bluuebunny/crossref_metadata_2025_split huggingface dataset:
New and emerging pharmacotherapies for the management of multiple myeloma
Authors: Moore Donald C , Oxencis Carolyn J , Shank Brandon R 
Published: March 2022

Abstract

Purpose
The pharmacology, efficacy, safety, and dosing/administration of new and emerging therapies for the treatment of multiple myeloma are summarized.

Summary
There have been significant advancements in the treatment of multiple myeloma in recent years, with an expansion of available drug therapies. Newer therapies for multiple myeloma include the anti-CD38 monoclonal antibodies daratumumab and isatuximab, the exportin 1 inhibitor selinexor, the anti–B-cell maturation antigen (BCMA) antibody-drug conjugate belantamab mafodotin, and the chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel. These agents have unique toxicity profiles, specific monitoring parameters, and operational considerations that clinicians treating multiple myeloma should be aware of. There is likely to be continued rapid expansion of new agents for patients with multiple myeloma, as there are many novel investigational agents in the drug development pipeline, such as bispecific antibodies and additional CAR T-cell therapies.

Conclusion
Several therapeutic agents have been recently approved by the Food and Drug Administration for the treatment of multiple myeloma. There are many novel agents in the pipeline, including bispecific antibodies and CAR T-cell therapies that have the potential to continue to change the treatment landscape of multiple myeloma.
Benchmarking differential expression, imputation and quantification methods for proteomics data
Authors: Lin Miao-Hsia , Wu Pei-Shan , Wong Tzu-Hsuan , Lin I-Ying , Lin Johnathan , Cox Jürgen , Yu Sung-Huan 
Published: March 2022

Abstract
Data analysis is a critical part of quantitative proteomics studies in interpreting biological questions. Numerous computational tools for protein quantification, imputation and differential expression (DE) analysis were generated in the past decade and the search for optimal tools is still going on. Moreover, due to the rapid development of RNA sequencing (RNA-seq) technology, a vast number of DE analysis methods were created for that purpose. The applicability of these newly developed RNA-seq-oriented tools to proteomics data remains in doubt. In order to benchmark these analysis methods, a proteomics dataset consisting of proteins derived from humans, yeast and drosophila, in defined ratios, was generated in this study. Based on this dataset, DE analysis tools, including microarray- and RNA-seq-based ones, imputation algorithms and protein quantification methods were compared and benchmarked. Furthermore, applying these approaches to two public datasets showed that RNA-seq-based DE tools achieved higher accuracy (ACC) in identifying DEPs. This study provides useful guidelines for analyzing quantitative proteomics datasets. All the methods used in this study were integrated into the Perseus software, version 2.0.3.0, which is available at https://www.maxquant.org/perseus.
Coaptation length predicts early- and intermediate-term durability following degenerative mitral repair
Authors: Hage Fadi , Hage Ali , Malik Mohsyn I , Tzemos Nikolaos , Chu Michael W A 
Published: March 2022

Abstract

OBJECTIVES
The impact of coaptation length on recurrent mitral regurgitation following degenerative mitral repair is not fully understood.

METHODS
Between May 2008 and February 2021, 386 consecutive patients underwent mitral repair for degenerative mitral regurgitation at a single centre. We compared patients with a post-repair coaptation length &gt;11 mm (long-coaptation group, n = 230) and ≤11 mm (short-coaptation group, n = 156). The coaptation length cutoff was selected based on published postoperative transesophageal echocardiographic measurement of mitral repair patients and healthy controls. Propensity score with inverse probability of treatment weighting (IPTW) analyses were performed. The median duration of clinical follow-up was 41 months and follow-up was complete in the entire cohort.

RESULTS
The long-coaptation patients underwent more neochord implantation (89% vs 65%, P &lt; 0.001) and less leaflet resection (11% vs 29%, P &lt; 0.001). Overall in-hospital/30-day mortality and mitral reintervention occurred in 3 (1%) and 4 (1%) patients, respectively, and freedom from recurrent mitral regurgitation was 98% at 1 year and 94% at 5 years. Freedom from recurrent mitral regurgitation moderate or greater was significantly higher in the long-coaptation patients (IPTW-adjusted difference in average time to recurrent mitral regurgitation: 31 months, 95% confidence interval 9–53, P = 0.006). However, there was no difference in intermediate-term survival between both groups (IPTW-adjusted difference in average time to death: 9.5 months, 95% confidence interval −27 to 46, P = 0.61). Stratified analysis and pairwise comparison of different coaptation intervals also appeared to support the protective effect of longer coaptation on repair durability.

