bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal perfluorooctane sulfonic acid exposure during rat pregnancy causes hypersensitivity to angiotensin II and attenuation of endothelium-dependent vasodilation in the uterine arteries
Authors: Dangudubiyyam Sri Vidya , Mishra Jay S , Song Ruolin , Kumar Sathish 
Published: July 2022

AbstractEpidemiological studies show a strong association between environmental exposure to perfluorooctane sulfonic acid (PFOS) and preeclampsia and fetal growth restriction; however, the underlying mechanisms are unclear. We tested the hypothesis that gestational PFOS exposure leads to pregnancy complications via alterations in uterine vascular endothelium-independent angiotensin II-related mechanisms and endothelium-derived factors such as nitric oxide. Pregnant Sprague-Dawley rats were exposed to PFOS 0.005, 0.05, 0.5, 5, 10, and 50 μg/mL through drinking water from gestational day 4 to 20, and dams with PFOS 50 μg/mL were used to assess mechanisms. PFOS exposure dose dependently increased maternal blood pressure but decreased fetal weights. Uterine artery blood flow was lower and resistance index was higher in the PFOS dams. In PFOS dams, uterine artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. Plasma angiotensin II levels were not significantly different between control and PFOS dams; however, PFOS exposure significantly increased Angiotensin II type 1 receptor (AGTR1) and decreased AGTR2 protein levels in uterine arteries. Endothelium-dependent relaxation response to acetylcholine was significantly reduced with decreased endothelial nitric oxide synthase expression in the uterine arteries of PFOS dams. Left ventricular hypertrophy and fibrosis were observed, along with increased ejection fraction and fractional shortening in PFOS dams. These results suggest that elevated maternal PFOS levels decrease uterine blood flow and increase vascular resistance via heightened angiotensin II-mediated vasoconstriction and impaired endothelium-dependent vasodilation, which provides a molecular mechanism linking elevated maternal PFOS levels with gestational hypertension and fetal growth restriction.
Temporal variation in DNA methylation during gonadal development in a reptile with temperature-dependent sex determination
Authors: Liu Fang , Xu Haoyang , Ni Wei , Wang Yakun , Hong Xiaoyou , Li Wei , Yu Lingyun , Chen Chen , Wei Chengqing , Liu Xiaoli , Zhu Xinping 
Published: July 2022

AbstractDNA methylation plays a significant role in transducing external environmental signals to a cellular response in reptiles; however, whether the methylation patterns are conserved across species remains unclear. Here, we examined the genome-wide DNA methylation differentiation between male and female hatchling gonads of the temperature-dependent sex determination (TSD) Mauremys mutica (M. mutica) using methylation-dependent restriction-site associated DNA sequencing (MethylRAD-seq) to test differentially methylated genes underlying sexual development. Several categories, including heat-shock genes (HSP90A, HSP30C), histone- (KDM8) and ubiquitin-related genes (TRIM39), kinases (WNK3), and gonad differentiation or gonadal-development-related genes (HSD17B8, HSD17B12), were identified as candidates for future study. Additionally, we identified several regulatory pathways potentially mediating TSD thermosensitivity such as the GnRH signaling pathway and calcium signaling pathway. These findings provide evidence that sexually dimorphic DNA methylation may be associated with sex determination or sex differentiation in TSD M. mutica.
A Direct Posterior Approach for Subtalar Distraction Arthrodesis
Authors: Lindsey Benjamin B. , Bettin Clayton C. 
Published: July 2022

Summary:
Because of soft tissue constraints, definitive management of hindfoot trauma occasionally requires a direct posterior approach via a coronal split of the Achilles tendon. This article and the accompanying video demonstrate a direct posterior approach for subtalar distraction arthrodesis and review treatment decisions involved with management of these complex cases.
Delayed Distraction Bone Block Arthrodesis for a Sanders IV Calcaneus Fracture Nonunion Using Tricortical Iliac Crest Allograft and Reamer/Irrigator/Aspirator Femoral Autograft
Authors: Solasz Sara Jo , Ganta Abhishek , Konda Sanjit R. 
Published: July 2022

