bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of CTNNB1 by deubiquitinase UCHL3-mediated stabilization facilitates bladder cancer progression
Authors: Liu Tao , Fan Meng-Qi , Xie Xiao-Xiao , Shu Qi-Peng , Du Xue-Hua , Qi Lin-Zhi , Zhang Xiao-Dong , Zhang Ming-Hui , Shan Guang , Du Run-Lei , Li Shang-Ze
Published: September 2023

Background

The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Recent studies have suggested that CTNNB1 hyperactivation is closely related to the occurrence and development of bladder cancer (BCa). As a member of the deubiquitinating enzyme (DUB) family, ubiquitin C-terminal hydrolase L3 (UCHL3) is abnormally expressed in various cancers. In this study, we discovered that UCHL3 is a novel oncogene in bladder cancer, suggesting it is a promising target against bladder cancer.

Methods

We utilized CRISPR‒Cas9 technology to construct cell lines with UCHL3 stably overexpressed or knocked out. The successful overexpression or knockout of UCHL3 was determined using Western blotting. Then, we performed CCK-8, colony formation, soft agar and Transwell migration assays to determine the impact of the UCHL3 gene on cell phenotype. RNA-seq was performed with UCHL3-depleted T24 cells (established via CRISPR–Cas9-mediated genomic editing). We analyzed differences in WNT pathway gene expression in wild-type and UCHL3-deficient T24 cell lines using a heatmap and by gene set enrichment analysis (GSEA). Then, we validated the effect of UCHL3 on the Wnt pathway using a dual fluorescence reporter. We then analyzed the underlying mechanisms involved using Western blots, co-IP, and immunofluorescence results. We also conducted nude mouse tumor formation experiments. Moreover, conditional UCHL3-knockout mice and bladder cancer model mice were established for research.

Results

We found that the overexpression of UCHL3 boosted bladder cancer cell proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed tumor tumorigenesis in vitro and in vivo. UCHL3 was highly associated with the Wnt signaling pathway and triggered the activation of the Wnt signaling pathway, which showed that its functions depend on its deubiquitination activity. Notably, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer cells and associated with indicators of advanced clinicopathology.

Conclusion

In summary, we found that UCHL3 is amplified in bladder cancer and functions as a tumor promoter that enhances proliferation and migration of tumor cells in vitro and bladder tumorigenesis and progression in vivo. Furthermore, we revealed that UCHL3 stabilizes CTNNB1 expression, resulting in the activation of the oncogenic Wnt signaling pathway. Therefore, our findings strongly suggest that UCHL3 is a promising therapeutic target for bladder cancer.
The effect of hyperthyroidism on cognitive function, neuroinflammation, and necroptosis in APP/PS1 mice
Authors: Lou Kai , Liu Shudong , Zhang Fengxia , Sun Wenxiu , Su Xinhuan , Bi Wenkai , Yin Qingqing , Qiu Yaxin , Zhang Zhenyuan , Jing Mengzhe , Ma Shizhan
Published: September 2023

Background

Increasing evidence has linked the thyroid dysfunction to the pathogenesis of dementia. Evidence from clinical studies has demonstrated that hypothyroidism is related to an increased risk of dementia. But the association of hyperthyroidism with dementia is largely unknown.

Methods

We used the adenovirus containing thyrotropin receptor (TSHR) amino acid residues 1-289 (Ad-TSHR289)-induced Graves’ disease (GD) phenotype in Alzheimer’s disease (AD) model mice (APP/PS1 mice) to evaluate the effect of hyperthyroidism on the cognitive function and β-amyloid (Aβ) accumulation.

Results

GD mice exhibited a stable long-term hyperthyroidism and cognitive deficits. Single Cell RNA-sequencing analysis indicated that microglia function played a critical role in the pathophysiological processes in GD mice. Neuroinflammation and polarization of microglia (M1/M2 phenotype) and activated receptor-interacting serine/threonine protein kinase 3 (RIPK3)/mixed lineage kinase domain–like pseudo-kinase (MLKL)-mediated necroptosis contributed to the pathological process, including Aβ deposition and neuronal loss. RIPK3 inhibitor could inhibit GD-mediated Aβ accumulation and neuronal loss.

Conclusions

Our findings reveal that GD hyperthyroidism aggravates cognitive deficits in AD mice and induces Aβ deposition and neuronal loss by inducing neuroinflammation and RIPK3/MLKL-mediated necroptosis.
Investigating the interactions of endornaviruses with each other and with other viruses in common bean, Phaseolus vulgaris
Authors: Brine Thomas J. , Viswanathan Satish B. , Murphy Alex M. , Pate Adrienne E. , Wamonje Francis O. , Carr John P.
Published: September 2023

Background

Plant viruses of the genus Alphaendornavirus are transmitted solely via seed and pollen and generally cause no apparent disease. It has been conjectured that certain plant endornaviruses may confer advantages on their hosts through improved performance (e.g., seed yield) or resilience to abiotic or biotic insult. We recently characterised nine common bean (Phaseolus vulgaris L.) varieties that harboured either Phaseolus vulgaris endornavirus (PvEV1) alone, or PvEV1 in combination with PvEV2 or PvEV1 in combination with PvEV2 and PvEV3. Here, we investigated the interactions of these endornaviruses with each other, and with three infectious pathogenic viruses: cucumber mosaic virus (CMV), bean common mosaic virus (BCMV), and bean common mosaic necrosis virus (BCMNV).

