bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo neutron crystallography demonstrates influence of RNA 2′-OH orientation on conformation, sugar pucker and water structure
Authors: Harp Joel M , Lybrand Terry P , Pallan Pradeep S , Coates Leighton , Sullivan Brendan , Egli Martin 
Published: July 2022

Abstract
The ribose 2′-hydroxyl is the key chemical difference between RNA and DNA and primary source of their divergent structural and functional characteristics. Macromolecular X-ray diffraction experiments typically do not reveal the positions of hydrogen atoms. Thus, standard crystallography cannot determine 2′-OH orientation (H2′-C2′-O2′-HO2′ torsion angle) and its potential roles in sculpting the RNA backbone and the expansive fold space. Here, we report the first neutron crystal structure of an RNA, the Escherichia coli rRNA Sarcin-Ricin Loop (SRL). 2′-OD orientations were established for all 27 residues and revealed O-D bonds pointing toward backbone (O3′, 13 observations), nucleobase (11) or sugar (3). Most riboses in the SRL stem region show a 2′-OD backbone-orientation. GAGA-tetraloop riboses display a 2′-OD base-orientation. An atypical C2′-endo sugar pucker is strictly correlated with a 2′-OD sugar-orientation. Neutrons reveal the strong preference of the 2′-OH to donate in H-bonds and that 2′-OH orientation affects both backbone geometry and ribose pucker. We discuss 2′-OH and water molecule orientations in the SRL neutron structure and compare with results from a solution phase 10 μs MD simulation. We demonstrate that joint cryo-neutron/X-ray crystallography offers an all-in-one approach to determine the complete structural properties of RNA, i.e. geometry, conformation, protonation state and hydration structure.
In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing
Authors: Karlowicz Anna , Dubiel Andrzej B , Czerwinska Jolanta , Bledea Adela , Purzycki Piotr , Grzelewska Marta , McAuley Ryan J , Szczesny Roman J , Brzuska Gabriela , Krol Ewelina , Szczesny Bartosz , Szymanski Michal R 
Published: July 2022

Abstract
The removal of RNA primers is essential for mitochondrial DNA (mtDNA) replication. Several nucleases have been implicated in RNA primer removal in human mitochondria, however, no conclusive mechanism has been elucidated. Here, we reconstituted minimal in vitro system capable of processing RNA primers into ligatable DNA ends. We show that human 5′-3′ exonuclease, EXOG, plays a fundamental role in removal of the RNA primer. EXOG cleaves short and long RNA-containing flaps but also in cooperation with RNase H1, processes non-flap RNA-containing intermediates. Our data indicate that the enzymatic activity of both enzymes is necessary to process non-flap RNA-containing intermediates and that regardless of the pathway, EXOG-mediated RNA cleavage is necessary prior to ligation by DNA Ligase III. We also show that upregulation of EXOG levels in mitochondria increases ligation efficiency of RNA-containing substrates and discover physical interactions, both in vitro and in cellulo, between RNase H1 and EXOG, Pol γA, Pol γB and Lig III but not FEN1, which we demonstrate to be absent from mitochondria of human lung epithelial cells. Together, using human mtDNA replication enzymes, we reconstitute for the first time RNA primer removal reaction and propose a novel model for RNA primer processing in human mitochondria.
Induction of senescence upon loss of the Ash2l core subunit of H3K4 methyltransferase complexes
Authors: Bochyńska Agnieszka , Stenzel Alexander T , Sayadi Boroujeni Roksaneh , Kuo Chao-Chung , Barsoum Mirna , Liang Weili , Bussmann Philip , Costa Ivan G , Lüscher-Firzlaff Juliane , Lüscher Bernhard 
Published: July 2022

Abstract
Gene expression is controlled in part by post-translational modifications of core histones. Methylation of lysine 4 of histone H3 (H3K4), associated with open chromatin and gene transcription, is catalyzed by type 2 lysine methyltransferase complexes that require WDR5, RBBP5, ASH2L and DPY30 as core subunits. Ash2l is essential during embryogenesis and for maintaining adult tissues. To expand on the mechanistic understanding of Ash2l, we generated mouse embryo fibroblasts (MEFs) with conditional Ash2l alleles. Upon loss of Ash2l, methylation of H3K4 and gene expression were downregulated, which correlated with inhibition of proliferation and cell cycle progression. Moreover, we observed induction of senescence concomitant with a set of downregulated signature genes but independent of SASP. Many of the signature genes are FoxM1 responsive. Indeed, exogenous FOXM1 was sufficient to delay senescence. Thus, although the loss of Ash2l in MEFs has broad and complex consequences, a distinct set of downregulated genes promotes senescence.
The silencing of ets-4 mRNA relies on the functional cooperation between REGE-1/Regnase-1 and RLE-1/Roquin-1
Authors: Sobańska Daria , Komur Alicja A , Chabowska-Kita Agnieszka , Gumna Julita , Kumari Pooja , Pachulska-Wieczorek Katarzyna , Ciosk Rafal 
Published: July 2022

