bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Health Optimization (BHO) in Spine Surgery
Authors: Anderson Paul A. , Binkley Neil C. , Bernatz James T.
Published: March 2023

Study Design.

Literature review

Objective.

To educate spine surgeons on the importance of bone health optimization in surgical patients.

Summary of Background Data.

Osteoporosis is common and underdiagnosed in spine surgery patients. Poor bone health has been linked to worse outcomes and complications after spine surgery. Guidelines are available to inform decision making on screening and treatment in this population.

Methods.

Available literature is reviewed regarding bone health screening and treatment. Studies reporting outcomes related to osteoporosis, bone density, and vitamin D status are summarized. Pharmacologic treatment and nutritional considerations are discussed. Bone health optimization practice models and outcomes are also reviewed.

Results.

Bone health screening should be considered in all adults over age 50. Gender-specific guidelines are available to determine which patients need dual-energy x-ray absorptiometry. Osteoporosis can be diagnosed by dual-energy x-ray absorptiometry T-score, fracture risk calculator or by history of low-energy fracture. Advanced imaging including computed tomography and magnetic resonance imaging can be used to opportunistically assess bone health. If diagnosed, osteoporosis can be treated with either antiresorptive or anabolic agents. These medications can be started preoperatively or postoperatively and, in high-risk patients, surgical delay can be considered. The implementation of bone health optimization programs has been shown to greatly increasing screening and treatment rates.

Conclusion.

Bone health assessment and optimization are important for decreasing surgical risks and improving outcomes in spine surgery patients.
Single-cell profiling of the copy-number heterogeneity in colorectal cancer
Authors: Song Shiyu , Feng Lin , Xi Kexing , Sun Zhigang , Kong Deyang , Luo Zhenkai , Pei Wei , Zhang Haizeng
Published: March 2023

Background:

With functionally heterogeneous cells, tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment. Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth, invasion, and immune evasion. However, no reliable method to classify tumor cell subtypes is yet available. In this study, we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable (MSS) colorectal cancer (CRC).

Methods:

To characterize the somatic copy number alteration (SCNA) of MSS CRC in a single cell profile, we analyzed 26 tissue samples from 19 Korean patients (GSE132465, the Samsung Medical Center [SMC] dataset) and then verified our findings with 15 tissue samples from five Belgian patients (GSE144735, the Katholieke Universiteit Leuven 3 [KUL3] dataset). The Cancer Genome Atlas (TCGA) cohort, GSE39582 cohort, and National Cancer Center (NCC) cohort (24 MSS CRC patients were enrolled in this study between March 2017 and October 2017) were used to validate the clinical features of prognostic signatures.

Results:

We employed single cell RNA-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics. Among these three types of tumor cells, C1 and C3 had a higher SCNA burden; C1 had significant chromosome 13 and 20 amplification, whereas C3 was the polar opposite of C1, which exhibited deletion in chromosome 13 and 20. The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations. C1 and C2 were linked to the immune response and hypoxia, respectively, while C3 was critical for cell adhesion activity and tumor angiogenesis. Additionally, one gene (OLFM4) is identified as epithelium-specific biomarker of better prognosis of CRC (TCGA cohort: P = 0.0110; GSE39582 cohort: P = 0.0098; NCC cohort: P = 0.0360).

Conclusions:

On the basis of copy number characteristics, we illustrated tumor heterogeneity in MSS CRC and identified three types of tumor cells with distinct roles in tumor microenvironment. By understanding heterogeneity in the intricate tumor microenvironment, we gained an insight into the mechanisms of tumor evolution, which may support the development of therapeutic strategies.
Progress in blood biomarkers of subjective cognitive decline in preclinical Alzheimer's disease
Authors: Yu Xianfeng , Shao Kai , Wan Ke , Li Taoran , Li Yuxia , Zhu Xiaoqun , Han Ying
Published: March 2023

Alzheimer's disease (AD) is a neurodegenerative disease that gradually impairs cognitive functions. Recently, there has been a conceptual shift toward AD to view the disease as a continuum. Since AD is currently incurable, effective intervention to delay or prevent pathological cognitive decline may best target the early stages of symptomatic disease, such as subjective cognitive decline (SCD), in which cognitive function remains relatively intact. Diagnostic methods for identifying AD, such as cerebrospinal fluid biomarkers and positron emission tomography, are invasive and expensive. Therefore, it is imperative to develop blood biomarkers that are sensitive, less invasive, easier to access, and more cost effective for AD diagnosis. This review aimed to summarize the current data on whether individuals with SCD differ reliably and effectively in subjective and objective performances compared to cognitively normal elderly individuals, and to find one or more convenient and accessible blood biomarkers so that researchers can identify SCD patients with preclinical AD in the population as soon as possible. Owing to the heterogeneity and complicated pathogenesis of AD, it is difficult to make reliable diagnoses using only a single blood marker. This review provides an overview of the progress achieved to date with the use of SCD blood biomarkers in patients with preclinical AD, highlighting the key areas of application and current challenges.
Emerging role of miRNAs, lncRNAs, and circRNAs in pregnancy-associated diseases
Authors: Fu Xiaoxiao , Li Yuling , Zhang Zhen , Wang Bin , Wei Ran , Chu Chu , Xu Ke , Li Lihua , Liu Yonglin , Li Xia
Published: March 2023

Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), functioning as important regulators of transcription and translation, are involved in the establishment and maintenance of pregnancy, especially the maternal immune adaptation process. The endometrial stromal cells (ESCs), trophoblast cells, and decidua immune cells that reside at the maternal–fetal interface are thought to play significant roles in normal pregnancy and pregnancy-associated diseases. Here, we reviewed the up-to-date evidence on how microRNA, long non-coding RNA, and circular RNA regulate ESCs, trophoblast cells, and immune cells and discussed the potential applications of these ncRNAs as diagnostic and therapeutic markers in pregnancy complications.
Severe Bacterial Infection Initially Misdiagnosed as MIS-C: Caution Needed
Authors: Stanzelova Anna , Debray Agathe , Allali Slimane , Belhadjer Zahra , Taha Muhamed-Kheir , Cohen Jérémie F. , Toubiana Julie
Published: March 2023

Working in the era of the novel coronavirus disease 2019 can predispose to cognitive bias. We present a case of life-threatening bacterial infection misdiagnosed as multisystem inflammatory syndrome in children. While multisystem inflammatory syndrome in children-related myocardial dysfunction is now a well-recognized complication of coronavirus disease 2019, a rigorous differential diagnosis approach, notably for infectious etiologies, is paramount.
Fibromyalgia predicts increased odds of pain-related addiction exacerbation among individuals with pain and opioid use disorder
Authors: Hall Orman Trent , Teater Julie , Entrup Parker , Deaner Megan , Bryan Craig , Harte Steven E. , Kaplan Chelsea M. , Phan Kihn Luan , Clauw Daniel J.
Published: March 2023

Fibromyalgia and opioid use disorder (OUD) are highly impactful chronic illnesses with substantially overlapping psychosocial, biological, and clinical features. Little previous research has examined interactions between fibromyalgia and OUD. Limiting such research has been the previous requirement of a clinical examination to diagnose fibromyalgia. The 2011 American College of Rheumatology Fibromyalgia Survey (ACR-FMS) is a validated self-report instrument with high sensitivity and specificity for fibromyalgia intended to enable fibromyalgia research in settings where a clinical examination is impractical. The present observational study uses the ACR-FMS to determine whether fibromyalgia affects odds of acknowledging pain-related OUD exacerbations among a sample of participants with pain and OUD. Participants with pain and OUD (n = 125) were recruited from an academic substance use treatment facility. The ACR-FMS, along with an original scale measuring pain-related OUD exacerbation—the Pain-related OUD Exacerbation Scale—was administered through an electronic survey. The factor structure, internal consistency, and construct validity of Pain-related OUD Exacerbation Scale were tested. In addition, descriptive analyses, multiple hierarchical linear regression, ordinal logistic regression, and multinomial logistic regression analyses were performed. Although all participants had pain, those with fibromyalgia demonstrated significantly greater odds of acknowledging pain-related OUD exacerbations. Pain-related OUD Exacerbation Scale was found to have a single-factor solution, strong internal consistency, and construct validity. This study provides first evidence of fibromyalgia as a risk factor for pain-related exacerbation of OUD and introduces a new scale with promising psychometric properties to measure pain-related OUD exacerbation.
Forensic Nurses' Understanding of Emergency Contraception Mechanisms
Authors: Downing Nancy R. , Avshman Elaine , Valentine Julie L. , Johnson Luke M. , Chapa Hector
Published: March 2023

Background

An estimated 25,000 pregnancies result from sexual assault in the United States annually. Numerous professional healthcare organizations endorse offering emergency contraception (EC) as an integrated aspect of post-sexual-assault care. Lack of knowledge surrounding EC's mechanism of action, including misinterpreting ECs as abortifacients, might restrict patient access to this important healthcare option.

Purpose

We evaluated sexual assault nurse examiners' understanding of the mechanism of action of oral ECs levonorgestrel (LNG) and ulipristal acetate (UPA).

Methods

A cross-sectional survey of practicing sexual assault nurse examiners was conducted through the International Association of Forensic Nurses.

Results

Among 173 respondents, 96.53% reported they prescribed/dispensed EC at the time of medical forensic examinations. LNG was prescribed more frequently than UPA (57.80% vs. 38.2%, respectively). When asked if they agreed or disagreed if LNG and UPA can disrupt an established pregnancy, 83.2% selected disagree/strongly disagree for LNG versus 78.6% for UPA, which were not significantly different. When asked whether the Supreme Court ruling overturning Roe v. Wade would change their EC prescribing, 79.77% reported it will have no change, 6.94% said it would increase, and 12.72% reported they were unsure. Several commented they were concerned whether state laws would prohibit EC and at least one program stopped prescribing EC because of their state laws.

Implications

Addressing misinformation regarding EC's mechanism of action and increasing access to oral EC options after sexual assault have the potential to reduce the incidence of rape-related pregnancy.
Corporal Punishment
Authors:   International Association of Forensic Nurses
Published: March 2023

Globally, it is estimated that more than one billion children experience corporal punishment in the home despite the fact that the use of corporal punishment is associated with a variety of negative consequences for children. The International Association of Forensic Nurses opposes the use of corporal punishment and encourages screening and education on its effects in health and school settings.
Exercise Habits and Resources for Southeastern US Firefighters
Authors: Agostinelli Philip , Hirschhorn Rebecca , Sefton JoEllen
Published: March 2023

Background

This study aimed to assess exercise habits and facility resources accessible to southeastern US firefighters.

Methods

Firefighters completed questionnaires on topics including demographics, work demands, exercise methods, and facility resources.

