bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Botulinum Toxin in Raynaud Phenomenon
Authors: Lawson Olivia , Sisti Andrea , Konofaos Petros 
Published: July 2023

Background
Raynaud phenomenon (RP) is a vasospastic condition of the digits that can be primary or secondary to systemic disease. Symptoms are triggered by cold or stress and can cause pain and skin color changes. The chronic ischemia may lead to necrosis, ulceration, and amputation. There are no Food and Drug Administration–approved treatments and cases refractory to pharmacologic and surgical treatments are difficult to control. Local botulinum toxin injections have been increasingly used in the treatment of Raynaud disease and have shown promising results.

Aim of the study
To examine the outcomes, techniques, and complications of botulinum toxin use for the treatment of Raynaud disease.

Methods
The PubMed database was queried using “botulinum toxin” AND “Raynaud phenomenon” as title key words. Preferred reporting items for systematic reviews and meta-analysis criteria were used. Additional articles were selected while reviewing the references of the articles from PubMed. No time restrictions were followed. Articles of all languages were included. Articles were analyzed for study type, demographics, diagnosis/inclusion criteria, treatment methods, outcome measures, length of follow-up, results, and complications. A positive outcome was defined as subjective improvement in symptoms and/or improvement in the outcome measures. A poor outcome was defined as harm done to the patient by the injection that would not have occurred otherwise.

Results
Forty-two clinical studies describing the use of botulinum toxin for Raynaud's phenomenon were found. A total of 425 patients with primary or secondary Raynaud's were treated, with ages ranging from 14 to 91 years. There were 342 women and 81 men, with a female-to-male ratio of 38:9. Outcomes were positive in 96.2% of patients. There were 14.2% of the studies that reported 3.5% of all patients showing no subjective improvement. A single study reported a poor outcome for 1 patient. There were 40.5% of the studies that reported complications, affecting 20.2% of all patients. The most frequently reported complication was transient hand weakness, affecting 44.2% of patients with complications and 8.9% of total patients. Weakness resolved in hours to months after injection. Pain at the injection site lasting minutes to days was reported in 40.7% of patients with complications, and 8.2% of total patients.

Conclusions
Botulinum toxin treatment for RP is effective. Complications are minor and self-limiting.
Preoperative Glucose Predicts Postoperative Complications After Complex Abdominal Wall Reconstruction
Authors: Marxen Troy , Su Shannon , Brown Ciara , Faulkner Heather R. , Losken Albert 
Published: July 2023

BackgroundDespite advances in surgical methods, complication rates after complex abdominal wall reconstruction (CAWR) remain high. Identification of preoperative risk factors can assist surgeons with risk stratification and patient counseling. The deleterious effects of hyperglycemia on wound healing are well established. With the increasing prevalence of diabetes (diabetes mellitus) and prediabetes, a greater proportion of patients are likely to have increased blood glucose levels that may contribute to poor surgical outcomes. The primary aim of this study was to determine whether preoperative hyperglycemia predicted surgical outcome. The secondary aim was to establish glucose thresholds to assist with surgical risk stratification.MethodsAll patients who underwent CAWR by the senior author at a single institution from 2002 to 2021 were retrospectively reviewed. Patients were stratified into 4 groups based on preoperative blood glucose: <100 mg/dL (n = 184), 100–140 mg/dL (n = 207), 140–180 mg/dL (n = 41), and >180 mg/dL (n = 16). Patient demographics, risk factors, surgical techniques, complications, and outcomes were recorded and compared.ResultsThe study cohort comprised of 478 patients. Mean age was 53.9 ± 12.3 years. Mean body mass index was 32.1 ± 7.8 kg/m2. Higher age (P= 0.0085), higher body mass index (P= 0.0005), the presence of diabetes (P< 0.0001), and hypertension (P= 0.0004) were significantly associated with higher glucose. Overall complication rates ranged from 26% (glucose <100 mg/dL) to 94% (glucose >180 mg/dL), whereas recurrence rates ranged from 10% (glucose <100 mg/dL) to 37% (glucose 140–180 mg/dL). Multivariate logistic regression analysis revealed preoperative glucose to have a significant, independent effect on overall complication rate (P< 0.0001), major complication rate (P< 0.0001), and recurrence rate (P< 0.0031).ConclusionsPreoperative hyperglycemia is an important predictor of postoperative complications and recurrence after CAWR. Point-of-care glucose levels are routinely gathered before surgery and may help to establish thresholds for which elective CAWR might be deferred. Strategies to lower preoperative glucose should be part of an optimization protocol for improving outcomes.
A Surgical Desirability of Outcome Ranking (DOOR) Reveals Complex Relationships between Race/Ethnicity, Insurance Type and Neighborhood Deprivation
Authors: Jacobs Michael A. , Schmidt Susanne , Hall Daniel E. , Stitzenberg Karyn B. , Kao Lillian S. , Brimhall Bradley B. , Wang Chen-Pin , Manuel Laura S. , Su Hoah-Der , Silverstein Jonathan C. , Shireman Paula K. 
Published: July 2023

