bluuebunny/crossref_metadata_2025_split huggingface dataset:
RBBP4 is an epigenetic barrier for the induced transition of pluripotent stem cells into totipotent 2C-like cells
Authors: Ping Wangfang , Sheng Yingliang , Hu Gongcheng , Zhong Hongxin , Li Yaoyi , Liu YanJiang , Luo Wei , Yan Chenghong , Wen Yulin , Wang Xinxiu , Li Qing , Guo Rong , Zhang Jie , Liu Ake , Pan Guangjin , Yao Hongjie 
Published: April 2023

Abstract
Cellular totipotency is critical for whole-organism generation, yet how totipotency is established remains poorly illustrated. Abundant transposable elements (TEs) are activated in totipotent cells, which is critical for embryonic totipotency. Here, we show that the histone chaperone RBBP4, but not its homolog RBBP7, is indispensable for maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms mESCs to the totipotent 2C-like cells. Also, loss of RBBP4 enhances transition from mESCs to trophoblast cells. Mechanistically, RBBP4 binds to the endogenous retroviruses (ERVs) and functions as an upstream regulator by recruiting G9a to deposit H3K9me2 on ERVL elements, and recruiting KAP1 to deposit H3K9me3 on ERV1/ERVK elements, respectively. Moreover, RBBP4 facilitates the maintenance of nucleosome occupancy at the ERVK and ERVL sites within heterochromatin regions through the chromatin remodeler CHD4. RBBP4 depletion leads to the loss of the heterochromatin marks and activation of TEs and 2C genes. Together, our findings illustrate that RBBP4 is required for heterochromatin assembly and is a critical barrier for inducing cell fate transition from pluripotency to totipotency.
Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation
Authors: van der Veer Bernard K , Chen Lehua , Custers Colin , Athanasouli Paraskevi , Schroiff Mariana , Cornelis Riet , Chui Jonathan Sai-Hong , Finnell Richard H , Lluis Frederic , Koh Kian Peng 
Published: April 2023

Abstract
Gastrulation begins when the epiblast forms the primitive streak or becomes definitive ectoderm. During this lineage bifurcation, the DNA dioxygenase TET1 has bipartite functions in transcriptional activation and repression, but the mechanisms remain unclear. By converting mouse embryonic stem cells (ESCs) into neuroprogenitors, we defined how Tet1–/– cells switch from neuroectoderm fate to form mesoderm and endoderm. We identified the Wnt repressor Tcf7l1 as a TET1 target that suppresses Wnt/β-catenin and Nodal signalling. ESCs expressing catalytic dead TET1 retain neural potential but activate Nodal and subsequently Wnt/β-catenin pathways to generate also mesoderm and endoderm. At CpG-poor distal enhancers, TET1 maintains accessible chromatin at neuroectodermal loci independently of DNA demethylation. At CpG-rich promoters, DNA demethylation by TET1 affects the expression of bivalent genes. In ESCs, a non-catalytic TET1 cooperation with Polycomb represses primitive streak genes; post-lineage priming, the interaction becomes antagonistic at neuronal genes, when TET1’s catalytic activity is further involved by repressing Wnt signalling. The convergence of repressive DNA and histone methylation does not inhibit neural induction in Tet1-deficient cells, but some DNA hypermethylated loci persist at genes with brain-specific functions. Our results reveal versatile switching of non-catalytic and catalytic TET1 activities based on genomic context, lineage and developmental stage.
Prediction of intradialytic hypotension using pre-dialysis features—a deep learning–based artificial intelligence model
Authors: Lee Hanbi , Moon Sung Joon , Kim Sung Woo , Min Ji Won , Park Hoon Suk , Yoon Hye Eun , Kim Young Soo , Kim Hyung Wook , Yang Chul Woo , Chung Sungjin , Koh Eun Sil , Chung Byung Ha 
Published: April 2023

ABSTRACT

Background
Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning–based artificial intelligence (AI) model to predict IDH using pre-dialysis features.

Methods
Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost).

Results
IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session.

Conclusions
Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.
Unexpected Increase in Invasive Group A Streptococcal Infections in Children After Respiratory Viruses Outbreak in France: A 15-Year Time-Series Analysis
Authors: Lassoued Yannis , Assad Zein , Ouldali Naim , Caseris Marion , Mariani Patricia , Birgy Andre , Bonacorsi Stephane , Bidet Philippe , Faye Albert 
Published: April 2023

Abstract
In a 15-year pediatric time-series analysis, we showed a rise of invasive Group A streptococcal (iGAS) infections since October 2022, mainly involving pleural empyema, simultaneously to a respiratory virus outbreak. Physicians should be aware of this increased risk of pediatric iGAS infections, especially in settings with intense respiratory viruses' circulation.
Security Design in Non-Exclusive Markets with Asymmetric Information
Authors: Asriyan Vladimir , Vanasco Victoria 
Published: April 2023

