bluuebunny/crossref_metadata_2025 huggingface dataset:
Museums and the Educational Mission from the Progressive Era to World War II
Authors: Swigger Jessie
Published: July 2022

In May 1906, museum workers from across the country gathered in New York City at the American Museum of Natural History for the first annual meeting of the American Association of Museums (AAM). Over the course of two days, AAM members elected officers, ratified a constitution, and shared ideas about how best to collect, store, and display objects and specimens. The meeting culminated with a resolution to create a formal partnership with the National Education Association (NEA).

AAM members’ interest in linking their work with the NEA signified that by the early 20th century, most museum leaders agreed that educating the public was a priority. This commitment to education shaped exhibition and collecting practices and the services that museums provided and expanded the power of museum visitors and audiences. While administrators, curators, and exhibit preparers often agreed on the collective goal of educating the public, their approaches varied. How museum education was defined and assessed depended on the type of museum in which one was employed, and it changed over time in response to broader social, cultural, and political forces. By 1945, however, museums of all types had formalized and institutionalized their practices in ways that placed education at the core of their purpose and actions.
Elliott, Doreen
Authors: Hoefer Richard
Published: July 2022

Dr. Doreen Elliott (1941–2018) earned her bachelor of arts from Queen Mary University of London; a postgraduate certificate in education from the University of Hull, England, Institute of Education; her advance diploma in the educational rehabilitation of young people from the University of London, England, Institute of Education; and her doctoral degree from the University of Wales, United Kingdom, School of Social Work, University College Cardiff, UK.

Elliott became a faculty member at the University of Wales in the field of social work and worked as a visiting associate professor at the University of Texas at Arlington for the 1986–1987 academic year. The University of Texas at Arlington became her home institution, first as Associate Professor (1988–1992) and then, from 1992 until retirement in 2013, as Professor.
Notch effector recombination signal binding protein for immunoglobulin kappa J signaling is required for the initiation of endometrial stromal cell decidualization
Authors: Moldovan Genna E , Song Yong , Kim Tae Hoon , Su Ren-Wei , Jeong Jae-Wook , Gruzdev Artiom , Spencer Thomas E , Fazleabas Asgerally T
Published: July 2022

The Notch signaling pathway is required for reproductive success. This pathway activates its transcriptional effector, recombination signal binding protein for immunoglobulin kappa J (Rbpj), to induce transcription of its target genes. This signaling pathway is required for successful decidualization, implantation, and uterine repair following parturition. To identify the compartmental specific roles of the Notch signaling pathway in the establishment of pregnancy, we generated epithelial and decidual stromal cell specific knockouts of Rbpj utilizing lactoferrin iCre and Prl8A2 iCre, respectively. Both conditional knockout mouse models were fertile. The Rbpj epithelial knockout mice displayed 27% resorption sites at E15.5, but this did not significantly impact the number of live born pups compared with controls. In addition, the Rbpj epithelial knockout mice displayed increased estrogen signaling in their stromal compartment. Given that both mouse models exhibited fertility comparable to control animals, the epithelial and stromal specific nature of the iCre recombinases utilized, and previously published Rbpj total uterine knockout mouse models, we conclude that Notch effector Rbpj signaling is required at the initiation of pregnancy to support decidualization in stromal cells, but that Rbpj is not required in the epithelial compartment nor is it required for post-implantation pregnancy success.
Ovine conceptus tissue metabolizes fructose for metabolic support during the peri-implantation period of pregnancy
Authors: Moses Robyn M , Halloran Katherine M , Stenhouse Claire , Sah Nirvay , Kramer Avery C , McLendon Bryan A , Seo Heewon , Johnson Gregory A , Wu Guoyao , Bazer Fuller W
Published: July 2022

Roles of fructose in elongating ovine conceptuses are poorly understood, despite it being the major hexose sugar in fetal fluids and plasma throughout gestation. Therefore, we determined if elongating ovine conceptuses utilize fructose via metabolic pathways for survival and development. Immunohistochemical analyses revealed that trophectoderm and extra-embryonic endoderm express ketohexokinase and aldolase B during the peri-implantation period of pregnancy for conversion of fructose into fructose-1-phosphate for entry into glycolysis and related metabolic pathways. Conceptus homogenates were cultured with 14C-labeled glucose and/or fructose under oxygenated and hypoxic conditions to assess contributions of glucose and fructose to the pentose cycle (PC), tricarboxylic acid cycle, glycoproteins, and lipid synthesis. Results indicated that both glucose and fructose contributed carbons to each of these pathways, except for lipid synthesis, and metabolized to pyruvate and lactate, with lactate being the primary product of glycolysis under oxygenated and hypoxic conditions. We also found that (1) conceptuses preferentially oxidized glucose over fructose (P < 0.05); (2) incorporation of fructose and glucose at 4 mM each into the PC by Day 16 conceptus homogenates was similar in the presence or absence of glucose, but incorporation of glucose into the PC was enhanced by the presence of fructose (P < 0.05); (3) incorporation of fructose into the PC in the absence of glucose was greater under oxygenated conditions (P < 0.01); and (4) incorporation of glucose into the PC under oxygenated conditions was greater in the presence of fructose (P = 0.05). These results indicate that fructose is an important metabolic substrate for ovine conceptuses.
Parental Inbred Lines of the Nested Association Mapping (NAM) Population of Corn Show Sources of Resistance to Tar Spot in Northern Indiana
Authors: Singh Raksha , Shim Sujoung , Telenko Darcy E. P. , Goodwin Stephen B.
Published: July 2022

