bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiemetic Administration and Its Association with Race: A Retrospective Cohort Study
Authors: White Robert S. , Andreae Michael H. , Lui Briana , Ma Xiaoyue , Tangel Virginia E. , Turnbull Zachary A. , Jiang Silis Y. , Nachamie Anna S. , Pryor Kane O. ,   Multicenter Perioperative Outcomes Group Collaborators
Published: May 2023

Background

Anesthesiologists’ contribution to perioperative healthcare disparities remains unclear because patient and surgeon preferences can influence care choices. Postoperative nausea and vomiting is a patient- centered outcome measure and a main driver of unplanned admissions. Antiemetic administration is under the sole domain of anesthesiologists. In a U.S. sample, Medicaid insured versus commercially insured patients and those with lower versus higher median income had reduced antiemetic administration, but not all risk factors were controlled for. This study examined whether a patient’s race is associated with perioperative antiemetic administration and hypothesized that Black versus White race is associated with reduced receipt of antiemetics.

Methods

An analysis was performed of 2004 to 2018 Multicenter Perioperative Outcomes Group data. The primary outcome of interest was administration of either ondansetron or dexamethasone; secondary outcomes were administration of each drug individually or both drugs together. The confounder-adjusted analysis included relevant patient demographics (Apfel postoperative nausea and vomiting risk factors: sex, smoking history, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use; as well as age) and included institutions as random effects.

Results

The Multicenter Perioperative Outcomes Group data contained 5.1 million anesthetic cases from 39 institutions located in the United States and The Netherlands. Multivariable regression demonstrates that Black patients were less likely to receive antiemetic administration with either ondansetron or dexamethasone than White patients (290,208 of 496,456 [58.5%] vs. 2.24 million of 3.49 million [64.1%]; adjusted odds ratio, 0.82; 95% CI, 0.81 to 0.82; P < 0.001). Black as compared to White patients were less likely to receive any dexamethasone (140,642 of 496,456 [28.3%] vs. 1.29 million of 3.49 million [37.0%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.78; P < 0.001), any ondansetron (262,086 of 496,456 [52.8%] vs. 1.96 million of 3.49 million [56.1%]; adjusted odds ratio, 0.84; 95% CI, 0.84 to 0.85; P < 0.001), and dexamethasone and ondansetron together (112,520 of 496,456 [22.7%] vs. 1.0 million of 3.49 million [28.9%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.79; P < 0.001).

Conclusions

In a perioperative registry data set, Black versus White patient race was associated with less antiemetic administration, after controlling for all accepted postoperative nausea and vomiting risk factors.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Postoperative Impedance-Based Estimation of Cochlear Implant Electrode Insertion Depth
Authors: Schraivogel Stephan , Aebischer Philipp , Wagner Franca , Weder Stefan , Mantokoudis Georgios , Caversaccio Marco , Wimmer Wilhelm
Published: May 2023

Objectives:

Reliable determination of cochlear implant electrode positions shows promise for clinical applications, including anatomy-based fitting of audio processors or monitoring of electrode migration during follow-up. Currently, electrode positioning is measured using radiography. The primary objective of this study is to extend and validate an impedance-based method for estimating electrode insertion depths, which could serve as a radiation-free and cost-effective alternative to radiography. The secondary objective is to evaluate the reliability of the estimation method in the postoperative follow-up over several months.

Design:

The ground truth insertion depths were measured from postoperative computed tomography scans obtained from the records of 56 cases with an identical lateral wall electrode array. For each of these cases, impedance telemetry records were retrieved starting from the day of implantation up to a maximum observation period of 60 mo. Based on these recordings, the linear and angular electrode insertion depths were estimated using a phenomenological model. The estimates obtained were compared with the ground truth values to calculate the accuracy of the model.

Results:

Analysis of the long-term recordings using a linear mixed-effects model showed that postoperative tissue resistances remained stable throughout the follow-up period, except for the two most basal electrodes, which increased significantly over time (electrode 11: ~10 Ω/year, electrode 12: ~30 Ω/year). Inferred phenomenological models from early and late impedance telemetry recordings were not different. The insertion depth of all electrodes was estimated with an absolute error of 0.9 mm ± 0.6 mm or 22° ± 18° angle (mean ± SD).

Conclusions:

Insertion depth estimations of the model were reliable over time when comparing two postoperative computed tomography scans of the same ear. Our results confirm that the impedance-based position estimation method can be applied to postoperative impedance telemetry recordings. Future work needs to address extracochlear electrode detection to increase the performance of the method.
Smoking is associated with surgical site infection, unplanned reoperation, and unplanned 30-day readmission with distal upper extremity fractures
Authors: Johnson Charles A. , Heffron Walker M. , Newton William N. , Daley Dane N.
Published: May 2023

Background:

The purpose of this study is to 1) determine the effect of smoking status on the rate of acute postoperative complications and 2) evaluate smoking as an independent risk factor for complications following open reduction and internal fixation (ORIF) of distal upper extremity fractures.

