cssi/SciSciGPT-SciSciNet huggingface dataset:
Testosterone replacement therapy and voiding dysfunction

Testosterone replacement therapy (TRT) represents an increasing popular treatment option for men with late-onset hypogonadism (LOH). Because of unsubstantiated beliefs of testosterone’s effect on the prostate, the FDA has recently placed a warning on testosterone products, stating that TRT may worsen benign prostatic hyperplasia (BPH). Within this review article we have demonstrated the current understanding of the physiology of testosterone and its relationship with prostatic and lower urinary tract physiology. The current evidence suggests that not only does TRT not worsen lower urinary tract symptoms (LUTS), but that hypogonadism itself is an important risk factor for LUTS/BPH.
146. Regulation of Inflammation in Cystic Fibrosis Lung Epithelial Cells by miR-155

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, F508del, is associated with failure of the mutant CFTR to traffic to the plasma membrane, with concomitant loss of cAMP-activated chloride conductance, and hypersecretion of pro-inflammatory IL-8. Our data indicate that the mis-expression of microRNAs (miRNAs, miRs) in CF cells, both in culture and in ex vivo bronchial biopsies, contribute to the inflammatory disease phenotype of CF. Our studies have demonstrated that the aberrant up-regulation of miR-155, in CF cells compared to CFTR-repaired control cells, induces hyper-expression of IL-8 through reduction in AKT1 activation. Our data indicate that, in addition to regulation of IL-8 mRNA stability by targeting SHIP1 gene, miR-155 also promotes increased translation of IL-8 mRNA. Therefore, we have analyzed the role of pro-inflammatory RNA-binding proteins (RBPs) and RNAs in miR-155-mediated regulation of IL-8 expression in CF lung epithelial cells. We have employed an in vivo cross-linking and affinity purification strategy to isolate and identify proteins and RNA in the miR-155-induced IL-8-mRNP complexes that regulate IL-8 expression in CF cells. We have thus identified the antagonistic role of HuR and miR-16 in the regulation of IL-8 expression in CF. Additionally, we have also identified CF disease-specific inflammatory target genes of miR-155, viz. RPTOR, SIRT1 and NR2F2, in CF lung epithelial cells that regulate the CF disease phenotype. Understanding these mechanisms will ultimately lead to the development of novel miR-based anti-inflammatory therapeutics for CF and other pulmonary disorders.
Squamous Lesions of the Cervix

Many neoplastic and preneoplastic lesions of the cervix are related to human papillomavirus (HPV) infection, particularly the high-risk ­subtypes. Squamous papillomas are benign proliferation of squamous epithelium and are related to low-risk HPV subtypes. Condyloma acuminatum is a manifestation of HPV infection, mostly in low-risk groups (HPV 6 and 11). Cervical intraepithelial neoplasia (CIN) 1 can harbor both the high- and low-risk subtypes of HPV. High-grade CIN (CIN 2 and 3) and invasive squamous cell carcinoma (SCC) are caused by high-risk HPV (HPV 16 and 18) and are associated with integrated viral genome. Primary adenocarcinomas of the cervix are associated with high-risk HPV infection in most, if not all, cases. The histologic spectrum of cervical adenocarcinomas includes usual endocervical adenocarcinoma, endometrioid carcinoma, and intestinal mucinous carcinoma, each of them may be accompanied by their corresponding in situ lesions. Rare variants include minimal deviation adenocarcinoma (adenoma malignum), villoglandular adenocarcinoma, adenosquamous carcinoma, adenobasal cell carcinoma, serous carcinoma, clear cell carcinoma, and neuroendocrine carcinomas.
An Agent-Based Model for Information Diffusion over Online Social Networks

AbstractOnline social networks have become a new channel for urban citizens to acquire information. The efficient information diffusion in their communities ensures wide awareness of updated specia...
Imaging mass spectrometry tackles interfacial challenges in electrochemistry

Summary Electrochemistry has played a significant role in many research fields. Owing to its sensitivity and selectivity, in situ electroanalysis has been widely used as a fast and economical means for achieving outstanding results. Although many spectroscopic techniques have been used in electrochemistry, the challenges to capture short-lived intermediate species as a result of electron transfer in the buried solid electrode and electrolyte solution interface remains a grand challenge. In situ imaging mass spectrometry (IMS) recently has been extended to capture transient species in electrochemistry. This review intends to summarize newest development of IMS and its applications in advancing fundamental electrochemistry.
Multivariate techniques for energy reconstruction in highly granular calorimeters

The overall trend in calorimetry is towards high granularity, both laterally and longitudinally. This trend is a requirement for the full exploitation of the Particle Flow Algorithms, which reconstruct individual particles using the sub-detector that provides the best resolution for this specific particle. The increased level of detail in the event topologies due to higher segmentation of the calorimeter provides additional handles for energy reconstruction. Here, the power of using multivariate statistical techniques using various topological variables in the reconstruction of the energy of single particles in highly granular calorimeters is demonstrated.
ARM Instructions Part II

