bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Statin Therapy on the Healing of Diabetic Foot Ulcers: A Retrospective Chart Review.
Authors: O'Dell Brennen , Rothenberg Gary , Holmes Crystal , Priesand Sari , Mizokami-Stout Kara , Brandt Eric , Schmidt Brian
Published: October 2023

Background
Diabetic foot ulcers (DFU) are a costly complication of diabetes mellitus (DM), with significant implications for the patient and the healthcare professionals that treat them. The primary objective of this study was to evaluate if there were improved healing rates in patients with DFU that were taking a statin medication compared to those patients with a DFU who were not taking a statin medication. Secondary outcomes assessed were associations with wound healing or statin use on data obtained from retrospective chart review.
Methods
A retrospective chart review was performed to obtain appropriate demographic information, comorbid conditions, laboratory values, and physical examination findings. From the time of presentation with DFU, these patients were followed for 12 weeks to evaluate for healing. Healing was defined as full epithelialization of the DFU with no further drainage. Wound healing and statin use association testing was then done for collected variables and each cohort. A univariate analysis was then performed with a linear regression calculator to identify any significant associations.
Results
Our study identified 109 patients, 75 patients with DFU on statin medication and 34 patients with DFU not on statin medication. The statin cohort was more likely to be older, less than 5-year duration of diabetes, have more comorbidities, decreased low-density lipoprotein (LDL) cholesterol, and decreased total cholesterol (p < 0.05). 48.0% (36/75) of patients taking a statin medication healed their DFU within 12 weeks. Among those patients not taking a statin medication, 44.1% (15/34) healed their DFU within 12 weeks. No association was noted between wound healing and statin use (p = 0.71). For wound healing, associations were noted for prior minor amputations (p < 0.05). For statin use, associations were noted between age, duration of DM, LDL cholesterol level, total cholesterol level, HTN, CAD, and HLD (p < 0.05).
Conclusions
Statin medication did not influence DFU healing rates between cohorts. There was an association noted between wound healing and prior minor amputations and between statin use and age, duration of DM, LDL cholesterol, total cholesterol, HTN, CAD and HLD. Additionally, we observed no association between DFU healing rates and use of a statin medication.
Co-Existence of Moyamoya Syndrome With Arteriovenous Malformation. Systematic Review and Illustrative Case Report
Authors: Stanishevskiy Artem , Svistov Dmitriy , Babichev Konstantin , Savello Alexander , Zelenskiy Bogdan
Published: October 2023

The co-existence of moyamoya syndrome with arteriovenous malformation is extremely rare. We describe the case of a 37-year-old female patient suffering from arteriovenous malformation in the right parietal lobe combined with severe stenosis of the right middle cerebral artery, and right anterior cerebral artery, accompanied by moyamoya collateral induction. We aimed to investigate the frequency, mutual influence of the diseases on each other, and preferable treatment strategy by reviewing previous case reports. We searched PubMed, Scopus, and Web of Science databases following preferred reporting items for systematic reviews and meta-analyses guidelines and reviewed 36 publications reporting 64 cases of arteriovenous malformation with moyamoya syndrome. In a half of cases, stenosis was bilateral. Among the patients with unilateral stenosis, AVM was localized in the opposite hemisphere only in 2 cases. In 18 cases, both stenosis and AVM were actively treated; in 11 cases, stenosis was treated prior to AVM; in 5 cases, AVM was treated at first; and in three cases, both AVM and stenosis were treated simultaneously. Embolization was used in six cases and was supplemented by stereotactic radiosurgery in two. Stereotactic radiosurgery alone was used in 12 cases. In 15 patients, the AVM was removed surgically. Our findings may benefit neurosurgeons who treat patients with co-existing arteriovenous malformations and moyamoya syndrome and researchers who perform further systematic reviews and meta-analyses on the topic.
Sex-specific associations between phenotypes and environmental exposures
Authors: Zarzar Tomás González , Palmiero Nicole , Kim Dokyoon , Shen Li , Hall Molly
Published: October 2023

Sex and gender differences are ubiquitous in health and disease. We used data from the National Health and Nutrition Examination Survey to identify associations between environmental exposures and health-related phenotypes that differ between males and females. We found a total of 119 sex-specific exposure-phenotype associations, which included phenotypes such as albumin, homocysteine, bilirubin, and hemoglobin levels and exposures to cadmium, lead, benzene, toluene, ethylbenzene, and xylene. Smoking-related exposures were among the exposures with the greatest number of sex-specific phenotypic associations. The positive effects of smoking-related exposure on homocysteine and hemoglobin levels, hematocrit, and red blood cell counts were larger in females than in males. Conversely, the negative effects of smoking-related exposures on albumin and bilirubin levels were larger in males than in females. Our results show potential mechanisms by which women who smoke are at higher risk of cardiovascular diseases, and men have a heightened inflammatory response.
Factors associated with health-related quality of life in women with systemic lupus erythematosus and permanent skin damage – a cross-sectional study
Authors: Oliveira Fernando A Palmeira , Moura Fabiana Miranda , Dias Ana Flávia Madureira de Pádua , Santoro Claudia Neiva , Pereira Fernando Henrique , Telles Rosa Weiss , Lanna Cristina Costa Duarte
Published: October 2023

