bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Validated Grading Scale for Downturned Oral Commisure in Asian Faces
Authors: Lee Jong Hun , Kim Dong Gyu , Park Eun Soo 
Published: May 2021

BACKGROUND
Downturned oral commissures develop gradually with aging. Tools have been developed to evaluate the marionette line or the lower face. However, there is no validated and reproducible tool to evaluate the progress after oral commissure treatment in clinical practice.

OBJECTIVE
The authors aimed to develop a scoring system to evaluate therapeutic interventions for downturned oral commissures and to verify its reliability, reproducibility, and clinical significance.

METHODS AND MATERIALS
In the Scale Development Group, the Delphi method was used to establish a 5-graded scoring system to evaluate oral commissure position. The scoring system was applied to 50 participants. The authors recorded and compared the intrarater agreement, interrater agreement, and significance of the grade-dependent scale.

RESULTS
Delphi analysis of the scoring system verified the grade description adequacy. Intrarater agreement showed almost perfect agreement, and the intraclass correlation coefficient of the interrater agreement had a significantly higher agreement rate. The differences between the clinical grades were significant.

CONCLUSION
The Hugel Downturned Oral Commissure Scale is precise, reproducible, and reflective of the clinical differences for downturned oral commissure. Its novelty lies in the use of specific angles and ratio. This scale has clinical trial potential owing to its standardized and quantitative assessment.
Skin Preparation for Photodynamic Therapy, Chemexfoliation, and Ablative Laser Resurfacing: a Systematic Literature Review
Authors: Cox Surget V. , Zachary Christopher B. , Cohen Joel L. 
Published: May 2021

BACKGROUND
Photodynamic therapy, chemexfoliation, and ablative laser resurfacing are common practices for dermatologists, yet no formal protocols exist regarding preprocedural skin preparation.

OBJECTIVE
To review and summarize the skin preparation protocols for photodynamic therapy, chemexfoliation, and ablative laser resurfacing available in the literature.

METHODS
Data Sources A systematic review of English and non-English articles using the PubMed database was performed. A manual search of bibliographies from relevant articles was also performed to collect additional studies. Study Selection Only articles in the English language with full texts available that pertained to skin preparation for photodynamic therapy, chemexfoliation, and ablative laser resurfacing were included. Data Extraction Article selection was performed by one author, and relevant sources were verified by other authors using predefined inclusion and exclusion criteria.

RESULTS
There is a paucity of scientific research regarding efficacy and safety of dermatologic preprocedural skin preparation agents. Only 2 studies have compared various cleansing agents for these measures. Yet, strong statements regarding the importance of degreasing are published without supportive data.

CONCLUSION
Consensus guidelines for preprocedural protocols are lacking for photodynamic therapy, chemexfoliation, and ablative laser resurfacing. Further studies are warranted to explore the efficacy and safety of various preprocedural cleansing agents.
Efficacy of Checkpoint Inhibitors in Neuroendocrine Neoplasms
Authors: Gile Jennifer J. , Liu Alex J. , McGarrah Patrick W. , Eiring Rachel A. , Hobday Timothy J. , Starr Jason S. , Sonbol Mohamad B. , Halfdanarson Thorvardur R. 
Published: May 2021

Objectives
Checkpoint inhibitors (CPIs) for low- and intermediate-grade neuroendocrine tumors (NETs) have been associated with limited efficacy; recent studies suggest CPIs may represent promising treatment for high-grade neuroendocrine neoplasms (NENs).

Methods
We examined 57 patients with NENs who were treated with CPIs to determine if NETs and neuroendocrine carcinomas (NECs) respond to immunotherapy.

Results
Patients with poorly differentiated NECs on CPI monotherapy had an objective response rate (ORR) of 0% and median progression-free survival (PFS) of 2.1 months (95% confidence interval [CI], 0.5–4.6). Patients with poorly differentiated NECs on dual CPI therapy had an ORR of 13% and PFS of 3.5 months (95% CI, 1.4–not reached [NR]). Patients with poorly differentiated NECs on CPI and cytotoxic therapy had an ORR of 36% with PFS of 4.2 months (95% CI, 1.6–NR). Well-differentiated grade 1 and 2 NETs on CPI monotherapy had an ORR of 25% with PFS NR. Well-differentiated grade 3 NETs had 0% ORR with a PFS of 2.9 months (95% CI, 1.4–4.2) on CPI monotherapy.

