bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ABT-263 on Intestinal Fibrosis in Human Myofibroblasts, Human Intestinal Organoids, and the Mouse Salmonella typhimurium Model
Authors: Johnson Laura A , Rodansky Eva S , Tran Anhdao , Collins Stephen G , Eaton Kathryn A , Malamet Benjamin , Steiner Calen A , Huang Sha , Spence Jason R , Higgins Peter D R 
Published: July 2021

Abstract

Background
Intestinal fibrosis and subsequent intestinal obstruction are common complications of Crohn’s disease (CD). Current therapeutics combat inflammation, but no pharmacological therapy exists for fibrostenotic disease. Pathological persistence of activated intestinal myofibroblasts is a key driver of fibrosis in CD. In other organ systems, BH-3 mimetic drugs that affect Bcl-2 apoptotic pathways induce apoptosis in activated myofibroblasts and reduce fibrogenic gene expression, thereby reducing fibrosis.

Methods
We evaluated the proapoptotic and antifibrotic efficacy of several classes of BH-3 mimetics in 2 in vitro fibrogenesis models. The candidate molecule, ABT-263, was advanced to a 3-dimensional human intestinal organoid (HIO) model. Finally, the therapeutic efficacy of ABT-263 was evaluated in the mouse Salmonella typhimurium intestinal fibrosis model.

Results
The BH-3 mimetics induced apoptosis, repressed fibrotic protein expression, and reduced fibrogenic gene expression in normal human intestinal myofibroblasts. The BH-3 mimetics that target Bcl-2 and Bcl-xl demonstrated the greatest efficacy in vitro. The ABT-199 and ABT-263 induced apoptosis and ameliorated fibrogenesis in the in vitro myofibroblast models. In the HIO model, ABT-263 inhibited fibrogenesis and induced apoptosis. In the mouse S. typhimurium model, dose-dependent reduction in macroscopic pathology, histological inflammation, inflammatory and fibrotic gene expression, and extracellular matrix protein expression indicated ABT-263 may reduce intestinal fibrosis.

Conclusions
In vitro, the antifibrotic efficacy of BH-3 mimetics identifies the Bcl-2 pathway as a druggable target and BH-3 mimetics as putative therapeutics. Reduction of inflammation and fibrosis in the mouse intestinal fibrosis model by ABT-263 indicates BH-3 mimetics as potential, novel antifibrotic therapeutics for Crohn’s disease.
Temporal Issues Relating to BIT Dispute Resolution
Authors: Murphy Sean D 
Published: July 2021

Abstract
An investor–State tribunal formed under a bilateral investment treaty (BIT) may be called upon to determine its jurisdiction ratione temporis based on various ‘critical dates’ such as: the date of entry into force of the BIT; the date when the investment was made; the date when the investor acquired the requisite nationality; the date of the alleged breach; the date when the investor first acquired knowledge of the alleged breach and of its loss; and/or the date when the dispute arose. When confronted with such temporal issues, tribunals over the past two decades have often reverted to the ‘secondary’ rules found in the International Law Commission’s 2001 Articles on the Responsibility of States for Internationally Wrongful Acts, and found in the law of treaties. This article identifies a series of propositions that may be extracted from recent investor–State jurisprudence concerning those secondary rules, with particular attention to application of the rule on non-retroactivity. Except in relatively limited situations, tribunals appear disinclined to find temporal jurisdiction over breaches or disputes that are based on pre-BIT acts. Consequently, this article considers as well recent jurisprudence on whether the host State’s alleged breach has a continuing or composite character, thus overcoming any temporal bar. While it would be excessive to say that the secondary rules in this area have provided the perfect means for addressing temporal issues, they appear to have generated a comprehensible framework within which investor–State tribunals are successfully operating.
Does preoperative dual antiplatelet therapy affect bleeding and mortality after total arch repair for acute type A dissection?
Authors: Xiao Fu-Cheng , Ma Wei-Guo , Ge Yi-Pen , Zhu Jun-Ming , Sun Li-Zhong 
Published: July 2021

