bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trogocytosis-mediated immune evasion in the tumor microenvironment
Authors: Kim Jeonghyun , Park Soyeon , Kim Jungseo , Kim Yewon , Yoon Hong Min , Rayhan Bima Rexa , Jeong Jaekwang , Bothwell Alfred L. M. , Shin Jae Hun 
Published: January 2025

Abstract
Trogocytosis is a dynamic cellular process characterized by the exchange of the plasma membrane and associated cytosol during cell-to-cell interactions. Unlike phagocytosis, this transfer maintains the surface localization of transferred membrane molecules. For example, CD4 T cells engaging with antigen-presenting cells undergo trogocytosis, which facilitates the transfer of antigen-loaded major histocompatibility complex (MHC) class II molecules from antigen-presenting cells to CD4 T cells. This transfer results in the formation of antigen-loaded MHC class II molecule-dressed CD4 T cells. These “dressed” CD4 T cells subsequently participate in antigen presentation to other CD4 T cells. Additionally, trogocytosis enables the acquisition of immune-regulatory molecules, such as CTLA-4 and Tim3, in recipient cells, thereby modulating their anti-tumor immunity. Concurrently, donor cells undergo plasma membrane loss, and substantial loss can trigger trogocytosis-mediated cell death, termed trogoptosis. This review aims to explore the trogocytosis-mediated transfer of immune regulatory molecules and their implications within the tumor microenvironment to elucidate the underlying mechanisms of immune evasion in cancers.
Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases
Authors: Guo Wei , Zhou Bolun , Dou Lizhou , Guo Lei , Li Yong , Qin Jianjun , Wang Zhen , Huai Qilin , Xue Xuemin , Li Yin , Ying Jianming , Xue Qi , Gao Shugeng , He Jie 
Published: January 2025

Abstract
Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals.
Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential
Authors: Sesti Valentina , Magni Arianna , Moschetta Matteo , Florindi Chiara , Pfeffer Marlene E. , DiFrancesco Mattia Lorenzo , Guizzardi Michele , Folpini Giulia , Sala Luca , Ritacca Alessandra Gilda , Campanelli Beatrice , Moretti Paola , Paternò Giuseppe Maria , Maragliano Luca , Tommasini Matteo , Lodola Francesco , Colombo Elisabetta , Benfenati Fabio , Bertarelli Chiara , Lanzani Guglielmo 
Published: January 2025

AbstractWe introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response. Specifically, MTs photoisomerization induces clear and reproducible depolarization. The most promising species, MTP2, was extensively studied. Time-resolved spectroscopy techniques provide insights into the excited state evolution and a complete understanding of its isomerization reaction. Molecular Dynamics simulations reveal the spontaneous and stable partitioning of the compound into the cellular membrane, without significant alterations to the bilayer thickness. MTP2 was tested in different cell types, including HEK293T cells, primary neurons, and cardiomyocytes, and a steady depolarization is always recorded. The observed membrane potential modulation in in-vitro models is attributed to the variation in membrane surface charge, resulting from the light-driven modulation of the MT dipole moment within the cell membrane. Additionally, a developed mathematical model successfully captures the temporal evolution of the membrane potential upon photostimulation. Despite being insufficient for triggering action potentials, the rapid light-induced depolarization holds potential applications, particularly in cardiac electrophysiology. Low-intensity optical stimulation with these modulators could influence cardiac electrical activity, demonstrating potential efficacy in destabilizing and terminating cardiac arrhythmias. We anticipate the MTs approach to find applications in neuroscience, biomedicine, and biophotonics, providing a tool for modulating cell physiology without genetic interventions.
Near-infrared germanium PIN-photodiodes with >1A/W responsivity
Authors: Liu Hanchen , Pasanen Toni P. , Fung Tsun Hang , Isometsä Joonas , Haarahiltunen Antti , Hesse Steven , Werner Lutz , Vähänissi Ville , Savin Hele 
Published: January 2025