Results

Sixty-six percent of participants reported they engage in exercise ≥30 min/d. More firefighters engaged in exercise when better on-site equipment options were available (P = 0.001). Perception of how on-shift exercise impacts occupational performance did not impact their on-shift exercise (P = 0.17).

Conclusions

Although 34% reported not meeting exercise guidelines, the majority of southeastern US firefighters reported meeting these guidelines and allotted exercise time on-shift. Exercise habits are impacted by equipment options, but not call volume or perception of on-shift exercise. Open-ended question responses suggested that perception of on-shift exercise did not deter firefighters from exercising on-shift but may impact intensity.
Factor Analysis in Distinguishing Coronavirus Disease 2019 From Other Influenza-like Illness Using a Validated Patient-Reported Outcome Instrument FLU-PRO Plus
Authors: Chrenka Ella A. , Roblin Douglas W. , Gander Jennifer C. , Powers John H. , Cromwell Lee X. , Kodthala Prasanthi X. , Whiting Thomas S. , Sesay Musu M. , Segall Marni F. , Deneal Adrienne N. , Truitt Anjali R. , Sour Elanadora U. , Martinson Brian C.
Published: March 2023

Background/Objective:

InFLUenza Patient-reported Outcome (FLU-PRO Plus) is a 34-item patient-reported outcome instrument designed to capture the intensity and frequency of viral respiratory symptoms. This study evaluates whether FLU-PRO Plus responses could discriminate between symptoms of coronavirus disease 2019 (COVID-19) and influenza-like illness (ILI) with no COVID diagnosis, as well as forecast disease progression.

Methods:

FLU-PRO Plus was administered daily for 14 days. Exploratory factor analysis was used to reduce the FLU-PRO Plus responses on the first day to 3 factors interpreted as “symptom clusters.” The 3 clusters were used to predict COVID-19 versus ILI diagnosis in logistic regression. Correlation between the clusters and quality of life (QoL) measures was used to assess concurrent validity. The timing of self-reported return to usual health in the 14-day period was estimated as a function of the clusters within COVID-19 and ILI groups.

Results:

Three hundred fourteen patients completed day 1 FLU-PRO Plus, of which 65% had a COVID-19 diagnosis. Exploratory factor analysis identified 3 symptom clusters: (1)general Body, (2) tracheal/bronchial, and (3) nasopharyngeal. Higher nasopharyngeal scores were associated with higher odds of COVID-19 compared with ILI diagnosis [adjusted odds ratio = 1.61 (1.21, 2.12)]. Higher tracheal/bronchial scores were associated with lower odds of COVID-19 [0.58 (0.44, 0.77)]. The 3 symptom clusters were correlated with multiple QoL measures (r = 0.14–0.56). Higher scores on the general body and tracheal/bronchial symptom clusters were associated with prolonged time to return to usual health [adjusted hazard ratios: 0.76 (0.64, 0.91), 0.80 (0.67, 0.96)].

Conclusion:

Three symptom clusters identified from FLU-PRO Plus responses successfully discriminated patients with COVID-19 from non-COVID ILI and were associated with QoL and predicted symptom duration.
Pediatric Fellowship-Trained Anesthesiologists Improve Anesthesia-Controlled Time in a Pediatric Endoscopy Suite
Authors: Carlson Adlei , McElrath Angela , Herrera Germaine , Patzkowski Michael
Published: March 2023

Objectives:

The objective of this study was to determine the difference in anesthesia-controlled time (ACT) between subspecialty-trained pediatric anesthesiologists and general anesthesiologists during esophagogastroduodenoscopy (EGD) and colonoscopy. We hypothesized pediatric anesthesiologists would demonstrate a shorter ACT compared to general anesthesiologists.

Methods:

We conducted a retrospective analysis of pediatric endoscopy cases requiring general endotracheal anesthesia within our pediatric sedation unit from 2017 to 2020. Demographic and procedural variables were collected and assessed for potential confounding. The imbalance in baseline variables was controlled for utilizing a generalized linear model (GLM). The GLM had a model fit of adjusted R
2 = 0.146 and was statistically significant with P < 0.001. A priori power analysis was performed for a 2-tailed independent means t test with alpha = 0.05, and Power = 0.80, which revealed a minimum sample size of 64 patients per group to detect a mean difference of 3 minutes of ACT.

Results:

A total of 269 cases met inclusion criteria. Adjusted results demonstrated fellowship-trained pediatric anesthesiologists were associated with a 3.7-minute (95% CI: 2.005–5.478; P < 0.001) reduction in ACT when compared to general practice anesthesiologists. Patient age was associated with a 0.4-minute (95% CI: –0.558 to –0.243; P < 0.001) decrease in ACT for each advancing year in age.

