bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Parathyroid Hormone Analog (3–34/29–34) promotes wound re-epithelialization through inducing keratinocyte migration and epithelial–mesenchymal transition via PTHR1-PI3K/AKT activation
Authors: Zhou Chunhao , Guan Donghua , Guo Jialiang , Niu Shangbo , Cai Zhihai , Li Chengfu , Qin Chenghe , Yan Wenjuan , Yang Dehong 
Published: August 2023

Abstract
Background
Re-epithelialization is important in the process of wound healing. Various methods have been identified to expedite the process, but their clinical application remains limited. While parathyroid hormone (PTH) has shown promising results in wound healing due to its role in promoting collagen deposition and cell migration, application is limited by its potentially inhibitive effects when being continuously and locally administrated. Herein, we developed a novel PTH analog, Human parathyroid hormone (hPTH) (3–34/29–34) (henceforth MY-1), by partially replacing and repeating the amino acid sequences of hPTH (1–34), and evaluated its effect on skin wound re-epithelialization.

Methods
CCK-8, colony formation unit assay, and Ki67 immunofluorescent staining were performed to evaluate the effect of MY-1 on HaCaT cell proliferation. Then, wound scratch assay, Transwell assay and lamellipodia staining were carried out to evaluate the effect of MY-1 on cell migration. Moreover, the epithelial–mesenchymal transition (EMT) markers were measured using qPCR and western blot analysis. For in-vivo drug delivery, gelatin methacryloyl (GelMA) hydrogel was employed to load the MY-1, with the physicochemical characteristics evaluated prior to its application in wound models. Then, MY-1’s role in wound healing was determined via acute skin wound models. Finally, the mechanism that MY-1 activated was also detected on HaCaT cells and in-vivo wound models.

Results
In-vitro, MY-1 accelerated the migration and EMT of HaCaT cells, while having little effect on cell proliferation. GelMA and MY-1-incorporated GelMA hydrogels showed similar physicochemical characteristics and were used in the in-vivo studies, where the results revealed that MY-1 led to a stronger re-epithelialization by inducing basal keratinocyte migration and EMT. Further studies on in-vivo wound models and in-vitro HaCaT cells revealed that MY-1 regulated cell migration and EMT through activating PI3K/AKT signaling. The parathyroid hormone type 1 receptor (PTHR1), the main receptor of PTH, was found to be the upstream of PI3K/AKT signaling, through interfering PTHR1 expression with a small interference RNA following detection of the PI3K/AKT activation.

Conclusion
Collectively, our study demonstrated that MY-1 accelerates skin wound re-epithelialization by inducing keratinocyte migration and EMT via PTHR1-PI3K/AKT axis activation.
RepID represses megakaryocytic differentiation by recruiting CRL4A-JARID1A at DAB2 promoter
Authors: Jo Jae-Hyun , Park Jong-Uk , Kim Yeong-Mu , Ok Seon-Mi , Kim Dong-Kyu , Jung Dong-Hyun , Kim Hye-Ji , Seong Hyun-A , Cho Hyo Je , Nah Jihoon , Kim Sangjune , Fu Haiqing , Redon Christophe E. , Aladjem Mirit I. , Jang Sang-Min 
Published: August 2023

Abstract
Background
Megakaryocytes (MKs) are platelet precursors, which arise from hematopoietic stem cells (HSCs). While MK lineage commitment and differentiation are accompanied by changes in gene expression, many factors that modulate megakaryopoiesis remain to be uncovered. Replication initiation determinant protein (RepID) which has multiple histone-code reader including bromodomain, cryptic Tudor domain and WD40 domains and Cullin 4-RING E3 ubiquitin ligase complex (CRL4) recruited to chromatin mediated by RepID have potential roles in gene expression changes via epigenetic regulations. We aimed to investigate whether RepID-CRL4 participates in transcriptional changes required for MK differentiation.

