bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critically Appraising the Quality of Reporting of American College of Surgeons TQIP Studies in the Era of Large Data Research
Authors: Gebran Anthony , Bejjani Antoine , Badin Daniel , Sabbagh Hadi , Mahmoud Tala , El Moheb Mohamad , Nederpelt Charlie J , Joseph Bellal , Nathens Avery , Kaafarani Haytham MA 
Published: June 2022

BACKGROUND:
The American College of Surgeons-Trauma Quality Improvement Program (ACS-TQIP) database is one of the most widely used databases for trauma research. We aimed to critically appraise the quality of the methodological reporting of ACS-TQIP studies.

STUDY DESIGN:
The ACS-TQIP bibliography was queried for all studies published between January 2018 and January 2021. The quality of data reporting was assessed using the Strengthening the Reporting of Observational studies in Epidemiology-Reporting of Studies Conducted Using Observational Routinely Collected Health Data (STROBE-RECORD) statement and the JAMA Surgery checklist. Three items from each tool were not applicable and thus excluded. The quality of reporting was compared between high- and low-impact factor (IF) journals (cutoff for high IF is >90th percentile of all surgical journals).

RESULTS:
A total of 118 eligible studies were included; 12 (10%) were published in high-IF journals. The median (interquartile range) number of criteria fulfilled was 5 (4–6) for the STROBE-RECORD statement (of 10 items) and 5 (5–6) for the JAMA Surgery checklist (of 7 items). Specifically, 73% of studies did not describe the patient population selection process, 61% did not address data cleaning or the implications of missing values, and 76% did not properly state inclusion/exclusion criteria and/or outcome variables. Studies published in high-IF journals had remarkably higher quality of reporting than those in low-IF journals.

CONCLUSION:
The methodological reporting quality of ACS-TQIP studies remains suboptimal. Future efforts should focus on improving adherence to standard reporting guidelines to mitigate potential bias and improve the reproducibility of published studies.
Does Adding a Measure of Social Vulnerability to a Surgical Risk Calculator Improve Its Performance?
Authors: Dyas Adam R , Carmichael Heather , Bronsert Michael R , Henderson William G , Madsen Helen J , Colborn Kathryn L , Velopulos Catherine G , Meguid Robert A 
Published: June 2022

BACKGROUND:
Emerging literature suggests that measures of social vulnerability should be incorporated into surgical risk calculators. The Social Vulnerability Index (SVI) is a measure designed by the CDC that encompasses 15 socioeconomic and demographic variables at the census tract level. We examined whether adding the SVI into a parsimonious surgical risk calculator would improve model performance.

STUDY DESIGN:
The eight-variable Surgical Risk Preoperative Assessment System (SURPAS), developed using the entire American College of Surgeons (ACS) NSQIP database, was applied to local ACS-NSQIP data from 2012 to 2018 to predict 12 postoperative outcomes. Patient addresses were geocoded and used to estimate the SVI, which was then added to the model as a ninth predictor variable. Brier scores and c-indices were compared for the models with and without the SVI.

RESULTS:
The analysis included 31,222 patients from five hospitals. Brier scores were identical for eight outcomes and improved by only one to two points in the fourth decimal place for four outcomes with addition of the SVI. Similarly, c-indices were not significantly different (p values ranged from 0.15 to 0.96). Of note, the SVI was associated with most of the eight SURPAS predictor variables, suggesting that SURPAS may already indirectly capture this important risk factor.

CONCLUSION:
The eight-variable SURPAS prediction model was not significantly improved by adding the SVI, showing that this parsimonious tool functions well without including a measure of social vulnerability.
Effect of Lactate Export Inhibition on Anaplastic Thyroid Cancer Growth and Metabolism
Authors: Zhao Bixiao , Aggarwal Abha , Im Soo-Yeon , Viswanathan Keya , Landa Iñigo , Nehs Matthew A 
Published: June 2022

BACKGROUND:
Anaplastic thyroid cancer (ATC) is an aggressive malignancy without effective treatments. ATC cells demonstrate upregulated glycolysis (Warburg effect), generating lactate that is subsequently exported by monocarboxylate transporter 4 (MCT4). This study aims to determine whether MCT4 inhibition can suppress ATC growth.

STUDY DESIGN:
ATC cell lines 8505C, JL30, and TCO1 were grown in low (3 mmol/L; LG) or high (25 mmol/L; HG) glucose medium containing the lactate shuttle inhibitors acriflavine (10–25 μmol/L; ACF), syrosingopine (100 µmol/L; SYR), or AZD3965 (20 µmol/L; AZD). Lactate level and cell proliferation were measured with standard assays. Seahorse analysis was performed to determine glycolytic response.

