bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal exposure to Di-n-butyl phthalate (DBP) inhibit orexin receptor 1 (OX1R) expression to prevent Sertoli cells proliferation through the AKT signaling pathway
Authors: Xie Zhiwen , Jiang Juntao , Li Tiewen , Xu Xinyu , Wu Lei , Zhang Yongqing , Chen Min , Sun Yang 
Published: September 2024

Abstract
Background: Studies have demonstrated that Sertoli cells are the direct target of Dibutyl phthalate (DBP). However, the role of neurotransmitter receptors is not elucidated. Methods: Based on our previous studies, maternal Sprague–Dawley (SD) rats in Gestation Day (GD) 14–18 and TM4 cells exposure to 750 mg/kg/day and 100 μM DBP were regarded as treated groups. Firstly, qRT-PCR array was used to determine the different expression of neurotransmitter receptors. We examined the OX1R expression on Rats in Control and DBP groups by immunohistochemistry. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of OX1R in vivo and in vitro. The potential downstream signaling pathways were explored by analyzing the GSE99690 cohort. In addition, we extracted Primary Sertoli Cells (PSCs) from the testis of control group. The apoptosis-related proteins, AKT signaling pathway-related proteins and mRNA expressions were detected by Western Blot and Real-time PCR in PSCs. The validity of PSCs was measured by CCK-8 assay and flow cytometric analysis was used to demonstrate the apoptotic rates of PSCs after DBP exposure. Results: The Orexin receptor 1 (OX1R) was screened out by qRT-PCR array. Our results showed that DBP could significantly suppress the OX1R expression of Sertoli cells in vivo and in vitro. Functional analysis showed the AKT signaling pathway was mediated by OX1R. The highly expressed apoptosis level and impaired cell activity were observed in PSCs, which can be reversed by Orexin A. Meanwhile, the p-AKT signaling pathway were hindered after DBP exposure while rescued in DBP + Orexin-A group. Conclusions: DBP can induce Sertoli cell apoptosis through its toxicological effect by suppressing OX1R and p-AKT expression, which provide a novel insight on the role of neurotransmitter receptors.
Modulation of osteoblastogenesis by NRF2: NRF2 activation suppresses osteogenic differentiation and enhances mineralization in human bone marrow‐derived mesenchymal stromal cells
Authors: Onoki Takahiro , Kanczler Janos , Rawlings Andrew , Smith Melanie , Kim Yang‐Hee , Hashimoto Ko , Aizawa Toshimi , Oreffo Richard O. C. 
Published: September 2024

AbstractMesenchymal stromal stem cells (MSCs) or skeletal stem cells (SSCs) play a major role in tissue repair due to their robust ability to differentiate into osteoblasts, chondrocytes, and adipocytes. Complex cell signaling cascades tightly regulate this differentiation. In osteogenic differentiation, Runt‐related transcription factor 2 (RUNX2) and ALP activity are essential. Furthermore, during the latter stages of osteogenic differentiation, mineral formation mediated by the osteoblast occurs with the secretion of a collagenous extracellular matrix and calcium deposition. Activation of nuclear factor erythroid 2‐related factor 2 (NRF2), an important transcription factor against oxidative stress, inhibits osteogenic differentiation and mineralization via modulation of RUNX2 function; however, the exact role of NRF2 in osteoblastogenesis remains unclear. Here, we demonstrate that NRF2 activation in human bone marrow‐derived stromal cells (HBMSCs) suppressed osteogenic differentiation. NRF2 activation increased the expression of STRO‐1 and KITLG (stem cell markers), indicating NRF2 protects HBMSCs stemness against osteogenic differentiation. In contrast, NRF2 activation enhanced mineralization, which is typically linked to osteogenic differentiation. We determined that these divergent results were due in part to the modulation of cellular calcium flux genes by NRF2 activation. The current findings demonstrate a dual role for NRF2 as a HBMSC maintenance factor as well as a central factor in mineralization, with implications therein for elucidation of bone formation and cellular Ca2+ kinetics, dystrophic calcification and, potentially, application in the modulation of bone formation.
Medications for Alcohol Use Disorder Among Birthing People With an Alcohol-related Diagnosis
Authors: Roberts Sarah C. M. , Liu Guodong , Terplan Mishka 
Published: September 2024

Objectives
Although safety and effectiveness of medications for alcohol use disorder (AUD) are well established for adults, literature on these medications in pregnancy is limited. Given known adverse effects of untreated AUD during pregnancy, clinicians and researchers have recently begun to call for reconsidering use of medications for AUD in pregnancy. Thus, we sought to estimate the proportion of birthing people with an alcohol-related diagnosis who received a prescription for medication related to AUD treatment.