Background: Skin manifestations occur in up to 85% of systemic lupus erythematosus (SLE) patients and can result in cutaneous atrophy and scarring, which can have a negative influence on health-related quality of life (HRQoL). Our study aims to describe HRQoL in SLE patients with permanent skin damage and explore its association with sociodemographic characteristics, self-esteem, and depression and anxiety symptoms.
Methods: Cross-sectional study of women with SLE and permanent skin damage on the face and low systemic disease activity. HRQoL was assessed by the Systemic Lupus Erythematosus Quality of Life (SLEQOL) and Dermatology Life Quality Index (DLQI) questionnaires - higher scores indicating worse HRQoL. The Rosenberg self-esteem scale was used to assess self-esteem, and depression/anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale.
Results: Fifty-six consecutive patients were enrolled with a median (interquartile range - IQR) age of 47.0 (37.3 - 55.0) years and disease duration of 15.0 (8.0 - 24.8) years. The median (IQR) of the modified SLEDAI-2k was 2 (0-2) and that of the SLICC-DI was 2 (1-3). 42.8% were married, 71.4% had less than eight years of education, 71.4% were unemployed and 75.0% had a family income between 1 and 3 times the minimum wage. Higher scores in SLEQOL symptoms domain were associated with a low educational level. Higher DLQI and SLEQOL total scores were associated with low self-esteem and symptoms of depression and anxiety. SLEQOL domains, physical functioning and symptoms, were associated with low self-esteem, depression and anxiety symptoms, and the presence of scarring alopecia, whereas the activities domain was associated with low self-esteem and depression and anxiety symptoms. Mood domain was associated with low self-esteem, self-image, depression and anxiety symptoms, and treatment domain with symptoms of depression.
Conclusion: We identified low HRQoL in patients with permanent skin damage and low systemic disease activity, whether in the physical, self-image, mood or psychological domains. Associated factors were low educational level, presence of scarring alopecia, presence of anxiety and depression symptoms, and low self-esteem. These results highlight the importance of strategies to minimize the burden of permanent skin damage on the HRQoL of women with SLE.
Trial Registration: UTN code U1111-1210-2554.
BET inhibition induces synthetic lethality in PTEN deficient colorectal cancers via dual action on p21CIP1/WAF1
Authors: Shim Joong Sup , Ren Guowen , Chen Jinghong , Pu Yue , Yang Eun Ju , Tao Shishi , Mou Pui Kei , Chen Li-Jie , Zhu Wenli , Chan Kin Long , Luo Guanghui , Deng Chuxia
Published: October 2023

Loss of PTEN tumor suppressor is an important event during colorectal cancer (CRC) development and is a target for therapeutic exploitation. This study reports that bromodomain and extra-terminal motif (BET) is a synthetic lethal partner of PTEN in CRC. BET inhibition (BETi) selectively induced G1 cell cycle arrest and apoptosis in PTEN−/− CRC. Further, BETi selectively and dose-dependently suppressed the growth of PTEN−/− CRC tumor xenografts in mice and patient-derived organoids. Mechanistically, PTEN-deficient CRC cells elevated the level of cytoplasmic p21CIP1/WAF1 that is hyper-phosphorylated at Thr145 by AKT. BETi suppressed AKT activation in PTEN-deficient CRC cells, followed by the reduction in p21 phosphorylation at Thr145, thereby promoting its nuclear translocation. In addition, BETi suppressed MYC level and this in turn increased the total p21 level in the nuclei. Over-expression of a phospho-mimetic p21 mutant (T145D) significantly rescued the BETi effect on PTEN-deficient CRC. These results suggest that BETi has a dual action on p21: elevating the level of p21 by inhibiting MYC and converting the oncogenic (cytoplasmic) p21 into the tumor suppressive (nuclear) p21 by inhibiting AKT. Taken together, this study identified the synthetic lethal interaction between PTEN and BET, and provides a potential actionable target for CRC with PTEN loss.
Augmenting Mitochondrial Respiration in Immature Smooth Muscle Cells with an ACTA2 Pathogenic Variant Mitigates Moyamoya-like Cerebrovascular Disease
Authors: Kaw Anita , Wu Ting , Starosolski Zbigniew , Zhou Zhen , Pedroza Albert , Majumder Suravi , Duan Xue-yan , Kaw Kaveeta , Pinelo Jose Esparza , Fischbein Michael P , Lorenzi Philip , Tan Lin , Martinez Sara , Mahmud Iqbal , Devkota Laxman , Taegtmeyer Heinrich , Ghaghada Ketan , Marrelli Sean , Kwartler Callie , Milewicz Dianna
Published: October 2023

ACTA2 pathogenic variants altering arginine 179 cause childhood-onset strokes due to moyamoya disease (MMD)-like occlusion of the distal internal carotid arteries. A smooth muscle cell (SMC)-specific knock-in mouse model (Acta2SMC-R179C/+) inserted the mutation into 67% of aortic SMCs, whereas explanted SMCs were uniformly heterozygous. Acta2R179C/+ SMCs fail to fully differentiate and maintain stem cell-like features, including high glycolytic flux, and increasing oxidative respiration (OXPHOS) with nicotinamide riboside (NR) drives the mutant SMCs to differentiate and decreases migration. Acta2SMC-R179C/+ mice have intraluminal MMD-like occlusive lesions and strokes after carotid artery injury, whereas the similarly treated WT mice have no strokes and patent lumens. Treatment with NR prior to the carotid artery injury attenuates the strokes, MMD-like lumen occlusions, and aberrant vascular remodeling in the Acta2SMC-R179C/+ mice. These data highlight the role of immature SMCs in MMD-associated occlusive disease and demonstrate that altering SMC metabolism to drive quiescence of Acta2R179C/+ SMCs attenuates strokes and aberrant vascular remodeling in the Acta2SMC-R179C/+ mice.
Drug-associated Porphyria: A Pharmacovigilance Study
Authors: wang qi , zhuang ling jun , han bing , chen miao , zhao bin
Published: October 2023

