that electroacupuncture improves glucose-lipid metabolism disorders in db/db mice, and this mechanism is related to the AMPK/ACC signaling pathway.
Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression
Authors: Rabl Miriam , Zullo Leonardo , Lewczuk Piotr , Kornhuber Johannes , Karikari Thomas K. , Blennow Kaj , Zetterberg Henrik , Bavato Francesco , Quednow Boris B. , Seifritz Erich , von Gunten Armin , Clark Christopher , Popp Julius 
Published: July 2024

Abstract
Background
Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer’s disease (AD) pathology and cognitive decline.

Methods
One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest.

Results
None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081).

Conclusion
Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.
Clinical presentation, outcome and prognostic factors in dogs with immune-mediated haemolytic anaemia: a retrospective single-centre study of 104 cases in Ireland (2002–2020)
Authors: Duclos Antoine A. , Bailén Esther López , Barr Kathryn , Le Boedec Kevin , Cuq Benoît 
Published: July 2024

Abstract
Background
Immune-mediated haemolytic anaemia (IMHA) has a high mortality rate within the first weeks to months of diagnosis. Identifying dogs at increased risk of death may help guide decision-making for owners and veterinarians. Prior studies have identified several but inconsistent prognostic factors. The objectives of the study were to describe the clinical presentation and outcome of canine immune-mediated haemolytic anaemia in Ireland and to assess for independent factors associated with survival including long-term survival. Medical records from a single centre were reviewed between 2002 and 2020 to identify dogs with immune-mediated haemolytic anaemia using the American College of Veterinary Internal Medicine (ACVIM) consensus statement algorithm. Survival analysis was performed using univariable Cox proportional hazards regression models with Breslow method for ties to identify prognostic factors.

Results
One hundred and four cases were included. The diagnosis of immune-mediated haemolytic anaemia was classified as definitive, supportive and suspicious in 42 (40%), 50 (48%), and 12 dogs (12%) respectively. Twenty-two dogs (21%) were diagnosed with associative IMHA and 82 dogs were diagnosed with non-associative IMHA (79%). 65% of the cases received more than one immunosuppressive medication during the course of treatment. The mortality rate at one and three months was 16% (95% confidence interval [CI] 9–26) and 31% (95% CI 21–43) respectively. Excluding dogs that died within three months, the median survival time was 2664 days. The relapse rate during the follow-up period was 7%. Survival did not improve over the course of the study period. Thrombocytopenia and hyperbilirubinaemia were identified as negative prognostic indicators (Hazard ratio 2.2 and 2.5, 95% CI 1.1–4.1 and 1.1–5.6, respectively).

Conclusions
Excluding dogs that died within three months, the outcome was good in dogs with non-associative immune-mediated haemolytic anaemia in Ireland. The relapse rate was low regardless of the presence of associative causes. Thrombocytopenia and hyperbilirubinaemia were the only independent negative prognostic factors. The one-month and three-month mortality rates were similar compared to prior studies and survival did not improve over time during the study period: the mortality rate of canine immune-mediated haemolytic anaemia remains high in the acute phase.
Generative innovations for paleography: enhancing character image synthesis through unconditional single image models
Authors: Aswathy A. , Maheswari P. Uma 
Published: July 2024

Abstract
Data scarcity in paleographic image datasets poses a significant challenge to researchers and scholars in the field. Unlike modern printed texts, historical manuscripts and documents are often scarce and fragile, making them difficult to digitize and create comprehensive datasets. Recently many innovations have been arrived on single image generative models for natural images but none of them are focused on paleographic character images and other handwritten datasets. In paleographic images like stone inscription characters, maintaining exact shape and structure of character is important unlike natural images. In this paper we propose an unconditional single image generative model, CharGAN for isolated paleographic character images. In the proposed system, augmented images are generated from a single image using generative adversarial networks, while maintaining their structure. Specifically, an external augmentation inducer is used to create higher-level augmentations in the generated images. In addition, the input to the generator is replaced with dynamic sampling from a Gaussian mixture model to make changes to the low-level features. From our experimental results, we infer that these two enhancements make single-image generative models suitable not only for natural images, but also for paleographic character images and other handwritten character datasets, the AHCD dataset, and EMNIST, where the global structure is important. Both the qualitative and quantitative results show that our approach is effective and superior in single-image generative tasks, particularly in isolated character image generation.
Biostimulation of humic acids on Lepidium sativum L. regulated by their content of stable phenolic O⋅ radicals
Authors: Vitti Antonella , Coviello Leonardo , Nuzzaci Maria , Vinci Giovanni , Deligiannakis Yiannis , Giannakopoulos Evangelos , Ronga Domenico , Piccolo Alessandro , Scopa Antonio , Drosos Marios 
Published: July 2024

Abstract
Background
Humic acid affects plant growth. Its source and structure may play a central role to its functionality. The relationship between humic acid and plant bioactivity is still unclear. This study investigated the biostimulation effects of two natural humic acids derived from soil (SHA) and lignite (LHA) on Lepidium sativum in comparison to a synthetic humic acid model (HALP) with known structure.

