bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of methylene blue on hemodynamic response in the early phase of septic shock: A case series
Authors: Luis-Silva Fabio , Menegueti Mayra Gonçalves , Sato Lucas , Peres Leandro Moreira , dos Reis Sepeda Corina , Petroski-Moraes Bruno C. , Donadel Mariana Dermínio , Gallo Gabriela Bortoleto , Jordani Maria Cecília , Mestriner Fabiola , Becari Christiane , Basile-Filho Anibal , Evora Paulo R. B. , Martins-Filho Olindo Assis , Auxiliadora-Martins Maria 
Published: February 2023

Rationale:
Methylene blue (MB) has been used to increase blood pressure in septic shock, acting on the activity of guanylate cyclase and nitric oxide synthase.

Patience concerns:
The aim of this study is to demonstrate the benefit of MB in early phase of septic shock.
Diagnoses: We report 6 cases of patients with septic shock with up to 72 hours of evolution.

Interventions:
We used MB after fluid replacement, use of norepinephrine and vasopressin. Patients received a loading dose of MB and maintenance for 48 hours.

Outcomes:
All patients presented a reduction in the dose of vasopressors and lactate levels soon after the administration of the loading dose of MB, an effect that was maintained with the maintenance dose for 48 hours. Interleukin 6 and interleukin 8 were elevated at the beginning of the septic condition, with a progressive and marked reduction after the beginning of MB infusion, demonstrating a role of MB in reducing the inflammatory activity.

Lessons:
This case series suggests that MB used early in the treatment of septic shock may be useful in reducing vasopressor dose and lactate levels. Further studies are still required to further validate these findings.
Large intramural hematoma of the esophagus after endoscopic injection sclerotherapy: A case report
Authors: Wu Bo , Xie Xincheng , Li Xiao , Zhu Qun , Zhou Chunhua 
Published: February 2023

Rationale:
Endoscopic injection sclerotherapy (EIS) is a common treatment for patients with liver cirrhosis and esophageal varices. It can effectively treat variceal rupture and bleeding caused by liver cirrhosis. However, EIS has many complications, including postoperative bleeding, retrosternal pain, esophageal ulcers, esophageal stenosis, and ectopic embolism. Intramural hematoma of the esophagus (IHE) is a rare complication of EIS that can lead to chest tightness, chest pain, and dysphagia.

Patient’s concerns:
A 55-year-old man developed severe nausea and vomiting accompanied by chest pain after EIS.

Diagnosis:
Comprehensive imaging features, the patient was diagnosed as IHE.

Interventions:
A vascular clamp was used for hemostasia, and a feeding tube was placed in the patient’s jejunum.

Outcomes:
After the removal of the jejunal feeding tube and the intake of a semiliquid diet, the patient had no episodes of chest pain, chest tightness, or dysphagia and was discharged after 2 days of observation.

Lessons:
Although IHE rarely occurs after EIS, we should not overlook its risk. The occurrence of IHE is not directly related to the number of EISs received or the degree of liver cirrhosis but is more likely related to postoperative nausea and vomiting. Therefore, timely medication and observation are particularly important for patients with nausea and vomiting after endoscopic treatment.
Association of physical activity and the risk of COVID-19 hospitalization: A dose–response meta-analysis
Authors: Li Dan , Jin Shengzhen , He Ziying , Lu Songtao 
Published: February 2023

Background:
Many people have experienced a high burden due to the spread of the coronavirus disease (COVID-19) and its serious consequences for health and everyday life. Prior studies have reported that physical activity (PA) may lower the risk of COVID-19 hospitalization. The present meta-analysis explored the dose–response relationship between PA and the risk of COVID-19 hospitalization.

Methods:
Epidemiological observational studies on the relationship between PA and the risk of COVID-19 hospitalization were included. Categorical dose–response relationships between PA and the risk of COVID-19 hospitalization were assessed using random effect models. Robust error meta-regression models assessed the continuous relationship between PA (metabolic equivalent [Met]-h/wk) and COVID-19 hospitalization risk across studies reporting quantitative PA estimates.