AbstractOBJECTIVESData are scarce and mixed regarding the impact of preoperative dual antiplatelet therapy (DAPT) on the surgical outcomes of acute type A aortic dissection (ATAAD). We seek to evaluate the impact of DAPT on bleeding-related events and early- and mid-term mortality after total arch replacement and frozen elephant trunk in such patients.METHODSThis study comprised 48 ATAAD patients on preoperative DAPT and 418 without DAPT (the whole series, i.e. unmatched cohort), from which 45 matched pairs were selected by propensity score (matched cohort). Bleeding-related events (reoperation for bleeding, bleeding of ≥1500 ml within the first 12 h postoperatively or transfusion of ≥10 units of red blood cell or use of recombinant activated factor VII), operative mortality and mid-term survival were compared in the unmatched and matched cohorts. The impact of preoperative DAPT was evaluated with multivariable analysis.RESULTSIn the unmatched cohort, bleeding of ≥1500 ml/12 h postoperatively was more common in the DAPT group (18.8% vs 8.4%, P = 0.020); operative mortality was 9.7%, which did not differ with DAPT (12.5% vs 9.3%, P = 0.48). Nor did bleeding-related events (54.2% vs 43.5%, P = 0.16) differ significantly between 2 groups. In the matched cohort, neither were drainage of ≥1500 ml/12 h (20% vs 6.7%, P = 0.063) and bleeding-related events (53.3% vs 42.2%, P = 0.30), nor operative mortality (13.8 vs 8.9%, P = 0.50) and mid-term survival (79.3% vs 76.4%, P = 0.93) significantly different between 2 groups. DAPT was not identified as a predictor for operative mortality [odd ratio (OR) 0.97, 95% confidence interval (CI) 0.31–3.08; P = 0.96; adjusted OR 1.28, 95% CI 0.22–7.20; P = 0.78] and bleeding-related events (OR 1.50, 95% CI 0.76–2.95; P = 0.24; adjusted OR 2.03, 95% CI 0.80–3.66; P = 0.14).CONCLUSIONSIn patients with ATAAD undergoing total arch replacement and frozen elephant trunk, although preoperative DAPT led to more postoperative bleeding, it did not increase bleeding-related events nor operative mortality nor mid-term death. The results of this study imply that for patients with ATAAD, emergency surgical repair, even if as extensive as total arch repair, should not be contraindicated or delayed simply because of ongoing DAPT.
Bilinear Forms With Modular Square Roots and Twisted Second Moments of Half Integral Weight Dirichlet Series
Authors: Shkredov Ilya D , Shparlinski Igor E , Zaharescu Alexandru 
Published: July 2021

Abstract
We establish new results on equations and bilinear forms with modular square roots. The main motivation and application of these results is our new bound on the fourth moment of the error term in the asymptotic formula for the twisted second moment of half integral weight Dirichlet series on average over moduli.
Exploring “Return to Productivity” Among People Living With Burn Injury: A Burn Model System National Database Report
Authors: Sheckter Clifford C , Brych Sabina , Carrougher Gretchen J , Wolf Steven E , Schneider Jeffrey C , Gibran Nicole , Stewart Barclay T 
Published: July 2021

Abstract
Burn survivors experience barriers to returning to work. For those who do return to work, little is known regarding whether they achieve preinjury productivity (i.e., equivalent or gain in income compared to preinjury income). Identifying patients at risk of not achieving preinjury productivity is important for targeting services that support this population. They extracted occupational and income data through 24 months postinjury from the multicenter, longitudinal Burn Model System National Database. Annual income was reported in six groups: &lt;$25k, $25k–50k, $50k–99k, $100k–149k, $150k–199k, and $&gt;199k. Participants were classified by change in income at each follow-up (i.e., gain, loss, and equivalent). Explanatory variables included demographics, injury characteristics, insurance payer, employment status, and job type. Multilevel, multivariable logistic regression was used to model return to productivity. Four hundred fifty-three participants provided complete income data at discharge and follow-up. Of the 302 participants employed preinjury, 180 (60%) returned to work within 24 months postinjury. Less than half (138) returned to productivity (46% of participants employed preinjury; 77% of those who returned to work). Characteristics associated with return to productivity included older age (median 46.9 vs 45.9 years, OR 1.03, P = .006), Hispanic ethnicity (24% vs 11%, OR 1.80, P = 0.041), burn size &gt;20% TBSA (33.7% vs 33.0%, OR 2.09, P = 0.045), and postinjury employment (54% vs 26%, OR 3.41, P &lt; 0.001). More than half of employed people living with burn injury experienced loss in productivity within 24 months postinjury. Even if they return to work, people living with burn injuries face challenges returning to productivity and may benefit from vocational rehabilitation and/or financial assistance.
Early Palliative Care Consultation in the Burn Unit: A Quality Improvement Initiative to Increase Utilization
Authors: Carmichael Heather , Brackett Hareklia , Scott Maurice C , Dines Margaret M , Mather Sarah E , Smith Tyler M , Duffy Patrick S , Wiktor Arek J , Lambert Wagner Anne 
Published: July 2021

