bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Legalizing Recreational Cannabis on the Children of a Neighboring State
Authors: Chen Benny , Fullerton Lynne , Smolinske Susan , Seifert Steven , Tuuri Rachel 
Published: August 2024

Objectives
In the United States, cannabis is legal for adult recreational use in 24 states and Washington, DC. Unintentional pediatric cannabis exposures have increased in many states following legalization.
We evaluated the relationship between recreational cannabis legalization and the rates of unintentional pediatric exposures in a neighboring state that had not undergone legalization.

Methods
We obtained cannabis exposure cases for children 0–12 years from the New Mexico Poison and Drug Information Center electronic database. Only deidentified patient data from closed-case exposure encounters were abstracted. Data were grouped as precommercial and postcommercial availability in neighboring Colorado, demarcated by January 2014. We coded cannabis products as edible, not edible, or unknown. For bivariable comparisons, we used odds ratios, risk ratio, χ2 test, and Wilcoxon rank sum test. We chose a type 1 error rate of 0.05 to determine significance.

Results
There were 269 exposures over 24 years of calls. Following neighboring legalization, the median number of exposures per year increased from 4 (interquartile range 2, 5) to 24.5 (16.5, 34), the median age increased from 1.9 to 3.0 (P = 0.007), and the relative risk of the exposure involving edible products was double (relative risk = 2.0, 95% confidence interval = 1.6, 2.6). The severity of the exposures' medical effects also increased (P = 0.008).

Conclusions
The number, severity, and type of pediatric cannabis exposures in New Mexico changed after neighboring recreational cannabis legalization. States neighboring those undergoing cannabis legalization should be prepared to respond to increased acute exposures in children.
The effect of vibration-hinged ankle foot orthoses on gait and spasticity in children with cerebral palsy: A randomized clinical trial design
Authors: Jiryaei Zahra , Amini Malek , Sanjari Mohammad Ali , Hajiaghaei Behnam , Babazadeh Roozbeh , Jalali Maryam 
Published: August 2024

Background:
Hinged ankle foot orthoses (HAFO) are commonly prescribed for children with cerebral palsy (CP) to improve their ambulatory function.

Objectives:
The aim of this study was to compare the effect of vibration-HAFO with that of the same orthosis without vibration on gait, function, and spasticity in hemiplegic CP children.

Study Design:
Randomized Control Trial Design (a pilot study).

Methods:
Twenty-three children with hemiplegic CP participated in this study. The control group (n = 12) used HAFO, and the intervention group (n = 11) used vibration-HAFO for four weeks. Pre-post three-dimensional gait analysis was done. Calf muscle spasticity and function were also measured.

Results:
Results showed significant differences between the two groups in the one-minute walking test (p = 0.023) and spasticity (after intervention [p = 0.022], after follow-up [p = 0.020]). Also, significant differences were detected between the two groups in the step width (p = 0.042), maximum hip abduction (p = 0.008), stance maximum dorsiflexion (p = 0.036) and mean pelvic tilt (p = 0.004) in the barefoot condition. Gait cycle time (p = 0.005), maximum hip abduction (p = 0.042), and cadence (p = 0.001) were different between groups in the braced condition. We couldn't find any significant within and between groups differences in knee kinematic parameters. The mean time of using vibration was 16.83 minutes per day.

Conclusions:
The vibration-hinged AFO is feasible, safe, and acceptable for children with hemiplegic CP to be integrated into practice. Temporospatial and clinical parameters, especially spasticity, were improved. There were slight trends toward improvement in pelvic and knee kinematics. Vibration-HAFO is of benefit to ambulatory CP children with mild and moderate spasticity. It improved the walking capacity of the children.
Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer
Authors: Overtoom Hidde C.G. , Eyck Ben M. , van der Wilk Berend J. , Noordman Bo J. , van der Sluis Pieter C. , Wijnhoven Bas P.L. , van Lanschot J. Jan B. , Lagarde Sjoerd M. ,   on behalf of the SANO study group*
Published: August 2024

Objective:
To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer.

