bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis
Authors: Aldridge Jonathan , Andersson Kerstin , Gjertsson Inger , Hultgård Ekwall Anna-Karin , Hallström Magnus , van Vollenhoven Ronald , Lundell Anna-Carin , Rudin Anna 
Published: May 2021

AbstractObjectiveTreatment with CTLA-4Ig blocks T-cell activation and is clinically effective in RA. However, it is unknown if specific CD4+ T-cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA).MethodsThis study included 60 patients with untreated eRA from a larger randomized trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI ≤ 2.8) at week 24. Proportions of 12 CD4+ T-cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment.ResultsIn patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T-cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.ConclusionThese findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.
DOSE EVALUATION AND PROPOSAL OF LOCAL DIAGNOSTIC REFERENCE LEVELS FOR PAEDIATRIC CARDIAC CATHETERIZATIONS PERFORMED ON A HIGH-SENSITIVITY ANGIOGRAPHIC SYSTEM ALLOWING LOW-DOSE IMAGING
Authors: Hultenmo Maria , Nygren Anders , Söderberg Björn , Wåhlander Håkan 
Published: May 2021

Abstract
Radiation doses from paediatric cardiac catheterizations were analysed based on procedure type and patient weight, and local diagnostic reference levels (LDRLs) were proposed. The procedures were performed on a Siemens Artis Q.zen biplane system with high-sensitivity detectors allowing low-dose imaging. Good radiological practice, e.g. adapting dose level and frame rate continuously and minimizing the x-ray field with collimators, was routine during procedures. The median total dose-area-product (DAP) value was 58 μGym2 for diagnostic catheterizations, 48 μGym2 for interventional catheterizations and 33 μGym2 for myocardial biopsies. The median DAP per body weight was 4.0 μGym2 kg−1. The median total fluoroscopy time varied from 6.0 min for myocardial biopsies, to 9.7 and 10.5 min, respectively, for diagnostic and interventional catheterizations. The third quartile of the DAP values in each weight group was proposed as LDRL. LDRLs for fluoroscopy time were determined solely based on procedure type, due to the absence of weight dependence.
Precision Medicine on the Fly: Using Drosophila to Decipher Gene-Environment Interactions in Parkinson’s Disease
Authors: Sarkar Souvarish , Feany Mel B 
Published: May 2021

Abstract
Big data approaches have profoundly influenced state-of-the-art in many fields of research, with toxicology being no exception. Here, we use Parkinson’s disease as a window through which to explore the challenges of a dual explosion of metabolomic data addressing the myriad environmental exposures individuals experience and genetic analyses implicating many different loci as risk factors for disease. We argue that new experimental approaches are needed to convert the growing body of omics data into molecular mechanisms of disease that can be therapeutically targeted in specific patients. We outline one attractive strategy, which capitalizes on the rapid generation time and advanced molecular tools available in the fruit fly, Drosophila, to provide a platform for mechanistic dissection and drug discovery.
Imaging-Based Resistance Assay Using Enhanced Luminescence-Tagged Pseudomonas syringae Reveals a Complex Epigenetic Network in Plant Defense Signaling Pathways
Authors: Pujara Dinesh S. , Kim Sung-Il , Nam Ji Chul , Mayorga José , Elmore Isabella , Kumar Manish , Koiwa Hisashi , Kang Hong-Gu 
Published: May 2021

High-throughput resistance assays in plants have a limited selection of suitable pathogens. In this study, we developed a Pseudomonas syringae strain chromosomally tagged with the Nanoluc luciferase (NL) from the deep-sea shrimp Oplophorus gracilirostris, a bioluminescent marker significantly brighter than the conventional firefly luciferase. Our reporter strain tagged with NL was more than 100 times brighter than P. syringae tagged with the luxCDABE operon from Photorhabdus luminescens, one of the existing luciferase-based strains. In planta imaging was improved by using the surfactant Silwet L-77, particularly at a lower reporter concentration. Using this imaging system, more than 30 epigenetic mutants were analyzed for their resistance traits because the defense signaling pathway is known to be epigenetically regulated. SWC1, a defense-related chromatin remodeling complex, was found to be a positive defense regulator, which supported one of two earlier conflicting reports. Compromises in DNA methylation in the CG context led to enhanced resistance against virulent Pseudomonas syringae pv. tomato. Dicer-like and Argonaute proteins, important in the biogenesis and exerting the effector function of small RNAs, respectively, showed modest but distinct requirements for effector-triggered immunity and basal resistance to P. syringae pv. tomato. In addition, the transcriptional expression of an epigenetic component was found to be a significant predictor of its immunity contribution. In summary, this study showcased how a high-throughput resistance assay enabled by a pathogen strain with an improved luminescent reporter could provide insightful knowledge about complex defense signaling pathways. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Teaching Spiritual and Religious Competencies to Psychiatry Residents: A Scoping and Systematic Review
Authors: Hathaway David B. , de Oliveira e Oliveira Fabrício H. A. , Mirhom Mena , Moreira-Almeida Alexander , Fung Wai Lun Alan , Peteet John R. 
Published: May 2021