CONCLUSIONS
Longer coaptation length appears to be associated with improved intermediate-term durability after mitral repair.
Thoracoabdominal aortic aneurysm repair based on pre- and postoperative evaluation of the artery of Adamkiewicz
Authors: Imamura Yuki , Kin Hajime , Yoshioka Kunihiro , Tabayashi Azuma , Saitoh Daiki 
Published: March 2022

Abstract

OBJECTIVES
The aim of this study was to evaluate our experience with thoraco-abdominal aortic aneurysm repair based on the pre- and postoperative evaluation of the artery of Adamkiewicz (AKA).

METHODS
Between April 2017 and May 2021, 32 patients who underwent thoracoabdominal aortic repair underwent pre- and postoperative multidetector row computed tomography (MDCT) for AKA evaluation. Based on the identification of the AKA on preoperative MDCT, only 1 critical segmental artery was reattached to the AKA (CSA-AKA). Postoperative MDCT was used to evaluate the patency of the reattached CSA-AKA.

RESULTS
Pre- and postoperative MDCT helped identify and visualize the AKA in all patients (100%). In 8 patients, alternative continuity to the AKA developed through collateral circulation. The total number of CSA-AKA with collateral circulation was 48 among the 32 cases; the number of reattached segmental arteries per case was 1.3 ± 0.9 (range, 0–4). The overall rate of patency of the reattached CSA-AKA was 53% (23/43). Three patients exhibited spinal cord injuries (paraplegia, 2; paraparesis, 1). In the 2 paraplegia cases exhibiting partial or complete occlusion of the reattached CSA-AKA, the development of collateral circulation was not visualized via postoperative MDCT. In the paraparesis case, postoperative MDCT helped visualize the development of collateral circulation to the CSA-AKA, resulting in full recovery at discharge.

CONCLUSIONS
The study findings suggest that spinal cord injuries do not occur in the presence of a patent preoperatively identified CSA-AKA or the development of collateral circulation. Pre- and postoperative identification of collateral pathways to the AKA may help reveal paraplegia risk factors.
The genome of Hibiscus hamabo reveals its adaptation to saline and waterlogged habitat
Authors: Wang Zhiquan , Xue Jia-Yu , Hu Shuai-Ya , Zhang Fengjiao , Yu Ranran , Chen Dijun , Van de Peer Yves , Jiang Jiafu , Song Aiping , Ni Longjie , Hua Jianfeng , Lu Zhiguo , Yu Chaoguang , Yin Yunlong , Gu Chunsun 
Published: March 2022

Abstract
Hibiscus hamabo is a semi-mangrove species with strong tolerance to salt and waterlogging stress. However, the molecular basis and mechanisms that underlie this strong adaptability to harsh environments remain poorly understood. Here, we assembled a high-quality, chromosome-level genome of this semi-mangrove plant and analyzed its transcriptome under different stress treatments to reveal regulatory responses and mechanisms. Our analyses suggested that H. hamabo has undergone two recent successive polyploidy events, a whole-genome duplication followed by a whole-genome triplication, resulting in an unusually large gene number (107 309 genes). Comparison of the H. hamabo genome with that of its close relative Hibiscus cannabinus, which has not experienced a recent WGT, indicated that genes associated with high stress resistance have been preferentially preserved in the H. hamabo genome, suggesting an underlying association between polyploidy and stronger stress resistance. Transcriptomic data indicated that genes in the roots and leaves responded differently to stress. In roots, genes that regulate ion channels involved in biosynthetic and metabolic processes responded quickly to adjust the ion concentration and provide metabolic products to protect root cells, whereas no such rapid response was observed from genes in leaves. Using co-expression networks, potential stress resistance genes were identified for use in future functional investigations. The genome sequence, along with several transcriptome datasets, provide insights into genome evolution and the mechanism of salt and waterlogging tolerance in H. hamabo, suggesting the importance of polyploidization for environmental adaptation.
Animal Study Translation: The Other Reproducibility Challenge
Authors: Berridge Brian R 
Published: March 2022