Results

In lines harbouring PvEV1, PvEV1 and PvEV2, or PvEV1, PvEV2 plus PvEV3, the levels of PvEV1 and PvEV3 RNA were very similar between lines, although there were variations in PvEV2 RNA accumulation. In plants inoculated with infectious viruses, CMV, BCMV and BCMNV levels varied between lines, but this was most likely due to host genotype differences rather than to the presence or absence of endornaviruses. We tested the effects of endornaviruses on seed production and seedborne transmission of infectious pathogenic viruses but found no consistent relationship between the presence of endornaviruses and seed yield or protection from seedborne transmission of infectious pathogenic viruses.

Conclusions

It was concluded that endornaviruses do not interfere with each other’s accumulation. There appears to be no direct synergy or competition between infectious pathogenic viruses and endornaviruses, however, the effects of host genotype may obscure interactions between endornaviruses and infectious viruses. There is no consistent effect of endornaviruses on seed yield or susceptibility to seedborne transmission of other viruses.
Dose delivery reproducibility for PBS proton treatment of breast cancer patients with and without mask immobilization
Authors: Kang Yixiu , Bues Martin , Halyard Michele Y. , McGee Lisa A. , Vern-Gross Tamara Z. , Wong William W. , Keole Sameer R. , Vargas Carlos , James Sarah E. , Ahmed Safia K. , Archuleta James P. , Ridgway Ana K. , Lara Pedro R. , Fatyga Mirek
Published: September 2023

Background

Setup reproducibility of the tissue in the proton beam path is critical in maintaining the planned clinical target volume (CTV) dose coverage and sparing the organs at risk (OAR). In this study, we retrospectively evaluated radiation therapy dose reproducibility for proton pencil beam scanning (PBS) treatment of breast cancer patients with and without mask immobilization.

Methods

Ninety-four patients treated between January 2019 and September 2022 with at least one verification CT scan (V-CT) in treatment position were included for this study. All patients were set up with arms up using the Orfit AIO patient positioning system, with (69 patients) or without (25 patients) mask immobilization in chin, neck, shoulder, upper arm, and chest areas. Two to three enface or near enface single field uniform dose PBS beams were optimized using a commercial treatment planning system. Prescription doses were 25 to 60 GyRBE in 5 to 45 fractions. Treatment plan doses re-calculated on V-CTs were compared to the corresponding planned doses. Cumulative doses were also calculated for patients with at least 3 V-CTs by deform and weighted sum doses from V-CTs to corresponding P-CTs. CTV D95%, ipsilateral-lung V40%, esophagus D0.01cc, and heart mean dose were evaluated and reported as percentages of prescription doses. Differences were large dose deteriorations (LDD) if: (1) CTV (V-CT/cumulative D95%) – (Planned D95%) < − 5%; or (2) Ipsilateral-lung (V-CT/cumulative V40%) – (Planned V40%) > 5%; or (3) Esophagus (V-CT/cumulative D0.01cc) – (Planned D0.01cc) > 10%; or (4) Heart (V-CT/cumulative mean) – (Planned mean) > 1.5%.

Results

On average, V-CT/cumulative and planned CTV/OAR dose parameter differences were less than 2.2%/1.7% and 3.4%/3.7% for masked and maskless patients, respectively. The percentages of patients with at least one CTV or OAR V-CT/cumulative dose LDD were 20.3%/25.0% and 72.0%/54.0% for masked and maskless patients, respectively.

Conclusions

On average, masked/maskless setups achieved delivered and planned CTV/OAR dose parameters agreed within 2.2%/3.7% for PBS treatment of breast cancer patients in this study. Maskless patients had higher rate of CTV/OAR LDDs compared to masked patients. Dosimetric differences large enough to raise clinical concerns in either group were able to be addressed with replannings.
Health-related quality of life in a european sample of adults with early-treated classical PKU
Authors: Maissen-Abgottspon Stephanie , Muri Raphaela , Hochuli Michel , Reismann Péter , Barta András Gellért , Alptekin Ismail Mucahit , Hermida-Ameijeiras Álvaro , Burlina Alessandro P. , Burlina Alberto B. , Cazzorla Chiara , Carretta Jessica , Trepp Roman , Everts Regula
Published: September 2023

Background

Phenylketonuria (PKU) is a rare inborn error of metabolism affecting the catabolism of phenylalanine (Phe). To date, findings regarding health-related quality of life (HRQoL) in adults with early-treated classical PKU are discrepant. Moreover, little is known about metabolic, demographic, and cognitive factors associated with HRQoL. Hence, we aimed to investigate HRQoL and its association with demographic, metabolic, and cognitive characteristics in a large European sample of adults with early-treated classical PKU.