Summary:
We present the surgical technique for arthrodesis of the subtalar and calcaneocuboid joints of a Sanders type IV calcaneal fracture nonunion via a distraction bone block arthrodesis technique with tricortical iliac crest allograft combined with reamer/irrigator/aspirator autograft from the patient's femur. A lateral extensile approach to the calcaneus was used for the exposure, which allowed the surgeon to follow the stepwise complex surgical plan outlined here. Calcaneal nonunions are difficult to treat, but good outcomes can be achieved if proper technique with bone grafting is used.
The path to personalized treatment in advanced and metastatic biliary tract cancers: a review of new targeted therapies and immunotherapy
Authors: Demols Anne , Bucalau Ana-Maria , Mans Laura 
Published: July 2022

Purpose of review
To summarize targeted therapies and immunotherapy as treatment for advanced/metastatic biliary tract cancers and discuss ongoing clinical trials.

Recent findings
For the first time since gemcitabine–cisplatin was set as the standard of care in first-line advanced/metastatic biliary tract cancers in the ABC-02 trial, the combination of durvalumab and gemcitabine–cisplatin has demonstrated a statistically significant improvement of median overall survival in the TOPAZ-1 phase 3 trial. The ABC-06 trial showed a significant increase of median overall survival for FOLFOX and active symptom control compared with active symptom control alone in second-line regardless of molecular and genetic alterations. However, faced with a heterogeneous cancer, patient prognosis remains poor, leaving room for new, personalized, treatment options such as targeted therapies. Efficacy of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors has been demonstrated in different phase 2 trials for previously treated intrahepatic cholangiocarcinomas harboring FGFR2 fusions. Ivosidenib increases significantly median progression-free survival in previously treated cholangiocarcinomas with isocitrate dehydrogenase-1 (IDH-1) mutation. Other targeted therapies are tested for tumors with HER2 amplifications/mutations, BRAFV600E mutations or KRASG12C mutations.

Summary
In this review, we aim to follow the changes in the treatment of these tumors, moving from very few chemotherapy options to immunotherapy and targeted therapies in the context of molecular selection of biliary tract cancers subtypes.
Evolving nonvasodilator treatment options for pulmonary arterial hypertension
Authors: Medrek Sarah , Melendres-Groves Lana 
Published: July 2022

Purpose of review
With the establishment of vasodilator therapy as a mainstay of treatment for pulmonary arterial hypertension (PAH), new therapeutic approaches are needed to prevent the development of the vasculopathy associated with this disease. Many studies are currently underway to investigate nonvasodilator treatment options.

Recent findings
Modulation of bone morphogenic protein receptor type 2 (BMPR2) signaling with sotatercept showed promising results in phase 2 studies. Rituximab, an anti-CD20 monoclonal antibody, showed some signal for beneficial effect in patients with scleroderma-associated PAH. Studies evaluating agents including tocilizumab, selonsertib, bardoxolone, 10-nitro-9(E)-enoic acid (CXA-10) and intravenous iron have not shown acceptable efficacy in treating PAH.

Summary
Pharmacologic approaches for the treatment of PAH include altering of transforming growth factor β/BMPR2 signaling, proliferation via growth factors, immune response, oxidative stress, estrogen signaling, metabolism, and neurohormonal modulation. Other treatment modalities including pulmonary artery nerve denervation, stem cell therapy, and inter-atrial shunt formation are also being explored.
Update in approaches to pulmonary hypertension because of left heart disease
Authors: Kennedy Jamie L.W. , Mihalek Andrew D. 
Published: July 2022

Purpose of review
Left heart disease is the most common cause of pulmonary hypertension. This review summarizes the current care of patients with pulmonary hypertension caused by left heart disease (PH-LHD) and discusses recent and active clinical trials in this patient population.

