bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of glucagon response and its association with glycemic control and variability after administration of ipragliflozin as an adjunctive to insulin treatment in patients with type 1 diabetes (Suglat-AID)
Authors: Nakamura Yuta , Horie Ichiro , Tashiro Shigeki , Kobayashi Masaki , Kitamura Tadahiro , Kusunoki Yoshiki , Nishida Kenro , Yamamoto Akane , Hirota Yushi , Fukui Tomoyasu , Sekiguchi Dan , Maeda Yasutaka , Minami Masae , Matsui Takanori , Kawakami Atsushi , Abiru Norio 
Published: September 2021

Abstract

Background:
Despite advances in insulin preparation, insulin delivery systems and glucose monitoring, it is extremely difficult to maintain glucose levels within the non-diabetic range in patients with type 1 diabetes (T1D). Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently raised the prospect of improving glucometabolic outcomes in an insulin-independent manner. SGLT2 inhibitors adjunctive to insulin treatment have been shown in T1D clinical trials to improve glycemic variability without increasing hypoglycemia. Conversely, some meta-analyses raised valid concerns regarding increased risk of euglycemic ketoacidosis after treatment of SGLT2 inhibitors in T1D. Increased hepatic ketogenesis caused by elevated glucagon secretion in patients receiving SGLT2 inhibitors has been discussed as a potential mechanism for euglycemic ketoacidosis in insulinopenic T1D, but the mechanism has not been fully elucidated. In this study, we investigate 1) whether glucagon secretions are altered by treatment with the SGLT2 inhibitor ipragliflozin as an adjunctive to insulin therapy in T1D patients, and 2) whether the glucagon responses are associated with amelioration/deterioration in glycemic control and serum ketone levels.

Methods/design:
This is a single-arm, multicenter, open-label, prospective exploratory trial designated Suglat-AID. Eligible participants are absolute-insulin-deficient T1D patients with glycated hemoglobin levels over 7.5%, who are receiving intensive insulin therapy using intermittently scanned continuous glucose monitoring. Thirty patients will be recruited and will take orally administered ipragliflozin as an add-on to insulin therapy. The primary endpoint is the change in glucagon levels during a mixed meal tolerance test between before and 12 weeks after initiation of ipragliflozin. Secondary endpoints include the changes in insulin and glucose levels during mixed meal tolerance test, the change in the patients’ glycemic control, change in the intermittently scanned continuous glucose monitoring-based profile and others.

Discussion:
To the best of our knowledge, this will be the first study assessing changes in glucagon response to an SGLT2 inhibitor in patients with T1D in a clinical setting. This study may help to clarify the pathophysiological role of glucagon in glycemia and ketogenesis in patients with T1D receiving SGLT2 inhibitors.

Trial registration:
This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (https://umin.ac.jp) on 24 March, 2020 under registration no. UMIN000039635.
Catching Fire: Are Operating Room Fires a Concern in Orthopedics?
Authors: Jardaly Achraf , Arguello Alexandra , Ponce Brent A. , Leitch Kellie , McGwin Gerald , Gilbert Shawn R. 
Published: September 2021

Objective
Operating room (OR) fires are considered “never events,” but approximately 650 events occur annually in the United States. Our aim was to detail fires occurring during orthopedic procedures via a questionnaire because of the limited information present on this topic.

Methods
A 25-question survey on witnessing surgical fires, hospital policies on surgical fires, and surgeons’ perspective on OR fires was sent to 617 orthopedic surgeons in 18 institutions whose residency program is a member of the Collaborative Orthopaedic Educational Research Group. The response rate was 28%, with 172 surgeons having completed the survey.

Results
Twelve of the 172 orthopedic surgeons surveyed reported witnessing at least 1 surgical fire in an OR setting. Electrocautery was the leading ignition source, causing fires in 7 events. A saw, laser, and light source were reported to have caused 1 fire each. Regarding fuel source for the fires, bone cement was a common culprit (n = 4), followed by gauze (n = 3). Oxygen delivery to patients was via a closed system in most cases (n = 9). No patient harm was reported in any of these cases.
Just under half of the respondents (47.7%) reported not receiving any formal OR fire prevention or response training. The most common answer for frequency of concern about a surgical fire was “never” (42.4%).