Tar spot is a major foliar disease of corn caused by the obligate fungal pathogen Phyllachora maydis, first identified in Indiana in 2015. Under conducive weather conditions, P. maydis causes significant yield losses in the United States and other countries, constituting a major threat to corn production. Relatively little is known about resistance to tar spot other than a major quantitative gene that was identified in tropical maize lines. To test for additional sources of resistance against populations of P. maydis in North America, 26 parental inbred lines of the nested associated mapping (NAM) population were evaluated for tar spot resistance in Indiana in replicated field trials under natural infection for 3 years. Tar spot disease severity was scored visually using a 0-to-100% scale. Maximum disease severity (MDS) for tar spot scoring at reproductive growth stage ranged from 0 to 48.3%, with 0% being most resistant and 48.3% being most susceptible. Nine inbred lines were resistant to P. maydis with MDS ranging from 0 to 5.0%, six were moderately resistant (5.2 to 10.6% MDS), two were moderately susceptible (11.7 to 26.0% MDS), and the remaining eight inbred lines were rated as susceptible (30.0 to 48.3% MDS). There was some variability between years, due to higher disease pressure after 2019. Inbred B73, the common parent of the NAM populations, was rated as susceptible, with MDS of 30.0%. The nine highly resistant lines provide a potential source of new genes for genetic analysis and mapping of tar spot resistance in corn.
Immunotherapy and breast cancer: an overview
Authors: Mezni Essia , Behi Khalil , Gonçalves Anthony
Published: July 2022

Purpose of review

Recently, immune checkpoint inhibitors (ICI) have demonstrated survival benefits in triple-negative breast cancer (TNBC) patients, treated in both the advanced and the early settings.

Recent findings

As monotherapy, ICI failed to demonstrate a superiority over chemotherapy in pretreated advanced TNBC. In the first-line setting, ICI in combination with chemotherapy have shown consistent gains in progression-free survival in programmed death-ligand 1-positive TNBC, but only pembrolizumab indisputably demonstrated a significant overall survival benefit. In early-stage TNBC patients treated with neoadjuvant chemotherapy (NAC), ICI may improve the pathological complete response (pCR) rate. In the KEYNOTE-522 trial enrolling stage II to III TNBC patients, pembrolizumab, in combination with a NAC composed of carboplatin-paclitaxel followed by anthracyclines, and continued in the adjuvant phase led to significant increases in both pCR and disease-free survival, a practice-changing result in the field. Importantly, no unexpected safety signal was observed, but the possibility of definitive ICI-related toxicities may be challenging in curable early disease.

Immunotherapy is now an important component in the therapeutic management of TNBC. Unresolved issues include the best chemotherapy partners, additional biomarkers to maximize the clinical benefit, and the possible extension of its use to other breast cancer subtypes.
Effects of secukinumab and adalimumab on serum uric acid level in patients with plaque psoriasis
Authors: Zhao Zheng , Cai Lin , Zhang Si , Zhang Heng , Liu Xiaoyang , Li Chenglong , Zhao Yan , Zhang Jianzhong
Published: July 2022

Background:

Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy. The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia.

Methods:

A total of 196 patients with psoriasis and 191 age- and sex-matched healthy controls were enrolled in this retrospective cohort study. One hundred and twenty-seven patients with severe psoriasis were treated with biologics. Sixty-eight patients received adalimumab, and 59 patients received secukinumab. Serum uric acid levels were measured at baseline, week 24, and week 48 of treatment.

Results:

Patients with psoriasis had higher serum uric acid levels than healthy controls (6.4 ± 1.7 mg/dL vs. 5.7 ± 1.5 mg/dL, P < 0.001). Hyperuricemia was found in 33.7% (66/196) of patients with psoriasis, which was significantly higher than that in healthy controls (13.1% [25/191], P < 0.001). Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis (P > 0.05). No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment (P > 0.05). The serum uric acid level in patients treated with secukinumab was 6.7 ± 1.6 mg/dL at week 24, which was not statistically different from that at baseline (6.6 ± 1.4 mg/dL, P = 0.885). Serum uric acid levels were significantly decreased at week 48 (6.3 ± 1.5 mg/dL vs. 6.6 ± 1.4 mg/dL, P = 0.007) in patients treated with secukinumab. Secukinumab had no significant effect on hyperuricemia either (P > 0.05).