Methods:

The National Surgical Quality Improvement Program (NSQIP) database was queried to identify adult patients (>18 yr old) who underwent open reduction and internal fixation (ORIF) of distal upper extremity fractures between 2005 and 2018. Closed fractures of the distal radius, distal ulna, carpals, metacarpals, and phalanx were included. Open fractures, closed reduction and percutaneous pinning (CRPP) procedures, and operations with concomitant procedure codes were excluded. Patients were classified as either current smokers or non-smokers. Univariate analysis and multivariate logistic regression were used to assess the risk of perioperative complications based on current smoking status.

Results:

A total of 22,002 patients met inclusion criteria. Smoking was independently associated with an increased risk of post-operative complications (OR 1.43, 1.15-1.78, P<0.001), specifically, superficial surgical site infections (OR 2.11, CI 1.23–3.60, P=0.007). Current smokers were additionally associated with an increased risk of unplanned reoperation (OR 1.65, CI 1.10–2.48, P=0.022), and unplanned readmission (OR 1.39, CI 1.02-1.90, P=0.037).

Conclusions:

Smoking independently increases the risk for overall complications including superficial infections, unplanned reoperation, and unplanned readmission following ORIF of distal upper extremity fractures.

Level of Evidence:

III.
Developing a Classification Algorithm for Prediabetes Risk Detection From Home Care Nursing Notes
Authors: Jeon Eunjoo , Kim Aeri , Lee Jisoo , Heo Hyunsook , Lee Hana , Woo Kyungmi
Published: May 2023

This study developed and validated a rule-based classification algorithm for prediabetes risk detection using natural language processing from home care nursing notes. First, we developed prediabetes-related symptomatic terms in English and Korean. Second, we used natural language processing to preprocess the notes. Third, we created a rule-based classification algorithm with 31 484 notes, excluding 315 instances of missing data. The final algorithm was validated by measuring accuracy, precision, recall, and the F1 score against a gold standard testing set (400 notes). The developed terms comprised 11 categories and 1639 words in Korean and 1181 words in English. Using the rule-based classification algorithm, 42.2% of the notes comprised one or more prediabetic symptoms. The algorithm achieved high performance when applied to the gold standard testing set. We proposed a rule-based natural language processing algorithm to optimize the classification of the prediabetes risk group, depending on whether the home care nursing notes contain prediabetes-related symptomatic terms. Tokenization based on white space and the rule-based algorithm were brought into effect to detect the prediabetes symptomatic terms. Applying this algorithm to electronic health records systems will increase the possibility of preventing diabetes onset through early detection of risk groups and provision of tailored intervention.
Hormone therapy for sexual function in perimenopausal and postmenopausal women: a systematic review and meta-analysis update
Authors: Meziou Nadia , Scholfield Clare , Taylor Caroline A. , Armstrong Heather L.
Published: May 2023

Importance

Distressing sexual problems are a common complaint of menopausal women. In 2013, a Cochrane review assessed the effect of hormone therapy on sexual function in menopausal women; however, new evidence has since been published, which should be considered.

Objective

This systematic review and meta-analysis aims to update the evidence synthesis on the effect of hormone therapy, compared with control, on sexual function in perimenopausal and postmenopausal women.

Evidence Review

Thirteen databases and clinical trial registries (Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Literatura Latino-Americana e do Caribe em Ciéncias da Saúde, Database of Abstracts of Reviews of Effects, ClinicalTrials.gov, International Clinical Trials Registry Platform, Iranian Registry of Clinical Trials, Chinese Clinical Trial Registry, ISRCTN) were searched from December 2012 to March 30, 2022. Backward reference searching on all retrieved full texts was also performed. Study quality was assessed using the Cochrane ROB.2 tool. Data were pooled in random-effect model meta-analyses, which included all studies identified in the present search and all studies previously included in the 2013 Cochrane review.

Findings

Forty-seven randomized controlled trials (35,912 participants) were included in the systematic review, and 34 randomized controlled trials (15,079 participants) were included in the meta-analysis. The meta-analysis revealed that, in comparison to control, estrogen therapy (standardized mean difference [SMD], 0.16; 95% confidence interval [CI], 0.02 to 0.29; I
2 = 59%; 2,925 participants, 16 studies), estrogen plus progestogen therapy (SMD, 0.11; 95% CI, −0.07 to 0.29; I
2 = 65%; 2,432 participants, 7 studies), tibolone (SMD, 0.15; 95% CI, 0.02 to 0.28; I
2 = 0%; 916 participants, 2 studies), and selective estrogen receptor modulators (SMD, 0.18; 95% CI, 0.06 to 0.30; I
2 = 0%; 1,058 participants, 4 studies) may result in no effect to small benefit on sexual function composite score.