Abstract
Despite significant morbidity and mortality for major burns, palliative care consultation (PCC) is underutilized in this population. The purpose of this study is to examine the impact of a protocol using recommended “triggers” for PCC at a single academic burn center. This is a retrospective review of patient deaths over a 4-year period. The use of life-sustaining treatments, comfort care (de-escalation of one or more life-sustaining treatments), and do not attempt resuscitation (DNAR) orders were determined. The use of PCC was compared during periods before and after a protocol establishing recommended triggers for early (&lt;72 hours of admission) PCC was instituted in 2019. A total of 33 patient deaths were reviewed. Most patients were male (n = 28, 85%) and median age was 62 years [IQR: 42–72]. Median-revised Baux score was 112 [IQR: 81–133]. Many patients had life-sustaining interventions such as intubation, dialysis, or cardiopulmonary resuscitation, often prior to admission. Amongst patients who survived &gt;24 hours, 67% (n = 14/21) had PCC. Frequency of PCC increased after protocol development, with 100% vs 36% of these patients having PCC before death (P = .004). However, even during the later period, less than half of patients had early PCC despite meeting criteria at admission. In conclusion, initiation of life-sustaining measures in severely injured burn patients occurs prior to or early during hospitalization. Thus, value-based early goals of care discussions are valuable to prevent interventions that do not align with patient values and assist with de-escalation of life-sustaining treatment. In this small sample, we found that while there was increasing use of PCC overall after developing a protocol of recommended triggers for consultation, many patients who met criteria at admission did not receive early PCC. Further research is needed to elucidate reasons why providers may be resistant to PCC.
Impact of Opioid-Minimizing Pain Protocols After Burn Injury
Authors: Donthula Deepanjli , Conner Christopher R , Truong Van Thi Thanh , Green Charles , Jiang Chuantao , Wandling Michael W , Komak Spogmai , Huzar Todd F , Adams Sasha D , Freet Daniel J , Wainwright David J , Wade Charles E , Kao Lillian S , Harvin John A 
Published: July 2021

Abstract
In 2019, we implemented a pill-based, opioid-minimizing pain protocol and protocolized moderate sedation for dressing changes in order to decrease opioid exposure in burn patients. We hypothesized that these interventions would reduce inpatient opioid exposure without increasing acute pain scores. Two groups of consecutive patients admitted to the burn service were compared: Pre-group (from January 1, 2018 to July 31, 2019) and Post-group (from January 1, 2020 to June 30, 2020) from before and after the implementation of the protocols (from August 1, 2019 to December 31, 2019). We abstracted patient demographics and burn injury characteristics from the burn registry. We obtained opioid exposure and pain scale scores from the electronic medical record. The primary outcome was total morphine milligram equivalents (MMEs). Secondary outcomes included MMEs/day, pain domain-specific MMEs, and pain scores. Pain was estimated by creating a normalized pain score (range 0–1), which incorporated three different pain scales (Numeric Rating Scale, Behavioral Pain Scale, and Behavioral Pain Assessment Scale). Groups were compared using Wilcoxon rank-sum and chi-square tests. Treatment effects were estimated using Bayesian generalized linear models. There were no differences in demographics or burn characteristics between the Pre-group (n = 495) and Post-group (n = 174). The Post-group had significantly lower total MMEs (Post-group 110 MMEs [32, 325] vs Pre-group 230 [60, 840], P &lt; .001), MMEs/day (Post-group 33 MMEs/day [15, 54] vs Pre-group 52 [27, 80], P &lt; .001), and domain-specific total MMEs. No difference in average normalized pain scores was seen. Implementation of opioid-minimizing protocols for acute burn pain was associated with a significant reduction in inpatient opioid exposure without an increase in pain scores.
TheAedes aegypti(Diptera: Culicidae)hsp83Gene Promoter Drives Strong Ubiquitous DsRed and ZsGreen Marker Expression in Transgenic Mosquitoes
Authors: Webster Sophia H , Scott Maxwell J 
Published: July 2021