Conclusions:

The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls. Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis, whereas adalimumab had no significant effect on serum uric acid levels.
Radiation-induced Sarcoma in the Head and Neck: Clinical, Imaging, Histopathological, and Therapeutic Characterization
Authors: Bernaola-Paredes Wilber Edison , Filippetti Eloah Pascuotte , Rodrigues Monica Lucia , Carvalho Henrique Perez , Coutinho Marcelo Carvalho , Arruda Arthur Ferrari , Pinto Pedro Jorge Joffily , Costa Felipe D’Almeida , Celestino Miriã Andrade , Pellizzon Antonio Cassio Assis
Published: July 2022

Radiation-induced head and neck sarcoma (RIHNS) is a rare and serious long-term complication of radiotherapy (RT), with poor prognosis and high morbidity and mortality. Diagnosis is based on immunohistochemistry and molecular biomarker analysis, and therapy is usually surgical. Other adjuvant therapies might be considered. This case report aimed to describe the clinical, imaging, histopathological, and therapeutic characteristics of a rare case of RIHNS in the mandible after 21 years of RT. A 68-year-old male patient underwent a partial left parotidectomy in 1995, was diagnosed with pleomorphic adenoma, and after recurrence of the lesion in 2000, underwent an ipsilateral total parotidectomy with adjuvant RT. In May 2021, he complained of an ulcerated nodular lesion on the tongue that extended toward the lower gingiva, associated with oral bleeding and difficulties with swallowing. After biopsy in the gingival margin and histopathological analysis, the diagnosis of high-grade spindle-cell sarcoma was established. Complete surgical resection with microsurgical reconstruction using a fibular osteomusculocutaneous free flap was performed. RIHNS could appear after a period of almost 20 years after RT. Surgical resection with reconstructive surgery was a reliable and feasible therapeutic option that showed favorable clinical results after an appropriate follow-up.
To sell or not to sell: considerations when evaluating private equity acquisitions
Authors: Makadia Frini , Roskam Jacob , Williams Ruth D.
Published: July 2022

Purpose of review

Many private practice ophthalmology groups are considering a partnership with private equity. When evaluating whether to remain independent or to engage an equity partner, practice leaders must analyze their existing practice, address issues of equity transitions, management, and governance, and determine strategic goals. This paper discusses the factors that need to be considered when evaluating the possibility of an acquisition model.

When considering a partnership with private equity, a thriving and mature private practice must conduct an in-depth analysis of four factors: how to transition the equity of a mature practice, how to continue growth, how to manage an increasingly complex organization, and the after-effects of a sale. These same issues must be addressed whether the group decides to pursue private equity or decides to remain independent.
The use of MRI in urothelial carcinoma
Authors: Messina Emanuele , Pisciotti Martina Lucia , Pecoraro Martina , Borrelli Antonella , Del Giudice Francesco , Panebianco Valeria
Published: July 2022

Purpose of review

To conduct a nonsystematic review of the existing literature to investigate the role of Magnetic Resonance Imaging (MRI) in urothelial carcinomas (UCs).

Recent findings

Imaging is becoming progressively more crucial in local and distant staging of UCs, especially in cases of bladder cancer (BCa). The primary objective of imaging in patients with BCa is to detect lesions and distinguish T1 from T2 stages, since the treatment varies significantly.

The applicability of MRI in the management of UCs has been investigated, particularly focusing on the new evidence on multiparametric MRI (mpMRI) of the bladder and Vesical Imaging-Reporting And Data System score for the description of BCa and discussing the possible utility of MRI for upper tract urothelial carcinomas . Imaging modalities, in particular CT and MRI, are essential tools for the local and distant staging of UCs. MpMRI of the bladder and VI-RADS score accurately define the risk of muscle invasiveness, promoting tailored therapeutic planning. Moreover, mpMRI has also been included in patients’ follow-up and in the assessment of response to systematic therapy. MRI utility and possible application in upper tract urothelial carcinomas cases are yet to be discovered.
Progression-free survival is an adequate endpoint for clinical trials of locally advanced and metastatic urothelial carcinoma
Authors: Martini Alberto , Fallara Giuseppe , Ploussard Guillaume , Pradere Benjamin
Published: July 2022

Purpose of review

To evaluate intermediate clinical endpoints that have been proposed as potential surrogates for overall survival amongst patients with locally advanced and metastatic urothelial carcinoma.

