bluuebunny/crossref_metadata_2025 huggingface dataset:
Buprenorphine Receipt and Retention for Opioid Use Disorder Following an Initiative to Increase Access in Primary Care
Authors: Hawkins Eric J. , Malte Carol A. , Hagedorn Hildi J. , Gordon Adam J. , Williams Emily C. , Trim Ryan S. , Blanchard Brittany E. , Lott Aline , Danner Anissa N. , Saxon Andrew J.
Published: February 2024

Objectives

Buprenorphine, a medication for opioid use disorder (OUD), is underutilized in general medical settings. Further, it is inequitably received by racialized groups and persons with comorbidities. The Veterans Health Administration launched an initiative to increase buprenorphine receipt in primary care. The project's objective was to identify patient-related factors associated with buprenorphine receipt and retention in primary care clinics (n = 18) participating in the initiative.

Methods

Retrospective cohort quality improvement evaluation of patients 18 years or older with 2 or more primary care visits in a 1-year period and an OUD diagnosis in the year before the first primary care visit (index date). Buprenorphine receipt was the proportion of patients with OUD who received 1 or more buprenorphine prescriptions from primary care providers during the post–index year and retention the proportion who received buprenorphine for 180 days or longer.

Results

Of 2880 patients with OUD seen in primary care, 11.7% (95% confidence interval [CI], 10.6%–12.9%) received buprenorphine in primary care, 58.2% (95% CI, 52.8%–63.3%) of whom were retained on buprenorphine for 180 days or longer. Patients with alcohol use disorder (adjusted odds ratio [AOR], 0.39; 95% CI, 0.27–0.57), nonopioid drug use disorder (AOR, 0.64; 95% CI, 0.45–0.93), and serious mental illness (AOR, 0.60; 95% CI, 0.37–0.97) had lower buprenorphine receipt. Those with an anxiety disorder had higher buprenorphine receipt (AOR, 1.42; 95% CI, 1.04–1.95). Buprenorphine receipt (AOR, 0.55; 95% CI, 0.35–0.87) and 180-day retention (AOR, 0.40; 95% CI, 0.19–0.84) were less likely among non-Hispanic Black patients.

Conclusions

Further integration of addiction services in primary care may be needed to enhance buprenorphine receipt for patients with comorbid substance use disorders, and interventions are needed to address disparities in receipt and retention among non-Hispanic Black patients.
Understanding New Recommendations for Respiratory Syncytial Virus Prevention in Pregnancy
Authors: Horgan Rebecca , Hughes Brenna L. , Waller Jerri , Hage Diab Yara , Saade George
Published: February 2024

Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide with peak hospitalization rates for RSV-mediated illnesses between 2 and 3 months of life. Until very recently, prevention strategies for RSV involved primarily passive immunization of neonates at high risk with monoclonal antibodies and promotion of breastfeeding. The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices now recommends passive immunization of all neonates with monoclonal antibodies during RSV season, and the American Association of Pediatrics has endorsed this practice. The U.S. Food and Drug Administration (FDA) recently approved a vaccination for RSV in pregnancy. The CDC's Advisory Committee on Immunization Practices has recently recommended RSV vaccination for all pregnant patients between 32 and 36 weeks of gestation who are anticipated to deliver during RSV season if they are not planning nirsevimab for their infants. This recommendation has been endorsed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine. In this clinical perspective, we review the scientific evidence, potential concerns, challenges, and future considerations for RSV vaccination in pregnancy.
Endometrial Cancer in a Transgender Man with Prolonged Exogenous Testosterone Use
Authors: Gill Stephanie , Anderson Michelle , Neveu Joannie
Published: February 2024

BACKGROUND:

Hormone therapy (HT) in transgender males requires monitoring. For amenorrheic transmasculine individuals on HT, episodes of abnormal vaginal bleeding should be assessed promptly.

CASE:

A 33-year-old transgender man on exogenous testosterone therapy for medical gender transition was found to have stage IV endometrioid endometrial adenocarcinoma. Surgical resection was performed for symptom control, and the patient was treated with palliative chemotherapy. The tumor was androgen receptor–negative, and, after a multidisciplinary discussion of the risks and benefits of continuing exogenous testosterone, testosterone therapy was restarted postoperatively.

CONCLUSION:

Long-term androgen use may have unknown implications for the development of malignancy, and treating reproductive organ cancer in transgender males may be complicated by the desire to continue androgen therapy.
Neonatal Birth Weight With Daily Compared With Every-Other-Day Glucose Monitoring in Gestational Diabetes Mellitus
Authors: Feldman Kristina Martimucci , Coughlin Arielle , Feliciano Jasmin , Stoffels Guillaume , Wang Kelly Z. , Strauss Tirtza Spiegel , Grubman Olivia , Al-Ibraheemi Zainab , Cole David , Ashmead Graham , Hussain Farrah , Shchur Sophia Scarpelli , Lee Deborah , Brustman Lois
Published: February 2024

OBJECTIVE:

To assess whether universal use of every-other-day glucose monitoring in patients with gestational diabetes mellitus (GDM) resulted in similar birth weights and medication use and was preferred by the patient compared with traditional daily glucose monitoring.