Methods
The PCR array was performed using cDNAs derived from RepID-proficient or RepID-deficient K562 erythroleukemia cell lines. Correlation between RepID and DAB2 expression was examined in the Cancer Cell Line Encyclopedia (CCLE) through the CellMinerCDB portal. The acceleration of MK differentiation in RepID-deficient K562 cells was determined by estimating cell sizes as well as counting multinucleated cells known as MK phenotypes, and by qRT-PCR analysis to validate transcripts of MK markers using phorbol 12-myristate 13-acetate (PMA)-mediated MK differentiation condition. Interaction between CRL4 and histone methylation modifying enzymes were investigated using BioGRID database, immunoprecipitation and proximity ligation assay. Alterations of expression and chromatin binding affinities of RepID, CRL4 and histone methylation modifying enzymes were investigated using subcellular fractionation followed by immunoblotting. RepID-CRL4-JARID1A-based epigenetic changes on DAB2 promoter were analyzed by chromatin-immunoprecipitation and qPCR analysis.

Results
RepID-deficient K562 cells highly expressing MK markers showed accelerated MKs differentiation exhibiting increases in cell size, lobulated nuclei together with reaching maximum levels of MK marker expression earlier than RepID-proficient K562 cells. Recovery of WD40 domain-containing RepID constructs in RepID-deficient background repressed DAB2 expression. CRL4A formed complex with histone H3K4 demethylase JARID1A in soluble nucleus and loaded to the DAB2 promoter in a RepID-dependent manner during proliferation condition. RepID, CRL4A, and JARID1A were dissociated from the chromatin during MK differentiation, leading to euchromatinization of the DAB2 promoter.

Conclusion
This study uncovered a role for the RepID-CRL4A-JARID1A pathway in the regulation of gene expression for MK differentiation, which can form the basis for the new therapeutic approaches to induce platelet production.
GSDMD knockdown attenuates phagocytic activity of microglia and exacerbates seizure susceptibility in TLE mice
Authors: Yang Xiaoxia , Cao Qingqing , Guo Yi , He Jingchuan , Xu Demei , Lin Aolei 
Published: August 2023

Abstract
Background
Temporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Phagocytic activity of microglia is essential for clearing apoptotic neuronal debris, allowing for repair and regeneration. Our previous research has shown that gasdermin D (GSDMD)-mediated pyroptosis is involved in the pathogenesis of TLE. However, whether GSDMD-mediated pyroptosis influences the accumulation of apoptotic neurons remains unclear. Therefore, the present study was designed to investigate whether phagocytic activity of microglia is involved in GSDMD-mediated pyroptosis and the pathogenesis of TLE.

Methods
To establish a TLE model, an intra-amygdala injection of kainic acid (KA) was performed. The Racine score and local field potential (LFP) recordings were used to assess seizure severity. Neuronal death in the bilateral hippocampus was assessed by Nissl staining and TUNEL staining. Microglial morphology and phagocytic activity were detected by immunofluorescence and verified by lipopolysaccharide (LPS) and the P2Y12R agonist 2MeSADP.

Results
GSDMD knockdown augmented the accumulation of apoptotic neurons and seizure susceptibility in TLE mice. Microglia activated and transition to the M1 type with increased pro-inflammatory cytokines. Furthermore, GSDMD knockdown attenuated the migration and phagocytic activity of microglia. Of note, LPS-activated microglia attenuated seizure susceptibility and the accumulation of apoptotic neurons in TLE after GSDMD knockdown. A P2Y12R selective agonist, 2MeSADP, enhanced the migration and phagocytic activity of microglia.

Conclusions
Our results demonstrate that GSDMD knockdown exacerbates seizure susceptibility and the accumulation of apoptotic neurons by attenuating phagocytic activity of microglia. These findings suggest that GSDMD plays a protective role against KA-induced seizure susceptibility.
A scoping review of the discrepancies in the measurement of cerebral blood flow in idiopathic intracranial hypertension: oligemia, euvolemia or hyperemia?
Authors: Bateman Grant A 
Published: August 2023

Abstract
Background
The literature regarding the global cerebral blood flow (CBF) in idiopathic intracranial hypertension (IIH) is divergent leading to skepticism about the significance of blood flow to the disease’s underlying pathophysiology.

Methods
The purpose of the current paper is to perform a PRISMA scoping review of the literature describing the CBF in IIH. The review investigated the PUBMED and Scopus data bases looking at case mix, technique and the methodologies employed by the studies selected.

