bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic resveratrol–curcumin hybrid derivative exhibits chemopreventive effects on colon pre-neoplastic lesions by targeting Wnt/β-catenin signaling, anti-inflammatory and antioxidant pathways
Authors: Baptistella Mariane Minussi , Assunção Raphaela Rebeca Silveira , Sales de Oliveira Carolina , Siqueira Aléxia Polo , Gonçalves dos Santos Elda , de Freitas Silva Matheus , Lima Ellen Tardelli Faleiros , Caixeta Ester Siqueira , Novaes Rômulo Dias , Ferreira Eric Batista , Ionta Marisa , Viegas Jr. Claudio , Francielli de Oliveira Pollyanna 
Published: October 2023

Abstract

Based on the effectiveness of resveratrol and curcumin in carcinogenesis, (E)-3-(4-hydroxy-3-methoxyphenyl)-Nʹ-((E)-4-methoxybenzylidene) acrylohydrazide (PQM-162), curcumin–resveratrol hybrid derivative, was designed by molecular hybridization using a hydrazone functionality as a spacer moiety between pharmacophoric fragments inspired by the parent compounds.

Objectives
The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents.

Methods
The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.).

Key findings
PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and β-catenin protein markers and increased Nrf2 expression.

Conclusion
Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.
‘I Did Not Choose to Be in Your Country’: Social-Racial Hierarchies in Peru and Venezuelan Migrant Women’s Responses
Authors: Pérez Leda M 
Published: October 2023

Abstract
Drawing on 72 interviews with Venezuelan migrant women across five Peruvian cities between 2018 and 2020, this article discusses the prevailing intersectional discriminations they have experienced. I also explore their resistance to social marginalizations that position them along a social-racial hierarchy based on xenophobia, sexism, and racialization. My research has found that their responses to these treatments are to reposition themselves as politically and morally equal, if not superior, to host country nationals. I close the article with questions about what these dynamics portend for future inquiries on south–south migrations.
Transcatheter aortic valve implantation for aortic regurgitation in HeartMate II supported patient using Myval THV: a case report
Authors: Hamieh Mohamad , Nassereddine Zahra , Moussa Malek , Al Ali Firas , Dbouk Mohamad , Saab Mohamad 
Published: October 2023

AbstractDe novo aortic regurgitation (AR) presents a great challenge following left ventricular assist device (LVAD) implantation and requires valve replacement in some cases. Patients with LVAD are frequently those who underwent multiple previous sternotomies or suffer from multiple comorbidities. Thus, they are at high surgical risk for further sternotomy. Transcatheter aortic valve implantation (TAVI) previously approved for treatment of severe aortic stenosis is also used for this category of patients. Here, we report the case of a young female patient supported with heart mate II LVAD who presented with severe de novo AR. The patient was successfully treated with TAVI using Myval trancatheter heart valve (THV) in our center. To our knowledge, our patient is the first to be treated with such type of valve using TAVI procedure in LVAD supported patients.
Concurrent dermoid and epidermoid cysts in an adolescent patient: a case report
Authors: Taylor Justin J , Scherer Andrea G , Shao Lei , Westmoreland Tamarah J 
Published: October 2023

Abstract
Dermoid and epidermoid cysts are benign lesions of ectodermal origin which are pathologically distinct entities, although often clinically indistinguishable. Cyst location, mobility, and appearance on MRI can help distinguish the two, however the distinction is mostly academic since both types have similar management. Co-occurrence of dermoid and epidermoid cysts together in the same patient has not been observed in the literature, however one case of an epidermoid cyst evolving into a dermoid cyst has been documented. In this case report, we identify a 16-year-old male with three separate cysts of the scalp and leg which, after histopathological analysis following surgical resection, were found to represent both dermoid and epidermoid cysts. We offer potential explanations for this rare occurrence in the absence of a genetic syndrome and highlight the importance of performing a thorough work-up of patients with multiple cysts.
Familial Mediterranean fever and scleroderma: a rare case report from Syria
Authors: Nahas Lujain , Al Khudari Rawan , Khalil Basheer 
Published: October 2023

Abstract
Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease that affects the skin, joints, serous membranes and other various organs. Presentation of FMF can be solely but it can coexist with other conditions. It has been shown that it can be accompanied by various different disorders. Scleroderma is an autoimmune dermatologic condition that can present with systemic manifestations. No previous cases about the coexistence of FMF and scleroderma were previously documented, therefore we report the first case in Syria of a 10-year-old female that presented with clinically clear signs of both conditions (periodic fever and serous chest pain in addition to skin hyperpigmentation). The patient’s symptoms required full genetic testing along with the proper antibody detection and The diagnosis of FMF and scleroderma was confirmed by genetic testing and treatment was started.
Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles
Authors: Xu Yuanming , Wen Natalie , Haddad Robert I , Sonis Stephen T , Villa Alessandro 
Published: October 2023

Abstract

Objectives
Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs.

Methods
A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs.

Results
Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ± 12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental.