Methods
Data were from Meritive MarketScan, a national private insurance claims database. The study cohort included birthing people aged 25–50 who gave birth to a singleton in the United States between 2006 and 2019 and were matched with an infant. Variables included an alcohol-related diagnosis within a year of birth and receiving a prescription for a medication related to AUD treatment. We calculated proportions with alcohol-related diagnoses who received any AUD medication and each medication type.

Results
Of 1,432,979 birthing person-infant dyads, 2517 (0.18%) had an alcohol-related diagnosis. Of those with an alcohol-related diagnosis, 8.70% (n = 219) received any medication. The most common was gabapentin (4.69%, n = 118), with benzodiazepines for withdrawal as the second most common (2.19%, n = 55). Approximately 2% received naltrexone (1.91%, n = 48) and/or disulfiram (1.39%, n = 35); 0.56% (n = 14) received acamprosate. No one with an alcohol-related diagnosis received phenobarbital. Almost all medications were received postpartum.

Conclusions
Very few pregnant/postpartum people with alcohol-related diagnoses are prescribed medications related to AUD treatment. Research is needed to examine whether benefits of these medications during pregnancy outweigh harms.
Association between radiotherapy and the risk of second primary malignancies in breast cancer patients with different estrogen receptor statuses
Authors: Zhao Chengshan , Yu Yang , Xiang Pi’ao , Liao Jiahu , Yu Boyang , Xing Yifeng , Yin Guobing 
Published: September 2024

Background
Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses.

Methods
We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(−) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups.

Results
Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(−) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50–70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20–30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(−) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50.

Conclusion
Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.
Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1-mutated oral squamous cell carcinoma
Authors: Lin Yumeng , Huang Yibo , Yang Bowen , Zhang You , Ji Ning , Li Jing , Zhou Yu , Shen Ying-Qiang , Chen Qianming 
Published: September 2024

Abstract

Background:
Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.

Methods:
To evaluate the efficacy of the combination of the Ca2+/calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 (FAT1)-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro. The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated.

Results:
OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1-mutated OSCC cells and suppressed tumor growth in vivo. Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1-mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression.

Conclusion:
Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Cerebellar involvement in Parkinson’s disease: Pathophysiology and neuroimaging
Authors: Qiu Tao , Liu Meichen , Qiu Xinhui , Li Tianbai , Le Weidong 
Published: September 2024

Abstract
Parkinson’s disease (PD) is a neurodegenerative disease characterized by various motor and non-motor symptoms. The complexity of its symptoms suggests that PD is a heterogeneous neurological disorder. Its pathological changes are not limited to the substantia nigra-striatal system, but gradually extending to other regions including the cerebellum. The cerebellum is connected to a wide range of central nervous system regions that form essential neural circuits affected by PD. In addition, altered dopaminergic activity and α-synuclein pathology are found in the cerebellum, further suggesting its role in the PD progression. Furthermore, an increasing evidence obtained from imaging studies has demonstrated that cerebellar structure, functional connectivity, and neural metabolism are altered in PD when compared to healthy controls, as well as among different PD subtypes. This review provides a comprehensive summary of the cerebellar pathophysiology and results from neuroimaging studies related to both motor and non-motor symptoms of PD, highlighting the potential significance of cerebellar assessment in PD diagnosis, differential diagnosis, and disease monitoring.
Jarisch–Herxheimer Reactions with artemether/lumefantrine: an uncommon side effect of anti-malarial medications
Authors: Abdallah Abdallah M. , Abbasher Hussien Mohamed Ahmed Khabab , Mohamed Malaz Tarig AbdAlla , Mohamed Imam B. , Mubarak Ismail Manasik M. El Murtada , Mosa Mohammed Hosham Mohammed , Balla Mustafa Monzer Hassan , Abdalla Mustafa Abubaker Mustafa , Abubakr Mahdi Niam Adam , Mahmmoud Fadelallah Eljack Mohammed , E. Mustafa Ahmed Ghassan 
Published: September 2024

Background:
The Jarisch–Herxheimer reaction (JHR) was a nonspecific adverse effect manifested by fever, chills, headache, myalgia, and exacerbations of skin rash that’s firstly described with anti-spirochetes medications and later with fluoroquinolones, cephalosporins, meropenem, and tetracyclines but not with antiparasitic drugs. Herein we reported JHR in a young Sudanese male due to antimalarial medications with good outcomes.

Case Presentation:
A 27-year-old Sudanese man presented with malaria-like symptoms and was given an oral artemisinin combination. However, within 8 h, the patient developed high-grade fever, chills, rigors, recurrence of the headache, tachycardia, myalgia, and tachypnoea, which was diagnosed as a JHR. The drug was temporarily stopped, the patient was hydrated, and an antipyretic was given, then the drug was restarted with a good response. Viral screening and syphilis tests were negative while blood tests showed leukocytosis, lymphopenia, and left shift in granulocytes.