Results

This cross-sectional study included 124 adults with early-treated classical PKU from Hungary, Italy, Spain, Switzerland, and Turkey. All participants prospectively completed the PKU quality of life questionnaire (PKU-QoL), a questionnaire specifically designed to evaluate the impact of PKU and its treatment on HRQoL in individuals with PKU. In addition, information about Phe levels (concurrent and past year), demographic (age and sex), and cognitive variables (intelligence quotient, IQ) were collected. Most domains revealed little or no impact of PKU on HRQoL and more than three-quarters of the patients rated their health status as good, very good, or excellent. Nevertheless, some areas of concern for patients were identified. Patients were worried about the guilt that they experience if they do not adhere to the dietary protein restriction and they were most concerned about high Phe levels during pregnancy. Further, tiredness was the most affected symptom, and the supplements’ taste was considered a main issue for individuals with PKU. The overall impact of PKU on HRQoL was higher in women (U = 1315.5,p = .012) and in adults with a lower IQ (rs = − 0.448,p = .005). The overall impact of dietary protein restriction was higher in adults with higher concurrent Phe levels (rs= 0.272,p = .007) and higher Phe levels during the past year (rs= 0.280,p = .009).

Conclusion

The impact of PKU on most domains assessed in the PKU-QoL was considered to be low. These results likely reflect the successful implementation of the newborn screening resulting in the prevention of severe adverse long-term outcomes. However, a particular clinical focus should be given to patients with lower IQ, higher Phe levels, and women, as these variables were associated with a lower HRQoL.
Overhead squat assessment reflects treadmill running kinematics
Authors: Sever Ozan , Kır Rıdvan , Baykal Cihan , Akyildiz Zeki , Nobari Hadi
Published: September 2023

Purpose

Overhead squat assessment (OHSA) is a pre-activity dynamic movement analysis tool used to define deviations from an ideal motion pattern which known as compensation. Compensatory movements may result from abnormality in myofascial activity, length-tension relationships, neuro-motor control strategies, osteokinematics and arthrokinematics. The aim of this study is to identify the association between selected biomechanical variables of the ankle, knee, hip, pelvis, torso during OHSA and 16 km/h treadmill running tasks.

Methods

Thirteen national long distance male runners (17.3 ± 0.5 age (years); 5.89 ± 1.95 experience (years), 57.9 ± 3.7 body mass (kg); 175.4 ± 5.7 height (cm)) participated in this 2controlled laboratory study. Three-dimensional kinematics were collected at 250 Hz using a 9-camera Qualisys motion analysis system (Qualisys AB, Goteborg, Sweden) while participants performed 16 km/h treadmill running and OHSA tasks.

Results

Correlation coefficients demonstrated that OHSA pelvic anterior tilt angle was in a positive association with foot strike (FS), mid-stance (MS), and toe-off (TO) pelvic anterior tilt angles and MS tibial internal rotation on talus, MS ankle pronation, MS hip internal rotation. OHSA pelvic anterior tilt angle was in a negative association with TO hip extension. OHSA maximal hip adduction was positively correlated with MS and stance maximal knee adduction. FS, MS, stance maximal angular dorsiflexion values were positively correlated with OHSA dorsiflexion. Increased OHSA dorsiflexion angle was negatively associated with TO plantar flexion. OHSA pronation was positively associated with MS and stance pronation. MS hip internal rotation, MS hip adduction angles were increased, and MS ankle dorsiflexion was significantly decreased with the increase of trunk forward lean relative to tibia during OHSA.

Conclusions

OHSA was associated with some important and dysfunction-related hip, knee and ankle kinematics. Running coaches, may use OHSA as an assessment tool before the corrective training plan to detect injury-related compensation patterns to reduce the risk of injury and improve running technique.
Head-to-head comparison between plasma p-tau217 and flortaucipir-PET in amyloid-positive patients with cognitive impairment
Authors: Mundada Nidhi S. , Rojas Julio C. , Vandevrede Lawren , Thijssen Elisabeth H. , Iaccarino Leonardo , Okoye Obiora C. , Shankar Ranjani , Soleimani-Meigooni David N. , Lago Argentina L. , Miller Bruce L. , Teunissen Charlotte E. , Heuer Hillary , Rosen Howie J. , Dage Jeffrey L. , Jagust William J. , Rabinovici Gil D. , Boxer Adam L. , La Joie Renaud
Published: September 2023

Background

Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer’s disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables.

Methods

We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (11C-PIB), tau-PET (18F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years).

Results

Plasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR (r = 0.26, p = 0.02), but not with p-tau217 (r = 0.10, p = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model.

Conclusion

Plasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration.
Menin orchestrates hepatic glucose and fatty acid uptake via deploying the cellular translocation of SIRT1 and PPARγ
Authors: Liu Tingjun , Li Ranran , Sun Lili , Xu Zhongjin , Wang Shengxuan , Zhou Jingxuan , Wu Xuanning , Shi Kerong
Published: September 2023

Background

Menin is a scaffold protein encoded by the Men1 gene, which interacts with various transcriptional proteins to activate or repress cellular processes and is a key mediator in multiple organs. Both liver-specific and hepatocyte-specific Menin deficiency promotes high-fat diet-induced liver steatosis in mice, as well as insulin resistance and type 2 diabetic phenotype. The potential link between Menin and hepatic metabolism homeostasis may provide new insights into the mechanism of fatty liver disease.

Results

Disturbance of hepatic Menin expression impacts metabolic pathways associated with non-alcoholic fatty liver disease (NAFLD), including the FoxO signaling pathway, which is similar to that observed in both oleic acid-induced fatty hepatocytes model and biopsied fatty liver tissues, but with elevated hepatic Menin expression and inhibited FABP1. Higher levels of Menin facilitate glucose uptake while restraining fatty acid uptake. Menin targets the expression of FABP3/4/5 and also CD36 or GK, PCK by binding to their promoter regions, while recruiting and deploying the cellular localization of PPARγ and SIRT1 in the nucleus and cytoplasm. Accordingly, Menin binds to PPARγ and/or FoxO1 in hepatocytes, and orchestrates hepatic glucose and fatty acid uptake by recruiting SIRT1.

