bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vertebral destruction in tuberculous spondylitis correlates with Toll-like Receptor 4 (TLR-4) levels: a cross-sectional study
Authors: Arifin Jainal , Sakti Muhammad , Massi Nasrum , Bukhari Agussalim , Hamid Firdaus , Winangun Putu A.N. 
Published: January 2024

Background:
Tuberculous (TB) spondylitis is a hazardous infectious disease causing significant spinal deformity. Increased toll-like receptor-4 (TLR-4) activity promotes more extensive infections in patients with TB spondylitis, so it has the potential to be used as a biomarker to predict the severity. This study aims to determine the relationship between TLR-4 levels and the degree of vertebral destruction in TB spondylitis patients.

Materials and methods:
A cross-sectional study was conducted from May to October 2023. A total of 27 TB spondylitis samples were then measured for TLR-4 serum levels. Vertebral destruction is assessed based on the Spine At Risk Signs (SARS) criteria on X-ray and MRI examinations. Moreover, the degree of sensory and motor impairment was also assessed in this study. The Spearman correlation test assessed the correlation between TLR-4 levels and vertebral destruction.

Results:
Most of the samples in this study were less than 30 years old (10 people, 37%), female (14 people, 51.9%), had spinal destruction at 1 level (11 people, 40.7%), had paraplegia (8 people, 29.6%), and had hypoesthesia (11 people, 40.7%). TLR-4 levels had a mean value of 8254.1±1076.1 ng/ml. TLR-4 levels were positively correlated with the degree of vertebral destruction (r=0.599, P=0.001), motor disorders (r=0.632.x, P=0.000), and sensory disorders (r=0.574, P=0.002).

Conclusion:
TLR-4 levels are associated with the severity of vertebral destruction in TB spondylitis, so it has the potential to be used as a prognostic biomarker.
Need to Take Heart? Talk to Your Psychiatrist for 20 Minutes
Authors: Dinca Eduard B. , Balseanu Adrian T. 
Published: January 2024

Abstract
A powerful correlation exists between the equilibrium of the sympathetic and parasympathetic nervous systems and heart rate variability (HRV). Thus, HRV is useful as a physiological index of both physical and emotional health; autonomic nervous system dysregulation, with a sympathetic predominance and a low HRV, has been associated with a variety of physical (cardiovascular, neurological) and psychiatric disorders. We used a validated algorithm of measuring the HRV (noninvasive, 2-minute approach) in new psychiatric outpatients in first author's private practice. The subjects had an initial measurement, followed by a 20-minute consultation with minimal supportive psychotherapy, followed by an exit measurement. The initial study spanned the “COVID months”; to control for this variable, an identical study was performed in 2023. There was a highly significant decrease in the sympathetic predominance in the test groups; no such trend was found in the control groups. A short psychiatry consultation may be sufficient to decrease patients' sympathetic hyperactivity and improve their well-being.
A pediatric teletrauma program pilot project: Improves access to pediatric trauma care and timely assessment of pediatric traumas
Authors: Eldredge R. Scott , Moore Zachary , Smith Julia , Barnes Kasey , Norton Sidney P. , Larsen Kezlyn , Padilla Benjamin E. , Swendiman Robert A. , Fenton Stephen J. , Russell Katie W. 
Published: January 2024

BACKGROUND
Geographic location is a barrier to providing specialized care to pediatric traumas. In 2019, we instituted a pediatric teletrauma program in collaboration with the Statewide Pediatric Trauma Network at our level 1 pediatric trauma center (PTC). Triage guidelines were provided to partnering hospitals (PHs) to aid in evaluation of pediatric traumas. Our pediatric trauma team was available for phone/video trauma consultation to provide recommendations on disposition and management. We hypothesized that this program would improve access and timely assessment of pediatric traumas while limiting patient transfers to our PTC.

METHODS
A retrospective cohort study was conducted at the PTC between January 2019 and May 2023. All pediatric trauma patients younger than 18 years who had teletrauma consults were included. We also evaluated all avoidable transfers without teletrauma consults defined as admission for less than 36 hours without an intervention or imaging as a comparison group.