Objective:
Develop an ordinal Desirability of Outcome Ranking (DOOR) for surgical outcomes to examine complex associations of Social Determinants of Health (SDoH).

Summary background data:
Studies focused on single or binary composite outcome may not detect health disparities.

Methods:
Three healthcare system cohort study using NSQIP (2013-2019) linked with EHR and risk-adjusted for frailty, Preoperative Acute Serious Conditions (PASC), case status and operative stress assessing associations of multi-level SDoH of race/ethnicity, insurance type (Private 13,957; Medicare 15,198; Medicaid 2,835; Uninsured 2,963) and Area Deprivation Index (ADI) on DOOR and the binary Textbook Outcomes (TO).

Results:
Patients living in highly deprived neighborhoods (ADI>85) had higher odds of PASC (aOR=1.13, CI=1.02-1.25, P<0.001) and urgent/emergent cases (aOR=1.23, CI=1.16-1.31, P<0.001). Increased odds of higher/less desirable DOOR scores were associated with patients identifying as Black versus White, and on Medicare, Medicaid or Uninsured versus Private insurance. Patients with ADI>85 had lower odds of TO (aOR=0.91, CI=0.85-0.97, P=0.006) until adjusting for insurance but increased odds of higher DOOR (aOR=1.07, CI=1.01-1.14, P<0.021) after adjusting for insurance but similar odds after adjusting for PASC and urgent/emergent cases.

Conclusions:
DOOR revealed complex interactions between race/ethnicity, insurance type and neighborhood deprivation. ADI>85 was associated with higher odds of worse DOOR outcomes while TO failed to capture the effect of ADI. Our results suggest that presentation acuity is a critical determinant of worse outcomes in patients in highly deprived neighborhoods and without insurance. Including risk adjustment for living in deprived neighborhoods and urgent/emergent surgeries could improve the accuracy of quality metrics.
Parathyroidectomy and the Risk of Major Cerebrovascular and Cardiovascular Events in the Elderly
Authors: Grant Robert R.C. , Moroz Brian E. , Nilubol Chanigan , Cahoon Elizabeth K. , Pfeiffer Ruth M. , Nilubol Naris 
Published: July 2023

Objective:
We aimed to determine the incidence of major cardiovascular and cerebrovascular events in elderly patients with primary hyperparathyroidism (pHPT) and the impact of parathyroidectomy.

Summary Background Data:
pHPT is under-diagnosed and under-treated in the United States. It is associated with increased cardiovascular disease risk but its association with cerebrovascular disease risk is not well-established. It is also unknown if parathyroidectomy reduces these risks.

Methods:
The incidence of major cerebrovascular and cardiovascular events in 108,869 patients with pHPT diagnosed in the Medicare database between 2008 and 2018 and a matched comparison group of 1,088,690 Medicare subjects was prospectively evaluated. We estimated hazards ratios (HR) for the association of pHPT and parathyroidectomy for the risk of these outcomes from Cox proportional hazards models. Survival curves were calculated to obtain five-year disease-free survival (DFS) estimates.