RESULTS:
Compared with HG, addition of ACF to LG decreased lactate secretion for both 8505C (p < 10-5) and JL30 (p < 10-4) cells, whereas proliferation was also reduced (p < 10-4 and 10-5, respectively). During Seahorse analysis, addition of oligomycin increased acidification by 84 mpH/min in HG vs 10 mpH/min in LG containing ACF (p < 10-5). Treatment with LG and SYR drastically diminished 8505C and TCO1 growth vs HG (p < 0.01 for both). LG and AZD treatment also led to reduced proliferation in tested cell lines (p ≤ 0.01 for all) that was further decreased by addition of ACF (p < 10-4 vs HG, p ≤ 0.01 vs LG and AZD).

CONCLUSION:
Inhibition of lactate shuttles significantly reduced proliferation and glycolytic capacity of ATC cells in a low-glucose environment. Targeting suppression of glycolytic and lactate processing pathways may represent an effective treatment strategy for ATC.
Contemporary Matched-Cohort Comparison of Surgical Approach to Inguinal Hernia Repair: Are Minimally Invasive Approaches Associated with Higher Rates of Recurrence?
Authors: Tonelli Celsa M , Lorenzo Isabela , Bunn Corinne , Kulshrestha Sujay , Abdelsattar Zaid M , Cohn Tyler , Luchette Frederick A , Baker Marshall S 
Published: June 2022

BACKGROUND:
Current studies evaluating outcomes for open, laparoscopic, and robotic inguinal hernia repair, in general, include small numbers of robotic cases and are not powered to allow a direct comparison of the 3 approaches to repair.

STUDY DESIGN:
We queried the Veterans Affairs Surgical Quality Improvement Program Database to identify patients undergoing initial elective inguinal hernia repair between 2013 and 2017. Propensity score matching and multivariable logistic regression were used to make risk-adjusted assessments of association between surgical approach and outcome.

RESULTS:
A total of 39,358 patients underwent initial elective inguinal hernia repair; 32,881 (84%) underwent an open approach, 6,135 (16%) underwent a laparoscopic approach, and 342 (1%) underwent a robotic-assisted approach. Two hundred sixty-six (1%) patients had a recurrent repair performed during follow-up. On univariate comparison, patients undergoing a robotic-assisted approach had longer operative times for unilateral repair than those undergoing either an open or laparoscopic (73 ± 31 vs 74 ± 29 vs 107 ± 41 minutes; p < 0.001) approach. On multivariable logistic regression, patients with a higher BMI had an increased adjusted risk of a postoperative complication, but there was no association between surgical approach and complication rate. Three hundred forty-two patients undergoing robotic repair were 1:3:3 propensity score matched to 1,026 patients undergoing laparoscopic and 1,026 undergoing open repair. On comparison of matched cohorts, there were no statistical differences between approaches regarding recurrence (0.6% vs 0.8% vs 0.6%, p > 0.05) or complication rate (0.6% vs 1.2% vs 1.2%, p > 0.05).

CONCLUSIONS:
In patients undergoing initial elective inguinal hernia repair, rates of hernia recurrence are low independent of surgical approach. Both robotic and laparoscopic approaches demonstrate rates of early postoperative morbidity and recurrence similar to those for the open approach. The robotic approach is associated with longer operative time than either laparoscopic or open repair.
Are Residents Able to Perform a Laparoscopic Cholecystectomy with Acceptable Outcomes When the Attending Is Not Scrubbed?
Authors: Tonelli Celsa M , Lorenzo Isabela , Bunn Corinne , Kulshrestha Sujay , Cohn Tyler , Abdelsattar Zaid , Luchette Frederick A , Baker Marshall S 
Published: June 2022

BACKGROUND:
Recent socioeconomic pressures in healthcare and work hour resections have limited opportunities for resident autonomy and independent decision-making. We sought to evaluate whether contemporary senior residents are being given the opportunity to operate independently and whether patient outcomes are affected when the attending is not directly involved in an operation.

STUDY DESIGN:
The VA Surgical Quality Improvement Program (VASQIP) Database was queried to identify patients undergoing elective laparoscopic cholecystectomy between 2004 and 2019. Cases were categorized as “attending” or “resident” depending on whether the attending surgeon was scrubbed. Cohorts were 1:1 propensity score–matched (PSM) for demographics, comorbidities, and facility case-mix. Clinical outcomes for matched cohorts were compared by standard methods.