AbstractEven though efficient near-infrared (NIR) detection is critical for numerous applications, state-of-the-art NIR detectors either suffer from limited capability of detecting incoming photons, i.e., have poor spectral responsivity, or are made of expensive group III-V non-CMOS compatible materials. Here we present a nanoengineered PIN-photodiode made of CMOS-compatible germanium (Ge) that achieves a verified external quantum efficiency (EQE) above 90% over a wide wavelength range (1.2–1.6 µm) at zero bias voltage at room temperature. For instance, at 1.55 µm, this corresponds to a responsivity of 1.15 A/W. In addition to the excellent spectral responsivity at NIR, the performance at visible and ultraviolet wavelengths remains high (EQE exceeds even 100% below 300 nm) resulting in an exceptionally wide spectral response range. The high performance is achieved by minimizing optical losses using surface nanostructures and electrical losses using both conformal atomic-layer-deposited aluminum oxide surface passivation and dielectric induced electric field -based carrier collection instead of conventional pn-junction. The dark current density of 76 µA/cm2 measured at a reverse bias of 5 V is lower than previously reported for Ge photodiodes. The presented results should have an immediate impact on the design and manufacturing of Ge photodiodes and NIR detection in general.
Optical sectioning methods in three-dimensional bioimaging
Authors: Zhang Jing , Qiao Wei , Jin Rui , Li Hongjin , Gong Hui , Chen Shih-Chi , Luo Qingming , Yuan Jing 
Published: January 2025

AbstractIn recent advancements in life sciences, optical microscopy has played a crucial role in acquiring high-quality three-dimensional structural and functional information. However, the quality of 3D images is often compromised due to the intense scattering effect in biological tissues, compounded by several issues such as limited spatiotemporal resolution, low signal-to-noise ratio, inadequate depth of penetration, and high phototoxicity. Although various optical sectioning techniques have been developed to address these challenges, each method adheres to distinct imaging principles for specific applications. As a result, the effective selection of suitable optical sectioning techniques across diverse imaging scenarios has become crucial yet challenging. This paper comprehensively overviews existing optical sectioning techniques and selection guidance under different imaging scenarios. Specifically, we categorize the microscope design based on the spatial relationship between the illumination and detection axis, i.e., on-axis and off-axis. This classification provides a unique perspective to compare the implementation and performances of various optical sectioning approaches. Lastly, we integrate selected optical sectioning methods on a custom-built off-axis imaging system and present a unique perspective for the future development of optical sectioning techniques.
Asparagine endopeptidase regulates lysosome homeostasis via modulating endomembrane phosphoinositide composition
Authors: Yao Linli , Zi GuangHui , He Miao , Xu Yuhong , Wang Lulu , Peng Baowei 
Published: January 2025

AbstractAsparagine endopeptidase (AEP) is ubiquitously expressed in both physiological and pathological contexts, yet its precise role and functional mechanism in breast cancer remain elusive. Here, we identified increased AEP expression in breast cancer tissues, which correlated with poorer survival rates and a propensity for lung metastasis among breast cancer patients. Loss of AEP impaired colony formation by breast cancer cells in vitro and suppressed lung metastasis in mice. By Gene Set Enrichment Analysis (GSEA) analysis, we uncovered a positive association between aberrant AEP expression and autophagy as well as lysosomal function. Loss of AEP in breast cancer cells led to reduced autophagosome clearance and impaired lysosomal degradation. Mechanically, by co-immunoprecipitation and in vitro enzymatic cleavage assays, we identified the regulatory subunit p85 of class IA PI3K phosphatidylinositol 3-kinase (PI3K), as a substrate of AEP. Loss of AEP led to elevated endo/lysosomal PI3K activity and subsequent conversion of PtdIns(4,5)P2 (PIP2) to PtdIns(3,4,5)P3 (PIP3) on endo/lysosome membranes. Notably, the novel function of endo/lysosomal PI3K which was differently with its role in cytomembrane, was revealed by pharmacological inhibition with a potent endo/lysosomal PI3K inhibitor PIK75. PIK75 treatment showed increased vacuolar-ATPase assembly endo/lysosome membranes, prevented over lysosome perinuclear clustering/fusion and enhanced autophagosome clearance. Our findings demonstrate that AEP regulates cellular autophagy by modulating lysosomal function through its control over endo/lysosomal PI3K activity. These results suggest that AEP may serve as a potential target for suppressing metabolic adaptations in cancer.
ALT Donor Area Compartment Syndrome: A Rare and Devastating Complication
Authors: Alsina Gloria , Nunez-Villaveirán Teresa , Camporro Daniel , Martin Clara 
Published: January 2025