Recent findings
The primary focus of interventions aimed at treating PH-LHD address the treatment of left heart disease. Significant advancements in the treatment of heart failure with preserved ejection fraction (HFpEF), a frequent cause of PH-LHD, are supported in the current literature. Patients with residual pulmonary hypertension despite optimal treatment of left heart disease have poor outcomes. Yet, interventions targeting the pulmonary vasculature in PH-LHD patients have not demonstrated significant benefits in studies to date. Current work focuses on differentiating isolated postcapillary pulmonary hypertension (IpcPH) from combined precapillary and postcapillary pulmonary hypertension (CpcPH) in a clinically consistent manner. It is hopeful that thorough phenotyping of PH-LHD patients will translate into effective treatment strategies addressing pulmonary vascular disease.

Summary
Referral to centers of excellence, considerations for enrollment in clinical trials, and evaluation for transplant is recommended for patients with residual pulmonary hypertension despite optimal treatment of left heart disease, particularly those with CpcPH.
Environmental and occupational exposures in interstitial lung disease
Authors: Lee Cathryn T. , Feary Johanna , Johannson Kerri A. 
Published: July 2022

Purpose of review
We highlight recent advances in the understanding of how environmental and occupational exposures increase the risk of developing interstitial lung disease (ILD), and how to evaluate a patient for potential exposures.

Recent findings
A review of emerging literature suggests that environmental and occupational exposures can be directly causal, as in the case of the pneumoconioses and smoking-related ILDs, or one of many contributors to disease, as in the case of idiopathic pulmonary fibrosis (IPF). Regardless of the level of association, exposures are clearly prevalent across all ILD subtypes studied.

Summary
Inhalational exposures are increasingly recognized as an important component in the development of ILDs, and novel exposure-disease associations continue to be discovered. These exposures represent potential opportunities for further understanding the pathobiology of disease and for the prevention of these often progressive and debilitating disorders. Prospective, comprehensive data collection regarding occupational and environmental exposures are needed in ILD patients to fully elucidate specific antigens and their relationships to disease incidence and outcomes. Systematically collected exposure information will also inform potential interventions to remediate exposures and thus mitigate the course of frequently progressive and fatal diseases.
Sexual violence experiences among adolescent and young adult males: a review to empower healthcare providers
Authors: Blackburn Katelin , Grubb Laura K. , Vargas Gabriela 
Published: July 2022

Purpose of review
Despite 3–17% of adolescent and young adult males (AYAMs) experiencing sexual violence, there is a paucity of information regarding their sexual violence experiences leaving them vulnerable to dangerous and detrimental sequelae.

Recent findings
There is underreporting and under-discussion of AYAMs’ experiences of sexual violence, with disclosure influenced by societal perceptions of male sexuality, shame, and fear of discrimination. AYAMs experience sexual violence from individuals known to them, with many experiencing physical violence, threats, coercion, and electronic harassment. Intersectionality, previous traumas, inappropriate childhood exposures to sexually explicit situations, select online media consumption, and adverse childhood experiences (ACEs) increase the risk of sexual violence. AYAMs who experience sexual violence are at increased risk of re-victimization, perpetrating sexual violence, experiencing bodily harm, contracting sexually transmitted infections (STIs), and experiencing internalizing and externalizing symptoms, which can lead to significant morbidity and mortality. Research on male-specific protective and resilience factors is scarce and represents an ongoing need.

Summary
After reviewing AYAMs’ experiences of sexual violence, including risk and protective factors, media influences, detrimental sequelae, and resilience factors, we provide a screening framework to empower the healthcare provider (HCP) to champion tailored prevention, screening, intervention, and advocacy efforts to support AYAMs.
Monitoring of paediatric type 1 diabetes
Authors: Marks Brynn E. , Wolfsdorf Joseph I. 
Published: July 2022

Purpose of review
This article reviews recent developments in methods used to monitor paediatric type 1 diabetes (T1D), including an examination of the role of glycated haemoglobin (haemoglobin A1c) and its limitations for long-term assessment of glycaemia in individual patients, self-monitoring of blood glucose, continuous glucose monitoring (CGM) systems and ketone monitoring.