Conclusion and Relevance

Hormone therapy may slightly improve sexual functioning. This potential small benefit should be considered when discussing treatment options for other menopausal symptoms.
Single-cell RNA sequencing of liver fine-needle aspirates captures immune diversity in the blood and liver in chronic hepatitis B patients
Authors: Genshaft Alex S. , Subudhi Sonu , Keo Arlin , Sanchez Vasquez Juan Diego , Conceição-Neto Nádia , Mahamed Deeqa , Boeijen Lauke L. , Alatrakchi Nadia , Oetheimer Chris , Vilme Mike , Drake Riley , Fleming Ira , Tran Nancy , Tzouanas Constantine , Joseph-Chazan Jasmin , Arreola Villanueva Martin , van de Werken Harmen J. G. , van Oord Gertine W. , Groothuismink Zwier M. A. , Beudeker Boris J. , Osmani Zgjim , Nkongolo Shirin , Mehrotra Aman , Spittaels Kurt , Feld Jordan , Chung Raymond T. , de Knegt Robert J. , Janssen Harry L. A. , Aerssens Jeroen , Bollekens Jacques , Hacohen Nir , Lauer Georg M. , Boonstra Andre , Shalek Alex K. , Gehring Adam J.
Published: May 2023

Background and Aims:

HBV infection is restricted to the liver, where it drives exhaustion of virus-specific T and B cells and pathogenesis through dysregulation of intrahepatic immunity. Our understanding of liver-specific events related to viral control and liver damage has relied almost solely on animal models, and we lack useable peripheral biomarkers to quantify intrahepatic immune activation beyond cytokine measurement. Our objective was to overcome the practical obstacles of liver sampling using fine-needle aspiration and develop an optimized workflow to comprehensively compare the blood and liver compartments within patients with chronic hepatitis B using single-cell RNA sequencing.

Approach and Results:

We developed a workflow that enabled multi-site international studies and centralized single-cell RNA sequencing. Blood and liver fine-needle aspirations were collected, and cellular and molecular captures were compared between the Seq-Well S3 picowell-based and the 10× Chromium reverse-emulsion droplet–based single-cell RNA sequencing technologies. Both technologies captured the cellular diversity of the liver, but Seq-Well S3 effectively captured neutrophils, which were absent in the 10× dataset. CD8 T cells and neutrophils displayed distinct transcriptional profiles between blood and liver. In addition, liver fine-needle aspirations captured a heterogeneous liver macrophage population. Comparison between untreated patients with chronic hepatitis B and patients treated with nucleoside analogs showed that myeloid cells were highly sensitive to environmental changes while lymphocytes displayed minimal differences.

Conclusions:

The ability to electively sample and intensively profile the immune landscape of the liver, and generate high-resolution data, will enable multi-site clinical studies to identify biomarkers for intrahepatic immune activity in HBV and beyond.
Increasing risk of cannabis use disorder among U.S. veterans with chronic pain: 2005-2019
Authors: Mannes Zachary L. , Malte Carol A. , Olfson Mark , Wall Melanie M. , Keyes Katherine M. , Martins Silvia S. , Cerdá Magdalena , Gradus Jaimie L. , Saxon Andrew J. , Keyhani Salomeh , Maynard Charles , Livne Ofir , Fink David S. , Gutkind Sarah , Hasin Deborah S.
Published: May 2023

In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. From VHA electronic health records from 2005 to 2019 (∼4.3-5.6 million patients yearly), we extracted diagnoses of CUD and chronic pain conditions (International Classification of Diseases [ICD]-9-CM, 2005-2014; ICD-10-CM, 2016-2019). Differential trends in CUD prevalence overall and age-stratified (<35, 35-64, or ≥65) were assessed by any chronic pain and number of pain conditions (0, 1, or ≥2). From 2005 to 2014, the prevalence of CUD among patients with any chronic pain increased significantly more (1.11%-2.56%) than those without pain (0.70%-1.26%). Cannabis use disorder prevalence increased significantly more among patients with chronic pain across all age groups and was highest among those with ≥2 pain conditions. From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive.
Supportive Care Needs Trajectories in Patients With Advanced Non-Small-Cell Lung Cancer Receiving Chemotherapy: A Longitudinal Study
Authors: YEN Chun-Ju , HSU Hsin-Tien , HSIEH Hsiu-Fen , CHEN Ying-Ju , HUANG Ming-Shyan , LIN Pei-Chao
Published: May 2023

Background

The supportive care needs trajectories in patients with advanced non-small-cell lung cancer (NSCLC) during chemotherapy and the related factors have yet to be explored or addressed in the literature.

Purpose

This study was designed to investigate supportive care needs trajectories in patients with advanced NSCLC receiving chemotherapy and the association between the sociodemographic and disease characteristics of these patients over the four cycles of chemotherapy.