Purpose
For many persons worldwide, mental health is inseparably linked with spirituality and religion (S&R), yet psychiatrists have repeatedly expressed doubts regarding their preparedness to address patients’ spirituality or religion appropriately. In recent decades, medical educators have developed and implemented curricula for teaching S&R-related competencies to psychiatry residents. The authors reviewed the literature to understand the scope and effectiveness of these educational initiatives.

Method
The authors searched 8 databases to identify studies for a scoping review and a systematic review. The scoping review explored educational approaches (topics, methods) used in psychiatry residency programs to teach S&R-related competencies. The systematic review examined changes in psychiatry trainees’ competencies and/or in patient outcomes following exposure to these educational interventions.

Results
Twelve studies met criteria for inclusion in the scoping review. All reported providing residents with both (1) a general overview of the intersections between mental health and S&R and (2) training in relevant interviewing and assessment skills. Seven of these studies—representing an estimated 218 postgraduate psychiatry trainees and at least 84 patients—were included in the systematic review. Residents generally rated themselves as being more competent in addressing patients’ S&R-related concerns following the trainings. One randomized controlled trial found that patients with severe mental illness who were treated by residents trained in S&R-related competencies attended more appointments than control patients.

Conclusions
S&R-related educational interventions appeared generally well tolerated and appreciated by psychiatry trainees and their patients; however, some topics (e.g., Alcoholics Anonymous) received infrequent emphasis, and some experiential teaching methodologies (e.g., attending chaplaincy rounds) were less frequently used for psychiatry residents than for medical students. The positive association between teaching S&R-related competencies to psychiatry residents and patient appointment attendance merits further study. Future trainings should supplement classroom learning with experiential approaches and incorporate objective measures of resident competence.
The Women Before Me: My Journey Painting Honor Wall Portraits of Women Physicians
Authors: Chen Pamela , Kasper Jennifer , Khoshbin Shahram 
Published: May 2021

In this article, the authors briefly review the history and status of institutional honor wall portraits at medical schools, and they highlight the implications of a lack of diversity in these portraits for current medical students and the academic medicine pipeline. The authors then describe how contemporary portrait artists have used art as a tool for advocacy. They detail the first author’s empowering and intimate journey as a medical student as she identified, connected with, and painted a portrait gallery of some of her medical school’s prominent alumnae of color. This unique effort highlighted the unsung accomplishments of these women physicians and served to combat the visual disparity in honor wall portraits on campus.
The authors also outline the common barriers faced by the portrait subjects and the key validation they offered the first author, a fellow woman of color. The authors describe the historical and psychological significance of several artistic decisions made for these portraits in weighing the intersections of race, gender, and profession. They then emphasize the reciprocal nature of oil portraiture and how, through painting these women, the first author was able to better envision her community of mentors, deepen her commitment to diversity and inclusion, and strengthen her own career aspirations. These portraits will hang in the student center of Harvard Medical School and will serve as a lasting reminder to future trainees, especially women and people of color, that they belong in the halls of medicine.
Patient monitoring in the nonoperating room anesthesia (NORA) setting: current advances in technology
Authors: Routman Justin , Boggs Steven Dale 
Published: May 2021

Purpose of review
Nonoperating room anesthesia (NORA) procedures continue to increase in type and complexity as procedural medicine makes technical advances. Patients presenting for NORA procedures are also older and sicker than ever. Commensurate with the requirements of procedural medicine, anesthetic monitoring must meet the American Society of Anesthesiologists standards for basic monitoring.

Recent findings
There have been improvements in the required monitors that are used for intraoperative patient care. Some of these changes have been with new technologies and others have occurred with software refinements. In addition, specialized monitoring devises have also been introduced into NORA locations (depth of hypnosis, respiratory monitoring, point-of care ultrasound). These additions to the monitoring tools available to the anesthesiologist working in the NORA-environment push the boundaries of procedures which may be accomplished in this setting.

