bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the cluster MabR prophages of Mycobacterium abscessus and Mycobacterium chelonae
Authors: Cote Jacob , Welch Colin , Kimble Madeline , Archambault Dakota , Ross John Curtis , Orellana Hector , Amero Katelyn , Bourett Claire , Daigle Andre , Hutchison Keith W , Molloy Sally D
Published: July 2022

Mycobacterium abscessus is an emerging pathogen of concern in cystic fibrosis and immunocompromised patients and is considered one of the most drug-resistant mycobacteria. The majority of clinical Mycobacterium abscessus isolates carry 1 or more prophages that are hypothesized to contribute to virulence and bacterial fitness. The prophage McProf was identified in the genome of the Bergey strain of Mycobacterium chelonae and is distinct from previously described prophages of Mycobacterium abscessus. The McProf genome increases intrinsic antibiotic resistance of Mycobacterium chelonae and drives expression of the intrinsic antibiotic resistance gene, whiB7, when superinfected by a second phage. The prevalence of McProf-like genomes was determined in sequenced mycobacterial genomes. Related prophage genomes were identified in the genomes of 25 clinical isolates of Mycobacterium abscessus and assigned to the novel cluster, MabR. They share less than 10% gene content with previously described prophages; however, they share features typical of prophages, including polymorphic toxin–immunity systems.
Radiated seismic energy and source damage evolution from the analysis of simulated dynamic rupture and far-field seismograms
Authors: Kurzon Ittai , Lyakhovsky Vladimir , Sagy Amir , Ben-Zion Yehuda
Published: July 2022

We present results on radiated seismic energy during simulations of dynamic ruptures in a continuum damage-breakage rheological model incorporating evolution of damage within the seismic source region. The simulations vary in their initial damage zone width and rate of damage diffusion with parameter values constrained by observational data. The radiated energy recorded at various positions around the source is used to calculate seismic potency and moment. We also calculate the normalized radiated energy from the source, in a way that allows comparing between results of different simulations and highlighting aspects related to the dilatational motion during rupture. The results show that at high-frequencies, beyond the dominant frequency of the source ($( {f > 3{f}_d} )$, the damage process produces an additional burst of energy mainly in the Pwaves. This eccess of high-frequency energy is observed by comparing the radiated energy to a standard Brune's model with a decay slope of the radiated energy of n = 2. While the Swaves show good agreement with the n = 2 slope, the Pwaves have a milder slope of n = 1.75 or less depending on the damage evolution at the source. In the used damage-breakage rheology, the rate of damage diffusivity governs the damage evolution perpendicular to the rupture direction and dynamic changes of the damage zone width. For increasing values of damage diffusivity, dilatational energy becomes more prominent during rupture, producing a high-frequency dilatational signature within the radiation pattern. The high-frequency radiation pattern of the Pwaves includes two main lobes perpendicular to the rupture direction, reflecting high-rate local tensile cracking during the overall shear rupture process. Analysing the possible existence and properties of such high-frequency radiation pattern in observed Pwaves could provide important information on earthquake source processes.
Three-dimensional Gauss–Newton constant-Q viscoelastic full-waveform inversion of near-surface seismic wavefields
Authors: Mirzanejad Majid , Tran Khiem T , Wang Yao
Published: July 2022

Full-waveform inversion (FWI) methods rely on accurate numerical simulation of wave propagation in the analysed medium. Acoustic or elastic wave equations are often used to model seismic wave propagation. These types of simulations do not account for intrinsic attenuation effects due to material anelasticity, and thus correction techniques have been utilized in practice to partially compensate the anelasticity. These techniques often only consider the waveform amplitude correction based on averaging of overall amplitude response over the entire data set, and ignore the phase correction. Viscoelastic wave equations account for the anelastic response in both waveform amplitude and phase, and are therefore a more suitable alternative. In this study, we present a novel 3-D Gauss–Newton viscoelastic FWI (3-D GN-VFWI) method. To address the main challenge of the Gauss–Newton optimization, we develop formulas to compute the Jacobian efficiently by the convolution of virtual sources and backward wavefields. The virtual sources are obtained by directly differentiating the viscoelastic wave equations with respect to model parameters. In order to resolve complex 3-D structures with reasonable computational effort, a homogeneous attenuation (Q factor) is used throughout the analysis to model the anelastic effects. Synthetic and field experiments are performed to demonstrate the utility of the method. The synthetic results clearly demonstrate the ability of the method in characterizing a challenging velocity profile, including voids and reverse velocity layers. The field experimental results show that method successfully characterizes the complex substructure with two voids and undulating limestone bedrock, which are confirmed by invasive tests. Compared to 3-D elastic FWI results, the presented viscoelastic method produces more accurate results regarding depths of the voids and bedrock. This study suggests that the improvement of imaging accuracy would warrant the widespread use of viscoelastic wave equations in FWI problems. To our best knowledge, this is the first reported study on 3-D GN-VFWI at any scale. This study provides the new theory and formulation for the use of Gauss–Newton optimization on the 3-D viscoelastic problem.
Movement, Space Use, and the Responses of Coral Reef Fish to Climate Change
Authors: Manning J C
Published: July 2022