Abstract
Regnase-1 is an evolutionarily conserved endoribonuclease. It degrades diverse mRNAs important for many biological processes including immune homeostasis, development and cancer. There are two competing models of Regnase-1-mediated mRNA silencing. One model postulates that Regnase-1 works together with another RNA-binding protein, Roquin-1, which recruits Regnase-1 to specific mRNAs. The other model proposes that the two proteins function separately. Studying REGE-1, the Caenorhabditis elegans ortholog of Regnase-1, we have uncovered its functional relationship with RLE-1, the nematode counterpart of Roquin-1. While both proteins are essential for mRNA silencing, REGE-1 and RLE-1 appear to associate with target mRNA independently of each other. Thus, although the functional interdependence between REGE-1/Regnase-1 and RLE-1/Roquin-1 is conserved, the underlying mechanisms may display species-specific variation, providing a rare perspective on the evolution of this important post-transcriptional regulatory mechanism.
Video observations of tiny near-Earth objects with Tomo-e Gozen
Authors: Beniyama Jin , Sako Shigeyuki , Ohsawa Ryou , Takita Satoshi , Kobayashi Naoto , Okumura Shin-ichiro , Urakawa Seitaro , Yoshikawa Makoto , Usui Fumihiko , Yoshida Fumi , Doi Mamoru , Niino Yuu , Shigeyama Toshikazu , Tanaka Masaomi , Tominaga Nozomu , Aoki Tsutomu , Arima Noriaki , Arimatsu Ko , Kasuga Toshihiro , Kondo Sohei , Mori Yuki , Takahashi Hidenori , Watanabe Jun-ichi 
Published: July 2022

Abstract
We report the results of video observations of tiny (diameter less than 100 m) near-Earth objects (NEOs) with Tomo-e Gozen on the Kiso 105 cm Schmidt telescope. The rotational period of a tiny asteroid reflects its dynamical history and physical properties since smaller objects are sensitive to the Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) effect. We carried out video observations of 60 tiny NEOs at 2 fps from 2018 to 2021 and successfully derived the rotational periods and axial ratios of 32 NEOs including 13 fast rotators with rotational periods less than 60 s. The fastest rotator found during our survey is 2020 HS$_\mathsf {7}$ with a rotational period of 2.99 s. We statistically confirmed that there is a certain number of tiny fast rotators in the NEO population, which have been missed with all previous surveys. We have discovered that the distribution of the tiny NEOs in a diameter and rotational period (D–P) diagram is truncated around a period of 10 s. The truncation with a flat-top shape is not explained well by either a realistic tensile strength of NEOs or the suppression of YORP by meteoroid impacts. We propose that the dependence of the tangential YORP effect on the rotational period potentially explains the observed pattern in the D–P diagram.
Rates of Loosening, Failure, and Revision of Iliac Fixation in Adult Deformity Surgery
Authors: Eastlack Robert K. , Soroceanu Alex , Mundis Gregory M. , Daniels Alan H. , Smith Justin S. , Line Breton , Passias Peter , Nunley Pierce D. , Okonkwo David O. , Than Khoi D. , Uribe Juan , Mummaneni Praveen V. , Chou Dean , Shaffrey Christopher I. , Bess Shay ,   the International Spine Study Group
Published: July 2022

Study Design.
Retrospective cohort review of a prospective multicenter database.

Objective.
Identify rates and variations in lumbopelvic fixation failure after adult spinal deformity (ASD) correction.

Summary of Background Data.
Traditional iliac (IS) and S2-alar-iliac (S2AI) pelvic fixation methods have unique technical characteristics for their application, and result in varied bio-mechanical and anatomic impact. These differences may lead to variance in lumbopelvic fixation failure types/rates.

Methods.
ASD patients undergoing correction with more than five level fusion and pelvic fixation, separated by pelvic fixation type (IS vs. S2AI). Fixation fracture or loosening assessed radiographically (Figure 1). Multivariate logistic regression, accounting for significant confounders, was used to examine differences between the two groups for screw loosening/fracture, rod fracture, and revision surgery. Level of significance set at P< 0.05.