Methods

For this longitudinal study, 95 patients with advanced NSCLC were recruited using convenience sampling at a medical center in Taiwan. The supportive care needs of the participants were assessed in each of the four chemotherapy cycles using the Needs Evaluation Questionnaire–Chinese version (NEQ-C) with 23 dichotomous items on the day before and the seventh day after the end of each cycle. Group-based trajectory modeling was applied to identify the classes of supportive care needs trajectories, whereas chi-square tests were used to examine the factors related to these classes.

Results

Seventy-one participants completed all eight questionnaire sessions across the four cycles. The mean NEQ-C scores for these participants ranged between 14.4 and 14.6. Three classes of supportive care needs trajectories (low, moderate, and high) were identified for the entire NEQ-C and for each domain. Marital status was found to be associated with the classes of trajectories related to supportive care and assistance/care needs, spouse as the primary caregiver was found to be associated with the classes of trajectories related to information needs, and educational level was found to be associated with the classes of trajectories related to psychoemotional support needs.

Conclusions

The results of this study indicate that marital status and spouse as primary caregiver relate significantly to supportive care needs trajectories in patients with advanced NSCLC during chemotherapy. Healthcare professionals should provide continuous, tailored supportive care interventions that address the needs of patients and their spouses/partners.
Workplace Social Support and Work Engagement Among Japanese Workers
Authors: Mori Takahiro , Nagata Tomohisa , Odagami Kiminori , Nagata Masako , Adi Nuri Purwito , Mori Koji ,   for the W2S-Ohpm Study
Published: May 2023

Objectives

We investigated the relationship between employees’ perceptions of the number of sources of workplace social support and work engagement and whether each type of workplace social support is independently related to work engagement.

Methods

A cross-sectional study was conducted using a questionnaire survey in Japan. In total, 12,017 participants were analyzed. Participants were asked about 4 sources of workplace social support: supervisors, colleagues/subordinates, occupational health staff, and external counselors contracted by the workplace. Work engagement was measured using the 9-item Utrecht Work Engagement Scale. Coefficients were estimated using multiple regression analyses.

Results

The coefficient of work engagement increased as the number of sources of perceived workplace social support increased. Each support was also positively related to work engagement.

Conclusions

Organizations should develop systems comprising various sources of workplace social support to increase employee work engagement.
Nurse practitioners' preferences for online learning regarding driving and dementia
Authors: Stasiulis Elaine , Tymianski Dawn , Byszewski Anna , Gélinas Isabelle , Naglie Gary , Rapoport Mark J. , Vrkljan Brenda ,   on behalf of the Canadian Consortium on Neurodegeneration in Aging Driving and Dementia Team
Published: May 2023

With a growing population of older adults living with dementia in the community, nurse practitioners (NPs) are increasingly expected to address issues of medical fitness to drive (MFTD) and driving cessation within their clinical practice. With their expertise in clinical assessment and communication skills, NPs are well suited to this area of practice. Studies that examined MFTD and/or driving cessation suggest that NPs want and need further knowledge and training with this population. As part of our aim to develop an online educational program on driving and dementia for health care providers, including NPs, this mixed-methods study explored NPs' preferences regarding the format and content for the proposed online program. Results from an online survey completed by 90 NPs and interviews with six NPs highlighted key areas of focus for virtual modules, where communication strategies, tools to assess MFTD, and the reporting process for medically unfit drivers were emphasized. Reflecting on their team approach to care, participants in this study preferred a hybrid approach of asynchronous and synchronous learning delivery for this educational program. The next step will be to evaluate this program and its impact on both NP knowledge and skills in terms of its real-world application.
The Role of Care Coordination
Authors: JaKa Meghan M. , Beran Mary Sue , Andersen Julia A. , Whitebird Robin R. , Bergdall Anna R. , Kindt Joan M. , Dehmer Steven P. , Winger Melissa , Solberg Leif I.
Published: May 2023

Background:

Care coordination is important for patients with complex needs; yet, little is known about the factors impacting implementation from the care coordinator perspective.

Purpose:

To understand how care coordination implementation differs across clinics and what care coordinators perceive as barriers and facilitators of effective coordination.

Methods:

Nineteen care coordinators from primary care clinics in Minnesota participated in interviews about their perceptions of care coordination. A team of analysts coded interviews using inductive thematic analysis.

Results:

Four major themes emerged: variety in care coordination implementation; importance of social needs; necessity for leader buy-in; and importance of communication skills.

Conclusions:

Described differences in care coordination implementation were often logistical, but the implications of these differences were foundational to care coordinator perceived effectiveness.
Essential Competencies in Entry-Level Neurologic Physical Therapist Education
Authors: Bradford Elissa C. Held , Fell Nancy , Zablotny Cynthia M. , Rose Dorian K.
Published: May 2023

Background and Purpose:

The Academy of Neurologic Physical Therapy's (ANPT) 2021 Strategic Plan identified development of core competencies for neurologic physical therapy as a priority. The Curricular Competencies Task Force was appointed to establish competencies for entry-level neurologic physical therapist (PT) education to facilitate the delivery of current and consistent content across educational programs.