Summary Background Data:
Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity.

Methods:
Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT.

Results:
Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups.

Conclusion:
Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.
Successful Implementation of a Multidisciplinary Weight Loss Program Including GLP1 Receptor Agonists for Liver Transplant Candidates With High Body Mass Index
Authors: Gonzalez Humberto C. , Myers Daniel T. , Venkat Deepak 
Published: August 2024

Background.
Body mass index (BMI) >40 is considered a relative contraindication to liver transplant. However, there is little research regarding best practices for weight loss in this population. We hypothesized that providing multidisciplinary support, including the use of glucagon-like protein 1 receptor agonists would facilitate patients’ achievement of weight loss necessary for transplant eligibility.

Methods.
Patients 18 y or older were referred to the Henry Ford Health Liver Metabolic Clinic from August 2019 to September 2023, with either BMI >40 or >35 with abdominal adiposity that would complicate surgery. Patients were provided individualized support from hepatologists, dieticians, and counselors, as well as prescribed antiobesity medication and monitored closely for weight loss progress.

Results.
Among 19 patients referred to the Liver Metabolic Clinic, median baseline BMI was 42 (range, 34.6–48.8) with median goal weight loss of 14.1 kg (range, 4.1–31.4). Sixteen patients (84%) had metabolic dysfunction-associated steatohepatitis and 3 patients had alcohol-associated liver disease. Seven had comorbid hepatocellular carcinoma. Median Model for End-stage Liver Disease score was 14 (range, 7–22). Fifteen patients were treated with a glucagon-like peptide 1 receptor agonist (6 patients received liraglutide, 8 received semaglutide, and 1 received tirzepatide) and 4 received phentermine. Median weight loss was 11.7 kg for all 19 patients (range, 0–33). Eight patients received a transplant and 4 more patients were waitlisted. Time from baseline to waitlisting was ~5.5 mo (median 166 d; range, 68–840). Three patients remained on treatment, whereas 4 were deceased due to progressive liver disease or infection.

Conclusions.
Providing high BMI patients with individualized dietary and medical support can facilitate weight loss necessary to achieve liver transplant eligibility.
Exploring Methylphenidate-Induced Intraocular Pressure: A Cautionary Tale in Pediatric ADHD Management
Authors: Yıldırım Selman , Özel Mahya , Günay Murat , Hoşoğlu Esra , Turan Bahadir 
Published: August 2024

Objectives
This case report explores the intricate relationship between methylphenidate (MTX) use and increased intraocular pressure (IOP) in a pediatric patient with a preexisting history of eye disease. Despite existing literature presenting cases of IOP elevation linked to MTX, a significant gap remains in understanding nuanced risk factors.

Methods
This case study used patients' medical records and a comprehensive literature review.

Results
A 6-year-old girl with attention deficit hyperactivity disorder and a family history of eye conditions exhibited elevated IOP after 12 days of MTX use, prompting discontinuation. The patient successfully transitioned to atomoxetine with normalized IOP and improved attention duration.

Conclusions
Existing cases emphasize the potential link between sympathetic nerve activity and IOP elevation induced by central nervous system stimulants like MTX. Notably, the patient's high hyperopia contributed to the impact of MTX on IOP, suggesting the need for cautious use in susceptible individuals. This case underscores the importance of individualized treatment strategies, particularly in attention deficit hyperactivity disorder patients with family history and additional eye findings, emphasizing safety and comprehensive patient care.
Population coding of predator imminence in the hypothalamus
Authors: Cheung Kathy Y.M. , Nair Aditya , Li Ling-yun , Shapiro Mikhail G. , Anderson David J. 
Published: August 2024