Summary
NORA procedures constitute a growing percentage of total administered anesthetics. There is no difference in the monitoring standard between that of an anesthetic administered in an operating room and a NORA location. Anesthesiologists in the NORA setting must have the same compendium of monitors available as do their colleagues working in the operating suite.
Radial Head Replacement for Acute Radial Head Fractures: Outcome and Survival of Three Implant Designs With and Without Cement Fixation
Authors: Songy Chad E. , Kennon Justin C. , Barlow Jonathan D. , Sanchez-Sotelo Joaquin , O'Driscoll Shawn W. , Morrey Mark E. 
Published: May 2021

Objectives:
To determine outcomes of radial head replacement (RHR) for acute fractures using 3 different implant designs with or without cement fixation.

Design:
Retrospective.

Setting:
Tertiary referral hospital.

Patients/Participants:
One hundred fourteen elbows underwent RHR for an acute radial head fracture using either (1) a nonanatomic design and smooth stem (n = 60), (2) a nonanatomic design with a grit-blasted, ingrowth, curved stem (n = 21), or (3) an anatomic design with a grit-blasted ingrowth straight stem (n = 33). Cemented (25%) or uncemented (75%) fixation was used at the discretion of the treating surgeon.

Intervention:
RHR.

Main Outcome Measurements:
The primary outcome was implant survivorship free of revision or removal for any reason. All elbows were evaluated clinically (the Mayo Elbow Performance Score and reoperations/complications) and radiographically.

Results:
Fourteen implants (12%) were revised. Of elbows with a minimum 2-year clinical follow-up, the average Mayo Elbow Performance Score was 88. The rate of survivorship free from revision was 92% [95% confidence interval (CI) = 87%–98%] at 2 years, 90% (CI = 84%–96%) at 5 years and 84% (CI = 75%–94%) at 10 years. The differences in survivorship between the 3 implants did not reach statistical significance, but the nonanatomic design with a grit-blasted ingrowth curved stem had a hazard ratio of 4.6 (95% CI = 0.9%–23%) for failure. There were no differences in survivorship between cemented versus uncemented stems. For those elbows with a minimum of 2 years of radiographic follow-up, implant tilt was observed in 10 (16%) elbows and loosening in 16 (26%) elbows. Stress shielding was present in 19 (42%) of well-fixed implants.

Conclusions:
RHR for acute trauma leads to survivorship greater than 80% at 10 years. Radiographic changes (loosening, stress shielding, and implant tilting) can be expected in a substantial portion of elbows at long-term follow-up.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Opioid Prescriptions After Pediatric Orthopedic Surgery: Analyzing Rates of Unfilled Prescriptions
Authors: Cazzulino Alejandro , Meza Blake C. , Woodard Thaddeus , Swarup Ishaan , Shah Apurva S. 
Published: May 2021

Background:
The prevalence of nonmedical use of prescription opioids among American teenagers is staggering. Reducing the quantity of postoperative opioid prescriptions can help address this epidemic by decreasing the availability of opioids. As the fourth most common opioid prescribers, orthopaedic surgeons are primed to lead efforts to reverse this crisis. The purpose of this study was to determine patient factors associated with filling opioid prescriptions after pediatric orthopaedic surgery and to recommend potential methods to limit excess opioid prescriptions.

Methods:
This retrospective cohort study included 1413 patients who were prescribed opioids upon discharge after an orthopaedic surgical procedure at a single urban children’s hospital from 2017 to 2018. The state’s Prescription Drug Monitoring Program was used to determine which patients filled their opioid prescriptions. Comparisons of demographic, clinical, and surgical factors were made between patients that filled their opioid prescription upon discharge and those that did not. Statistical analysis included λ2, Mann-Whitney U, and binary logistic regression for significant factors from bivariate analysis.

Results:
Nine percent (n=127) of patients did not fill their opioid prescriptions after discharge. Those who filled and did not fill prescriptions were similar in terms of sex, ethnicity, race, insurance type, and age at surgery (P>0.05). Patients who did not fill their opioid prescriptions received significantly fewer opioids during their postoperative hospital course (5.3 vs. 7.7 mg oxycodone, P=0.01). Not receiving oral oxycodone during postoperative hospitalization (odds ratio=2.16, 95% confidence interval: 1.49-3.14) and undergoing upper extremity surgery (odds ratio=2.00, 95% confidence interval: 1.37-2.91) were independently associated with not filling opioid prescriptions after surgery in the multivariate analysis.