Results:
For patients with pHPT, five-year DFS was lower and HRs were higher than the comparison group for any outcome (75.9% vs. 78.4; HR 1.11, 95% confidence interval [CI] 1.09-1.13), major cerebrovascular events (84.5% vs. 86.3%; HR 1.14, 95% CI 1.12-1.17), and major cardiovascular events (87.7% vs. 88.8%; HR 1.06, 95% CI 1.03-1.08). However, in patients who had parathyroidectomy, the risks of major cerebrovascular and cardiovascular events did not differ from the comparison cohort. The lower risk in patients who had parathyroidectomy were maintained in subgroup analyses.

Conclusions:
Older patients with pHPT have an increased risk of major cerebrovascular and cardiovascular events compared to patients without the disease. Physicians treating older patients with primary hyperparathyroidism should consider parathyroidectomy.
Ruth M. Pfeiffer, Naris Nilubol These authors contributed equally to the preparation of this manuscript.
Predicting Long-term Disease-free Survival After Resection of Pancreatic Ductal Adenocarcinoma
Authors: van Goor Iris W.J.M. , Schouten Thijs J. , Verburg Daphne N. , Besselink Marc G. , Bonsing Bert A. , Bosscha Koop , Brosens Lodewijk A.A. , Busch Olivier R. , Cirkel Geert A. , van Dam Ronald M. , Festen Sebastiaan , Koerkamp Bas Groot , van der Harst Erwin , de Hingh Ignace H.J.T. , Intven Martijn P.W. , Kazemier Geert , Los Maartje , Meijer Gert J. , de Meijer Vincent E. , Nieuwenhuijs Vincent B. , Roos Daphne , Schreinemakers Jennifer M.J. , Stommel Martijn W.J. , Verdonk Robert C. , van Santvoort Hjalmar C. , Daamen Lois A. , Molenaar I. Quintus ,   for the Dutch Pancreatic Cancer Group
Published: July 2023

Objective:
To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after resection of pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data:
Despite high recurrence rates, approximately 10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making.

Methods:
This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best performing prognostic model was selected by Cox-proportional hazard analysis and Akaike’s Information Criterion, presented by hazard ratio’s (HR) with 95% confidence interval (CI). Internal validation was performed, and discrimination and calibration indices were assessed.

Results:
836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR1.21; 95%CI 1.10-1.32), no vascular resection (HR1.33; 95%CI 1.12-1.58), T1 or T2 tumor stage (HR1.52; 95%CI 1.14-2.04, and HR1.17; 95%CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR1.44; 95%CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR1.42; 95%CI 1.11-1.81 and HR1.14; 95%CI 0.96-1.36, respectively), N0 or N1 nodal status (HR1.92; 95%CI 1.54-2.40, and HR1.33; 95%CI 1.11-1.60, respectively), R0 resection margin status (HR1.25; 95%CI 1.07-1.46), no major complications (HR1.14; 95%CI 0.97-1.35) and adjuvant chemotherapy (HR1.74; 95%CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved.

Conclusions:
The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term disease-free survival after resection of pancreatic ductal adenocarcinoma.
The 2023 MANCTRA Acute Biliary Pancreatitis Care Bundle
Authors: Podda Mauro , Di Martino Marcello , Ielpo Benedetto , Catena Fausto , Coccolini Federico , Pata Francesco , Marchegiani Giovanni , De Simone Belinda , Damaskos Dimitrios , Mole Damian , Leppaniemi Ari , Sartelli Massimo , Yang Baohong , Ansaloni Luca , Biffl Walter , Kluger Yoram , Moore Ernest E. , Pellino Gianluca , Di Saverio Salomone , Pisanu Adolfo 
Published: July 2023

Objective:
To generate an up-to-date bundle to manage acute biliary pancreatitis using an evidence-based, artificial intelligence (AI)-assisted GRADE method.

Summary Background Data:
A care bundle is a set of core elements of care that are distilled from the most solid evidence-based practice guidelines and recommendations.

Methods:
The research questions were addressed in this bundle following the PICO criteria. The working group summarized the effects of interventions with the strength of recommendation and quality of evidence applying the GRADE methodology. ChatGPT AI system was used to independently assess the quality of evidence of each element in the bundle, together with the strength of the recommendations.