RESULTS
A total of 151 teletrauma consults were identified: 62% male and median age of 8 years (interquartile range [IQR], 4–12 years). Teletrauma consults increased from 12 in 2019 to 100 in 2022 to 2023, and the number of PHs increased from 2 to 32. Partnering hospitals were 15 to 554 miles from the PTC, with a median distance of 34 miles (IQR, 28–119 miles). Following consultation, we recommended discharge (34%), admission (29%), or transfer to PTC (35%). Of those who were not transferred, 3% (3 of 97) required subsequent treatment at the PTC. Nontransferred teletrauma consults had a higher percentage of TBI (61% vs. 31%, p < 0.001) and were from farther distances (40 miles [IQR, 28–150 miles] vs. 30 miles [IQR, 28–50 miles], p < 0.001) compared with avoidable transferred patients without a teletrauma consult.

CONCLUSION
Teletrauma consult is a safe and viable addition to a pediatric trauma program faced with providing care to a large geographical catchment area. The pediatric teletrauma program provided management recommendations to 32 PHs and avoided transfer in approximately 63% of cases.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Update on Outcomes of a Novel Pathway for Thoracic Surgery Training
Authors: Potts John R , Klingensmith Mary E , Merrill Walter H 
Published: January 2024

BACKGROUND:
The Joint Surgery-Thoracic Surgery (JS-TS) pathway began as a pilot program to grant both general surgery (GS) residency and thoracic surgery (TS) fellowship credit for 12 months of the PGY-4 and 5 years. This review updates the outcomes of this novel program.

STUDY DESIGN:
GS and TS programs in all approved JS-TS institutions were contacted for data collection, including JS-TS enrollee demographics and GS and TS case logs (CLs). National GS and TS CL data, and program and institutional data were publicly available. Enrollee case numbers were compared with those of their contemporaries. The American Board of Surgery and American Board of Thoracic Surgery provided certification data. Only enrollees who completed GS through 2019 were included.

RESULTS:
There were 90 JS-TS enrollees in 14 institutions. Two enrollees withdrew and 1 had not completed TS at the time of data collection leaving 87 for analysis. GS CLs were available for all 87 enrollees. TS CLs were available for all 62 enrollees who completed fellowship in 2016 or later. In GS, enrollees recorded fewer cases than their contemporary PGY-5s nationally in all domains except thoracic and endocrine. In TS, mean enrollee case numbers exceeded those of national contemporaries in every major category. Sixty-two JS-TS enrollees have achieved American Board of Surgery certification. Eighty-two enrollees are American Board of Thoracic Surgery certified with 5 currently in the certification process.

CONCLUSIONS:
The JS-TS pathway has proven a successful alternative route for TS training and could be a blueprint for other specialties considering novel avenues to specialty training.
Impact of Prehospital Exsanguinating Airway-Breathing-Circulation Resuscitation Sequence on Patients with Severe Hemorrhage
Authors: Ritondale Joseph , Piehl Mark , Caputo Sydney , Broome Jacob , McLafferty Bryant , Anderson Augustus , Belding Cameron , Tatum Danielle , Duchesne Juan ,   for the Damage Control Resuscitation Study Group
Published: January 2024

BACKGROUND:
At the 2023 ATLS symposium, the priority of circulation was emphasized through the “x-airway-breathing-circulation (ABC)” sequence, where “x” stands for exsanguinating hemorrhage control. With growing evidence from military and civilian studies supporting an x-ABC approach to trauma care, a prehospital advanced resuscitative care (ARC) bundle emphasizing early transfusion was developed in our emergency medical services (EMS) system. We hypothesized that prioritization of prehospital x-ABC through ARC would reduce in-hospital mortality.