RESULTS:
There were 23,831 records for patients who underwent laparoscopic cholecystectomy; 20,568 (86%) performed with the attending scrubbed, and 3,263 (14%) without the attending scrubbed. Over time there was a significant decrease in the proportion of cases without the attending scrubbed, 18% in 2004–2009 to 13% in 2015–2019 (p < 0.001). On PSM, 3,263 patients undergoing laparoscopic cholecystectomy by the residents without the attending scrubbed were successfully matched (1:1) to cases with the attending scrubbed. On comparison of matched cohorts, procedures performed without the attending scrubbed were statistically longer (102 vs 98 minutes, p = 0.001) but with no difference in rates of postoperative complications (5% vs 5%, p = 0.9).

CONCLUSION:
In comparison with cases done with more direct attending involvement, residents perform laparoscopic cholecystectomies efficiently without increased complications. Over time, attendings are more frequently scrubbed for the operation.
Emergency department care transition barriers: a qualitative study of care partners of older adults with cognitive impairment
Authors: Gettel Cameron J. , Serina Peter T. , Uzamere Ivie , Hernandez-Bigos Kizzy , Venkatesh Arjun K. , Cohen Andrew B. , Monin Joan K. , Feder Shelli L. , Fried Terri R. , Hwang Ula 
Published: June 2022

AbstractINTRODUCTIONAfter emergency department (ED) discharge, persons living with cognitive impairment (PLWCI) and their care partners are particularly at risk for adverse outcomes. We sought to identify the barriers experienced by care partners of PLWCI during ED discharge care transitions.METHODSWe conducted a qualitative study of 25 care partners of PLWCI discharged from four EDs. We used the validated 4AT and care partner-completed AD8 screening tools, respectively, to exclude care partners of older adults with concern for delirium and include care partners of older adults with cognitive impairment. We conducted recorded, semi-structured interviews using a standardized guide, and two team members coded and analyzed all professional transcriptions to identify emerging themes and representative quotations.RESULTSCare partners’ mean age was 56.7 years, 80% were female, and 24% identified as African American. We identified four major barriers regarding ED discharge care transitions among care partners of PLWCI: 1) unique care considerations while in the ED setting impact the perceived success of the care transition, 2) poor communication and lack of care partner engagement was a commonplace during the ED discharge process, 3) care partners experienced challenges and additional responsibilities when aiding during acute illness and recovery phases, and 4) navigating the health care system after an ED encounter was perceived as difficult by care partners.DISCUSSIONOur findings demonstrate critical barriers faced during ED discharge care transitions among care partners of PLWCI. Findings from this work may inform the development of novel care partner-reported outcome measures as well as ED discharge care transition interventions targeting care partners.
Assessment of urinary exosome NHE3 as a biomarker of acute kidney injury
Authors: Yu Yanting , Ren Zhiyun , Xie Anni , Jia Yutao , Xue Ying , Wang Ping , Ji Daxi , Wang Xiaoyan 
Published: June 2022