This chapter covers ARM data transfer instructions such as load and store, pseudo instructions, data transfer instruction format, data transfer addressing mode such as register indirect addressing and pre-indexed addressing, data representation in memory, and several examples related to data transfer instructions.
Characteristics and Outcomes of Children With Conversion Disorder Admitted to a Single Inpatient Rehabilitation Unit, A Retrospective Study

Abstract Background Conversion disorder (CD) can lead to impaired functioning. Few studies present demographic and outcome data for pediatric patients. Many have had success with rehabilitation; however, further details are not known. Objective To identify characteristics and outcomes of children admitted to a pediatric inpatient rehabilitation program with CD symptoms. Design Retrospective study. Setting Inpatient rehabilitation unit within a large children’s hospital. Patients All patients with diagnosis of CD or functional gait disorder (FGD) during designated time period. Methods Data were obtained from chart review and United Data Systems for Medical Rehabilitation. Descriptive statistics and Wilcoxon signed rank tests were used to analyze data. A P value of Outcome Measures Average length of stay, Functional Independence Measure for Children (WeeFIM) scores, WeeFIM change, WeeFIM efficiency, recommended therapies, number of repeat admissions to the same hospital for conversion disorder symptoms in the 12 months following discharge, and school reentry characteristics. Results Thirty admissions were identified that met criteria. Before diagnosis, duration of symptoms was 58 ± 145 days, physician visits averaged 1.9 ± 2.1, hospital admissions to the same hospital averaged 0.7 ± 0.9, and absence from school was 6 ± 12 weeks. Overall, 83% exhibited mixed symptoms. Length of inpatient rehabilitation stay was 8.4 ± 4.2 days with WeeFIM score change of 30 ± 11.9 (P Conclusions This study suggests that a multidisciplinary inpatient rehabilitation approach is a potentially effective and efficient treatment for children and adolescents with conversion disorder and leads to sustained functional improvement and return to school after discharge. Level of Evidence III
Non-Parametric Path Analysis in Structural Causal Models

One of the fundamental tasks in causal inference is to decompose the observed association between a decision X and an outcome Y into its most basic structural mechanisms. In this paper, we introduce counterfactual estimands for effects along with a specific mechanism, represented as a path from X to Y in an arbitrary structural causal model. We introduce a novel non-parametric decomposition formula which expresses the covariance of X and Y as a sum over unblocked paths from X to Y contained in an arbitrary causal model. This formula allows a fine-grained path analysis without requiring a commitment to any particular parametric form, and can be seen as a generalization of Wright's decomposition method in linear systems (1923,1932) and Pearl's non-parametric mediation formula (2001).
Desmoid Tumors: A Comprehensive Review of the Evolving Biology, Unpredictable Behavior, and Myriad of Management Options

Desmoid tumors are rare, clonal collections of benign fibrous tissue that exhibit a highly variable clinical course. This article presents a comprehensive review of desmoid tumors and summarizes the current literature pertaining to clinical presentation, diagnostic modalities, pathogenesis, prognostic factors, and management options.
Classical and Quantum Constraints

Many systems involve constraints that generally lead to dynamical motion that is constrained in one way or another. For example, three-dimensional dynamical motion that is constrained to lie on a fixed two-dimensional surface, e.g., motion effectively lying on the surface of the Earth, would constitute constrained motion. Oftentimes, constraints are accompanied by superfluous degrees of freedom, variables whose values are not determined by the equations of motion but whose values must be chosen to fully determine the temporal evolution of the remaining variables. Such variables whose values are left undetermined by the equations of motion are called “gauge” variables; and the somewhat arbitrary choice of such variables to fix the behavior of all the variables is called “choosing a gauge.”
Temperature Effect on Drop-Weight Impact of Woven Composites

This paper investigates the effect of temperature on hybrid woven composite panels (100mm×100mm×25mm) which underwent drop-weight impact at five different test temperatures: -60°C, -20°C, room temperature, 75°C and 125°C. The studies were conducted by using experimental and 3-D dynamic finite element approaches. The specimens tested were made of plain-weave hybrid S2 glass and IM7 graphite fibers imbedded in toughened epoxy (cured at 177°C). The composite panels were impacted using an instrumented drop-weight impact tester. The time-histories of impact-induced dynamic strains and impact forces were recorded. The damaged specimens were inspected visually and using the ultrasonic C-scan method.
Quantifying the Smooth Muscle Content of the Prostate Using Double Immunoenzymatic Staining and Color-Assisted Image Analysis

Benign prostatic hyperplasia (BPH) describes a hyperplastic process of the stromal and epithelial elements of the prostate (Franks 1975). The clinical manifestations of BPH are related primarily to symptoms of bladder outlet obstruction (Barry 1990). The specific histologic features of the prostate which lead to the development of bladder outlet obstruction are unknown.
Adherence to extended release naltrexone: Patient and treatment characteristics.

