bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acupuncture regulates the apoptosis of ovarian granulosa cells in polycystic ovarian syndrome-related abnormal follicular development through LncMEG3-mediated inhibition of miR-21-3p
Authors: Chen Xiaohong , He Hengzhen , Long Bingcai , Wei Binli , Yang Peng , Huang Xiaoying , Wang Qian , Lin Jing , Tang Hongliang 
Published: June 2023

Abstract
Background
The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p.

Methods
A PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS.

Results
LncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3.

Conclusion
These results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS.
Reflections on patient engagement by patient partners: how it can go wrong
Authors: Richards Dawn P. , Poirier Sabrina , Mohabir Vina , Proulx Laurie , Robins Sue , Smith Jeffery 
Published: June 2023

AbstractAs six patient partners in Canada, we aim to contribute to learning and to provide an opportunity to reflect on patient engagement (PE) in research and healthcare environments. Patient engagement refers to “meaningful and active collaboration in governance, priority setting, conducting research and knowledge translation” with patient partners as members of teams, rather than participants in research or clinical care. While much has been written about the benefits of patient engagement, it is important to accurately document and share what we term ‘patient engagement gone wrong.’ These examples have been anonymized and presented as four statements: patient partners as a check mark, unconscious bias towards patient partners, lack of support to fully include patient partners, and lack of recognizing the vulnerability of patient partners. The examples provided are intended to demonstrate that patient engagement gone wrong is more common than discussed openly, and to simply bring this to light. This article is not intending to lay blame, rather to evolve and improve patient engagement initiatives. We ask those who interact with patient partners to reflect so we can all work towards improving patient engagement. Lean into the discomfort with these conversations as that is the only way to change these all too recognizable examples, and which will lead to better project outcomes and experiences for all team members.
Sub-lethal toxicity of indigo dye (Indigofera tinctoria) on Oreochromis niloticus juveniles
Authors: Ayebidun Omotola Victoria , Ajibare Adefemi Olatayo 
Published: June 2023

Abstract
Background
Textile dyes which are eliminated as unfixed dyes through the effluent from textile industry cause deleterious effect on the fresh water fish. Thus, toxicity tests were conducted using indigo dye on Oreochromis niloticus juveniles (mean weight 30.00 ± 0.73 g) as a test fish under bioassay system. Varying concentration of 0.00 (control), 0.5, 1.0, 1.5, 2.0, and 2.5 mg/l containing graded levels of Indigofera were applied in experimental tanks to determine the lethal concentration. The LC50 of dye at 96 h was 1.3 mg/l of water. The histopathology (heart, gills, kidney and spleen) and water quality parameters (Dissolved oxygen, pH and temperature) were determined using standard methods and behavioural responses were observed.

Results
Histopathology of heart, gills, kidney and spleen revealed degeneration of cells, space formation, slight cellular changes and vacuolation among the treatments especially in the higher concentration of 1.5 mg/l, 2.0 mg/l, and 2.5 mg/l of the dye solution used except in the control. The pH and DO of control were significantly different from the experimental units while there was no significant variation in the temperature of the control and all the experimental units. Effects of indigo dye on water parameters were significant (P < 0.05) throughout the experiment. Behavioural responses exhibited by the experimental fish include irregular swimming, hyperventilation, rapid opercula movement, and restlessness. The dye concentration and exposure period both boosted these behaviours.

Conclusions
The findings of this study indicated that indigo dye solution is toxic to fish, and that fish opercula movement and mortality were influenced by the dosage of each concentration and the duration of exposure.
Development of HPV16 mouse and dog models for more accurate prediction of human vaccine efficacy
Authors: Totain Emmanuelle , Lindner Loïc , Martin Nicolas , Misseri Yolande , Iché Alexandra , Birling Marie-Christine , Sorg Tania , Herault Yann , Bousquet-Melou Alain , Bouillé Pascale , Duthoit Christine , Pavlovic Guillaume , Boullier Severine 
Published: June 2023

Abstract
Background
Animal models are essential to understand the physiopathology of human diseases but also to evaluate new therapies. However, for several diseases there is no appropriate animal model, which complicates the development of effective therapies. HPV infections, responsible for carcinoma cancers, are among these. So far, the lack of relevant animal models has hampered the development of therapeutic vaccines. In this study, we used a candidate therapeutic vaccine named C216, similar to the ProCervix candidate therapeutic vaccine, to validate new mouse and dog HPV preclinical models. ProCervix has shown promising results with classical subcutaneous murine TC-1 cell tumor isografts but has failed in a phase II study.