Anthropogenic climate change and other localized stressors have led to the widespread degradation of coral reefs, characterized by losses of live coral, reduced structural complexity, and shifts in benthic community composition. These changes have altered the composition of reef fish assemblages with important consequences for ecosystem function. Animal movement and space use are critically important to population dynamics, community assembly, and species coexistence. In this perspective, I discuss how studies of reef fish movement and space use could help us to elucidate the effects of climate change on reef fish assemblages and the functions they provide. In addition to describing how reef fish space use relates to resource abundance and the intrinsic characteristics of reef fish (e.g., body size), we should begin to take a mechanistic approach to understanding movement in reef fish and to investigate the role of movement in mediating species interactions on coral reefs. Technological advances in animal tracking and biotelemetry, as well as methodological advances in the analysis of movement, will aid in this endeavor. Baseline studies of reef fish movement and space use and their effect on community assembly and species coexistence will provide us with important information for predicting how climate change will influence reef fish assemblages.
A combination of polyglycolic acid fabric and fibrin glue prevents air leakage from a lung defect
Authors: Suzuki Akiyo , Konishi Hayato , Suzuki Tatsuya , Katsumata Takahiro , Hanaoka Nobuharu , Nakamura Koichiro , Matsubara Chisa , Fujii Shota , Nemoto Shintaro
Published: July 2022

OBJECTIVES

Air leakage after lung resection is a common morbidity that may lengthen hospital stay. Applying sealant to a lesion is an effective prophylaxis in clinical practice. This study aimed to examine the effect of a combination of a bioabsorbable polyglycolic acid (PGA) fabric and fibrin glue (FG) on air sealing by measuring the in vitro mechanical strength and degradation of the fabric, and in vivo histological changes after implantation.

METHODS

A defect was created in the canine left upper lung lobe, and then filled with a fibrinogen solution and covered with a PGA sheet spray-coated with fibrinogen and thrombin. After 1 and 4 weeks, air leakage from the lesion was examined in vivo under airway pressure. Tissue samples were harvested for histological assessment.

RESULTS

The mechanical strength of the PGA fabric remained at 80–90% of the baseline level for 1 week in phosphate-buffered saline, and then rapidly decreased to zero thereafter. Air leakage from the lung defect was prevented by the combination of PGA fabric and FG at 1 and 4 weeks. Histological examinations showed that PGA bundles persisted with a non-specific inflammatory response for 2 weeks and then gradually broke into sparse yarns surrounded by collagen fibres and capillaries by 8 weeks. The lung defect was filled with FG at 1 week and by granulation tissue thereafter.

CONCLUSIONS

These results provide evidence for the efficacy of a combination of PGA fabric and FG for the prevention of air leakage in the critical period after lung surgery.
The Amazonian Tropical Bites Research Initiative, a hope for resolving zoonotic neglected tropical diseases in the One Health era
Authors: Taylor Emma , Aguilar-Ancori Elsa Gladys , Banyard Ashley C , Abel Isis , Mantini-Briggs Clara , Briggs Charles L , Carrillo Carolina , Gavidia Cesar M , Castillo-Neyra Ricardo , Parola Alejandro D , Villena Fredy E , Prada Joaquin M , Petersen Brett W , Falcon Perez Nestor , Cabezas Sanchez Cesar , Sihuincha Moises , Streicker Daniel G , Maguina Vargas Ciro , Navarro Vela Ana Maria , Vigilato Marco A N , Wen Fan Hui , Willoughby Rodney , Horton Daniel L , Recuenco Sergio E
Published: July 2022

Background

Neglected tropical diseases (NTDs) disproportionately affect populations living in resource-limited settings. In the Amazon basin, substantial numbers of NTDs are zoonotic, transmitted by vertebrate (dogs, bats, snakes) and invertebrate species (sand flies and triatomine insects). However, no dedicated consortia exist to find commonalities in the risk factors for or mitigations against bite-associated NTDs such as rabies, snake envenoming, Chagas disease and leishmaniasis in the region. The rapid expansion of COVID-19 has further reduced resources for NTDs, exacerbated health inequality and reiterated the need to raise awareness of NTDs related to bites.

Methods

The nine countries that make up the Amazon basin have been considered (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Surinam and Venezuela) in the formation of a new network.

Results

The Amazonian Tropical Bites Research Initiative (ATBRI) has been created, with the aim of creating transdisciplinary solutions to the problem of animal bites leading to disease in Amazonian communities. The ATBRI seeks to unify the currently disjointed approach to the control of bite-related neglected zoonoses across Latin America.