METHODS:

This was a noninferiority randomized controlled trial conducted at a single New York City hospital between April 2021 and May 2022. Patients with singleton pregnancies who were diagnosed with GDM after 20 weeks of gestation and had a minimum of 7 days of previous daily blood glucose testing were randomly assigned to test blood glucose values daily or every other day. The primary outcome was neonatal birth weight. We calculated a total sample size of 196 participants needed for noninferiority to be tested, assuming the mean birth weight in the every-other-day group, compared with the daily group, was no higher than the predefined noninferiority margin of 200 g (80% power and one-sided alpha of 0.05). Postrandomization characteristics, including blood glucose values and medication initiation and timing, were recorded. Satisfaction with treatment group was assessed using the validated Oxford Maternity Diabetes Treatment Satisfaction Questionnaire.

RESULTS:

A total of 197 patients were randomized: 98 in the daily group and 99 in the every-other-day group. Baseline characteristics were similar between groups. The mean neonatal birth weight was similar between groups (mean±SD 3,090±418 g among newborns in the daily group compared with 3,181±482 g among newborns in the every-other-day group). For the primary outcome, the every-other-day group was found to be noninferior to the daily group with an upper confidence limit for the mean difference in mean birth weight of 197 g, which was below the noninferiority margin of 200 g (P=.046). Postrandomization, there were no significant differences in the number of patients who required medication, the gestational age at which medication was started, or the type of medication used. Average fasting and postprandial glucose values were similar between groups. There was an increase in adherence to treatment group in those randomized to every-other-day blood sugars, but no difference in patient satisfaction.

CONCLUSION:

In patients with GDM, testing blood glucose values every other day was as effective as testing daily, without apparent effects on birth weight, medication initiation, or glucose control. Reduced frequency of blood glucose monitoring might help decrease the emotional, physical, and financial burden experienced by patients with GDM.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04857073.
In Vitro Characterization of Fat Grafts Processed Using the REVOLVE ENVI System versus Decantation
Authors: Gabriel Allen , Kabaria Nimesh , Fang Carrie H. , Lombardi Jared A. , Stec Eric , Huang Li Ting , Li Hui , Sandor Maryellen
Published: February 2024

Background:

This preclinical study evaluated benchtop/in vitro properties and fat viability and activity of grafts processed using the REVOLVE ENVI 600 system compared with decantation and evaluated properties of REVOLVE ENVI waste.

Methods:

Lipoaspirate from six donors was processed using REVOLVE ENVI or decantation. The composition of each graft, hematocrit/red blood cell content, fat particle size/macrostructure, viable adipocyte count, and adipocyte activity were analyzed. Stromal vascular fraction was analyzed for viable progenitor cell count and colony-forming units.

Results:

REVOLVE ENVI grafts had a higher mean (±SD) fat content at 85.6% ± 6.1% than decanted grafts at 72.1% ± 4.0% (P < 0.001), with negligible free oil (0.4% ± 1.1%) and cellular debris (<0.1%), whereas REVOLVE ENVI waste contained primarily aqueous fluid (91.0% ± 2.2%) with negligible viable fat. REVOLVE ENVI grafts had significantly lower hematocrit levels (P < 0.001) and contained significantly more large fat globules (P < 0.001) than decanted grafts or REVOLVE ENVI waste. The percentage of tissue particles of more than 1000 µm was highest for REVOLVE ENVI grafts at 61.6% ± 9.2% (decantation: 52.5% ± 13.4%; REVOLVE ENVI waste: 0.49% ± 1.50%), and the percentage of particles less than 200 µm was lowest for REVOLVE ENVI grafts at 15.7% ± 2.6% (decantation: 32.2% ± 8.9%; REVOLVE ENVI waste: 97.9% ± 4.5%). REVOLVE ENVI grafts contained 145.2% ± 36.0% more viable adipocytes, 145.7% ± 46.2% greater activity, 195.5% ± 104.2% more progenitors in SVF, and 363.5% ± 161.2% more SVF colony-forming units than decanted grafts.

Conclusion:

Fat grafts processed using REVOLVE ENVI demonstrated greater viability and activity than decanted grafts in vitro.
Endocarditis in a Community Teaching Hospital
Authors: Yang Ji Hyun , Tavares Liliana , Moon Soo Jin , Yoo Tae Kyung , Wagner Leonardo , Barbosa Felipe , Kinzfogl George , Chen Lucas , Treadwell Thomas
Published: February 2024

Background

Endocarditis is a life-threatening condition with protean manifestations. The clinical syndrome continues to evolve with an aging population, the opioid epidemic, and changing microbiological profiles. Much of the clinical data for endocarditis comes from tertiary care centers with on-site cardiac surgery. Previous community cohorts do not reflect the current patient populations or current microbiology and predate the current opioid epidemic. We retrospectively reviewed the baseline clinical characteristics, microbiologic spectrum, surgical indication, tertiary referral, and outcomes for patients presenting to a community hospital with infective endocarditis (IE).