Conclusions:

We observed an association between the subspecialty training of the anesthesiology provider and ACT for EGDs and colonoscopies. When EGDs and colonoscopies are performed under the supervision of pediatric anesthesiologists, ACT reduction potentially reduces cost and improves efficiency.
Liver Disease in GLIS3 Mutations: Transplant Considerations and Bile Duct Paucity on Explant Histology
Authors: Couper Michael R. , Brown Rachel M. , Gupte Girish , Perera M. Thamara P.R. , Kelgeri Chayarani
Published: March 2023

GLI-similar 3 (GLIS3) gene mutation heterozygosity is characterized by neonatal diabetes and hypothyroidism. It has wide phenotypic variability. Liver disease is prevalent, and its complications in some phenotypes are life-limiting. Transplantation and the pathogenesis of GLIS3 liver disease are not well explored in the literature. We report 2 cases of children with GLIS3 mutations with chronic liver disease who required liver transplantation and we present a literature review discussing the pathogenic mechanisms and liver histology. Histology demonstrated predominantly biliary cirrhosis consistent with abnormal bile duct development. Both patients were considered for multi-organ transplantation (liver, pancreas with or without kidney) before receiving a liver transplant alone. Postoperative management can be challenging due to infection, renal disease, and brittle diabetes. GLIS3 mutations need to be added to the list of non-syndromic causes of bile duct paucity in the liver. Liver transplantation should be considered in patients with life-limiting complications related to liver disease.
Validity and reliability of the assessment of hand flexors stiffness using a new electromechanical oscillatory device in people with stroke
Authors: Selves Clara , Lejeune Thierry , Detrembleur Christine , Haustrate Marie-Adeline , Stoquart Gaëtant
Published: March 2023

Hyper-resistance after a central nervous system injury has been largely referred to as spasticity, which is but one of its neural components. Assessment largely relies on clinical scales (Modified Ashworth scale – MAS and Modified Tardieu scale, MTS) which are unable to distinguish between the non-neural (tissue-related) and the neural (central nervous system-related) components. This study assessed criterion validity and reliability (reproducibility) of muscle stiffness measures, namely, maximum elastic stiffness (ELmax), viscous stiffness (VI), and path length (L-path) in the hand flexor muscles among people with stroke. Measurements were obtained with a wrist-electromechanical oscillatory device (w-EOD). Twenty-four people with arm impairment after stroke were evaluated with the w-EOD and clinical assessment (MAS and MTS), twice on the same day (short-term reliability) and once 10 days later (long-term reliability). For criterion validity, a Spearman coefficient (r) was calculated between stiffness values and the clinical scales. For reliability, intraclass correlation coefficients (ICCs), SEM, and MDC95 were calculated. Moderate correlations were observed between ELmax and MAS (r = 0.49) and MTS (V2, r = 0.43; V3, r = 0.49) of the wrist flexors, and finger flexors (MAS, r = 0.60; MTS V2, r = 0.56; MTS V3, r = 0.55). There was a poor correlation between the clinical scales and VI and L-path. Reliability was excellent for all stiffness measurements at short term (ELmax: 0.95, VI: 0.94, L-path: 0.92) and good at long term (ELmax: 0.87, VI: 0.76, L-path: 0.82). In conclusion, stiffness measurements are valid and reliable to evaluate hyper-resistance in people with stroke.
Liver Transplantation for Refractory Congenital Cytomegaloviral Hepatitis
Authors: Aufhauser David D. , Condit Paige , Schmit Kathryn M. , Conway James H. , Cook Shelly , D’Alessandro Anthony M. , Furuya Katryn N.
Published: March 2023

Congenital cytomegalovirus (cCMV) is the most common congenital infection. Here, we report on a case of severe, refractory cCMV hepatitis resulting in end-stage liver disease. A male infant born at 37 weeks gestational age presented with petechiae, splenomegaly, and jaundice associated with a direct hyperbilirubinemia, elevated transaminases, and thrombocytopenia. Urine screen was positive for CMV, and he was treated with valganciclovir. He progressed to decompensated cirrhosis with ascites, hypoglycemia, and coagulopathy and was listed for liver transplant at 4 months of age. At 5 months of age, he developed massive hematemesis with hemorrhagic shock and underwent emergent portocaval shunt followed by living donor liver transplant with a left lateral segment graft. Postoperatively, he received CMV immune globulin and intravenous ganciclovir and cleared his viremia by 2 months post-transplant. This case illustrates the diagnostic and management challenges of severe cCMV hepatitis and reports a successful liver transplantation despite active CMV viremia.
A Biopsychosocial Approach to Complex Regional Pain Syndrome in a Pediatric Inflammatory Bowel Disease Patient
Authors: Sehdev Manmeet , Zoffness Rachel , Fritz Katelyn , Ali Sabina A.
Published: March 2023

Pediatric chronic pain is typically framed as a purely biomedical problem requiring exclusively biomedical solutions. However, research indicates that pain is biopsychosocial, produced and reduced by a combination of biological, psychological, sociological, and environmental factors, and that treatment must therefore also be biopsychosocial, incorporating interventions such as pain psychology and physical therapy. We report a case of a 16-year-old patient with Crohn disease and complex regional pain syndrome, and the multidisciplinary approach to care that was crucial for his return to function.
Resolving Co-contraction of the Elbow in Patient with the Sequelae of Obstetric Brachial Plexus Palsy: A Cohort Study
Authors: Zelenski Nicole A. , Lu Johnny Chuieng-Yi , Chang Tommy Nai-Jen , Chuang David Chwei-Chin
Published: March 2023

Background:

Obstetric brachial plexus palsy (OBPP) can cause deformities of the upper extremity in up to 92% (S-OBPP). Reconstruction of the elbow is difficult because co-contraction of the elbow flexor (EF) and extensor (EE) muscles makes the traditional strategy of treatment ineffective. We propose a novel strategy to minimize the effect of co-contraction, comprising of transfer of an EF to the triceps, followed by a staged gracilis muscle transplantation (FFMT) to augment EF. We hypothesize this will lead to improved EE, maintaining the EF, as well as decrease elbow flexion contracture.