Results:
Seventeen observational studies (cohort\case–control\cross-section) met the criteria for inclusion in the meta-analysis. Categorical dose-relationship analysis showed a 40% (risk ratio [RR] 0.60, 95% confidence interval [CI]: 0.48–0.71) reduction in the risk of COVID-19 hospitalization compared to the lowest dose of PA. The results of the continuous dose–response relationship showed a non-linear inverse relationship (Pnon-linearity < .05) between PA and the risk of COVID-19 hospitalization. When total PA was < or >10 Met-h/wk, an increase of 4 Met-h/wk was associated with a 14% (RR = 0.83, 95% CI: 0.85–0.87) and 11% (RR = 0.89, 95% CI: 0.87–0.90) reduction in the risk of COVID-19 hospitalization, respectively.

Conclusions:
There was an inverse non-linear dose–response relationship between PA level and the risk of COVID-19 hospitalization. Doses of the guideline-recommended minimum PA levels by the World Health Organization may be required for more substantial reductions in the COVID-19 hospitalization risk.
Ethics of allocation of donor organs
Authors: Bunnik Eline M. 
Published: February 2023

Purpose of review
There is no widely accepted single ethical principle for the fair allocation of scarce donor organs for transplantation. Although most allocation systems use combinations of allocation principles, there is a particular tension between ‘prioritizing the worst-off’ and ‘maximizing total benefits’. It is often suggested that empirical research on public preferences should help solve the dilemma between equity and efficiency in allocation policy-making.

Recent findings
This review shows that the evidence on public preferences for allocation principles is limited, and that the normative role of public preferences in donor organ allocation policy making is unclear. The review seeks to clarify the ethical dilemma to the transplant community, and draws attention to recent attempts at balancing and rank-ordering of allocation principles.

Summary
This review suggests that policy makers should make explicit the relative weights attributed to equity and efficiency considerations in allocation policies, and monitor the effects of policy changes on important ethics outcomes, including equitable access among patient groups. Also, it draws attention to wider justice issues associated not with the distribution of donor organs among patients on waiting lists, but with barriers in referral for transplant evaluation and disparities among patient groups in access to waiting lists.
GGEM: Gender, Geography, and EMployment differences based on mobility levels among lower limb prosthesis users living in the United States
Authors: England Dwiesha L. , Miller Taavy A. , Stevens Phillip M. , Campbell James H. , Wurdeman Shane R. 
Published: February 2023

Background:
For individuals with a disability, an increase in functional mobility may improve their quality of life and well-being. Greater understanding is needed on how factors such as gender, geography, and employment may play a role in mobility levels among individuals with lower limb amputation.

Objectives:
To assess the relationship between gender, geography, and employment status on mobility among lower limb prosthesis users.

Methods:
A cross-sectional analysis of 7,524 patient mobility outcomes completed across the United States was performed. The regression model included the independent variables, such as age, gender, region, employment status, and amputation level. Mobility was entered as the dependent variable.

Results:
Individuals who were employed had 3.6 times the odds of reaching increased mobility (Prosthetic Limb Users’ Survey of Mobility ≥ 50) than those unemployed (odds ratio 3.56, 95% confidence interval 3.10–4.09). Gender and geography were significantly associated with mobility as well.

Conclusions:
Being employed is associated with greater odds of reaching increased mobility. Addressing factors such as returning to employment may aid in improving mobility levels among prosthesis users.
High-dimensional proteomics identifies organ injury patterns associated with outcomes in human trauma
Authors: Li Shimena R. , Moheimani Hamed , Herzig Brachman , Kail Michael , Krishnamoorthi Neha , Wu Junru , Abdelhamid Sultan , Scioscia Jacob , Sung Eunseo , Rosengart Anna , Bonaroti Jillian , Johansson Par I. , Stensballe Jakob , Neal Matthew D. , Das Jishnu , Kar Upendra , Sperry Jason , Billiar Timothy R. 
Published: February 2023

INTRODUCTION
Severe traumatic injury with shock can lead to direct and indirect organ injury; however, tissue-specific biomarkers are limited in clinical panels. We used proteomic and metabolomic databases to identify organ injury patterns after severe injury in humans.