Background: The potentially fatal attacks experienced by carriers of porphyria are triggered by various porphyrinogenic drugs; however, it is difficult to determine the safety of a particular drug.
Mothed: we retrospectively used the FDA’s Adverse Event Reporting System (FAERS) to determine drugs associated with porphyria as an adverse event (AE). Reports with porphyria as an AE were extracted from FAERS data from January 2004 to March 2022. Search terms used to identify the AEs included “Porphyria,” “Porphyria screen,” “Porphyria non-acute,” “Porphyria acute,” “Acquired porphyria,” and “Pseudoporphyria.” Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms “ROR,” “PRR,” “BCPNN,” and “MGPS.”
Results: FAERS reported 1470 cases of porphyria-related AEs and 406 drugs were obtained after combining trade and generic names of the same drug. Fifty-two drugs with signals were identified by all four algorithms. The characteristics of all the reports and signaling drugs were analyzed.
Conclusions: This is the first report of drug-associated porphyria analysis, that provides critical information on drug porphyrogenicity, thus allowing rational and evidence-based prescribing of drugs and improving the accuracy of predicted porphyrogenicity by model algorithms. In addition, this study provides references for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.
A comparative trial of blood pressure monitoring in a self- care kiosk, in office, and with ambulatory blood pressure monitoring
Authors: Nilsson Gunnar , Lindam Anna
Published: October 2023

Background: If kiosk blood pressure (BP) monitoring provides results equivalent to daytime ambulatory BP monitoring (ABPM), follow-up of patients could be managed primarily by self-checks. We therefore designed a trial of automated BP monitoring in three settings: a designated BP kiosk, by nurses and physicians in clinic, and by ABPM. We also evaluated the diagnostic performance of kiosk- and office-based BP (nurse- versus physician-measured) compared with ABPM.
Methods: In-office and in-kiosk BP measurements were taken with Omron meters and ABPM with a Meditech device. The primary outcome was systolic and diastolic BP, with respective diagnostic thresholds of ≥135 mmHg and/or ≥85 mmHg for daytime ABPM and kiosk BP and ≥140 mmHg and/or ≥90 mmHg for office BP (nurse- and physician-measured).
Results: Compared with daytime ABPM, mean systolic kiosk BP was higher by 6.2 mmHg (95% confidence interval [CI] 3.8–8.6) and diastolic by 7.9 mmHg (95% CI 6.2–9.6; p < 0.001). Mean systolic BP taken by nurses was similar to daytime ABPM values (+2.0 mmHg; 95% CI -0.2–4.2; p = 0.071), but nurse-measured diastolic values were higher, by 7.2 mmHg (95% CI 5.9–9.6; p < 0.001). Mean systolic and diastolic physician-measured BPs were higher compared with daytime ABPM (systolic, by 7.6 mmHg [95% CI 4.5–10.2] and diastolic by 5.8 mmHg [95% CI 4.1–7.6]; p < 0.001). Receiver operating characteristic curves of BP monitoring across pairs of systolic/diastolic cut-off levels among the three settings, with daytime ABPM as reference, demonstrated overall similar diagnostic performance between kiosk and nurse-measured values and over the curve performance for physician-measured BP. Accuracy with nurse-measured BP was 69.2% (95% CI 60.0%–77.4%), compared with 65.8% (95% CI 56.5%–74.3%) for kiosk BP.
Conclusions: Kiosk BP monitoring is not comparable to daytime ABPM but can be an alternative to in-office BP monitoring by trained nurses.
The diagnostic performance of kiosk and nurse-measured BP monitoring was similar and better than that of physician-measured BP.
Trial registration: The study was registered at ClinicalTrials.gov (NCT04488289) 27/07/2020.
Decreased long-chain acyl-CoA dehydrogenase mediates cardiac energy deficiency and injury induced by β-adrenergic stimulation
Authors: Xiao Han , Xu Wenli , Zhao Mingming , Zhang Mi , Chen Xianda , Song Yao , Liu Huirong , Dong Erdan , Zhang You-Yi
Published: October 2023