STUDY DESIGN:
This was a single-year prospective analysis of patients with severe hemorrhage. These patients were combined with our institution’s historic controls before prehospital blood implementation. Included were patients with systolic blood pressure (SBP) less than 90 mmHg. Excluded were patients with penetrating head trauma or prehospital cardiac arrest. Two-to-one propensity matching for x-ABC to ABC groups was conducted, and the primary outcome, in-hospital mortality, was compared between groups.

RESULTS:
A total of 93 patients (x-ABC = 62, ABC = 31) met the inclusion criteria. There was no difference in patient age, sex, initial SBP, initial Glasgow Coma Score, and initial shock index between groups. When compared with the ABC group, x-ABC patients had significant improvement in vitals at emergency department admission. Overall mortality was lower in the x-ABC group (13% vs 47%, p < 0.001). Multivariable regression revealed that prehospital circulation-first prioritization was independently associated with decreased in-hospital mortality (odds ratio 0.15, 95% CI 0.04 to 0.54, p = 0.004).

CONCLUSIONS:
This is the first analysis to demonstrate a prehospital survival benefit of x-ABC in this subset of patient with severe injury and hemorrhagic shock. Standardization of prehospital x-ABC management in this patient population warrants special consideration.
How areAPOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis
Authors: Holmes Rachel , Duan Hongzhe , Bagley Olivia , Wu Deqing , Loika Yury , Kulminski Alexander , Yashin Anatoliy , Arbeev Konstantin , Ukraintseva Svetlana 
Published: January 2024

AbstractThe ε4 allele of theAPOEgene (APOE4)is known for its negative association with human longevity, however, the mechanism is unclear.APOE4was also linked to changes in body weight, and the latter changes were associated with survival in some studies. Here we explore the role of aging changes in weight in the connection betweenAPOE4and longevity, using a Causal Mediation Analysis (CMA) approach to uncovering mechanisms of genetic associations. Using the Health and Retirement Study (HRS) data, we tested a hypothesis, whether the association ofAPOE4with reduced survival to age 85+ is mediated by key characteristics of age-trajectories of weight, such as age at reaching peak values, and slope of the decline in weight afterwards. Mediation effects were evaluated by the Total Effect (TE), Natural Indirect Effect, and Proportion Mediated. Controlled Direct Effect and Natural Direct Effect are also reported. The CMA results suggest thatAPOE4carriers have 19%-22% (TE p=0.019-0.038) lower chances of surviving to age 85 and beyond in part because they reach peak values of weight at younger ages, and their weight declines faster afterwards, compared to non-carriers. This finding is in line with the idea that detrimental effect ofAPOE4on longevity is in part related to accelerated physical aging of ε4 carriers.
Phase angle clusters in bioimpedance: An alternative to body mass index
Authors: Jesús Fuentes Sebio Ma 
Published: January 2024

AbstractBackgroundThe “Body Mass Index” (BMI) or “Quetelet Index” is the most widely used tool to diagnose the degree of obesity. Anyone can calculate it, with no other tools than a scale and a measuring rod. However, its accuracy in predicting body fat percentage is low. The aim of this study is to find an alternative to BMI that is more reliable, accessible and easily applicable in daily clinical practice.MethodsUsing the K-means method (an unsupervised classification algorithm), we performed aclusteranalysis of the two phase angles obtained with bioimpedance analysis (BIA) of 641 women with different health status. BMI, age, diseases, treatments and any other data other than the phase angle values of the participants were not taken into account.ResultsTheclustersgenerated by the K-means algorithm do not coincide with the BMI categories, nor with the predetermined division of individuals into healthy and pathological.The K-means clustering algorithm identified new patterns that provide information on the greater or lesser predisposition of different individuals to suffer from diseases, taking as a reference their pathological peers in the samecluster.ConclusionsThe categories generated by the K-means algorithm based on the phase angles obtained by BIA classify individuals according to their health status independently of other variables such as age or BMI.
Immune checkpoint inhibitor response in sarcomas associates with immune infiltrates and increased expression of transposable elements and viral response pathways
Authors: Nacev Benjamin A. , Bradic Martina , Woo Hyung Jun , Richards Allison L. , Kelly Ciara M. , Dickson Mark A. , Gounder Mrinal M. , Keohan Mary L. , Chi Ping , Movva Sujana , Maki Robert , Slotkin Emily K. , Rosenbaum Evan , Avutu Viswatej , Chan Jason E. , Banks Lauren , Adamson Travis , Singer Samuel , Antonescu Cristina R. , Tap William D. , Donoghue Mark T.A. , D’Angelo Sandra P. 
Published: January 2024

