bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis
Authors: Yan Wenqing , Li Chen , Song Xin , Zhou Wenqiang , Chen Zhi 
Published: October 2022

Background:
Up to 80% of patients in the intensive care unit (ICU) suffer from delirium. Studies on the preventative use of melatonin in the ICU have produced mixed results. We performed a systematic review and meta-analysis to evaluate whether early administration of melatonin reduces the prevalence of delirium in critically ill patients.

Methods:
We searched Medline, Embase, and the Cochrane Library for randomized controlled trials comparing melatonin or melatonin agonists to placebo in ICU setting. The population included adult patients in the ICU. The primary outcome was the prevalence of delirium. Secondary outcomes included duration of delirium, delirium-free day, serum melatonin concentration, need for sedation, duration of mechanical ventilation, hospital and ICU length of stay (LOS), all-cause mortality, sleep quality, and adverse events. Trial sequential analysis (TSA) was performed on the primary outcome to prevent the risk of random error and multiplicity phenomenon as a result of repeated significance testing across all the included trials.

Results:
Twelve trials with a total of 2538 patients were analyzed. When all trials were pooled, the incidence of delirium in ICU patients who received melatonin was significantly lower than in those who received placebo (risk ratio, 0.77; 95% confidence interval: 0.61–0.96; I
2 = 56%). There were no significant differences in secondary outcomes including duration of delirium, duration of mechanical ventilation, ICU LOS, hospital LOS, and mortality. TSA indicated that Z-curve crossed the traditional boundary, but did not cross the monitoring boundary for benefit, which indicated that it is still inconclusive that melatonin affects the incidence of delirium.

Conclusions:
This meta-analysis found that early administration of melatonin may result in a decreased delirium prevalence in critically ill patients. However, the sensitivity analysis of high-quality studies did not support this finding. In addition, TSA demonstrated that the result may have false-positive error. Therefore, this finding should be interpreted with caution. Further studies are needed to examine the effectiveness of prophylactic melatonin on the prevalence and duration of ICU delirium in the future.
Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology
Authors: Huang Yuanshe , Wang Xiaodong , Yan Chen , Li Chen , Zhang Lidan , Zhang Lai , Liang E , Liu Tianlei , Mao Jingxin 
Published: October 2022

Background:
Whether metformin is related to nonalcoholic fatty liver disease (NAFLD) is controversial. Our aim was to investigate the relationship between metformin and NAFLD that may predict the metformin potential of these lesions and new prevention strategies in NAFLD patients.

Methods:
The meta-analysis was analyzed by Revman 5.3 softwares systematically searched for works published through July 29, 2022. Network pharmacology research based on databases, Cytoscape 3.7.1 software and R software respectively.

Results:
The following variables were associated with metformin in NAFLD patients: decreased of alanine aminotransferase (ALT) level (mean difference [MD] = −10.84, 95% confidence interval [CI] = −21.85 to 0.16, P = .05); decreased of aspartate amino transferase (AST) level (MD = −4.82, 95% CI = −9.33 to −0.30, P = .04); decreased of triglyceride (TG) level (MD = −0.17, 95% CI = −0.26 to −0.08, P = .0002); decreased of total cholesterol (TC) level (MD = −0.29, 95% CI = −0.47 to −0.10, P = .003); decreased of insulin resistance (IR) level (MD = −0.42, 95% CI = −0.82 to −0.02, P = .04). In addition, body mass index (BMI) (MD = −0.65, 95% CI = −1.46 to 0.16, P = .12) had no association with metformin in NAFLD patients. 181 metformin targets and 868 NAFLD disease targets were interaction analyzed, 15 core targets of metformin for the treatment of NAFLD were obtained. The effect of metformin on NAFLD mainly related to cytoplasm and protein binding, NAFLD, hepatitis B, pathway in cancer, toll like receptor signaling pathway and type 2 diabetes mellitus (T2DM). The proteins of hypoxia inducible factor-1 (HIF1A), nuclear factor erythroid 2-related factor (NFE2L2), nitric oxide synthase 3 (NOS3), nuclear receptor subfamily 3 group C member 1 (NR3C1), PI3K catalytic subunit alpha (PIK3CA), and silencing information regulator 2 related enzyme 1 (SIRT1) may the core targets of metformin for the treatment of NAFLD.