Background: Overactivation of β-adrenergic receptor (β-AR) signaling underlies the cardiotoxic effects of sympathetic hyperactivity in cardiovascular disease. However, the mechanism through which metabolic changes caused by β-AR overactivation leads to cardiac injury is poorly understood.
Methods: A comprehensive multi-omics profile was performed on myocardial tissue following exposure to isoproterenol (ISO, a β-AR agonist). Cardiac-specific overexpression or downregulation of the relevant metabolic enzyme was established to investigate the mechanism. During ISO stimulation, profiles for substrate oxidation and ATP production in cardiomyocytes were also examined.
Results: Through a non-targeted metabolomics approach, lipids were identified as the most significantly affected metabolites in mouse hearts following β-AR overactivation, and subsequent targeted lipidomics analysis revealed that acylcarnitine levels were most notably elevated. Consistent with these results, patients with acute coronary syndrome showed a higher circulating acylcarnitine profile which correlated with catecholamine levels and cardiac pathologies. Mechanistic studies found that excess acylcarnitine exposure triggered inflammasome-dependent cardiomyocyte pyroptosis. Expression level of long-chain acyl-coenzyme A dehydrogenase (LCAD), an enzyme that metabolizes acylcarnitines, was markedly decreased in cardiomyocytes upon β-AR overactivation. Furthermore, ISO inhibited LCAD enzymatic activity by inhibiting sirtuin 3-mediated deacetylation, leading to ATP deficiency and acylcarnitine accumulation. Activation of AMP-activated protein kinase (AMPK) attenuated the effects of ISO on cardiomyocytes that reduced LCAD, ATP depletion, acylcarnitine-induced pyroptosis, and cardiac dysfunction in vivo.
Conclusions: Upon β-AR overactivation, decreased LCAD in cardiomyocytes leads to energy deficiency and pyroptosis, subsequently impair cardiac function. Upregulation of LCAD by AMPK activators may be a therapeutic strategy for treating sympathetic stress-induced cardiac injury.
Can pre-treatment assessment of aqueous vascular and inflammatory biomarkers in patients with macular oedema secondary to retinal vein occlusion guide treatment options?
Authors: Shankar Jai , Hughes Stephen , Ella-Tongwiis Peter
Published: October 2023

Background: Macular oedema following Retinal Vein occlusion is the second most common cause of visual loss due to retinal vascular disease. The Royal College of Ophthalmologists recommends intra-vitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) for patients with glaucoma and in young patients & steroid injections in those with recent cardiovascular events. Treatment is, both, expensive and demanding on secondary care. There is no recommendation regarding pre-treatment biomarker testing to determine which would be a better treatment option.

Aims: The study aimed to determine whether vascular and inflammatory biomarkers in BRVO and CRVO differ from normal levels, and whether one can formulate an individualised treatment plan to predict whether anti-VEGF or steroids are more likely to be beneficial.

Methods: Eight patients each with newly diagnosed BRVO and CRVO with macular oedema without any previous intra-vitreal injections were recruited (n=16). 100-200μl of aqueous sample was taken from the anterior chamber just prior to intra-vitreal injection of anti-VEGF agent or steroid. Aqueous samples were also collected from eight patients undergoing routine cataract surgery (n=8). ELISA was employed to assess the samples for VEGF and IL-8 levels.

Results: VEGF and IL-8 levels were significantly higher in RVO as compared to controls and higher in CRVO as compared to BRVO. There were some samples with predominance of VEGF and others with IL-8.

Conclusion: This study concludes that pre-treatment assessment of biomarkers may help determine whether anti-VEGF or steroid would be a better treatment option and thereby result in a significant cost reduction for the healthcare provider.
Evaluating the impact of technological innovation and energy efficiency on load capacity factor: Empirical analysis of India
Authors: Özkan Oktay , Saleem Faiza , Sharif Arshian
Published: October 2023

The determinants of environmental degradation have been investigated many times by utilizing carbon dioxide emissions and/or ecological footprint. However, these traditional environmental degradation indicators do not consider the supply side of environmental problems. Therefore, this study focuses on the dynamic influence of financial development, energy efficiency, economic growth, and technological innovation on environmental degradation in India through the load capacity factor, including both supply and demand sides of environmental problems. For that purpose, the recently developed dynamically simulated autoregressive distributed lag (ARDL) method is employed using the annual time-series data extending from 1980–2020. The dynamically simulated ARDL results demonstrate that financial development, economic growth, and technological innovation have a dynamic adverse impact on the load capacity factor, whereas energy efficiency has a positive dynamic influence on environmental quality. In addition, the results support the validity of the environmental Kuznets curve hypothesis as the negative effect of economic growth on environmental quality decreases over time. Based on the study findings, policy recommendations are provided for India. Finally, this study utilizing load capacity factor as an indicator for environmental quality will provide new topics in exploring the determinants of environmental degradation.
Nanoparticles' Role in Advancing Agriculture: A comparative study of green and chemically synthesized nanoparticles and their influence on root and shoot morphology of Sunflower
Authors: Pruthviraj N , Geetha K N , Kumar G N Anil , Shruthi D L , Shankar A G , Prakash S S , Sridh Shankarappa , Raghu A V
Published: October 2023