Conclusion

Menin plays an orchestration role as a transcriptional activator and/or repressor to target downstream gene expression levels involved in hepatic energy uptake by interacting with the cellular energy sensor SIRT1, PPARγ, and/or FoxO1 and deploying their translocations between the cytoplasm and nucleus, thereby maintaining metabolic homeostasis. These findings provide more evidence suggesting Menin could be targeted for the treatment of hepatic steatosis, NAFLD or metabolic dysfunction-associated fatty liver disease (MAFLD), and even other hepatic diseases.

Graphical Abstract
Increasing the transparency of systematic reviews: presenting a generalized registration form
Authors: van den Akker Olmo R. , Peters Gjalt-Jorn Ygram , Bakker Caitlin J. , Carlsson Rickard , Coles Nicholas A. , Corker Katherine S. , Feldman Gilad , Moreau David , Nordström Thomas , Pickering Jade S. , Riegelman Amy , Topor Marta K. , van Veggel Nieky , Yeung Siu Kit , Call Mark , Mellor David T. , Pfeiffer Nicole
Published: September 2023

This paper presents a generalized registration form for systematic reviews that can be used when currently available forms are not adequate. The form is designed to be applicable across disciplines (i.e., psychology, economics, law, physics, or any other field) and across review types (i.e., scoping review, review of qualitative studies, meta-analysis, or any other type of review). That means that the reviewed records may include research reports as well as archive documents, case law, books, poems, etc. Items were selected and formulated to optimize broad applicability instead of specificity, forgoing some benefits afforded by a tighter focus. This PRISMA 2020 compliant form is a fallback for more specialized forms and can be used if no specialized form or registration platform is available. When accessing this form on the Open Science Framework website, users will therefore first be guided to specialized forms when they exist. In addition to this use case, the form can also serve as a starting point for creating registration forms that cater to specific fields or review types.
The application of 3D-printed oral stents in intensity-modulated radiotherapy for oropharyngeal cancer and their dosimetric effect on organs at risk
Authors: Ma Jungang , Chen Zhuo , Liu Shuixia , Hu Wei , Su Kunpu , He Rong , Zhou Peng , Xiao He , Ju Jia , Hou Qianying , Zhou Yinying , Wang Bin
Published: September 2023

Background

This study investigates the accuracy of 3D-printed dental stents in intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) and their dosimetric effects on normal tissues.

Methods

We selected 60 patients with OPC who underwent IMRT in the Department of Oncology, Special Medical Center of Army Medical University. These patients were randomly assigned into 3D-printed oral stent, simple glass bottle, and nonstent groups (20 patients/group). The positioning error was analyzed with the onboard imaging system once a week after 5 fractions of IMRT. The conformity index (CI), homogeneity index (HI), radiation dose of organs at risk (OARs), and oral mucosal reaction were compared among the three groups.

Results

No significant difference was observed in the conformity and uniformity of the target dose and the dose received by the spinal cord, larynx, and bilateral parotid glands among the three groups (P > 0.05). Meanwhile, the dose received by the upper cheek, hard palate, and soft palate of patients was significantly lower in the 3D-printed oral stent group than in the nonstent group (P < 0.05) but insignificantly different between the 3D-printed oral stent and simple glass bottle groups (P > 0.05). When compared with the nonstent group, the simple glass bottle group showed a markedly lower dose received by the upper cheek (P < 0.05) and an insignificantly different dose received by the hard palate and soft palate (P > 0.05). According to Common Terminology Criteria for Adverse Events v.5.0, the adverse response rate of the hard palate mucosa was lower in the 3D-printed oral stent group than in the simple glass bottle and nonstent groups (P < 0.05).

Conclusions

For OPC patients undergoing IMRT, the application of 3D-printed oral stents can significantly reduce the exposure dose of the upper cheek and hard palate and decrease the occurrence of adverse events such as oral mucositis although it cannot affect the positioning error.
Smooth transition regression model relating inflation to economic growth in Tunisia
Authors: Becha Hamdi , Kalai Maha , Helali Kamel
Published: September 2023

Since its independence, Tunisia has embarked on monetary and financial sector reforms aimed at boosting economic growth. However, these reforms have not been effective due to inflation pressures in this country. Thus, this paper examines the nature of the relationship between financial development and economic growth between 1965 and 2019, using the non-linear logistic smooth transition regression model and considering inflation as a threshold financial development. The results show the existence of a non-linear abrupt relationship with an inflation threshold equal to 3.63%. Specifically, when inflation is below 3.63%, all variables, including inflation, have a significant and positive impact on economic growth. However, when inflation exceeds the estimated threshold, inflation has a significant and negative impact with an elasticity equal to − 0.365. To effectively manage inflation, the Tunisian authorities are encouraged to set and embrace specific inflation targets as a goal. This approach aims to mitigate inflationary pressures and foster a favourable environment for financial development in Tunisia, thereby promoting economic growth. Hence, it becomes imperative to implement such measures that alleviate inflationary pressures and drive economic growth through the facilitation of development finance by the banking sector.
Characterization of the Tumor Microenvironment of De Novo Oligometastatic Breast Cancer in a Nationwide Cohort
Authors: Steenbruggen Tessa G. , Wolf Denise M. , Thijssen Bram , Sanders Joyce , Cornelissen Sten , Salgado Roberto , Mittempergher Lorenza , Bhaskaran Rajith , Broeks Annegien , Lips Esther H. , Siesling Sabine , Sonke Gabe S. , Horlings Hugo M. , van ’t Veer Laura J.
Published: September 2023