Methods

We retrospectively reviewed all adult medical patient admitted over a 5-year period with a clinical diagnosis of IE, from February 2016 to September 2021, to a single suburban safety net community hospital without on-site cardiac surgery.

Results

We identified 99 patients with a clinical diagnosis of IE. We observed a bimodal age distribution, with more comorbidities and predisposing cardiac conditions in the older patients and more intravenous drug use in the younger patients. Surgical indications were present in 44% of patients. Staphylococcus aureus was the most common pathogen. Overall survival was associated with fewer comorbidities and the absence of methicillin-resistant S. aureus infection. There was no difference in survival between patients with and without surgical indications.

Conclusions

IE continues to primarily affect older patients with comorbidities and results in a high 1-year mortality of 33%. A simple score including age, Charlson comorbidity index of 6.5, and methicillin-resistant S. aureus infection was predictive for in-patient, 30-day, and 1-year mortality.
Substantial decline of organ preservation fluid contamination following adoption of Ischemia-Free liver transplantation：a Post-hoc analysis
Authors: Lin Jianwen , Li Yefu , Fang Tongdi , Wang Tielong , Liao Kang , Zhao Qiang , Wang Dongping , Chen Maogen , Zhu Xiaofeng , Chen Yinghua , Chen Honghui , Guo Yiwen , Zhan Liqiang , Zhang Jiayi , Zhang Tao , Zeng Ping , Peng Yaqin , Yang Lu , Cai Changjie , Guo Zhiyong , He Xiaoshun
Published: February 2024

Introduction:

Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, we evaluated the impact of IFLT on organ PF contamination.

Methods:

A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination.

Results:

Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group (P<0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance (P=0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF.

Conclusion:

PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.
An Exploratory Analysis of Physical Examination Subtypes in Pediatric Athletes With Concussion
Authors: McPherson Jacob I. , Marsh Amanda C. , Cunningham Adam , Leddy John J. , Corrado Cathlyn , Cheema Zaheerud D. , Nazir Muhammad S. Z. , Nowak Andrew S. , Farooq Osman , Willer Barry S. , Haider Mohammad N.
Published: February 2024

Objective:

Pediatric athletes with concussion present with a variety of impairments on clinical assessment and require individualized treatment. The Buffalo Concussion Physical Examination is a brief, pertinent clinical assessment for individuals with concussion. The purpose of this study was to identify physical examination subtypes in pediatric athletes with concussion within 2 weeks of injury that are relevant to diagnosis and treatment.

Design:

Secondary analysis of a published cohort study and clinician consensus.

Setting:

Three university-affiliated sports medicine centers.

Participants:

Two hundred seventy children (14.9 ± 1.9 years).

Independent Variables:

Orthostatic intolerance, horizontal and vertical saccades, smooth pursuits, vestibulo-ocular reflex, near-point convergence, complex tandem gait, neck range of motion, neck tenderness, and neck spasm.

Main Outcome Measures:

Correlations between independent variables were calculated, and network graphs were made. k-means and hierarchical clustering were used to identify clusters of impairments. Optimal number of clusters was assessed. Results were reviewed by experienced clinicians and consensus was reached on proposed subtypes.

Results:

Physical examination clusters overlapped with each other, and no optimal number of clusters was identified. Clinician consensus suggested 3 possible subtypes: (1) visio-vestibular (horizontal and vertical saccades, smooth pursuits, and vestibulo-ocular reflex), (2) cervicogenic (neck range of motion and spasm), and (3) autonomic/balance (orthostatic intolerance and complex tandem gait).

Conclusions:

Although we identified 3 physical examination subtypes, it seemed that physical examination findings alone are not enough to define subtypes that are both statistically supported and clinically relevant, likely because they do not include symptoms, assessment of mood or cognitive problems, or graded exertion testing.
Advanced magnetic resonance neuroimaging techniques: feasibility and applications in long or post-COVID-19 syndrome - a review
Authors: Mohammadi Sana , Ghaderi Sadegh
Published: February 2024

Long-term or post-COVID-19 syndrome (PCS) is a condition that affects people infected with SARS‑CoV‑2, the virus that causes COVID-19. PCS is characterized by a wide range of persistent or new symptoms that last months after the initial infection, such as fatigue, shortness of breath, cognitive dysfunction, and pain. Advanced magnetic resonance (MR) neuroimaging techniques can provide valuable information on the structural and functional changes in the brain associated with PCS as well as potential biomarkers for diagnosis and prognosis. In this review, we discuss the feasibility and applications of various advanced MR neuroimaging techniques in PCS, including perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), functional MR imaging (fMRI), diffusion tensor imaging (DTI), and tractography. We summarize the current evidence on neuroimaging findings in PCS, the challenges and limitations of these techniques, and the future directions for research and clinical practice. Although still uncertain, advanced MRI techniques show promise for gaining insight into the pathophysiology and guiding the management of COVID-19 syndrome, pending larger validation studies.
Nutritional Status, Dietary Intake, Quality of Life and Dysphagia in Women With Fibromyalgia
Authors: Rodríguez María Correa , del Carmen Villaverde Rodríguez María , Barragán Antonio Casas , Haro Rosa María Tapia , Ferrándiz María Encarnación Aguilar
Published: February 2024

Background

Fibromyalgia syndrome (FMS) is an idiopathic chronic disease characterized by widespread musculoskeletal pain, hyperalgesia, and allodynia that has been recently associated with risk of dysphagia.