Conclusions
Fires pose a risk in surgery, even in an orthopedics setting. Room oxygen can supply enough oxidizing power for a fire to occur, especially with the ubiquitous nature of ignition sources and fuels in the OR. Prevention is key with these events. Operating room personnel education must be sought, and surgeons should be mindful of the fire components in the OR.
Classification of Distinct Patterns of Ischemic Cholangiopathy Following DCD Liver Transplantation: Distinct Clinical Courses and Long-term Outcomes From a Multicenter Cohort
Authors: Croome Kristopher P. , Mathur Amit K. , Aqel Bashar , Yang Liu , Taner Timucin , Heimbach Julie K. , Rosen Charles B. , Paz-Fumagalli Ricardo , Taner C. Burcin 
Published: September 2021

Background.
As the number of donation after circulatory death (DCD) liver transplants (LTs) performed in the United States continues to increase annually, there has been interest by policy makers to develop a more robust exception point safety net for patients who develop ischemic cholangiopathy (IC) following DCD LT. As such, there is a need for better understanding of the clinical course and long-term outcomes in patients who develop IC, as well as determining if IC can be classified into distinct categories with distinctly different clinical outcomes.

Methods.
All DCD LT performed at Mayo Clinic Florida, Mayo Clinic Arizona, and Mayo Clinic Rochester from January 1999 to March 2020 were included (N = 770). Outcomes were compared between 4 distinct radiologic patterns of IC: diffuse necrosis, multifocal progressive, confluence dominant, and minor form.

Results.
In total, 88 (11.4%) patients developed IC, of which 42 (5.5%) were listed for retransplantation of liver (ReLT). Patients with diffuse necrosis and multifocal progressive patterns suffered from frequent hospital admissions for cholangitis in the first year following DCD LT (median 3 and 2), were largely stent dependent (100% and 85.7%), and almost universally required ReLT. Patients with confluence dominant disease were managed with multiple stents and frequently recovered, ultimately becoming stent free without need for ReLT. Patients with the minor form IC did well with limited need for stent placement or repeat procedures and did not require ReLT. Graft survival was different between the 4 distinct IC patterns (P < 0.001).

Conclusions.
The present analysis provides a detailed analysis on the natural history and clinical course of IC. Patients developing IC can be classified into 4 distinct patterns with distinct clinical courses.
Chemotherapy in Cases of Trypanosoma cruzi Reinfection: Assessing for Chagas Disease Endemic Areas
Authors: Rebouças Mônica Cardozo , Silva Guerreiro Marcos Lázaro da , Eduardo Anderson Aires , Andrade Sonia Gumes 
Published: September 2021

ABSTRACTPeople living in endemic areas of Chagas disease are submitted to multiple infections during their lives. This is an important factor in the development and morbidity of the disease. In the present investigation, evaluate the treatment outcome of triple infection mice with 21SF clones compared to the parental strain and with clones were investigated. Mice were infected and divided into groups: G1, infected with 21SF strain; G2, infected with 3 clones’s 21SF strain; and G3, infected with each clone alone. Subsequently, the groups were subdivided in treated and untreated controls. After the treatment the mice were euthanized. Serological tests and parasitological tests were performed. Sections of the heart and skeletal muscle were collected, fixed and then processed for the histopathological study in sections stained with Hematoxilin end Eosin. Parasitological tests for animals treated have shown positive results that varied from 25 to 66.7% and the serology titers varied from 1:10 a 1:280 in treated mice. Cure rates ranged from 11.1 to 30.8%. Histopathological examination revealed that treated animals presented clear reduction of lesions in myocardium and in skeletal muscle. Animals subjected to multiple infections have low rates of cure and worsening of tissue lesions.
Non-additive QTL mapping of lactation traits in 124,000 sequence-imputed cattle reveals novel recessive loci
Authors: Reynolds Edwardo GM , Lopdell Thomas , Wang Yu , Tiplady Kathryn M , Harland Chad S , Johnson Thomas JJ , Neeley Catherine , Carnie Katie , Sherlock Richard G , Couldrey Christine , Davis Stephen R , Harris Bevin L , Spelman Richard J , Garrick Dorian J , Littlejohn Mathew D 
Published: September 2021