Extracellular-matrix features distinguish between long-term versus shorter-term survivors with OligoMBC.
Trends in Prevalence of Thyroid Dysfunction and its Associations With Mortality Among US Participants, 1988-2012
Authors: Zhang Xiaowen , Wang Yong , Wang Hongwei , Zhang Xinlin
Published: September 2023

Context

Various dynamic factors could influence the prevalence and distribution of thyroid dysfunction.

Objective

To provide national estimates and temporal trends in prevalence of thyroid dysfunction over the past 3 decades in United States and determine the impact of thyroid dysfunction on mortality in US adults.

Methods

A cross-sectional analysis of data from 33 117 participants aged 12 years or older in the National Health and Nutrition Examination Survey III (1988-1994), 1999-2002, and 2007-2012.

Results

The weighted mean age was 41.6 years, and 48.3% were men. In 2007 through 2012, the prevalence of subclinical and overt hypothyroidism, subclinical and overt hyperthyroidism was 4.3%, 0.33%, 3.2%, and 0.2% respectively. Eighty percent of individuals with thyroid dysfunction were previously undiagnosed. The prevalence of subclinical hypothyroidism and hyperthyroidism was stable, whereas overt hypothyroidism (0.54% [95% CI, 0.35-0.8] vs 0.33% [95% CI, 0.23-0.48]) and hyperthyroidism (0.8% [95% CI, 0.58-1.1] vs 0.2% [95% CI, 0.12-0.33]) were less prevalent in 2007–2012 compared to 1988–1994. Older age, White Americans, obesity, and positivity for thyroid peroxidase antibody and thyroglobulin antibody were risk factors for hypothyroidism, whereas older age, women, and Black Americans were risk factors for hyperthyroidism. Over a median follow-up of 17.2 years, no significant association was observed between any type of thyroid dysfunction with the risk of total or cardiovascular mortality. However, among individuals aged 65 years or older, subclinical hypothyroidism was associated with a higher risk of total mortality (hazard ratio, 1.17; 95% CI, 1.00-1.37; P = .05) and cardiovascular mortality (HR, 1.29; 95% CI, 1.04-1.62; P = .02).

Conclusions

The prevalence of subclinical thyroid dysfunction remained relatively unchanged, whereas that of overt thyroid dysfunction decreased. Subclinical hypothyroidism was associated with a higher mortality among individuals aged 65 years or older.
Research Progress of Metformin in the Treatment of Oral Squamous Cell Carcinoma
Authors: Liu Jiayi , Zhao Jing , Qiao Xue
Published: September 2023

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a high mortality, posing a great threat to both human physical and mental health. With the advancement of scientific research, a variety of cancer therapies have been used for OSCC treatment. However, the prognosis of OSCC shows no significant improvement. Metformin has been recognized as the first-line drug for the treatment of diabetes, and recent studies have shown that metformin has a remarkable suppressive effect on tumor progression. Metformin can not only affect the energy metabolism of tumor cells but also play an antitumor role by modulating the tumor microenvironment and cancer stem cells. In this review, the molecular mechanism of metformin and its anticancer mechanism in OSCC are summarized. In addition, this article summarizes the side effects of metformin and the future prospects of its application in the treatment of OSCC.
Puberty Suppression Followed by Testosterone Therapy Does Not Impair Reproductive Potential in Female Mice
Authors: Godiwala Prachi , Uliasz Tracy F , Lowther Katie M , Kaback Deborah , Mehlmann Lisa M
Published: September 2023

More adolescents are coming out as transgender each year and are put on puberty blockers to suppress natal puberty, which is then followed by cross-hormone treatment to achieve puberty of the desired gender. Studies to examine the effects of puberty suppression and virilizing therapy on future reproductive potential among transgender males are lacking. This study used a translational murine in vitro fertilization model to examine the effects of female puberty suppression with depot leuprolide acetate (LA), followed by virilizing therapy with testosterone cypionate (T), on embryologic and pregnancy outcomes. LA effectively inhibited puberty when mice were treated beginning at 3 weeks of age. LA treatment was associated with higher mouse weight but lower ovarian weight. LA-treated mice ovulated developmentally competent eggs in response to gonadotropin administration, albeit at a higher dose than controls. Ovaries from mice treated with LA and T produced oocytes that had morphologically normal meiotic spindles after in vitro maturation and responded to gonadotropin stimulation. Eggs from mice treated with LA and T were fertilizable and produced developmentally competent embryos that led to births of fertile pups. These results suggest that fertility may not be impaired after puberty suppression and cross-hormone therapy for transgender males.
Cultural Criticism and Its Generations: The Achievement of Maureen Warner-Lewis
Authors: Smith Faith
Published: September 2023