Conclusions

The coordination of different sectors and inclusion of all stakeholders will advance this field and generate evidence for policy-making, promoting governance and linkage across a One Health arena.
Patterns of Democracy over Space and Time
Authors: Boese Vanessa Alexandra , Gates Scott , Knutsen Carl Henrik , Nygård Håvard Mokleiv , Strand Håvard
Published: July 2022

Unidimensional measures of democracy fail to account for the complex and varied nature of political systems. This article disaggregates the concept of democracy and proposes a multidimensional conceptualization to account for this variation in institutional configurations. Three theoretically informed dimensions are featured: participation, electoral contestation, and constraints on the executive. The three dimensions constitute a cube covering all regime types, in which we place countries using V-Dem data from 1789 to 2019. This cube of democracy patterns reveals several interesting observations. We trace historical patterns of democratization and discuss how countries across the world have taken different paths at different times. Our conceptualization shows that political systems with a similar score along a unidimensional scale are often quite distinct. In addition, across the globe for 200 years, certain configurations of political institutions rarely occur. Furthermore, our approach reveals interesting patterns of regime convergence and divergence over time. Finally, we show that the typical pathways to democracy have changed since 1789. This multidimensional conceptualization ultimately opens up new avenues for research in which institutional variation and change can be studied in greater detail.
Forum: New Perspectives on Transnational Non-State Actors—A Forum Honoring the Work of Thomas Risse
Authors: Berger Tobias , Holzscheiter Anna , Jetschke Anja , Schmitz Hans Peter , Esguerra Alejandro
Published: July 2022

This forum seeks to honor the contributions of a scholar who has greatly influenced international relations (IR) scholarship on transnational relations and constructivist research: Thomas Risse. Best known for his pathbreaking studies on the importance of transnational actors, the power of international norms and ideas in international relations, and the influence of domestic structures on international interactions, his work has significantly contributed to several interrelated research agendas within IR. The forum takes a fresh look at some of his contributions, focusing on assumptions about the nature of non-state actors, the content of human rights, and the evolution of knowledge that underpin his work. Interrogating especially some of the liberal assumptions that have informed these lines of research, we ask: are we still dealing with the same kinds of non-state actors that Thomas Risse and early constructivist research have analyzed? How has the nature of these actors changed, and how has this affected the processes and mechanisms by which they shape transnational politics? To what extent do these changes require different research methodologies? And, finally, which directions for future research on non-state actors, human rights, and constructivism emerge from these discussions?
Lunapark ubiquitinates atlastin-2 for the tubular network formation of the endoplasmic reticulum
Authors: Anggrandariyanny Putri Chynthia , Kajiho Hiroaki , Yamamoto Yasunori , Sakisaka Toshiaki
Published: July 2022

Endoplasmic reticulum (ER) tubules are interconnected by three-way junctions, resulting in the formation of a tubular ER network. Lunapark (Lnp) localizes to and stabilizes the three-way junctions. The N-terminal cytoplasmic domain in Lnp has a ubiquitin ligase activity. However, the molecular mechanism of how the ubiquitin ligase activity of Lnp is involved in the formation of the tubular ER network remains unknown. In this study, we examined whether the ER membrane proteins responsible for the formation of the tubular ER network are ubiquitinated by Lnp. We found that atlastin-2 (ATL2), an isoform of the ATL family mediating the generation of the three-way junctions by connecting the ER tubules, is a novel substrate for ubiquitination by Lnp. The localization of Lnp at the three-way junctions is important for ubiquitination of ATL2. Lysine 56, 57, 282 and 302 are the potential ubiquitination sites by Lnp. Silencing ATL2 decreased the number of the three-way junctions, and the expression of the ATL2 mutant in which the lysine residues are substituted with arginine failed to rescue the decrease of the three-way junctions in the ATL2 knocked-down cells. These results suggest that Lnp ubiquitinates ATL2 at the three-way junctions for the proper tubular ER network formation.
Endogenous Lemon Markets: Risky Choices and Adverse Selection
Authors: Lichtig Avi , Weksler Ran
Published: July 2022

The severity of adverse selection depends, to a great extent, on the underlying distribution of the asset. This distribution is commonly modeled as exogenous; however, in many real-world applications, it is determined endogenously. A natural question in this context is whether one can predict the severity of the adverse selection problem in such environments. In this paper, we study a bilateral trade model in which the distribution of the asset is affected by pre-trade unobservable actions of the seller. Analyzing general trade mechanisms, we show that the seller’s actions are characterized by a risk-seeking disposition. In addition, we show that (location-independent) riskier underlying distributions of the asset induce lower social welfare. That is, “lemon markets” arise endogenously in these environments.
Delayed Post-Traumatic Hemobilia in a Patient With Blunt Abdominal Trauma: A Case Report and Review of the Literature
Authors: Schütz Štěpán-Ota , Rousek Michael , Pudil Jiří , Záruba Pavel , Malík Jozef , Pohnán Radek
Published: July 2022