Results
We first generated E7/HPV16 syngeneic transgenic mice in which the expression of the E7 antigen could be switched on through the use of Cre–lox recombination. Non-integrative LentiFlash® viral particles were used to locally deliver Cre mRNA, resulting in E7/HPV16 expression and GFP reporter fluorescence. The expression of E7/HPV16 was monitored by in vivo fluorescence using Cellvizio imaging and by local mRNA expression quantification. In the experimental conditions used, we observed no differences in E7 expression between C216 vaccinated and control groups. To mimic the MHC diversity of humans, E7/HPV16 transgenes were locally delivered by injection of lentiviral particles in the muscle of dogs. Vaccination with C216, tested with two different adjuvants, induced a strong immune response in dogs. However, we detected no relationship between the level of cellular response against E7/HPV16 and the elimination of E7-expressing cells, either by fluorescence or by RT-ddPCR analysis.

Conclusions
In this study, we have developed two animal models, with a genetic design that is easily transposable to different antigens, to validate the efficacy of candidate vaccines. Our results indicate that, despite being immunogenic, the C216 candidate vaccine did not induce a sufficiently strong immune response to eliminate infected cells. Our results are in line with the failure of the ProCervix vaccine that was observed at the end of the phase II clinical trial, reinforcing the relevance of appropriate animal models.
Potential molecular mechanism underlying cardiac fibrosis in diabetes mellitus: a narrative review
Authors: Ridwan Muhammad , Dimiati Herlina , Syukri Maimun , Lesmana Ronny 
Published: June 2023

Abstract
Background
Diabetes mellitus (DM) is among the most common risk factors for cardiovascular disease in the world with prevalence of more than 500 million population in 2021. Cardiac fibrosis with its complex process has been hypothesized as one of the mechanisms explaining development of heart failure in diabetic patients. Recently, the biomolecular mechanism of cardiac fibrosis in the hyperglycemia setting has been focusing around transforming growth factor β-1 (TGFβ-1) as a major factor. However, there is interplay role of several factors including microRNAs (miRNAs) which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. This narrative review included articles from the PubMed and Science Direct databases published in the last 10 years (2012–2022).

Main text
In diabetic patients, excessive activation of myofibroblasts occurs and triggers pro-collagen to convert into mature collagen to fill the cardiac interstitial space resulting in a pathological process of extracellular matrix remodeling. The balance between matrix metalloproteinase (MMP) and its inhibitor (tissue inhibitor of metalloproteinase, TIMP) is crucial in degradation of the extracellular matrix. Diabetes-related cardiac fibrosis is modulated by increasing level of TGF-β1 mediated by cellular components, including cardiomyocyte and non-cardiomyocyte cells involving fibroblasts, vascular pericytes smooth muscle cells, endothelial cells, mast cells, macrophages, and dendritic cells. Several miRNAs such as miR-21, miR-9, miR-29, miR-30d, miR-144, miR-34a, miR-150, miR-320, and miR-378 are upregulated in diabetic cardiomyopathy. TGF-β1, together with inflammatory cytokines, oxidative stress, combined sma and the mothers against decapentaplegic (smad) protein, mitogen-activated protein kinase (MAPK), and microRNAs, is interconnectedly involved in extracellular matrix production and fibrotic response. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus.

Conclusions
Long-term hyperglycemia activates cardiac fibroblast via complex processes involving TGF-β1, miRNA, inflammatory chemokines, oxidative stress, smad, or MAPK pathways. There is increasing evidence of miRNA’s roles lately in modulating cardiac fibrosis.
Role of preoperative SPECT/CT standardized uptake values in medication-related osteonecrosis of the jaw: a preliminary study of SPECT/CT in relation to cone-beam CT and histopathological findings of the resected bone of mandibulectomy
Authors: Kobayashi Eizaburo , Tezuka Yasuhito , Ono Junya , Okada Yasuo , Ogura Ichiro 
Published: June 2023

Abstract
Background
SPECT/CT has been applied for preoperative planning of MRONJ. Furthermore, the SUV using bone SPECT/CT has enabled quantitative analysis of jaw lesions. This study aimed to evaluate the role of preoperative SPECT/CT SUVs in MRONJ, especially SPECT/CT in relation to CBCT and histopathological findings of the resected bone of mandibulectomy. The preliminary study was conducted on five MRONJ patients who underwent mandibulectomy after SPECT/CT.