Results.
Four hundred eighteen of 1422 patients were included (IS = 287, S2AI = 131). The groups had similar age, body mass index (BMI), baseline comorbidities, number of levels fused (P>0.05), baseline health related quality of life measures (HRQLs) (short form survey-36, Oswestry Disability Index [ODI], Scoliosis Research Society [SRS-22], numeric rating scale [NRS] leg and back, P>0.05) and deformity (pelvic tilt [PT], pelvic incidence-lumbar lordosis [PI-LL], and sagittal vertical axis [SVA], P> 0.05). The IS group had more unilateral fixation versus S2AI (12.9% vs. 6%; P = 0.02). The overall lumbopelvic fixation failure rate was 23.74%. Pelvic fixation (13.4%) and S1 screw (2.9%) loosening was more likely with S2AI (odds ratio [OR] 2.63, P = 0.001; OR 6.05, P = 0.022). Pelvic screw (2.3%) and rod fracture (14.1%) rates similar between groups but trended toward less occurrence with S2AI (OR 0.47, P= 0.06). Revision surgery occurred in 22.7%, and in 8.5% for iliac fixation specifically, but with no differences between fixation types (P = 0.55 and P = 0.365). Pelvic fixation failure conferred worse HRQL scores (physical component score [PCS] 36.23 vs. 39.37, P= 0.04; ODI 33.81 vs. 27.93, P = 0.036), and less 2 years improvement (PCS 7.69 vs. 10.46, P = 0.028; SRS 0.83 vs. 1.03, P = 0.019; ODI 12.91 vs. 19.77, P = 0.0016).

Conclusion.
Lumbopelvic fixation failure rates were high following ASD correction, and associated with lesser clinical improvements. S2AI screws were more likely to demonstrate loosening, but less commonly associated with rod fractures at the lumbopelvic region.
Milrinone Versus Sildenafil in Treatment of Neonatal Persistent Pulmonary Hypertension: A Randomized Control Trial
Authors: Imam Safaa S. , El-Farrash Rania A. , Taha Amr S. , Saleh Ghada A. 
Published: July 2022

Abstract:
Persistent pulmonary hypertension of the newborn (PPHN) is a condition caused by failure of pulmonary vascular adaptation at birth, resulting in severe hypoxia. Several therapeutic modalities are being tried in developing countries where established therapies (inhaled nitric oxide and extracorporeal membrane oxygenation) are widely unavailable. This study aimed to assess the efficacy of milrinone versus sildenafil as available alternative therapeutics in treating PPHN. Forty neonates (>34 weeks) admitted to neonatal intensive care units with evidence of PPHN were randomly allocated to receive either oral sildenafil (0.5–2 mg/kg/6 hours) or intravenous milrinone (0.25–0.75 mic/kg/min). Primary outcomes included improvements in systolic pulmonary artery pressure and oxygen saturation index (OSI) at 24 and 48 hours after treatment. Secondary outcomes included the duration of hospitalization and mechanical ventilation. The ClinicalTrials identifier is NCT04391478. Both groups showed significant improvement in the post-treatment hemodynamic variables compared with pretreatment levels (P < 0.05 for all parameters). Systolic pulmonary artery pressure and OSI values significantly improved in both study groups compared with baseline (P < 0.001). The 24-hour and 48-hour post-treatment OSI values were much lower in the milrinone group than those in the sildenafil group (P < 0.05). The length of hospital stay was significantly shorter in the milrinone group than that in the sildenafil group (P < 0.05). There were no significant differences in the duration of mechanical ventilation, incidence of intracranial hemorrhage and pulmonary hemorrhage, or mortality between the 2 groups (P > 0.05). In conclusion, milrinone and sildenafil are effective and well-tolerated in neonates with PPHN, particularly when inhaled nitric oxide and extracorporeal membrane oxygenation are not available. Milrinone is superior to sildenafil in improving oxygenation without lowering blood pressure parameters.
Adverse Childhood Experiences and Neurocognition in Borderline Personality Disorder: A Call-to-Action Perspective Review
Authors: Estric Clémentine , Calati Raffaella , Lopez-Castroman Jorge 
Published: July 2022