Hemobilia is a rare condition defined as bleeding in the biliary tract. The clinical presentation is variable. The typical manifestation consists of jaundice, upper gastrointestinal bleeding, and right upper quadrant abdominal pain. This set of symptoms is known as “Quincke’s triad.” It is present in only 22%-35% of cases. Post-traumatic hemobilia is an extraordinarily rare condition occurring in only 6% of the patients with hemobilia. In general, it occurs in less than 0.2% of patients with liver trauma. A delay in the development of bleeding after liver trauma is frequent. Early diagnosis is essential because massive bleeding into the biliary tract is a potentially life-threatening condition. We present a case of a patient with massive hemobilia developed 12 days after blunt abdominal trauma. Computed tomography angiography showed two pseudoaneurysms in hepatic segments V and VIII with contrast medium extravasation. We successfully performed digital subtraction angiography with selective transcatheter arterial embolization of the leaking segment VIII pseudoaneurysm. Embolization of the pseudoaneurysm in segment V was technically impracticable. Our article provides a review of the published literature focussing on the prevalence, diagnostics, and treatment of post-traumatic hemobilia.
Can superbubbles accelerate ultrahigh energy protons?
Authors: Vieu T , Reville B , Aharonian F
Published: July 2022

We critically assess limits on the maximum energy of protons accelerated within superbubbles around massive stellar clusters, considering a number of different scenarios. In particular, we derive under which circumstances acceleration of protons above peta-electronvolt (PeV) energies can be expected. While the external forward shock of the superbubble may account for acceleration of particles up to 100 TeV, internal primary shocks such as supernova remnants expanding in the low density medium or the collective wind termination shock which forms around a young compact cluster provide more favourable channels to accelerate protons up to 1 PeV, and possibly beyond. Under reasonable conditions, clustered supernovae launching powerful shocks into the magnetized wind of a young and compact massive star cluster are found to be the most promising systems to accelerate protons above 10 PeV. On the other hand, stochastic re-acceleration in the strongly turbulent plasma is found to be much less effective than claimed in previous works, with a maximum proton energy of at most a few hundred TeV.
Intensity mapping from the sky: synergizing the joint potential of [O iii] and [C ii] surveys at reionization
Authors: Padmanabhan Hamsa , Breysse Patrick , Lidz Adam , Switzer Eric R
Published: July 2022

We forecast the ability of future-generation experiments to detect the fine-structure lines of the carbon and oxygen ions, [C ii] and [O iii] in intensity mapping (IM) from the Epoch of Reionization (z ∼ 6–8). Combining the latest empirically derived constraints relating the luminosity of the [O iii] line to the ambient star formation rate, and using them in conjunction with previously derived estimates for the abundance of [C ii] in haloes, we predict the expected autocorrelation IM signal to be observed using new experiments based on the Fred Young Submillimetre Telescope (FYST) and the balloon-borne facility, Experiment for Cryogenic Large-Aperture Intensity Mapping (EXCLAIM) over z ∼ 5.3–7. We describe how improvements to both the ground-based and balloon-based surveys in the future will enable a cross-correlation signal to be detected at ∼10–30σ over z ∼ 5.3–7. Finally, we propose a space-based mission targeting the [O iii] 88 and 52 $\mu$m lines along with the [C ii] 158 $\mu$m line, configured to enhance the signal-to-noise ratio of cross-correlation measurements. We find that such a configuration can achieve a high-significance detection (hundreds of σ) in both auto and cross-correlation modes.
Effects of the environment and feedback physics on the initial mass function of stars in the STARFORGE simulations
Authors: Guszejnov Dávid , Grudić Michael Y , Offner Stella S R , Faucher-Giguère Claude-André , Hopkins Philip F , Rosen Anna L
Published: July 2022

One of the key mysteries of star formation is the origin of the stellar initial mass function (IMF). The IMF is observed to be nearly universal in the Milky Way and its satellites, and significant variations are only inferred in extreme environments, such as the cores of massive elliptical galaxies and the Central Molecular Zone. In this work, we present simulations from the STARFORGE project that are the first cloud-scale radiation-magnetohydrodynamic simulations that follow individual stars and include all relevant physical processes. The simulations include detailed gas thermodynamics, as well as stellar feedback in the form of protostellar jets, stellar radiation, winds, and supernovae. In this work, we focus on how stellar radiation, winds, and supernovae impact star-forming clouds. Radiative feedback plays a major role in quenching star formation and disrupting the cloud; however, the IMF peak is predominantly set by protostellar jet physics. We find that the effect of stellar winds is minor, and supernovae ‘occur too late’ to affect the IMF or quench star formation. We also investigate the effects of initial conditions on the IMF. We find that the IMF is insensitive to the initial turbulence, cloud mass, and cloud surface density, even though these parameters significantly shape the star formation history of the cloud, including the final star formation efficiency. Meanwhile, the characteristic stellar mass depends weakly on metallicity and the interstellar radiation field, which essentially set the average gas temperature. Finally, while turbulent driving and the level of magnetization strongly influence the star formation history, they only influence the high-mass slope of the IMF.
Precise tuning of bacterial translation initiation by non-equilibrium 5′-UTR unfolding observed in single mRNAs
Authors: Ray Sujay , Dandpat Shiba S , Chatterjee Surajit , Walter Nils G
Published: July 2022