AbstractTransgenic strains of the mosquito disease vector Aedes aegypti (L.) are being developed for population suppression or modification. Transgenic mosquitoes are identified using fluorescent protein genes. Here we describe DsRed and ZsGreen marker genes driven by the constitutive Ae. aegypti heat shock protein 83 (hsp83) promoter in transgenic mosquitoes. Transgenic larvae and pupae show strong full body expression of the red and green fluorescent proteins. This greatly assists in screening for transgenic individuals while making new or maintaining already established lines. Transient marker gene expression after embryo microinjection was readily visible in developing larvae allowing the separation of individuals that are more likely to produce transgenic offspring. The strongly expressed marker genes developed in this study should facilitate the detection of transgenic Ae. aegypti larvae or pupae in the field.
In situ observation of the chemical bonding state of Si in the molten state of eutectic Au–Si alloy of Au81Si19 by using a soft X-ray emission spectroscopy electron microscope
Authors: Terauchi Masami , Umemoto Naoya , K. Sato Yohei , Ageishi Masaki , Tsai An-Pang 
Published: July 2021

Abstract
Phase diagram of Au–Si binary alloy system shows a large drop in melting temperature of about 1000K compared with that of Si at a composition of Au:Si = 81:19, where the melting temperature is about 636K. Mixing of Au and Si below the melting temperature was observed by transmission electron microscopy experiment, and it was found that the mixed region shows a diffraction pattern of a diffuse ring intensity indicating an amorphous structure of the mixed area. Si L-emission spectra, which reflect the energy state of bonding electrons of Si atom, of molten Au81Si19 alloy were measured for the first time to investigate the energy state of valence electrons of Si. The Si L-emission spectrum showed a characteristic loss of L1 peak, which is related to sp3 directional bonding in crystalline Si. The intensity profile is also different from that of molten Si reported. This suggests a characteristic atomic arrangement that exists in the molten state. The intensity profile also indicated a small density of state in the molten state at Fermi energy. The obtained spectrum was compared with the calculated density of state of possible crystal structures reported. The comparison suggested that Si atoms are surrounded by eight Au atoms in the molten state of Au81Si19 alloy. The formation of this local atomic arrangement can be an origin of a large drop of melting temperature at about Au:Si = 81:19.
Rank-Based Inference for Survey Sampling Data
Authors: Adekpedjou Akim , Bindele Huybrechts F 
Published: July 2021

AbstractFor regression models where data are obtained from sampling surveies, the statistical analysis is often based on approaches that are either non-robust or inefficient. The handling of survey data requires more appropriate techniques, as the classical methods usually result in biased and inefficient estimates of the underlying model parameters. This article is concerned with the development of a new approach of obtaining robust and efficient estimates of regression model parameters when dealing with survey sampling data. Asymptotic properties of such estimators are established under mild regularity conditions. To demonstrate the performance of the proposed method, Monte Carlo simulation experiments are carried out and show that the estimators obtained from the proposed methodology are robust and more efficient than many of those obtained from existing approaches, mainly if the survey data tend to result in residuals with heavy-tailed or skewed distributions and/or when there are few gross outliers. Finally, the proposed approach is illustrated with a real data example.
A co-designed integrated kidney and diabetes model of care improves mortality, glycaemic control and self-care
Authors: Zimbudzi Edward , Lo Clement , Ranasinha Sanjeeva , Earnest Arul , Teede Helena , Usherwood Tim , Polkinghorne Kevan R , Fulcher Gregory , Gallagher Martin , Jan Stephen , Cass Alan , Walker Rowan , Russell Grant , Johnson Greg , Kerr Peter G , Zoungas Sophia 
Published: July 2021

ABSTRACT

Background
Current healthcare models are ill-equipped for managing people with diabetes and chronic kidney disease (CKD). We evaluated the impact of a new diabetes and kidney disease service (DKS) on hospitalization, mortality, clinical and patient-relevant outcomes.