Methods:

A single-center retrospective review of patients who received a gracilis FFMT for EF after EF-to-EE transfer was performed. EF/EE strength and range of motion were collected from the last clinical visit. Patients were excluded if they had less than 1.5 years of follow-up. A control group who had S-OBPP but non-surgical treatment was used for comparison.

Results:

Twenty-one patients were included. Average age at muscle transfer was 7.6 ±5.5 (3-22) Y/O and at gracilis FFMT was 10.4 ± 6.0 (5-26) Y/O. Average follow-up was 7.3 ± 6.5 (1.5-14.8) years. After EF-to-EE transfer, EE strength increased significantly from MRC 2.2 ± 0.4 to 3.4 ± 0.5 (p<0.0001) and EF decreased from 3.2 ± 1.1 to 1.1 ± 1.1 (p<0.0001) and recovered to MRC grade 3.3 ± 0.7 after gracilis FFMT. EF contracture was significantly less compared to non-surgical cohort (p=0.029).

Conclusion:

Patients who undergo EF-to-EE, followed by gracilis FFMT have equivalent EF strength with significantly improved EE and improved elbow flexion contracture.
Development and validation of a Bayesian network predicting neurosurgical intervention after injury in children and adolescents
Authors: Sullivan Travis M. , Sippel Genevieve J. , Matison Elizabeth A. , Gestrich-Thompson Waverly V. , DeWitt Peter E. , Carlisle M. Adam , Oluigbo David , Oluigbo Chima , Bennett Tellen D. , Burd Randall S.
Published: March 2023

BACKGROUND

Timely surgical decompression improves functional outcomes and survival among children with traumatic brain injury and increased intracranial pressure. Previous scoring systems for identifying the need for surgical decompression after traumatic brain injury in children and adults have had several barriers to use. These barriers include the inability to generate a score with missing data, a requirement for radiographic imaging that may not be immediately available, and limited accuracy. To address these limitations, we developed a Bayesian network to predict the probability of neurosurgical intervention among injured children and adolescents (aged 1–18 years) using physical examination findings and injury characteristics observable at hospital arrival.

METHODS

We obtained patient, injury, transportation, resuscitation, and procedure characteristics from the 2017 to 2019 Trauma Quality Improvement Project database. We trained and validated a Bayesian network to predict the probability of a neurosurgical intervention, defined as undergoing a craniotomy, craniectomy, or intracranial pressure monitor placement. We evaluated model performance using the area under the receiver operating characteristic and calibration curves. We evaluated the percentage of contribution of each input for predicting neurosurgical intervention using relative mutual information (RMI).

RESULTS

The final model included four predictor variables, including the Glasgow Coma Scale score (RMI, 31.9%), pupillary response (RMI, 11.6%), mechanism of injury (RMI, 5.8%), and presence of prehospital cardiopulmonary resuscitation (RMI, 0.8%). The model achieved an area under the receiver operating characteristic curve of 0.90 (95% confidence interval [CI], 0.89–0.91) and had a calibration slope of 0.77 (95% CI, 0.29–1.26) with a y intercept of 0.05 (95% CI, −0.14 to 0.25).

CONCLUSION

We developed a Bayesian network that predicts neurosurgical intervention for all injured children using four factors immediately available on arrival. Compared with a binary threshold model, this probabilistic model may allow clinicians to stratify management strategies based on risk.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Impact of an opioid use disorder consult service on hospitalized trauma patients with opioid use disorder
Authors: Muller Megan , Weyer George , Zakrison Tanya , Ari Mim
Published: March 2023

BACKGROUND

Opioid use disorder (OUD) is common in the hospitalized trauma population, being a comorbid diagnosis in approximately 1% of operative trauma cases. The impact of an addiction consult service in this population has been less well studied but may lead to increased provision of evidence-based OUD treatment and improved postdischarge outcomes.

METHODS

One hundred thirteen patients with an International Classification of Diseases diagnosis of OUD who were admitted to the trauma service at a single academic hospital between January 2020 to December 2021 were included in a retrospective chart review. Wilcoxon rank-sum tests were used to evaluate differences between patients who received an OUD consult and those who did not. Regression analysis was used to assess differences in postdischarge acute care utilization, attendance of follow-up appointments, initiation of and discharge on medication for opioid use disorder (MOUD), naloxone prescribing at discharge, and length of stay (LOS) between the consult and no-consult groups.

RESULTS

Eighty-one patients in the study population received a consult and 32 did not. Patients in the consult group were more likely to have started MOUD during their admission (odds ratio [OR], 2.09; p < 0.001), be discharged with naloxone (OR, 1.89; p < 0.001), have a plan in place for continued OUD treatment at discharge (OR, 1.43; p < 0.001), and attend scheduled follow-up appointments with the trauma team (OR, 1.76; p = 0.02). Differences in acute care utilization and LOS between the two groups were not statistically significant.