Noncoding, structured 5′-untranslated regions (5′-UTRs) of bacterial messenger RNAs (mRNAs) can control translation efficiency by forming structures that either recruit or repel the ribosome. Here we exploit a 5′-UTR embedded preQ1-sensing, pseudoknotted translational riboswitch to probe how binding of a small ligand controls recruitment of the bacterial ribosome to the partially overlapping Shine-Dalgarno (SD) sequence. Combining single-molecule fluorescence microscopy with mutational analyses, we find that the stability of 30S ribosomal subunit binding is inversely correlated with the free energy needed to unfold the 5′-UTR during mRNA accommodation into the mRNA binding cleft. Ligand binding to the riboswitch stabilizes the structure to both antagonize 30S recruitment and accelerate 30S dissociation. Proximity of the 5′-UTR and stability of the SD:anti-SD interaction both play important roles in modulating the initial 30S-mRNA interaction. Finally, depletion of small ribosomal subunit protein S1, known to help resolve structured 5′-UTRs, further increases the energetic penalty for mRNA accommodation. The resulting model of rapid standby site exploration followed by gated non-equilibrium unfolding of the 5′-UTR during accommodation provides a mechanistic understanding of how translation efficiency is governed by riboswitches and other dynamic structure motifs embedded upstream of the translation initiation site of bacterial mRNAs.
The first-in-class ERK inhibitor ulixertinib shows promising activity in mitogen-activated protein kinase (MAPK)-driven pediatric low-grade glioma models
Authors: Sigaud Romain , Rösch Lisa , Gatzweiler Charlotte , Benzel Julia , von Soosten Laura , Peterziel Heike , Selt Florian , Najafi Sara , Ayhan Simay , Gerloff Xenia F , Hofmann Nina , Büdenbender Isabel , Schmitt Lukas , Foerster Kathrin I , Burhenne Jürgen , Haefeli Walter E , Korshunov Andrey , Sahm Felix , van Tilburg Cornelis M , Jones David T W , Pfister Stefan M , Knoerzer Deborah , Kreider Brent L , Sauter Max , Pajtler Kristian W , Zuckermann Marc , Oehme Ina , Witt Olaf , Milde Till
Published: July 2022

Background

Pediatric low-grade gliomas (pLGG) are the most common pediatric central nervous system tumors, with driving alterations typically occurring in the MAPK pathway. The ERK1/2 inhibitor ulixertinib (BVD-523) has shown promising responses in adult patients with mitogen-activated protein kinase (MAPK)-driven solid tumors.

Methods

We investigated the antitumoral activity of ulixertinib monotherapy as well as in combination with MEK inhibitors (MEKi), BH3-mimetics, or chemotherapy in pLGG. Patient-derived pLGG models reflecting the two most common alterations in the disease, KIAA1549:BRAF-fusion and BRAFV600E mutation (DKFZ-BT66 and BT40, respectively) were used for in vitro and in vivo (zebrafish embryos and mice) efficacy testing.

Results

Ulixertinib inhibited MAPK pathway activity in both models, and reduced cell viability in BT40 with clinically achievable concentrations in the low nanomolar range. Combination treatment of ulixertinib with MEKi or BH3-mimetics showed strong evidence of antiproliferative synergy in vitro. Ulixertinib showed on-target activity in all tested combinations. In vivo, sufficient penetrance of the drug into brain tumor tissue in concentrations above the in vitro IC50 and reduction of MAPK pathway activity was achieved. In a preclinical mouse trial, ulixertinib mono- and combined therapies slowed tumor growth and increased survival.

Conclusions

These data indicate a high clinical potential of ulixertinib for the treatment of pLGG and strongly support its first clinical evaluation in pLGG as single agent and in combination therapy in a currently planned international phase I/II umbrella trial.
Postponing development: dormancy in the earliest developmental stages of a high-latitude calanoid copepod
Authors: Roncalli Vittoria , Cieslak Matthew C , Castelfranco Ann M , Hartline Daniel K , Lenz Petra H
Published: July 2022