Results
The SUVmax and SUVmean of MRONJ in all cases (19.5 ± 5.6 and 5.5 ± 0.8) were significantly higher than those of right side of the MRONJ (8.5 ± 2.0 and 2.7 ± 0.5) and left side of the MRONJ (7.2 ± 1.6 and 2.7 ± 0.4), respectively. The CBCT of all cases showed osteolytic and sclerotic internal texture and sequestrum. The histopathological characteristics of all cases showed necrotic bone and granulation tissue with the bone circumference surrounded by inflammatory cells.

Conclusions
The preliminary results indicated a difference between MRONJ and right and left sides of the MRONJ in SPECT/CT SUVs. The SUVs has enabled quantitative analysis for surgical planning of MRONJ.
Cardiac Substructure Radiation Dose and Risk of Late Cardiac Disease in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Bates James E. , Shrestha Suman , Liu Qi , Smith Susan A. , Mulrooney Daniel A. , Leisenring Wendy , Gibson Todd , Robison Leslie L. , Chow Eric J. , Oeffinger Kevin C. , Armstrong Gregory T. , Constine Louis S. , Hoppe Bradford S. , Lee Choonsik , Yasui Yutaka , Howell Rebecca M. 
Published: June 2023

PURPOSE Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished. METHODS Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships. RESULTS The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 to 4.3) for CAD, 3.8% (95% CI, 3.4 to 4.2) for HF, 1.2% (95% CI, 1.0 to 1.5) for VD, and 1.4% (95% CI, 1.1 to 1.6) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiotherapy. Quadratic ERR models improved fit compared with linear ERR models for the dose-response relationship between mean whole heart and CAD, HF, and arrhythmia, suggesting a potential threshold dose; however, such departure from linearity was not observed for most cardiac substructure end point dose-response relationships. Mean doses of 5-9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. Mean doses of 5-9.9 Gy to the right coronary artery (rate ratio [RR], 2.6 [95% CI, 1.6 to 4.1]) and left ventricle (RR, 2.2 [95% CI, 1.3 to 3.7]) increased risk of CAD, and to the tricuspid valve (RR, 5.5 [95% CI, 2.0 to 15.1]) and right ventricle (RR, 8.4 [95% CI, 3.7 to 19.0]) increased risk of VD. CONCLUSION Among children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.
A Visual Diagnosis: Lipodystrophy
Authors: Bhat Salman Zahoor , Brown Rebecca J , Banerjee Ronadip R 
Published: June 2023

Abstract
Lipodystrophy syndromes are rare metabolic disorders characterized by local or generalized loss of adipose tissue, resulting in insulin resistance, dyslipidemia, and cosmetic disfiguration. The lipodystrophic phenotype is highly variable, with partial lipodystrophy often missed or misdiagnosed as other diseases from a lack of a proper physical examination and low physician awareness. Correct diagnosis is important for optimal treatment and follow-up strategies in these patients. The use of GLP-1 analogs has not been systematically evaluated in lipodystrophy and could be a potential precision medicine therapy. We aim to make the reader, particularly generalists or endocrinologists outside of tertiary referral centers, aware of the presentation and clinical features of partial lipodystrophy, emphasize the role of a full physical examination in diagnosis, and discuss therapeutic options, including GLP-1–based glycemic management illustrated by our clinical case.
A Point-Based Risk Calculator for Mortality After Hepatectomy
Authors: Luu Tiffany , Curran Brian P. , Macias Alvaro A. , Mehdipour Soraya , Simpson Sierra , Gabriel Rodney A. 
Published: June 2023

BACKGROUND:
Preoperative risk stratification for hepatectomy patients can aid clinical decision making. The objective of this retrospective cohort study was to determine postoperative mortality risk factors and develop a score-based risk calculator using a limited number of preoperative predictors to estimate mortality risk in patients undergoing hepatectomy.

METHODS:
Data were collected from patients that underwent hepatectomy from the National Surgical Quality Improvement Program dataset from 2014 to 2020. Baseline characteristics were compared between survival and 30-day mortality cohorts using the χ2 test. Next, the data were split into a training set to build the model and a test set to validate the model. A multivariable logistic regression model modeling 30-day postoperative mortality was trained on the training set using all available features. Next, a risk calculator using preoperative features was developed for 30-day mortality. The results of this model were converted into a score-based risk calculator. A point-based risk calculator was developed that predicted 30-day postoperative mortality in patients who underwent hepatectomy surgery.