Abstract
We study the problem of a seller (e.g. a bank) who is privately informed about the quality of her asset and wants to exploit gains from trade with uninformed buyers (e.g. investors) by issuing securities backed by her asset cash flows. In our setting, buyers post menus of contracts to screen the seller, but the seller cannot commit to trade with only one buyer, i.e. markets are non-exclusive. We show that non-exclusive markets behave very differently from exclusive ones: (1) separating contracts are never part of equilibrium; (2) mispricing of claims faced by the seller is always greater than in exclusive markets; (3) there is always a semi-pooling equilibrium where all sellers issue the same debt contract priced at average-valuation, and sellers of low-quality assets issue remaining cash flows at low-valuation; (4) market liquidity can be higher or lower than in exclusive markets, but (5) the average quality of originated assets is always lower. Our model’s predictions are consistent with empirical evidence on the issuance and pricing of mortgage-backed securities, and we use the theory to evaluate recent reforms aimed at enhancing transparency and exclusivity in markets.
Treatment decisions in axial spondyloarthritis daily clinical practice are more than treat-to-target
Authors: Bolt Janne W , Aalbers Caroline J , Walet Laura , van Mens Leonieke J J , van Denderen Christiaan , van der Horst-Bruinsma Irene , van Baarsen Lisa G M , Landewé Robert , van de Sande Marleen G H 
Published: April 2023

Abstract

Objective
‘Treat-to-target principles’ are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are unknown. Therefore, we studied the presence of residual disease activity according physician’s opinion, patient’s opinion and composite indices and compared them to the subsequent treatment decisions.

Methods
This cross-sectional multicentre study included 249 patients with a clinical diagnosis of axSpA ≥6 months. Remission and low disease activity according to the BASDAI (&lt;1.9 and &lt;3.5, respectively) and physician’s and patient’s opinion were assessed. Questionnaires included patient-reported outcomes and patients and physicians completed questions regarding treatment decisions.

Results
A total of 115/249 (46%) patients were in remission according to the physician and 37% (n = 43) of these patients reached remission according to the BASDAI. In 51/83 (60%) of the patients with residual disease activity according to the physician and a BASDAI &gt;3.5 the treatment was left unchanged, either because of low disease activity as rated by the physician [n = 15 (29%)] or because of a combination of low disease activity with non-inflammatory complaints or comorbidities [n = 11 (25%)]. Retrospective treat-to-target evaluations showed that treatments were most frequently intensified in patients with arthritis or inflammatory back pain and less often in patients with other (non-inflammatory) musculoskeletal comorbidities.

Conclusion
This study shows that physicians do not always strictly apply treat-to-target in case of residual disease activity in axSpA. Usually, they accept low disease activity as satisfactory.
Chronic exposure to a mixture of phthalates shifts the white and brown adipose tissue phenotypes in female mice
Authors: Graceli Jones B , da Costa Charles S , Laws Mary J , Deviney Ashley R K , Meling Daryl , Flaws Jodi A 
Published: April 2023

Abstract
Phthalates are endocrine-disrupting chemicals used in consumer products. Although phthalates are obesogens and affect metabolic function, it is unknown if chronic exposure for 6 months to a phthalate mixture alters adipose tissue phenotype in female mice. After vehicle or mixture exposure, white adipose tissue and brown adipose tissue (WAT and BAT) were analyzed for expression of adipogenesis, proliferation, angiogenesis, apoptosis, oxidative stress, inflammation, and collagen deposition markers. The mixture altered WAT morphology, leading to an increase in hyperplasia, blood vessel number, and expression of BAT markers (Adipoq and Fgf2) in WAT. The mixture increased the expression of the inflammatory markers, Il1β, Ccl2, and Ccl5, in WAT. The mixture also increased expression of the proapoptotic (Bax and Bcl2) and antiapoptotic (Bcl2l10) factors in WAT. The mixture increased expression of the antioxidant Gpx1 in WAT. The mixture changed BAT morphology by increasing adipocyte diameter, whitening area, and blood vessel number and decreased expression of the thermogenic markers Ucp1, Pgargc1a, and Adrb3. Furthermore, the mixture increased the expression of adipogenic markers Plin1 and Cebpa, increased mast cell number, and increased Il1β expression in BAT. The mixture also increased expression of the antioxidant markers Gpx and Nrf2 and the apoptotic marker Casp2 in BAT. Collectively, these data indicate that chronic exposure to a phthalate mixture alters WAT and BAT lipid metabolism phenotypes in female mice, leading to an apparent shift in their normal morphology. Following long-term exposure to a phthalate mixture, WAT presented BAT-like features and BAT presented WAT-like features.
Evaluation of Biological Control Agents for the Protection of Almond Pruning Wounds Against Infection by Fungal Canker Pathogens
Authors: Travadon Renaud , Lawrence Daniel P. , Li Sampson , Trouillas Florent P. 
Published: April 2023