Large lipid-rich copepods inhabiting high-latitude environments synchronize growth with the annual spring phytoplankton bloom. However, reproduction often precedes the bloom, raising the question of how the nauplii survive long enough to encounter the bloom. Are their energy stores sufficient to maintain an active life until then, or do they occupy a state of inactivity or dormancy, postponing development until food appears? These alternative hypotheses were tested in nauplii of Neocalanus flemingeri using gene-expression profiling. Stage NII and NIII nauplii were incubated for three days in either the presence or absence of food. Gene-expression differences between developmental stages and between food/no food treatments in individual nauplii were assessed using RNASeq. In the absence of food, nauplii exhibited transcriptional profiles typical of a dormant state. Similar to diapausing N. flemingeri females, genes involved in anaerobic metabolism, chromatin silencing and longevity were highly expressed. Nauplii of both stages responded to the food with the up-regulation of genes associated with diapause termination in copepods and insects, as well as genes involved in transcription and energy metabolism. The ability of nauplii to remain dormant could be a key adaptation that allows them to delay development and conserve energy, while they await the phytoplankton bloom.
U-shaped association between dietary thiamine intake and new-onset diabetes: a nationwide cohort study
Authors: Liu C , Meng Q , Zu C , Li R , Yang S , He P , Li H , Zhang Y Y , Zhou C , Liu M , Ye Z , Wu Q , Zhang Y J , Gan X , Qin X
Published: July 2022

Background

The association between dietary thiamine intake and the risk of diabetes remains unknown.

Aim

We aimed to evaluate the relation of dietary thiamine intake with new-onset diabetes and examine possible effect modifiers.

Design

Prospective cohort study.

Methods

A total of 16 272 participants who were free of diabetes at baseline were enrolled from China Health and Nutrition Survey (CHNS). Dietary nutrients intake information was collected by 3-day dietary recalls in addition to using a 3-day food-weighed method to assess cooking oil and condiment consumption. New-onset diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a glycated haemoglobin (HbA1c) ≥6.5% (48 mmol/mol) or diagnosed by a physician during the follow-up.

Results

During a median follow-up duration of 9.0 years, new-onset diabetes occurred in 1101 participants. Overall, the association between dietary thiamine intake and new-onset diabetes followed a U-shape (P for non-linearity <0.001). Consistently, when thiamine intake was assessed as quartiles, compared with those in the 2–3 quartiles (0.75 to 1.10 mg/day), the significantly higher risks of new-onset diabetes were found in participants in the first quartile [adjusted hazard ratio (HR), 1.33; 95% confidence interval (CI): 1.10, 1.61] and the fourth quartile (adjusted HR, 1.39; 95% CI: 1.17, 1.67). Similar results were found when further adjusting for the intake of other major nutrients or food groups; or using the propensity score weighting to control the imbalance of covariates.

Conclusion

Our results suggested that there was a U-shape association between dietary thiamine intake and new-onset diabetes in general Chinese adults, with a minimal risk at 0.75–1.10 mg/day.
Predictors and prognostic stratification for lupus low disease activity state: results from a prospective clinical trial
Authors: Zhang Kai , An Yuan , Zhao Peng , Huang Bo , Wang Yifan , Zhou Xingyu , Cheng Gong , Xing Xiaoyan , Wang Naidi , Feng Ruiling , Yu Siyue , Li Min , He Jing , Li Zhanguo
Published: July 2022

Objective

To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients.

Method

A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established.

Results

The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan–Meier estimates for the three risk groups based on the identified risk factors.

Conclusion

Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.
A phase 2 trial investigating the effects of the angiotensin II type 2 receptor agonist C21 in systemic sclerosis-related Raynaud’s
Authors: Herrick Ariane L , Batta Rohit , Overbeck Kamilla , Raud Johan , Manning Joanne , Murray Andrea , Dinsdale Graham , Tornling Göran
Published: July 2022

Objective

Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP.

Methods

This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3–7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models.

Results

For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°C*s vs 19 558°C*s), but not significantly (P = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P = 0.036). C21 was well tolerated.

Conclusion

Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT04388176.
3Disability Studies
Authors: DiLodovico Amanda
Published: July 2022

This review of literature examines the disability-centered experiences of Covid-19 in disability studies scholarship published in 2021. Under such examination, four main points of synthesis emerge as ways to make sense of the first full year of disability studies scholarship in the pandemic. This chapter, then, proceeds in four sections. First, a focus on the primary methods used in the literature under review as forms of sense-making and conversation that radically engage with the present. Second, a consideration of the eruption of disability politics that emerged in the wake of mask-mandates throughout the United States of America. Third, an observation of the spaces throughout the pandemic in which crip culture served, or had the potential to serve, as an epistemology in changing a seemingly unfamiliar global landscape. Lastly, a movement through the calls to action made by and through the scholarship under review.
Reasons Washington State Women Use Marijuana During Pregnancy/Breastfeeding, Their Trusted Information Sources, and Communication Strategies for Informed Decision-Making
Authors: Macario Everly , Thomas Rosita M.
Published: July 2022

Objective:

To understand reproductive-aged women's marijuana use beliefs and attitudes.

Methods:

Qualitative research (10 focus groups and 2 bulletin boards) with 95 Washington State women, aged 18 to 44 years, segmented by marijuana-using pregnant/breastfeeding; marijuana-using not-pregnant/breastfeeding; and nonmarijuana users. Participants completed up to 10 survey questions. We used deductive and inductive coding to analyze findings.