RESULTS:
The final dataset included 38,561 patients who underwent hepatectomy. The data were then split into a training set from 2014 to 2018 (n = 26,397) and test set from 2019 to 2020 (n = 12,164). Nine independent variables associated with postoperative mortality were identified and included age, diabetes, sex, sodium, albumin, bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), international normalized ratio, and American Society of Anesthesiologists classification score. Each of these features were then assigned points for a risk calculator based on their odds ratio. A univariate logistic regression model using total points as independent variables were trained on the training set and then validated on the test set. The area under the receiver operating characteristics curve on the test set was 0.719 (95% confidence interval, 0.681–0.757).

CONCLUSIONS:
Development of risk calculators may potentially allow surgical and anesthesia providers to provide a more transparent plan to support patients planned for hepatectomy.
Dexmedetomidine Prevents Chronic Incisional Pain After Brain Tumor Resection: A Secondary Analysis of the Randomized Control Trial
Authors: Zeng Min , Xu Xin , Li Ruowen , Zhang Xingyue , Ma Tingting , Cui Qianyu , Wang Juan , Li Shu , Peng Yuming 
Published: June 2023

BACKGROUND:
Dexmedetomidine was reported to reduce postoperative acute pain after neurosurgery. However, the efficacy of dexmedetomidine for preventing chronic incisional pain is uncertain.

METHODS:
This article is a secondary analysis of a randomized, double-blind, placebo-controlled trial. Eligible patients were randomly allocated to either the dexmedetomidine group or the placebo group. Patients assigned to the dexmedetomidine group were given a 0.6 μg kg−1 dexmedetomidine bolus followed by a 0.4 μg kg−1 h−1 maintenance dose until dural closure; placebo patients were given comparable amounts of normal saline. The primary end point was the incidence of incisional pain at 3 months after craniotomy evaluated by numerical rating scale scores and defined as any score >0. The secondary end points were postoperative acute pain scores, sleep quality, and Short-Form McGill Pain Questionnaire (SF-MPQ-2) at 3 months after craniotomy.

RESULTS:
From January 2021 to December 2021, a total of 252 patients were included in the final analysis: the dexmedetomidine group (n = 128) and the placebo group (n = 124). The incidence of chronic incisional pain was 23.4% (30 of 128) in the dexmedetomidine group versus 42.7% (53 of 124) in the placebo group (risk ratio, 0.55; 95% confidence interval, 0.38–0.80; P = .001). The overall severity of chronic incisional pain was mild in both groups. Patients in the dexmedetomidine group had lower acute pain severity on movement than those in the placebo group for the first 3 days after surgery (all adjusted P < .01). Sleep quality did not differ between groups. However, the SF-MPQ-2 total sensory (P = .01) and neuropathic pain descriptor (P = .023) scores in the dexmedetomidine group were lower than those in the placebo group.

CONCLUSIONS:
Prophylactic intraoperative dexmedetomidine infusion reduces the incidence of chronic incisional pain as well as acute pain score after elective brain tumor resections.
Totality in a Box
Authors: Menozzi Filippo 
Published: June 2023

Abstract
This essay proposes a reading of the American photographer Allan Sekula’s 1995 essay “Dismal Science” alongside The Forgotten Space, an essay film he directed with Noël Burch in 2010. These works are still resonant today because they suggest the possibility of picturing the totality of capitalist modernity. Sekula’s representations of the shipping container and the subsequent shifts in maritime economy recuperate the prospect of a panoramic, totalizing view in an era marked by a prevalence of detail and data over meaningful grand narrative. The totality the container embodies and represents, however, is not the whole of a frictionless and seamless accumulation of capital but a nonsynchronous, polemical, and critical totality of struggle and antagonism. Sekula turns the shipping container from a stand-in for a system of commodity circulation to an allegorical sign of the continuing fight between labor and capital. Rather than envisioning this totality of struggle as a merely thematic concern, Sekula’s compositions eschew commodification on the level of form by delving into the constitutive tensions of realism and reintroducing a living context of militancy and resistance into the matter of representation itself.
From Fetish to Totality
Authors: Mansoor Jaleh 
Published: June 2023

Abstract
This essay argues that the artwork’s opacity and purposively purposeless quality are a tacit refusal of the compulsory division between intellectual and manual labor, which afford the artwork a unique capacity to access an otherwise occluded totality. By analyzing conceptual work by the artist duo Claire Fontaine—who deploy Alfred Sohn-Rethel’s notion of market exchangism in their work—in relation to twentieth-century intellectual debates around representation, abstraction, and social synthesis, the essay develops a model of totality in a descriptive rather than prescriptive register. At issue is the artwork’s potential for dereification, whereby a given work of art may provide perceptual experience of the transactional logic that underpins and structures the social field.