Results:
The seven elements of the bundle discourage antibiotic prophylaxis in patients with acute biliary pancreatitis, support the use of a full-solid diet in patients with mild to moderately-severe acute biliary pancreatitis, and recommend early enteral nutrition in patients unable to feed by mouth. The bundle states that ERCP should be performed within the first 48-72 hours of hospital admission in patients with cholangitis. Early laparoscopic cholecystectomy should be performed in patients with mild acute biliary pancreatitis. When operative intervention is needed for necrotizing pancreatitis, this should start with the endoscopic step-up approach.

Conclusions:
We have developed a new care bundle with seven key elements for managing patients with acute biliary pancreatitis. This new bundle, whose scientific strength has been increased thanks to the alliance between human knowledge and AI from the new ChatGPT software, should be introduced to emergency departments, wards, and ICUs.
Detailed Analysis of Simultaneous Renal and Liver Allografts in the Presence of DSA
Authors: O’Leary Jacqueline G. , Farris Alton B. , Gebel Howard M. , Asrani Sumeet K. , Askar Medhat , Garcia Vanessa , Snipes George J. , Lo Denise J. , Knechtle Stuart J. , Klintmalm Goran B. , Demetris Anthony J. 
Published: July 2023

Background.Liver allografts protect renal allografts from the same donor from some, but not all, preformed donor specific alloantibodies (DSA). However, the precise mechanisms of protection and the potential for more subtle alterations/injuries within the grafts resulting from DSA interactions require further study.Methods.We reevaluated allograft biopsies from simultaneous liver-kidney transplant recipients who had both allografts biopsied within 60 d of one another and within 30 d of DSA being positive in serum (positive: mean florescence intensity ≥5000). Routine histology, C4d staining, and specialized immunohistochemistry for Kupffer cells (KCs; CD163) and a C4d receptor immunoglobulin-like transcript-4 were carried out in 4 patients with 6 paired biopsies.Results.Overt antibody-mediated rejection was found in 3 of 4 renal and liver allografts. One patient had biopsy-confirmed renal and liver allograft antibody-mediated rejection despite serum clearance of DSA. All biopsies showed KC hypertrophy (minimal: 1; mild: 2; moderate: 1; severe: 2) and cytoplasmic C4d KC staining was easily detected in 2 biopsies from 2 patients; minimal and negative in 2 biopsies each. Implications of which are discussed. Control 1-y protocol liver allograft biopsies from DSA– recipients showed neither KC hypertrophy nor KC C4d staining (n = 6).Conclusions.Partial renal allograft protection by a liver allograft from the same donor may be partially mediated by phagocytosis/elimination of antibody and complement split products by KCs, as shown decades ago in controlled sensitized experimental animal experiments.
Systems immunology reveals the molecular mechanisms of heterogeneous influenza vaccine response in the elderly
Authors: Kumar Saumya , Zoodsma Martijn , Nguyen Nhan , Pedroso Rodrigo , Trittel Stephanie , Riese Peggy , Botey-Bataller Javier , Zhou Liang , Alaswad Ahmed , Arshad Haroon , Netea Mihai G. , Xu Cheng-Jian , Pessler Frank , Guzmán Carlos A. , Graca Luis , Li Yang 
Published: July 2023

SUMMARYVaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five timepoints) a cohort of 234 elderly influenza vaccinees across two independent seasons including up to six modalities (multi-omics and immunological parameters). System-level analyses revealed responders exhibited time-dependent changes attributed to a productive vaccine response across all omics layers whereas non-responders did not follow such dynamics, suggestive of systemic dysregulation. Through multi-omics integration, we identified key metabolites and proteins and their likely role in immune response to vaccination. High pre-vaccination IL-15 concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven NK-cell axis with a suppressing role on antibody production. Finally, we propose certain long-chain fatty acids as modulators of persistent inflammation in non-responders. Our findings highlight the potential for stratification of vaccinees and open avenues for possible pharmacological interventions to enhance vaccine responses.HIGHLIGHTSPre-vaccination pro-inflammatory status impedes vaccine responsiveness in the elderly.Multi-omics integration reveals key molecules involved in vaccine response.High pre-vaccination concentrations of IL-15 suppresses vaccine response through NK cell activation.Certain long-chain fatty acids may act as modulators against chronic inflammation and are potential targets to improve vaccine response.
Engineering cGAS-agonistic oligonucleotides as therapeutics and vaccine adjuvants for cancer immunotherapy
Authors: Zhou Shurong , Su Ting , Cheng Furong , Cole Janet , Liu Xiang , Zhang Bei , Alam Shaheer , Liu Jinze , Zhu Guizhi 
Published: July 2023