AbstractDeleterious recessive conditions have primarily been studied in a Mendelian disease context. Recently, several large effect, deleterious recessive mutations were discovered via non-additive GWAS of quantitative growth and developmental traits in cattle. This showed quantitative traits can be used as proxies of genetic disorders if they are indicative of whole animal health status and susceptible to underlying genetic conditions. Lactation traits might also reflect genetic disorders in cattle, given the increased energy demands of lactation and the substantial stresses imposed on the animal. Here, we report a screen of over 124,000 cows for recessive effects based on lactation traits. We discovered novel loci associated with five large recessive impacts on milk yield traits represented by missense variants (DOCK8, IL4R, KIAA0556, and SLC25A4) or premature stop variants (ITGAL, LRCH4, and RBM34) as candidate causal mutations. On milk composition traits, we identified several small effect dominance contributions to previously reported additive QTL. In contrasting analyses of milk yield and milk composition phenotypes, we note differing genetic architectures. Milk yield phenotypes presented lower heritabilities and fewer additive QTL, but higher non-additive genetic variance and a higher proportion of loci exhibiting dominance compared to milk composition phenotypes. Large-effect recessive QTL are segregating at surprisingly high frequencies in cattle. We speculate that the differences in genetic architecture between milk yield and milk composition phenotypes derive from underlying dissimilarities in the cellular and molecular representation of these traits. Lactation yields may act as a better proxy than milk composition traits for a wide range of underlying biological disorders affecting animal fitness
Distribution and habitat use of the Madagascar Peregrine Falcon: first estimates for area of habitat and population size
Authors: Sutton Luke J. , Réné de Roland Lily-Arison , Thorstrom Russell , McClure Christopher J.W. 
Published: September 2021

AbstractAccurately demarcating species distributions has long been at the core of ecology. Yet our understanding of the factors limiting species range limits is incomplete, especially for tropical species in the Global South. Human-driven threats to the survival of many taxa are increasing, particularly habitat loss and climate change. Identifying distributional range limits of at-risk and data-limited species using Species Distribution Models (SDMs) can thus inform spatial conservation planning to mitigate these threats. The Madagascar Peregrine Falcon (Falco peregrinus radama) is the resident sub-species of the Peregrine Falcon complex distributed across Madagascar, Mayotte, and the Comoros Islands. Currently, there are significant knowledge gaps regarding its distribution, habitat preferences and population size. Here, we use point process regression models and ordination to identify Madagascar Peregrine Falcon environmental range limits and propose a population size estimate based on inferred habitat. From our models, the core range of the Madagascar Peregrine Falcon extends across the central upland plateau of Madagascar with a patchier range across coastal and low-elevation areas. Range-wide habitat use indicated that the Madagascar Peregrine Falcon prefers areas of high elevation and aridity, coupled with high vegetation heterogeneity and > 95 % herbaceous landcover, but generally avoids areas of > 30 % cultivated land and > 10 % mosaic forest. Based on inferred high-class habitat, we estimate this habitat area could potentially support a population size ranging between 150-300 pairs. Following International Union for Conservation of Nature Red List guidelines, we recommend this sub-species be classed as Vulnerable, due to its small population size. Despite its potentially large range, the Madagascar Peregrine has specialized habitat requirements and would benefit from targeted conservation measures based on spatial models in order to maintain viable populations.
De NovoPrediction of RNA 3D Structures with Deep Learning
Authors: Ramakers Julius , Blum Christopher Frederik , König Sabrina , Harmeling Stefan , Kollmann Markus 
Published: September 2021