Conclusion
Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.
Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor
Authors: Lin Feng , Jacqueline Kwong Winghan , Pan Irene , Ye Xin , Dai Dong , Tap William 
Published: October 2023

Abstract

Background
Pexidartinib (Turalio) is the only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant-cell tumor (TGCT) associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. This study assessed patient-reported treatment experiences and symptom improvement among patients receiving pexidartinib.

Methods
A cross-sectional, web-based survey collected data on demographics, disease history, pexidartinib dosing, and symptoms before and after pexidartinib use.

Results
Of 288 patients enrolled in the Turalio REMS program in May 2021, 83 completed the survey: mean age was 44.2 years, 62.7% were female, and most common tumor sites were in knee (61%) and ankle (12%). Mean initial dose was 622 mg/day: 29 patients reported reduction from initial dose and 8 had dose reduction after titrating up to a higher dose. At the time of survey completion, median time on pexidartinib was 6.0 months; 22 (26.5%) patients discontinued pexidartinib due to physician suggestion, abnormal laboratory results, side effect, or symptom improvement. Compared with before pexidartinib initiation, most patients reported improvement in overall TGCT symptom (78.3%) and physical function (77.2%) during pexidartinib treatment. Significant improvement was reported during pexidartinib treatment in worst stiffness numeric rating scale (NRS) (3.0 vs. 6.2, P &lt; .05) and worst pain NRS (2.7 vs. 5.7, P &lt; .05).

Conclusion
Findings from this cross-sectional survey confirmed the benefit of pexidartinib in improving symptoms and functional outcomes among patients with symptomatic TGCTs from the patients’ perspective. Future research is warranted to examine the long-term benefit and risk of pexidartinib.
Praying
Authors: Reynolds Paige 
Published: October 2023

AbstractThe Catholic Church’s power over the Irish imaginary has been executed in part through its disciplining of the ritualized practice of prayer, a force that has landed most heavily on the artificially privatized experience of women. Representing prayer through the tactics of the modernist mode, Irish women writers draw attention to the ways that female consciousness submits to, as well as eludes, the formidable structures imposed by organized religion. In Kate O’Brien’s The Land of Spices (1941), Mary Lavin’s twentieth-century short fiction, Emma Donoghue’s Hood (1995), and Eimear McBride’s A Girl Is a Half-formed Thing (2013), prayer surfaces in the narrative as public practice and as private meditation. These works acknowledge the unfathomable nature of prayer and provide readers sophisticated and sympathetic accounts of this practice, even as they critique how prayer creates a specious feeling of individual well-being and binds practitioners uncritically to an institution.
Quantifying the Energy Spillover between Photosystems II and I in Cyanobacterial Thylakoid Membranes and Cells
Authors: Akhtar Parveen , Balog-Vig Fanny , Han Wenhui , Li Xingyue , Han Guangye , Shen Jian-Ren , Lambrev Petar H 
Published: October 2023

Abstract
The spatial separation of photosystems I and II (PSI and PSII) is thought to be essential for efficient photosynthesis by maintaining a balanced flow of excitation energy between them. Unlike the thylakoid membranes of plant chloroplasts, cyanobacterial thylakoids do not form tightly appressed grana stacks that enforce strict lateral separation. The coexistence of the two photosystems provides a ground for spillover—excitation energy transfer from PSII to PSI. Spillover has been considered as a pathway of energy transfer from the phycobilisomes to PSI and may also play a role in state transitions as means to avoid overexcitation of PSII. Here, we demonstrate a significant degree of energy spillover from PSII to PSI in reconstituted membranes and isolated thylakoid membranes of Thermosynechococcus (Thermostichus) vulcanus and Synechocystis sp. PCC 6803 by steady-state and time-resolved fluorescence spectroscopy. The quantum yield of spillover in these systems was determined to be up to 40%. Spillover was also found in intact cells but to a considerably lower degree (20%) than in isolated thylakoid membranes. The findings support a model of coexistence of laterally separated microdomains of PSI and PSII in the cyanobacterial cells as well as domains where the two photosystems are energetically connected. The methodology presented here can be applied to probe spillover in other photosynthetic organisms.
How Americans Respond to Idiosyncratic and Exogenous Changes in Household Wealth and Unearned Income
Authors: Golosov Mikhail , Graber Michael , Mogstad Magne , Novgorodsky David 
Published: October 2023

Abstract
We study how Americans respond to idiosyncratic and exogenous changes in household wealth and unearned income. Our analyses combine administrative data on U.S. lottery winners with an event study design. We first examine individual and household earnings responses to these windfall gains, finding significant and sizable wealth and income effects. On average, an extra ${\$}$1 of unearned income in a given period reduces household labor earnings by about 50 cents, decreases total labor taxes by 10 cents, and increases consumption expenditure by 60 cents. These effects are heterogeneous across the income distribution, with households in higher quartiles of the income distribution reducing their earnings by a larger amount. Next we examine margins of adjustment other than earnings and, in the course of doing so, address a number of important economic questions about how additional wealth or unearned income affect retirement decisions and labor market dynamics, family formation and dissolution, entrepreneurship and self-employment, and geographic mobility and neighborhood choice. Last, we carefully compare our findings to those reported in existing lottery studies. This comparison reveals that existing U.S. studies substantially underestimate wealth and income effects because they use measures that understate the earnings responses and overstate the after-tax wealth changes associated with lottery wins.
The Bruce–Roberts Numbers of a Function on an ICIS
Authors: Lima-Pereira B K , Nuno-Ballesteros J J , Orefice-Okamoto B , Tomazella J N 
Published: October 2023