Discussion:
In this case, the patient received Coartem 80/480 (artemether 80 mg/lumefantrine 480 mg). Eight hours after starting treatment, his fever dropped to 37.8°C, with other symptoms improving. Surprisingly at 8 h, the patient developed a second fever of 39.4°C, with chills, headache, tachycardia, a pulse rate of 103, myalgia, and hyperventilation. This is comparable with Koefoed’s case, where the patient received Fansidar (sulfadoxine/pyrimethamine). His JHR started 10 h later, indicated by the second rise in temperature.

Conclusion:
JHR can occur with antimalarial medications, most commonly by non-specific symptoms and worsening of pre-existing skin lesions; this requires a high clinical susceptibility, particularly within the first 24 h, with treatment discontinuation and hydration as the mainstay of management, with good outcomes.
Exploring menopausal symptoms, attitudes, and behaviors among menopausal women in China: an online research perspective
Authors: You Yang , Lin Lin , Yu Qi 
Published: September 2024

Abstract

Objective
The number of perimenopausal women in China is rising, but the population's concept of menopausal hormone therapy (MHT) is still relatively outdated.

Methods
In this study, we used the Knowledge-Attitude-Practice (KAP) theory and collected online questionnaires from 1,100 women aged 40 to 60 years nationwide to find out their menopausal symptom profiles; to learn about their perceptions, attitudes, and behaviors toward menopause and MHT; to explore the factors influencing the acceptance of hormone treatments; and to look for better ways to promote the dissemination of menopausal knowledge.

Results
The results revealed that among women aged 40 to 60 years, 82.36% experienced possible menopausal symptoms, with hot flushes/sweating, sleep disorders, mood disorders, and fatigue being the most prevalent; 55.90% reported moderate to severe symptoms, but only 46.99% of them sought healthcare services. Among those who sought medical care, 16.00% had their first visit to climacteric clinics/gynecological endocrinology, and 5.66% accepted MHT. Furthermore, 77.82% of participants never heard of MHT or were unaware of its existence. The healthcare-seeking behavior of menopausal women in response to symptoms and their willingness to accept MHT were found to be closely associated with their level of self-care.

Conclusions
The prevalence of menopausal symptoms is higher in China than previous research findings, but due to a lack of relevant knowledge, the rate of seeking treatment from the appropriate medical department and accepting MHT is relatively low. Enhancing physicians' knowledge of the menopausal transition and using Internet tools might help improve Chinese women's knowledge of menopause and help them pass through this period smoothly.
Factors Associated With Elder Abuse According to the Levels of Social Determinants in Brazil
Authors: de Araújo Monteiro Gleicy Karine Nascimento , dos Santos Renata Clemente , de Moraes Brandão Wesley Ferreira , Costa Gabriela Maria Cavalcanti , de Almeida Ana Maria , Souto Rafaella Queiroga 
Published: September 2024

ABSTRACT

Objective
The aim of this study was to analyze the factors associated with elder abuse according to the levels of social determinants.

Methodology
This is a quantitative and multicentric study, with a cross-sectional cut. It was developed in two teaching hospitals in Paraíba, Brazil, with 323 older adults, from July 2019 to February 2020. Data were collected using the Hwalek–Sengstock Elder Abuse Screening Test and Conflict Tactics Scale-1 and then analyzed using descriptive and inferential statistics.

Results
There was a significant association between risk for violence and female gender (p = 0.004), residing with grandchildren (p = 0.025), and having four or more comorbidities (p < 0.00). Physical violence was associated with income (p = 0.048). A positive correlation was observed between the number of comorbidities and the risk for violence score (p < 0.001), psychological violence (p = 0.004), and physical violence (p = 0.005). The probability of presenting a risk to violence increased by 2.08 times for women, 1.03 times for those who were illiterate, and 7.03 times for those with four or more comorbidities.

Conclusion
The social determinants of health that integrate the macrosystem, such as income and number of comorbidities, correlate with situations of violence.
The safety and efficacy of Baricitinib for systemic lupus erythematosus: a systematic review and meta-analysis of randomized controlled trials
Authors: Ramadan Alaa , Gowaily Ibrahim , Saleh Othman , Abuelazm Mohamed , Ahmad Unaiza , Elzeftawy Mohammad A. , Nathan Ezie Kengo , Abdelazeem Basel 
Published: September 2024

Background and objective:
Baricitinib is a JAK1 and JAK2 inhibitor approved for treating active rheumatoid arthritis and atopic dermatitis. Therefore, the authors aim to evaluate the safety and efficacy of once-daily oral Baricitinib 2 mg or 4 mg versus placebo in active SLE patients receiving standard care.