Objective

We aimed to analyze the association between nutritional status, micro- and macronutrient intake and quality of life (QoL) in a cohort of women with FMS and risk of dysphagia compared to women with FMS without risk of dysphagia.

Methods

A cross-sectional study was conducted in 46 women with FMS. Risk of dysphagia was assessed by the Eating Assessment Tool (EAT) and the Volume–Viscosity Test (V–VST). The Food Frequency Questionnaire and the Swallowing Quality of Life Questionnaire were used to assess dietary intake and QoL, respectively.

Results

Thirty women with FMS were at risk for dysphagia (65.21%) assessed by the EAT–10. Based on the V–VST, the frequency of risk of dysphagia was 63.04%. Significant differences in body mass index (BMI) were found between women at risk for dysphagia and those without risk. Women at risk for dysphagia had significantly lower overall QoL scores than those women without risk. No significant differences were found for dietary intake and dysphagia risk.

Discussion

Women with FMS at risk for dysphagia have significantly lower BMI values and worse QoL than women without dysphagia risk, supporting the importance of assessing dysphagia in clinical practice in persons with FMS.
Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children*
Authors: Pelletier Jonathan H. , Rakkar Jaskaran , Au Alicia K. , Fuhrman Dana Y. , Clark Robert S.B. , Kochanek Patrick M. , Horvat Christopher M.
Published: February 2024

OBJECTIVES:

Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial.

DESIGN:

Retrospective, electronic medical record linkage, cohort study.

SETTING:

Quaternary PICU.

PATIENTS:

Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1–6 hours, and pharmacologic neuromuscular blockade (NMB).

MEASUREMENTS AND MAIN RESULTS:

ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Paco
2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10–43) ABGs per encounter at a duration of 3.6 (2.1–4.2) hours. The median (IQR) Paco
2 prediction error was 0.00 (–3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was –0.10 mm Hg (95% CI, –0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome.

CONCLUSIONS:

A computerized equation to predict minute ventilation requirements outperformed clinicians’ ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.
Age-associated dementia among older people aging with HIV in the United States: a modeling study
Authors: Hyle Emily P. , Wattananimitgul Nattanicha , Mukerji Shibani S. , Foote Julia H.A. , Reddy Krishna P. , Thielking Acadia , Yu Liyang , Viswanathan Anand , Rubin Leah H. , Shebl Fatma M. , Althoff Keri N. , Freedberg Kenneth A.
Published: February 2024

Objective:

Almost 400 000 people with HIV (PWH) in the United States are over age 55 years and at risk for age-associated dementias (AAD), including Alzheimer's disease and vascular contributions to cognitive impairment and dementia (VCID). We projected the cumulative incidence and mortality associated with AAD among PWH at least 60 years in the United States compared with the general population.

Design/methods:

Integrating the CEPAC and AgeD-Pol models, we simulated two cohorts of 60-year-old male and female individuals: PWH, and the general US population. We estimated AAD incidence and AAD-associated mortality rates. Projected outcomes included AAD cumulative incidence, life expectancy, and quality-adjusted life-years (QALYs). We performed sensitivity and scenario analyses on AAD-specific (e.g. incidence) and HIV-specific (e.g. disengagement from HIV care) parameters, as well as premature aging among PWH.

Results:

We projected that 22.1%/16.3% of 60-year-old male individuals/female individuals with HIV would develop AAD by 80 years compared with 15.9%/13.3% of male individuals/female individuals in the general population. Accounting for age-associated and dementia-associated quality of life, 60-year-old PWH would have a lower life expectancy (QALYs): 17.4 years (14.1 QALYs) and 16.8 years (13.4 QALYs) for male and female individuals, respectively, compared with the general population [male individuals, 21.7 years (18.4 QALYs); female individuals, 24.7 years (20.2 QALYs)]. AAD cumulative incidence was most sensitive to non-HIV-related mortality, engagement in HIV care, and AAD incidence rates.

Conclusion:

Projected estimates of AAD-associated morbidity, mortality, and quality of life can inform decision-makers and health systems planning as the population of PWH ages. Improved AAD prevention, treatment, and supportive care planning are critical for people aging with HIV.
Inflammatory Knee Synovitis
Authors: Feuerriegel Georg C. , Goller Sophia S. , von Deuster Constantin , Sutter Reto
Published: February 2024

Objectives

The aim of this study was to assess the diagnostic value and accuracy of a deep learning (DL)–accelerated fluid attenuated inversion recovery (FLAIR) sequence with fat saturation (FS) in patients with inflammatory synovitis of the knee.