CONCLUSION

An OUD consult service can provide benefit to hospitalized trauma patients by increasing likelihood of starting MOUD, of discharging with MOUD and naloxone, and of attending trauma follow-up appointments without increasing LOS or acute care utilization. Thus, addiction consult service interventions during hospital admissions for trauma may serve to facilitate both evidence-based OUD care and posthospitalization trauma care.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Abnormal trophoblast invasion in early onset preeclampsia: involvement of cystathionine β-synthase, specificity protein 1 and miR-22
Authors: Arora Pallavi , Mochan Sankat , Gupta Sunil Kumar , Rani Neerja , Kshetrapal Pallavi , Dwivedi Sadanand , Bhatla Neerja , Dhingra Renu
Published: March 2023

Introduction

Impaired trophoblast invasion has been observed in early onset Preeclampsia patients (EOPE). Trophoblast cell invasion during human placentation is majorly regulated by the balance between MMPs 2, 9 and their inhibitors [tissue inhibitors of matrix metalloproteinases (TIMPs 1, 2)]. Exogenous NaHS (hydrogen sulphide donor) treatment was shown to significantly increase the expression levels of matrix metalloproteinases (MMPs 2, 9) in human bladder cancer EJ cells. Epigentically, the gene expression of hydrogen sulphide synthesising enzyme CBS (cystathionine β-synthase) could be further regulated by various mi-RNAs via the transcription factors like Sp1. Specificity protein 1 (Sp1) has been identified as a target gene for miR-22 to regulate the invasion and metastasis of gastric cancer cells. However, the mechanism of MMPs regulation by either CBS, Sp1 and miRNA-22 in the pregnancies having EOPE is not known.

Aims and Objectives

To determine and compare the expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1 and miRNA-22 in EOPE patients and normotensive, non-proteinuric controls.

Materials and methods

100 pregnant women were enrolled from Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. EOPE women (n=50) after clinical diagnosis as per ACOG guidelines were enrolled as cases and normotensive, non-proteinuric pregnant women (n=50) were enrolled as controls. Protocol of the study was approved by Institute Ethics Committee, AIIMS, New Delhi. 5 ml of venous blood was collected from all the recruited women (2.5 ml in each EDTA and sera vial) followed by plasma and sera separation. Plasma samples were used subsequently to determine gene expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1 and miRNA-22 by qRT-PCR and sera samples were used to estimate their protein levels by ELISA. Data were analyzed by STATA 14 and Graph Pad Prism 8.

Results

Significantly down regulated expression of MMPs 2, 9, CBS and Sp1 whereas up regulated expression for that of TIMPs 1, 2 was observed in EOPE patients as compared to healthy pregnant women at both transcription and translation levels. Expression of miR-22 (pre miR-22 and miR-22-3p) was found to be significantly elevated in EOPE patients as compared to normotensive, non-proteinuric controls.

Conclusion

This is the very first study of its kind which implicates that down regulated MMPs 2, 9, CBS, Sp1 levels and simultaneously upregulation of miR-22 expression in EOPE patients could have some association. In vitro experiments are needed to prove their association which if proven may provide a new, potential therapeutic target to treat early onset Preeclampsia.
Altered expression of MMP9 and TIMP1 leads to impaired placentation in early onset preeclamptic patients: a case control study
Authors: Arora Pallavi , Mochan Sankat , Gupta Sunil Kumar , Rani Neerja , Kshetrapal Pallavi , Dwivedi Sadanand , Bhatla Neerja , Dhingra Renu
Published: March 2023

Introduction

Matrix metalloproteinases (MMPs) specifically MMP-9 is a key regulator of vascular and uterine spiral artery remodelling and its activity is controlled at multiple levels, including gene transcription, activation of its latent forms and endogenous inhibition by tissue inhibitors of metalloproteinases [TIMPs (specifically TIMP-1)]. Alteration in MMP-9 and TIMP-1 expression may contribute to uterine and vascular dysfunction leading to adverse pregnancy outcomes such as Preeclampsia (PE). Depending on time, PE is classified as early-onset preeclampsia, which is diagnosed before 34 weeks of gestation, or late-onset preeclampsia, which is diagnosed after 34 weeks. Early-onset preeclampsia (EOPE) is a severe obstetrics disease which threatens mother and foetus. Therefore, in the present study, we aimed to investigate the levels of MMP-9 and its inhibitor TIMP-1 in the placentae of EOPE patients and their maternal age matched normotensive, non-proteinuric controls at both mRNA and protein levels.

Methods

A total of 30 caesarean delivered placentae (15 EOPE patients and 15 controls) were collected from Department of Obstetrics and Gynaecology, AIIMS, New Delhi after taking permission from Institute Ethics Committee. MMP-9 and TIMP-1 protein expression was observed by immunohistochemistry and immunofluorescence stainings. Gelatin Gel Zymography was done to evaluate MMP-9 activity and Western Blot was done for the quantification of MMP-9 and TIMP-1 proteins. mRNA levels of MMP-9 and TIMP-1 were determined by qRT-PCR

Results

Immunohistochemistry and Immunofluorescence staining discerned stronger expression of MMP-9 in normotensive placentae as compared to EOPE placentae whereas stronger expression of TIMP-1 was seen in EOPE placentae in comparison to those of normotensive placentae. Gelatin Gel Zymography reflected that MMP-9 activity was found elevated in maternal placental side in normotensive placentae as compared to EOPE placentae. Western Blot analysis revealed that protein expression of MMP-9 was elevated whereas for that of TIMP-1 was reduced in normotensive placentae in comparison to EOPE placentae. mRNA expression of MMP-9 was found up-regulated whereas for that of TIMP-1 was down-regulated in normotensive placentae as compared to EOPE placentae.