Abstract
We relate a number of invariants of a function germ with isolated singularity over an isolated complete intersection singularity (ICIS), generalizing our previous results, [17, 18], as a consequence we present a new relatively elementary proof of Greuel’s theorem that for a weighted homogeneous ICIS the Milnor number is equal to Tjurina number. With this relation, we are able to prove that the relative logarithmic characteristic variety is Cohen–Macaulay at any point and the logarithmic characteristic variety is Cohen–Macaulay at any point not in $X\times \{0\}$.
Differences in bone microarchitecture between genetic and secondary iron‐overload mouse models suggest a role for hepcidin deficiency in iron‐related osteoporosis
Authors: Robin François , Chappard Daniel , Leroyer Patricia , Latour Chloé , Mabilleau Guillaume , Monbet Valérie , Cavey Thibault , Horeau Mathieu , Derbré Frédéric , Roth Marie‐Paule , Ropert Martine , Guggenbuhl Pascal , Loréal Olivier 
Published: October 2023

AbstractIron overload is one of the secondary osteoporosis etiologies. Cellular and molecular mechanisms involved in iron‐related osteoporosis are not fully understood.AimThe aim of the study was to investigate the respective roles of iron excess and hepcidin, the systemic iron regulator, in the development of iron‐related osteoporosis.Material and MethodsWe used mice models with genetic iron overload (GIO) related to hepcidin deficiency (Hfe−/− and Bmp6−/−) and secondary iron overload (SIO) exhibiting a hepcidin increase secondary to iron excess. Iron concentration and transferrin saturation levels were evaluated in serum and hepatic, spleen, and bone iron concentrations were assessed by ICP‐MS and Perl's staining. Gene expression was evaluated by quantitative RT‐PCR. Bone micro‐architecture was evaluated by micro‐CT. The osteoblastic MC3T3 murine cells that are able to mineralize were exposed to iron and/or hepcidin.ResultsDespite an increase of bone iron concentration in all overloaded mice models, bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) only decreased significantly in GIO, at 12 months for Hfe−/− and from 6 months for Bmp6−/−. Alterations in bone microarchitecture in the Bmp6−/− model were positively correlated with hepcidin levels (BV/TV (ρ = +.481, p < .05) and Tb.Th (ρ = +.690, p < .05). Iron deposits were detected in the bone trabeculae of Hfe−/− and Bmp6−/− mice, while iron deposits were mainly visible in bone marrow macrophages in secondary iron overload. In cell cultures, ferric ammonium citrate exposure abolished the mineralization process for concentrations above 5 μM, with a parallel decrease in osteocalcin, collagen 1, and alkaline phosphatase mRNA levels. Hepcidin supplementation of cells had a rescue effect on the collagen 1 and alkaline phosphatase expression level decrease.ConclusionTogether, these data suggest that iron in excess alone is not sufficient to induce osteoporosis and that low hepcidin levels also contribute to the development of osteoporosis.
Research Priorities to Improve Treatment of Patients Exposed to Xylazine-fentanyl: Rapid Communication from a National Institute on Drug Abuse Center for the Clinical Trials Network Meeting
Authors: Haroz Rachel , Huntley Kristen , Perrone Jeanmarie 
Published: October 2023

Abstract
In response to the rapid escalation in the detection of xylazine in the unregulated drug supply, in April 2023, the White House designated fentanyl contaminated with xylazine an “emerging threat.” The National Institute on Drug Abuse Center for Clinical Trials Network convened a multidisciplinary meeting of stakeholders, federal staff members, researchers, and clinicians caring for patients with fentanyl and xylazine exposures. This convening focused on the most critical areas of concern with the goal of describing current practices and a xylazine-fentanyl research agenda. Discussions focused on the domains of epidemiology and laboratory detection, xylazine withdrawal and overdose, and dermal manifestations. The authors were involved in planning and moderating the program and providing a summary of the proceedings.
METTL3 regulates glucose transporter expression in placenta exposed to hyperglycemia through the mTOR signaling pathway
Authors: Ning Jie , Huai Jing , Wang Shuxian , Yan Jie , Su Rina , Zhang Muqiu , Liu Mengtong , Yang Huixia 
Published: October 2023

AbstractBackground:Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal–fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods:We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL,n= 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM,n= 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia.Results:mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity andvice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485.Conclusion:High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.
Global and regional trends in the incidence and mortality burden of endometrial cancer, 1990–2019: Updated results from the Global Burden of Disease Study, 2019
Authors: Feng Jianyang , Lin Rongjin , Li Haoxian , Wang Jiayan , He Hong 
Published: October 2023

Abstract

Background:
The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.

Methods:
The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.

Results:
The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, -1.0 to -0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019.

Conclusions:
Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.