bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL6-STAT3-C/EBPβ-IL6 positive feedback loop in tumor-associated macrophages promotes the EMT and metastasis of lung adenocarcinoma
Authors: Hu Zhengyang , Sui Qihai , Jin Xing , Shan Guangyao , Huang Yiwei , Yi Yanjun , Zeng Dejun , Zhao Mengnan , Zhan Cheng , Wang Qun , Lin Zongwu , Lu Tao , Chen Zhencong 
Published: February 2024

Abstract
Background
Lung cancer is one of the most common tumors in the world, and metastasis is one of the major causes of tumor-related death in lung cancer patients. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are frequently associated with tumor metastasis in human cancers. However, the regulatory mechanisms of TAMs in lung cancer metastasis remain unclear.

Methods
Single-cell sequencing analysis of lung cancer and normal tissues from public databases and from 14 patients who underwent surgery at Zhongshan Hospital was performed. In vitro co-culture experiments were performed to evaluate the effects of TAMs on lung cancer migration and invasion. Changes in the expression of IL-6, STAT3, C/EBPΒ, and EMT pathway were verified using RT-qPCR, western blotting, and immunofluorescence. Dual luciferase reporter assays and ChIP were used to reveal potential regulatory sites on the transcription factor sets. In addition, the effects of TAMs on lung cancer progression and metastasis were confirmed by in vivo models.

Results
TAM infiltration is associated with tumor progression and poor prognosis. IL-6 secreted by TAMs can activate the JAK2/STAT3 pathway through autocrine secretion, and STAT3 acts as a transcription factor to activate the expression of C/EBPβ, which further promotes the transcription and expression of IL-6, forming positive feedback loops for IL6-STAT3-C/EBPβ-IL6 in TAMs. IL-6 secreted by TAMs promotes lung cancer progression and metastasis in vivo and in vitro by activating the EMT pathway, which can be attenuated by the use of JAK2/STAT3 pathway inhibitors or IL-6 monoclonal antibodies.

Conclusions
Our data suggest that TAMs promote IL-6 expression by forming an IL6-STAT3-C/EBPβ-IL6 positive feedback loop. Released IL-6 can induce the EMT pathway in lung cancer to enhance migration, invasion, and metastasis. The use of IL-6-neutralizing antibody can partially counteract the promotion of LUAD by TAMs. A novel mechanism of macrophage-promoted tumor progression was revealed, and the IL6-STAT3-C/EBPβ-IL6 signaling cascade may be a potential therapeutic target against lung cancer.

Graphical Abstract
IL-6 secreted by TAM acts on itself to promote STAT3 phosphorylation, and pSTAT3 transfers into the nucleus, promotes the expression of C/EBPβ. C/EBPβ is able to further promote IL-6 expression, which forms positive feedback for IL-6 secretion. IL-6 secreted by TAMs acts on lung cancer to promote their metastasis through activation of EMT.
Scleritis following intravitreal brolucizumab injection: a case series
Authors: Takayama Takuya , Inoda Satoru , Takahashi Hidenori , Tsukii Rika , Yoshida Hana , Kasuya Yuka , Nagaoka Kosuke , Takahashi Ryota , Arai Yusuke , Kawashima Hidetoshi 
Published: February 2024

Abstract
Background
This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections.

Case presentation
Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon’s capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. Case 2. An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn’t due to progression of nAMD.