Fungal canker pathogens of almond initiate infection in trees primarily through pruning wounds. Biological control agents (BCAs) have the potential to provide long-term protection of pruning wounds by colonizing the wound surfaces and underlying tissues. Laboratory and field tests were performed to assess the efficacy of various commercial and experimental BCAs as wound protectants against almond canker pathogens. Four Trichoderma-based BCAs were evaluated using detached almond stems in the laboratory against the canker pathogens Cytospora plurivora, Eutypa lata, Neofusicoccum parvum, and Neoscytalidium dimidiatum. Results indicated that Trichoderma atroviride SC1 and T. paratroviride RTFT014 significantly reduced infections by all four pathogens. The abilities of these four BCAs to protect almond pruning wounds against E. lata and N. parvum were further evaluated in field trials using two almond cultivars and during two consecutive years. Both T. atroviride SC1 and T. paratroviride RTFT014 protected almond pruning wounds against E. lata and N. parvum as efficiently as thiophanate-methyl, the recommended fungicide for treatment of almond pruning wounds. Comparisons of different application timings of BCA in relation to pathogen inoculation revealed a significant improvement in wound protection when inoculations were conducted 7 days versus 24 h post-BCA application for N. parvum, but not for E. lata. T. atroviride SC1 and T. paratroviride RTFT014 are promising candidates for the preventive protection of almond pruning wounds and for inclusion in integrated pest management programs and organic almond production systems.
Systemic Progestins and Progestin-Releasing Intrauterine Device Therapy for Premenopausal Patients With Endometrial Intraepithelial Neoplasia
Authors: Suzuki Yukio , Chen Ling , Hou June Y. , St. Clair Caryn M. , Khoury-Collado Fady , de Meritens Alexandre Buckley , Matsuo Koji , Melamed Alexander , Hershman Dawn L. , Wright Jason D. 
Published: April 2023

OBJECTIVE:
To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia.

METHODS:
The MarketScan Database was used to identify patients aged 18–50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed.

RESULTS:
A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 (P=.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 (P<.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8–39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5–30.0%) of those treated with progestin-releasing IUD (P<.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6–13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1–16.6%) of those treated with progestin-releasing IUD (P=.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD.

CONCLUSION:
The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy.
Diagnosis of Pregnancy Complications Using Blind Ultrasound Sweeps Performed by Individuals Without Prior Formal Ultrasound Training
Authors: Toscano Marika , Marini Thomas , Lennon Clare , Erlick Mariah , Silva Hannah , Crofton Kathryn , Serratelli William , Rana Neel , Dozier Ann M. , Castaneda Benjamin , Baran Timothy M. , Drennan Kathryn 
Published: April 2023

OBJECTIVE:
To estimate the diagnostic accuracy of blind ultrasound sweeps performed with a low-cost, portable ultrasound system by individuals with no prior formal ultrasound training to diagnose common pregnancy complications.

METHODS:
This is a single-center, prospective cohort study conducted from October 2020 to January 2022 among people with second- and third-trimester pregnancies. Nonspecialists with no prior formal ultrasound training underwent a brief training on a simple eight-step approach to performing a limited obstetric ultrasound examination that uses blind sweeps of a portable ultrasound probe based on external body landmarks. The sweeps were interpreted by five blinded maternal–fetal medicine subspecialists. Sensitivity, specificity, and positive and negative predictive values for blinded ultrasound sweep identification of pregnancy complications (fetal malpresentation, multiple gestations, placenta previa, and abnormal amniotic fluid volume) were compared with a reference standard ultrasonogram as the primary analysis. Kappa for agreement was also assessed.

RESULTS:
Trainees performed 194 blinded ultrasound examinations on 168 unique pregnant people (248 fetuses) at a mean of 28±5.85 weeks of gestation for a total of 1,552 blinded sweep cine clips. There were 49 ultrasonograms with normal results (control group) and 145 ultrasonograms with abnormal results with known pregnancy complications. In this cohort, the sensitivity for detecting a prespecified pregnancy complication was 91.7% (95% CI 87.2–96.2%) overall, with the highest detection rate for multiple gestations (100%, 95% CI 100–100%) and noncephalic presentation (91.8%, 95% CI 86.4–97.3%). There was high negative predictive value for placenta previa (96.1%, 95% CI 93.5–98.8%) and abnormal amniotic fluid volume (89.5%, 95% CI 85.3–93.6%). There was also substantial to perfect mean agreement for these same outcomes (range 87–99.6% agreement, Cohen κ range 0.59–0.91, P<.001 for all).