The eco-friendly synthesis approach was employed to create nanoparticles by harnessing the inherent properties of natural sources. Cassia fistula leaf extract was utilized for boron nitride production, while Simarouba glauca was employed for sulphur nanoparticles. The nanoparticles' characterization involved identifying functional groups through various analytical techniques, including FT-IR, Raman spectroscopy, and UV-visible spectroscopy. Furthermore, ab initio studies were conducted to uncover the electronic properties of the boron nitride and sulphur nanostructures. The structural analysis of the boron nitride nanoparticles revealed a hexagonal configuration through Powder X-ray diffraction tests, while the sulphur nanoparticles exhibited an orthorhombic structure. In-depth examinations utilizing scanning electron microscopy and transmission electron microscopy showcased particle sizes below 100 nm. In a laboratory experiment, sunflower seeds treated with 1500 ppm green-synthesized nano boron nitride demonstrated remarkable root morphology and achieved the highest germination percentage of an impressive 98.2%, surpassing other concentration levels. Importantly, the eco-friendly synthesized nanoparticles displayed greater efficacy when compared to both chemically synthesized nanoparticles and conventional fertilizers.
Dietary intake of whale oil containing ω-3 long-chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice
Authors: Yanai Ryoji , Yasunaga Genta , Tsuji Shunya , Honda Takeshi , Iwata Arihiro , Miyagawa Eiji , Yoshida Koji , Kishimoto Mitsuhiro , Sakai Hiroki , Fujise Yoshihiro , Asagiri Masataka , Kimura Kazuhiro
Published: October 2023

Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) protect against age-related macular degeneration (AMD). We here examined the effects of whale oil, which contains ω-3 LCPUFAs, in a mouse model of AMD. Mice were fed either a diet supplemented with whale oil or a control diet free of ω-3 LCPUFAs beginning 2 weeks before induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice. The plasma concentrations of ω-3 LCPUFAs were higher, whereas those of ω-6 LCPUFAs were lower, in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of vascular endothelial growth factor (VEGF) was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil containing ω-3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and that it therefore warrants further study as a means to protect against AMD in humans.
HRH4 may be a new predictor for preterm birth
Authors: Peng Juan , Yu Caixian , Wang Huizi , Dong Xudong
Published: October 2023

Background
Preterm birth remains a significant contributor to infant morbidity and mortality rates worldwide. It is the primary cause of neonatal deaths and is second only to pneumonia in causing deaths in children under the age of five. The main objective of this study was to identify potential genes associated with preterm birth, with the aim of gaining insight into its underlying mechanisms.
Methods
We retrieved the mRNA dataset GSE960863 from the Gene Expression Omnibus (GEO) database, subsequently identified differentially expressed genes (DEGs) between preterm and full-term birth cohorts. We employed least absolute shrinkage and selection operator (LASSO) regression analysis, support vector machine-recursive feature elimination (SVM-RFE), and random forest methodologies to discern the central hub gene. The diagnostic potential of this hub gene was evaluated using receiver operating characteristic (ROC) analysis. Furthermore, we harnessed CIBERSORT to gauge the density of infiltrating immune cells (IICs), probing the relationship between our identified hub genes and IICs. Utilizing the GSE108876 miRNA database, we constructed an miRNA-mRNA regulatory framework on the Cytoscape platform. To validate our results, we assessed the expression levels of the hub genes via qPCR within a cohort of 68 patients from our facility, comprising 31 preterm and 37 full-term pregnancies
Result
Our analysis identified a total of 329 differentially expressed genes (DEGs). From the interplay of LASSO, SVM-RFE, and random forest methods, HRH4 emerged as the central hub gene. ROC analysis further validated HRH4's efficacy in diagnosing preterm birth, with an AUC of 0.834. Moreover, a differential infiltration of seven immune cell types was observed between the control and preterm birth groups: these included memory B cells, CD8 T cells, naive CD4 T cells, resting memory CD4 T cells, monocytes, activated mast cells, and neutrophils. Pearson's correlation underscored a significant association between HRH4 and both resting memory CD4 T cells and monocytes. Delving deeper, a miRNA-mRNA network was articulated, pinpointing seven miRNAs that exhibited an inverse regulatory pattern with HRH4 gene expression. Furthermore, clinical specimen validation revealed a statistically significant upregulation of HRH4 mRNA expression in the preterm group (p༜0.001).
Conclusion
HRH4 may serve to predict the PTB development and provide a new therapeutic target for PTB.
Integration of B-to-B trade network models of structural evolution and monetary flows reproducing all major empirical laws
Authors: Ozaki Jun'ichi , Viegas Eduardo , Takayasu Hideki , Takayasu Misako
Published: October 2023

We develop a single two-layered model framework that captures and replicates both the statistical properties of the network as well as those of the intrinsic quantities of the agents. Our model framework consistently unifies two distinct yet interconnected elements that were previously only studied in isolation, namely methods related to temporal network structures and those associated with money transport flows. In this manner, we can explain how the micro-level dynamics of the agents within the network lead to the exogenous manifestation of the aggregated system statistical data en-wrapping the very same agents within the system. This is done by capturing the essential dynamics of collective motion in complex networks that enable the simultaneous emergence of tent-shaped distributions in growth rates within the agents, together with the emergence of scaling properties within the network in the study. We can validate the model framework and dynamics by applying these to the context of the real-world inter-firm trading network of firms in Japan and comparing the results of the statistical distributions at both network and agent levels in a temporal manner. In particular, we compare our results to the fundamental quantities supporting the seven empirical laws observed in data: the degree distribution, the mean degree growth rate over time, the age distribution of the firms, the preferential attachment, the sales distribution in steady states, their growth rates, their scaling relations generated by the model. We find these results to be nearly identical to the real-world data. The framework has the potential to be transformed into a forecasting tool to support decision-makers on financial and prudential policies.
Effect of liver transplantation with retrograde reperfusion on early postoperative recovery of liver function and its risk factors
Authors: Shen Jiajia , Wang Ming , Yang Chengkai , Cai Qiucheng , Jiang Yi
Published: October 2023