Summary of Key Points:

A sequential exploratory process was used. First, the task force chairs, utilizing an established conceptual framework for competency-based education and a review of the broader literature, established competency domains to specifically apply to neurologic PT practice. Second, Nominal Group Technique (NGT), a structured method for small group discussion to reach consensus, was adopted. Nominal Group Technique meetings focused on developing specific competencies within each domain of neurologic PT practice by the full task force. After competencies were identified through the NGT process, the task force chairs reviewed and refined the competencies to ensure they represented distinct and specific knowledge, skill, and/or attitude within neurologic PT practice. The domains and competencies were then submitted to ANPT membership via survey for review. Member comments were qualitatively analyzed, with edits made to the competencies prior to submission to ANPT Board of Directors for approval.

Recommendations for Entry-Level PT Neurologic Education:

Seven essential domains were identified: participation, communication and collaboration, health promotion and wellness, movement science, assistive technology and equipment, evidence-based practice, and provider health and wellness. Essential competencies operationalize each domain. Competencies are not prescriptive but provide guidance, allowing educators to determine how to best incorporate into their curricula.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A427).
The Clinical Efficacy Evaluation of Thigh Liposuction Based on 3-Dimensional Digital Technology
Authors: Li Zhifeng , Gu Yunpeng , Liu Yicheng , Lv Qianwen , Sun Jingjing , Qi Yue , Liu Zhenjun , Jin Ji , Ma Guie
Published: May 2023

Background

There is a lack of convenient and accurate objective methods to evaluate the clinical efficacy of thigh liposuction.

Methods

This retrospective study involved the 3-dimensional images of 19 patients who underwent bilateral thigh liposuction. Data such as volume change and volume change rate before and after surgery, circumference change, and circumference change rate of 3 planes (upper, middle, and lower) were analyzed. The correlation between body mass index and volume change rate and between preoperative circumference and circumference change rate of different planes were determined.

Results

There were significant differences between the preoperative and postoperative volume and circumference of 3 planes of 19 patients (38 thighs). The rate of change in total volume (16.90 ± 5.55%) correlated with the circumference change rate at the top of the thigh. There was also a linear relationship between body mass index and volume change rate, but not between preoperative circumference and circumference change rate.

Conclusions

Three-dimensional imaging technology can accurately quantify the volume and circumference change of the thigh to objectively evaluate the clinical efficacy of thigh liposuction.
A scoping review of two decades of pediatric humanitarian care during wartime
Authors: Kocik Veronica I. , Borgman Matthew A. , April Michael D. , Schauer Steven G.
Published: May 2023

Humanitarian care is a vital component of the wartime mission. Children comprise a significant proportion of casualties injured by explosives and penetrating weapons. Children face a variety of unique injury patterns in the combat setting as high-powered firearms and explosives are rarely seen in the civilian setting. We sought to perform a scoping review of pediatric research from the recent US-led wars in Afghanistan, and Iraq conflicts beginning in 2001. We used Google Scholar and PubMed to identify pediatric combat literature published between 2001 and 2022. We utilized the PRISMA-ScR Checklist to conduct this review. We identified 52 studies that met inclusion for this analysis—1 prospective observational study, 50 retrospective studies, and 1 case report. All the original research studies were retrospective in nature except for one. We identified one prospective study that was a post hoc subanalysis from an overall study assessing the success of prehospital lifesaving interventions. Most of the articles came from varying registries created by the United States and British militaries for the purposes of trauma performance improvement. The deployed health service support mission often includes treatment of pediatric trauma patients. The deployed health service support mission often includes treatment of pediatric trauma patients. We found that available literature from this setting is limited to retrospective studies except for one prospective study. Our findings suggest that pediatric humanitarian care was a significant source of medical resource consumption within both of the major wars. Further, many of the lessons learned have directly translated into changes in civilian pediatric trauma care practices highlighting the need for collaborative scientific developments between the military and civilian trauma programs.

LEVEL OF EVIDENCE

Systematic Review/Meta-Analyses; Level III.
Cytokine fluctuation during acute stress is correlated to life trauma
Authors: Speakman Storm , White Kelsey , LaPorta Anthony J. , Payton Mark E. , Gubler K. Dean , Ryznar Rebecca J.
Published: May 2023

BACKGROUND

Multiple studies have demonstrated that human neurobiology and behavior are inextricably linked to the activity of our immune systems. Trauma is associated with a multitude of immune system changes; reflecting this, posttraumatic stress disorder (PTSD) is often comorbid with immune-related conditions such as autoimmune disorders. To further investigate this phenomenon, we tested our hypothesis that cytokine fluctuations during and after an acute stress response correlates with experienced life trauma.