Results:

Marijuana-using pregnant/breastfeeding participants use marijuana to manage physical/mental pain and because of stigma, feel guilty, and sometimes hide use. Medicines have failed to address symptoms. Participants perceived marijuana safer than alcohol, tobacco, and illicit substances. Participants believed in the legitimacy of marijuana for health maintenance and want others to take their personally experienced benefits seriously. Participants interpreted lack of conclusive research as marijuana use not being unsafe. They want more information. All segments preferred hearing from other women about marijuana use experiences, with the marijuana-using pregnant/breastfeeding segment feeling strongest about this.

Conclusions:

Personal experiences with, and anecdotes from family/friends about, the effects of marijuana use during pregnancy/breastfeeding influence marijuana-using participants' decision making.

Nursing Implications:

It is important to speak with perinatal patients in a nonjudgmental/nonthreatening manner that acknowledges why reproductive-aged women may use marijuana and that conveys validation of patients' positive experiences with marijuana and a harm-reduction goal.
Outcomes of Cannabis Use During Pregnancy Within the American Association of Birth Centers Perinatal Data Registry 2007-2020
Authors: Joseph-Lemon Lodz , Thompson Heather , Verostick Lori , Shizuka Oura Haley , Jolles Diana R
Published: July 2022

Background:

Healthcare providers require data on associations between perinatal cannabis use and birth outcomes.

Methods:

This observational secondary analysis come from the largest perinatal data registry in the United States related to the midwifery-led birth center model care (American Association of Birth Centers Perinatal Data Registry; N = 19 286). Births are planned across all birth settings (home, birth center, hospital); care is provided by midwives and physicians.

Results:

Population data show that both early and persistent self-reports of cannabis use were associated with higher rates of preterm birth, low-birth-weight, lower 1-minute Apgar score, gestational weight gain, and postpartum hemorrhage. Once controlled for medical and social risk factors using logistic regression, differences for childbearing people disappeared except that the persistent use group was less likely to experience “no intrapartum complications” (adjusted odds ratio [aOR] = 0.49; 95% confidence interval [CI], 0.32-0.76; P < .01), more likely to experience an indeterminate fetal heart rate in labor (aOR = 3.218; 95% CI, 2.23-4.65; P < .05), chorioamnionitis (aOR = 2.8; 95% CI, 1.58-5.0; P < .01), low-birth-weight (aOR = 1.8; 95% CI, 1.08-3.05; P < .01), and neonatal intensive care unit (NICU) admission (aOR = 2.4; 95% CI, 1.30-4.69; P < .05).

Conclusions:

Well-controlled data demonstrate that self-reports of persistent cannabis use through the third trimester are associated with an increased risk of low-birth-weight and NICU admission.
Urinary extracellular vesicles: does cargo reflect tissue?
Authors: van Heugten Martijn H. , Hoorn Ewout J. , Fenton Robert A.
Published: July 2022

Purpose of review

To review recent developments in urinary extracellular vesicles (uEVs) to study kidney physiology and disease.

Recent findings

Proteomic analysis in rats showed significant correlations between kidney and uEV protein abundances. Consistent with uEV biogenesis, these correlations were stronger for membrane-associated proteins than for e.g. soluble kinases or E3 ubiquitin ligases. When challenged with a high potassium diet, the physiologically predicted protein changes occurred both in kidney and uEVs, suggesting that analysis of uEVs might be utilized as a proxy or even replacement for tissue analysis. Although kidney–uEV correlations are more difficult to obtain in humans, analysis of uEV cargo from patients with inherited tubulopathies or with primary aldosteronism were also consistent with the predicted changes at the tissue level. The kidney appears to be the main source of uEVs, with a recent study showing that nephron mass determines uEV excretion rate. Therefore, a measure of nephron mass should be included for between-subject comparisons.

The overall good correlation between kidney and uEV protein abundances renders uEVs an attractive noninvasive source of biomarkers for studying kidney physiology or disease. However, differences in per-protein kidney–uEV correlations and per-person uEV excretion rates should be considered in uEV biomarker studies.
Defining improvement in chronic kidney disease: regression and remission
Authors: Taal Maarten W.
Published: July 2022

Purpose of review

International definitions exist for chronic kidney disease (CKD) progression and kidney failure but despite evidence that kidney function may improve, there are no agreed definitions for regression and remission of CKD. In the light of recent novel kidney protective therapies and the promise of regenerative medicine to reverse kidney damage, it is time to critically examine these neglected aspects of CKD epidemiology.

Recent findings

We propose that CKD regression is viewed as a process of improvement defined as a sustained increase in glomerular filtration rate (GFR) by ≥25% and an improvement in GFR category or increase in GFR of 1≥ml/min/year, whereas remission is considered a category of improvement defined as GFR ≥60 ml/min/1.73m2 and urine albumin to creatinine ratio <30 mg/g. Several recent studies have reported improvement in kidney function in populations with CKD, even in the absence of specific therapy. Regression and remission of CKD are associated with increased likelihood of sustained improvement in kidney function as well as improved survival.