METHODS
Plasma samples (times 0, 24, and 72 hours after arrival to trauma center) from injured patients enrolled in two randomized prehospital trials were subjected to multiplexed proteomics (SomaLogic Inc., Boulder, CO). Patients were categorized by outcome: nonresolvers (died >72 hours or required ≥7 days of critical care), resolvers (survived to 30 days and required <7 days of critical care), and low Injury Severity Score (ISS) controls. Established tissue-specific biomarkers were identified through a literature review and cross-referenced with tissue specificity from the Human Protein Atlas. Untargeted plasma metabolomics (Metabolon Inc., Durham, NC), inflammatory mediators, and endothelial damage markers were correlated with injury biomarkers. Kruskal-Wallis/Mann-Whitney U tests with false discovery rate correction assessed differences in biomarker expression across outcome groups (significance; p < 0.1).

RESULTS
Of 142 patients, 78 were nonresolvers (median ISS, 30), 34 were resolvers (median ISS, 22), and 30 were low ISS controls (median ISS, 1). A broad release of tissue-specific damage markers was observed at admission; this was greater in nonresolvers. By 72 hours, nine cardiac, three liver, eight neurologic, and three pulmonary proteins remained significantly elevated in nonresolvers compared with resolvers. Cardiac damage biomarkers showed the greatest elevations at 72 hours in nonresolvers and had significant positive correlations with proinflammatory mediators and endothelial damage markers. Nonresolvers had lower concentrations of fatty acid metabolites compared with resolvers, particularly acyl carnitines and cholines.

CONCLUSION
We identified an immediate release of tissue-specific biomarkers with sustained elevation in the liver, pulmonary, neurologic, and especially cardiac injury biomarkers in patients with complex clinical courses after severe injury. The persistent myocardial injury in nonresolvers may be due to a combination of factors including metabolic stress, inflammation, and endotheliopathy.
The effects of hypocalcemia in severely injured pediatric trauma patients
Authors: Ciaraglia Angelo , Lumbard Derek , Deschner Benjamin , Barry Lauran , Braverman Maxwell , Eastridge Brian , Stewart Ronald , Liao Lillian , Jenkins Donald , Nicholson Susannah 
Published: February 2023

INTRODUCTION
The role of calcium is ubiquitous in human physiology. Emerging evidence suggests that the lethal triad be revised to include hypocalcemia (hypoCa) and thus be known as the lethal diamond. There are data showing that traumatic injury may result in hypoCa independent from the mechanism of calcium chelation by citrate-based blood preservatives. Minimal literature exists analyzing the role of hypoCa in pediatric trauma patients. We hypothesize that there is an independent association of hypoCa with increased blood product requirements and mortality.

METHODS
A retrospective cohort study of severely injured pediatric trauma patients was conducted. Trauma registry data were collected from January 2016 to August 2021. Ionized calcium (iCa) levels were obtained from arrival blood draws. Subjects were categorized into two groups by a threshold iCa level of 1.00 mmol/L and compared. Shock Index Pediatric Adjusted scores were used to adjust for age-specific differences in vital signs.

RESULTS
A total of 142 patients were compared, of which 46.5% were hypocalcemic (iCa <1.00 mmol/L). Patients were well matched in terms of demographics and injury severity. The hypocalcemic group had lower systolic blood pressure and a higher percentage of Shock Index Pediatric Adjusted–positive patients. Weight-adjusted transfusion volumes were significantly higher in the hypocalcemic group at both the 4-hour and 24-hour time points without a difference in prehospital transfusion requirements. There was no observed difference in early or in-hospital mortality.

CONCLUSION
This study contributes to the body of literature regarding the association between hypoCa and traumatic injury in the pediatric population. Hypocalcemia was associated with increased blood product requirements without a difference in prehospital transfusion requirements, suggesting a possible independent association. Further prospective studies are needed to better understand this relationship.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Elucidating the molecular mechanisms of fibrinolytic shutdown after severe injury: The role of thrombin-activatable fibrinolysis inhibitor
Authors: Coleman Julia R. , Moore Ernest E. , Kelher Marguerite R. , Jones Kenneth , Cohen Mitchell J. , Banerjee Anirban , Silliman Christopher C. 
Published: February 2023

BACKGROUND
The mechanisms underlying trauma-induced coagulopathy remain elusive. Hyperfibrinolysis has been linked to increased plasminogen activation and antiprotease consumption; however, the mechanistic players in its counterpart, fibrinolysis shutdown, remain unclear. We hypothesize that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a major role in fibrinolytic shutdown after injury.