Maureen Warner-Lewis’s extraordinary body of cultural criticism proposes a new temporal engagement with the place of the African continent in the Caribbean. Her work and career suggest some of the dispositions of the Mona Generation (UWI) of the mid-1960s to early 1970s. Read against some of the debates of the era, her work veers from an expected ideological path; or the path she takes, read as ideological in a particular way, shines an unexpected light on an adjacent path. Inevitably, the demands and desires of subsequent generations are highlighted as well, as is the realization that the assessment of Africa’s entanglement with the region is ongoing.
Echoes in the Bone: Hearing Africa in Maureen Warner-Lewis’s Caribbean
Authors: Cobham-Sander Rhonda
Published: September 2023

Framed by the author’s three encounters with Maureen Warner-Lewis’s voice, this essay evaluates three aspects of her work: her commitment to pedagogical approaches that privilege orature; her commitment to research methodologies that privilege the language and history of Caribbean community members who have preserved explicit connections to African cultural institutions; and the decolonial theoretical orientation of her scholarship, which raises questions about the role of “indigenous” epistemologies in Caribbean literary theory.
Cimarrón and the Reordering of the Living World
Authors: Rodríguez-Silva Ileana M.
Published: September 2023

This essay examines three historical moments in the signification of the term cimarrón across the hispanophone Caribbean. It explores its origin during the conquest, simultaneously naming runaway livestock and Native and Black enslaved peoples who challenged colonization. In the twentieth century, the cimarrón became attached to masculinist nationalist tropes key to postwar anticolonial movements. In the new millennium, Black and Brown women and LBTQ+ folks use the term to convey an ethos of antipatriarchal, community-centered activism. The essay argues that the origins of the term demand a close consideration of the relationship between conquest, othering, racialization, commodification, and the reordering of the animal world with human animals as supreme beings. The contemporary reappropriation of the term alludes to a decolonial reframing, a unique opportunity to reject Western ontologies grounded on the violent practices of othering while also pointing us toward new conditions of possibility based on relationality.
Embracing Our Animal Selves: The Liberatory Politics of Andil Gosine’s Nature’s Wild
Authors: Willis Kedon
Published: September 2023

This essay on Andil Gosine’s Nature’s Wild: Love, Sex, and Law in the Caribbean (2021) reflects on the author’s application of animal studies as a productive analytic of the enduring anxieties around respectable citizenship in the Caribbean as expressed by contemporary regulations governing sex, marriage, and public dress. The pairing of antisodomy laws and bestiality codes during the early colonial era, Gosine contends, underwrites contemporary attitudes that marginalize a variety of nonheteronormative expressions and continues to influence a collective compulsion to constantly affirm the respectability of the region’s inhabitants. Gosine’s investment in understanding and dismantling the historical hold of needing to prove one’s humanity, the author argues, falls in line with a movement among a multidisciplinary field of queer artists and scholars who embrace animality as a form of radical postcolonial thinking.
This Is How You Become the Animal You Are So Bent on Becoming
Authors: Rowley Michelle V.
Published: September 2023

Taking Andil Gosine’s invitation in Nature’s Wild: Love, Sex, and Law in the Caribbean (2021) to consider the possibilities of animality, this essay sits with the two valences that are potentially inherent in his framing—first, that we reassess the generative possibilities of animality, and second, that we consider how in refusing the demarcating line between humanity and animality they potentially remake each other. Centering “animality” as an analytic, the author considers the kinds of relations that animality allows us to imagine with ourselves and each other. The essay frames Gosine’s questions as ones that pursue the decolonial possibilities of animality and suggests that Nature’s Wild offers us a blueprint for a Caribbean queer decolonial politic. Its primary inquiry resides in asking how animality adapts and signifies in potentially intersectional ways and whether this framing makes room for us to envision the ways “gender” also holds generative possibilities in relation to ideas of animality.
LGBT Hareketin Gelişimi, Kurumsallaşması ve Batı Medeniyet Projesine Dönüşümü
Authors: Albayrak H. Şule
Published: September 2023

Bu çalışma, Batı ülkelerindeki yükselişinin ardından kültürel, politik ve ekonomik küreselleşmenin etkisiyle daha çok karşılaşılan ve 2010 sonrası dönemde dijitalleşme ve yeni medya sahalarındaki gelişmelerle küresel düzeyde büyük bir ivme kazanan eşcinsel hareketin ortaya çıkışını, yükselişini, kurumsallaşma sürecini ve küreselleşmesini konu edinmektedir. Bu çerçevede makale, LGBT hareketin haklar söylemi bağlamında nasıl kurgulandığını ve bir medeniyet projesi olarak nasıl uygulandığını mercek altına almaktadır. Çalışmada cevap aradığımız temel soru şudur: “Eşcinsel haklarının insan hakları bağlamına oturtulmasının Batı’nın (medeniyet) Batı dışı (medeniyet dışı) üzerindeki iktidar pratiklerine ve medeniyet söylemine yansımaları nelerdir?” Bu soru çerçevesinde öncelikle eşcinsel hareketin ortaya çıkışı ve gelişim süreci tasvirî şekilde ele alınacaktır. Ardından eşcinsel hareketin küreselleşmesi, ulus aşırı ve ulus üstü kurumlar tarafından himaye ediliş süreci sorunsallaştırılacaktır. Son olarak eşcinsel haklar söyleminin bir medeniyet projesi olarak nasıl kurgulandığı ve Batılı hegemonyanın sürdürülmesindeki işlevselliği sorgulanacaktır. Bu minvalde çalışmada konuyla ilgili akademik yazın, kamuoyu araştırmaları ve raporlardan faydalanılmıştır.
Frantz Fanon’un Gözünden Erken Cumhuriyet Dönemi Batılılaşmasını Okumak: Cumhuriyet Gazetesi’nin 1930 Yılı Ses Kraliçesi Yarışması
Authors: Türedi Hümeyra
Published: September 2023