Recent findings

Several endpoints have been proposed as potential surrogates for overall survival. They are: pathologic downstaging or complete response after neoadjuvant treatments and progression-free survival in the adjuvant setting and metastatic setting. Formal surrogacy, as per Prentice, has not been established among any of the aforementioned intermediate clinical endpoints and overall survival. Despite that, regulatory agencies have recently approved adjuvant nivolumab for patients with high-risk muscle invasive bladder cancer, based on the results of a trial that had disease-free survival as primary endpoint.

Despite the lack of proven surrogacy between progression-free survival and overall survival, this endpoint seems adequate for trial design and medication approval, as the recent case of adjuvant nivolumab demonstrates.
Opioid Dependence and Overdose After Surgery
Authors: Wylie Jennifer A. , Kong Lixi , Barth Richard J.
Published: July 2022

Objective:

To determine: (1) incidence of “opioid never events” (ONEs), defined as the development of opioid dependence or overdose in an opioid-naive surgical patient who is prescribed opioids postoperatively and (2) risk factors predicting ONEs.

Background:

Patients receiving opioids after surgery are at risk of experiencing life-threatening opioid-related adverse events.

Methods:

An electronic medical record review identified surgical patients at an academic medical center between January 1, 2015, and December 31, 2018, followed through March 31, 2020. ONEs were determined by International Classification of Diseases, Ninth/10th Revision (ICD-9/10) codes, and electronic medical record review.

Results:

A total of 35,335 opioid-naive surgical patients received a perioperative opioid prescription. The median follow-up was 3.47 years (range: 1.25–5.25 years). ONEs occurred in 0.19% (67/35,335) of patients. The ONE rate was 5.6 per 10,000 person-years of follow-up. Ten of 67 ONE patients overdosed on opioids. The median time to ONE was 1.6 years; the highest ONE rate was observed 1 to 2 years after surgery. In multivariate analysis, patients receiving opioid prescriptions 90 to 180 or 90 to 360 days after surgery had the highest risk of developing ONEs [hazard ratio (HR)=6.39, confidence interval (CI): 3.72–10.973; HR=6.87, CI: 4.24–11.12, respectively]. Surgical specialty (HR=5.21, 2.65–0.23) and patient age (HR=4.17, CI: 2.50–6.96) were also risk factors for ONEs. Persistent opioid use 90 to 360 days after surgery was present in 45% of patients developing ONEs.

Conclusions:

Postoperative opioid dependence or overdose is a significant health problem, affecting roughly 2 per 1000 opioid-naive surgical patients prescribed an opioid and followed for 5 years. Risk factors for the development of ONEs include opioid use 3 to 12 months after surgery, patient age, and surgical procedure.
Impact of Propofol-based Total Intravenous Anesthesia Versus Inhalation Anesthesia on Long-term Survival After Cancer Surgery in a Nationwide Cohort
Authors: Yoon Susie , Jung Sun-Young , Kim Myo-Song , Yoon Danbi , Cho Younghae , Jeon Yunseok
Published: July 2022

Objective:

To compare the impact of propofol-based total intravenous anesthesia (TIVA) versus inhalational anesthesia (IA) on the overall survival following cancer surgery.

Background:

The association between intraoperative anesthetics and patients’ long-term outcomes following cancer surgery remains controversial.

Methods:

This retrospective cohort study used nationwide data from the Korean National Health Insurance Service. Adult patients who underwent cancer resection surgery (breast, gastric, lung, liver, kidney, colorectal, pancreatic, esophageal, and bladder cancer) under general anesthesia between January 2007 and December 2016 were included. Patients were divided into propofol-based TIVA or IA groups according to the type of anesthesia received. A total of 312,985 patients (37,063 in the propofol-based TIVA group and 275,922 patients in the IA group) were eligible for analysis. The primary outcome was the comparison of overall survival following surgery between the groups in each cancer type. We compared the all-cause mortality between the 2 groups, stratified by cancer type using time-dependent Cox regression after propensity score–based inverse probability of treatment weighting. We further examined the comparison of overall survival in a meta-analysis using data from our study and previously published data comparing propofol-based TIVA with IA after cancer surgery.

Results:

The number of deaths in the propofol-based TIVA and IA groups was 5037 (13.6%) and 45,904 (16.6%), respectively; the median (interquartile range) follow-up duration was 1192 (637–2011) days. Multivariable Cox proportional hazards regression analysis revealed no significant association between the type of general anesthesia and overall survival after cancer surgery in the weighted cohort for each cancer type (all P>0.05) and for total population [adjusted hazard ratio (HR): 0.98, 95% confidence interval (CI): 0.93–1.04]. In a meta-analysis, single-center studies showed higher overall survival in the TIVA group than in the IA group (pooled adjusted HR: 0.65, 95% CI: 0.47–0.91, P=0.01), while multicenter studies showed insignificant pooled adjusted HRs (pooled adjusted HR: 1.05, 95% CI: 0.82–1.33, P=0.71).

