bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Embryo Transfer Versus Double Embryo Transfer: A Cost-Effectiveness Analysis in a Non-IVF Insurance Mandated System
Authors: Sitler Collin , Lustik Michael , Levy Gary , Pier Bruce 
Published: July 2020

ABSTRACT

Introduction
Because of increased morbidity seen in multiple gestations, the American Society of Reproductive Medicine recommends transfer of blastocysts one at a time for most patients. While cost-effectiveness models have compared single embryo transfer (SET) versus double embryo transfer (DET), few incorporate maternal and neonatal morbidity, and none have been performed in U.S. Military facilities. The purpose of this study was to determine the cost effectiveness of sequential SET versus DET in a U.S. Military treatment facility.

Materials and Methods
A cost-effectiveness model was created based on 250 patients between the ages of 20–44 who previously underwent in vitro fertilization (IVF) at our facility. The model consisted of patients pursuing either SET or DET with two total embryos. Cycle outcomes were determined using the published SARTCORS success calculator. Neonatal and obstetrical outcomes were simulated based on singleton and twin IVF pregnancies. Neonatal and obstetrical cost estimates were based on internal data as well.

Results
If 250 model patients pursue SET, 140 live births would occur, with total cost of $5.7 million, and cost per delivery of $40,500. If the model patients pursued DET, 117 live births would occur, with total cost of $9.2 million and a cost per delivery of $77.700. DET would lead to more total infants (207 vs. 143 in SET cohort). Personal costs are higher in SET versus DET cohorts ($23,036 vs. $20,535).

Conclusions
SET in a system with no infertility coverage saves approximately $3.5 million per 250 patients. Higher personal costs as seen with SET may incentivize patients to seek DET. The total savings should encourage alteration to practice patterns with the U.S Military Healthcare System.
Start the Right Way: A Foundation for Improving Connection to Service and People in Medical Education
Authors: Nevo Ofir Noah , Lambert Laura 
Published: July 2020

ABSTRACT
Bottom Line Up Front: In this perspective essay, ENS Ofir Nevo and Dr Laura Lambert briefly discuss the concept of an outward mindset and how they have applied it in the context of medical education. ENS Nevo shares his story of deciding to attend medical school at the Uniformed Services University, as part of his desire and commitment to serve others. Early on, the requirements of medical school created intense demands that began to disconnect him from the commitment and connection that first drew him to a medical career. ENS Nevo describes how an awareness of the choice of mindset helped him address these challenges and stay better connected to his purpose and calling. A case analysis by Dr Lambert further explores how the awareness and practice of an outward mindset may help students, residents, and attendings see how they can improve their own well-being and connection to the people that brought them to medicine in the first place. Their experiences demonstrate how outward mindset principles can be a valuable tool for empowering students and physicians with a perspective that invites new solutions for the challenges of life and work.
Simulations of the Milky Way’s Central Molecular Zone – II. Star formation
Authors: Sormani Mattia C , Tress Robin G , Glover Simon C O , Klessen Ralf S , Battersby Cara D , Clark Paul C , Hatchfield H Perry , Smith Rowan J 
Published: July 2020

ABSTRACTThe Milky Way’s Central Molecular Zone (CMZ) has emerged in recent years as a unique laboratory for the study of star formation. Here we use the simulations presented in Tress et al. to investigate star formation in the CMZ. These simulations resolve the structure of the interstellar medium at sub-parsec resolution while also including the large-scale flow in which the CMZ is embedded. Our main findings are as follows. (1) While most of the star formation happens in the CMZ ring at $R\gtrsim 100 \, {\rm pc}$, a significant amount also occurs closer to Sgr A* at $R \lesssim 10\, {\rm pc}$. (2) Most of the star formation in the CMZ happens downstream of the apocentres, consistent with the ‘pearls-on-a-string’ scenario, and in contrast to the notion that an absolute evolutionary timeline of star formation is triggered by pericentre passage. (3) Within the time-scale of our simulations (∼100 Myr), the depletion time of the CMZ is constant within a factor of ∼2. This suggests that variations in the star formation rate are primarily driven by variations in the mass of the CMZ, caused, for example, by active galactic nuclei (AGN) feedback or externally induced changes in the bar-driven inflow rate, and not by variations in the depletion time. (4) We study the trajectories of newly born stars in our simulations. We find several examples that have age and 3D velocity compatible with those of the Arches and Quintuplet clusters. Our simulations suggest that these prominent clusters originated near the collision sites where the bar-driven inflow accretes on to the CMZ, at symmetrical locations with respect to the Galactic Centre, and that they have already decoupled from the gas in which they were born.
Have hierarchical three-body mergers been detected by LIGO/Virgo?
Authors: Veske Doğa , Márka Zsuzsa , Sullivan Andrew G , Bartos Imre , Rainer Corley K , Samsing Johan , Márka Szabolcs 
Published: July 2020