Materials and Methods

Patients with suspected knee synovitis were retrospectively included between January and September 2023. All patients underwent a 3 T knee magnetic resonance imaging including a DL-accelerated noncontrast FLAIR FS sequence (acquisition time: 1 minute 38 seconds) and a contrast-enhanced (CE) T1-weighted FS sequence (acquisition time: 4 minutes 50 seconds), which served as reference standard. All knees were scored by 2 radiologists using the semiquantitative modified knee synovitis score, effusion synovitis score, and Hoffa inflammation score. Diagnostic confidence, image quality, and image artifacts were rated on separate Likert scales. Wilcoxon signed rank test was used to compare the semiquantitative scores. Interreader and intrareader reproducibility were calculated using Cohen κ.

Results

Fifty-five patients (mean age, 52 ± 17 years; 28 females) were included in the study. Twenty-seven patients (49%) had mild to moderate synovitis (synovitis score 6–13), and 17 patients (31%) had severe synovitis (synovitis score >14). No signs of synovitis were detected in 11 patients (20%) (synovitis score <5). Semiquantitative assessment of the whole knee synovitis score showed no significant difference between the DL-accelerated FLAIR sequence and the CE T1-weighted sequence (mean FLAIR score: 10.69 ± 8.83, T1 turbo spin-echo FS: 10.74 ± 10.32;P= 0.521). Both interreader and intrareader reproducibility were excellent (range Cohen κ [0.82–0.96]).

Conclusions

Assessment of inflammatory knee synovitis using a DL-accelerated noncontrast FLAIR FS sequence was feasible and equivalent to CE T1-weighted FS imaging.
Increased Musculoskeletal Deformities And Decreased Lung Volume In Patients After Ea/Tef Repair – A Real-Time Mri Study
Authors: Aubert Ophelia , Lacher Martin , Mayer Steffi , Frahm Jens , Voit Dirk , Rosolowski Maciej , Widenmann Anke , Hirsch Franz Wolfgang , Gräfe Daniel
Published: February 2024

Objective:

This study aims to assess morphological and functional postoperative changes after open or minimally invasive (MIS) repair of esophageal atresia (EA) compared to healthy controls by thoracic real-time MRI.

Summary Background Data:

Musculoskeletal deformities and pulmonary morbidity are common in children after EA repair. The real-time MRI is a novel technique that provides ultrafast, high-quality images during spontaneous breathing, without sedation even in young children.

Methods:

Children aged 3-18 years were prospectively examined with a 3 Tesla MRI. Musculoskeletal deformities, static thoracic cross-sectional areas (CSA) at three different levels and lung volumes, as well as dynamic right-to-left ratio of CSA of hemithoraces and lung volumes during forced breathing were evaluated.

Results:

72 children (42 open, 8 MIS, 22 controls) were recruited. In the EA group, rib fusions and adhesions (78%, P<0.01) and scoliosis (15%, P=0.32) were found after thoracotomy, but not after MIS. Mean right-to-left ratio of CSA and lung volumes were lower after EA repair compared to controls (P <0.05), indicating impaired thoracic and lung development. The number of thoracotomies was a significant risk factor for smaller thoracic volumes (P<0.05).

Conclusions:

For the first time, morphological changes and thoracic motility after EA repair were visualized by dynamic real-time MRI. Children after EA repair show decreased right-sided thoracic and lung development compared to controls. Open repair leads to significantly more musculoskeletal deformities. This study emphasizes that musculoskeletal morbidity following a thoracotomy in infancy is high.
The role of caffeine in headache disorders
Authors: Charles Andrew
Published: February 2024

Purpose of review

Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management.

Recent findings

Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy.

There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.
State-Level Analysis of Intimate Partner Violence, Abortion Access, and Peripartum Homicide: Call for Screening and Violence Interventions for Pregnant Patients
Authors: Keegan Grace , Hoofnagle Mark , Chor Julie , Hampton David , Cone Jennifer , Khan Abid , Rowell Susan , Plackett Timothy , Benjamin Andrew , Bhardwaj Neha , Rogers Selwyn O , Zakrison Tanya L , Cirone Justin M
Published: February 2024

BACKGROUND:

Despite representing 4% of the global population, the US has the fifth highest number of intentional homicides in the world. Peripartum people represent a unique and vulnerable subset of homicide victims. This study aimed to understand the risk factors for peripartum homicide.

STUDY DESIGN:

We used data from the 2018 to 2020 National Violent Death Reporting System to compare homicide rates of peripartum and nonperipartum people capable of becoming pregnant (12 to 50 years of age). Peripartum was defined as currently pregnant or within 1-year postpartum. We additionally compared state-level peripartum homicide rates between states categorized as restrictive, neutral, or protective of abortion. Pearson’s chi-square and Wilcoxon rank-sum tests were used.