Discussion
Many studies indicate that the flow in IIH is normal but others show the flow to be altered. These later studies show a range of flows from a reduction of 20% to an increase of 50% compared to control values. Obesity is a common finding in IIH and is known to reduce CBF, anemia occurs in approximately 20% of IIH patients and is a potent cause of an increased CBF. Thus, variations in case mix may have a significant effect on the final outcome in those studies which are underpowered. The varying techniques which have been used to estimate CBF have differing strengths and weaknesses which may also have a bearing on the outcome. Some papers have significant confounding methodological issues.

Conclusions
This review suggests each of the variables investigated are responsible for the divergent CBF findings in IIH.
Public health advocacy strategies to influence policy agendas: lessons from a narrative review of success in trade policy
Authors: Townsend Belinda , Tenni Brigitte Frances , Goldman Sharni , Gleeson Deborah 
Published: August 2023

Abstract
Background
Despite accumulating evidence of the implications of trade policy for public health, trade and health sectors continue to operate largely in silos. Numerous barriers to advancing health have been identified, including the dominance of a neoliberal paradigm, powerful private sector interests, and constraints associated with policymaking processes. Scholars and policy actors have recommended improved governance practices for trade policy, including: greater transparency and accountability; intersectoral collaboration; the use of health impact assessments; South-South networking; and mechanisms for civil society participation. These policy prescriptions have been generated from specific cases, such as the World Trade Organization’s Doha Declaration on TRIPS and Public Health or specific instances of trade-related policymaking at the national level. There has not yet been a comprehensive analysis of what enables the elevation of health goals on trade policy agendas. This narrative review seeks to address this gap by collating and analysing known studies across different levels of policymaking and different health issues.

Results
Sixty-five studies met the inclusion criteria and were included in the review. Health issues that received attention on trade policy agendas included: access to medicines, food nutrition and food security, tobacco control, non-communicable diseases, access to knowledge, and asbestos harm. This has occurred in instances of domestic and regional policymaking, and in bilateral, regional and global trade negotiations, as well as in trade disputes and challenges. We identified four enabling conditions for elevation of health in trade-related policymaking: favourable media attention; leadership by trade and health ministers; public support; and political party support. We identified six strategies successfully used by advocates to influence these conditions: using and translating multiple forms of evidence, acting in coalitions, strategic framing, leveraging exogenous factors, legal strategy, and shifting forums.

Conclusion
The analysis demonstrates that while technical evidence is important, political strategy is necessary for elevating health on trade agendas. The analysis provides lessons that can be explored in the wider commercial determinants of health where economic and health interests often collide.
Long-term follow-up in a pediatric patient with Ligneous Conjunctivitis due to PLG gene mutation in topical plasminogen treatment after successful use of ocular prosthesis for aesthetic rehabilitation: a case report
Authors: Panfili Filippo Maria , Valente Paola , Ficari Andrea , Cortellessa Fabiana , Vecchio Davide , Gonfiantini Michaela Veronika , Buonuomo Paola Sabrina , Colafati Giovanna Stefania , Agolini Emanuele , Bartuli Maria , Modugno Alessandra Claudia , Macchiaiolo Marina 
Published: August 2023

Abstract
Background
Ligneous Conjunctivitis (LC) is the most common clinical manifestation of Type I Plasminogen deficiency (T1PD; OMIM# 217090), and it is characterized by the formation of pseudomembranes (due to deposition of fibrin) on the conjunctivae leading to progressive vision loss.
In past times, patients with LC were treated with surgery, topical anti-inflammatory, cytostatic agents, and systemic immunosuppressive drugs with limited results (Blood 108:3021-3026, 2006, Ophthalmology 129:955-957, 2022, Surv Ophthalmol 48:369-388, 2003, Blood 131:1301-1310, 2018). The surgery can also trigger the development of membranes, as observed in patients needing ocular prosthesis (Surv Ophthalmol 48:369-388, 2003). Treatment with topical purified plasminogen is used to prevent pseudomembranes formation (Blood 108:3021-3026, 2006, Ophthalmology 129:955-957, 2022).

Case presentation
We present the case of a sixteen-year-old girl with LC with severe left eye involvement. We reported the clinical conditions of the patient before and after the use of topical plasminogen eye drops and described the treatment schedule allowing the surgical procedure for the pseudomembranes debulking and the subsequent use of ocular prosthesis for aesthetic rehabilitation.