METHODS

Using a prospective observational approach, this cohort study measured biomarker profiles in firefighter participants (n = 63), with 9 participants having prior PTSD diagnoses and 54 without prior PTSD diagnoses. In addition, life trauma scores were determined from all participants using the Life Events Checklist 5 (LEC-5) survey. Baseline salivary biomarker concentrations were determined, along with levels immediately before, immediately after, and 1 hour following a standardized stressful training event. Biomarkers measured using these salivary samples included 42 cytokines and 6 steroid and thyroid hormones. The concentrations of these markers were then correlated, using Pearson correlation coefficients, with the participants' LEC-5 scores. t Tests were also performed to compare cytokine values between the populations with and without prior PTSD diagnosis.

RESULTS

Included in the cytokine panel were interleukin (IL)-8, IL-10, IL-1B, GCSF, IL1-Ra, Groα, IFNa2, PDGFAA, and VEGF, all of which demonstrated positive correlation at various time points in individuals with increased severity of LEC-5 scores (and thus increased experienced life trauma). Concentrations of Groα, PDGFAA, IL1-Ra, IL-1a, Mip1a, IL-1a, IL-6, Mip1b, TNFα, and TGFα were also found to be significantly altered at various time points in participants with prior PTSD diagnoses, demonstrating some overlap with the LEC-5 Pearson correlations.

CONCLUSION

The results support our hypothesis and demonstrate that LEC-5 scores are indeed significantly correlated to cytokine concentrations and fluctuations surrounding a stress test.

LEVEL OF EVIDENCE

Diagnostic Tests or Criteria; Level IV.
Binding of respiratory syncytial virus particles to platelets does not result in their degranulation in vitro
Authors: Lakerveld Anke J. , van Erp Elisabeth A. , van Kasteren Puck B.
Published: May 2023

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infection in infants and elderly. The mechanisms behind severe RSV disease are incompletely understood, but a dysregulated immune response likely plays an important role. Platelets are increasingly being recognized as immune cells and are involved in pathology of several viruses. The release of chemokines from platelets upon activation may attract for example neutrophils to the site of infection, which is a hallmark of RSV pathology. In addition, since RSV infections are sometimes associated with cardiovascular events and platelets express several known RSV receptors, we investigated the effect of RSV exposure on platelet degranulation. Washed human platelets were incubated with sucrose-purified RSV particles. P-selectin and CD63 surface expression and CCL5 secretion were measured to assess platelet degranulation. We found that platelets bind and internalize RSV particles, but this does not result in degranulation. Our results suggest that platelets do not play a direct role in RSV pathology by releasing chemokines to attract inflammatory cells.
Representational drift as a result of implicit regularization
Authors: Ratzon Aviv , Derdikman Dori , Barak Omri
Published: May 2023

Recent studies show that, even in constant environments, the tuning of single neurons changes over time in a variety of brain regions. This representational drift has been suggested to be a consequence of continuous learning under noise, but its properties are still not fully understood. To investigate the underlying mechanism, we trained an artificial network on a simplified navigational task. The network quickly reached a state of high performance, and many units exhibited spatial tuning. We then continued training the network and noticed that the activity became sparser with time. Initial learning was orders of magnitude faster than ensuing sparsification. This sparsification is consistent with recent results in machine learning, in which networks slowly move within their solution space until they reach a flat area of the loss function. We analyzed four datasets from different labs, all demonstrating that CA1 neurons become sparser and more spatially informative with exposure to the same environment. We conclude that learning is divided into three overlapping phases: (i) Fast familiarity with the environment; (ii) slow implicit regularization; (iii) a steady state of null drift. The variability in drift dynamics opens the possibility of inferring learning algorithms from observations of drift statistics.
Metabolic crosstalk between hydroxylated monoterpenes and salicylic acid in tomato defence response againstPseudomonas syringaepvtomato
Authors: Pérez-Pérez J , Minguillón S , Kabbas-Piñango E , Payá C , Campos L , Rodríguez-Concepción M , Rodrigo I , Bellés JM , López-Gresa MP , Lisón P
Published: May 2023

Hydroxylated monoterpenes (HMTPs) are differentially emitted by tomato plants efficiently resisting a bacterial infection. We have studied the defensive role of these volatiles in the tomato response to bacteria, whose main entrance are stomata apertures. Treatments with some HMTPs resulted in stomatal closure andPR1induction. Particularly, α-terpineol induced stomatal closure in a salicylic (SA) and abscisic acid-independent manner, and conferred resistance to bacteria. Interestingly, transgenic tomato plants overexpressing or silencing the monoterpene synthaseMTS1,which displayed alterations in the emission of HMTPs, exhibited changes in the stomatal aperture but not in plant resistance. Measures of both 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) and SA levels, revealed a competition for MEcPP by the methylerythritol phosphate (MEP) pathway and the SA biosynthesis activation, thus explaining the absence of phenotype in transgenic plants. These results were confirmed by chemical inhibition or activation of the MEP pathway. Besides, treatments with BTH, a SA functional analogue, conferred enhanced resistance in transgenic tomato plants overexpressingMTS1.Finally, plants overexpressingMTS1inducedPR1and stomata closure in neighbouring plants. Our results confirm the role of HMTPs in both intra and inter-plant immune signalling, and reveal a metabolic crosstalk between the MEP and SA pathways in tomato plants.