Conclusions:
This study identified a subset of pediatric orthopaedic surgery patients who were prescribed opioids upon discharge but did not fill those prescriptions. Factors that increased the likelihood that patients did not fill their prescriptions upon discharge included fewer postoperative hospital course opioids, no oral oxycodone, and surgery on the upper extremity. Future studies must be performed to help decrease the number of opioids prescribed unnecessarily.

Level of Evidence:
Level III—prognostic cohort study.
Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC)
Authors: Oikonomou Dimitrios , Karamouzis Michalis V. , Moris Dimitrios , Dimitrokallis Nikolaos , Papamichael Demetris , Kountourakis Panteleimon , Astras Georgios , Davakis Spyridon , Papalampros Alexandros , Schizas Dimitrios , Petrou Athanasios S. , Felekouras Evangelos 
Published: May 2021

Objectives:
Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy.

Materials and Methods:
From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy.

Results:
All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive.

Conclusion:
The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.
Association of endocannabinoids with pain in endometriosis
Authors: Andrieu Thomas , Chicca Andrea , Pellegata Daniele , Bersinger Nick A. , Imboden Sara , Nirgianakis Konstantinos , Gertsch Juerg , Mueller Michael D. 
Published: May 2021

Abstract
Endocannabinoid (eCB) levels fluctuate in inflammatory conditions and as such may take part in endometriosis-associated pain or even in endometriosis pathogenesis. In this case–control (23 cases and 19 controls) study, targeted lipids were measured in the serum and peritoneal fluid collected during laparoscopy. Endometriosis was confirmed histologically. Dysmenorrhea, abdominal pain, and dyspareunia were assessed using the Numeric Rating Scale for pain. Steroids, eCBs, and related lipids were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tumor necrosis factor alpha, IL-8, PAPP-A, PP14, RANTES, OPG, MIDKINE, MCP-1, VEGF, leptin, and defensins were quantified by ELISA. We found that eCB levels were significantly influenced by both noncyclic and cyclic abdominal pain. Specifically, women suffering from noncyclic abdominal pain were characterized by a higher 2-AG level in the peritoneal fluid throughout the menstrual cycle, whereas women suffering from dysmenorrhea had higher 2-AG levels and lower AEA levels during the proliferative phase alone. In addition, 2-AG positively correlated with prostaglandin E2 (PGE2), and the ratio AEA/2-AG positively correlated with defensins, suggesting a possible link between endocannabinoids system and inflammatory pain. The results of the current study indicate that the eCB system may play a role in endometriosis-associated pain, but additional studies are needed to investigate the causal relationship.
Longitudinal, bidirectional relationships of insomnia symptoms and musculoskeletal pain across adolescence: the mediating role of mood
Authors: Arnison Tor , Schrooten Martien G.S. , Hesser Hugo , Jansson-Fröjmark Markus , Persson Jonas 
Published: May 2021

Abstract
Previous studies have established a bidirectional relationship between sleep and pain, and mood has been proposed as a mediator of this relationship. There are only a limited number of longitudinal studies examining the mediational role of mood, and the directionality of effects between sleep, pain, and mood is uncertain. In addition, despite the high prevalence of pain and sleep problems during adolescence, these relationships have rarely been examined in a longitudinal sample of adolescents. Here, longitudinal survey data with 5 yearly measurements were used to examine the bidirectional relationship between insomnia symptoms and pain across adolescence (Mbaseline age = 13.65 years, Nbaseline = 2767). We also explored if depressed mood, positive affect, and anxious mood are mediators in both directions of the sleep–pain relationship. Using latent variables for insomnia, pain, and mood at multiple time points, the data were analyzed with cross-lagged panel models for longitudinal data with structural equation modeling. Current results confirmed a bidirectional relationship between insomnia symptoms and pain, where the effect of insomnia symptoms on pain was stronger than vice versa. Depressed mood and anxious mood mediated the effect of insomnia symptoms on pain, but not the reverse effect of pain on insomnia symptoms. Positive affect did not serve as a mediator in either direction. These findings add novel insights into the temporal directionality of sleep, pain, and mood during adolescence, suggesting a temporal path from sleep to pain, through mood, rather than a reciprocal relationship between the constructs.