Conclusion

The present study implies that aberrant functioning of MMP-9 and TIMP-1 in EOPE patients contribute to impaired placentation which might be relevant for possible future screening programs in order to predict and to design therapies for early onset preeclamptic patients.
Hybrid Value-Aware Transformer Architecture for Joint Learning from Longitudinal and Non-Longitudinal Clinical Data
Authors: Shao Yijun , Cheng Yan , Nelson Stuart J. , Kokkinos Peter , Zamrini Edward Y. , Ahmed Ali , Zeng-Treitler Qing
Published: March 2023

Transformer is the latest deep neural network (DNN) architecture for sequence data learning that has revolutionized the field of natural language processing. This success has motivated researchers to explore its application in the healthcare domain. Despite the similarities between longitudinal clinical data and natural language data, clinical data presents unique complexities that make adapting Transformer to this domain challenging. To address this issue, we have designed a new Transformer-based DNN architecture, referred to as Hybrid Value-Aware Transformer (HVAT), which can jointly learn from longitudinal and non-longitudinal clinical data. HVAT is unique in the ability to learn from the numerical values associated with clinical codes/concepts such as labs, and also the use of a flexible longitudinal data representation called clinical tokens. We trained a prototype HVAT model on a case-control dataset, achieving high performance in predicting Alzheimer’s disease and related dementias as the patient outcome. The result demonstrates the potential of HVAT for broader clinical data learning tasks.
Integrating the environmental and genetic architectures of mortality and aging
Authors: Argentieri M. Austin , Amin Najaf , Nevado-Holgado Alejo J. , Sproviero William , Collister Jennifer A. , Keestra Sarai M. , Doherty Aiden , Hunter David J. , Alvergne Alexandra , van Duijn Cornelia M.
Published: March 2023

It has long been suggested that environmental exposures (i.e., the exposome) play a dominant role in shaping trajectories of human aging and premature mortality. Here we aimed to quantify the contribution of the exposome and genome to aging and mortality. We conducted an exposome-wide analysis in the UK Biobank (n=492,567) to systematically identify exposures associated with mortality while accounting for exposure correlation and mismeasurement. We found that the exposome is a major mortality determinant irrespective of genetic disease risk via shaping distinct biological and multimorbidity patterns. We identified 41 independent exposures associated with mortality, and demonstrate that most identified exposures are associated with a common signature of age-related multimorbidity, aging biomarkers, and major cardiometabolic risk factors. Compared with age and sex, polygenic risk for 22 major diseases and aging phenotypes explained an additional 2% of mortality variation, whereas the exposome explained an additional 19%. While genetics explained the majority of variation in dementias and breast, prostate, and colorectal cancers, the exposome explained the majority of variation for diseases of the lung, heart, and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and common age-related diseases.
Analyzing the amplification of Auditory sensation in visually impaired individuals and comparison with normal individuals
Authors: Desai Dev Himanshubhai
Published: March 2023

Background

It is commonly believed that if a person loses one of their basic senses like sight or hearing, other senses will be amplified to compensate the loss. It has been proven that this amplification does indeed help the person up to an extent, but this increase in the senses as compared to other individuals, who have all senses intact, has not been quantified.

Aim

To estimate and compare Auditory Acuity between visually impaired and normal people

To calculate the amount of amplification in the Auditory sense in the visually impaired individuals in compared to Normal Individuals

Methodology

A Cross Sectional Case-control Pilot Experimental Study was carried out using a method that has been developed by the authors, wherein a pure tone sound at a specific intensity was brought inwards towards the subject from multiple directions and the distance was measured where the participant could hear the sound and was noted. The same experiment was carried out in Normal Individuals with normal 6/6 vision and these measurements were compared. Positon of nose in respect to the direction of sound source was used to denote the results in angles made by the two. A pure tone of 256 Hz, of 30db was used as the sound source and the distance from the subject was measured in meters.

Results

Out of total 60 individuals in the study, 45 had some degree of blindness. In both groups, the highest sensitivity is at 0° followed by 45°-315°, then comes 90°-270° and 135°-215° to put nose position of 180° at least amount of sensitivity. A 10% amplification in the distance is present between any and all type of visually impaired individuals and normal individuals whereas totally blind individuals have around 20% amplification compared to normal individuals in the distance to appreciate the sound.

Conclusion

A visible difference can be seen in the distance where a total blind person can hear, which is higher than the distance at which a normal individual can hear. High loss of vision, low loss of vision and one eye blind individuals come in the range between these two. Although, the results are not statistically significant, they are clinically present, and a with a larger sample size, a better assessment of this amplification can be done.
Genome-wide association studies reveal novel loci controlling tuber flesh color and oxidative browning inDioscorea alata
Authors: Dossa Komivi , Morel Angélique , Ezékiel Houngbo Mahugnon , Mota Ana Zotta , Malédon Erick , Irep Jean-Luc , Diman Jean-Louis , Mournet Pierre , Causse Sandrine , Van Kien Nguyen , Cornet Denis , Chair Hâna
Published: March 2023

Background

Consumers’ preferences for food crops are guided by quality attributes. This study aimed at deciphering the genetic basis of quality traits, especially tuber flesh color (FC) and oxidative browning (OB) inDioscorea alata, based on the genome-wide association studies (GWAS) approach. TheD. alatapanel was planted at two locations in Guadeloupe. At harvest, the FC was scored visually as white, cream, or purple on longitudinally sliced mature tubers. The OB was scored visually as the presence or absence of browning after 15 minutes of exposure of the sliced samples to ambient air.