AbstractWe present a Deep Learning approach to predict 3D folding structures of RNAs from their nucleic acid sequence. Our approach combines an autoregressive Deep Generative Model, Monte Carlo Tree Search, and a Score Model to find and rank the most likely folding structures for a given RNA sequence. We confirm the predictive power of our approach by setting new benchmarks for some longer sequences in a simulated blind test of the RNA Puzzles prediction challenge.
Edible fire buffers: mitigation of wildfire with multifunctional landscapes
Authors: Fu Xiao , Lidar Abigail , Kantar Michael , Raghavan Barath 
Published: September 2021

AbstractWildfires ravage lands in seasonally-dry regions, imposing high costs on infrastructure maintenance and human habitation at the wildland-urban interface (WUI). Current fire mitigation approaches present upfront costs with uncertain long-term payoffs. Instead, we show that a simple landscape intervention on human-managed wildlands – buffers of a low-flammability crop species such as banana irrigated using recycled water – can mitigate wildfires, produce food profitably, and provide additional ecosystem services. Recreating a recent, major fire in simulation, we find that a medium-sized banana buffer decreases fireline intensity by 96%, similar to prescribed burns and mechanical thinning combined, and delays the fire by 316 minutes, enabling safe and effective firefighting. We find that under climate change, despite worsened fires, banana buffers will still have a protective effect. We also find that banana buffers with average yield could produce a profit of $56k USD/hectare through fruit sales, in addition to fire mitigation and other benefits.
Evaluating host to host transplants as a method to study plant bacterial assembly
Authors: Baldock Christopher , Wilson Neil , Deaker Rosalind 
Published: September 2021

AbstractThe ability to predict plant microbiome assembly will enable new bacterial-based technologies for agriculture. A major step towards this is quantifying the roles of ecological processes on community assembly. This is challenging, in part because individual plants are colonised by different communities of soil bacteria and it is difficult to estimate if the absence of a given species was a) because it was not present in the soil to colonise a given plant or b) it went locally extinct from competition, predation or similar. To minimise this uncertainty, the authors develop a mesocosm system to study bacterial communities of individual plants by replicated transplantation to a recipient host plant population, ensuring new hosts receive a homogenous species pool for colonisation. We sought to understand which factors affected the transplant and, what the main drivers of variation in the model communities were. A nested factorial design was used to investigate the transplantation of cultured or total, root or leaf associated bacterial communities from donor host species to surrogate host species. Specific metrics were developed to quantify colonisation efficiency of communities. The results show the root communities were more effectively transplanted than leaf communities, with leaf communities more susceptible to contamination. For root communities the strongest driver of beta diversity was the donor host species, and for leaves it was the surrogate host species. Overall, the results reveal that root, but not leaf communities are amenable to transplant reflecting their differing ecological drivers. This work provides the basis to develop a plant microbiome transplant system.
Immunogenicity and efficacy of Heat Inactivated Whole-Cell Vaccine to increase murine survival after Extensively drug-resistant Acinetobacter baumannii infection
Authors: Sharmin Nazmun , Khoda Mahbub E , Shamsuzzaman SM , Uddin Mohammad Nazim 
Published: September 2021