AbstractHypothalamic VMHdmSF1neurons are activated by predator cues and are necessary and sufficient for instinctive defensive responses. However, such data do not distinguish which features of a predator encounter are encoded by VMHdmSF1neural activity. To address this issue, we imaged VMHdmSF1neurons at single-cell resolution in freely behaving mice exposed to a natural predator in varying contexts. Our results reveal that VMHdmSF1neurons do not represent different defensive behaviors, but rather encode predator identity and multiple predator-evoked internal states, including threat-evoked fear/anxiety; neophobia or arousal; predator imminence; and safety. Notably, threat and safety are encoded bi-directionally by anti-correlated subpopulations. Finally, individual differences in predator defensiveness are correlated with differences in VMHdmSF1response dynamics. Thus, different threat-related internal state variables are encoded by distinct neuronal subpopulations within a genetically defined, anatomically restricted hypothalamic cell class.HighlightsDistinct subsets of VMHdmSF1neurons encode multiple predator-evoked internal states.Anti-correlated subsets encode safety vs. threat in a bi-directional mannerA population code for predator imminence is identified using a novel assayVMHdmSF1dynamics correlate with individual variation in predator defensiveness.
Using quantitative bias analysis to adjust for misclassification of COVID-19 outcomes: An applied example of inhaled corticosteroids and COVID-19 outcomes
Authors: Bokern Marleen , Rentsch Christopher T. , Quint Jennifer K. , Hunnicutt Jacob , Douglas Ian , Schultze Anna 
Published: August 2024

1AbstractDuring the pandemic, there was concern that underascertainment of COVID-19 outcomes may impact treatment effect estimation in pharmacoepidemiologic studies. We assessed the impact of outcome misclassification on the association between inhaled corticosteroids (ICS) and COVID-19 hospitalisation and death in the UK during the first pandemic wave using probabilistic bias analysis (PBA).Using data from Clinical Practice Research Datalink Aurum, we defined a cohort with chronic obstructive pulmonary disease (COPD) on 01 Mar 2020. We compared the risk of COVID-19 hospitalisation and death among users of ICS/long-acting β-agonist (LABA) and users of LABA/LAMA using inverse-probability of treatment weighted (IPTW) logistic regression. We used PBA to assess the impact of non-differential outcome misclassification. We assigned beta distributions to sensitivity and specificity and sampled from these 100,000 times for summary-level and 10,000 times for record-level PBA. Using these values, we simulated outcomes and applied IPTW logistic regression to adjust for confounding and misclassification. Sensitivity analyses excluded ICS+LABA+LAMA (triple therapy) users.Among 161,411 patients with COPD, ICS users had increased odds of COVID-19 hospitalisations and death compared with LABA/LAMA users (OR for COVID-19 hospitalisation 1.59 (95% CI 1.31 – 1.92), OR for COVID-19 death 1.63, 95% CI 1.26 – 2.11). After IPTW and exclusion of people using triple therapy, ORs moved towards null. All implementations of QBA, both record and summary-level PBA, modestly shifted ORs away from the null and increased uncertainty.The results provide reassurance that outcome misclassification was unlikely to change the conclusions of the study but confounding by indication remains a concern.
Automated Craniofacial Biometry with 3D T2w Fetal MRI
Authors: Matthew Jacqueline , Uus Alena , Collado Alexia Egloff , Luis Aysha , Arulkumaran Sophie , Fukami-Gartner Abi , Kyriakopoulou Vanessa , Cromb Daniel , Wright Robert , Colford Kathleen , Deprez Maria , Hutter Jana , O’Muircheartaigh Jonathan , Malamateniou Christina , Razavi Reza , Story Lisa , Hajnal Jo , Rutherford Mary A. 
Published: August 2024