Conclusions
Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.
Optimal decay-in-time rates of solutions to the Cauchy problem of 3D compressible magneto-micropolar fluids
Authors: Cui Xinyu , Fu Shengbin , Sun Rui , Tian Fangfang 
Published: February 2024

AbstractThis paper focuses on the long time behavior of the solutions to the Cauchy problem of the three-dimensional compressible magneto-micropolar fluids. More precisely, we aim to establish the optimal rates of temporal decay for the highest-order spatial derivatives of the global strong solutions by the method of decomposing frequency. Our result can be regarded as the further investigation of the one in (Wei, Guo and Li in J. Differ. Equ. 263:2457–2480, 2017), in which the authors only provided the optimal rates of temporal decay for the lower-order spatial derivatives of the perturbations of both the velocity and the micro-rotational velocity.
Updates and future directions regarding hand hygiene in the healthcare setting: insights from the 3rd ICPIC alcohol-based handrub (ABHR) task force
Authors: Tartari Ermira , Bellissimo-Rodrigues Fernando , Pires Daniela , Fankhauser Carolina , Lotfinejad Nasim , Saito Hiroki , Suchomel Miranda , Kramer Axel , Allegranzi Benedetta , Boyce John , Sax Hugo , Stewardson Andrew J. , Pittet Didier ,   the ICPIC Alcohol-Based Handrub Task Force, Rodin Aeschbach , Yuichi Kumashita , Benjamin Alléard , Pamela Lee , Tingxu Lu , Jim Arbogast , Leonard Mermel , Chedly Azzouz , Emma Barrett , Ben Park , Lelyn Quan , Martina Bühler , Andreea Capilna , César Serna Jiménez , Nizam Damani , Sven Eggerstedt , Peter Teska , Nicole van Hall , Sonja Hansen , Margreet Vos , Thomas Hennig , Andreas Widmer , Loreen Herwaldt , Kazuko Yakata , Deborah Yokoe , Mike Bell , Noel Bertho Jean , Tcheun-How Borzykowski , John Conly , Carlos Da Silva , Kazuko Yakata , Ariel Geva , Tamas Haidegger , Loreen Herwaldt , Carolyn Holland , Bonnie Okeke , Kevin Ormandy , Pierre Parneix , Alexandra Peters , Vanessa Pouget , Lionel Robert , Cesar Serna Jimenez , Walter Zingg 
Published: February 2024

AbstractHealthcare-associated infections (HAIs) and antimicrobial resistance (AMR) pose threats to global health. Effective hand hygiene is essential for preventing HAIs and the spread of AMR in healthcare. We aimed to highlight the recent progress and future directions in hand hygiene and alcohol-based handrub (ABHR) use in the healthcare setting. In September 2023, 42 experts in infection prevention and control (IPC) convened at the 3rd International Conference on Prevention and Infection Control (ICPIC) ABHR Taskforce in Geneva, Switzerland. The purpose of this meeting was to provide a synthesis of recent evidence and formulate a research agenda on four critical areas for the implementation of effective hand hygiene practices: (1) ABHR formulations and hand rubbing techniques, (2) low-resource settings and local production of ABHR, (3) hand hygiene monitoring and technological innovations, and (4) hand hygiene standards and guidelines.
From bedside to recovery: exercise therapy for prevention of post-intensive care syndrome
Authors: Liu Keibun , Tronstad Oystein , Flaws Dylan , Churchill Luke , Jones Alice Y. M. , Nakamura Kensuke , Fraser John F. 
Published: February 2024

Abstract
Background
As advancements in critical care medicine continue to improve Intensive Care Unit (ICU) survival rates, clinical and research attention is urgently shifting toward improving the quality of survival. Post-Intensive Care Syndrome (PICS) is a complex constellation of physical, cognitive, and mental dysfunctions that severely impact patients’ lives after hospital discharge. This review provides a comprehensive and multi-dimensional summary of the current evidence and practice of exercise therapy (ET) during and after an ICU admission to prevent and manage the various domains of PICS. The review aims to elucidate the evidence of the mechanisms and effects of ET in ICU rehabilitation and highlight that suboptimal clinical and functional outcomes of ICU patients is a growing public health concern that needs to be urgently addressed.