Oryantalizm; Batılı olmayan toplumların yönetilmesi gerektiğini düşünen, aynı zamanda da bu toplumları ötekileştiren Batılı zihniyetin kavramsallaştırılması olarak ifade edilebilir. Bu bağlamda oryantalizm, sömürgeciliği meşrulaştıran, sömürgecinin sömürgelerini ötekileştirmesine yardım eden bir düşünce biçimi olarak da görülebilir. Batı’nın bu tahkir edici anlayışının, nesneleştirilen toplumlar üzerinde önemli psikolojik sonuçları olduğunu belirtmek gerekir. Bu sonuçları inceleyen F. Fanon, Malik bin Nebi, A. Cesaire gibi araştırmacılar, ezilen toplumların psikolojisini açığa çıkarmaya çalışır. Ezilen toplumlarda tespit edilebilen psikolojik sonuçlardan biri milliyetçi duygularda artış olarak sayılabilirken; bir diğeri de Batılı değerlerin içselleştirilerek Batı’ya öykünmek şeklinde ortaya çıkar. F. Fanon da bu görüşü benimseyen düşünürlerdendir. Bu çalışmada, oryantalist bakış açısına maruz kalmış Türklerin, Cumhuriyet’in ilk dönemlerinde içinde bulunduğu psikoloji, F. Fanon’un çalışmalarından yola çıkarak incelenmiştir. Bu noktada, Cumhuriyet’in erken dönemlerinde hızlı bir Batılılaşmanın yaşandığını belirtmek gerekir. Dolayısıyla makalenin araştırma sorusu: “Erken Cumhuriyet Dönemi’ndeki Batılılaşmanın ardındaki psikolojik faktörler ile F. Fanon’un tespitleri arasında bir ilinti kurulabilir mi?” şeklindedir. Örnek olay olarak, 1930 yılında düzenlenen Ses Kraliçesi Yarışması, Cumhuriyet gazetesinden söylem analizi yöntemiyle takip edilmiştir. Ses Kraliçesi Yarışması’nın, tıpkı dönemin güzellik yarışmaları gibi bir Batılılaşma aracı olduğu bu noktada belirtilmelidir. Yapılan okuma ışığında, Cumhuriyet dönemi aydınları, milliyetçi duygulardaki yoğunluk ve Batıya öykünme konusunda önemli tespitler yapılmıştır.
Antioxidant of the putat air (barringtonia racemosa) as a herbal remedy to improve sperm quality due to cigarette smoke in rats
Authors: Dahril Dahril , Badiri San Winata , Dasrul Dasrul , Mutiawati Vivi Keumala , Khalilullah Said Alfin
Published: September 2023

Background: The objective of this study is to analyse the antioxidant in putat air (barringtonia racemosa) as an herbal to improve sperm quality due to cigarette smoke.

Methods: An experimental study was conducted at animal laboratory, Faculty Veteriner University of Syiah Kuala, Banda Aceh, Indonesia. A total of 30 male rats (Rattus norvegicus) were divided into 5 treatment groups. Group 1 as a negative control (N) were not exposed to cigarette smoke. Group 2 as a positive control (P) were exposed to cigarette smoke. Group 3 as treatment 1 (P1) were exposed to cigarette smoke and 100 mg/kg BW/day of the barringtonia racemosa seed extract. Group 4 as treatment 2 (P2) were exposed to cigarette smoke and given 150mg/kg BW/day of the barringtonia racemosa seed extract. Group 5 as treatment 3 (P3) were exposed to cigarette smoke and given 200 mg/kg BW/day of the barringtonia racemosa seed extract. The cigarette smoke exposure was carried out in a smoking chamber for a total of 1 hour/rat, and the barringtonia racemosa seed extract is given orally once a day for 30 days.

Results: The results of this study were analyzed by one-way ANOVA showed significant differences in the quality of the sperm group that received cigarette smoke exposure (p <0.05) compared to the administration of the barringtonia racemosa.

Improved sperm quality was seen better with the administration of barringtonia racemosa 150 kg/kg BW/day compared with 100 and 200 kg.

Conclusions: Antioxidants from barringtonia racemosa can improve sperm quality due to cigarette smoke.
Privacy-Preserving Personalized Revenue Management
Authors: Lei Yanzhe (Murray) , Miao Sentao , Momot Ruslan
Published: September 2023

This paper examines how data-driven personalized decisions can be made while preserving consumer privacy. Our setting is one in which the firm chooses a personalized price based on each new customer’s vector of individual features; the true set of individual demand-generating parameters is unknown to the firm and so must be estimated from historical data. We extend the existing personalized pricing framework by requiring also that the firm’s pricing policy preserve consumer privacy, or (formally) that it be differentially private: an industry standard for privacy preservation. We develop privacy-preserving personalized pricing algorithms and show that they achieve near-optimal revenue by deriving theoretical (upper and lower) performance bounds. Our analyses further suggest that, if the firm possesses a sufficient amount of historical data, then it can achieve a certain level of differential privacy almost “for free.” That is, the revenue loss due to privacy preservation is of smaller order than that due to estimation. We confirm our theoretical findings in a series of numerical experiments based on synthetically generated and online auto lending (CPRM-12-001) data sets. Finally, motivated by practical considerations, we also extend our algorithms and findings to a variety of alternative settings, including multiproduct pricing with substitution effect, discrete feasible price set, categorical sensitive features, and personalized assortment optimization.