Recent findings
Monitoring of glycemia and ketones, when indicated, is a cornerstone of paediatric T1D management and is essential to optimize glycaemic control. Ongoing technological advancements have led to rapid changes and considerable improvement in the methods used to monitor glucose concentrations in people with T1D. As a result of recent innovations that have enhanced accuracy and usability, CGM is now considered the optimal method for monitoring glucose concentrations and should be introduced soon after diagnosis of T1D.

Summary
Patients/families and healthcare providers must receive comprehensive education and proper training in the use of CGM and interpretation of the vast amounts of data. Future challenges include ensuring equal access to and optimizing clinical use of CGM to further improve T1D care and outcomes.
Metabolic dysfunction-associated fatty liver disease in obese youth with insulin resistance and type 2 diabetes
Authors: Mastromauro Concetta , Polidori Nella , Giannini Cosimo 
Published: July 2022

Purpose of review
The aim of this review is to present the new definition of the disease, defining the epidemiology, risk factors with a particular attention to the role of insulin resistance (IR) and to define the main treatments explored.

Recent findings
Nonalcoholic fatty liver disease (NAFLD) was previously considered a primary liver disease, but it would be more correct to consider it a component of the metabolic syndrome (MetS) in which IR might play a key role. Based on these findings, it has been recently proposed to modify the classic term of NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) that better reflects the pathophysiology of this complex disease.

Summary
Currently, no treatments approved in childhood are available, thus the only recommended approach is the prevention and correction of the known risk factors, and particularly of IR. However, further studies are needed to better clarify the pathogenetic mechanisms of NAFLD in order to establish more tailored therapies.
Advancements and future directions in the teamwork, targets, technology, and tight control—the 4T study: improving clinical outcomes in newly diagnosed pediatric type 1 diabetes
Authors: Zaharieva Dessi P. , Bishop Franziska K. , Maahs David M. 
Published: July 2022

Purpose of review
The benefits of intensive diabetes management have been established by the Diabetes Control and Complications Trial. However, challenges with optimizing glycemic management in youth with type 1 diabetes (T1D) remain across pediatric clinics in the United States. This article will review our Teamwork, Targets, Technology, and Tight Control (4T) study that implements emerging diabetes technology into clinical practice with a team approach to sustain tight glycemic control from the onset of T1D and beyond to optimize clinical outcomes.

Recent findings
During the 4T Pilot study and study 1, our team-based approach to intensive target setting, education, and remote data review has led to significant improvements in hemoglobin A1c throughout the first year of T1D diagnosis in youth, as well as family and provider satisfaction.

Summary
The next steps include refinement of the current 4T study 1, developing a business case, and broader implementation of the 4T study. In study 2, we are including a more pragmatic cadence of remote data review and disseminating exercise education and activity tracking to both English- and Spanish-speaking families. The overall goal is to create and implement a translatable program that can facilitate better outcomes for pediatric clinics across the USA.
Inflammatory Myofibroblastic Tumor of the Placenta With Subsequent Successful Pregnancy and Benign Hysterectomy: A Case Report With 59-Month Follow-up
Authors: Schwartz Cooper , Gundogan Fusun , Singh Kamaljeet , Schoolmeester J. Kenneth , Banet Natalie 
Published: July 2022