RESULTS:

There were 496 peripartum compared with 8,644 nonperipartum homicide victims. The peripartum group was younger (27.4 ± 71 vs 33.0 ± 9.6, p < 0.001). Intimate partner violence causing the homicide was more common in the peripartum group (39.9% vs 26.4%, p < 0.001). Firearms were used in 63.4% of homicides among the peripartum group compared with 49.5% in the comparison (p < 0.001). A significant difference was observed in peripartum homicide between states based on policies regarding abortion access (protective 0.37, neutral 0.45, restrictive 0.64; p < 0.01); the same trend was not seen with male homicides.

CONCLUSIONS:

Compared with nonperipartum peers, peripartum people are at increased risk for homicide due to intimate partner violence, specifically due to firearm violence. Increasing rates of peripartum homicide occur in states with policies that are restrictive to abortion access. There is a dire need for universal screening and interventions for peripartum patients. Research and policies to reduce violence against pregnant people must also consider the important role that abortion access plays in protecting safety.
Microbial Primer: Bacterial growth kinetics
Authors: Fernández-Martínez Lorena T. , Javelle Arnaud , Hoskisson Paul A.
Published: February 2024

Growth of microorganisms and interpretation of growth data are core skills required by microbiologists. While science moves forward, it is of paramount importance that essential skills are not lost. The bacterial growth curve and the information that can gleaned from it is of great value to all of microbiology, whether this be a simple growth experiment, comparison of mutant strains or the establishment of conditions for a large-scale multi-omics experiment. Increasingly, the basics of plotting and interpreting growth curves and growth data are being overlooked. This primer article serves as a refresher for microbiologists on the fundamentals of microbial growth kinetics.
Novel syndromic neurodevelopmental disorder caused by de novo deletion ofCHASERR, a long noncoding RNA
Authors: Ganesh Vijay S. , Riquin Kevin , Chatron Nicolas , Lamar Kay-Marie , Aziz Miriam C. , Monin Pauline , O’Leary Melanie , Goodrich Julia K. , Garimella Kiran V. , England Eleina , Yoon Esther , Weisburd Ben , Aguet Francois , Bacino Carlos A. , Murdock David R. , Dai Hongzheng , Rosenfeld Jill A. , Emrick Lisa T. , Ketkar Shamika ,   Undiagnosed Diseases Network, Sarusi Yael , Sanlaville Damien , Kayani Saima , Broadbent Brian , Isidor Bertrand , Pengam Alisée , Cogné Benjamin , MacArthur Daniel G. , Ulitsky Igor , Carvill Gemma L. , O’Donnell-Luria Anne
Published: February 2024

Abstract/Summary

Genes encoding long non-coding RNAs (lncRNAs) comprise a large fraction of the human genome, yet haploinsufficiency of a lncRNA has not been shown to cause a Mendelian disease.CHASERRis a highly conserved human lncRNA adjacent toCHD2–a coding gene in whichde novoloss-of-function variants cause developmental and epileptic encephalopathy. Here we report three unrelated individuals each harboring an ultra-rare heterozygousde novodeletion in theCHASERRlocus. We report similarities in severe developmental delay, facial dysmorphisms, and cerebral dysmyelination in these individuals, distinguishing them from the phenotypic spectrum ofCHD2haploinsufficiency. We demonstrate reducedCHASERRmRNA expression and corresponding increasedCHD2mRNA and protein in whole blood and patient-derived cell lines–specifically increased expression of theCHD2allele inciswith theCHASERRdeletion, as predicted from a prior mouse model ofChaserrhaploinsufficiency. We show for the first time thatde novostructural variants facilitated by Alu-mediated non-allelic homologous recombination led to deletion of a non-coding element (the lncRNACHASERR) to cause a rare syndromic neurodevelopmental disorder. We also demonstrate thatCHD2has bidirectional dosage sensitivity in human disease. This work highlights the need to carefully evaluate other lncRNAs, particularly those upstream of genes associated with Mendelian disorders.
Internal Transcribed Spacers as Phylogenetic Markers Enable Species-level Metataxonomic Analysis of Ciliated Protozoa
Authors: Somasundaram Sripoorna , Yu Zhongtang
Published: February 2024

Background

The conventional morphology-based classification of ciliates is often inaccurate and time-consuming. To address this issue, sequencing, and analysis of the 18S rRNA gene of ciliates have been used as an alternative. However, this method has limitations because the highly conserved nature of this gene makes it challenging to achieve species-level resolution. This study assesses the capability of two internal transcribed spacers, ITS1 and ITS2, along with the 28S rRNA gene, to enhance the taxonomic resolution beyond that offered by the 18S rRNA gene in free-living and host-associated ciliates.

Results

We compared sequences of ITSI, ITS2, and the 18S and the 28S rRNA genes downloaded from public databases and found that ITS1 and ITS2 are more divergent at both inter- and intra-specific levels than the 18S rRNA gene. We designed universal primers specific to the two ITS regions and the 28S rRNA gene for free-living and rumen ciliates. We then systematically evaluated these primers usingin-silicoanalysis, PCR assays, and metataxonomic or metabarcoding analysis and compared them to universal 18S rRNA gene primers. We found that the new primers are specific and inclusive, with an inclusiveness rate of over 80% based onin-silicoanalysis and confirmed their specificity using PCR evaluation. We validated the new primers with metagenomic DNA from freshwater samples and from rumen samples. Our metataxonomic analysis demonstrated that the ITS regions and the 28S rRNA gene could reveal greater ciliate diversity than the 18S rRNA gene in both environments. In particular, ITS1 detected the highest number of ciliate species, including species and genera that were not detected by the 18S rRNA gene.