This paper was accepted by Vishal Gaur, operations management.

Funding: R. Momot acknowledges financial support from the HEC Paris Foundation and the Agence Nationale de la Recherche (French National Research Agency) “Investissements d’Avenir” [Grant LabEx Ecodec/ANR-11-LABX-0047] during the initial stages of this project.

Supplemental Material: The data files and online appendices are available at https://doi.org/10.1287/mnsc.2023.4925 .
Computation of Systemic Risk Measures: A Mixed-Integer Programming Approach
Authors: Ararat Çağın , Meimanjan Nurtai
Published: September 2023

Mixed-Integer Programming Formulations for Systemic Risk Measures

Measurement and allocation of systemic risk have become important tasks in interconnected financial networks. In “Computation of Systemic Risk Measures: A Mixed-Integer Programming Approach,” Ararat and Meimanjan consider a clearing model that considers external assets and business costs of a bank simultaneously by extending the Rogers–Veraart network model with default costs. They prove that clearing payment vectors can be calculated by solving mixed-integer programming problems in which the existence of business costs and default costs are represented by binary variables. The systemic risk measure corresponding to this model yields nonconvex sets of capital allocation vectors. The authors compute these nonconvex sets by solving a multiobjective optimization problem whose scalarizations are two-stage mixed-integer programming problems with an expectation constraint. The computational procedure is versatile enough to accommodate other applications of systemic risk where the risk factors are aggregated by solving a general mixed-integer programming problem.
Disentangling the Atlantic
Authors: Griffin Patrick
Published: September 2023

This chapter discusses how the War for the Atlantic led to far-reaching discussions of how to rationalize the Atlantic system, to make it comprehensible and manageable. Reformers hoped that the tangled nature of a system they saw as inherently anarchic could be made straight along national lines. In so doing, all peoples were using the concepts they had at hand to try to order and rationalize a world which they saw as unregulated, but in which the stakes had grown. The task could not be ignored, and they used the only tool they had—sovereignty—however ill or well adapted it was for the job. Eighteenth-century understandings of state power came with rigid and inelegant apparatuses—bureaucracies, decrees, laws, and assumptions—that had to be fitted on a complicated space defined by fluid movement. Ultimately, reform did not only involve imperial governance. It revealed disequilibrium between imperial political structures and economic and social realities.
The Web of War
Authors: Griffin Patrick
Published: September 2023

This chapter assesses how, as the age of revolution progressed, the main solvent that broke down society was war. Because of how enmeshed European power politics had become with Atlantic-wide dynamics, war in one place would touch off conflict in others. Through connectedness, even places on the very margins of the Atlantic would be transformed by aggression and the fears and hopes it generated. One chapter of warfare could be called the French Revolutionary Wars, and the next the Napoleonic Wars. War, in both the French and the British cases, buttressed the state and the search for order. In other places, war initiated revolution, as more than anything else, it quickly de-stated regimes. The sum total of the period's aggression was what can be called the War of the Revolutionary Age, and it trapped nearly everybody in its web.
Singeing the Fray
Authors: Griffin Patrick
Published: September 2023

This chapter evaluates how the end of revolution marked the beginning of new sovereignties. The revolutionary settlements had to cohere to the distinctive natures of the societies in which they were hammered out. Therefore, the age of revolution became an age of revolutions to bring the period to a close and to canonize a new order in which the strong and agile could survive. To be sure, the Constitution was a cornerstone of settlement. The republic would be composed of a union of smaller republics, all distinctive and bound together through a central government. However, the developing federal system is only one part of the story. In the main, the settlement cohered because of boundaries; these were established through political culture. Ultimately, the state sustained a new series of arrangements that allowed the United States to compete in the new Atlantic economic order. The chapter then looks at the War of 1812, which gave Americans distinctive identities as a people in a still integrated world. It also considers the events in Latin America to show how the tangles implicit in revolutionary origins foreshadowed the difficulties of bringing revolution to a close.
Reknitting the Fabric
Authors: Griffin Patrick
Published: September 2023

This chapter addresses how memorialization became the stuff that bound new nations to a new order. Memorials offered for men and women a way to valorize suffering, to psychically deal with fear and death, to explain how they moved from one form of sovereignty to another and the trauma that went hand in hand with the transition. In what they shared, memorials offered silent testimony to how deeply connected the Atlantic remained. They also spoke of supposed national distinctiveness. Memorials arose to anoint the only thing that could provide a basis of order for the continued entanglements of the age: the nation-state. Hand in hand with the rise of sovereignty arose memorials that announced new foundational myths that took the place of those wiped away by revolution and war. However, it has taken nations much more time to memorialize the most traumatic aspect of the age of revolution: slavery.