Inflammatory myofibroblastic tumors (IMT) are rare neoplasms of intermediate malignant potential which have been described in the gynecologic tract, predominantly in the myometrial wall, but also in association with the placenta. Like those in other organs, IMT of the placenta are characterized by molecular abnormalities, most commonly anaplastic lymphoma kinase gene rearrangements, and are often positive for anaplastic lymphoma kinase immunohistochemically. Although the clinical behavior of placental IMTs has so far proven benign, a successful intrauterine pregnancy with subsequent negative hysterectomy following a placental IMT has not been documented. Herein is presented a case of a 27-yr-old noted to have a 2 cm IMT of the extraplacental membranes at delivery, after which the patient received no further treatment. After 56 mo, the patient experienced a subsequent normal delivery in a pregnancy complicated by gestational diabetes. No longer desiring fertility, the patient elected to have a hysterectomy to confirm the absence of IMT at 59 mo and the uterus was unremarkable. This case provides insight into possible outcomes for patients with a rare tumor who may desire future fertility and may otherwise be advised to undergo hysterectomy in the setting of an unclear clinical course.
An Unusual Benign Uterine Stromal Spindle Cell Tumor Harboring JAZF1::BCORL1
Authors: Rodriguez Pena Maria D.C. , Mubeen Aysha , Harada Shuko , Prieto Granada Carlos N. 
Published: July 2022

Uterine mesenchymal lesions demonstrate various underlying genomic alterations involving MED12, JAZF1, YWHAE, BCOR, and ALK genes, among others. Recent publications describe a subset of high-grade endometrial stromal sarcoma lesions harboring BCORL1 gene aberrations including JAZF1::BCORL1. Herein, we present an unusual benign endomyometrial spindle cell lesion that defies classificatory efforts by demonstrating mixed histomorphologic and immunohistochemical features of endometrial stromal nodule, leiomyoma, and uterine inflammatory myofibroblastic tumor while harboring a JAZF1::BCORL1. The lesion was found in a 43-yr-old woman with pelvic pain and heavy menses as a 5.5 cm well-circumscribed ulcerated mass fungating from the cervical os. Microscopic examination revealed a polypoid, well-circumscribed, moderately cellular endomyometrial tumor composed by bland spindle cells haphazardly disposed within a slightly edematous stroma enriched by a delicate network of thin-walled vessels that were occasionally encircled by the tumor cells. Unequivocal evidence of tongue-like growth pattern into the myometrium, tumor-type necrosis or increased mitotic activity was not identified after sampling the entire lesion. The lesion showed patchy immunoreactivity for both smooth muscle actin-alpha and desmin while negative for CD10, HMB45, ALK (D5F3), and BCOR. An Archer FusionPlex panel assay demonstrated a fusion involving both exons 4 from the JAZF1 and BCORL1 genes. The JAZF1::BCORL1 has not, to the best of our knowledge, been previously reported in a benign/low-grade mesenchymal uterine lesion.
The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy
Authors: Lewis-Lloyd Christopher A. , Humes David J. , West Joe , Peacock Oliver , Crooks Colin J. 
Published: July 2022

Objective:
To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates.

Summary Background Data:
Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not.

Methods:
English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type and surgical indication, absolute incidence rates (IRs) per 1000 person-years and adjusted incidence rate ratios (aIRRs) for postdischarge VTE were calculated for the first 4 weeks following resection and postdischarge VTE IRs for each postoperative week to 12 weeks postoperative.

Results:
Of 104,744 patients, 663 (0.63%) developed postdischarge VTE within 12 weeks after colectomy. Postdischarge VTE IRs per 1000 person-years for the first 4 weeks postoperative were low following elective resections [benign: 20.66, 95% confidence interval (CI): 13.73–31.08; malignant: 28.95, 95% CI: 23.09–36.31] and higher following emergency resections (benign: 47.31, 95% CI: 34.43–65.02; malignant: 107.18, 95% CI: 78.62–146.12). Compared with elective malignant resections, there was no difference in postdischarge VTE risk within 4 weeks following elective benign colectomy (aIRR=0.92, 95% CI: 0.56–1.50). However, postdischarge VTE risks within 4 weeks following emergency resections were significantly greater for benign (aIRR=1.89, 95% CI: 1.22–2.94) and malignant (aIRR=3.13, 95% CI: 2.06–4.76) indications compared with elective malignant colectomy.

Conclusions:
Postdischarge VTE risk within 4 weeks of colectomy is ∼2-fold greater following emergency benign compared with elective malignant resections, suggesting emergency benign colectomy patients may benefit from extended VTE prophylaxis.