Conclusions
Checkpoint inhibitor therapy shows limited activity in patients with NENs. Future studies should identify biomarkers that can help identify patients who are likely responders to immunotherapy.
A Low Total Psoas Muscle Area Index Is a Strong Prognostic Factor in Metastatic Pancreatic Cancer
Authors: Williet Nicolas , Fovet Marion , Maoui Khawla , Chevalier Clément , Maoui Meriem , Le Roy Bertrand , Roblin Xavier , Hag Bachir , Phelip Jean-Marc 
Published: May 2021

Objectives
The total psoas area index (TPI) is an emerging alternative to the total skeletal muscle area index as a prognostic factor but has never been evaluated in metastatic pancreatic cancer (mPC).

Methods
Areas were manually recorded, as previously described. Sex-specific cutoffs were identified by optimum stratification of TPI using log-rank χ2 statistic associated with mortality to define sarcopenic psoas. Progression-free survival (PFS) and overall survival (OS) were the primary objectives. Two period groups were used as internal validation.

Results
During the period study, 79 patients were treated for mPC. The TPI was correlated with PFS (hazards ratio, 0.81; P = 0.02) and OS (hazards ratio, 0.7; P < 0.001). Optimum thresholds defining sarcopenic psoas were less than 5.73 cm2/m2 in men and less than 4.37 cm2/m2 in women. Patients with sarcopenic psoas (62.0%) had shorter median PFS (2.9 months) compared with the others (6.6 months, adjusted P log-rank = 0.01), independently to the intensity of chemotherapy, weight loss, and performance status greater than 1. Similarly, OS was independently shorter in patients with sarcopenic psoas (7.6 months) versus the others (22.2 months, adjusted P < 0.001). These results were confirmed in the 2 period groups.

Conclusions
A low TPI is a stronger independent prognostic factor in mPC.
Comparison Between Lumen-Apposing Metal Stents and Plastic Stents in Endoscopic Ultrasound–Guided Drainage of Pancreatic Fluid Collection
Authors: Lyu Yunxiao , Li Ting , Wang Bin , Cheng Yunxiao , Chen Liang , Zhao Sicong 
Published: May 2021

Objectives
This study aimed to explore efficacy and safety between LAMSs (lumen-apposing metal stents) and DPPSs (double-pigtail plastic stents) in endoscopic ultrasound–guided drainage for pancreatic fluid collections.

Methods
Electronic databases were searched to identify relevant studies published until July 20, 2020.

Results
Fifteen studies were identified in this study. Endoscopic ultrasound–guided drainage with LAMS has higher clinical success (90.01% vs 82.56%) (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.79–3.33; P < 0.00001), less recurrence (OR, 0.44; 95% CI, 0.29–0.68; P = 0.0002), and fewer additional interventions (OR, 0.34; 95% CI, 0.211–0.55; P < 0.001). There was no significant difference between LAMS and DPPS in technical success (97.45% vs 97.38%) (OR, 0.92; 95% CI, 0.50–1.70; P = 0.80), adverse events (OR, 0.92; 95% CI, 0.41–2.09; P = 0.84), stent-related adverse events (OR, 0.78; 95% CI, 0.39–1.54; P = 0.47), and bleeding (OR, 1.47; 95% CI, 0.57–3.28; P = 0.42). Lumen-apposing metal stents have slightly more perforations (OR, 7.10; 95% CI, 1.22–41.30; P = 0.03) in studies of walled-off necrosis.