Main body
This review commences with a brief overview of the current relationship between PICS and ET, describing the latest research on this topic. It subsequently summarises the use of ET in ICU, hospital wards, and post-hospital discharge, illuminating the problematic transition between these settings. The following chapters focus on the effects of ET on physical, cognitive, and mental function, detailing the multi-faceted biological and pathophysiological mechanisms of dysfunctions and the benefits of ET in all three domains. This is followed by a chapter focusing on co-interventions and how to maximise and enhance the effect of ET, outlining practical strategies for how to optimise the effectiveness of ET. The review next describes several emerging technologies that have been introduced/suggested to augment and support the provision of ET during and after ICU admission. Lastly, the review discusses future research directions.

Conclusion
PICS is a growing global healthcare concern. This review aims to guide clinicians, researchers, policymakers, and healthcare providers in utilising ET as a therapeutic and preventive measure for patients during and after an ICU admission to address this problem. An improved understanding of the effectiveness of ET and the clinical and research gaps that needs to be urgently addressed will greatly assist clinicians in their efforts to rehabilitate ICU survivors, improving patients’ quality of survival and helping them return to their normal lives after hospital discharge.
Surgical management of retinal detachment and macular holes secondary to ocular toxoplasmosis: a systematic review and meta-analysis
Authors: Amaral Dillan Cunha , Lane Mark , Aguiar Eduardo Henrique Cassins , Marques Guilherme Nunes , Cavassani Luiza Visentin , Rodrigues Márcio Penha Morterá , Alves Milton Ruiz , Manso José Eduardo Ferreira , Monteiro Mário Luiz Ribeiro , Louzada Ricardo Noguera 
Published: February 2024

Abstract
Background
Toxoplasma gondii causes ocular toxoplasmosis (OT), involving inflammation, scarring, and retinal complications. The OT complications were retinal detachment (RD), and retinal breakage (RB). Surgical interventions like scleral buckling (SB) and vitrectomy are common. Limited understanding exists of the safety and efficacy of surgical management of RD/RB secondary to OT. Another complication is toxoplasmosis-related macular holes (tMH), with sparse evidence on surgical outcomes. This meta-analysis aims to clarify clinical characteristics, and surgical results, and enhance understanding of RD, RB, and MH secondary to OT.

Methods
PubMed, Cochrane, Embase and Web of Science database were queried for retrospective studies, case series and case reports that provided information on RD, RB and MH associated with OT and reported the outcomes of: (1) Retinal reattachment of RD/RB and tMH closure; (2) Best-corrected visual acuity (BCVA) improvement; and (3) Complications. Heterogeneity was examined with I2 statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was performed using the software R (version 4.2.3, R Foundation for Statistical Computing, Vienna, Austria).

Results
Fourteen final studies, comprising a total of 96 patients were analyzed, 81 with RD or RB and 15 with tMH. Overall, surgical management was associated with several advantages: a high rate of retinal reattachment of RD/RB of 97% (95% Confidence Interval [CI] 92–100%; I2 = 0%), retinal reattachment of just RD of 96% (95% CI 89–100%; I2 = 30%) and tMH closure 97% (95% CI 87–100; I2 = 12%). There were significant differences in BCVA after surgeries in studies of RD/RB (MD 0.60; 95% CI 0.35–0.65; I2 = 20%) and MH (MD 0.67; 95% CI 0.50–0.84; I2 = 0%). The overall complication rate associated with surgical procedures in RD/RB secondary to OT was confirmed to be 25%.

Conclusions
The systematic review and meta-analysis showed that the treatment approaches currently in use are effective, with a remarkable rate of retinal reattachment of RD/RB, tMH closure, and substantial improvements in visual acuity. More randomized, long-term studies on disease and surgical factors can provide valuable insights into their impact on anatomical and visual outcomes.
Correlation between retinal sensitivity assessed by microperimetry and structural abnormalities on optical coherence tomography after successful epiretinal membrane surgery
Authors: Matos Aline Mota Freitas , Defina Raphael Lucas Sampaio , Costa-Cunha Luciana Virgínia Ferreira , Zacharias Leandro Cabral , Preti Rony Carlos , Monteiro Mário Luiz Ribeiro , Cunha Leonardo Provetti 
Published: February 2024

Abstract
Background
To verify the correlation between retinal sensitivity (RS) assessed by the microperimetry (MP) and optical coherence tomography (OCT) parameters measured in eyes submitted to pars-plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM) treatment.