Conclusion:
Metformin might be a candidate drug for the treatment of NAFLD which exhibits therapeutic effect on NAFLD patients associated with ALT, AST, TG, TC and IR while was not correlated with BMI. HIF1A, NFE2L2, NOS3, NR3C1, PIK3CA, and SIRT1 might be core targets of metformin for the treatment of NAFLD.
Effect of vitamin and mineral supplementation on nutritional status in children with chronic kidney disease: Protocol for a systematic review and meta-analysis
Authors: Mutsuddi Archi , Das Jyoti , Tashrik Symom , Ara Rifat , Hawlader Mohammad Delwer Hossain 
Published: October 2022

Background:
Persistent kidney illness in children and those on dialysis therapy, risk of vitamin and mineral deficiencies due to abnormal renal metabolism, anorexia, inadequate intake, poor gastrointestinal absorption, drug-nutrient interaction, and dialysis-related losses. Adequate nutritional management is essential to achieve and maintain an optimal nutritional status for the usual pattern of growth, sexual and neurocognitive development, metabolic abnormalities, and ultimately reducing the risk of chronic mortality and morbidity in adulthood. The purpose of this paper is to describe a protocol for a systematic review to assess the effects of vitamin and mineral supplementation in children with chronic renal disease.

Methods:
This systematic review protocol is developed according to the Preferred Reporting Item for Systematic Review and Meta-Analysis Protocols (PRISMA-P) as well as the Cochrane group guidelines. Comprehensive searching for all possible relevant works of literature- such as PubMed, Google Scholar, MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Science-Direct, Scopus, Research-Gate, Clinical Trials for all randomized controlled studies, full paper articles, and articles written in English will be considered. The primary outcome of this review will be measuring any changes (such as changes in body mass, BMI, and overall Z-score) in the nutritional status of the children (age < 18 years) with chronic kidney disease following vitamin and mineral supplementations. This review will help better understand the effects of vitamin and mineral supplementation to improve nutritional status in CKD children and will create a guideline to determine the applicability of these interventions in different feasible settings.

Conclusion:
The systematic review protocol has been evaluated and approved by the institutional review board of North South University. Finding will be shared using traditional approaches, including scientific presentations, open-access peer-reviewed platforms.

PROSPERO registered number
CRD42022341339
The 12 weeks, randomized, double-blinded, placebo-controlled human study to evaluate the effectiveness and safety of KGC deer antlers on the growth of children
Authors: Kim Sang Min , Lee Jin Yong , Chang Gyu Tae , Hwangbo Su Min , Lee Sun Haeng 
Published: October 2022

Background:
Cervi parvum cornu is a dried section of the young horns of Cervus nippon Temminck, Cervus elaphus Linnaeus, or Cervus canadensis Erxleben. It is a representative yang-tonifying medicine that warms the viscera and bowels, activates the overall physiological function, and has effects such as tonifying kidney yang, replenishing essence and blood, and strengthening muscles and bones.

Objective:
This clinical study is aimed to evaluate the effectiveness of deer antler extract on child growth.

Methods:
This clinical trial is designed to be conducted on 100 children aged 3 to 12 years for 12 weeks (Trial registration code: KCT0007386). We will evaluate changes in height, height percentile, standard deviation score of height, weight, body mass index, waist circumference, hip circumference, bone age, predicted adult height estimated by bone age, human growth hormone level, insulin-like growth factor-1 (IGF-1) level, IGF-binding protein-3 (IGFBP-3) level, IGF-1/IGFBP-3 ratio, and estradiol level. Additionally, we also will evaluate the adverse events during the study.
Short-term recurrence of reversible cerebral vasoconstriction syndrome
Authors: Kobayashi Naoki , Miyamoto Nobukazu , Wakamori Ryo , Watanabe Kouzou , Hirai Takuya , Hira Kenichiro , Kijima Chikage , Ueno Yuji , Tamura Naoto , Hattori Nobutaka 
Published: October 2022

Rationale:
Reversible cerebral vasoconstriction syndrome is considered a monophasic disease; however, a previous study reported that several patients had recurrent attacks. Herein, we report a rare case of reversible cerebral vasoconstriction syndrome that recurred within a short period at the same cerebral artery position.