Results
All humic acids positively affected cress seed germination and root elongation. Greater root hairs density and dry matter, compared to control, were observed using concentration of 5 mg L−1 for HALP, 50 mg L−1 for LHA, and 100 mg L−1 for SHA. The germination index was the largest (698% more effective than control) with 50 mg L−1 of SHA, while it was 528% for LHA, and 493% for HALP at 5 mg L−1. SHA contained the lowest aromatic and phenolic C content, the largest pK2 value of 9.0 (7.7 for LHA and 7.6 for HALP), the least ratio between the aromaticity index and lignin ratio (ARM/LigR) of 0.15 (0.66 for LHA and 129.92 for HALP), and at pH 6.3 the lowest amount of free radicals with a value of 0.567 × 1017 spin g−1 (1.670 × 1017 and 1.780 × 1017 spin g−1 for LHA and HALP, respectively), with the greatest g value of 2.0039 (2.0035 for LHA and 2.0037 for HALP).

Conclusions
The overall chemical structure of humic acids exerted a biostimulation of cress plantlets. The level of the intrinsic stable free radicals identified by EPR in the humic acids resulted well correlated to the ARM/LigR ratio calculated by NMR. Our results suggested that HA biostimulation effect is related to its applied concentration, which is limited by its free radical content. The modulation of the humic supramolecular structure by ROS and organic acids in root exudates can determine the release of bioactive humic molecules. When the content of the intrinsic humic free radicals is high, possible molecular coupling of the bioactive humic molecules may hinder their biostimulation activity. In such cases, a low humic acid concentration appears to be required to achieve the optimum biostimulation effects.

Graphical Abstract
Comparison of human milk bottle with infant/toddler test weights in the community setting
Authors: Esquerra-Zwiers Anita L. , Heter Madeline , Perecki Anastasia , Jackson Olivia , Jongekryg D. Addam , Yurk Brian 
Published: July 2024

Abstract
Background
The accuracy of infant intake using test weights (TWs), the change in weight before and after an infant feeds, has only been validated in hospitalized premature infants. This study’s primary aim was to identify how accurate parent infants/toddler (< 2 years old) TWs are at measuring infant intake.

Methods
Data were collected from 101 paired bottle and infant/toddler TWs with 31 participants. Parents participated in the feeding sessions by completing infant/toddler TWs blinded to the researcher. Research assistants completed human milk bottle TWs. Infants were fed previously expressed human milk, initially 30 g, but volumes were increased to not exceed the scale’s capacity.

Results
The mean difference between the bottle TWs measured using the Tanita and OHAUS scales was not significantly different from zero (95% CI (Tanita – OHAUS): (-0.251, 0.108) g). The mean difference between infant/toddler and bottle TWs was significantly different from 0 (95% CI (infant—bottle): (-3.45, -0.915 g or -3.57, -0.95 mL). Infant/toddler and bottle TWs were in agreement with a difference of 2.18 g (SD = 6.63) or 2.25 mL within the scale stated accuracy.

Conclusions
The Tanita infant digital scale accurately measures bottle TWs. The differences in parent infant/toddler TWs are within a clinically acceptable range.
Intrauterine device (IUD) migration to the fallopian tube: a rare location for a translocated IUD with no visceral injury
Authors: Wangwe Peter Joseph , Awadh Najma , Angelus Magreth 
Published: July 2024

Abstract
Background
Loss of Intra Uterine Device (IUD) following silent perforation of the uterus either during or after IUD insertion is an uncommon finding due to a lack of immediate follow-up. We report a rare case in which uterine perforation following the migration of IUD to the right fallopian tube without visceral injury. The patient presented with lower abdominal pain and pain during sex for one year since IUD insertion. On examination, we noted tenderness on the right suprapubic region and on speculum examination, no IUD thread was seen. A radiological pelvic examination showed an empty uterus without an IUD. Laparotomy and retrieval of migrated IUD was done followed by repair of perforated uterus.

Conclusion
Migrated IUD with silent uterine perforation without visceral injury is a distressing clinical condition both to the patient and the clinician. This case is reported to increase awareness in doing immediate vaginal examination and pelvic ultrasound post-IUD insertion.
Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications
Authors: Akaike Tomoko , Thakuria Manisha , Silk Ann W. , Hippe Daniel S. , Park Song Youn , So Naomi A. , Maloney Nolan J. , Gunnell Lindsay , Eschholz Alec , Kim Emily Y. , Sinha Sumi , Hall Evan Thomas , Bhatia Shailender , Reddy Sunil , Rodriguez Angel Augusto , Aleshin Alexey , Choi Jacob S. , Tsai Kenneth Y. , Yom Sue S. , Yu Siegrid S. , Choi Jaehyuk , Chandra Sunandana , Nghiem Paul , Zaba Lisa C. 
Published: July 2024

PURPOSE Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.
Tetraspanin proteins in membrane remodeling processes
Authors: Dharan Raviv , Sorkin Raya 
Published: July 2024

ABSTRACT
Membrane remodeling is a fundamental cellular process that is crucial for physiological functions such as signaling, membrane fusion and cell migration. Tetraspanins (TSPANs) are transmembrane proteins of central importance to membrane remodeling events. During these events, TSPANs are known to interact with themselves and other proteins and lipids; however, their mechanism of action in controlling membrane dynamics is not fully understood. Since these proteins span the membrane, membrane properties such as rigidity, curvature and tension can influence their behavior. In this Review, we summarize recent studies that explore the roles of TSPANs in membrane remodeling processes and highlight the unique structural features of TSPANs that mediate their interactions and localization. Further, we emphasize the influence of membrane curvature on TSPAN distribution and membrane domain formation and describe how these behaviors affect cellular functions. This Review provides a comprehensive perspective on the multifaceted function of TSPANs in membrane remodeling processes and can help readers to understand the intricate molecular mechanisms that govern cellular membrane dynamics.