Conclusions
Lumen-apposing metal stents have the advantage of higher clinical success, less recurrence, and fewer additional interventions. However, LAMS may increase perforation for walled-off necrosis.
Long Noncoding RNA CERS6-AS1 Accelerates the Proliferation and Migration of Pancreatic Cancer Cells by Sequestering MicroRNA-15a-5p and MicroRNA-6838-5p and Modulating HMGA1
Authors: Shen Rongxi , Wang Xinbo , Wang Sizhen , Zhu Daojun , Li Min 
Published: May 2021

Objectives
As one of the most aggressive human tumors, pancreatic cancer (PC) is accompanied by poor treatment and prognosis. Although emerging evidence has highlighted the importance of long noncoding RNAs in multiple cancers, the specific regulatory roles mostly remain obscure. Our aim was to disclose the role of CERS6 antisense RNA 1 (CERS6-AS1) in PC.

Methods
Quantitative real-time polymerase chain reaction analysis was used to examine the expression of CERS6-AS1 in PC cell lines. Western blot analysis was used to assess the protein levels of high-mobility group AT-hook 1 (HMGA1). Colony formation, 5-ethynyl-20-deoxyuridine, transwell, and wound healing assays were performed to detect the functions of CERS6-AS1 on PC development. In addition, RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were implemented to delve into the regulatory mechanism of CERS6-AS1 in PC.

Results
CERS6-AS1 was significantly upregulated in PC. CERS6-AS1 silence obviously inhibited cell proliferation and migration in PC. Furthermore, CERS6-AS1 sponged microRNA-15a-5p (miR-15a-5p) and microRNA-6838-5p (miR-6838-5p) to regulate HMGA1. Moreover, rescue assays verified that CERS6-AS1 was involved in cell proliferation and migration in PC via targeting miR-15a-5p/miR-6838-5p/HMGA1 axis.

Conclusions
CERS6-AS1 enhanced HMGA1 expression to contribute to the progression of PC by sequestering miR-15a-5p and miR-6838-5p.
Does the Initiation of Fluoxetine Postacute Stroke Result in Improved Functional Recovery?
Authors: Knox Molly G. , Demaerschalk Bart M. , Alcott Sally B. , Marks Lisa A. , Wingerchuk Dean M. , O’Carroll Cumara B. 
Published: May 2021

Background:
Stroke is a leading cause of disability worldwide. Selective serotonin reuptake inhibitors are often prescribed following stroke due to high rates of depression. Interest in selective serotonin reuptake inhibitor use for poststroke motor and functional recovery was generated after the publication of the Fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011, which showed improved motor recovery in ischemic stroke patients with moderate to severe motor deficits. The objective of this study was to critically assess current evidence regarding the use of fluoxetine compared with placebo for poststroke functional recovery.

Methods:
The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario and question, literature search, critical appraisal, results, evidence summary, commentary, and clinical bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, clinical epidemiologists, and content experts in the field of cerebrovascular neurology and physical medicine and rehabilitation.

Results:
A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the functional outcomes of subjects poststroke receiving fluoxetine versus placebo. There was no significant difference in functional outcome measured by the Modified Rankin Scale between the 2 groups. Prespecified secondary analysis showed significantly decreased rates of depression in the fluoxetine group, but significantly increased rates of bone fracture.

Conclusion:
Among patients with stroke, early initiation of fluoxetine did not result in improved functional recovery. Lower rates of depression were observed in the fluoxetine-treated group; however these patients experienced higher rates of bone fracture.
Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid
Authors: Smith Kelsey M. , Britton Jeffrey W. , Hocker Sara E. , Toledano Michel 
Published: May 2021

Background:
Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA.

Methods:
Charts of adult patients with SE from St. Mary’s Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic.

Results:
There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P<0.001). Hyperammonemia was identified in 32 and associated with younger age, being in a non-neurological intensive care unit, and liver disease, but was not statistically associated with VPA. Only one patient had valproate-induced hyperammonemic encephalopathy; however, many patients received treatment for hyperammonemia such as lactulose, levocarnitine, or VPA dose reductions.