BACKGROUND AND OBJECTIVES Despite the promise of extended release naltrexone in the treatment of the opioid and alcohol use disorders, challenges with initiation and subsequent adherence have limited its potential. The purpose of this study is to identify the patient and treatment characteristics associated with adherence to extended release naltrexone. METHODS Retrospective cohort study of 155 veterans who initiated the medication in FY 2014 and FY2015. Medical records were abstracted for patient and treatment data including preferred drug and utilization of substance use treatment in the year before and after medication initiation. RESULTS Sample characteristics include 94% male, 70% domiciled, 60% without current legal problems, 30% employed, and preferred drug being opioids for 55% and alcohol for 45%. The mean of five extended release naltrexone injections did not differ by preferred drug. Treatment variables associated with medication adherence included concurrent substance use residential, individual, group, and psychiatric therapies (all p < .05) with inpatient detoxification admissions halved afterward (p < .0001) . DISCUSSION AND CONCLUSIONS Whereas most studies of extended release naltrexone have focused on patients with either alcohol or opioid use disorders for 6 months, this study allowed for a direct comparison of adherence in both groups over a year. The average treatment persistence in this veteran sample is greater than described in other public sector studies and may illustrate the importance of concurrent psychosocial therapies. SCIENTIFIC SIGNIFICANCE Results extend the findings of other studies and add to an emerging appreciation of the factors associated with treatment retention for extended release naltrexone. (Am J Addict 2018;27:524-530).
Silicon Carbide Power Devices: A 35 Year Journey from Conception to Commercialization

A relationship between the basic properties of semiconductor materials and the performance of unipolar power devices was first published in 1982 [1]. This theory produced the Baliga's Figure-of-Merit (BFOM) which allows determination of which semiconductors can be used to reduce the specific on-resistance in power devices. Accurate measurements of the impact ionization coefficients for SiC [2] determined a BFOM to more than 1000 for 4H-SiC. This encouraged the development of practical SiC devices during the 1990s culminating in the announcement of commercial devices by 2003. Today, high voltage JBS rectifiers and power MOSFETs have become commercially available from multiple sources. This paper reviews the history of development of SiC power devices, their potential applications, and the social impact.
The Digital Storywork Partnership: Community-centered social studies to revitalize Indigenous histories and cultural knowledges

Abstract Indigenous communities have always cultivated social studies learning that is interactive, dynamic, and integrated with traditional knowledges. To confront the assimilative and deculturalizing education that accompanied European settlement of the Americas, Montana has adopted Indian Education for All (IEFA). This case study evaluates the Digital Storywork Partnership (DSP), which strives to advance the goals of IEFA within and beyond the social studies classroom through community-centered research and filmmaking. Results demonstrate the potential for DSP projects to advance culturally revitalizing education, community connectedness, and identity-development. The DSP offers a model for social studies education that is not only culturally affirming and revitalizing for Indigenous communities, but also holds potential for use in all communities. We conclude with recommendations for educators, scholars, and community members engaged in similar efforts.
Engineering Crisis Response Software: Lessons Learnt from a Flint Water Crisis App Platform

As the role of software evolves to become more ubiquitous and pervasive by the proliferation of mobile devices in conjunction with vast computational cloud assets, its potential to facilitate targeted humanitarian relief efforts in real-time is unparalleled. Regrettably, effectively leveraging this potential is a new frontier as dominant efforts converge to more commercial endeavors. In 2014, policymakers for the City of Flint in Michigan made the decision to switch its water supply from the Detroit Water and Sewerage system to the Flint River. The result was a spike in lead levels for residential water supplies triggering a health crisis. In response, a team comprising of students and faculty from the University of Michigan campuses and Google volunteers designed and built a responsive mobile software platform. The forefront features of the MyWater-Flint platform allows for residents to geolocate resources, be informed on crisis developments, crowdsource data for decision making, and affords risk prediction through data analysis. In this paper, we overview the design considerations with a focus on the challenges encountered throughout the process. We present the generic multi platform architecture and methodology for community engagement through user experience design, and the consolidation, dissemination and synthesis of hyper-local information for rapid deployment during a crisis.
Postsynthetic Metal Exchange in a Metal-Organic Framework Assembled from Co(III) Diphosphine Pincer Complexes

A Zr metal-organic framework (MOF) 1-CoCl3 has been synthesized by solvothermal reaction of ZrCl4 with a carboxylic acid-functionalized CoIII-PNNNP pincer complex H4(L-CoCl3) ([L-CoCl3]4- = [(2,6-(NHPAr2)2C6H3)CoCl3]4-, Ar = p-C6H4CO2-). The structure of 1-CoCl3 has been determined by X-ray powder diffraction and exhibits a csq topology that differs from previously reported ftw-net Zr MOFs assembled from related PdII- and PtII-PNNNP pincer complexes. The Co-PNNNP pincer species readily demetallate upon reduction of CoIII to CoII, allowing for transmetalation with late second and third row transition metals in both the homogeneous complex and 1-CoCl3. Reaction of 1-CoCl3 with [Rh(nbd)Cl]2 (nbd = 2,5-nobornadiene) results in complete Rh/Co metal exchange at the supported diphosphine pincer complexes to generate 1-RhCl, which has been inaccessible by direct solvothermal synthesis. Treating 1-CoCl3 with PtCl2(SMe2)2 in the presence of the mild reductant NEt3 resulted in nearly complete Co substitution by Pt. In addition, a mixed metal pincer MOF, 1-PtRh, was generated by sequential substitution of Co with Pt followed by Rh.
Disentangled Representations of Cellular Identity