Results

Phenotypic characterization for FC and OB of a diverse panel ofD. alatagenotypes highlighted significant variation within the panel and across two locations. The genotypes within the panel displayed a weak structure and could be classified into 3 subpopulations. GWAS identified 14 and 4 significant associations for tuber FC and OB, respectively, with phenotypic variance, explained values ranging from 7.18 to 18.04%. Allele segregation analysis at the significantly associated loci highlighted the favorable alleles for the desired traits, i.e., white FC and no OB. A total of 24 putative candidate genes were identified around the significant signals. A comparative analysis with previously reported quantitative trait loci indicated that numerous genomic regions control these traits inD. alata.

Conclusion

Our study provides important insights into the genetic control of tuber FC and OB inD. alata. The major and stable loci can be further utilized to improve selection in breeding programs for developing new cultivars with enhanced tuber quality.
Rab46: a novel player in mast cell function
Authors: Pedicini Lucia , Smith Jessica , Savic Sinisa , McKeown Lynn
Published: March 2023

Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involves selective and agonist-specific release of these active mediators. Whilst a filtering mechanism at the plasma membrane could regulate selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways. The molecular mechanisms underlying differential trafficking and exocytosis of these granules are not known, neither is it clear how granule trafficking is coupled to the stimulus. In endothelial cells, a Rab GTPase, Rab46, responds to histamine but not thrombin signals, and this regulates the trafficking of a subpopulation of endothelial-specific granules. Here, we sought to explore if Rab46 has a similar function in mast cells. We demonstrate, for the first time, that Rab46 is highly expressed in human and murine mast cells and Rab46 genetic deletion has an effect on mast cell degranulation that depends on both stimuli and mast cell developmental stage. Rab46 could therefore be an important regulator of stimuli-coupled responses in mast cells and future studies will seek to understand these mechanisms in order to develop novel and specific therapeutic targets for treatment of the diverse pathologies mediated by mast cells.
Zobellia alginoliquefacienssp. nov., a new flavobacteria isolated from the epibiota of the brown algaEricaria zosteroides(C.Agardh) Molinari & Guiry 2020
Authors: Barbeyron Tristan , Le Duff Nolwenn , Duchaud Eric , Thomas François
Published: March 2023

Strain LLG6346-3.1T, isolated from the thallus of the brown algaEricaria zosteroidescollected in Mediterranean Sea near Bastia in Corsica, France, was characterized using a polyphasic method. Cells were Gram-stain-negative, strictly aerobic, non-flagellated, motile by gliding, rod-shaped and grew optimally at 30-33 °C, at pH 8-8.5 and with 4-5 % NaCl. Strain LLG6346-3.1Tused the seaweed polysaccharide alginic acid as sole carbon source which was vigorously liquefied. Phylogenetic analyses showed that the bacterium is affiliated to the genusZobellia(familyFlavobacteriaceae, classFlavobacteriia). Strain LLG6346-3.1Texhibited 16S rRNA gene sequence similarity values of 98.5 and 98.3 % to the type strains ofZobellia russelliiandZobellia roscoffensisrespectively, and of 97.4-98.2 % to other species of the genusZobellia. The DNA G+C content of strain LLG6346-3.1Twas determined to be 38.28 mol%. Digital DNA-DNA hybridization predictions by the ANI and GGDC methods between strain LLG6346-3.1Tand other members of the genusZobelliashowed values of 76-88 %, and below 37 %, respectively. The phenotypic, phylogenetic and genomic analyses show that strain LLG6346-3.1Tis distinct from species of the genusZobelliawith validly published names and that it represents a novel species of the genusZobellia, for which the nameZobellia alginoliquefacienssp. nov. is proposed. The type strain is LLG6346-3.1T(RCC 7657T= LLG 32918T).
An ancient gene regulatory network sets the position of the forebrain in chordates
Authors: Gattoni Giacomo , Keitley Daniel , Sawle Ashley , Benito-Gutiérrez Elia
Published: March 2023

The evolutionary origin of the vertebrate brain is still a major subject of debate. Its distinctive dorsal position and development from a tubular neuroepithelium are unique to the chordate phylum. Conversely, apical organs (AO) are larval sensory/neurosecretory centers found in many invertebrate taxa, including in animals without a brain. Previous studies have shown that AOs are specified by a conserved set of genes under the influence of Wnt signalling. Although most of these genes are expressed in chordate nervous systems (including vertebrates), no AOs have ever been described in this group of animals. Here we have exploited single-cell genomic approaches to characterize cells showing AO profiles in sea urchin (ambulacrarian), amphioxus (invertebrate chordate) and zebrafish (vertebrate chordate). This, in combination with co-expression analysis in amphioxus embryos, has allowed us to identify an active and dynamic anterior Gene Regulatory Network (aGRN) in the three deuterostome species. We have further discovered that as well as controlling AO specification in sea urchin, this aGRN is involved in the formation of the hypothalamic region in amphioxus and zebrafish. Using a functional approach, we find that the aGRN is controlled by Wnt signalling in amphioxus, and that suppression of the aGRN by Wnt overactivation leads to a loss of forebrain cell types. The loss of the forebrain does not equate to a reduction of neuronal tissue, but to a loss of identity, suggesting a new role for Wnt in amphioxus in specifically positioning the forebrain. We thus propose that the aGRN is conserved throughout bilaterians and that in the chordate lineage was incorporated into the process of neurulation to position the brain, thereby linking the evolution of the AO to that of the chordate forebrain.