Conclusions
The patient showed a progressive response to the topical plasminogen, with a complete absence of pseudomembrane formation at a twelve-year follow-up, despite using an ocular prosthesis.
Analysis of state 1—state 2 transitions by genome editing and complementation reveals a quenching component independent from the formation of PSI-LHCI-LHCII supercomplex in Arabidopsis thaliana
Authors: Cutolo Edoardo Andrea , Caferri Roberto , Guardini Zeno , Dall’Osto Luca , Bassi Roberto 
Published: August 2023

Abstract
Background
The light-harvesting antennae of photosystem (PS) I and PSII are pigment-protein complexes responsible of the initial steps of sunlight conversion into chemical energy. In natural environments plants are constantly confronted with the variability of the photosynthetically active light spectrum. PSII and PSI operate in series but have different optimal excitation wavelengths. The prompt adjustment of light absorption by photosystems is thus crucial to ensure efficient electron flow needed to sustain downstream carbon fixing reactions. Fast structural rearrangements equilibrate the partition of excitation pressure between PSII and PSI following the enrichment in the red (PSII-favoring) or far-red (PSI-favoring) spectra. Redox imbalances trigger state transitions (ST), a photoacclimation mechanism which involves the reversible phosphorylation/dephosphorylation of light harvesting complex II (LHCII) proteins by the antagonistic activities of the State Transition 7 (STN7) kinase/TAP38 phosphatase enzyme pair. During ST, a mobile PSII antenna pool associates with PSI increasing its absorption cross section. LHCII consists of assorted trimeric assemblies of Lhcb1, Lhcb2 and Lhcb3 protein isoforms (LHCII), several being substrates of STN7. However, the precise roles of Lhcb phosphorylation during ST remain largely elusive.

Results
We inactivated the complete Lhcb1 and Lhcb2 gene clades in Arabidopsis thaliana and reintroduced either wild type Lhcb1.3 and Lhcb2.1 isoforms, respectively, or versions lacking N-terminal phosphorylatable residues proposed to mediate state transitions. While the substitution of Lhcb2.1 Thr-40 prevented the formation of the PSI-LHCI-LHCII complex, replacement of Lhcb1.3 Thr-38 did not affect the formation of this supercomplex, nor did influence the amplitude or kinetics of PSII fluorescence quenching upon state 1—state 2 transition.

Conclusions
Phosphorylation of Lhcb2 Thr-40 by STN7 alone accounts for ≈ 60% of PSII fluorescence quenching during state transitions. Instead, the presence of Thr-38 phosphosite in Lhcb1.3 was not required for the formation of the PSI-LHCI-LHCII supercomplex nor for re-equilibration of the plastoquinone redox state. The Lhcb2 phosphomutant was still capable of ≈ 40% residual fluorescence quenching, implying that a yet uncharacterized, STN7-dependent, component of state transitions, which is unrelated to Lhcb2 Thr-40 phosphorylation and to the formation of the PSI-LHCI-LHCII supercomplex, contributes to the equilibration of the PSI/PSII excitation pressure upon plastoquinone over-reduction.
Comparison of two handgrip dynamometers in older adults before elective surgery
Authors: Andrade Maricarmen S. , Honorato Macarena P. , Vargas Javiera P. , de los Angeles Galvez María , Rojas Mariana R. 
Published: August 2023

Abstract
Background
Handgrip strength is a useful measurement of muscle strength and has been proposed as a single predictor of postoperative outcomes in older adults. The aim of this study was to assess the correlation and concordance of Camry digital hand grip dynamometer (EH101) with gold standard Jamar® hydraulic handgrip dynamometer in older adults previous to elective surgery.

Methods
A cross-sectional study was conducted on patients ≥ 65 years old admitted to a Chilean private hospital for elective surgery between March 2018 and February 2019. Handgrip strength was assessed 2 times with each hand prior to surgery, using both the Jamar® dynamometer and the Camry digital dynamometer. The highest value of each dynamometer was used for analysis.