ABSTRACTObjectivesEvaluating craniofacial phenotype-genotype correlations prenatally is increasingly important; however, it is subjective and challenging with 3D ultrasound. We developed an automated landmark propagation pipeline using 3D motion-corrected, slice-to-volume reconstructed (SVR) fetal MRI for craniofacial measurements.MethodsA literature review and expert consensus identified 31 craniofacial biometrics for fetal MRI. An MRI atlas with defined anatomical landmarks served as a template for subject registration, auto-labelling, and biometric calculation. We assessed 108 healthy controls and 24 fetuses with Down syndrome (T21) in the third trimester (29-36 weeks gestational age, GA) to identify meaningful biometrics in T21. Reliability and reproducibility were evaluated in 10 random datasets by four observers.ResultsAutomated labels were produced for all 132 subjects with a 0.03% placement error rate. Seven measurements, including anterior base of skull length and maxillary length, showed significant differences with large effect sizes between T21 and control groups (ANOVA, p<0.001). Manual measurements took 25-35 minutes per case, while automated extraction took approximately 5 minutes. Bland-Altman plots showed agreement within manual observer ranges except for mandibular width, which had higher variability. Extended GA growth charts (19-39 weeks), based on 280 control fetuses, were produced for future research.ConclusionThis is the first automated atlas-based protocol using 3D SVR MRI for fetal craniofacial biometrics, accurately revealing morphological craniofacial differences in a T21 cohort. Future work should focus on improving measurement reliability, larger clinical cohorts, and technical advancements, to enhance prenatal care and phenotypic characterisation.
Three Year Outcomes after Programmatic Transitioning to Dolutegravir in the Context of Severe Civil Unrest in Haiti
Authors: Liautaud Bernard , Chico Ana Sanchez , Macius Youry , Joseph Patrice , Reeder Harrison , Bolas Theo , Marcelin Adias , Moïse Colette Guiteau , Apollon Alexandra , Dai Angela , Cremieux Pierre , Pape Jean W. , Koenig Serena P. 
Published: August 2024

ABSTRACTBackgroundDolutegravir (DTG) has been widely scaled-up worldwide. Data on long-term outcomes are limited.MethodsWe included all persons living with HIV (PLWH) ≥15 years of age who initiated or switched to DTG in Port-au-Prince, Haiti. We described treatment outcomes by pre-switch viral load and assessed predictors of virologic failure using multivariable logistic regression.FindingsA total of 10,354 PLWH initiated or switched to DTG from November 5, 2018 to March 21, 2021, and were included in the analyses. Of these, 2217 (21.4%) were ART-naïve and 8137 (78.6%) switched from an NNTRI-based regimen. Median follow-up time on DTG was 2.8 years (IQR: 2.3, 3.1). Among PLWH with ≥2 tests on DTG, 83.5% of ART-naïve, 93.1% with pre-switch suppression, 64.8% with pre-switch failure, and 90.2% without pre-switch viral load had <1000 copies/mL at latest test. Among treatment-experienced patients, predictors of HIV-1 RNA ≥1000 copies/mL at latest test included younger age (adjusted odds ratio [aOR]: 2.33 for ≤30 vs. ≥50 years), shorter pre-switch time on ART (aOR: 0.91; 95% CI: 0.89, 0.94/year), lower education (aOR: 1.31; 95% CI: 1.10, 1.55), and higher pre-switch viral load: (aOR: 7.00; 95% CI; 5.74, 8.54 for ≥10,000 vs. <1000 copies/mL).InterpretationVirologic outcomes on DTG-based regimens are outstanding for PLWH with pre-switch suppression, even in the context of severe civil unrest in Haiti. However, rates of persistent viremia are high among PLWH who experienced pre-switch failure; additional interventions are critically needed, including access to genotypic resistance testing and provision of alternative regimens as clinically-indicated.FundingNone
Cognitive dysfunction following brain trauma results from sex-specific reactivation of the developmental pruning processes
Authors: Arizanovska Dena , Dallera Carlos A. , Folorunso Oluwarotimi O. , Bush Gerald F. , Frye Jennifer B. , Doyle Kristian P. , Jagid Jonathan R. , Wolosker Herman , Monaco Bernardo A. , Cordeiro Joacir Graciolli , Atkins Coleen M. , Griswold Anthony J. , Liebl Daniel J. 
Published: August 2024