AbstractDue to the rapid emergence of extensively drug-resistant (XDR) strains worldwide there is a necessity for greater consideration for the role of preventive vaccines to combat these pathogens. The study reported the effectiveness of a heat-inactivated whole-cell vaccine (HI-WCV) against A. baumannii to produce protective immunity with evaluation of the bactericidal antibody responses in mice after intramuscular inoculation with different XDR strains of A. baumannii. Six XDR A. baumannii strains emulsified with complete freund’s adjuvant (CFA) were used for intramuscular inoculation in the experimental group of mice (n=4) in three different phases on 14 days interval whereas placebo-controlled mice (n=4) received phosphate-buffered saline emulsified with CFA in same the schedule. Serum was collected from tail blood of each mouse on 10th day after each inoculation and by cardiac puncture on 14th day after lethal dose from the experimental group and after death of the placebo-controlled group. Mice inoculated with heat-inactivated whole-cell vaccine survived and showed a higher neutralizing (IgG) antibody response after 2nd (>7-fold titre) and 3rd inoculation (>12-fold titre) whereas all mice from placebo-controlled group did not survived. Sera from experimental group of mice collected (38th day) after 3rd inoculation resulted in higher serum bactericidal killing index (42.12) after three hours incubation with an XDR A. baumannii over sera collected after 1st and 2nd inoculation (50% cutoff value=14.5). These results suggest that intramuscular vaccination with heat-inactivated whole-cell vaccine stimulated IgG antibody responses that can increase murine survival after XDR A. baumannii infection.
Evaluation of patient experience for a computationally-guided intranasal spray protocol to augment therapeutic penetration
Authors: Basu Saikat , Khawaja Uzzam Ahmed , Rizvi Syed A A , Gong BoLiang , Yeung Waiman , Sanchez-Gonzalez Marcos A , Ferrer Gustavo 
Published: September 2021

AbstractThe global respiratory outbreak in the form of COVID-19 has underlined the necessity to devise more effective and reproducible intranasal drug delivery modalities, that would also be user-friendly for adoption compliance. In this study, we have collected evaluation feedback from a cohort of 13 healthy volunteers, who assessed two different nasal spray administration techniques, namely the vertical placement protocol (or, VP), wherein the nozzle is held vertically upright at a shallow insertion depth of 0.5 cm inside the nasal vestibule; and the shallow angle protocol (or, SA), wherein the spray axis is angled at 45° to the vertical, with a vestibular insertion depth of 1.5 cm. The SA protocol is derived from published findings on alternate spray orientations that have been shown to enhance targeted delivery at posterior infection sites, e.g., the ostiomeatal complex and the nasopharynx. All study participants reported that the SA protocol offered a more gentle and soothing delivery experience, with less impact pressure. Additionally, 60% participants opined that the VP technique caused painful irritation. We also tracked the drug transport processes for the two spray techniques in a computed tomography-based nasal reconstruction; the SA protocol marked a distinct improvement in therapeutic penetration when compared to the VP protocol.
Nanomechanical and molecular characterization of aging in dentinal collagen
Authors: Schuh Christina MAP , Leiva-Sabadini Camila , Huang Sophia , Barrera Nelson P , Bozec Laurent , Aguayo Sebastian 
Published: September 2021

AbstractMethylglyoxal (MGO) is an important molecule derived from glucose metabolism with the capacity of attaching to collagen and generating advanced glycation end-products (AGEs), which accumulate in tissues over time and are associated to aging and diseases. However, the accumulation of MGO-derived AGEs in dentin and their effect on the nanomechanical properties of dentinal collagen remain unknown. Thus, the aim of the present study was to quantify MGO-based AGEs in the organic matrix of human dentin as a function of age and associate these changes with alterations in the nanomechanical and ultrastructural properties of dentinal collagen. For this, twelve healthy teeth from <26 year-old and >50 year-old patients were collected and prepared to obtain crown and root dentin discs. Following demineralization, MGO-derived AGEs were quantified with a competitive ELISA assay. In addition, atomic force microscopy (AFM) nano-indentation was utilized to measure changes in elastic modulus in both peritubular (PT) and intertubular (IT) collagen fibrils. Finally, principal component analysis (PCA) was carried out to determine aging profiles for both crown and root dentin. Results showed increased presence of MGO AGEs in the organic matrix of dentin in the >50 year-old compared to <26 year-old samples in both crown and root. Furthermore, an overall increase in PT and IT collagen elasticity was observed in the >50 year-old group associated to ultrastructural changes in the organic matrix determined by AFM analysis. Furthermore, PCA loading plots suggested different ‘aging profiles’ in both crown and root dentin, which could potentially have important therapeutic implications in restorative and adhesive dentistry approaches. Overall, these results demonstrate that the organic matrix of human dentin undergoes aging-related changes due to MGO-derived AGEs with important changes in nanomechanical behavior of collagen that may impact diagnostic and restorative procedures in the elderly.