AbstractThe diagnosis of acute kidney injury (AKI) traditionally depends on the serum creatinine (SCr) and urine output, which lack sufficient sensitivity and specificity. Urinary exosome as a biomarker has unique advantages. To assessed whether urinary exosome Na+/H+ exchanger isoform 3 (NHE3) protein as a nonivasive diagnostic biomarker of AKI, we constructed 4 AKI rat models: cisplatin (7.5mg/kg) injection intraperitoneally (IP), furosemide (20mg/kg, IP) with low NaCl (0.03%) diet, low NaCl (0.03%) diet with candesartan (1mg/kg, IP) and bilaterally ischemia and reperfusion(I/R) injury for 40 minutes. Besides, we assessed 6 sepsis associated AKI patients and 6 healthy volunteers. Urinary exosomes were extracted by ultra-centrifugation and NHE3 protein abundance was tested by immunoblotting in all AKI rats and human subjects. The isolated cup-shape particles with an average diameter of 70nm and enrichment in CD63 were identified as exosomes. NHE3 abundance was 6 times higher in exosome than in original urine. In cisplatin induced AKI rats, urinary exosome NHE3 was increased at day 2, 1 day earlier than the increases of serum creatinine creatinine (SCr) and blood urea nitrogen (BUN). In additional rats, urinary exosome NHE3 decreased along with the decline of SCr after EPO pretreatment. In volume depletion AKI induced by furosemide injection with low NaCl diet, urinary exosome NHE3 expression was higher than control. In low NaCl diet with candesartan related AKI, urinary exosome NHE3 was elevated at day 5, 2 days earlier than SCr. In I/R injury AKI, urinary exosome NHE3 was also raised compared with control. In humans, the urinary exosome NHE3 level was also elevated in sepsis associated AKI patients in comparison with the healthy volunteers. Then urinary exosome NHE3 protein may be used as a noninvasive diagnostic biomarker of AKI.Impact StatementThe high non-recognition acute kidney injury (AKI) is due to lacking of alarming symptoms or specific early biomarkers. Urinary exosome as a biomarker has unique advantages. In our study, we detected urinary exosome NHE3 protein abundance in 4 different cause of AKI rat model. Urinary exosome NHE3 was increased in all 4 AKI, and even elevated earlier than SCr in some cases. Another novel point was we established a new AKI model of low NaCl diet with candesartan injection, which was common in patients with hypertension or proteinuria clinically. The detailed methods and mechanisms of this new AKI model were presented in another article being submitted. Third, we are not limited to animals, but also selected sepsis associated AKI patients to study. The conclusion that urinary exosome NHE3 may be used as a diagnosis biomarker of AKI has important clinical application value.
Acute sleep deprivation induces synaptic remodeling at the soleus muscle neuromuscular junction in rats
Authors: Sharma Binney , Roy Avishek , Sengupta Trina , Vishwakarma Lal Chandra , Singh Anuraag , Netam Ritesh , Nag Tapas Chandra , Akhtar Nasreen , Mallick Hruda Nanda 
Published: June 2022

AbstractSleep is important for cognitive and physical performance. Sleep deprivation not only affects neural functions but also results in muscular fatigue. A good night’s sleep reverses these functional derangements caused by sleep deprivation. The role of sleep in brain function has been extensively studied. However, its role in neuromuscular junction or skeletal muscle morphology is sparsely addressed although skeletal muscle atonia and suspended thermoregulation during rapid eye movement sleep possibly provides a conducive environment for the muscle to rest and repair; somewhat similar to slow-wave sleep for synaptic downscaling. In the present study, we have investigated the effect of 24 h sleep deprivation on the neuromuscular junction morphology and neurochemistry using electron microscopy and immunohistochemistry in the rat soleus muscle. Acute sleep deprivation altered synaptic ultra-structure viz. mitochondria, synaptic vesicle, synaptic proteins, basal lamina, and junctional folds needed for neuromuscular transmission. Further acute sleep deprivation showed the depletion of the neurotransmitter acetylcholine and the overactivity of its degrading enzyme acetylcholine esterase at the neuromuscular junction. The impact of sleep deprivation on synaptic homeostasis in the brain has been extensively reported recently. The present evidence from our studies shows new information on the role of sleep on neuromuscular junction homeostasis and its functioning.Statement of significanceSleep causes synaptic downscaling in the brain, and allows the brain to carry out various housekeeping functions. Here we have reported that the function of the sleep-wake cycle on the synaptic homeostasis extends beyond the brain. Acute sleep deprivation caused significant alteration at ultra and macrostructure of antigravity muscle and the neuromuscular junction along with adaptation to new fiber type in rats. These morpho-functional changes were well correlated with the biochemical assessment of the acetylcholine at the neuromuscular junction. These changes were partially recovered when the rats were allowed to recover from sleep deprivation. The findings suggest a new avenue for a sleep study; employing the neuromuscular junction for exploring the effect of sleep at energy and synaptic homeostasis levels.
Allele-specific gene regulation, phenotypes, and therapeutic vulnerabilities in estrogen receptor alpha mutant endometrial cancer
Authors: Blanchard Zannel , Rush Craig M. , Arnesen Spencer , Vahrenkamp Jeffery M. , Rodriguez Adriana C. , Jarboe Elke A. , Brown Callie , Chang Matthew E. K. , Flory Mark R. , Mohammed Hisham , Modzelewska Katarzyna , Lum David H. , Gertz Jason 
Published: June 2022

