bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combating the challenges of COVID-19 pandemic: Insights into molecular mechanisms, immune responses and therapeutics against SARS-CoV-2
Authors: Negi Kriti , Agarwal Meetu , Pahuja Isha , Bhardwaj Bhavya , Rawat Mansi , Bhaskar Ashima , Dwivedi Ved Prakash 
Published: January 2023

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lethal coronavirus disease (COVID-19). SARS-CoV-2 has been the chief source of threat to public health and safety from 2019 to the present. SARS-CoV-2 caused a sudden and significant rise in hospitalization due to respiratory issues and pneumonia. We are consistently uncovering new information about SARS-CoV-2, and yet so much is to explore to implement efficient interventions to combat the emergent variants and spread of the ongoing pandemic. Information regarding the existing COVID-19 pandemic is streamlining continuously. However, clinical symptoms of SARS-CoV-2 infections spanning from asymptomatic infection to severe death-instigating disease remain consistent with preliminary reports. In this review, we have briefly introduced highlights of the COVID-19 pandemic and features of SARS-CoV-2. We have focused on current knowledge of innate and adaptive immune responses during SARS-CoV-2 infections and persisting clinical features of recovered patients. Furthermore, we have discussed how these immune responses are not tightly regulated and imbalance can direct the latter phases of COVID-19, long-COVID symptoms, and cause detrimental immunopathogenesis. COVID-19 vaccines are also discussed in detail to describe the efforts going around the world to control and prevent the infection. Overall, we have summarized the current knowledge on the immunology of SARS-CoV-2 infection and the utilization of that knowledge in the development of a suitable COVID-19 therapeutics and vaccines.
Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients*
Authors: Roh David J. , Chang Tiffany R. , Kumar Aditya , Burke Devin , Torres Glenda , Xu Katherine , Yang Winni , Cottarelli Azzurra , Moore Ernest , Sauaia Angela , Hansen Kirk , Velazquez Angela , Boehme Amelia , Vrosgou Athina , Ghoshal Shivani , Park Soojin , Agarwal Sachin , Claassen Jan , Connolly E. Sander , Wagener Gebhard , Francis Richard O. , Hod Eldad 
Published: January 2023

OBJECTIVES:
Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU.

DESIGN:
Observational cohort study and separate in vitro laboratory study.

SETTING:
Multicenter tertiary referral ICUs.

PATIENTS:
Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: –0.52, p = 0.002; TEG r: –0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings.

CONCLUSIONS:
Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient’s hemoglobin concentration.
Mean Arterial Pressure Targets and Patient-Important Outcomes in Critically Ill Adults: A Systematic Review and Meta-Analysis of Randomized Trials*
Authors: Carayannopoulos Kallirroi Laiya , Pidutti Andrew , Upadhyaya Yashita , Alshamsi Fayez , Basmaji John , Granholm Anders , Alhazzani Waleed , Lewis Kimberley 
Published: January 2023

OBJECTIVE:
To conduct a systematic review and meta-analysis to determine whether targeting a higher mean arterial pressure (MAP) compared with a lower MAP in adults with shock results in differences in patient important outcomes.

DATA SOURCES:
We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov through May 2021.

STUDY SELECTION:
Titles and abstracts were screened independently and in duplicate to identify potentially eligible studies, then full text for final eligibility. We included parallel-group randomized controlled trials in adult patients with a diagnosis of shock requiring vasoactive medications. The higher MAP group was required to receive vasoactive medications to target a higher MAP as established by study authors, whereas the lower MAP group received vasoactive medications to target lower MAP.

DATA EXTRACTION:
In triplicate, reviewers independently extracted data using a prepiloted abstraction form. Statistical analyses were conducted using the RevMan software Version 5.3.

DATA SYNTHESIS:
Six randomized controlled trials (n = 3,690) met eligibility criteria. Targeting a higher MAP (75–85 mm Hg) compared with lower MAP of 65 mm Hg resulted in no difference in mortality (relative risk [RR], 1.06; 95% CI, 0.98–1.15; I
2 = 0%; p = 0.12; moderate certainty. Targeting a higher MAP resulted in no difference in the risk of undergoing renal replacement therapy (RR, 0.96; 95% CI, 0.83–1.11; I
2 = 24%; p = 0.57; moderate certainty); however, a subgroup analysis comparing patients with and without chronic hypertension demonstrated that a higher MAP may reduce the risk of undergoing renal replacement therapy (RR, 0.83; 95% CI, 0.71–0.98; I
2 = 0%; p = 0.02).