Background
The purpose of this study was to investigate effect of liver transplantation with retrograde reperfusion on early postoperative recovery of liver function and its risk factors.
Methods
The clinical data of 136 patients who underwent liver transplantation at the 900th Hospital of the Chinese People's Liberation Army Joint Support Army from January 2015 to January 2021 were retrospectively analyzed. There were 115 males and 21 females; the age of these patients ranged from 20 to 70 years, with a median age of 51 years. All patients signed an informed consent, in accordance with medical ethics regulations. The patients were divided into retrograde reperfusion (RTR) group (n=108) and initial portal reperfusion (IPR) group (n=28) according to different liver perfusion methods during transplantation. After the two groups were matched by propensity score of 1:1, 23 patients in the two groups were compared in the recovery of liver function after operation.Within the cohort of 114 patients under scrutiny, rigorous exclusions were applied to the RTR group. Specifically, 8 cases presenting initial hepatic artery unveiling after retrograde reperfusion, and 14 cases with simultaneous hepatic artery and portal vein unveiling post RTR, were omitted. Consequently, the study's focal analysis encompassed 86 cases in the RTR subset and 28 cases within the IPR subset.
The patients in RTR group (n=86) were further divided into EAD group (n=19) and non-EAD group (n=67) according to whether early hepatic allograft dysfunction (EAD) occurred after operation. The effects of preoperative and intraoperative parameters and liver perfusion methods on EAD after liver transplantation were analyzed.
Results
Alanine aminotransferase (ALT) was 329 (211~548) and 176 (98~282) U/L on the 3rd and 7th day after RTR, respectively, which was significantly lower than 451 (288~918) and 251 (147~430) U/L in the IPR group (Z =-1.979, -2.299, P= 0.048, 0.021). Aspartate aminotransferase (AST) on postoperative days 3, 5, and 7 was 252 (193, 522), 105 (79, 163), and 93 (41, 135) U/L in the RTR group, respectively; it was also significantly lower than 328 (251, 724), 179 (129, 306), and 150 (91, 200)U/L in the IPR group (Z=-2.212, -3.221, -2.979; P=0.027, 0.001, 0.003). Logistic regression analysis showed that MELD score was an independent risk factor for EAD after liver transplantation.
Conclusion
RTR liver transplantation is more favorable for patients' early postoperative liver function recovery. For patients undergoing liver transplantation for RTR, preoperative MELD score was an independent risk factor for their postoperative development of EAD.
A Case Report of a Long-Surviving Elderly Patient with Lung Squamous Cell Carcinoma and Oncogenic Driver Alterations
Authors: Xun Pei , Zong Jiabao , Lu Yanli , Niu Xueliang , Song Chunqing
Published: October 2023

Background: MET (mesenchymal-epithelial transition) and Epidermal growth factor receptor (EGFR) mutations have a low incidence in lung squamous cell carcinoma (LUSC). For patients with MET/EGFR TKI (Tyrosine Kinase Inhibitor)-resistant driver gene mutation-related non-small cell lung cancer, selection of an appropriate treatment strategy is more difficult.
Case presentation: This paper describes a patient who was diagnosed with local advanced LUSC (stage cT2N3M0), harboring MET and EGFR mutations. This patient received toripalimab in combination with chemotherapy and achieved a partial response, with long-term progression-free survival of more than 36 months. During the treatment, no adverse events occurred.
Conclusions: Immune checkpoint inhibitors may be considered as a later-line treatment option for patients with MET-mutated advanced LUSC.
Teaching Breaking Bad News in a gyneco-oncological setting: a feasibility study implementing the SPIKES framework for undergraduate medical students
Authors: Zemlin Cosima , Nourkami-Tutdibi Nasenien , Schwarz Pascal , Goedicke-Fritz Sybelle
Published: October 2023

BACKGROUND
Delivering life threatening information to patients described as “breaking bad news (BBN)” is a central task for physicians. Many aspects influence these conversations on both sides, patients, and doctors. BBN affects the patient-physician relationship, patients’ outcome, and physicians’ health. Many physicians are still untrained for this multi-facetted task and feel unprepared and overburdened when facing situations of BBN. Therefore, any faculties should aim to integrate communication skills into their medical curricula as early as possible. The SPIKES model is an effective framework to deliver BBN. We evaluated the feasibility and obstacles of a BBN seminar and its acceptance and learning curve among undergraduate medical students.
METHODS
158 2nd year undergraduate medical students attended a compulsory BBN seminar. The task was to deliver a cancer diagnosis to the patient in a patient - physician role-play in a gyneco-oncological setting before and after a presentation of the SPIKES model by the lecturer. The students evaluated important communication skills during these role-plays respectively. Self-assessment questionnaires were obtained at the beginning and end of the seminar.
RESULTS
Most students indicated that their confidence in BBN improved after the seminar (p=<0.001). They like the topic BBN to be part of lectures (76%) and electives (90%). Communication skills improved. Lecturer and seminar were positively evaluated (4.57/5).
CONCLUSION
The seminar significantly increased confidence and self-awareness in delivering life-threatening news to patients among undergraduate students. Important learning aspects of BBN and communication skills could be delivered successfully to the participants within a short time at low costs. The integration of communication skills should be implemented longitudinally into medical curricula starting before clinical education to increase the awareness of the importance of communication skills, to decrease anxiety, stress, and workload for future doctors and – most importantly – to the benefit of our patients.
Accidental traffickers: Qualitative findings on labour recruitment in Ethiopia
Authors: Busza Joanna , Shewamene Zewdneh , Zimmerman Cathy , Erulkar Annabel , Hailu Eyasu , Negeri Lemi , Anderson Elizabeth , Lo Yuki
Published: October 2023