Methods
Longitudinal analyses of adult patients with diabetes and CKD (Stages 3a–5) were performed using outpatient and hospitalization data from January 2015 to October 2018. Data were handled according to whether patients received the DKS intervention (n = 196) or standard care (n = 7511). The DKS provided patient-centred, coordinated multidisciplinary assessment and management of patients. Primary analyses examined hospitalization and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in estimated glomerular filtration rate (eGFR), glycated haemoglobin A1c (HbA1c), self-care and patient activation at 12 months.

Results
Patients who received the intervention had a higher hospitalization rate {incidence rate ratio [IRR] 1.20 [95% confidence interval (CI) 1.13–1.30]; P &lt; 0.0001}, shorter median length of stay {2 days [interquartile range (IQR) 1–6] versus 4 days [IQR 1–9]; P &lt; 0.0001} and lower all-cause mortality rate [IRR 0.4 (95% CI 0.29–0.64); P &lt; 0.0001] than those who received standard care. Improvements in overall self-care [mean difference 2.26 (95% CI 0.83–3.69); P &lt; 0.001] and in statin use and eye and feet examinations were observed. The mean eGFR did not change significantly after 12 months [mean difference 1.30 mL/min/1.73 m2 (95% CI −4.17–1.67); P = 0.40]. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12 months of follow-up, respectively.

Conclusions
A co-designed, person-centred integrated model of care improved all-cause mortality, kidney function, glycaemic control and self-care for patients with diabetes and CKD.
Thalamic Deep Brain Stimulation Ameliorates Mixed and Abductor Spasmodic Dysphonia: Case Reports and Proof of Concept
Authors: Honey C Michael , Hart Michael G , Rammage Linda A , Morrison Murray D , Hu Amanda , Honey Christopher R 
Published: July 2021

Abstract

BACKGROUND AND IMPORTANCE
Spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. A recent randomized controlled trial showed that thalamic deep brain stimulation (DBS) was safe and could improve this condition in the most common subtype—adductor SD. We investigated if thalamic DBS could also improve the other subtypes of abductor SD and mixed SD. These prospective blinded trials of 1 were designed to assess the safety of thalamic DBS in mixed and abductor SD and to quantify the magnitude of any benefit from unilateral or bilateral thalamic stimulation.

CLINICAL PRESENTATION
One patient with mixed SD and one patient with abductor SD received bilateral thalamic DBS. After optimizing their DBS settings for vocal improvement, they were blinded and prospectively randomized to receive 1 mo of left, right, both, or neither hemisphere stimulation. Outcome was assessed by a speech language pathologist, blinded to the settings, rating voice recordings with the Unified Spasmodic Dysphonia Rating Scale, and by patient self-reported quality-of-life questionnaires. Additional outcomes included scores of mood and cognition. There were no complications. Both patients reported a subjective improvement of their voice and quality of life with blinded left thalamic DBS. The quality of their voice was also objectively rated as improved with blinded left thalamic DBS.

CONCLUSION
This small proof-of-concept study suggests that left thalamic DBS can improve the quality of voice and quality of life of patients with mixed SD and abductor SD.
Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study
Authors: Burke Rebecca M , Chen Ching-Jen , Ding Dale , Buell Thomas J , Sokolowski Jennifer , Sheehan Kimball A , Lee Cheng-Chia , Sheehan Darrah E , Kano Hideyuki , Kearns Kathryn N , Tzeng Shih-Wei , Yang Huai-che , Huang Paul P , Kondziolka Douglas , Ironside Natasha , Mathieu David , Iorio-Morin Christian , Grills Inga S , Feliciano Caleb , Barnett Gene , Starke Robert M , Lunsford L Dade , Sheehan Jason P ,   on behalf of the International Radiosurgery Research Foundation
Published: July 2021

Abstract

BACKGROUND
Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood.

OBJECTIVE
To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs.

METHODS
We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC).

RESULTS
The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%, < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013).

CONCLUSION
Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.