SUMMARYCognitive losses resulting from severe brain trauma have long been associated with the focal region of tissue damage, leading to devastating functional impairment. For decades, researchers have focused on the sequelae of cellular alterations that exist within the perilesional tissues; however, few clinical trials have been successful. Here, we employed a mouse brain injury model that resulted in expansive synaptic damage to regions outside the focal injury. Our findings demonstrate that synaptic damage results from the prolonged increase in D-serine release from activated microglia and astrocytes, which leads to hyperactivation of perisynaptic NMDARs, tagging of damaged synapses by complement components, and the reactivation of developmental pruning processes. We show that this mechanistic pathway is reversible at several stages within a prolonged and progressive period of synaptic loss. Importantly, these key factors are present in acutely injured brain tissue acquired from patients with brain injury, which supports a therapeutic neuroprotective strategy.
Axonal mitochondria regulate gentle touch response through control of axonal actin dynamics
Authors: Hegde Sneha , Modi Souvik , Deihl Ennis W. , Glomb Oliver Vinzenz , Yogev Shaul , Hoerndli Frederic J. , Koushika Sandhya P. 
Published: August 2024

AbstractActin in neuronal processes is both stable and dynamic. The origin & functional roles of the different pools of actin is not well understood. We find that mutants that lack mitochondria,ric-7andmtx-2; miro-1, in neuronal processes also lack dynamic actin. Mitochondria can regulate actin dynamics upto a distance ∼80 μm along the neuronal process. Absence of axonal mitochondria and dynamic actin does not markedly alter the Spectrin Membrane Periodic Skeleton (MPS) in touch receptor neurons (TRNs). Restoring mitochondria inTRNs cell autonomously restores dynamic actin in asod-2dependent manner. We find that dynamic actin is necessary and sufficient for the localization of gap junction proteins in the TRNs and for theC. elegansgentle touch response. We identify anin vivomechanism by which axonal mitochondria locally facilitate actin dynamics through reactive oxygen species that we show is necessary for electrical synapses & behaviour.
Galvanotactic directionality of cell groups depends on group size
Authors: Copos Calina , Sun Yao-Hui , Zhu Kan , Zhang Yan , Reid Brian , Draper Bruce , Lin Francis , Yue Haicen , Bernadskaya Yelena , Zhao Min , Mogilner Alex 
Published: August 2024

ABSTRACTMotile cells migrate directionally in the electric field in a process known as galvanotaxis, important and under-investigated phenomenon in wound healing and development. We previously reported that individual fish keratocyte cells migrate to the cathode in electric fields, that inhibition of PI3 kinase reverses single cells to the anode, and that large cohesive groups of either unperturbed or PI3K-inhibited cells migrate to the cathode. Here we find that small uninhibited cell groups move to the cathode, while small groups of PI3K-inhibited cells move to the anode. Small groups move faster than large groups, and groups of unperturbed cells move faster than PI3K-inhibited cell groups of comparable sizes. Shapes and sizes of large groups change little when they start migrating, while size and shapes of small groups change significantly, lamellipodia disappear from the rear edges of these groups, and their shapes start to resemble giant single cells. Our results are consistent with the computational model, according to which cells inside and at the edge of the groups pool their propulsive forces to move but interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, the edge cells behave like individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, while larger PI3K-inhibited groups are directed by cell majority in the group interior to the cathode, while majority of the edge cells in small groups win the tug-of-war driving these groups to the anode.Significance statementMotile cells migrate directionally in electric fields. This behavior – galvanotaxis – is important in many physiological phenomena. Individual fish keratocytes migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Uninhibited cell groups move to the cathode. Surprisingly, groups of PI3K-inhibited cells exhibit bidirectional behavior: larger/smaller groups move to the cathode/anode, respectively. A mechanical model suggests that inner and outer cells interpret directional signals differently, and that a tug-of-war between the outer and inner cells directs the cell groups. These results shed light on general principles of collective cell migration.