Background
The growth of labour migration and associated risks of human trafficking and exploitation remain significant global human rights and health challenges. There is increasing policy interest in addressing structural determinants of adverse migration outcomes such as migrants’ use of informal employment recruiters. In Ethiopia, “safe migration” policies have introduced regulations for registered private employment agencies and penalties for anyone else placing migrants into work overseas. Yet migrants continue to use informal facilitators who are often demonised as traffickers without evidence of their motivations, experiences or perceptions. We conducted qualitative interviews with 28 informal facilitators as part of a study into how recruitment practices shape risks for female migrants seeking domestic work in the Middle East and Gulf States. We present the realities of irregular recruitment on the ground, and how these practices are affected by policies that dichotomise recruiters into legal/safe and illegal/unsafe categories.
Results
We identified four main themes. First, arranging migration from rural areas differs from in the capital, Addis Ababa, where laws and regulations originate. Outside Addis Ababa, registration was difficult for facilitators to arrange, with little incentive to do so due to its lack of importance to prospective migrants. Second, the ability to circumvent legal requirements was considered an advantage of informal facilitators because it reduced costs and expedited migrants’ departure. Third, facilitators did not work alone but operated in long “chains” of diverse actors. This meant migrants’ safety was not determined by any given individual, but spread across numerous people involved in sending a migrant abroad, some of whom might be registered and others not. And finally, facilitators did not believe they could realistically safeguard migrants once they were outside of Ethiopia and working under different laws and employers.
Conclusions
Findings from this study add to a growing body of work demonstrating the diversity of people involved in the migration process, and consequent oversimplification of popular policy solutions. A more effective approach might be to constructively engage informal facilitators and identify ways they could assist with referring migrant workers to registered agencies and safe employment, rather than criminalising their participation.
ZQL-4c exerts antitumor effects by specifically targeting SCD1 in triple-negative breast cancer both in vitro and in vivo
Authors: Li Xiaorui , Cao Hui , Sun Hongna , Wang Shuya , Guo Xiangyu , Wang Shisheng , Sun Tao
Published: October 2023

Breast cancer represents the most prevalent tumor among women and serves as a primary cause of cancer-associated mortality in China. Oleanolic acid, a pentacyclic triterpenoid isolated from various natural plants, has demonstrated a wide range of biological properties including anti-inflammatory, anti-viral, anti-cancer, etc. Our previous research indicated that ZQL-4c, an oleanolic acid derivative, can inhibit the proliferation of breast cancer cells, particularly those of triple-negative breast cancer. This study aims to delve deeper into the potential inhibitory mechanisms of ZQL-4c on triple-negative breast cancer. Our results illustrated that ZQL-4c suppressed the proliferation of MDA-MB-231 and MDA-MB-468 cells in both a dose- and time- dependent manner. Furthermore, ZQL-4c induced apoptosis and G2/M cell cycle arrest. Using transcriptomics and rescue experiments, our findings suggest SCD1 as a potential target of ZQL-4c. In vivo, ZQL-4c treatment noticeably curbed tumor growth in a mouse breast cancer xenograft model. In summary, ZQL-4c displays potent antitumor benefits both in vitro and in vivo, making it a potential therapeutic agent for triple-negative breast.
Slime mold algorithm for topology optimization: metagratings inverse design.
Authors: EDEE Kofi , Granet Gérard , Bonnet Pierre
Published: October 2023

In this paper we discuss the use of a metaheuristic (MH) gradient-free optimization method, specifically the slime mold algorithm (SMA), combined with the topology optimization (TO) method for metasurfaces using spectral modal methods. The motivation behind using a MH approach comes from the drawbacks associated with traditional gradient-based techniques.Normally, Gradient-based methods require the calculation of the electromagnetic (EM) field at certain nodes within the computation domain. However, in spectral modal methods, this is unnecessary since these methods can compute the EM response without the need for field component values. Second, optimizing metagratings often involves a multimodal objective function with multiple local minimums and Gradient-based methods might struggle with finding the global optimum.So to overcome these drawbacks, we propose using a MH approach, specifically the slime mold algorithm (SMA). We apply SMA to a metasurface design, especially in the context of TO and spectral methods, which is relatively unexplored. By coupling both TO with SMA, we successfully design metagratings capable of deflecting incident waves into a desired transmission angle.
Influence of Intraocular Pressure Status on the Formation of Functional Filtering Blebs after Trabeculectomy on Rhesus Monkey eyes
Authors: Tu Shu , Hu Dongpeng , Yang Runcai , Xu Xiaoyu , Luo Ziming , Ge Jian
Published: October 2023