CONCLUSION:
Blind ultrasound sweeps of the gravid abdomen guided by an eight-step protocol using only external anatomic landmarks and performed by previously untrained operators with a low-cost, portable, battery-powered device had excellent sensitivity and specificity for high-risk pregnancy complications such as malpresentation, placenta previa, multiple gestations, and abnormal amniotic fluid volume, similar to results of a diagnostic ultrasound examination using a trained ultrasonographer and standard-of-care ultrasound machine. This approach has the potential to improve access to obstetric ultrasonography globally.
Changing Practices in the Surgical Management of Adnexal Torsion
Authors: Ryles Hannah T. , Hong Christopher X. , Andy Uduak U. , Farrow Monique R. 
Published: April 2023

OBJECTIVE:
To evaluate trends in the surgical management of adnexal torsion and to evaluate these trends with respect to the updated American College of Obstetricians and Gynecologists (ACOG) guidelines.

METHODS:
We performed a retrospective cohort study using the National Surgical Quality Improvement Program database. Women who underwent surgery for adnexal torsion between 2008 and 2020 were identified on the basis of International Classification of Diseases codes. Surgeries were grouped as either ovarian conservation or oophorectomy with the use of Current Procedural Terminology codes. Patients were also grouped into year cohorts with respect to the publication of the updated ACOG guidelines (2008–2016 compared with 2017–2020). Multivariable logistic regression, weighted by cases per year, was used to assess differences between groups.

RESULTS:
Of the 1,791 surgeries performed for adnexal torsion, 542 (30.3%) involved ovarian conservation and 1,249 (69.7%) involved oophorectomy. Older age, higher body mass index, higher American Society of Anesthesiologists classification, anemia, and diagnosis of hypertension were significantly associated with oophorectomy. There was no significant difference in the proportion of oophorectomies performed before 2017 compared with after 2017 (71.9% vs 69.1%, odds ratio [OR] 0.89, 95% CI 0.69–1.16; adjusted OR 0.94, 95% CI 0.71–1.25). A significant decrease in proportion of oophorectomies performed each year was identified over the entire study period (−1.6%/y, P=.02, 95% CI −3.0% to −0.22%); however, the rates did not differ before and after 2017 (interaction P=.16).

CONCLUSION:
There was a modest decrease in the proportion of oophorectomies for adnexal torsion performed per year over the study period. However, oophorectomy is still commonly performed for adnexal torsion, despite updated guidelines from ACOG recommending ovarian conservation.
Hyperthermic Intraperitoneal Chemotherapy and Interval Debulking Surgery in Conjunction With Elective Cesarean Delivery
Authors: Tremblay Elizabeth , Pina Annick , Avon-Després Catherine , Mercier Frédéric , Cormier Béatrice 
Published: April 2023

BACKGROUND:
Ovarian cancer is rare during pregnancy. For patients beyond 20 weeks of gestation who choose to continue the pregnancy, neoadjuvant chemotherapy may be initiated, followed by interval debulking surgery. Hyperthermic intraperitoneal chemotherapy (HIPEC) may be used with interval debulking surgery for stage III epithelial ovarian cancer, but data are lacking on its administration in the peripartum period.

CASE:
We illustrate the case of a 40-year-old patient diagnosed with stage III epithelial ovarian cancer at 27 weeks of gestation who underwent neoadjuvant chemotherapy followed by cesarean delivery at term along with interval debulking surgery and HIPEC. The intervention was well tolerated and resulted in the birth of a healthy neonate. The postoperative period was unremarkable, and the patient is disease-free after 22-months of follow-up.

CONCLUSION:
We demonstrate the feasibility of peripartum HIPEC. Optimal oncologic care should not be jeopardized by the peripartum state of an otherwise healthy patient.
Levonorgestrel 52-mg Intrauterine Device Efficacy and Safety After More Than 8 Years of Use
Authors: Chen Beatrice A. , Kimble Thomas , Harris Lisa H. , Kerns Jennifer L. , Olariu Andrea I. , Creinin Mitchell D. 
Published: April 2023

The levonorgestrel 52-mg intrauterine device (IUD) is approved for contraception for 8 years. We evaluated outcomes for 339 phase 3 study participants aged 16–35 years at enrollment who used the IUD for more than 8 years. At study closure, 83 and 77 participants reached 9 and 10 years, respectively. No pregnancies occurred during years 9 and 10. Expulsion occurred in one (0.3%) participant, a partial expulsion during year 10. No perforations, pelvic infections, or IUD-related serious adverse events were noted. Absence of bleeding or spotting was reported by 33 (39.8%) and 28 (36.4%) participants at years 9 and 10, respectively. The levonorgestrel 52-mg IUD demonstrates continued efficacy and safety in a small population of users during years 9 and 10 of use.

FUNDING SOURCE:
Medicines360. The Sponsor, Medicines360, designed the study and oversaw its conduct, including funding the trial and providing all study product free of charge to participants.

CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov, NCT00995150.