AbstractAnimal research is currently an irreplaceable contributor to our efforts to protect and improve public health. Its relevance, importance, and contributions are represented in historical precedent, regulatory expectations, evidence of our rapidly developing understanding of human health and disease, as well as success in the development of novel therapeutics that are improving quality of life and extending human and animal life expectancy. The rapid and evolving success in responding to the current COVID pandemic significantly supported by animal studies is a clear example of the importance of animal research. But there is growing interest in reducing our dependence on animals and challenges to the effective translation of current animal studies to human applications. There are several potential contributors to gaps in the translatability of animal research to humans, including our approaches to choosing or rationalizing the relevance of a particular animal model, our understanding of their biological variability and how that applies to outcomes, the data we collect from animal studies, and even how we manage the animals. These important contributors to the success of animal research are explored in this issue of the ILAR Journal.
Development of a Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of 40 Drugs of Abuse in Human Urine: Application to Real Cases
Authors: Pascual-Caro Sergi , Borrull Francesc , Aguilar Carme , Calull Marta 
Published: March 2022

AbstractDrugs of abuse are constantly evolving, while new synthetized substances are constantly emerging to avoid regulations. However, traditional drugs such as cocaine and amphetamine are still two of the most consumed drugs in the world. It is important, therefore, to provide suitable multiresidue methods for determining a wide range of drugs for use in toxicological and forensic analyses. The aim of this study is to develop a method for determining several families of drugs of abuse, including classic drugs, new psychoactive substances and some of their metabolites, in urine by liquid chromatography–tandem mass spectrometry. Urine is one of the most common biological matrices used in drug analysis because of its easy collection and a wide window of detection. In this study, we used solid-phase extraction to remove interferences and extract analytes from urine. Four different mixed-mode cation-exchange commercial sorbents were evaluated. The best results, in terms of apparent recoveries, were achieved with one of the strong cationic sorbents, ExtraBond SCX. The method achieved detection limits from 0.003 to 0.500 ng/mL and quantification limits from 0.050 to 1.500 ng/mL, which are suitable for determining these compounds at the usual levels found in the urine of drug users. The applicability of this method was demonstrated by analyzing real urine specimens from women following a detoxification program. Our results showed that the drug most consumed was cocaine, since it was detected in most urine specimens together with its main metabolite, benzoylecgonine. The polyconsumption of drugs from different families was also observed in some urine samples analyzed.
T2 Global Hospital Infrastructure and Pediatric Burns
Authors: Puthumana Joseph S , Hultman Charles S , Redett Richard J 
Published: March 2022

Abstract

Introduction
Low income regions across the world carry the highest proportion and highest mortality burden of pediatric burns. In recent years, attention to remedy these inequities has shifted from isolated mission trips towards building infrastructure for lasting improvements in surgical care. This study aims to investigate disparities in pediatric burn care infrastructure and their relationship to mortality outcomes.

Methods
The multinational Global Burn Registry was queried for all burn cases between January 2018 and August 2021. Burn cases and mortality rates were compared across infrastructure factors by Pearson Chi-Square. Multinomial logistic regression was used to isolate independent modifiable risk factors for mortality controlling for total body surface area of burn (TBSA).

Results
There were a total of 8537 cases of which 3492 (40.9%) were pediatric. Significantly lower mortality rates were found in facilities with sophisticated nutritional supplementation (p &lt; 0.001), permanent internet connectivity (p &lt; 0.001), reliable critical care access (p &lt; 0.001), reliable burn OR access (p=0.003), dedicated burn unit (p &lt; 0.001), and advanced plastic and reconstructive skills available (p=0.003); there was no significant difference if specialist capabilities in supportive fields (e.g. nephrology, cardiology) were available (p=0.063). Significant disparities were found in the availability of these resources between high and low income countries, as well granular information within low income regions: though blood transfusion access was limited in the African (49.0%) and South-East (50.6%) regions compared to full access in the Americas and Europe (p &lt; 0.001), 100% of cases in the South-East had access to a specialized burn unit compared to 8.1% of cases in Africa. In a multinomial logistic regression controlling for TBSA, the most significant risk factor for mortality was limited critical care availability (OR 15.18, p&lt; 0.001). The most significant protective factor was sophisticated nutritional access (OR 0.40, p=0.024).