We introduce a disentangled representation for cellular identity that constructs a latent cellular state from a linear combination of condition specific basis vectors that are then decoded into gene expression levels. The basis vectors are learned with a deep autoencoder model from single-cell RNA-seq data. Linear arithmetic in the disentangled representation successfully predicts nonlinear gene expression interactions between biological pathways in unobserved treatment conditions. We are able to recover the mean gene expression profiles of unobserved conditions with an average Pearson r = 0.73, which outperforms two linear baselines, one with an average r = 0.43 and another with an average r = 0.19. Disentangled representations hold the promise to provide new explanatory power for the interaction of biological pathways and the prediction of effects of unobserved conditions for applications such as combinatorial therapy and cellular reprogramming. Our work is motivated by recent advances in deep generative models that have enabled synthesis of images and natural language with desired properties from interpolation in a “latent representation” of the data.
Role of cone-beam CT augmented by navigational software in the single-session management of gastrointestinal hemorrhage and infected deep postoperative fluid collections.

Abstract Utilization of cone-beam CT with navigational software augmentation allows performance of both vascular and nonvascular interventions in a traditional fluoroscopy suite without need for additional hardware. The improvements in target identification and procedure time associated with use of these technologies suggest that they may be particularly beneficial in emergent settings where decreased procedure time correlates with improved outcomes. We illustrate these potential advantages through the successful single-session management of a clinically unstable patient with both gastrointestinal (GI) hemorrhage and infected postoperative fluid collections.
Intervening in the Lives of Gang Members in Denver: A Pilot Evaluation of the Gang Reduction Initiative of Denver

There are over one million gang members in the United States, but effective practices and programs to facilitate disengagement from gangs are rare. This first aim of this article was to introduce t...
Comparing the risk of sudden unexpected infant death to common causes of childhood injury death

In a secondary analysis of publicly available data, the rate of sudden unexplained infant death in the first year exceeded the peak rates of the leading causes of injury death for youth (≤19 years of age). The absolute risk of sudden unexplained infant death exceeded age-specific risks of the major causes of child injury mortality regardless of race or ethnicity.
Assessing Liver Standard Uptake Value (SUV) in Patients with Congestive Heart Failure (CHF) versus those without CHF using Positron Emission Tomography (PET) as an Imaging Modality

2728 Objectives Liver standard uptake values (SUV) are commonly used as standard internal reference when interpreting PET/CT studies. Factors that could potentially impact this standard may affect diagnoses made by this imaging modality. The diagnosis of CHF is not uncommon in patients undergoing PET/CT examination. The purpose of this study is to compare the liver SUV in patients with and without CHF. Methods A retrospective study was conducted which included 79 patients with CHF and compared to 79 age and gender matched control patients without CHF. All 158 patients had FDG PET/CT examination according to standard imaging protocol. Liver SUV was recorded for each patient and analyzed for a statistically significant difference between the two groups. Results Of all 158 cases reviewed (82 males, 76 females; mean age 69 yrs; age range 30-95 yrs), those patients with CHF exhibited an average liver SUV of 2.69 +/- 1.15 while those without CHF exhibited an SUV of 2.56 +/- 0.75. A two-tailed test of significance was undertaken to yield a p-value of approximately 0.410. Conclusions We conclude that the presence of CHF does not have a statistically significant impact upon liver SUV. Therefore, the presence of CHF does not preclude the use of liver SUV as an internal reference in patients undergoing FDG PET/CT examination.
Causal Inference and Counterfactual Reasoning

As computing systems are more frequently and more actively intervening to improve people's work and daily lives, it is critical to correctly predict and understand the causal effects of these interventions. Conventional machine learning methods, built on pattern recognition and correlational analyses, are insufficient for causal analysis. This tutorial will introduce participants to concepts in causal inference and counterfactual reasoning, drawing from a broad literature on the topic from statistics, social sciences and machine learning. We will motivate the use of causal inference through examples in domains such as recommender systems, social media datasets, health, education and governance. To tackle such questions, we will introduce the key ingredient that causal analysis depends on---counterfactual reasoning---and describe the two most popular frameworks based on Bayesian graphical models and potential outcomes. Based on this, we will cover methods suitable for doing causal inference with large-scale online data, including randomized experiments, observational methods like matching and stratification, and natural experiment-based methods such as instrumental variables and regression discontinuity. We will also focus on best practices for evaluation and validation of causal inference techniques, drawing from our own experiences. We will show application of these techniques using DoWhy, a Python library for causal inference. Throughout, the emphasis will be on considerations of working with large-scale data, such as logs of user interactions or social data.
Understanding Data Motion in the Modern HPC Data Center

The utilization and performance of storage, compute, and network resources within HPC data centers have been studied extensively, but much less work has gone toward characterizing how these resources are used in conjunction to solve larger scientific challenges. To address this gap, we present our work in characterizing workloads and workflows at a data-center-wide level by examining all data transfers that occurred between storage, compute, and the external network at the National Energy Research Scientific Computing Center over a three-month period in 2019. Using a simple abstract representation of data transfers, we analyze over 100 million transfer logs from Darshan, HPSS user interfaces, and Globus to quantify the load on data paths between compute, storage, and the wide-area network based on transfer direction, user, transfer tool, source, destination, and time. We show that parallel I/O from user jobs, while undeniably important, is only one of several major I/O workloads that occurs throughout the execution of scientific workflows. We also show that this approach can be used to connect anomalous data traffic to specific users and file access patterns, and we construct time-resolved user transfer traces to demonstrate that one can systematically identify coupled data motion for individual workflows.
Calculated Decisions: Jones Criteria for Acute Rheumatic Fever Diagnosis