AbstractWe present two cases of acute compartment syndrome (ACS) in the donor area of an anterolateral thigh (ALT) flap, with extensive necrosis of the quadriceps muscle. An innervated latissimus dorsi (LD) flap was used to cover the defect and restore functionality of the lower extremity. ACS in the ALT donor area is extraordinarily uncommon. Its mechanism seems to be multifactorial, being more frequent in young athletic males and, possibly, in patients with anatomical vascular variations. It is important to detect it promptly to prevent irreversible muscular ischemia. Intense pain is an alarm sign but might be absent in patients with epidural infusion pumps. We recommend caution with the use of this analgesia and frequent monitoring of the donor area during the early postoperative period. The free functional LD muscle flap is an option to treat full-thickness quadriceps damage, allowing for wound closure, soft-tissue coverage, and restoration of the knee extension movement.
Defining and Achieving High-Quality Colon Cancer Surgery
Authors: Morris Arden M. , Kin Cindy J. 
Published: January 2025

AbstractThere have been extensive efforts to improve the quality of colon cancer surgery to reduce variation in practice and improve outcomes. Providing the most appropriate care begins with following guidelines for preoperative diagnostics and staging, which should lead to risk stratification, high-quality counselling, and even prehabilitation before an operation. Intraoperatively, adherence to standardized surgical protocols can enhance delivery of high-quality care, and documenting using synoptic formats can reduce ambiguity. Participating in programs that track data and provide feedback can further allow hospitals and surgeons to identify patterns and opportunities to improve the care they deliver.
Change in frailty status in the 12 months following solid organ transplantation: a systematic review and meta-analysis
Authors: Bevan Anna , Avery Jenny , Cheah Hoe Leong , Carter Ben , Hewitt Jonathan 
Published: January 2025

Abstract

Objectives
To investigate if frailty status alters following solid organ transplantation (lung, liver, kidney and heart) without rehabilitation intervention.

Research design and methods
Studies published between 1 January 2000 and 30 May 2023 were searched across five databases. Studies measuring frailty, using a validated or established frailty measure, pre- and post-transplant were included. Narrative synthesis was used to describe the included studies according to the time post-transplant and according to solid organ group. Where data allowed a meta-analysis was conducted to compare frailty prevalence pre- and 6–12 months post-transplant across studies.

Results
Twelve studies were included in this review (6 kidney transplant, 2 liver transplant, 3 lung transplant and 1 heart transplant), with a total of 3065 transplant recipients with 62% being male. The mean age across studies was 51.35 years old. When narratively synthesised after an initial worsening of frailty immediately post-transplant, there appears to be a significant improvement in frailty by 3 months post-transplant that is sustained by 6 to 12 months following solid organ transplantation. Five studies were included in the meta-analysis which demonstrated an odds ratio = 0.27 (95% CI, 0.12, 0.59, P = .001, ${I}^2$ = 82%) for frailty prevalence post-solid organ transplantation (SOT) compared to frailty prevalence pre-SOT. When the single paper deemed to be of poor quality was removed the remaining four studies demonstrated a reduced odds ratio of being frail at 6–12 months post-transplant (OR 0.45 (95% CI, 0.32, 0.65, P = .001, ${I}^2$ = 13%).