Methods
43 patients underwent PPV. Best-corrected visual acuity (BCVA) and OCT imaging were acquired preoperatively and 6 months after surgery. The RS values were recorded 6 months after the surgery. Total macular thickness (TMT) measurements and OCT-evaluated structural findings were also analyzed. The MP examination tested 44 points, with direct topographic correspondence with the OCT-ETDRS map. Correlations between BCVA, RS, and OCT parameters were assessed.

Results
TMT measurements in patients were significantly thicker preoperatively and reduced after surgery. All patients demonstrated BCVA improvements after surgery. The RS parameters after surgery were significantly lower in patients. For OCT structural analyses, patients with lower RS at the fovea correlated with the preexisting disorganization of retinal inner layers (DRIL). In addition, lower RS values were associated with DRIL, outer retinal changes (ORC), and intraretinal microcysts after surgery.

Conclusions
The RS values after surgery were significantly lower when compared to controls. The DRIL presence before and after surgery, and microcysts and ORC after surgery were related to worse visual outcomes.
Observation of single-molecule Raman spectroscopy enabled by synergic electromagnetic and chemical enhancement
Authors: Yang Haiyao , Mo Haoran , Zhang Jianzhi , Hong Lihong , Li Zhi-Yuan 
Published: February 2024

AbstractThere has been a long fundamental pursuit to enhance and levitate the Raman scattering signal intensity of molecule by a huge number of ~ 14–15 orders of magnitude, to the level comparable with the molecule fluorescence intensity and truly entering the regime of single-molecule Raman spectroscopy. In this work we report unambiguous observation of single-molecule Raman spectroscopy via synergic action of electromagnetic and chemical enhancement for rhodamine B (RhB) molecule absorbed within the plasmonic nanogap formed by gold nanoparticle sitting on the two-dimensional (2D) monolayer WS2 and 2 nm SiO2 coated gold thin film. Raman spectroscopy down to an extremely dilute value of 10–18 mol/L can still be clearly visible, and the statistical enhancement factor could reach 16 orders of magnitude compared with the reference detection sample of silicon plate. The electromagnetic enhancement comes from local surface plasmon resonance induced at the nanogap, which could reach ~ 10–11 orders of magnitude, while the chemical enhancement comes from monolayer WS2 2D material, which could reach 4–5 orders of magnitudes. This synergic route of Raman enhancement devices could open up a new frontier of single molecule science, allowing detection, identification, and monitor of single molecules and their spatial–temporal evolution under various internal and external stimuli.
Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors
Authors: Jotanovic Jelena , Tebani Abdellah , Hekmati Neda , Sivertsson Åsa , Lindskog Cecilia , Uhlèn Mathias , Gudjonsson Olafur , Tsatsaris Erika , Engström Britt Edén , Wikström Johan , Pontén Fredrik , Casar-Borota Olivera 
Published: February 2024