The Jones criteria are use to diagnose acute rheumatic fever based on major and minor criteria.
Solar-cycle dependence of galactic cosmic ray flux. II - The correlation between the nucleonic flux and solar indices

To investigate the relationship between solar activity and cosmic-ray modulation, time series of the nucleonic flux and of solar plages, sunspots, centimeter radio noise, and the brightness of the white-light corona at 1.1 and 1.5 solar radii from the center of sun are cross-correlated. Data pertain to the years 1964-1967 during the ascending phase of the current solar cycle. The amplitudes and phases of correlation functions for filtered and unfiltered indices are discussed. The existence of a superior solar index for relating solar activity to long-term modulation is not yet demonstrated conclusively, and the time lag of modulation is too poorly determined to permit its use in estimating the radius of the modulation region.
Increasing sensitivity of transcriptome profiling across species by depleting abundant RNAs

RNA-seq is a widely used technology with a broad range of applications. The technology has been pushed to extremes of very low and degraded samples but still battles with the challenge of having a large dynamic range of transcript expression. Highly expressed transcripts with minimal biological interest can dominate readouts, masking detection of more informative low-abundance transcripts. Here, we present an improved method to enrich for RNAs of interest by eliminating abundant, typically unwanted, RNAs. This method is based on hybridization of probes to the target RNA followed by degradation of the bound RNAs and probes. Optimized probes target rRNAs from human, mouse, rat or bacteria, and globin transcripts from multiple derivate blood samples. Incorporation of new enzymes and streamlining of the method make it more robust with increased specificity. Using strand-specific RNA sequencing we measured sequencing metrics before and after depletion across a wide range of samples, including UHRR, RNA from blood, bacterial monocultures, and communities with 10ng-1Âµg inputs. Across all samples we achieved high depletion efficiency (up to 99.9 %) with minimal off target effects. We detect a high number of transcripts, with even coverage across the transcript length, while retaining transcript complexity even at the lowest inputs. The method works efficiently with low input and highly degraded total RNA including FFPE samples. We have also developed a customizable approach designed to deplete unwanted RNA from any organism with a user-friendly web tool. Using this tool and method to deplete unwanted RNAs from various species, high depletion efficiency has been achieved for targeted RNAs. We conclude that the reduction of abundant transcripts for RNA-seq studies significantly increases the ability to detect true biological variation that could not be detected in non-depleted samples. The method described here is a reliable and simple solution that greatly improves se.
Abstract 6369: SHetA2 increases the activity of palbociclib in cervical cancer in vitro and in vivo

Introduction: Standard of care therapies for cervical cancer are harmful to normal cells and cause many side effects. New, less toxic treatments are needed in order to avoid these toxic effects. We are currently studying a promising low-toxicity drug, SHetA2. SHetA2 is a flexible heteroarotinoid that induces apoptosis and G1 cell cycle arrest in cancer cells, but only induces G1 cell cycle arrest in healthy cells. Part of the mechanism of SHetA2 is its degradation of cyclin D1. Cyclin D1 forms a complex with CDK 4/6 and is important for G1 progression. Therefore, we combined SHetA2 with palbociclib. Palbociclib is an FDA approved CDK 4/6 inhibitor that is currently used in the treatment of hormone positive breast cancers and is currently in clinical trials for the treatment of ovarian cancer. Therefore, we hypothesized that SHetA2 and palbociclib would synergistically inhibit growth of cervical cancer in vitro and in cervical cancer cell- derived xenograft tumors. Methods: The effects of SHetA2 and palbociclib alone and in combination were tested on cervical cancer cell lines using the MTT assay. Synergy was evaluated in cervical cancer cell lines by treating the cells with the drugs alone and in combination, then plotting their effects in an isobologram. Protein expression of phosphorylated Rb, and cleaved PARP were measured using western blot. An athymic nude mouse model was utilized to test the SHetA2/palbociclib combination in vivo. Mice were treated every day for 24 days with control solvent, 60mg/kg SHetA2, 100mg/kg palbociclib, or in combination. Differences in tumor growth inhibition between the groups were analyzed using repeated measure one-way ANOVA with multiple comparosions post-hoc analysis. Tumors were evaluated by immunohistochemistry and stained with CD31 and cyclin D1 antibodies. Results: The drug combination consistently demonstrated synergistic activity in three cervical cell lines (CI Conclusions: The drug combination was synergistic in vitro and significantly effective in vivo. The mechanism of synergy appears to involve induction of apoptosis and reduction of cyclin D1, phosphorylated Rb, and angiogenesis. Citation Format: Amy Bosley, Rajani Rai, Doris M. Benbrook. SHetA2 increases the activity of palbociclib in cervical cancer in vitro and in vivo [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6369.
Protecting Surgical Patient Safety During the Coronavirus Disease 2019 (COVID-19) Pandemic.