AbstractCurrent cancer immunotherapy (e.g., immune checkpoint blockade (ICB)) has only benefited a small subset of patients. Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) activation holds the potential to improve cancer immunotherapy by eliciting type-I interferon (IFN-I) responses in cancer cells and myeloid cells. Yet, current approaches to this end, mostly by targeting STING, have marginal clinical therapeutic efficacy. Here, we report a cGAS-specific agonistic oligonucleotide, Svg3, as a novel approach to cGAS-STING activation for versatile cancer immunotherapy. Featured with a hairpin structure with consecutive guanosines flanking the stem, Svg3 binds to cGAS and enhances cGAS-Svg3 phase separation to form liquid-like droplets. This results in cGAS activation by Svg3 for robust and dose-dependent IFN-I responses, which outperforms several state-of-the-art STING agonists in murine and human immune cells, and human tumor tissues. Nanocarriers efficiently delivers Svg3 to tissues, cells, and cytosol where cGAS is located. Svg3 reduces tumor immunosuppression and potentiates ICB therapeutic efficacy of multiple syngeneic tumors, in wildtype but neithercGas-/-nor goldenticketSting-/-mice. Further, as an immunostimulant adjuvant, Svg3 enhances the immunogenicity of peptide antigens to elicit potent T cell responses for robust ICB combination immunotherapy of tumors. Overall, cGAS-agonistic Svg3 is promising for versatile cancer combination immunotherapy.
Pooled tagging and hydrophobic targeting of endogenous proteins for unbiased mapping of unfolded protein responses
Authors: Sansbury Stephanie E. , Serebrenik Yevgeniy V. , Lapidot Tomer , Burslem George M. , Shalem Ophir 
Published: July 2023

AbstractSystem-level understanding of proteome organization and function requires methods for direct visualization and manipulation of proteins at scale. We developed an approach enabled by high-throughput gene tagging for the generation and analysis of complex cell pools with endogenously tagged proteins. Proteins are tagged with HaloTag to enable visualization or direct perturbation. Fluorescent labeling followed byin situsequencing and deep learning-based image analysis identifies the localization pattern of each tag, providing a bird’s-eye-view of cellular organization. Next, we use a hydrophobic HaloTag ligand to misfold tagged proteins, inducing spatially restricted proteotoxic stress that is read out by single cell RNA sequencing. By integrating optical and perturbation data, we map compartment-specific responses to protein misfolding, revealing inter-compartment organization and direct crosstalk, and assigning proteostasis functions to uncharacterized genes. Altogether, we present a powerful and efficient method for large-scale studies of proteome dynamics, function, and homeostasis.
Strain-dependent assessment of Powassan virus transmission to deer ticks
Authors: McMinn Rebekah J. , Courtney Samantha , Telford Sam R. , Ebel Gregory D. 
Published: July 2023

1.AbstractPowassan virus (POWV) is an emergent tick-borne encephalitis virus of Lyme disease endemic sites in North America. Due to range expansion and local intensification of deer tick vector (Ixodes scapularis) populations in the northeastern and upper midwestern U.S., encephalitis cases are increasingly being reported. A better understanding of the transmission cycle of POWV may allow for predicting the eventual public health burden. Recent phylogeographic analyses of POWV have identified geographical structuring, with well-defined northeastern and midwestern clades of the deer tick virus subtype (lineage II); sublineages exist within each clade. It may be that the local sublineages differ in their capacity to be transmitted by the deer tick vector. Accordingly, we determined whether there are strain-dependent differences in transmission. Five recent, low passage POWV isolates were used to measure aspects of vector competence, using viremic and artificial infection methods. Infection rates in experimental ticks remained consistent between all five isolates tested, resulting in 12-20% infection rate and no clear differences in viral load. We conclude that there is a genotype independent ability of POWV to infect deer ticks, and that differences in transmission efficiency are not likely to serve as the basis for regional differences in apparent public health burden.