Purpose: To improve the maintenance and management of filtering blebs after glaucoma filtering surgeries (GFS), it is essential to understand the effect of intraocular pressure on the formation of function blebs.
Here, we utilized a monkey model of chronic ocular hypertension (COHT) to reveal the relationship between pre-operative high-IOP and postoperative bleb fibrosis.
Methods: First, four eyes after high IOP induction and four with normal IOPs from eight monkeys received trabeculectomies. Subsequently, IOPs and volume of blebs were measured by Tonopen and anterior segment optical coherence tomography in different time points over 28 days after surgery. Then, histopathology and immunohistochemistry were performed to reveal myofibroblast cells and collagen deposition of filtering blebs.
Results: In the early stage after surgeries, IOPs were significantly reduced in the COHT eyes compared to the control eyes. However, IOPs of the COHT eyes gradually increased to 16.75±4.99 mmHg, which was in the normal range but overall higher at the end of the 28-day observation. Consistently, denser fibrosis and scar tissue deposition were observed in the COHT group.
Conclusions: Taken together, these results indicated that pre-operative high IOP status might promote bleb fibrosis, compromising the outcome of filtering surgeries. Furthermore, this finding suggested that pre-operative high IOP could induce confounding or effect modification, and more attention should be paid to the following anti-scarring research. From the perspective of translational medicine, controlling IOP before clinical operation is very important to improve the surgical effect.
Superior induced pluripotent stem cell generation through phactr-3-driven mechano-modulation of both early and late phases of cell reprogramming
Authors: Chowdhury Mohammad Mahfuz , Zimmerman Samuel , Leeson Hannah , Nefzger Christian Maximilian , Mar Jessica Cara , Laslett Andrew , Polo Jose Maria , Wolvetang Ernst , Cooper-White Justin John
Published: October 2023

Background:Human cell reprogramming traditionally involves time-intensive, multi-stage, costly tissue culture polystyrene (TCPS)-based cell culture practices that ultimately produce low numbers of reprogrammed cells of variable quality. Previous studies have shown that very soft two-and three-dimensional hydrogel substrates/matrices (of stiffnesses </= 1 kPa) can drive ~2X improvements in human cell reprogramming outcomes. Unfortunately, these similarly complex multi-stage protocols lack intrinsic scalability, and furthermore, the associated underlying molecular mechanisms remain to be fully elucidated, limiting the potential to further maximise reprogramming outcomes.
Methods:Polyacrylamide hydrogels of varying stiffness (1 kPa – 1.3 MPa) were surface activated with either Sulfo-SAMPAH or poly-L-dopamine and thereafter gelatin functionalised. Mouse and human fibroblast cells were reprogrammed on these substrates using endogenous (mouse) or exogenous (human) transcription factors for 18 days. Cells were phenotyped during the each of the reprogramming phases. RNA sequencing and bioinformatic analysis elucidated critical molecular drivers of reprogramming upon exposure to the hydrogels, confirmed through gene knockdown experiments.
Results:In screening the largest range of polyacrylamide hydrogels of varying stiffness to date, we found that a medium stiffness gel (~100 kPa) significantly increased the overall number of reprogrammed cells by up to ten-fold (10X), accelerated reprogramming kinetics, improved both early and late phases of reprogramming, and produced iPSCs having more naïve characteristics and lower remnant transgene expression, compared to the gold standard tissue culture polystyrene practice. Functionalisation of these pAAm hydrogels with poly-L-dopamine (PDA) enabled, for the first-time, continuous, single-step reprogramming of fibroblasts to iPSCs on hydrogel substrates (noting that even the TCPS practice is a two-stage process). Comparative RNA-Seq analyses coupled with experimental validation revealed that a novel reprogramming regulator, Phactr3, upregulated in the gel condition at a very early time-point, was responsible for the observed enhanced reprogramming outcomes.
Conclusions:This study provides a novel culture protocol and substrate for continuous hydrogel-based cell reprogramming and previously unattained clarity of the underlying mechanisms via which substrate stiffness modulates reprogramming kinetics and iPSC quality outcomes, opening new avenues for producing higher numbers of quality iPSCs or other reprogrammed cells at shorter timescales.
Rock Fluid Interactions During Seawater Injection in Carbonates: an Experimental Evaluation on Dolomitization and Anhydrite Precipitation
Authors: Novaes Aline Machado de Azevedo , Faria Rafaella Magliano Balbi , Silva Mônica Antunes Pereira da , Peçanha Ricardo Pires
Published: October 2023

Carbonates are expected to be reactive during the injection of fluids as a secondary recovery method in an oilfield reservoir. Desulphated seawater is usually chosen to reduce scaling potential for barium and strontium sulfates at the producer wells. However, desulfation presents some operational difficulties, often limiting the platform injection’s capacity. The chemical interactions between seawater and carbonate reservoirs affect produced water composition and must be considered for scaling predictions. Reactive transport models had shown that dolomitization increases anhydrite precipitation, reducing sulphate concentration in the produced water. This paper studied the reaction between calcite and three different fluids: seawater, seawater without sulphate and seawater without magnesium. All tests were performed in the presence of CO2 and using a semi-batch reactor. The focus was to analyze the effects of possible dolomitization on sulfate concentration in reservoir conditions. As the scale potential is strongly related to the sulphate concentration, the previous knowledge of this behaviour plays a key role at the water quality decision. Experimental results confirmed simulation predictions.