Patient concerns:
A 47-year-old female with systemic sclerosis, idiopathic thrombocytopenia, and Sjögren syndrome presented with left limb weakness and headache, with stenosis of the M1 portion in the right middle cerebral artery.

Diagnoses:
Brain imaging revealed no ischemic lesion. Stenosis recovered a few days later. Therefore, we diagnosed reversible cerebral vasoconstriction syndrome. Reversible cerebral vasoconstriction syndrome occurred with steroid treatment used to treat idiopathic thrombocytopenia.

Intervention:
We started treatment with lomerizine, a calcium channel blocker, and hydration on every reversible cerebral vasoconstriction syndrome occurrence.

Outcome:
After starting treatment, her weakness/M1-stenosis improved.

Lessons:
Many drugs induce reversible cerebral vasoconstriction syndrome, including serotonergic antidepressants, glucocorticoids, and tacrolimus. In the present case, reversible cerebral vasoconstriction syndrome may have worsened with steroid administration and recurred within a short period. Magnetic resonance angiography revealed vasoconstriction in each recurrence.
Evaluating the Clinical Impact of a Novel Pediatric Emergency Medicine Curriculum on Asthma Outcomes in Belize
Authors: Kosoko Adeola A. , Khoei Amelia A. , Khose Swapnil , Genisca Alicia E. , Mackey Joy M. 
Published: October 2022

Background
Respiratory-related complaints prompt most pediatric visits to Karl Heusner Memorial Hospital Authority's (KHMHA) Emergency Department (ED) in Belize. We developed and taught a novel pediatric respiratory emergencies module for generalist practitioners there. We assessed the curriculum's clinical impact on pediatric asthma emergency management.

Objective
This study assesses the clinical impact of a pediatric emergency medicine curriculum on management of pediatric asthma emergencies at KHMHA in Belize City, Belize.

Methods
We conducted a randomized chart review of pediatric (aged 2–16 y) visits for asthma-related diagnosis at the KHMHA ED between 2015 and 2018 to assess the training module's clinical impact. Primary outcomes included time to albuterol and steroids. Secondary outcomes included clinical scoring tool (Pediatric Respiratory Assessment Measure [PRAM]) usage, ED length of stay, usage of chest radiography, return visit within 7 days, and hospital admission rates. Kaplan-Meier survival analysis and Cox proportional hazard regression were used.

Results
Two hundred eighty-three pediatric asthma-related diagnoses met our inclusion criteria. The patients treated by trained and untrained physician groups were demographically and clinically similar. The time to albuterol was significantly faster in the trained (intervention) group compared with the untrained (control) physician group when evaluating baseline of the group posttraining (P < 0.05). However, the time to steroids did not reach statistical significance posttraining (P = 0.93). The PRAM score utilization significantly increased among both control group and intervention group. The untrained physician group was more likely to use chest radiography or admit patients. The trained physician group had higher return visit rates within 7 days and shorter ED length of stay, but this did not reach statistical significance.

Conclusions
The curriculum positively impacted clinical outcomes leading to earlier albuterol administration, increased PRAM score use, obtaining less chest radiographs, and decreased admission rates. The timeliness of systemic steroid administration was unaffected.
Pneumatization of the Sphenoidal Sinus May Affect Endonasal Cranial Base Reconstruction
Authors: Ramos Henrique Faria , Pinheiro-Neto Carlos Diogenes , Possatti Lucas Loss 
Published: October 2022

Objective:
The aim of this study is to verify if the length of the nasoseptal flap is sufficient to cover the tuberculum sellae and planum sphenoidale of sphenoidal sinuses with varied degrees of pneumatization