Abstract
Adverse childhood experiences (ACEs) contribute to the development of personality traits leading to adult borderline personality disorder (BPD). Neurocognitive changes could partly mediate the association between ACEs and BPD. We discuss how exposure to ACEs could induce alterations in neurocognition, which, in turn, would contribute to the development of BPD. We conducted a review of MEDLINE articles through 2021, documenting a link between ACEs, neurocognitive impairments, and BPD, and also focusing on the pairwise associations. ACEs appear to have a strong impact on neurocognition and are a predictive factor for BPD. Maltreated, abused, and emotionally invalidated children are more likely to present BPD traits. Neurocognitive impairments in adults exposed to ACEs and in patients with BPD arise from similar brain alterations in the amygdala, hippocampus, and prefrontal cortex. These impairments seem to be linked with clinical dimensions of BPD: increased impulsivity to altered inhibitory control; dissociative experiences to nonspecific autobiographical memory; and emotionally biased facial recognition to unstable interpersonal relationships. This perspective review highlights the contributory role of neurocognition in the association between ACEs and BPD. Additional research is needed, however, on the interconnections among ACEs, neurocognition, and BPD. Future studies could also focus on developing tools to assess early adversity in BPD specifically and on psychotherapeutic approaches to promptly remedy neurocognitive impairments.
Incontinentia pigmenti and the eye
Authors: Islam Yasmin Florence Khodeja , Khurshid Syed Gibran 
Published: July 2022

Purpose of Review:
Incontinentia pigmenti (IP) is a rare X-linked dominant phakomatosis that predominately presents with dermatologic manifestations but can also cause central nervous system and ocular abnormalities. Awareness of the ocular complications of IP is crucial to identify ocular abnormalities early and prevent permanent vision loss.

Recent Findings:
There have been significant recent advances in ocular diagnostic imaging in IP. Optical coherence tomography (OCT) has helped characterize outer plexiform layer abnormalities in the macula, which can help explain central vision loss in IP patients. OCT angiography (OCT-A) also identifies macular vascular changes that induce these foveal structural abnormalities and may supplement fluorescein angiography, the current standard of care to identify peripheral retinal ischemia and neovascularization for infants with IP. Additionally, recent studies have presented excellent anatomic outcomes years after laser photocoagulation to ischemic retina. Early data indicates that antivascular endothelial growth factor therapy can induce retinal revascularization, but runs the risk of late recurrent neovascularization and requires long-term monitoring.

Summary:
Ophthalmic imaging is evolving in the evaluation of IP and is increasingly guiding treatment modalities. A particular focus on the ocular manifestations of IP has been the ideal treatment for retinopathy in this disorder.
Artificial intelligence and corneal diseases
Authors: Kang Linda , Ballouz Dena , Woodward Maria A. 
Published: July 2022

Purpose of review
Artificial intelligence has advanced rapidly in recent years and has provided powerful tools to aid with the diagnosis, management, and treatment of ophthalmic diseases. This article aims to review the most current clinical artificial intelligence applications in anterior segment diseases, with an emphasis on microbial keratitis, keratoconus, dry eye syndrome, and Fuchs endothelial dystrophy.

Recent findings
Most current artificial intelligence approaches have focused on developing deep learning algorithms based on various imaging modalities. Algorithms have been developed to detect and differentiate microbial keratitis classes and quantify microbial keratitis features. Artificial intelligence may aid with early detection and staging of keratoconus. Many advances have been made to detect, segment, and quantify features of dry eye syndrome and Fuchs. There is significant variability in the reporting of methodology, patient population, and outcome metrics.

Summary
Artificial intelligence shows great promise in detecting, diagnosing, grading, and measuring diseases. There is a need for standardization of reporting to improve the transparency, validity, and comparability of algorithms.
A novel diagnostic tool for hyaline vascular Castleman disease versus lymphoma based on contrast-enhanced computed tomography in neck mass
Authors: Lin Huan-Yu , Liao Pei-Shao , Shih Liang-Chun , Hua Chun-Hung , Tsai Ming-Hsui , Lin Chia-Der 
Published: July 2022

Background:
Castleman disease and lymphoma each have a distinct treatment plan; however, they share the same features on contrast-enhanced computed tomography.

Methods:
To assess the quantitative outcomes of Castleman disease versus lymphoma using contrast-enhanced computed tomography based on Hounsfield units (HU). We retrospectively reviewed eight patients with unicentric Castleman disease and 30 patients with lymphoma based on pathological diagnosis at China Medical University Hospital between 2015 and 2020. Preoperative computed tomography with contrast scans was reviewed, and the HU of each tumor were measured.