Conclusions:

There is no association between the type of general anesthesia used during cancer surgery and postoperative overall, 1-, and 5-year survival.
Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT)
Authors: Peacock Oliver , Manisundaram Naveen , Dibrito Sandra R. , Kim Youngwan , Hu Chung-Yuan , Bednarski Brian K. , Konishi Tsuyoshi , Stanietzky Nir , Vikram Raghunandan , Kaur Harmeet , Taggart Melissa W. , Dasari Arvind , Holliday Emma B. , You Y Nancy , Chang George J.
Published: July 2022

Objective:

Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT).

Methods:

A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND.

Results:

A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10–32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P=0.003) was greater in the LPLND group, but median blood loss (P=0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P=0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65–8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19–6.08) were more likely to undergo LPLND.

Conclusions:

For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.
A Prospective Study on the Safety and Efficacy of Vascularized Lymph Node Transplant
Authors: Brown Stav , Mehrara Babak J. , Coriddi Michelle , McGrath Leslie , Cavalli Michele , Dayan Joseph H.
Published: July 2022

Purpose:

While vascularized lymph node transplant (VLNT) has gained popularity, there are a lack of prospective long-term studies and standardized outcomes. The purpose of this study was to evaluate the safety and efficacy of VLNT using all available outcome measures.

Methods:

This was a prospective study on all consecutive patients who underwent VLNT. Outcomes were assessed with 2 patient-reported outcome metrics, limb volume, bioimpedance, need for compression, and incidence of cellulitis.

Results:

There were 89 patients with the following donor sites: omentum (73%), axilla (13%), supraclavicular (7%), groin (3.5%). The mean follow-up was 23.7±12 months. There was a significant improvement at 2 years postoperatively across all outcome measures: 28.4% improvement in the Lymphedema Life Impact Scale, 20% average reduction in limb volume, 27.5% improvement in bioimpedance score, 93% reduction in cellulitis, and 34% of patients no longer required compression. Complications were transient and low without any donor site lymphedema.

Conclusions:

VLNT is a safe and effective treatment for lymphedema with significant benefits fully manifesting at 2 years postoperatively. Omentum does not have any donor site lymphedema risk making it an attractive first choice.
Fibrinogen supplementation for the trauma patient: Should you choose fibrinogen concentrate over cryoprecipitate?
Authors: Obaid Omar , Anand Tanya , Nelson Adam , Reina Raul , Ditillo Michael , Stewart Collin , Douglas Molly , Friese Randall , Gries Lynn , Joseph Bellal
Published: July 2022

BACKGROUND

Trauma-induced coagulopathy is frequently associated with hypofibrinogenemia. Cryoprecipitate (Cryo), and fibrinogen concentrate (FC) are both potential means of fibrinogen supplementation. The aim of this study was to compare the outcomes of traumatic hemorrhagic patients who received fibrinogen supplementation using FC versus Cryo.

METHODS

We performed a 2-year (2016–2017) retrospective cohort analysis of the American College of Surgeons Trauma Quality Improvement Program database. All adult trauma patients (≥18 years) who received FC or Cryo as an adjunct to resuscitation were included. Patients with bleeding disorders, chronic liver disease, and those on preinjury anticoagulants were excluded. Patients were stratified into those who received FC, and those who received Cryo. Propensity score matching (1:2) was performed. Outcome measures were transfusion requirements, major complications, hospital, and intensive care unit lengths of stay, and mortality.

RESULTS

A matched cohort of 255 patients who received fibrinogen supplementation (85 in FC, 170 in Cryo) was analyzed. Overall, the mean age was 41 ± 19 years, 74% were male, 74% were white and median Injury Severity Score was 26 (22–30). Compared with the Cryo group, the FC group required less units of packed red blood cells, fresh frozen plasma, and platelets, and had shorter in-hospital and intensive care unit length of stay. There were no significant differences between the two groups in terms of major in-hospital complications and mortality.