Conclusions

The ITS regions, particularly ITS1, offer superior taxonomic resolution, and the NCBI ITS RefSeq database allows more species to be classified. Therefore, ITS1, and to a lesser extent ITS2, is recommended for enhancing metataxonomic analysis of ciliate communities in both freshwater and rumen environments.
Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy
Authors: Wahl Devin , Risen Sydney J. , Osburn Shelby C. , Emge Tobias , Sharma Sadhana , Gilberto Vincenzo S. , Chatterjee Anushree , Nagpal Prashant , Moreno Julie A. , LaRocca Thomas J.
Published: February 2024

Neuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer’s disease, which is characterized by the aggregation of pathological tau. One major driver of both age- and tau-associated neuroinflammation is the NF-κB and NLRP3 signaling axis. However, current treatments targeting NF-κB or NLRP3 may have adverse/systemic effects, and most have not been clinically translatable. In this study, we tested the efficacy of a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically targeting both NF-κB and NLRP3 in the brain for reducing neuroinflammation and improving cognitive function in old (aged 19 months) wildtype mice, and in rTg4510 tau pathology mice (aged 2 months). We found that 4 weeks of NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles in the brain and improved cognitive-behavioral function in both old and rTg4510 mice. These effects of NF-κB/NLRP3-targeting Nanoligomers were also associated with reduced glial cell activation and pathology, favorable changes in transcriptome signatures of glia-associated inflammation (reduced) and neuronal health (increased), and positive systemic effects. Collectively, our results provide a basis for future translational studies targeting both NF-κB and NLRP3 in the brain, perhaps using Nanoligomers, to inhibit neuroinflammation and improve cognitive function with aging and neurodegeneration.
A coarse-grained model for disordered and multi-domain proteins
Authors: Cao Fan , von Bülow Sören , Tesei Giulio , Lindorff-Larsen Kresten
Published: February 2024

Many proteins contain more than one folded domain, and such modular multi-domain proteins help expand the functional repertoire of proteins. Because of their larger size and often substantial dynamics, it may be difficult to characterize the conformational ensembles of multi-domain proteins by simulations. Here, we present a coarse-grained model for multi-domain proteins that is both fast and provides an accurate description of the global conformational properties in solution. We show that the accuracy of a one-bead-per-residue coarse-grained model depends on how the interaction sites in the folded domains are represented. Specifically, we find excessive domain-domain interactions if the interaction sites are located at the position of the Cαatoms. We also show that if the interaction sites are located at the centre of mass of the residue, we obtain good agreement between simulations and experiments across a wide range of proteins. We then optimize our previously described CALVADOS model using this centre-of-mass representation, and validate the resulting model using independent data. Finally, we use our revised model to simulate phase separation of both disordered and multi-domain proteins, and to examine how the stability of folded domains may differ between the dilute and dense phases. Our results provide a starting point for understanding interactions between folded and disordered regions in proteins, and how these regions affect the propensity of proteins to self-associate and undergo phase separation.
Alterations of Pleiotropic Neuropeptide-Receptor gene couples in Cetacea
Authors: Valente Raul , Cordeiro Miguel , Pinto Bernardo , Machado André , Alves Filipe , Sousa-Pinto Isabel , Ruivo Raquel , Castro L. Filipe C.
Published: February 2024

Background

Habitat transitions have considerable consequences in organism homeostasis, as they require the adjustment of several concurrent physiological compartments to maintain stability and adapt to a changing environment. Within the range of molecules with a crucial role in the regulation of different physiological processes, neuropeptides are key agents. Here, we examined the coding status of several neuropeptides and their receptors with pleiotropic activity in Cetacea.

Results

Analysis of 202 mammalian genomes, including 41 species of Cetacea, exposed an intricate mutational landscape compatible with gene sequence modification and loss. Specifically for Cetacea, in the twelve genes analysed we have determined patterns of loss ranging from species-specific disruptive mutations (e.g., Neuropeptide FF-Amide Peptide Precursor;NPFF) to complete erosion of the gene across the cetacean stem lineage (e.g., Somatostatin Receptor 4;SSTR4).