Abstract
Although most pituitary neuroendocrine tumors (PitNETs)/pituitary adenomas remain intrasellar, a significant proportion of tumors show parasellar invasive growth and 6% to 8% infiltrate the bone structures, thus affecting the prognosis. There is an unmet need to identify novel markers that can predict the parasellar growth of PitNETs. Furthermore, mechanisms that regulate bone invasiveness of PitNETs and factors related to tumor vascularization are largely unknown.
We used genome-wide mRNA analysis in a cohort of 77 patients with PitNETs of different types to explore the differences in gene expression patterns between invasive and noninvasive tumors with respect to the parasellar growth and regarding the rare phenomenon of bone invasiveness. Additionally, we studied the genes correlated to the contrast enhancement quotient, a novel radiological parameter of tumor vascularization.
Most of the genes differentially expressed related to the parasellar growth were genes involved in tumor invasiveness. Differentially expressed genes associated with bone invasiveness are involved in NF-κB pathway and antitumoral immune response. Lack of clear clustering regarding the parasellar and bone invasiveness may be explained by the influence of the cell lineage-related genes in this heterogeneous cohort of PitNETs.
Our transcriptomics analysis revealed differences in the molecular fingerprints between invasive, including bone invasive, and noninvasive PitNETs, although without clear clustering. The contrast enhancement quotient emerged as a radiological parameter of tumor vascularization, correlating with several angiogenesis-related genes. Several of the top genes related to the PitNET invasiveness and vascularization have potential prognostic and therapeutic application requiring further research.
Functional opsin patterning for Drosophila color vision is established through signaling pathways in adjacent object-detection neurons
Authors: Kitamata Manabu , Otake Yoshiaki , Kitagori Hideaki , Zhang Xuanshuo , Maki Yusuke , Boku Rika , Takeuchi Masato , Nakagoshi Hideki 
Published: February 2024

ABSTRACT
Vision is mainly based on two different tasks, object detection and color discrimination, carried out by photoreceptor (PR) cells. The Drosophila compound eye consists of ∼800 ommatidia. Every ommatidium contains eight PR cells, six outer cells (R1-R6) and two inner cells (R7 and R8), by which object detection and color vision are achieved, respectively. Expression of opsin genes in R7 and R8 is highly coordinated through the instructive signal from R7 to R8, and two major ommatidial subtypes are distributed stochastically; pale type expresses Rh3/Rh5 and yellow type expresses Rh4/Rh6 in R7/R8. The homeodomain protein Defective proventriculus (Dve) is expressed in yellow-type R7 and in six outer PRs, and it is involved in Rh3 repression to specify the yellow-type R7. dve mutant eyes exhibited atypical coupling, Rh3/Rh6 and Rh4/Rh5, indicating that Dve activity is required for proper opsin coupling. Surprisingly, Dve activity in R1 is required for the instructive signal, whereas activity in R6 and R7 blocks the signal. Our results indicate that functional coupling of two different neurons is established through signaling pathways from adjacent neurons that are functionally different.
Learning from Failures: Differentiating Between Slip-ups and Knowledge Gaps
Authors: Anand Gopesh , Mukherjee Ujjal Kumar 
Published: February 2024

Our research investigates firm learning from failures by dividing them into two types, failures that occur due to slip-ups and those that occur due to knowledge gaps, and by examining whether learning occurs in the context of both types of failures. We study these phenomena in the context of product recalls in pharmaceuticals and medical devices. Based on text analysis of recall documents, recalls are divided into process related and design related to represent slip-up failures and knowledge gap failures. We further study how innovation capabilities, represented by accumulated stocks of patents and lagged research and development (R&D) intensity, impact learning from both types of failures. We test our hypotheses using negative binomial generalized linear models to analyze longitudinal data for 108 publicly traded U.S. firms over 2000–2016 comprising 7,984 recalls. Results indicate that design-related recalls generate learning to a greater extent than process-related recalls, and that accumulated patents and lagged R&D intensity enhance learning from design-related recalls. These findings suggest that the learning mechanisms invoked by failures are concentrated more on knowledge gap failures than slip-up failures, and such learning is impacted by innovation capabilities. Overall, this research extends organizational learning theory by differentiating between learning from different types of failures and extends absorptive capacity theory by incorporating the role of innovation capabilities in enhancing learning from failures. We develop recommendations for learning from slip-up failures by focusing on the cultural and social mechanisms of organizational learning in addition to the technical and structural mechanisms that may mainly impact learning from knowledge gap failures. Supplemental Material: The online appendices are available at https://doi.org/10.1287/orsc.2021.15663 .