METHODS
As part of this observational cohort study, whole blood was collected from trauma activation patients at a single, level 1 trauma center. Citrated rapid thrombelastography and the following enzyme-linked immunosorbent assays were conducted: thrombin, antithrombin, thrombin-antithrombin complex, TAFI, plasminogen, antiplasmin, plasmin-antiplasmin (PAP), tissue plasminogen activator, plasminogen activator inhibitor 1, and tissue plasminogen activator–plasminogen activator inhibitor 1 complex. Univariate and cluster analysis were performed.

RESULTS
Overall, 56 patients (median age, 33.5 years; 70% male) were included. The majority (57%) presented after blunt mechanism and with severe injury (median New Injury Severity Score, 27). Two clusters of patients were identified: Group 1 (normal fibrinolysis, n = 21) and Group 2 (fibrinolysis shutdown, n = 35). Group 2 had significantly lower fibrinolysis with a median LY30 of 1.1% (interquartile range [IQR], 0.1–1.9%) versus 2.1% (IQR, 0.5–2.8%) in Group 1; while the median LY30 was within physiologic range, 45% of patients in Group 2 were in shutdown (vs. 24% in Group 1, p = 0.09). Compared with Group 1, Group 2 had significantly higher PAP (median, 4.7 [IQR, 1.7–9.3] vs. 1.4 [1.0–2.1] μg/mL in Group 1; p = 0.002) and higher TAFI (median, 152.5% [IQR, 110.3–190.7%] vs. 121.9% [IQR, 93.2–155.6%]; p = 0.04). There was a strong correlation between PAP and TAFI (R
2 = 0.5, p = 0.0002).

CONCLUSION
The presented data characterize fibrinolytic shutdown, indicating an initial plasmin burst followed by diminished fibrinolysis, which is distinct from hypofibrinolysis (inadequate plasmin burst and fibrinolysis). After an initial thrombin and plasmin burst (increased PAP), fibrinolysis is inhibited, mediated in part by increased TAFI.
Pediatric DUCT Score: A Highly Specific Predictive Model for Choledocholithiasis in Children
Authors: Ignacio Romeo C , Kelley-Quon Lorraine I , Ourshalimian Shadassa , Padilla Benjamin E , Jensen Aaron R , Shew Stephen B , Lofberg Katrine M , Smith Caitlin A , Roach Jonathan P , Pandya Samir R , Russell Katie W , Wang Kasper ,   for the Western Pediatric Surgery Research Consortium Choledocholithiasis Investigative Group
Published: February 2023

Background:
Current adult guidelines in the management of choledocholithiasis (CDL) may not be appropriate for children. We hypothesized adult preoperative predictive factors are not reliable for predicting CDL in children.

Study Design:
A multicenter retrospective cohort study was performed evaluating children (≤18 years of age) who underwent cholecystectomy for gallstone disease at 10 children’s hospitals. Univariate and multivariable analyses were used to identify factors independently associated with CDL. Patients were stratified into risk groups demonstrating based on the presence of predictive factors for CDL. Statistical analyses were performed, and chi-square analyses were used with a significance of p<0.05

Results:
A total of 979 cholecystectomy patients were analyzed. The diagnosis of CDL was confirmed in 222 patients (22.7%) by MRCP, ERCP, or IOC. Three predictive factors were identified 1)
D
ilated common bile duct (CBD) ≥6mm, 2)
U
ltrasound (US) with
C
holedocholithiasis, and 3)
T
otal bilirubin ≥1.8 mg/dL (Pediatric DUCT criteria). Risk groups were based on the number of predictive factors: Very High (3), High (2), Intermediate (1) and Low (0). The Pediatric DUCT criteria demonstrated accuracies of >76%, specificity of >78%, and negative predictive values of >79%. Adult factors (elevated AST/ALT, pancreatitis, BMI, and age) did not independently predict CDL. Based on risk stratification, the high and very-high risk groups demonstrated higher predictive capacity for CDL.