Conclusions

Impairment of some of these neuromodulators, may have contributed to the unique energetic metabolism, circadian rhythmicity and diving response displayed by this group of iconic mammals.
Multiple plastid losses within photosynthetic stramenopiles revealed by comprehensive phylogenomics
Authors: Terpis Kristina X. , Salomaki Eric D. , Barcytė Dovilė , Pánek Tomáš , Verbruggen Heroen , Kolisko Martin , Bailey J. Craig , Eliáš Marek , Lane Christopher E
Published: February 2024

Ochrophyta is a vast and morphologically diverse group of algae with complex plastids, including familiar taxa with fundamental ecological importance (diatoms or kelp), and a wealth of lesser-known and obscure organisms. The sheer diversity of ochrophytes poses a challenge for reconstructing their phylogeny, with major gaps in sampling and an unsettled placement of particular taxa yet to be tackled. We sequenced transcriptomes from 25 strategically selected representatives and used these data to build the most taxonomically comprehensive ochrophyte-centered phylogenomic supermatrix to date. We employed a combination of approaches to reconstruct and critically evaluate the relationships among ochrophytes. While generally congruent with previous analyses, the updated ochrophyte phylogenomic tree resolved the position of several taxa with previously uncertain placement, and supported a redefinition of the class Synchromophyceae. Our results indicated that the heterotrophic plastid-lacking heliozoanActinophrys solis not a sister lineage of ochrophytes, as proposed recently, but rather phylogenetically nested among them. In addition, we foundPicophagus flagellatusto be a secondarily heterotrophic ochrophyte lacking all hallmark plastid genes, yet exhibiting mitochondrial proteins that seem to be genetic footprints of lost plastid organelle. We thus document, for the first time, plastid loss in two separate ochrophyte lineages. Altogether, our study provides a new framework for reconstructing trait evolution in ochrophytes and demonstrates that plastid loss is more common than previously thought.

Issue Section:Discoveries
Broad de-regulated U2AF1 splicing is prognostic and augments leukemic transformation via protein arginine methyltransferase activation
Authors: Venkatasubramanian Meenakshi , Schwartz Leya , Ramachandra Nandini , Bennett Joshua , Subramanian Krithika R. , Chen Xiaoting , Gordon-Mitchell Shanisha , Fromowitz Ariel , Pradhan Kith , Shechter David , Sahu Srabani , Heiser Diane , Scherle Peggy , Chetal Kashish , Kulkarni Aishwarya , Myers Kasiani C. , Weirauch Matthew T. , Grimes H. Leighton , Starczynowski Daniel T. , Verma Amit , Salomonis Nathan
Published: February 2024

The role of splicing dysregulation in cancer is underscored by splicing factor mutations; however, its impact in the absence of such rare mutations is poorly understood. To reveal complex patient subtypes and putative regulators of pathogenic splicing in Acute Myeloid Leukemia (AML), we developed a new approach called OncoSplice. Among diverse new subtypes, OncoSplice identified a biphasic poor prognosis signature that partially phenocopiesU2AF1-mutant splicing, impacting thousands of genes in over 40% of adult and pediatric AML cases.U2AF1-like splicing co-opted a healthy circadian splicing program, was stable over time and induced a leukemia stem cell (LSC) program. Pharmacological inhibition of the implicatedU2AF1-like splicing regulator, PRMT5, rescued leukemia mis-splicing and inhibited leukemic cell growth. Genetic deletion of IRAK4, a common target ofU2AF1-like and PRMT5 treated cells, blocked leukemia development in xenograft models and induced differentiation. These analyses reveal a new prognostic alternative-splicing mechanism in malignancy, independent of splicing-factor mutations.

Statement of significance

Using a new in silico strategy we reveal counteracting determinants of patient survival in Acute Myeloid Leukemia that co-opt well-defined mutation-dependent splicing programs. Broad poor-prognosis splicing and leukemia stem cell survival could be rescued through pharmacological inhibition (PRMT5) or target deletion (IRAK4), opening the door for new precision therapies.

Competing Interests

Conflict-of-interest disclosure: DTS. serves on the scientific advisory board at Kurome Therapeutics; is a consultant for and/or received funding from Kurome Therapeutics, Captor Therapeutics, Treeline Biosciences, and Tolero Therapeutics; and has equity in Kurome Therapeutics. AV has received research funding from GlaxoSmithKline, BMS, Jannsen, Incyte, MedPacto, Celgene, Novartis, Curis, Prelude and Eli Lilly and Company, has received compensation as a scientific advisor to Novartis, Stelexis Therapeutics, Acceleron Pharma, and Celgene, and has equity ownership in Throws Exception and Stelexis Therapeutics.
Serine mistranslation induces the integrated stress response without accumulation of uncharged tRNAs
Authors: Zhang Hong , Ling Jiqiang
Published: February 2024

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that support robust and accurate protein synthesis. A rapidly expanding number of studies show that mutations in aaRSs lead to multiple human diseases, including neurological disorders and cancer. Much remains unknown about how aaRS mutations impact human health. In particular, how aminoacylation errors affect stress responses and fitness in eukaryotic cells remains poorly understood. The integrated stress response (ISR) is an adaptive mechanism in response to multiple stresses. However, chronic activation of the ISR contributes to the development of multiple diseases (e.g., neuropathies). Here we show that Ser misincorporation into Ala and Thr codons, resulting from aaRS editing defects or mutations in tRNAs, constitutively active the ISR. Such activation does not appear to depend on the accumulation of uncharged tRNAs, implicating that Ser mistranslation may lead to ribosome stalling and collision.