ABSTRACT
One of the proposed channels of binary black hole mergers involves dynamical interactions of three black holes. In such scenarios, it is possible that all three black holes merge in a so-called hierarchical merger chain, where two of the black holes merge first and then their remnant subsequently merges with the remaining single black hole. Depending on the dynamical environment, it is possible that both mergers will appear within the observable time window. Here, we perform a search for such merger pairs in the public available LIGO and Virgo data from the O1/O2 runs. Using a frequentist p-value assignment statistics, we do not find any significant merger pair candidates, the most significant being GW170809-GW151012 pair. Assuming no observed candidates in O3/O4, we derive upper limits on merger pairs to be ∼11–110 yr−1 Gpc−3, corresponding to a rate that relative to the total merger rate is ∼0.1−1.0. From this, we argue that both a detection and a non-detection within the next few years can be used to put useful constraints on some dynamical progenitor models.
3-Dimensional architecture of the human multi-tRNA synthetase complex
Authors: Khan Krishnendu , Baleanu-Gogonea Camelia , Willard Belinda , Gogonea Valentin , Fox Paul L 
Published: July 2020

AbstractIn mammalian cells, eight cytoplasmic aminoacyl-tRNA synthetases (AARS), and three non-synthetase proteins, reside in a large multi-tRNA synthetase complex (MSC). AARSs have critical roles in interpretation of the genetic code during protein synthesis, and in non-canonical functions unrelated to translation. Nonetheless, the structure and function of the MSC remain unclear. Partial or complete crystal structures of all MSC constituents have been reported; however, the structure of the holo-MSC has not been resolved. We have taken advantage of cross-linking mass spectrometry (XL-MS) and molecular docking to interrogate the three-dimensional architecture of the MSC in human HEK293T cells. The XL-MS approach uniquely provides structural information on flexibly appended domains, characteristic of nearly all MSC constituents. Using the MS-cleavable cross-linker, disuccinimidyl sulfoxide, inter-protein cross-links spanning all MSC constituents were observed, including cross-links between eight protein pairs not previously known to interact. Intra-protein cross-links defined new structural relationships between domains in several constituents. Unexpectedly, an asymmetric AARS distribution was observed featuring a clustering of tRNA anti-codon binding domains on one MSC face. Possibly, the non-uniform localization improves efficiency of delivery of charged tRNA’s to an interacting ribosome during translation. In summary, we show a highly compact, 3D structural model of the human holo-MSC.
Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination
Authors: Wüst Hannah M , Wegener Amélie , Fröb Franziska , Hartwig Anna C , Wegwitz Florian , Kari Vijayalakshmi , Schimmel Margit , Tamm Ernst R , Johnsen Steven A , Wegner Michael , Sock Elisabeth 
Published: July 2020

AbstractSchwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.
Safety of Low-Dose Tanezumab in the Treatment of Hip or Knee Osteoarthritis: A Systemic Review and Meta-analysis of Randomized Phase III Clinical Trials
Authors: Yu Yang , Lu Shi-Tao , Sun Jin-Peng , Zhou Wei 
Published: July 2020

Abstract

Objectives
To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA).

Methods
Databases were searched up to September 2019 for phase III randomized controlled trials (RCTs). Eleven phase III RCTs comprising 11,455 patients were eligible. The pooled estimates of safety outcomes were assessed and expressed using relative risks (RRs) and 95% confidence intervals with a random-effects model.

Results
Tanezumab significantly increased the incidence of rapidly progressive OA (RPOA; RR = 9.07, 95% CI = 1.21–67.90, P = 0.03) and abnormal peripheral sensation (APS; RR = 2.68, 95% CI = 1.64–4.37, P &lt; 0.00001) compared with placebo. No significant difference was found in terms of incidence of total joint replacement (TJR; RR = 1.13, 95% CI = 0.76–1.68, P = 0.55) or withdrawal due to adverse effects (AEs; RR = 1.26, 95% CI = 0.79–2.00, P = 0.33). The tanezumab group showed a statistically higher incidence of RPOA (RR = 3.96, 95% CI = 2.23–7.04, P &lt; 0.00001) and APS (RR = 1.2, 95% CI = 1.44–2.56, P &lt; 0.00001) compared with the nonsteroidal anti-inflammatory drugs and opioids group. No significant difference was found in terms of TJR (RR = 1.51, 95% CI = 0.65–3.47, P = 0.33) and withdrawal (RR = 0.54, 95% CI = 0.20–1.40, P = 0.20). Subgroup analysis revealed that 2.5 mg of tanezumab did not show an advantage over 5 mg of tanezumab in reducing AEs.