Conclusions
Transplant may be associated with a reversal in frailty, although heterogeneity was demonstrated across studies.
Short- and Long-Term Effect of COVID-19 Pandemic on Rates of Suicide Attempts treated in Illinois Hospitals
Authors: Abid Imen Ben , Shannon Brett , Friedman Lee S 
Published: January 2025

Abstract
Previous studies on the impact of the COVID-19 pandemic on suicide trends have yielded inconsistent findings, with inadequate differentiation of short and long-term effects. Addressing this gap, our study evaluates the pandemic's short and long-term trends in suicide attempts across various demographics. Illinois statewide hospital data covering January 1, 2016, through December 31, 2022, was analyzed. Compared to the pre-pandemic baseline period, changes in daily rates of suicide attempts treated across four periods of State Executive Orders limiting public gatherings were evaluated. Segmented time series analysis was developed to evaluate specific temporal patterns across four pandemic periods. A total of 153,476 suicide attempts were registered, with 38.6% of cases occurring after March 16, 2020. A significant increase of 0.8353 attempts per day per 1 million (p-value &lt;0.0001) was found after the second "stay-at-home orders" period. A significant increase in suicide attempts was observed in females 11 to 16 years old, starting from the second "stay-at-home order" through the end of 2022, and in females 19 to 24 years old after the end of the second "stay-at-home order". The rise in suicide attempts among young females during the pandemic's later stages is alarming. Further investigation into specific risk factors is needed.
Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression
Authors: Garay María I , Mazo Tamara , Ferrero Victoria , Barotto Nelso N , Lagares Clarisa , Granton María F , Moreira-Espinoza María J , Cremonezzi David C , Comba Andrea , Brunotto Mabel N , Tolosa Ezequiel J , Fernandez-Zapico Martín E , Pasqualini María E 
Published: January 2025

Abstract
Pancreatic cancer is a devastating malignancy in great need of new and more effective treatment approaches. In recent years, studies have indicated that nutritional interventions, particularly nutraceuticals, may provide novel avenues to modulate cancer progression. Here, our study characterizes the impact of ω-3 polyunsaturated fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, as a nutraceutical intervention in pancreatic cancer using a genetically engineered mouse model driven by KrasG12D and Trp53R172H. This model closely resembles human pancreatic carcinogenesis, offering a disease relevant platform for translational research. Our findings showed that ω-3 polyunsaturated fatty acids intervention (using a diet supplemented with 6% cod liver oil) significantly reduced tumor volume as well as lung and liver metastasis and a trend toward improved survival rate compared with control treated mice. This antitumoral effect was accompanied by distinct changes in tumor membrane fatty acid profile and eicosanoids release. Furthermore, the eicosapentaenoic acid and docosahexaenoic acid intervention also reduced malignant histological parameters and induced apoptosis without affecting cell proliferation. Of note is the significant reduction in tumor fibrosis that was associated with decreased levels of Sonic Hedgehog, a major ligand controlling this cellular compartment in pancreatic cancer. All together our results demonstrate the impact of eicosapentaenoic acid and docosahexaenoic acid as antitumor regulators in pancreatic cancer, suggesting potential for ω-3 polyunsaturated fatty acids as a possible antitumoral dietary intervention. This research opens new avenues for integrating nutraceutical strategies in pancreatic cancer management.
Antibody–drug conjugates in breast cancer
Authors: Zhu Yinxing , Song Yaqi , Zhou Xilei , Zhang Wenwen , Luo Honglei 
Published: January 2025

Abstract
Antibody–drug conjugates (ADCs) have garnered significant attention as an innovative therapeutic strategy in cancer treatment. The mechanism of action for ADCs involves the targeted delivery of antibodies to specific receptors, followed by the release of cytotoxic payloads directly into tumor cells. In recent years, ADCs have made substantial progress in the treatment of breast cancer (BC), particularly demonstrating significant efficacy in the human epidermal growth factor receptor-2 (HER-2)-positive subgroup. Clinical evidence indicates that ADCs have notably improved treatment efficacy and survival outcomes for BC patients. However, challenges such as drug toxicities and the emergence of drug resistance necessitate further research and discussion. In this paper, we will summarize the advances in ADCs targeting various receptors in BC patients and explore the challenges and future directions in this field. We anticipate that the increasing availability of ADCs will lead to more effective and personalized treatment options for BC patients.
Gustatory dysfunction in multiple sclerosis: a systematic review and meta-analysis
Authors: Rajai Firouzabadi Shahryar , Mohammadi Ida , Alinejadfard Mohammadreza , Yazdan Panah Mohammad , Vaheb Saeed , Shaygannejad Vahid , Mirmosayyeb Omid 
Published: January 2025