Methods:
The authors synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, and Cochrane Library until 20 March 2023. The study protocol was registered in PROSPERO.

Results:
Three RCTs with 1849 participants were included. The Baricitinib group had a significant SRI-4 response [RR: 1.11 with 95% CI (1.03, 1.21), P=0.008] and greater than or equal to 4-point SLEDAI-2K domain improvement [RR: 1.13 with 95% CI (1.02, 1.25), P=0.02] compared to the placebo group; however, there was no statistically significant difference between the two groups, regarding the secondary endpoints. For safety outcomes, Baricitinib was significantly associated with a higher incidence of Any serious adverse event [RR: 1.48 with 95% CI (1.07, 2.05), P=0.02].

Conclusion:
Baricitinib is associated with significant outcomes of SRI-4 response, greater than or equal to 4-point improvement SLEDAI-2K score, and Joint Indices. Regarding safety, there was no difference in the outcomes other than the serious adverse events.
Ecologically Assessed Sleep Duration and Arterial Stiffness in Healthy Men and Women
Authors: Gaffey Allison E. , Walenczyk Kristie M. , Schwartz Joseph E. , Hall Martica H. , Burg Matthew M. 
Published: September 2024

ABSTRACT

Objective
Among younger adults, to determine the associations of actigraph- and self-reported sleep duration with arterial stiffness (AS) assessed in clinic and in ecologically valid contexts, and to examine sex-specific associations.

Methods
Healthy adults (n = 282, median age = 29 years, 67% women) completed a state-of-the-art assessment of AS at rest (SphygmoCor; carotid femoral pulse wave velocity [cfPWV]; central augmentation index [cAIx]) and 7 days of actigraphy-assessed sleep with concurrent, momentary cAIx assessment for 36 hours (Oscar-2). Multivariable regressions were conducted on the full sample and sex-stratified to examine cross-sectional linear and quadratic associations of average sleep duration with resting PWV and cAIx, average cAIx while awake and asleep, and nocturnal cAIx dipping, adjusted for demographic and health covariates. Exploratory analyses included self-reported sleep duration with AS, and actigraphy and self-reported sleep duration with the ambulatory arterial stiffness index (AASI; Oscar-2).

Results
Overall and by sex, associations of average sleep duration with resting cfPWV, resting cAIx, and awake cAIx were not significant. Sleep duration showed a positive, linear association with sleep cAIx in women (95% confidence interval =1.07 to 5.86, ΔR
2 = 0.021). Among women, sleep duration was also inversely associated with cAIx dipping (95% confidence interval = −4.48 to −0.95, ΔR
2 = 0.020). Analyses with self-reported sleep duration and AASI as alternate predictors and outcomes were not significant.

Conclusions
Certain sleep duration–AS associations may be sex-specific. Assessing sleep and momentary AS in ecologically valid conditions outside the research laboratory is valuable to understand these relations. Although this investigation should be replicated, findings raise the question of whether interventions to target sleep duration also reduce AS.
Psychological Factors Modulate Quantitative Sensory Testing Measures in Fibromyalgia Patients: A Systematic Review and Meta-Regression Analysis
Authors: Carneiro Adriana Munhoz , Pacheco-Barrios Kevin , Andrade Maria Fernanda , Martinez-Magallanes Daniela , Pichardo Elly , Caumo Wolnei , Fregni Felipe 
Published: September 2024

Objective
Considering the growing evidence that psychological variables might contribute to fibromyalgia syndrome (FMS), our study aims to understand the impact of psychological factors in quantitative sensory testing (QST) in FMS patients by performing a systematic review with meta-analysis.

Methods
A systematic search was carried out in PubMed/MEDLINE, EMBASE, Web of Science, and PsycINFO databases for records up until January 2024. We included 20 studies (n = 1623, 16 randomized controlled trials, and 4 nonrandomized controlled trials) with low or moderate risk of bias included.

Results
From nonrandomized evidence, our meta-analysis found a baseline relationship between anxiety, depression, and pain catastrophizing and QST measures in FMS patients. Higher pain catastrophizing levels were associated with less efficient conditioned pain modulation. Higher anxiety and depression were associated with lower pain threshold (PT). Randomized evidence showed a statistically significant increase in PT after fibromyalgia treatments (effect size = 0.29, 95% confidence interval = 0.03–0.56). The effect was not influenced by treatment type. Moreover, we found that only anxiety levels before treatment negatively influenced the PT improvements after treatment.

Conclusion
FMS patients with higher anxiety levels at baseline showed a smaller increase in PT after the intervention. Depression factor was not significant in either changes in anxiety or depression. Baseline anxiety levels should be monitored as possible confounders of QST measurements. Understanding how psychological factors and QST are related in FMS patients is critical for improving the syndrome’s management and treatment.

Protocol Registration: CRD42023429397