ABSTRACTResponse to immune checkpoint inhibition (ICI) in sarcoma is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. One potential mechanism is epigenetic de-repression of transposable elements (TEs), which stimulates antitumor immunity. Here, we used transcriptomic data to assign immune-hot versus immune-cold status to 67 pre-treatment biopsies of sarcomas from patients treated on ICI trials. Progression-free survival and overall response was superior in the immune-hot group. Expression of TEs and epigenetic regulators significantly predicted immune-hot status in a regression model in which specific TE subfamilies andIKZF1, a chromatin-interacting transcription factor, were significantly contributory. TE andIKZF1expression positively correlated with tumor immune infiltrates, inflammatory pathways, and clinical outcomes. Key findings were confirmed in a validation cohort (n=190). This work suggests that TE andIKZF1expression warrant investigation as predictive biomarkers for ICI response and as therapeutic targets in sarcomas.
A Method to Redesign and Simplify Schedules of Assessment and Quantify the Impacts. Applications to Merck Protocols
Authors: Cummings Steven R. , Chetham Scott , Lee Andy 
Published: January 2024

AbstractThe growing complexity of biopharmaceutical sponsored trials has adverse impacts on increased burdens on participants, clinical sites, and sponsors, including greater difficulty recruiting and retaining participants, difficulty engaging sites to participate in trials, excessive cost of trials, and increased cycle times. The schedule of assessments (SoAs) is the origin of and blueprint for complexity that is often generated by copying and pasting from previous SoAs. We developed an approach, termed Lean Design, for redesigning SoAs, restarting SoAs from ‘ground zero’, challenging the addition of assessments using several principles of trial design. We employed a system, the Faro Trial Designer Tool, to quantify the impacts of changes in an SoA to provide real-time feedback to the team and sponsor. We applied the approach in workshops with teams for six clinical trials in various stages of design and implementation. The approach resulted in recommendation for substantial savings in participant and site staff time, costs, and complexity of the trials. Application of this approach to very early stages of protocol design has the potential to reduce the complexity of biopharmaceutical sponsored trials and its consequences.
Effects of Diazepam on Hippocampal Blood Flow in People at Clinical High Risk for Psychosis
Authors: Livingston Nicholas R. , Kiemes Amanda , Devenyi Gabriel A. , Knight Samuel , Lukow Paulina B. , Jelen Luke A. , Reilly Thomas , Dima Aikaterini , Nettis Maria Antonietta , Casetta Cecilia , Agyekum Tyler , Zelaya Fernando , Spencer Thomas , Micheli Andrea De , Fusar-Poli Paolo , Grace Anthony A. , Williams Steve C.R. , McGuire Philip , Egerton Alice , Chakravarty M. Mallar , Modinos Gemma 
Published: January 2024