CONCLUSION

Fibrinogen supplementation in the form of FC for the traumatic hemorrhagic patient is associated with improved outcomes and reduced transfusion requirements as compared with Cryo. Further studies are required to evaluate the optimal method of fibrinogen supplementation in the resuscitation of trauma patients.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Embracing Allyship in Academic Surgery: How All Surgeons Can Become Effective Champions for Change
Authors: Peck Connor J , Roberts Sanford E , Ly Catherine L , Hsia Henry C , Aarons Cary B , Guerra Carmen E , Butler Paris D
Published: July 2022

As the surgical community continues to work towards greater diversity, equity, and inclusion, the need for buy-in from all surgeons—including those of the White majority—becomes increasingly apparent. This article invites all surgeons to aid in diversity, equity, and inclusion efforts as “allies,” “upstanders,” and “champions for change,” and provides 2 specific frameworks for enacting allyship within the surgical field. Overt and conscious efforts to embrace allyship are imperative as we seek to fulfill our professional responsibilities to patients and will help create a workplace environment where all persons feel accepted, valued, welcomed, and respected.
Genome-wide methylation analysis of early-onset schizophrenia
Authors: Srivastava Anil , Chaudhary Zanib , Qian Jessica , Al Chalabi Nzaar , Burhan Amer M. , Fischer Corinne E. , Gerretsen Philip , Kolla Nathan J. , Graff Ariel , Remington Gary , De Luca Vincenzo
Published: July 2022

Objective

Schizophrenia (SCZ) is a debilitating disease with a complex genetic cause in which age at onset may reflect genetic vulnerability. Though there has been some association between genetic polymorphisms and age of onset, there has been little exploration of the role of epigenetic processes. We sought to explore the influence of DNA methylation, a key epigenetic mechanism, and its association with the age of onset of illness.

Methods

One hundred thirty-eight participants aged 18–75 years and previously diagnosed with SCZ spectrum disorders by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID DSM-5) were recruited. Venous blood was collected and genome-wide DNA methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array. Individual CpG sites and regions of differential methylation were explored by the age of onset; covariates included age, sex, as well as white blood cell composition.

Results

Binary grouping (early vs. late onset) revealed four intergenic CpG sites on chromosome 2 that were above the expected P-value threshold, with hypermethylation of the CpG site cg10392614 most strongly associated with early-onset SCZ. The four most strongly associated CpG sites, including cg 10392614, were intergenic. Continuous analysis revealed the top CpG site to be cg11723066, which is linked to the JAM3 gene, with hypomethylation associated with earlier onset; however, results were below the expected P-value threshold.

Conclusion

Studies on DNA methylation in the first-episode psychosis population may help further our understanding of the role of epigenetics in the age of onset of SCZ.
Single-nucleus RNA-seq reveals disrupted cell maturation by chorioamnionitis in the preterm cerebellum of nonhuman primates
Authors: Newman Josef , Tong Xiaoying , Tan April , De Paiva Vanessa Nunes , Presicce Pietro , Kannan Paranthaman S , Williams Kevin , Damianos Andreas , Newsam Marione Tamase , Benny Merline , Wu Shu , Young Karen , Miller Lisa A. , Kallapur Suhas G , Chougnet Claire A , Jobe Alan H , Brambilla Roberta , Schmidt Augusto F.
Published: July 2022

Preterm birth is often associated with chorioamnionitis and increased risk of neurodevelopmental disorders. Preterm birth also leads to cerebellar underdevelopment but the mechanisms of disrupted cerebellar development in preterm infants are little understood. Here, we leveraged single-nuclei RNA-sequencing of the cerebellum in a rhesus macaque model of chorioamnionitis and preterm birth, to show that chorioamnionitis leads to Purkinje cell loss and disrupted maturation of granule cells and oligodendrocytes in the fetal cerebellum at late gestation. Purkinje cell loss is accompanied by decreased sonic hedgehog signaling from Purkinje cells to granule cells, which show an accelerated maturation. Chorioamnionitis also accelerated pre-oligodendrocyte maturation into myelinating oligodendrocytes, confirmed by increased expression of myelin basic protein in the cerebellum of chorioamnionitis-exposed fetuses. These findings are consistent with reported histopathological findings in individuals with autism and suggest a novel mechanism through which perinatal inflammation contributes to neurodevelopmental disorders.
Bayesian Shrinkage Priors in Zero-Inflated and Negative Binomial Regression models with Real World Data Applications of COVID-19 Vaccine, and RNA-Seq
Authors: Bhattacharyya Arinjita , Mitra Riten , Rai Shesh , Pal Subhadip
Published: July 2022

Background

Count data regression modeling has received much attention in several science fields in which the Poisson, Negative binomial, and Zero-Inflated models are some of the primary regression techniques. Negative binomial regression is applied to modeling count variables, usually when they are over-dispersed. A Poisson distribution is also utilized for counting data where the mean is equal to the variance. This situation is often unrealistic since the distribution of counts will usually have a variance that is not equal to its mean. Modeling it as Poisson distributed leads to ignoring under- or overdispersion, depending on if the variance is smaller or larger than the mean. Also, situations with outcomes having a larger number of zeros such as RNASeq data require Zero-inflated models. Variable selection through shrinkage priors has been a popular method to address the curse of dimensionality and achieve the identification of significant variables.