Conclusions:
This study demonstrated variability in ammonia testing and management changes in SE but does not support the routine monitoring of ammonia levels and showed that hyperammonemic encephalopathy was rare in this clinical setting.
Investigation of the Relationship between Delta Inflammatory Markers and Prognosis in Head and Neck Squamous Cell Carcinoma
Authors: Khaymovich Julian , Ko Andrew , Wong Amanda , Zhu Daniel , Gigante Christian , Garikapati Srilakshmi , Jeng Ginnie , Van Der Elst Sarah , Rong Charles , Tham Tristan 
Published: May 2021

AbstractPurposeInflammatory markers, such as Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), have been shown to hold significant prognostic value in the context of head and neck cancer (HNC). Recently, delta inflammatory markers, the difference between pre and post- treatment inflammatory marker ratios, have been suggested as potentially significant values in predicting cancer prognosis. Our objective was to evaluate the prognostic utility of delta LMR, NLR, and PLR in head and neck squamous cell carcinoma (HNSCC).MethodsRetrospective cohort study in a tertiary academic hospital setting. Patients diagnosed with HNSCC in the oral cavity, larynx, and oropharynx treated with curative intent treatment were included. The variables collected were age, sex, BMI, alcohol/tobacco exposure, performance scores, ACE-27, tumor characteristics, adjuvant treatment, ECOG score, and lab values. Overall Survival (OS) and Event-Free Survival (EFS) were chosen as endpoints. OS was defined as time from date of treatment to date of last follow-up or death from any cause, and EFS was defined as the start of treatment to any progression, recurrence, or death from any cause. Univariate and multivariate analyses were performed on the primary endpoints.ResultsA total of 89 patients were included from 2010 to 2017. In multivariate analysis, EFS was found to be significantly associated with an N stage of 3 (p=0.0005) and delta LMR > -1.48 (p=0.0241). No significant relationships were uncovered with OS in multivariate analysis.ConclusionA higher delta LMR value (>-1.48) was associated with poorer EFS, but was not associated with OS.
Retrospective Analysis of the Utility of Genetic Testing in Predicting Drug Response in Chronic Pain
Authors: Gupta Gaurav , Cpl Emilie Paquet-Proulx , Lalonde Sasha , Burton Kira , LCol Markus Besemann , Amir Minerbi 
Published: May 2021

AbstractIntroductionChronic pain is often unrecognized and/or undertreated, and as a result has significant impact on functional abilities, quality of life, societal participation and health care utilization. Medications remain a mainstay of treatment, but selection for any given patient remains a challenge when trying to predict efficacy and/or side effects. There is interest to see whether genetic analysis of how a given drug is processed for a patient can help with rational drug choices. This appears to have some early support in cardiac, psychiatric and acute pain studies. We studied whether genetic analysis of drug processing using the Pillcheck program could have helped in choosing the appropriate medications in a cohort of patients suffering from chronic pain. To our knowledge this type of study has not been completed in this environment and/or patient population.MethodsWe retrospectively studied a 31 patient cohort seen in the Canadian Forces Health Services Unit (Ottawa) Physiatry clinic. All patients suffered from a diagnosed chronic pain condition, completed the Pillcheck genetic drug processing analysis and filled-in questionnaires looking at efficacy and side effects of the drugs. We analyzed the correlation between the Pillcheck predictions and participants’ self-reported treatment efficacy and tolerability. The goal was to explore the clinical utility of Pillcheck results in guiding prescriptions for chronic pain patients.Results31 patients returned completed questionnaires and had samples taken. Forty eight percent of the participants were actively treated with one of the study pain medications, and 84% had been taking at least one of these medications and discontinued. Pillcheck scores did not correlate with self-reported efficacy of any of the medications, nor did it correlate with self-reported side effects. Furthermore, active medications were more likely to receive a score indicating caution should be exerted, than were medications which had been discontinued.DiscussionIn a small cohort of pain patients with comorbid psychiatric disorders, genetic profiling using Pillcheck did not seem to correlate with reported benefit or side effect profile of commonly prescribed pain medications. Furthermore, discontinued medications were no more likely to be marked as warranting caution than did actively used medications.ConclusionRetrospectively using pharmacogenetics to guide medication selection in Canadian Forces members with chronic pain did not correlate with response or side effects. A larger prospective controlled study, measuring numerous clinical and non- clinical outcomes would be worthwhile in the future before widespread adoption for patients living with chronic pain.
COVID-19 and acute kidney injury in German hospitals 2020
Authors: Walendy Victor , Girndt Matthias , Greinert Daniel 
Published: May 2021