Conclusions
These results demonstrate that RPOA and APS should be the most concerning AEs when using tanezumab in OA patients. Additional data are needed to define the optimal dose to minimize risk and to determine the optimal subjects to receive this treatment.
High-drug-loading capacity of redox-activated biodegradable nanoplatform for active targeted delivery of chemotherapeutic drugs
Authors: Zhang Hai , Yan Jianqin , Mei Heng , Cai Shengsheng , Li Sai , Cheng Furong , Cao Jun , He Bin 
Published: July 2020

Abstract
Challenges associated with low-drug-loading capacity, lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy. Herein, we constructed active-targeting, redox-activated polymeric micelles (HPGssML) self-assembled aptamer-decorated, amphiphilic biodegradable poly (benzyl malolactonate-co-ε-caprolactone) copolymer with disulfide linkage and π-conjugated moieties. HPGssML with a homogenous spherical shape and nanosized diameter (∼150 nm) formed a low critical micellar concentration (10−3 mg/mL), suggesting good stability of polymeric micelles. The anticancer drug, doxorubicin (DOX), can be efficiently loaded into the core of micelles with high-drug-loading content via strong π–π interaction, which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles. The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment. Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells. An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration (IC50) of DOX-loaded HPGssML was two times lower than that of the control group, demonstrating improved antitumor efficacy. Therefore, the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.
Measuring Reasoning in Paranoia: Development of the Fast and Slow Thinking Questionnaire
Authors: Hardy Amy , Tolmeijer Eva , Edwards Victoria , Ward Thomas , Freeman Daniel , Emsley Richard , Green Catherine , Rus-Calafell Maria , Greenwood Kathryn , Bebbington Paul , Kuipers Elizabeth , Fowler David , Sacadura Catarina , Collett Nicola , McGourty Alison , Dunn Graham , Garety Philippa 
Published: July 2020

Abstract
Paranoid thoughts are common across the psychosis continuum. It is well established that reasoning biases (conceived as an overreliance on fast thinking and lack of willingness and/or ability to engage in slow thinking) contribute to paranoia. Targeted therapies have shown promise in improving reasoning in order to reduce paranoia. Psychometrically robust and easy-to-use measures of these thinking styles will assist research and clinical practice. Existing assessments include experimental tasks that are complex to administer or self-report measures that have limitations in comprehensively assessing cognitive biases in paranoia. We have developed the first questionnaire to assess fast and slow thinking biases related to paranoid thoughts, and here report on its evaluation. In study 1, we generated, evaluated, and extracted items reflecting reasoning, and assessed their reliability and validity in a non-clinical sample (n = 209). In study 2, we replicated the factor analysis and psychometric evaluation in a clinical sample (n = 265). The resultant Fast and Slow Thinking (FaST) questionnaire consists of two 5-item scales reflecting fast and slow thinking and is therefore brief and suitable for use in both research and clinical practice. The fast thinking scale is reliable and valid. Reliability and criterion validity of the slow scale shows promise. It had limited construct validity with objective reasoning assessments in the clinical group, possibly due to impaired meta-cognitive awareness of slow thinking. We recommend the FaST questionnaire as a new tool for improving understanding of reasoning biases in paranoia and supporting targeted psychological therapies.
“The Other Side”: Assessing the Polarization of Gender Knowledge Through a Feminist Analysis of the Affective-Discursive in Anti-Feminist Online Communities
Authors: Rothermel Ann-Kathrin 
Published: July 2020

AbstractGiven the current polarization of gender knowledge in the public discourse, this article investigates the “other side” of gender knowledge production. Building on feminist standpoint literature, I conduct a close reading of the affective-discursive dynamics of knowledge production in two anti-feminist online communities in the United States and India. I find that anti-feminist communities appropriate feminist practices of consciousness-raising to construct a shared sense of victimization. This appropriation is, however, incomplete. In contrast to feminist practices, anti-feminist knowledge generation is premised on the polarizing themes of “ultimate victimhood” and “ultimate other,” which lead to violence and exclusion, rather than liberation.
Perianal Crohn’s Disease
Authors: Lightner Amy L. 
Published: July 2020

Case Summary:
A 22-year-old man presents to your office with a perianal abscess and occasional mild crampy abdominal pain. You take him to the operating room for an examination under anesthesia (EUA) with incision and drainage of the abscess and note a transphincteric fistula tract through which you place a seton and 2 large skin tags. The anal canal and rectum are without ulceration, but there are mild proctitis and nonprolapsing internal hemorrhoids. Because of a concern for Crohn’s disease (CD), he undergoes magnetic resonance enterography and colonoscopy. The magnetic resonance enterography shows inflammation in 20 cm of the distal terminal ileum, and colonoscopy reveals approximately 10 ulcers <5 mm in the terminal ileum without significant narrowing. He is seen in consultation for the initiation of a monoclonal antibody and returns to see you in the office after his first 3 infusions. He is feeling well, has significantly decreased drainage from the perianal fistula, but would really like his seton and skin tags removed while you are there.
RETINAL TISSUE PERFUSION REDUCTION BEST DISCRIMINATES EARLY STAGE DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Liu Zhiping , Jiang Hong , Townsend Justin H. , Wang Jianhua 
Published: July 2020

Purpose:
To determine retinal microcirculation measured as retinal tissue perfusion (RTP) in patients with type 2 diabetes mellitus and mild nonproliferative diabetic retinopathy, and to compare its discrimination ability to that of retinal microvasculature and microstructure.