As elective surgery slowly re-opens across the country, it is paramount that surgeons recognize and take responsibility for their roles in protecting patient safety during the COVID-19 pandemic. Namely, these include (1) to prevent further spread of the Severe Acute Respiratory Syndrome (SARS)-CoV-2 Virus, (2) to understand the shift in injuries that has occurred as a result of altered lifestyles led by our patients, (3) to leverage our platforms to disseminate information regarding how individuals can maintain musculoskeletal health during the pandemic. Efforts taken to reduce the spread of SARS-CoV-2 can be focused on three broad categories of provider-patient interaction: pre-operative and clinic visits, surgical encounters, and post-operative care.
The Role of General Risk Preferences in Messaging About COVID-19 Vaccine Take-Up

Development of an effective vaccine that protects against COVID-19 is widely considered one of the best paths to ending the current health crisis While the ab
Predictive Patterns of Antidepressant Response from Pre-Treatment Reward Processing using Functional MRI and Deep Learning: Key Results from the EMBARC Randomized Clinical Trial

Uncertainty in selecting the appropriate antidepressant for each patient is a major challenge in treatment of major depressive disorder (MDD). No biologically driven markers are currently available to improve precision in treatment selection, thus leading to a trial-and-error process and prolonged morbidity for most patients. This study developed deep learning models that accurately predict treatment outcomes for sertraline, bupropion and placebo. Models were trained on data from the EMBARC study, in which 223 un-medicated subjects with MDD underwent pre-treatment reward task fMRI and received 8 weeks of treatment with sertraline, bupropion, or placebo. These models integrate fMRI and clinical measures and they explain up to 37% of the variance in ΔHAMD, classify remitters with NNT of 2.3-4.3, and classify responders with NNT of 3.2-4.9. Findings reveal new regions predictive of treatment outcome such as the hippocampus and paracentral lobule, while additional regions implicated in existing research are corroborated. Distinct models were identified for each treatment and provide substantial evidence of their potential to improve precision in treatment selection for MDD.
44. Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Turner Syndrome: Experience from a Large Turner Syndrome Center

Background More than 80% of girls with Turner syndrome (TS) experience primary ovarian failure prior to the onset of menarche. Hormone replacement therapy (HRT) is recommended to start between 11-12 years of age, followed by titration to adult dosing over 18-24 months. Current guidelines recommend that HRT starts with transdermal estradiol, followed by the addition of oral progesterone once breakthrough bleeding occurs or after 18-24 months of unopposed estrogen therapy, whichever occurs first. In our TS population, several individuals have experienced abnormal uterine bleeding (AUB) while undergoing pubertal induction with transdermal estradiol. The objective of this study was to identify risk factors associated with and evaluate the management practices of AUB during pubertal induction among females with TS. Methods A retrospective case series of 45 TS females seen between January 2007 and June 2019 . Among these, 64% (n=29) served as controls and 55% (n=16) experienced AUB. Results Several risk factors for the development of AUB were identified: frequency of progestin cycling less than monthly (56.5% for cases vs. 0% for control), prolonged duration of unopposed estrogen (median of 21 months for cases vs. 17 months for controls), low dose ( Conclusions Based on our experience, we recommend the following to prevent AUB during pubertal induction with transdermal estrogen in TS girls: 1) Cycle with progestins monthly, 2) Introduce progestins at the onset of breakthrough bleeding or at 18 months, whichever occurs first, 3) Use progestin dosing at the upper end of the recommended range (e.g. 200 mg for micronized progesterone) 4) Counsel all patients regarding the risk of AUB, 5) Monitor all patients regularly during pubertal induction, 6) Monitor with heightened surveillance those patients who show rapid development of secondary sex characteristics on low dose estrogen.
Fear of Dependency and Life-Space Mobility as Predictors of Attitudes Toward Assistive Devices in Older Adults.

Assistive devices can help older adults remain independent; however, they may hesitate to use them due to fears of appearing dependent by embodying aging stereotypes. Reluctance to use assistive de...
Another look at the extinction of conditioned flavor preferences: Amount of training and tests for spontaneous recovery

A conditioned flavor preference develops when hungry or thirsty rats experience a neutral flavor mixed in solution with a nutrient. In two sets of studies, we previously demonstrated that this learned preference is highly sensitive to flavor nonreinforcement (i.e., exposure to the flavor without the nutrient) either prior to (latent inhibition), during (partial reinforcement), or following (extinction) flavor-nutrient pairings. In each of these studies we employed a nutrient devaluation procedure to assess the integrity of specific flavor-nutrient associations following extinction, but more recently Gonzalez, Morillas, and Hall (Journal of Experimental Psychology: Animal Learning & Cognition, 42, 380-390, 2016) observed that sensitivity to extinction in thirsty rats in this preparation may depend upon use of a post-conditioning nutrient devaluation procedure. To assess the generality of our earlier results, but without including a post-conditioning nutrient devaluation phase, we assessed in three experiments the role of the number of flavor-nutrient pairings given prior to extinction and the possibility of spontaneous recovery following a 3-week delay. We observed that extinction consistently weakened the flavor preference in thirsty rats (in spite of the absence of a nutrient devaluation procedure) and also found no evidence for spontaneous recovery. These results establish that our prior findings that conditioned flavor preferences are weakened by extinction are quite robust in thirsty rats and that these extinction effects may be fairly permanent.
Clinical and Functional Outcomes by Graft Type in Superior Capsular Reconstruction: A Systematic Review and Meta-analysis.