AbstractIntroductionThe SARS-CoV-2 pandemic is a major challenge for patients, healthcare professionals, and populations worldwide. While initial reporting focused mainly on lung involvement, the ongoing pandemic showed that multiple organs can be involved, and prognosis is largely influenced by multi-organ involvement. Our aim was to obtain nationwide retrospective population-based data on hospitalizations with COVID-19 and AKI.Materials & MethodsWe performed a query of G-DRG data for the year 2020 via the Institute for the hospital remuneration system (Institut für das Entgeltsystem im Krankenhaus GmbH, InEK) data portal and therefore included hospitalizations with a secondary diagnosis of RT-PCR proven COVID-19 infection, aged over 15 years. We included hospitalizations with acute kidney injury (AKI) stages 1 to 3. Age-specific and age-standardized hospitalization and in-hospital mortality rates (ASR) per 100.000 person years were calculated, with the German population of 2011 as the standard.ResultsIn 2020, there were 16.776.845 hospitalizations in German hospitals. We detected 154.170 hospitalizations with RT-PCR proven COVID-19 diagnosis. The age-standardized hospitalization rate for COVID-19 in Germany was 232,8 per 100.000 person years (95% CI 231,6-233,9). The highest proportion of hospitalizations associated with COVID-19 were in the age group over 80 years. AKI was diagnosed in 16.773 (10,9%) of the hospitalizations with COVID-19. The relative risk of AKI for males was 1,49 (95%CI 1,44-1,53) compared to females. Renal replacement therapy (RRT) was performed in 3.443 hospitalizations, 20,5% of the hospitalizations with AKI. For all hospitalizations with COVID-19, the in-hospital mortality amounted to 19,7% (n= 30.300). The relative risk for in-hospital mortality was 3,87 (95%CI 3,80-3,94) when AKI occurred. The age-standardized hospitalization rates for COVID-19 took a bimodal course during the observation period. The first peak occurred in April (ASR 23,95 per 100.000 person years (95%CI 23,58-24,33)), hospitalizations peaked again in November 2020 (72,82 per 100.000 person years (95%CI 72,17-73,48)). The standardized rate ratios (SRR) for AKI and AKI-related mortality with the overall ASR for COVID-19 hospitalizations in the denominator, decreased throughout the observation period and remained lower in autumn than they were in spring. In contrast to all COVID-19 hospitalizations, the SRR for overall mortality in COVID-19 hospitalizations diverged from hospitalizations with AKI in autumn 2020.DiscussionOur study for the first time provides nationwide data on COVID-19 related hospitalizations and acute kidney injury in Germany in 2020. AKI was a relevant complication and associated with high mortality. We observed a less pronounced increase in the ASR for AKI-related mortality during autumn 2020. The proportion of AKI-related mortality in comparison to the overall mortality decreased throughout the course of the pandemic.
Motor Function and White Matter Connectivity in Children Treated with Therapeutic Hypothermia for Neonatal Encephalopathy
Authors: Spencer Arthur P.C. , Brooks Jonathan C.W. , Masuda Naoki , Byrne Hollie , Lee-Kelland Richard , Jary Sally , Thoresen Marianne , Goodfellow Marc , Cowan Frances M. , Chakkarapani Ela 
Published: May 2021

AbstractTherapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in school-age children treated with therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched controls. Analysis of tract-level microstructure (33 cases, 36 controls) revealed correlations between total motor scores and fractional anisotropy, in cases but not controls, in the anterior thalamic radiation bilaterally, the inferior fronto-occipital fasciculus bilaterally and both the hippocampal and cingulate gyrus parts of the left cingulum. Analysis of structural brain networks (22 cases, 32 controls), in which edges were determined by probabilistic tractography and weighted by fractional anisotropy, revealed correlations between total motor scores and several whole-brain network metrics in cases but not controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores as well as for balance and manual dexterity domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. These findings demonstrate an association between impaired motor function and brain organisation in case children.