Abstract
Gustatory dysfunction is an often overlooked symptom in people with multiple sclerosis (PwMS), potentially leading to poor appetite, malnutrition, weight loss, and decreased quality of life. This systematic review and meta-analysis aimed to assess the pooled prevalence of gustatory dysfunction in PwMS and compare their gustatory test scores with healthy controls. An online database search of PubMed, Embase, Scopus, and Web of Science was conducted on 2024 June 29. Observational studies reporting gustatory dysfunction or gustatory test scores in PwMS were included. Pooled prevalence rates were calculated using a random-effects model, with subgroup analyses based on the type of gustatory test used. Standardized mean differences (SMD) were calculated for comparisons between PwMS and healthy controls. A total of 9 studies encompassing 1385 PwMS were included. The pooled prevalence of gustatory dysfunction among PwMS was 16.4% (95% confidence intervals [95% CI]: 8.7% to 24.1%, I² = 90%, P &lt; 0.01). Subgroup analysis showed a prevalence of 18.8% (95% CI: 10.5% to 27.2%, I² = 0%) in 4 studies using the Taste Strip Test (TST), while 3 non-TST studies using liquid tastants or self-reports reported a prevalence of 20.2% (95% CI: 7.2% to 33.3%, I² = 86%). PwMS had significantly lower gustatory test scores compared to healthy controls (SMD: −0.93, 95% CI: −1.20 to −0.65, I² = 0%, P = 0.48). Gustatory dysfunction affects a notable proportion of PwMS, with prevalence rates varying by assessment method. Future studies should assess the possible causes of gustatory dysfunction in PwMS using validated gustatory assessment scales.
DESIGN, MEASURES, AND CORRELATES OF CHANGES IN AD BLOOD BIOMARKERS AND ASSOCIATIONS WITH NEUROIMAGING OUTCOMES
Authors: Palta Priya , Pike James , Lu Yifei , Chen Jinyu , Walker Keenan , Sullivan Kevin , Mosley Thomas 
Published: January 2025

Abstract
Few studies have examined changes in blood-based biomarkers of AD pathology and neurodegeneration particularly during the mid- to late-life transition period and associations with brain pathology. Among 1525 (59.9% women, 25.8% Black) ARIC participants, we measured blood-based biomarkers of Aβ42, Aβ40, p-Tau181, NfL, and GFAP using stored specimens from midlife (1993-1995, mean age 58.3 years) and late-life (2011-2013, mean age 76.0 years followed to 2016-2019, mean age 80.7 years). Using linear mixed effects models, we examined whether known dementia-related risk factors in midlife (i.e., hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) are associated with 20-year biomarker changes. We also examined the associations of midlife, late-life, and mid- to late-life changes in blood biomarkers with measures of whole brain cortical thickness, brain volume, and white matter hyperintensity volume (WMH) from a 3T brain MRI scan in multivariable linear regression models. All models were adjusted for age, sex, race-center, education, APOE, eGFR, body mass index, cardiovascular risk factors, and intracranial volume for volumetric analyses. Decreasing Aβ42/Aβ40 and increasing p-Tau181, NfL, and GFAP were observed from midlife to late-life. Midlife hypertension and diabetes were associated with a steeper rise in NfL and GFAP. Lower late-life levels of Aβ42/Aβ40 and higher late-life levels of p-Tau181, p-Tau181/Aβ42, NfL, and GFAP were associated with smaller cortical thickness and total brain volume, and larger WMH volume. Blood biomarkers of AD neuropathology, neuronal injury, and astrogliosis rise with age and are associated with known dementia risk factors and markers of neurodegeneration and cerebrovascular disease.