Graphical Abstract

Metabolic crosstalk between hydroxylated monoterpenes and salicylic acid in tomato defence response against Pseudomonas syringae pv tomato.

Created with BioRender.com.
Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV2 infection and pathogenesis
Authors: Joshi Prerna , Garg Swati , Mani Shailendra , Jakhar Kamini , Marothia Manisha , Shoaib Rumaisha , Biswas Shreeja , Singhal Jhalak , Behl Ankita , Kahlon Amandeep Kaur , Shevtsov Maxim , Garg Pramod , Singh Shailja , Ranganathan Anand
Published: May 2023

One of the fundamental mechanisms developed by the host to contain the highly infectious and rapidly proliferating SARS coronavirus is elevation of body temperature, a natural fallout of which is Heat Shock Protein (HSP) over-expression. Here, for the first time, we demonstrate that the SARS-CoV-2 virus exploits the host Hsp70 chaperone for its entry and propagation and blocking it can combat the infection. SARS-CoV-2 infection as well as febrile temperature enhanced Hsp70 overexpression in host Vero E6 cells. In turn, Hsp70 overexpression elevated the host cell autophagic response that is a prerequisite for viral propagation. Suppressive and prophylactic treatment of Vero E6 cells with HSP70 inhibitor PES-Cl, a small molecule derivative of Pifithrin μ, abrogated viral infection more potently than the currently used drug Remdesivir by suppressing host HSP70 and autophagic response. In conclusion, our study not only provides a fundamental insight into the role of host Hsp70 in SARS-CoV-2 pathogenesis, it paves the way for the development of potent and irresistible anti-viral therapeutics.
Robust identification of perturbed cell types in single-cell RNA-seq data
Authors: Nicol Phillip B. , Paulson Danielle , Qian Gege , Liu X. Shirley , Irizarry Rafael , Sahu Avinash D.
Published: May 2023

Single-cell transcriptomics has emerged as a powerful tool for understanding how different cells contribute to disease progression by identifying cell types that change across diseases or conditions. However, detecting changing cell types is challenging due to individual-to-individual and cohort-to-cohort variability and naive approaches based on current computational tools lead to false positive findings. To address this, we propose a computational tool,scDist, based on a mixed-effects model that provides a statistically rigorous and computationally efficient approach for detecting transcriptomic differences. By accurately recapitulating known immune cell relationships and mitigating false positives induced by individual and cohort variation, we demonstrate thatscDistoutperforms current methods in both simulated and real datasets, even with limited sample sizes. Through the analysis of COVID-19 and immunotherapy datasets,scDistuncovers transcriptomic perturbations in dendritic cells, plasmacytoid dendritic cells, and FCER1G+NK cells, that provide new insights into disease mechanisms and treatment responses. As single-cell datasets continue to expand, our faster and statistically rigorous method offers a robust and versatile tool for a wide range of research and clinical applications, enabling the investigation of cellular perturbations with implications for human health and disease.
Outward-oriented sites within clustered CTCF boundaries are key for intraTAD chromatin interactions and gene regulation
Authors: Ge Xiao , Huang Haiyan , Han Keqi , Xu Wangjie , Wang Zhaoxia , Wu Qiang
Published: May 2023

CTCF plays an important role in adjusting insulation at TAD boundaries, where clustered CBS (CTCF-binding site) elements are often arranged in a somewhat tandem array with a complex divergent or convergent orientation. Here usingcPcdhandHOXDloci as a paradigm, we look into the clustered CTCF TAD boundaries and find that, counterintuitively, outward-oriented CBS elements are crucial for inward enhancer-promoter interactions as well as for gene regulation. Specifically, by combinatorial deletions of a series of putative enhancer elementsin vivoor CBS elementsin vitro, in conjunction with chromosome conformation capture and RNA-seq analyses, we show that deletions of outward-oriented CBS elements weaken the strength of intraTAD promoter-enhancer interactions and enhancer activation of target genes. Our data highlight the crucial role of outward-oriented CBS elements within the clustered CTCF TAD boundaries and have interesting implications on the organization principles of clustered CTCF sites within TAD boundaries.
Dimeric Transmembrane Structure of the SARS-CoV-2 E Protein
Authors: Zhang Rongfu , Qin Huajun , Prasad Ramesh , Fu Riqiang , Zhou Huan-Xiang , Cross Timothy A.
Published: May 2023