Background:In recent years, superior capsular reconstruction (SCR) has emerged as a promising treatment for massive rotator cuff tears and has been performed with an array of graft options, most co...
Dietary control of chromatin

Organisms must be able to rapidly alter gene expression in response to changes in their nutrient environment. This review summarizes evidence that epigenetic modifications of chromatin depend on particular metabolites of intermediary metabolism, enabling the facile regulation of gene expression in tune with metabolic state. Nutritional or dietary control of chromatin is an often-overlooked, yet fundamental regulatory mechanism directly linked to human physiology. Nutrient-sensitive epigenetic marks are dynamic, suggesting rapid turnover, and may have functions beyond the regulation of gene transcription, including pH regulation and as carbon sources in cancer cells.
Breastfeeding and Infant Health in the Indian Subcontinent: Problems and Solutions

The fourth Millennium Development Goal set by the United Nations aspires to reduce child mortality by two-thirds between 1990 and 2015 [1]. The World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) estimate that exclusive breastfeeding (EBF) for the first 6 months after birth could prevent the deaths of 1.5 million infants worldwide each year [2, 3]. According to the WHO, proper breastfeeding practices include initiation of breastfeeding within 1 h of birth, EBF for the first 6 months, and continued breastfeeding until the infant is 2 years of age [4]. EBF is the practice of feeding only breast milk (and medicine when prescribed) to the infant, and is recommended as the best feeding method for infants, as it protects against morbidity and mortality [5]. Other benefits include the immunological properties of breast milk, the long-term benefits of breastfeeding, and the decreased transmission of HIV in HIV-exposed infants when they are exclusively breastfed [4]. Unfortunately, EBF is not as widely practiced as it should be.
Neonatal overexpression of estrogen receptor-α alters midbrain dopamine neuron development and reverses the effects of low maternal care in female offspring.

Maternal behavior is dependent on estrogen receptor-alpha (ERα; Esr1) and oxytocin receptor (OTR) signaling in the medial preoptic area (MPOA) of the hypothalamus, as well as dopamine signaling from the ventral tegmental area (VTA) to forebrain regions. Previous studies in rats indicate that low levels of maternal care, particularly licking/grooming (LG), lead to reduced levels of MPOA ERα and VTA dopamine neurons in female offspring and predict lower levels of postpartum maternal behavior by these offspring. The aim of this study was to determine the functional impact on maternal behavior of neonatal manipulation of ERα in females that had experienced low versus high levels of postnatal maternal LG. Adenovirus expressing ESR1 was targeted to the MPOA in female pups from low and high LG litters on postnatal day 2–3. Overexpression of ESR1 in low LG offspring elevated the level of ERα-immunoreactive cells in the MPOA and of tyrosine hydroxylase cells in the VTA to that observed in high LG females. Amongst juvenile female low LG offspring, ESR1 overexpression also decreased the latency to engage in maternal behavior toward donor pups. These results show that virally mediated expression of ESR1 in the neonatal rat hypothalamus results in lasting changes in ESR1 expression through the juvenile period, and can “rescue” hormone receptor levels and behavior of offspring reared by low LG dams, potentially mediated by downstream alterations within reward circuitry. Thus, the transmission of maternal behavior from one generation to the next can be augmented by neonatal ERα in the MPOA. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1114–1124, 2015
Education at the Margins: Ubuntu at our Core

Jesuit Commons-Higher Education at the Margins (JC-HEM) offers a Jesuit education for students living at the margins in Kakuma Refugee Camp, Kenya; Dzaleka (Za-lēka) Refugee Camp, Malawi; and in Amman, Jordan. I have enjoyed teaching (and learning from) our diverse learners in our Program over the past few years. Having fled their warring homelands, our learners’ families, careers and lives scatter like shrapnel and fall to the dust of their forsaken refugee camps. In Kakuma Refugee Camp alone, there are more than 100,000 refugees most of whom have lived there for many years. The students in our three-year program indeed feel like the “chosen ones” and are a paragon of leadership and education for the others in the camps. With volunteer faculty from many Jesuit universities teaching online liberal arts curricula, the JC-HEM students and faculty together bring their passion for (freedom through) education, a need for strengthened community within and beyond the Camps. As the lead faculty of several communication and leadership courses, I awaken a bit more to our interconnectedness and mutual learning with each new student and course. Nelson Mandela reminds us, “Ubuntu: I am who I am because of who you are to me.” This paper reveals my students’ and my own online learning woven together in Ubuntu, various Jesuit teachings and many other scholars’ theories.
Splicing and 3'-processing of the tyrosine tRNA of Trypanosoma brucei.