Methods

We present a unified Bayesian hierarchical framework that implements and compares shrinkage priors in negative-binomial and zero-inflated negative binomial regression models. The key feature is the representation of the likelihood by a Polya-Gamma data augmentation, which admits a natural integration with a family of shrinkage priors. We specifically focus on the Horseshoe, Dirichlet Laplace, and Double Pareto priors. Extensive simulation studies address the efficiency of the model and mean square errors are reported. Further, the models are applied to data sets such as the Covid-19 vaccine, and Covid-19 RNA-Seq data among others.

Results

The models are robust enough to address variable selection, and MSE decreases as the sample size increases, having lower errors inp > ncases. The noteworthy results showed that the adverse events of Covid-19 vaccines were dependent on age, recovery, medical history, and prior vaccination with a remarkable reduction in MSE of the fitted values. No. of publications of Ph.D. students were dependent on the no. of children, and the no. of articles in the last three years.

Conclusions

The models are robust enough to conduct both variable selections and produce effective fit because of their high shrinkage property and applicability to a broad range of biometric and public health high dimensional problems.
Time-Dependent Maximum Entropy Model for Populations of Retinal Ganglion Cells†
Authors: Delamare Geoffroy , Ferrari Ulisse
Published: July 2022

The inverse Ising model is used in computational neuroscience to infer probability distributions of the synchronous activity of large neuronal populations. This method allows for finding the Boltzmann distribution with single neuron biases and pairwise interactions that maximizes the entropy and reproduces the empirical statistics of the recorded neuronal activity. Here we apply this strategy to large populations of retinal output neurons (ganglion cells) of different types, stimulated by multiple visual stimuli with their own statistics. The activity of retinal output neurons is driven by both the inputs from upstream neurons, which encode the visual information and reflect stimulus statistics, and the recurrent connections, which induce network effects. We first apply the standard inverse Ising model approach, and show that it accounts well for the system’s collective behavior when the input visual stimulus has short-ranged spatial correlations, but fails for long-ranged ones. This happens because stimuli with long-ranged spatial correlations synchronize the activity of neurons over long distances. This effect cannot be accounted for by pairwise interactions, and so by the pairwise Ising model. To solve this issue, we apply a previously proposed framework that includes a temporal dependence in the single neurons biases to model how neurons are driven in time by the stimulus. Thanks to this addition, the stimulus effects are taken into account by the biases, and the pairwise interactions allow for characterizing the network effect in the population activity and for reproducing the structure of the recurrent functional connections in the retinal architecture. In particular, the inferred interactions are strong and positive only for nearby neurons of the same type. Inter-type connections are instead small and slightly negative. Therefore, the retinal architecture splits into weakly interacting subpopulations composed of strongly interacting neurons. Overall, this temporal framework fixes the problems of the standard, static, inverse Ising model and accounts for the system’s collective behavior, for stimuli with either short or long-range correlations.
Brightness illusions evoke pupil constriction and a preceding primary visual cortex response in rats
Authors: Vasilev Dmitrii , Raposo Isabel , Totah Nelson K.
Published: July 2022

The mind affects the body via central nervous system (CNS) control of the autonomic nervous system (ANS). In humans, one striking illustration of the mind-body connection is that illusions, subjectively perceived as bright, drive constriction of the eye’s pupil by activating the sympathetic arm of the ANS. How the CNS is involved in this pupil response is unknown and requires an animal model for intracerebral investigation of potential regions, cell types, and neuronal projections. However, the physiological response to this illusion has long been thought to occur only in humans. Here, we report that the same brightness illusion that evokes pupil constriction in humans also does so in rats. Cortex-wide EEG recordings revealed that, compared to a luminance-matched control stimulus, the illusion (which appears subjectively brighter to humans) evoked a larger response only in primary visual cortex (V1). This cortical response preceded pupil constriction by ~335 msec suggesting a potential causal role for V1 on the pupil. Our results establish a new animal model of importance for studying how the CNS response involved in sensing a brightness illusion drives a physiological reaction in the body. We provide objective evidence that complex mind-body connections are not confined to humans and that V1 may be part of a shared, mammalian, neural network for bodily reactions to illusions.
Studying the age of onset and detection of Chronic Myeloid Leukemia using a three-stage stochastic model
Authors: Nag Suryadeepto , Bhat Ananda Shikhara , Chakrabarty Siddhartha P.
Published: July 2022

Chronic Myeloid Leukemia (CML) is a biphasic malignant clonal disorder that progresses, first with a chronic phase, where the cells have enhanced proliferation only, and then to a blast phase, where the cells have the ability of self-renewal. It is well-recognized that the Philadelphia chromosome (which contains the BCR-ABL fusion gene) is the “hallmark of CML”. However, empirical studies have shown that the mere presence of BCR-ABL may not be a sufficient condition for the development of CML, and further modifications related to tumor suppressors may be necessary. Accordingly, we develop a three-mutation stochastic model of CML progression, with the three stages corresponding to the non-malignant cells with BCR-ABL presence, the malignant cells in the chronic phase and the malignant cells in the blast phase. We demonstrate that the model predictions agree with age incidence data from the United States. Finally, we develop a framework for the retrospective estimation of the time of onset of malignancy, from the time of detection of the cancer.
Optimization of 4D Combined Angiography and Perfusion using Radial Imaging and Arterial Spin Labeling
Authors: Okell Thomas W. , Chiew Mark
Published: July 2022

Purpose

To extend and optimize a non-contrast MRI technique to obtain whole head 4D (time-resolved 3D) angiographic and perfusion images from a single scan.