The SARS-CoV-2 E protein is a transmembrane (TM) protein with its N-terminus exposed on the external surface of the virus. Here, the TM structure of the E protein is characterized by oriented sample and magic angle spinning solid-state NMR in lipid bilayers and refined by molecular dynamics simulations. This protein has been found to be a pentamer, with a hydrophobic pore that appears to function as an ion channel. We identified only a symmetric helix-helix interface, leading to a dimeric structure that does not support channel activity. The two helices have a tilt angle of only 6°, resulting in an extended interface dominated by Leu and Val sidechains. While residues Val14-Thr35 are almost all buried in the hydrophobic region of the membrane, Asn15 lines a water-filled pocket that potentially serves as a drug-binding site. The E and other viral proteins may adopt different oligomeric states to help perform multiple functions.
SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway
Authors: Sala Samuele , Nitschke Philipp , Masuda Reika , Gray Nicola , Lawler Nathan , Wood James M. , Buckler Joshua N. , Berezhnoy Georgy , Bolaños Alejandro , Boughton Berin A. , Lonati Caterina , Rössler Titus , Singh Yogesh , Wilson Ian D. , Lodge Samantha , Morillon Aude-Claire , Loo Ruey Leng , Hall Drew , Whiley Luke , Evans Gary B. , Grove Tyler L. , Almo Steven C. , Harris Lawrence D. , Holmes Elaine , Merle Uta , Trautwein Christoph , Nicholson Jeremy K. , Wist Julien
Published: May 2023

We present compelling evidence for the existence of an extended innate viperin dependent pathway which provides crucial evidence for an adaptive response to viral agents like SARS-CoV-2. We show the in vivo biosynthesis of a family of endogenous cytosine metabolites with potential antiviral activity. Two dimensional Nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase. Mass spectrometry additionally allowed the characterization and quantification of the most abundant serum metabolites showing potential diagnostic value of the compounds for viral infections. In total, we unveiled ten nucleoside (cytosine and uracil based) analogue structures, eight of which were previously unknown in humans. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ and IL-10, suggest an association with the viperin enzyme contributing to an endogenous innate immune defence mechanism against viral infection.
Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala
Authors: Mueller Madeleine , Fadai Tahmine , Rauh Jonas , Haaker Jan
Published: May 2023

Nicotine intake by cigarettes is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n=88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety.
Emergency department visits and boarding for pediatric patients with suicidality before and during the COVID-19 pandemic
Authors: Zipursky Amy R. , Olson Karen L. , Bode Louisa , Geva Alon , Jones James , Mandl Kenneth D. , McMurry Andrew
Published: May 2023

Objective

To quantify the increase in pediatric patients presenting to the emergency department with suicidality before and during the COVID-19 pandemic, and the subsequent impact on emergency department length of stay and boarding.

Methods

This retrospective cohort study from June 1, 2016, to October 31, 2022, identified patients presenting to the emergency department with suicidality using ICD-10 codes. Number of emergency department encounters for suicidality, demographic characteristics of patients with suicidality, and emergency department length of stay were compared before and during the COVID-19 pandemic. Unobserved components models were used to describe monthly counts of emergency department encounters for suicidality.

Results

There were 179,736 patient encounters to the emergency department during the study period, 6,168 (3.4%) for suicidality. There were, on average, more encounters for suicidality each month during the COVID-19 pandemic than before the COVID-19 pandemic. A time series unobserved components model demonstrated an initial drop in encounters for suicidality in April and May of 2020, followed by an increase starting in July 2020. The average length of stay for patients that boarded in the emergency department with a diagnosis of suicidality was 37.4 hours longer during the COVID-19 pandemic compared to before the COVID-19 pandemic.

Conclusions

The number of encounters for suicidality among pediatric patients and the emergency department length of stay for psychiatry boarders has increased during the COVID-19 pandemic. There is a need for acute care mental health services and solutions to emergency department capacity issues.
Exploration biases how forelimb reaches to a spatial target are learned
Authors: Mosberger AC , Sibener LJ , Chen TX , Rodrigues HFM , Hormigo R , Ingram JN , Athalye VR , Tabachnik T , Wolpert DM , Murray JM , Costa RM
Published: May 2023

The brain can learn to generate actions, such as reaching to a target, using different movement strategies. Understanding how different variables bias which strategies are learned to produce such a reach is important for our understanding of the neural bases of movement. Here we introduce a novel spatial forelimb target task in which perched head-fixed mice learn to reach to a circular target area from a set start position using a joystick. These reaches can be achieved by learning to move into a specific direction or to a specific endpoint location. We find that mice gradually learn to successfully reach the covert target. With time, they refine their initially exploratory complex joystick trajectories into controlled targeted reaches. The execution of these controlled reaches depends on the sensorimotor cortex. Using a probe test with shifting start positions, we show that individual mice learned to use strategies biased to either direction or endpoint-based movements. The degree of endpoint learning bias was correlated with the spatial directional variability with which the workspace was explored early in training. Furthermore, we demonstrate that reinforcement learning model agents exhibit a similar correlation between directional variability during training and learned strategy. These results provide evidence that individual exploratory behavior during training biases the control strategies that mice use to perform forelimb covert target reaches.