CONCLUSIONS:
In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in mortality when a higher MAP is targeted in critically ill adult patients with shock. Further studies are needed to determine the impact of mean arterial pressure on need for renal replacement therapy in this population.
Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury
Authors: Zusman Benjamin E. , Wu Yijen , Kochanek Patrick M. , Vagni Vincent E. , Janesko-Feldman Keri , Gerzanich Volodymyr , Simard J. Marc , Karahalios Katherine , Mihaljevic Sandra , Raikwar Sudhanshu , Rani Anupama , Rulney Jarrod , Desai Shashvat M. , Catapano Joshua , Jha Ruchira M. 
Published: January 2023

OBJECTIVES:
Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion.

DESIGN:
Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult).

SETTING:
Preclinical laboratory.

SUBJECTS:
Adult male C57BL/6J mice (n = 54).

INTERVENTIONS:
Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 μg/kg)/high-dose glibenclamide (10 μg/mouse). Seven-day subcutaneous infusions (0.4 μg/hr) were continued.

MEASUREMENTS AND MAIN RESULTS:
Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10–6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial.

CONCLUSIONS:
High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.
Development of Moral Injury in ICU Professionals During the COVID-19 Pandemic: A Prospective Serial Interview Study
Authors: Kok Niek , Zegers Marieke , Fuchs Malaika , van der Hoeven Hans , Hoedemaekers Cornelia , van Gurp Jelle 
Published: January 2023

OBJECTIVES:
During the COVID-19 pandemic, ICU professionals have faced moral problems that may cause moral injury. This study explored whether, how, and when moral injury among ICU professionals developed in the course of the COVID-19 pandemic.

DESIGN:
This is a prospective qualitative serial interview study.

SETTING:
Two hospitals among which one university medical center and one teaching hospital in the Netherlands.

SUBJECTS:
Twenty-six ICU professionals who worked during the COVID-19 pandemic.

INTERVENTIONS:
None.

MEASUREMENTS MAIN RESULTS:
In-depth interviews with follow-up after 6 and 12 months. In total, 62 interviews were conducted. ICU professionals narrated about anticipatory worry about life and death decisions, lack of knowledge and prognostic uncertainty about COVID-19, powerlessness and failure, abandonment or betrayal by society, politics, or the healthcare organization, numbness toward patients and families, and disorientation and self-alienation. Centrally, ICU professionals describe longitudinal processes by which they gradually numbed themselves emotionally from patients and families as well as potentially impactful events in their work. For some ICU professionals, organizational, societal, and political responses to the pandemic contributed to numbness, loss of motivation, and self-alienation.

CONCLUSIONS:
ICU professionals exhibit symptoms of moral injury such as feelings of betrayal, detachment, self-alienation, and disorientation. Healthcare organizations and ICU professionals themselves should be cognizant that these feelings may indicate that professionals might have developed moral injury or that it may yet develop in the future. Awareness should be raised about moral injury and should be followed up by asking morally injured professionals what they need, so as to not risk offering unwanted help.
Posterior instrumentation for osteoporotic fractures in the thoracic or lumbar spine: Cement-augmented pedicle screws vs hybrid constructs
Authors: Chou Po-Hsin , Lin Hsi-Hsien , Yao Yu-Cheng , Wang Shih-Tien , Chang Ming-Chau , Liu Chien-Lin 
Published: January 2023

Background:
Cement-augmented pedicle screws (CPS) and hybrid construct (HC), consisting of pedicle screws and additional hooks, are common fixation methods for osteoporotic spine fracture. No study has compared surgical results of CPS and HC for treating osteoporotic spine fracture. The aim of the study was to compare surgical results using CPS or HC for osteoporotic fractures of the thoracic or lumbar spine.

Methods:
This retrospective cohort study included 84 patients who received surgical treatment with CPS (n = 43) or HC (n = 41) for osteoporotic spine fractures from January 2011 to December 2015, with a mean follow-up of 67 months. Sixty-five patients with neurological deficits received long posterior instrumentation, short posterior decompression, and posterolateral fusion. The 19 patients without neurologic deficits received long posterior instrumentation without posterior decompression and fusion. Radiographic, clinical, and neurologic outcomes were evaluated.