Methods:
Retrospective study of paranasal sinus computed tomography comparing the potential length of the nasoseptal flap and the length of the nasoseptal flap required for reconstruction of transtuberculum and transplanum approaches in conchal, presellar, sellar, incomplete postsellar, and complete postsellar sphenoidal sinuses

Results:
The length of the nasoseptal flap required for reconstruction of transtuberculum and transplanum approaches was directly related to the degree of pneumatization of the sphenoidal sinus. The nasoseptal flap length was adequate to cover the cranial base after transtuberculum approaches of all cases from the conchal, presellar, and sellar groups and the majority of cases from postsellar pneumatization. For transplanum approaches, the nasosseptal flap was sufficient to reconstruct defects in most cases from conchal, pre-sellar, and sellar type sinuses and in 54,9% and 19,2% in incomplete and complete postsellar, respectively.

Conclusions:
In well pneumatized sphenoidal sinus, the nasoseptal flap may not be sufficient to cover the cranial base after transtuberculum and transplanum approaches.
Three-Dimensional Analysis of Vomer Volume and Deviation in Patients With Unilateral Cleft Lip and Alveolus
Authors: Li Si L. , Wu Di , Yin Ning B. , Song Tao , Wang Yong Q. 
Published: October 2022

Since almost all patients with an alveolar cleft have a deviated and thickened vomer bone, the purpose of this study was to investigate the relationship between the vomer shape and the size of the alveolar cleft in patients with unilateral cleft lip and alveolus (CLA). A total of 40 adult patients with unilateral CLA were enrolled, and 40 normal adults without CLA were enrolled as controls. All patients underwent preoperative computed tomography scans and analysis by computer-aided engineering software to obtain the vomer volume (VV), deviated septal angle (DSA), and alveolar cleft volume (ACV). An independent-sample t test or nonparametric test was used to compare the VV and DSA between the unilateral CLA and control groups. The correlation between ACV, VV, and DSA in the unilateral CLA group was assessed using Pearson correlation analysis or Spearman correlation analysis. Vomer volume was significantly higher in patients with CLA (1595.35±48.45 mm3) than in the control group (1043.2±164.976 mm3) (P<0.001), as was DSA (13.099±7.0 versus 3.4398±1.74 degrees) (P<0.001). In the CLA group, VV and DSA were significantly associated with ACV (VV and ACV: r=0.886, P<0.001; DSA and ACV: r=0.543, P<0.001), and VV was significantly correlated with DSA (VV and DSA: r=0.582, P<0.001). In conclusion, the vomer is thicker and more convex in patients with unilateral CLA than in people without, and the vomer angle and degree of volume deviation correlate with alveolar cleft severity.
Racial and Socioeconomic Disparities in Prompt Craniosynostosis Workup and Treatment
Authors: Badiee Ryan K. , Maru Johsias , Yang Stephen C. , Alcon Andre , Rosenbluth Glenn , Pomerantz Jason H. 
Published: October 2022

The purpose of this study was to identify racial and socioeconomic disparities in craniosynostosis evaluation and treatment, from referral to surgery. Patients diagnosed with craniosynostosis between 2012 and 2020 at a single center were identified. Chart review was used to collect demographic variables, age at referral to craniofacial care, age at diagnosis, age at surgery, and surgical technique (open versus limited incision). Multivariable linear and logistic regression models with lasso regularization assessed the independent effect of each variable. A total of 298 patients were included. Medicaid insurance was independently associated with a delay in referral of 83 days [95% confidence interval (CI) 4–161, P=0.04]. After referral, patients were diagnosed a median of 21 days later (interquartile range 7–40), though this was significantly prolonged in patients who were not White (β 23 d, 95% CI 9–38, P=0.002), had coronal synostosis (β 24 d, 95% CI 2–46, P=0.03), and had multiple suture synostosis (β 47 d, 95% CI 27–67, P<0.001). Medicaid insurance was also independently associated with diagnosis over 3 months of age (risk ratio 1.3, 95% CI 1.1–1.4, P=0.002) and undergoing surgery over 1 year of age (risk ratio 3.9, 95% CI 1.1–9.4, P=0.04). In conclusion, Medicaid insurance was associated with a 3-month delay in referral to craniofacial specialists and increased risk of diagnosis over 3 months of age, limiting surgical treatment options in this group. Patients with Medicaid also faced a 4-fold greater risk of delayed surgery, which could result in neurodevelopmental sequelae.
Maxillary and Mandibular Healing After Facial Allotransplantation
Authors: Chang Irene A. , Bassiri Gharb Bahar , Bergfeld Wilma F. , Sardiña Luis Antonio , Djohan Risal S. , Gastman Brian R. , Siemionow Maria Z. , Papay Francis A. , Rampazzo Antonio 
Published: October 2022