Conclusions
This is the first quantitative analysis of disparities in global burn infrastructure and their impact on pediatric mortality. The identification of nutritional support as an independent and significant protective factor suggests that low-cost interventions in hospital nutrition infrastructure merit further study and may realize significant gains in global burn care. Granular information in the variability of regional needs will begin to direct targeted infrastructure initiatives rather than a one-size-fits-all approach in developing nations.
5 Admission Frailty Is Associated with Acute Respiratory Failure and Mortality in Burn Patients &gt; 50
Authors: Galet Colette , Lawrence Kevin , Skipton Romanowski Kathleen S , Skeete Dionne , Mashruwala Neil 
Published: March 2022

Abstract

Introduction
Pre-injury frailty has been shown to predict mortality of older burn patients. Herein, we assessed the utility of the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS) to predict burn-specific outcomes. We hypothesize that frail patients are at greater risk for complications such as graft loss, acute respiratory failure, and acute kidney injury and will require increased healthcare support at discharge.

Methods
This is a retrospective cohort study. Patients 50 years and older admitted to our Institution for burn injuries between July 2009 and June 2019 were included. Patients with inhalation injury only, no data on total burn surface area, or for whom medical history was incomplete were excluded. Demographics; comorbidities; pre-injury functional status; admission, injury, and hospitalization information; complications (graft loss, acute respiratory failure, and acute kidney disease (AKI)); mortality, and discharge disposition were collected. Patients were scored on the CSHA-CFS based on pre-admission health and functional status. The frail and non-frail groups were compared. Multivariate analyses were performed to assess the association between admission frailty and outcomes. P &lt; 0.05 was considered significant.

Results
We included 851 patients, 697 were not frail and 154 were frail. Frail patients were significantly older (66.1 ± 10.8 vs. 63.5 ± 10.9, p = 0.002), more likely Caucasian (98.1% vs. 91%, p = 0.027) and to have suffered flame burn injuries (68.8% vs. 59.8%, p &lt; 0.001). Frail patients had a lower %TBSA (4.4 ± 8.1% vs. 10.1 ± 13.1, p &lt; 0.001) but were more likely to stay longer in hospital relative to %TBSA (3.6 ± 6.7 vs. 1.9 ± 3.1, p &lt; 0.001). Frail patients were less likely to have had skin graft procedures (27.3% vs. 57.4, p &lt; 0.001). On multivariate analysis, controlling for age, sex, race, mechanism of injury, %TBSA, 2nd degree and 3rd degree burn surface, inhalation injury, frailty was associated with acute respiratory failure (OR = 2.599 [1.460-4.628], p = 0.001). Frailty was also associated with mortality (OR = 6.915 [2.455-19.980]; p &lt; 0.001) when controlling for the same variables as well as acute respiratory failure and AKI. Frailty was also associated with discharge to home with healthcare services (OR = 2.678 [1.491-4.809], p = 0.001), to SNF, rehabilitation, or long-term acute care facilities (OR = 3.572 [1.933-6.602], p &lt; 0.001), and to hospice (OR = 5.759 [1.519-21.827], p = 0.010) when compared to home without healthcare services.

Conclusions
Frailty is associated with increased risk of acute respiratory failure, mortality, and requiring increased healthcare support post-discharge. Our data suggest frailty as a tool to predict morbidity and mortality as well as for goals of care discussions for the burn patient.
23 Chlorhexidine Delays Wound Healing in Human Skin
Authors: Gibson Angela , Liu Aiping , Tran Collin L , Hassan Sameeha E 
Published: March 2022

Abstract

Introduction
Chlorhexidine (CHG) is ubiquitous in surgical perioperative care. In vivo studies of CHG cytotoxicity on human skin are lacking. Given the use of CHG for daily wound cares and as a presurgical scrub, including donor site preparation, we sought to identify if CHG cytotoxicity would persist in a clinically relevant in vivo human skin xenograft model.