Conclusions:
Our study demonstrated that the Pediatric DUCT criteria, incorporating CBD dilation, choledocholithiasis seen on US, and total bilirubin ≥1.8 mg/dL, highly predicts the presence of choledocholithiasis in children. Other adult preoperative factors are not predictive of CBD stones in children.
Efficiency of an allosteric protein: Multiple affinity-efficacy correlations link agonist binding to nicotinic receptor activation
Authors: Indurthi Dinesh , Auerbach Anthony 
Published: February 2023

ABSTRACTReceptors signal by switching between resting and active shapes under the influence of agonists. The maximum response produced by an agonist (‘efficacy’) depends on its relative binding strength (‘affinity’) to active versus resting conformations. Efficiency, the logcorrelation between these two agonist properties, is the fraction of binding energy converted into energy for the receptor’s conformational change. In adult muscle nicotinic receptors, efficiencies estimated from 76 concentration-response curves (23 agonists, 53 mutations) segregate into 5 discrete classes (%): 0.56 (17), 0.51(32), 0.45(13), 0.41(26) and 0.31(12). There is a strong linear correlation between affinity and efficacy within each class, but the multiplicity of classes precludes the appearance of any overall relationship. The efficiency class distribution indicates that there are at least 5 resting versus active binding site structural pairs. We discuss efficiency as a quantitative measure of energy coupling between agonist binding and protein conformational change that is fundamental to receptor operation.
Chromatin remodeling enzyme Snf2h is essential for retinal cell proliferation and photoreceptor maintenance
Authors: Kuzelova Andrea , Dupacova Naoko , Antosova Barbora , Sunny Sweetu Susan , Kozmik Zbynek , Paces Jan , Skoultchi Arthur I. , Stopka Tomas , Kozmik Zbynek 
Published: February 2023

AbstractChromatin remodeling complexes are required for many distinct nuclear processes such as transcription, DNA replication and DNA repair. However, how these complexes contribute to the development of complex tissues within an organism is poorly characterized. Imitation switch (ISWI) proteins are among the most evolutionarily conserved ATP-dependent chromatin remodeling factors and are represented by yeast Isw1/Isw2, and their vertebrate counterparts Snf2h (Smarca5) and Snf2l (Smarca1). In this study, we focused on the role of theSnf2hgene during development of the mammalian retina. We show thatSnf2his expressed in both retinal progenitors and post-mitotic retinal cells. UsingSnf2hconditional knockout mice (Snf2hcKO), we found that whenSnf2his deleted the laminar structure of the adult retina is not retained, the overall thickness of the retina is significantly reduced compared with controls, and the outer nuclear layer (ONL) is completely missing. Depletion of Snf2h did not influence the ability of retinal progenitors to generate all of the differentiated retinal cell types. Instead, Snf2h function is critical for proliferation of retinal progenitor cells. Cells lacking Snf2h have a defective S-phase, leading to the entire cell division process impairments. Although, all retinal cell types appear to be specified in the absence of Snf2h function, cell cycle defects and concomitantly increased apoptosis inSnf2hcKO result in abnormal retina lamination, complete destruction of the photoreceptor layer and, consequently, in a physiologically non-functional retina.
Functional convergence of genomic and transcriptomic genetic architecture underlying sociability in a live-bearing fish
Authors: Corral-Lopez Alberto , Bloch Natasha I. , van der Bijl Wouter , Cortazar-Chinarro Maria , Szorkovszky Alexander , Kotrschal Alexander , Darolti Iulia , Buechel Severine D. , Romenskyy Maksym , Kolm Niclas , Mank Judith E. 
Published: February 2023

AbstractThe organization and coordination of fish schools provide a valuable model to investigate the genetic architecture of affiliative behaviors and dissect the mechanisms underlying social behaviors and personalities. We used quantitative genetic methods in replicate guppy selection lines that vary in schooling propensity to investigate the genetic basis of sociability phenotypes. Alignment and attraction, the two major traits forming the sociability personality axis in this species, showed heritability estimates at the upper end of the range previously described for social behaviors, with important variation across sexes. Consistent with findings in collective motion patterns, experimental evolution of schooling propensity increases the sociability of female, but not male, guppies when swimming with unfamiliar conspecifics, a highly relevant trait in a species with fission-fusion social systems in natural populations. Our results from PoolSeq and RNASeq convergently identify genes involved in neuron migration and synaptic function, highlighting a crucial role of glutamatergic synaptic function and calcium-dependent signaling processes in the evolution of schooling.