AbstractBackgroundElevated hippocampal perfusion has been observed in people at clinical high-risk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychosis, and that prophylactic treatment with diazepam during adolescence can prevent the development of psychosis-relevant phenotypes. Here we examined whether diazepam normalises hippocampal perfusion in CHR-P individuals.MethodsUsing a randomised, double-blind, placebo-controlled, crossover design, 24 CHR-P individuals were assessed with MRI on two occasions, once following a single oral dose of diazepam (5 mg) and once following placebo. Regional cerebral blood flow (rCBF) was measured using 3D pseudo-continuous arterial spin labelling and sampled in native space using participant-specific hippocampus/subfield masks (CA1, subiculum, CA4/dentate gyrus). Twenty-one healthy controls (HC) were scanned using the same acquisition sequence, but without administration of diazepam or placebo. Mixed-design ANCOVAs and linear mixed-effects models were used to examine the effects of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on rCBF in the hippocampus as a whole and by subfield.ResultsUnder the placebo condition, CHR-P individuals (mean[±SD] age: 24.1[±4.8] years, 15F) showed significantly elevated rCBF compared to HC (mean[±SD] age: 26.5[±5.1] years, 11F) in the hippocampus (F(1,36)=8.2,pFDR=0.004) and across its subfields (allpFDR<0.001). Following diazepam, rCBF in the hippocampus (and subfields, allpFDR<0.001) was significantly reduced (t(69)=-5.1,pFDR<0.001) and normalised to HC levels (F(1,41)=0.3,pFDR=0.225).ConclusionsDiazepam can normalise hippocampal hyperperfusion in CHR-P individuals, consistent with evidence implicating medial temporal GABAergic dysfunction in the pathophysiology of psychosis.
Modelling the within-host dynamics ofPlasmodium vivaxhypnozoite activation: an analysis of the SPf66 vaccine trial
Authors: Mehra Somya , Nosten Francois , Luxemburger Christine , White Nicholas J , Watson James A 
Published: January 2024

AbstractPlasmodium vivaxparasites can lie dormant in the liver as hypnozoites, activating weeks to months after sporozoite inoculation to cause relapsing malarial illness. It is not known what biological processes govern hypnozoite activation. We use longitudinal data from the most detailed cohort study ever conducted in an area where bothPlasmodium falciparumandP. vivaxwere endemic to fit a simple within-host mathematical model ofP. vivaxhypnozoite activation. 1344 children living on the Thailand-Myanmar border were followed each day for 21 months. There were 2504 vivax and 1164 falciparum malaria symptomatic episodes recorded over 1988 person-years. The model assumes that hypnozoites activate independently at a constant rate (‘exponential clock model’). When this model was embedded in a stochastic framework for repeated infectious mosquito bites, with seasonality inferred from the incidence of clinical falciparum malaria episodes, it explained the observed temporal patterns of multiple (up to 13) recurrent vivax malaria episodes. Under this model we estimate the mean dormancy period for a single hypnozoite to be 6 months (i.e. a half-life of 4 months). We use the calibrated within-host model to characterise population level overdispersion in the risk of relapse, and assess the potential utility of a serological test for radical cure in low transmission settings. We show that mefloquine treatment of falciparum malaria eliminates early vivax relapses; and that there are substantially moreP. vivaxrecurrences than expected under the model following artesunate monotherapy treatment for falciparum malaria. These results suggest that hypnozoites can be activated by symptomatic malarial illness.
Spatiotemporal Forecasting of Opioid-related Fatal Overdoses: Towards Best Practices for Modeling and Evaluation
Authors: Heuton Kyle , Kapoor Jyontika , Shrestha Shikhar , Stopka Thomas J. , Hughes Michael C. 
Published: January 2024

AbstractTo inform public health interventions, researchers have developed models to forecast opioid-related overdose mortality. However, these efforts often have limited overlap in the models and datasets employed, presenting challenges to assessing progress in this field. Furthermore, common error-based performance metrics, such as root mean squared error, are not directly suitable to assess a key modeling purpose: the identification of priority areas for public health interventions. We recommend a new intervention-aware performance metric and establish a set of baseline models with competitive performance. To show how model and metric choice vary across locations, we explore two distinct geographies: Cook County, Illinois and the state of Massachusetts. We introduce a new, intervention-aware evaluation metric: the Percentage of Best Possible Reach (%BPR). The top-performing models based on error-based metrics recommend fixed-budget interventions in areas that do not always reach the most possible overdose events. In Massachusetts the top models, as ranked by our proposed %BPR metric, could have reached 18 additional fatal overdoses per year in our 2020-2021 test period compared to models favored by error-based metrics, assuming the ability to intervene in 100 census tracts out of the 1620 in Massachusetts. We release open code and data for others to build upon.Repository for code and data:https://github.com/tufts-ml/opioid-overdose-models