Methods
Human skin tissues were obtained from elective surgeries. Partial thickness wounds were created ex vivo in human skin using a 4 mm punch biopsy. 2% CHG (treatment) or PBS (control) was applied to the wounds for 30 minutes followed by rinsing the tissue +/- mechanical disruptive irrigation. Tissues were cultured at the air-liquid interface for 24 hours in culture media after treatment and tissue viability was performed using an MTT assay. For in vivo studies, athymic mice (n=4) were grafted on bilateral flanks with human skin. Eight weeks after engraftment and normalization of skin architecture, 4 mm partial thickness wounds were created on each xenograft (2 per mouse – treatment and control). 2% CHG was applied daily for 2 minutes followed by irrigation with PBS in the treatment wound. The control wound received PBS application and irrigation. The xenografts received treatment daily for 14 days to mimic daily wound cares, and digital images were obtained to document presence of infection and gross wound healing. On day 14, the xenografts were harvested and stained for lactate dehydrogenase and H&E to assess cell viability and wound re-epithelization, respectively.

Results
An MTT assay on ex vivo human skin wounds showed that CHG treated groups (irrigation or non-irrigation) had lower cell viability compared to the PBS treated group, however irrigation mitigates the cytotoxicity of CHG on human skin. In the in vivo xenograft study, no signs of infection were identified in either PBS or CHG treated wounds throughout the study. The wound size appeared larger on gross inspection in the CHG treated group compared to the PBS group as early as day 2.Microscopically, the PBS treated wounds were fully re-epithelialized (n=2) or had significantly more re-epithelialization (n=2) than the CHG treated wounds (n=4) after 14 days of treatment. The PBS-treated wounds were viable throughout the tissue, indicating the irrigation procedure was not harmful to the cells. In the CHG-treated wounds, nonviable cells were observed in the dermis beneath the wound that was directly in contact with CHG suggesting penetration of CHG contributes to cytotoxicity in acute wounds.

Conclusions
Daily CHG use is cytotoxic to human skin and impedes wound healing.
24 The CD34+ Adipose-derived Stem Cells from Fat Grafts Accelerates Keratinocyte Wound Closure
Authors: Balko Stefan , Raouf Afshin , Kerr Evan , Logsetty Sarvesh 
Published: March 2022

Abstract

Introduction
Adipose derived stem cells (ADSCs) possess high regenerative potential and therefore are postulated to enhance re-epithelialization via recruitment of keratinocytes into the wound bed, and thusly improve healing of severe burns. Although ADSC’s are enriched in the stromal vascular fraction (SVF) of fat grafts, the ADSC frequency in these samples is very low (1%) which has hindered their further characterization. So far, the CD34+ subset of SVF cells has shown to contain up to 75% of all the ADSCs present in SVF samples but their ADSC frequency remains low (2.5%). Unfortunately, while the ADSC frequency increases in passaged SVF cells, the expression of CD34 is lost in these cells. Therefore, there is a pressing need to identify new ADSC biomarkers to study ADSC mechanisms that accelerate wound closure. In this study, we aim to identify new ADSC biomarkers and to examine the impact of ADSC-enriched cells on skin wound closure.

Methods
Single cells from SVFs were obtained from disassociated fat tissue, collected from excess lipoaspirates used in patients undergoing mastectomies. Native cells (P0), and passaged cells (P3) were placed in cell cultures and the ADSC numbers were obtained using the colony forming unit-fibroblast assays. The expression of 244 cell surface receptors was examined in P0 (low ADSCs) and P3 (high ADSCs) SVF cells to obtain new ADSC biomarkers. In another experiment, the impact of ADSC-enriched CD34+ SVF cells on wound closure was assessed. Using transwell inserts containing adult human epidermal keratinocyte (HEKa) cells in the bottom and the bulk SVF or CD34+ SVF cells in the top chamber, a scratch was induced in the HEKa cell layer and the scratch area was examined at 0h and 12h.

Results
Our cell surface antibody array experiments revealed 10 potentially new ADSC biomarkers that will be used to examine their ability to enrich for ADSCs. Both the bulk SVF and the CD34+ SVF cells showed a 2-fold increase in would closure. It is noteworthy that ADSCs frequency in the CD34+ SVF cells is still very low, and these experiments need to be conducted using the new SVF subsets with potentially higher ADSC frequencies based on our cell surface array.

Conclusions
The ADSC-enriched CD34+ SVF enhance keratinocyte wound closure, a function that is important to healing of severe burns. Further studies are needed to validate our findings using more purified SVF subsets to identify ADSC-regulated keratinocyte wound closure mechanisms.