Results:
This study included eight patients with unicentric Castleman disease (four men and four women; mean age, 33 years) and 25 patients with lymphoma (11 men and 14 women; mean age, 53 years). There was no significant difference in heterogeneity between the two diseases (0.161 ± 0.052 vs 0.239 ± 0.063, p = 0.22); however, enhancement in Castleman disease was higher than that in lymphoma (126.40 ± 31.90 vs 74.19 ± 7.11, p < 0.001), providing a very good diagnostic tool (cutoff point at 88.5–91.3, sensitivity 0.86/specificity 0.88). Furthermore, we found a highly linear relationship in Castleman disease, which was not noted in lymphoma.

Conclusion:
The value of HU provides a good diagnostic tool for the differential diagnosis of Castleman disease versus lymphoma in the neck lymph nodes. Considering the linear relationship in Castleman disease, an increasingly accurate differential diagnosis can be made.
Impact of the Virtual Format on Plastic Surgery Residency and Fellowship Interviews: A National Cross-Sectional Study
Authors: Ferry Andrew M. , Asaad Malke , Elmorsi Rami , Rajesh Aashish , Williams Elizabeth M. , Wolf Steven E. , Rohrich Rod J. , Pederson William C. , Maricevich Renata S. 
Published: July 2022

Background:
The 2020-2021 residency and fellowship application cycles were profoundly affected by the introduction of virtual interviews (VIs). The authors investigate the impact that the virtual format (VF) had on plastic surgery residency and fellowship interviews from the perspectives of program directors (PDs).

Methods:
Surveys were sent to PDs of integrated plastic surgery residency (RPD) and fellowship (FPD) programs to ascertain their perspectives regarding the VF’s impact on residency and fellowship interviews. PDs were stratified into residency and fellowship cohorts, and comparative analysis was performed.

Results:
A total of 92 PDs, 28 RPDs and 64 FPDs, completed our survey (35%). When compared to in-person interviews, VIs were reported to be more economical and time efficient by RPDs (100% and 46%, respectively) and FPDs (97% and 48%, respectively). Consequentially, 36% and 47% of residency and fellowship programs were able to interview more applicants, respectively. RPDs and FPDs reported that VIs hindered their ability to assess applicants’ fit with the program (75% and 63%, respectively), personality and communication skills (75% and 64%, respectively), and commitment to the field along with their ability to function as a trainee (57% and 50%, respectively). Overall, 71% of RPDs and 58% of FPDs preferred in-person interviews. The majority of residency (71%) and fellowship (56%) programs intend to conduct both in-person and VIs in future application cycles (p=0.12).

Conclusions:
Despite preferring in-person interviews, PDs intend on hosting both in-person and VIs in future application cycles. It remains to be seen how VIs will be employed moving forward.
Is It Really Safe to Discontinue Anticoagulant Treatment Before Ptosis Surgery From Serious Bleeding?
Authors: Lee Kangmin , Chang Minwook 
Published: July 2022

Purpose:
To evaluate the effects of discontinuing anticoagulants (ACs)/antiplatelets (APs) preoperatively on surgery for blepharoptosis.

Method:
A retrospective analysis included patients with acquired blepharoptosis who underwent surgical correction, and were followed for more than 1 month. Patients were classified into 2 groups depending on AC/AP treatment or otherwise. All patients taking AC/AP discontinued with the treatment 1 week prior to surgery in accordance with our clinical guidelines. Preoperative and postoperative marginal reflex distance 1 (MRD1) and ecchymosis grade were evaluated and compared.

Results:
Group 1 (AC/AP treatment cessation) included 47 patients with 93 eyelids, and group 2 (control) included 51 patients with 98 eyelids. The preoperative MRD1 showed no significant difference between groups. Group 1 showed a significantly higher rate of severe ecchymosis (41.8 versus 22.4%, P = 0.004) at 1 week of surgery as well as persistent ecchymosis (58.8 versus 7.3%, P = 0.000) compared with group 2 postoperatively at 1 month. Postoperative MRD1 was significantly lower in group 1 at 1 week (P = 0.019). However, the MRD1 and degree of improvement in lid height (postoperative MRD1 “preoperative MRD1) was not significantly different between the 2 groups (P = 0.499, P = 0.058) at 1 month postoperatively.

Conclusions:
Postoperative ecchymosis was more severe in group 1 at 1 month after ptosis surgery even though the ACs/APs were discontinued. Surgeons should be careful about this before operation.

The Synopsis:
Significant ecchymosis could occur even after discontinuation of antithrombotic agents in patients with a history of taking medication in ptosis surgery. Surgeons should be careful about this before operation.