ABSTRACTActivating estrogen receptor alpha (ER) mutations are present in primary endometrial and metastatic breast cancers, promoting estrogen-independent activation of the receptor. Functional characterizations in breast cancer have established unique molecular and phenotypic consequences of the receptor, yet the impact of ER mutations in endometrial cancer has not been fully explored. In this study, we used CRISPR-Cas9 to model the clinically prevalent ER-Y537S mutation and compared results to ER-D538G to discover allele-specific differences between ER mutations in endometrial cancer. We found that constitutive activity of mutant ER resulted in changes in the expression of thousands of genes, stemming from combined alterations to ER binding and chromatin accessibility. The unique gene expression programs resulted in ER mutant cells developing increased cancer associated phenotypes, including migration, invasion, anchorage independent growth, and growthin vivo. To uncover potential treatment strategies, we identified ER associated proteins via Rapid Immunoprecipitation and Mass Spectrometry of Endogenous Proteins (RIME) and interrogated two candidates, CDK9 and NCOA3. Inhibition of these regulatory proteins resulted in decreased growth and migration, representing potential novel treatment strategies for ER mutant endometrial cancer.ImplicationsThis study provides insight into mutant ER activity in endometrial cancer and identifies potential therapies for women with ER mutant endometrial cancer.STATEMENT OF SIGNIFICANCEActivating estrogen receptor alpha (ER) mutations promote ligand-independent activity of the receptor. This study evaluates ER-Y537S and ER-D538G mutations in primary endometrial cancer, revealing their effects on gene regulation and cancer-associated phenotypes. By identifying ER associated proteins, we also uncover potential novel treatments for women with ER mutant endometrial cancer.
Assembly of multi-subunit fusion proteins into the RNA-targeting type III-D CRISPR-Cas effector complex
Authors: Schwartz Evan A. , Bravo Jack P.K. , Macias Luis A. , McCafferty Caitlyn L. , Dangerfield Tyler L. , Walker Jada N. , Brodbelt Jennifer S. , Fineran Peter C. , Fagerlund Robert D. , Taylor David W. 
Published: June 2022

AbstractCRISPR (Clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems are a type of adaptive immune response in bacteria and archaea that utilize crRNA (CRISPR RNA)-guided effector complexes to target complementary RNA or DNA for destruction. The prototypical type III-A and III-B CRISPR-Cas systems utilize multi-subunit effector complexes composed of individual proteins to cleave ssRNA targets at 6-nt intervals, as well as non-specifically degrading ssDNA and activating cyclic oligoadenylate (cOA) synthesis. Recent studies have shown that type III systems can contain subunit fusions yet maintain canonical type III RNA-targeting capabilities. To understand how a multi-subunit fusion effector functions, we determine structures of a variant type III-D effector and biochemically characterize how it cleaves RNA targets. These findings provide insights into how multi-subunit fusion proteins are tethered together and assemble into an active and programmable RNA endonuclease, how the effector utilizes a novel mechanism for target RNA seeding, and the structural basis for the evolution of type III effector complexes. Furthermore, our results provide a blueprint for fusing subunits in class 1 effectors for design of user-defined effector complexes with disparate activities.Important noteWhile this manuscript was in preparation, a manuscript describing the structure of the type III-E effector was published1. We reference these important findings; however, a careful comparison of the structures will follow once the coordinates have been released by the PDB.
Structural analysis of SALL4 zinc-finger domain reveals a link between AT-rich DNA binding and Okihiro syndrome
Authors: Watson James A. , Pantier Raphaël , Jayachandran Uma , Chhatbar Kashyap , Alexander-Howden Beatrice , Kruusvee Valdeko , Prendecki Michal , Bird Adrian , Cook Atlanta G. 
Published: June 2022

AbstractSpalt-like 4 (SALL4) maintains vertebrate embryonic stem cell identity and is required for the development of multiple organs, including limbs. Mutations in SALL4 are associated with Okihiro syndrome and SALL4 is also a known target of thalidomide. SALL4 protein has a distinct preference for AT-rich sequences, recognised by a pair of zinc fingers at the C-terminus. However, unlike many characterised zinc finger proteins, SALL4 shows flexible recognition with many different combinations of AT-rich sequences being targeted. SALL4 interacts with the NuRD corepressor complex which potentially mediates repression of AT-rich genes. We present a crystal structure of SALL4 C-terminal zinc fingers with an AT-rich DNA sequence, which shows that SALL4 uses small hydrophobic and polar side chains to provide flexible recognition in the major groove. Missense mutations reported in patients that lie within the C-terminal zinc fingers reduced overall binding to DNA but not the preference for AT-rich sequences. Furthermore, these mutations altered association of SALL4 with AT-rich genomic sites, providing evidence that these mutations are likely pathogenic.