Abstract Trypanosoma brucei belongs to a family of protozoa that is characterized as having diverged early in the evolution of eukaryotes. Many unusual forms of RNA processing have been discovered in these cells, one of which is trans-splicing, and, although a great number of genes have been sequenced, no evidence for cis-splicing has yet been found. This study shows that tRNA(Tyr) of T. brucei contains an 11-nucleotide intron. tRNA of the size predicted for unspliced precursor was detected by Northern analysis using an oligonucleotide probe complementary to the putative intervening region. Direct sequence analysis of mature tRNA(Tyr) showed that the predicted intron region is absent from this form of the molecule. Mutated versions of the gene encoding tRNA(Tyr) were introduced into trypanosomes by DNA transformation and shown to be expressed in vivo. Introduction into the genome of a tRNA(Tyr) gene containing an amber suppressor mutation led to a significant accumulation of unspliced precursor molecules. Analysis of the tRNA(Tyr) species from both the wild type and transformed cells revealed unspliced and spliced processing intermediates. The relative abundance of each of these intermediates suggests that 3'-processing and splicing occur independently and that, in the wild type, splicing tends to precede 3'-processing and CCA addition.
AGU/AGI Showcase ODP on Capitol Hill

On Wednesday, June 13, lawmakers and their staffs jammed a Capitol Hill exhibit of research programs supported by the National Science Foundation (NSF). Sponsored by the Coalition for National Science Funding (CNSF), the exhibit is intended to demonstrate to members of Congress—who often wonder where the money they appropriate goes—the exciting research programs funded by NSF and their results. AGU joined with the American Geological Institute (AGI) in sponsoring an exhibit highlighting the Ocean Drilling Project (ODP). Frank Rack and Brecht Donoghue of the Joint Oceanographic Institutions (JOI) explained to interested legislators and congressional staff members that ODP is an international partnership of scientists and research institutions.
EFFECT OF PREDNISOLONE ON HUMAN BONE MARROW CULTURES.

Abstract Human bone marrow cultured in NCTC 109 and pooled human serum develops fibroblast-like cells, “macrophages” and limited proliferation of hemic cells. The addition of prednisolone 0.5 μg. to 50 μg./ml. results in increased proliferation of fibroblast-like cells in primary cultures. Morphologically, the steroid-treated cells are flat and squat, with large nucleoli, and frequently show in-creased cytoplasmic basophilia. The in-crease in cell growth observed in these cultures is in contrast to much of the experimental data regarding effects of glucocorticoids on other tissues in vitro. The mechanism(s) of action which result in this phenomenon are not known.
Direct Simulation of Evolution and Control of Nonlinear Instabilities in Attachment-Line Boundary Layers

The unsteady, incompressible Navier-Stokes equations are used for the direct numerical simulation (DNS) of spatially evolving disturbances in a three-dimensional (3-D) attachment-line boundary layer. Two-dimensional (2-D) disturbances are introduced either by forcing at the in ow or by harmonic-source generators at the wall; 3-D disturbances are introduced by harmonic-source generators at the wall. The DNS results are in good agreement with both 2-D non-parallel theory (for small-amplitude disturbances) and weakly nonlinear theory (for finite-amplitude disturbances), which validates the two theories. The 2-D DNS results indicate that nonlinear disturbance growth occurs near branch II of the neutral stability curve; however, steady suction can be used to stabilize this disturbance growth. For 3-D instabilities that are generated o the attachment line, spreading both toward and away from the attachment line causes energy transfer to the attachment-line and downstream instabilities; suction stabilizes these instabilities. Furthermore, 3-D instabilities are more stable than 2-D or quasi-2-D instabilities.
The disproportionation and combination of ethyl radicals: the photolysis of mercury diethyl

The photolysis of mercury diethyl vapour has been investigated in a static system over a pressure range of 0 to 80 mm. and a temperature range of 75 to 200° C. The products were analyzed for C 2 H 6 , C 2 H 4 , C 4 H 10 , C 4 H 8 . No significant amounts of H 2 , CH 4 , C 4 H 8 or higher hydrocarbons were found. Rotating sector experiments have enabled a complete determination of the velocity constants of the reactions: (1) C 2 H 6 + C 2 H 5 = C 2 H 4 + C 2 H 6 , (2) C 2 H 5 + C 2 H 5 = C 4 H 10 , (3) C 2 H 5 + Hg Et 2 = C 2 H 4 + C 2 H 6 + Hg + C 2 H 5 . Energies of activation and frequency factors for these reactions have been deduced. E 1 – E 2 = 0⋅8±0⋅2 kcal./mole, E 2 ≯ 0⋅65 kcal./mole has been deduced from k 2 at 150° C and the calculated collision frequency.
Crescentic lamellar keratoplasty for pellucid marginal degeneration.

Pellucid marginal degeneration is an uncommon, idiopathic, noninflammatory peripheral thinning disorder affecting the inferior cornea. 1 The resulting irregular corneal astigmatism frequently precludes spectacle or contact lens correction. Various surgical procedures have been used to modify the corneal astigmatism and improve visual acuity in severe cases. 2 We successfully treated pellucid marginal degeneration with an inferior, crescentic, lamellar keratoplasty.