Results:
The HC group had significantly shorter operative times (231 vs 258 minutes), greater blood loss (497 vs 427 mL), better immediate postoperative kyphosis reduction (10.6° vs 9.1°), and greater final reduction loss (9.8° vs 7.1°) than the CPS group. In both groups, significant loss of the kyphotic angle was apparent during follow-up. Improved ambulation after surgery occurred in 51.2% and 58.5% of patients in the CPS and HC groups, respectively. Neurologic function after surgery improved 0.5 and 0.7 grades in the CPS and HC groups, respectively. Implants failed in 2.3% and 2.4% of patients in the CPS and HC groups, respectively. The incidence of cement leakage from screw augmentation was 38.9%.

Conclusion:
The CPS and HC techniques for treating osteoporotic fractures of the thoracic or lumbar spine did not differ statistically in terms of improved radiologic and clinical outcomes, final neurologic and ambulatory function, or implant failure rates, making them equally comparable alternatives.
Using Trident distal radial locking plate to fix the fracture of distal radius volar rim
Authors: Huang Yin-Ming , Chen Chun-Yu , Lin Kai-Cheng , Lai Wei-Yi , Lin Yi-Ying , Fu Yun-Ju , Tarng Yih-Wen 
Published: January 2023

Background:
The volar locking plates have been widely used in a variety of distal radius fractures, but they still have several limitations when dealing with small fragments located around the watershed line with widely reported complications. The volar rim fragments play a critical role in radiocarpal joint stability and failing to secure the volar rim fragment usually results in carpal instability, subluxation, or even dislocation. This study investigates clinical outcomes in the use of a novel implant, the Trident distal radial (TDR) locking plate to treat distal radius fracture with the intermedium column edge (lunate fossa volar rim) fragment involvement.

Methods:
A retrospective study of 25 patients was conducted, all patients had intermedium column fractures with lunate fossa volar rim involvement and treat with the TDR between January 2016 and December 2019. The clinical assessment outcomes included VAS Pain, PRWE, and DASH scores. Objective measurements included ROM of the injured wrist and grip strength. Final radiographs were used to evaluate radial inclination, volar tilt, ulnar variance, and distal radioulnar joint instability. Secondary operations related to hardware complications were also recorded.

Results:
The outcome revealed that the mean VAS Pain Score was 1.3, mean DASH score was 10.5, and mean PRWE score was 9.3. Objective measurements revealed good ROM recovery and an 89% gripping strength recovery compared with contralateral hand. Radiographic measurements revealed good maintenance of volar tilt, radial inclination, and mean ulnar variance. There were no complications related to the implant and all fracture sites were union.

Conclusion:
We believe that the TDR provided more stable fixation among distal radial fractures that predominantly involved the intermedial column and volar rim fragment, and allowing early rehabilitation. We could obtain excellent results in the wrist ROM, gripping power, and Pain Score (VAS).
Estimating Effects of Wages on Smoking Prevalence Using Labor Unions as Instrumental Variables
Authors: Leigh J. Paul , Chakalov Bozhidar T. 
Published: January 2023

Objectives
To test for the effects of wages on smoking using labor unions as instrumental variables.

Methods
We analyzed four waves of the Panel Study of Income Dynamics (2013 to 2019 alternate years). The overall sample included workers aged 18 to 70 years in 2013 and subsamples within blue + clerical/white-collar and private/public sector jobs (N = 37,117 to 8446 person-years). We used two instrumental variables: worker's union membership and states' right-to-work laws.

Results
$1 (2019 US dollars) increases in wages-per-hour resulted in 1.3 (P < 0.001) percentage point decreases in smoking prevalence (8.2% decreases at the smoking mean). Larger effect sizes and strong statistical significance were found for blue-collar + clerical and private-sector subsamples; smaller sizes and insignificance were found for public-sector and white-collar subsamples.

Conclusions
Unions increase wages, and higher wages, in turn, reduce smoking. Wages and labor unions are underappreciated social determinants of health.
Pediatric Critical Care–Associated Parental Traumatic Stress: Beyond the First Year*
Authors: Whyte-Nesfield Mekela , Kaplan Daniel , Eldridge Peter S. , Gai Jiaxiang , Cuddy William , Breeden Karli , Ansari Nadia , Siller Pamela , Mennella Jenna M. , Nkromah Toah A. , Youtz Meghan , Thomas Neal , Li Simon 
Published: January 2023

OBJECTIVES:
Perform a longitudinal analysis of parental traumatic stress up to 30 months after PICU discharge.

DESIGN:
Prospective observational cohort study.

SETTING:
Two tertiary care children’s hospitals with mixed medical/surgical/cardiac PICUs.