Results
We included a total of 220 patients (mean age 73.1 years old ± 6.3). Maximal handgrip strength averaged 26.9 kg ± 9.6 with the Camry dynamometer and 26.9 kg ± 9.7 with the Jamar® dynamometer in the right hand and 25.5 kg ± 9.5 with the Camry dynamometer and 25.7 kg ± 9.2 with the Jamar® dynamometer with the left hand. The difference between both measures did not differ significantly from 0, with Pearson correlation index of 0.95 and Lin’s concordance index of 0.95 (p < 0001). The Bland–Altman graphics show that 90% of the measures were inside the confidence limits, without systematic bias.

Conclusion
Camry digital dynamometer is an inexpensive and valid device to measure handgrip strength in older adults previous to elective surgery, compared to the gold standard Jamar® hydraulic handgrip dynamometer.
Psychometric properties of an Arabic translation of the Nine Item Avoidant/Restrictive Food Intake Disorder Screen (NIAS) in a community sample of adults
Authors: Fekih-Romdhane Feten , Hallit Rabih , Malaeb Diana , Sakr Fouad , Dabbous Mariam , Sawma Toni , Obeid Sahar , Hallit Souheil 
Published: August 2023

Abstract
Background
No epidemiological data is yet available on Avoidant/Restrictive Food Intake Disorder (ARFID) in Arab countries, which may in part be due to the lack of measures available in Arabic language. This constitutes a major obstacle to further progress of our understanding of the nature, aetiology, course, treatment, and prevention of ARFID, especially as some evidence suggested that ARFID may vary across cultures and food environments. We aimed to contribute to the literature in the eating disorders field by examining the psychometric properties of an Arabic translation of the Nine Item ARFID Screen (NIAS).

Method
This was a cross-sectional, web-based study. A total of 515 Lebanese community adults (mean age of 27.55 ± 10.92 years, 69.9% females) participated. The forward–backward method was adopted to translate the NIAS from English to Arabic.

Results
Confirmatory Factor Analyses provided evidence for the adequate fit indices for the three-factor model (i.e., Picky eating, Fear, and Appetite) and the 9-item version of the NIAS. An adequate reliability of the Arabic NIAS was achieved, with McDonald’s ω ranging from .75 to .90 for the total score and all three subscores. Multi-group analyses demonstrated measurement invariance by sex (males vs. females) and weight groups (underweight/healthy weight [BMI ≤ 25] vs. overweight/obese [BMI > 25]) at the configural, metric, and scalar levels. Adequate patterns of correlations between the NIAS and measures of disordered eating symptoms, psychological distress and well-being were seen. In particular, fear was significantly associated with non-ARFID disordered eating symptoms. Appetite and Picky eating, but not Fear, were inversely correlated with well-being. All three NIAS subscores and the total score were positively correlated with psychological distress.

Conclusion
Findings provided evidence that the Arabic NIAS is a short, valid and reliable self-report measure to screen for ARFID symptoms. In light of these findings, we recommend its use for clinical and research purposes among Arabic-speaking adults.
Biomarkers for immune checkpoint inhibition in sarcomas – are we close to clinical implementation?
Authors: Yiong Chin Sern , Lin Tzu Ping , Lim Vivian Yujing , Toh Tan Boon , Yang Valerie Shiwen 
Published: August 2023

AbstractSarcomas are a group of diverse and complex cancers of mesenchymal origin that remains poorly understood. Recent developments in cancer immunotherapy have demonstrated a potential for better outcomes with immune checkpoint inhibition in some sarcomas compared to conventional chemotherapy. Immune checkpoint inhibitors (ICIs) are key agents in cancer immunotherapy, demonstrating improved outcomes in many tumor types. However, most patients with sarcoma do not benefit from treatment, highlighting the need for identification and development of predictive biomarkers for response to ICIs. In this review, we first discuss United States (US) Food and Drug Administration (FDA)-approved and European Medicines Agency (EMA)-approved biomarkers, as well as the limitations of their use in sarcomas. We then review eight potential predictive biomarkers and rationalize their utility in sarcomas. These include gene expression signatures (GES), circulating neutrophil-to-lymphocyte ratio (NLR), indoleamine 2,3-dioxygenase (IDO), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and mucin domain-containing protein 3 (TIM-3), TP53 mutation status, B cells, and tertiary lymphoid structures (TLS). Finally, we discuss the potential for TLS as both a predictive and prognostic biomarker for ICI response in sarcomas to be implemented in the clinic.