Methods:
Thirty eyes of 18 patients with mild nonproliferative diabetic retinopathy and 20 eyes of 20 age-matched and gender-matched normal controls were imaged. Retinal blood flow velocity and flow rate were measured using a retinal function imager. Retinal vessel density (Dbox) and intraretinal layer thicknesses were measured using optical coherence tomography angiography. Retinal tissue perfusion was measured as retinal blood flow divided by the volume of the inner retina.

Results:
Compared with normal control, RTP, vessel density, and the thickness of the retinal nerve fiber layer in patients with mild nonproliferative diabetic retinopathy showed significant reduction (P < 0.05). Retinal tissue perfusion had the best discrimination power (area under the curve = 0.97), with a sensitivity of 93.3% and specificity of 85.0%. In the eyes with mild nonproliferative diabetic retinopathy, RTP correlated with arteriolar blood flow velocity (r = 0.403, P = 0.027) but was unrelated to vessel density in any layer (r = −0.010 to 0.261, P > 0.05).

Conclusion:
Because of its highest discrimination power, RTP may become a promising biomarker for detecting early-stage diabetic retinopathy.
Flanged Sutureless Intrascleral Fixation of Dislocated Hard 1-Piece Polymethyl Methacrylate Intraocular Lenses
Authors: Walsh Mark K. , Williams Mark T. 
Published: July 2020

Purpose:
To describe the vitreoretinal surgical technique and report the outcomes of our method of sutureless flanged intrascleral haptic fixation of dislocated 1-piece polymethyl methacrylate intraocular lenses with rigid haptics.

Methods:
Ciliary sulcus–based scleral tunnels were created by placing valved 27-gauge (g) trocar cannulas limbus parallel with conjunctival displacement. After complete vitrectomy, the rigid haptics were then externalized using 27g forceps. Cautery was then used to form flanges at the haptic tips. The haptics were then pushed back into the mouths of the scleral tunnels.

Results:
Flanged intrascleral fixation was successfully achieved in eight eyes of seven patients. The average age at the time of surgery was 75 ± 13.7 years, with a mean follow-up of 17.9 ± 16.3 months (range 3–42 months). Intraocular lens dislocation/subluxation was the most common indication for surgery. All patients fully recovered to their potential acuity by their third postoperative visit. The most significant complication was erosion of one haptic in one patient, which was successfully managed without requiring intraocular lens exchange. There were no complications of subsequent dislocation, endophthalmitis, retinal detachment, or uveitis–glaucoma–hyphema syndrome.

Conclusion:
Flanged sutureless intrascleral fixation of dislocated 1-piece polymethyl methacrylate intraocular lenses with rigid haptics can be safely and successfully performed, avoiding the large wound creation accompanying intraocular lens exchange and the disadvantages of suture-based techniques.
Intrascleral Fixation of Flanged Polypropylene Suture(s) for Iridodialysis Repair
Authors: Ou Zhongmin , Zhang Qi , Jin Haiying 
Published: July 2020

Purpose:
We will describe a minimally invasive technique for the repair of iridodialysis, without conjunctival dissections, using intrasceral fixation of a 6-0 polypropylene suture with a flanged tip.

Methods:
A flange was created at the end of the suture with thermoplasticity. An ab interno passing of the needle attached to the suture was performed through the peripheral part of the iris and was further passed out from the eye 1.5 mm to 2 mm behind the limbus. Intrascleral fixation of the exterior suture was performed with the aid of the attached needle. After adjusting the tension of the iris relocation, the externalized end of the suture was cut flush to the sclera with scissors. For a wide dialysis, the same manipulations were repeated until the repair was completed.

Results:
The technique was used in three eyes of three patients. No visual impairments of monocular diplopia and glare were observed after surgery. Postoperatively, the irises remained well positioned, with no suture erosion, suture loosening, hypotony, scleral atrophy, or chronic inflammation being observed within the follow-up period. Mild postoperative hyphema was observed in one eye of blunt trauma.

Conclusion:
The present technique provides minimal surgical invasion for the repair of iridodialysis without creations of scleral flap/groove/pocket and conjunctival dissection.