Methods

4D combined angiography and perfusion using radial imaging and arterial spin labeling (CAPRIA) uses pseudocontinuous labeling with a 3D golden ratio (“koosh ball”) readout to continuously image the blood water as it travels through the arterial system and exchanges into the tissue. High spatial/temporal resolution angiograms and low spatial/temporal resolution perfusion images can be flexibly reconstructed from the same raw k-space data at any timepoint within the readout. A constant flip angle (CFA) and a quadratic variable flip angle (VFA) excitation schedule were optimized through simulations and tested in healthy volunteers. A conventional sensitivity encoding (SENSE) reconstruction was compared against a locally low rank (LLR) reconstruction, which leverages spatiotemporal correlations to improve reconstruction quality. Differences in image quality were assessed through split-scan repeatability.

Results

The optimized VFA schedule (2-9°) reduced initial signal attenuation whilst boosting the signal at later timepoints, resulting in a significant (p < 0.001) improvement in image quality (up to 84%), particularly for the lower SNR perfusion images. The LLR reconstruction provided effective denoising without biasing the signal timecourses, significantly improving angiographic and perfusion imaging repeatability (up to 143%, p < 0.001) and enabling the clear depiction of small distal vessels and late tissue perfusion.

Conclusion

4D CAPRIA can be optimized using a VFA schedule and LLR reconstruction to yield whole head 4D angiograms and perfusion images from a single scan.
Analysis of Chromatin Data Supports a Role For CD14+ Monocytes/Macrophages in Mediating Genetic Risk for Juvenile Idiopathic Arthritis
Authors: Crinzi Elizabeth A. , Haley Emma K. , Poppenberg Kerry E. , Jiang Kaiyu , Tutino Vincent M. , Jarvis James N.
Published: July 2022

Introduction

Genome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity.

Materials and Methods

We queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes.

Results

The LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood.

Conclusions

These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
Long read single cell RNA sequencing reveals the isoform diversity of Plasmodium vivax transcripts
Authors: Hazzard Brittany , Sá Juliana M. , Ellis Angela C. , Pascini Tales V. , Amin Shuchi , Wellems Thomas E. , Serre David
Published: July 2022

Plasmodium infections often consist of heterogenous populations of parasites at different developmental stages and with distinct transcriptional profiles, which complicates gene expression analyses. The advent of single cell RNA sequencing (scRNA-seq) enabled disentangling this complexity and has provided robust and stage-specific characterization of Plasmodium gene expression. However, scRNA-seq information is typically derived from the end of each mRNA molecule (usually the 3’-end) and therefore fails to capture the diversity in transcript isoforms documented in bulk RNA-seq data. Here, we describe the sequencing of scRNA-seq libraries using Pacific Biosciences (PacBio) chemistry to characterize full-length Plasmodium vivax transcripts from single cell parasites. Our results show that many P. vivax genes are transcribed into multiple isoforms, primarily through variations in untranslated region (UTR) length or splicing, and that the expression of these isoforms is often developmentally regulated. Our findings demonstrate that long read sequencing can be used to characterize mRNA molecules at the single cell level and provides an additional resource to better understand the regulation of gene expression throughout the Plasmodium life cycle.

Author Summary

Single cell RNA-sequencing is a valuable tool for identifying cell specific differences in heterogenous populations. However, scRNA-seq has limitations in assigning reads to genes of organisims with poorly annotated UTRs, due to the poly-A caputre utilized by some scRNA-seq technologies, this technical limitation also makes identifying transcript specific differences, like alternative splicing, difficult. Despite its importance in human disease the P. vivax genome annotation is still relatively sparce, especially in the UTRs, and very little is known about transcript differece in the different life stages of the parasite life cycle. Here, we utilize a modified version of 10X scRNA-seq technology to capture full length transcripts via PacBio sequencing from both sporozoite and blood stages of P. vivax. This allowed us to predict full length stage specific transcripts for P. vivax as well as identify important variation in the previously poorly annotated UTRs. These findings will aide in futhering our understanding of P. vivax transcript regulation across the life cycle stages.