Introduction:
Facial transplantation has emerged as a viable option in treating devastating facial injuries.
Despite the high healing rate of Le Fort III and bilateral sagittal split osteotomies (BSSO) in nontransplant patients, few studies have reported assessment of maxillary and mandibular healing in face transplant patients compared with nontransplant patients. The aim of this study was to examine differences in bone healing in our patients.

Patients and Methods:
A retrospective chart review was conducted of facial allotransplantation patients at the Cleveland Clinic from December 2008 to inception. Demographics such as age, date of birth, and sex were recorded. Additional variables included procedures, revisions, reoperations, medications, and bone stability and healing. Computed tomography (CT) images assessed the alignment of skeletal components, bony union quality, and stability of fixation.

Results:
Three patients were included: 2 had Le Fort III segment transplantation, and 1 had transplantation of both a Le Fort III segment and mandibular BSSO. The Le Fort III segment in all patients exhibited mobility and fibrous union at the Le Fort III osteotomy on CT. In contrast, the BSSO healed uneventfully after transplantation and revision surgery, with bony union confirmed by both CT and histology of the fixation area between the donor and recipient mandible bilaterally. No patients with midfacial fibrous union required revision of the nonunion as they were clinically asymptomatic.

Conclusion:
Le Fort osteotomy demonstrates inferior healing in facial transplantation compared with the nontransplant population. In contrast, the successful healing in the mandible is likely owing to the high density of rich cancellous bone.
Language as a mechanism for reasoning about possibilities
Authors: Grigoroglou Myrto , Ganea Patricia A. 
Published: October 2022

The ability to entertain and reflect on possibilities is a crucial component of human reasoning. However, the origin of this reasoning—whether it is language-based or not—is highly debated. We contribute to this debate by investigating the relation between language and thought in the domain of possibility from a developmental perspective. Our investigation focuses on disjunctive syllogism, a specific type of possibility reasoning that has been explored extensively in the developmental literature and has clear linguistic correlates. Seeking links between conceptual and linguistic representations, we review evidence on how children reason by the disjunctive syllogism and how they acquire logical and modal language. We sketch a proposal for how language and thought interact during development.This article is part of the theme issue ‘Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny’.
Imagination as a fundamental function of the hippocampus
Authors: Comrie Alison E. , Frank Loren M. , Kay Kenneth 
Published: October 2022

Imagination is a biological function that is vital to human experience and advanced cognition. Despite this importance, it remains unknown how imagination is realized in the brain. Substantial research focusing on the hippocampus, a brain structure traditionally linked to memory, indicates that firing patterns in spatially tuned neurons can represent previous and upcoming paths in space. This work has generally been interpreted under standard views that the hippocampus implements cognitive abilities primarily related to actual experience, whether in the past (e.g. recollection, consolidation), present (e.g. spatial mapping) or future (e.g. planning). However, relatively recent findings in rodents identify robust patterns of hippocampal firing corresponding to a variety of alternatives to actual experience, in many cases without overt reference to the past, present or future. Given these findings, and others on hippocampal contributions to human imagination, we suggest that a fundamental function of the hippocampus is to generate a wealth of hypothetical experiences and thoughts. Under this view, traditional accounts of hippocampal function in episodic memory and spatial navigation can be understood as particular applications of a more general system for imagination. This view also suggests that the hippocampus contributes to a wider range of cognitive abilities than previously thought.
This article is part of the theme issue ‘Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny’.