SUBJECTS:
Parents of patients unexpectedly admitted to the PICU.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Two hundred sixty-five parents of 188 children were enrolled. Of the 195 parents who completed the 3–9-month assessments, 29 (14.8%) met posttraumatic stress disorder (PTSD) qualification on the PTSD Symptom Scale Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Multivariable analysis showed parents who met acute stress disorder (ASD) qualification (odds ratio [OR] 8.01; 95% CI 2.64–24.3), parents of children with Pediatric Overall Performance Category score of severe or coma at discharge (OR 5.21; 95% CI 1.65–16.4), parents who had concerns for their child’s permanent injury (OR 1.82; 95% CI 1.36–2.43), and parents who reported increased knowledge of child illness during admission (OR 1.82; 95% CI 1.13–2.93) had increased odds of developing parental PTSD. Of the 175 parents (66%) who completed the 18–30-month assessments, 22 (12.5%) met PTSD qualification. Multivariable analysis showed parents who met ASD qualification (OR 4.19; 95% CI 1.12–15.7), parents who had a history of a family member or themselves being admitted to ICU (OR 6.51; 95% CI 1.43–29.6), and parents who had concerns of child’s susceptibility to death post discharge (OR 1.58; 95% CI 1.19–2.09) had increased odds of developing parental PTSD. At 18–30 months post discharge, parents who met the PTSD qualification were more likely to report a decrease in household income following discharge (OR 9.23; 95% CI 1.71–49.9).

CONCLUSIONS:
Parental PTSD remains a significant morbidity of PICU admission for a subgroup of parents greater than 18 months post admission. Identifiable risk factors will inform the development of targeted interventions.
Monitoring in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Bhalla Anoopindar , Baudin Florent , Takeuchi Muneyuki , Cruces Pablo ,   on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:
Monitoring is essential to assess changes in the lung condition, to identify heart-lung interactions, and to personalize and improve respiratory support and adjuvant therapies in pediatric acute respiratory distress syndrome (PARDS). The objective of this article is to report the rationale of the revised recommendations/statements on monitoring from the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2).

DATA SOURCES:
MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).

STUDY SELECTION:
We included studies focused on respiratory or cardiovascular monitoring of children less than 18 years old with a diagnosis of PARDS. We excluded studies focused on neonates.

DATA EXTRACTION:
Title/abstract review, full-text review, and data extraction using a standardized data collection form.

DATA SYNTHESIS:
The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. We identified 342 studies for full-text review. Seventeen good practice statements were generated related to respiratory and cardiovascular monitoring. Four research statements were generated related to respiratory mechanics and imaging monitoring, hemodynamics monitoring, and extubation readiness monitoring.

CONCLUSIONS:
PALICC-2 monitoring good practice and research statements were developed to improve the care of patients with PARDS and were based on new knowledge generated in recent years in patients with PARDS, specifically in topics of general monitoring, respiratory system mechanics, gas exchange, weaning considerations, lung imaging, and hemodynamic monitoring.
Craniocervical Instability in Oculoauriculovertebral Spectrum
Authors: Gomes Luiz Paulo , Ferraz Beatriz Gonçalves , Brandão Michele Madeira , Alonso Nivaldo , Pittoli Siulan Vendramini , Tonello Cristiano 
Published: January 2023

Introduction:
The oculoauriculovertebral spectrum (OAVS) are anomalies of the first and second pharyngeal arches, causing craniofacial changes, principally facial asymmetry, as well as anomalies in the spine, that can be a cause of instability of the craniocervical junction - manipulation of an unstable spine can result in morbimortality. However, few studies have related OAVS to craniocervical instability.

Objectives:
Correlate patients with OAVS through radiography with craniocervical instability and prediction of its occurrence.

Material and Methods:
Through a radiographic study of the cervical spine, the assessment of vertebral malformations and the presence of craniocervical instability was performed and clinical assessment using the OMENS score as a phenotypic criteria for patients with OAVS, by a specialized multidisciplinary team. Student’s t test, Kolmogorov-Smirnova, and χ2 were performed.

Results:
Twenty-six patients with OAVS were evaluated, 7 (26.9%) had craniocervical instability, the OMENS score was 3 times higher, but without statistical significance. All patients with instability also had spinal malformations, and of those without craniocervical instability (19 patients), 57.8% had spinal malformations. Vertebral malformations had a similar incidence in those with and without instability, the most common being scoliosis. There was no statistical significance in the presence or absence of spinal malformations with the presence or absence of craniocervical instability. Extracraniofacial findings were found in all patients with instability; 71.4% of them were radial.

Conclusions:
Patients with higher OMENS scores had more craniocervical instability but without statistical significance. It also did not show statistical relevance between the presence of malformations and craniocervical instability.