Further research is warranted to validate the proposed definitions and investigate associated mechanisms. We look to a future in which the goal of therapy is not merely to slow CKD progression but to improve kidney function and seek a cure.
Pediatric Delirium and All-Cause PICU Readmissions Within 1 Year*
Authors: Pilato Tara C. , Mauer Elizabeth A. , Gerber Linda M. , Traube Chani
Published: July 2022

Objectives:

Delirium in critically ill children is associated with increased in-hospital morbidity and mortality. Little is known about the lingering effects of pediatric delirium in survivors after hospital discharge. The primary objective of this study was to determine whether children with delirium would have a higher likelihood of all-cause PICU readmission within 1 calendar year, when compared with children without delirium.

Design:

Retrospective cohort study.

Setting:

Tertiary care, mixed PICU at an urban academic medical center.

Patients:

Index admissions included all children admitted between September 2014 and August 2015. For each index admission, any readmission occurring within 1 year after PICU discharge was captured.

Intervention:

Every child was screened for delirium daily throughout the PICU stay.

Measurements and Main Results:

Among 1,145 index patients, 166 children (14.5%) were readmitted at least once. Bivariate analyses compared patients readmitted within 1 year of discharge with those not readmitted: complex chronic conditions (CCCs), increased severity of illness, longer PICU length of stay, need for mechanical ventilation, age less than 6 months, and a diagnosis of delirium were all associated with subsequent readmission. A multivariable logistic regression model was constructed to describe adjusted odds ratios for readmission. The primary exposure variable was number of delirium days. After controlling for confounders, critically ill children who experienced greater than 2 delirium days on index admission were more than twice as likely to be readmitted (adjusted odds ratio, 2.2; CI, 1.1–4.4; p = 0.023). A dose-response relationship was demonstrated as children with longer duration of delirium had increased odds of readmission.

Conclusions:

In this cohort, delirium duration was an independent risk factor for readmission in critically ill children. Future research is needed to determine if decreasing prevalence of delirium during hospitalization can decrease need for PICU readmission.
Calcium Administration During Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest in Children With Heart Disease Is Associated With Worse Survival—A Report From the American Heart Association’s Get With The Guidelines-Resuscitation (GWTG-R) Registry*
Authors: Dhillon Gurpreet S. , Kleinman Monica E. , Staffa Steven J. , Teele Sarah A. , Thiagarajan Ravi R. ,   for the American Heart Association’s Get With The Guidelines - Resuscitation (GWTG-R) Investigators
Published: July 2022

Objectives:

IV calcium administration during cardiopulmonary resuscitation (CPR) for pediatric in-hospital cardiac arrest (IHCA) is associated with worse survival. We evaluated survival to hospital discharge in children with heart disease (HD), where calcium is more frequently administered during CPR.

Design:

Retrospective study of a multicenter registry database.

Setting:

Data reported to the American Heart Association’s (AHA) Get With The Guidelines-Resuscitation registry.

Patients:

Children younger than 18 years with HD experiencing an index IHCA event requiring CPR between January 2000 and January 2019. Using propensity score matching (PSM), we selected matched cohorts of children receiving and not receiving IV calcium during CPR and compared the primary outcome of survival to hospital discharge.

Interventions:

None.

Measurements and Main Results:

We included 4,556 children with HD experiencing IHCA. Calcium was administered in 1,986 (44%), more frequently in children younger than 1 year old (65% vs 35%; p < 0.001) and surgical cardiac (SC) compared with medical cardiac patients (51% vs 36%; p < 0.001). Calcium administration during CPR was associated with longer duration CPR (median 27 min [interquartile range (IQR): 10–50 min] vs 5 min [IQR, 2–16 min]; p < 0.001) and more frequent extracorporeal-CPR deployment (25% vs 8%; p < 0.001). In the PSM cohort, those receiving calcium had decreased survival to hospital discharge (39% vs 46%; p = 0.02) compared with those not receiving calcium. In a subgroup analysis, decreased discharge survival was only seen in SC cohorts.

Conclusions:

Calcium administration during CPR for children with HD experiencing IHCA is common and is associated with worse survival. Administration of calcium during CPR in children with HD should be restricted to specific indications as recommended by the AHA CPR guidelines.
“Surgical treatment of peripheral nerve neuromas – a systematic review and meta-analysis”
Authors: Langeveld Mirte , Hundepool Caroline A. , Duraku Liron S. , Power Dominic M. , Rajaratnam Vaikunthan , Zuidam J. Michiel
Published: July 2022

Background:

Despite many treatment options available, no consensus on the optimal surgical management of symptomatic peripheral nerve neuroma has been reached. The aim of this systematic review and meta-analysis was to evaluate effectiveness of different surgical techniques in treating painful neuromas and to help guide surgeons in electing optimal treatment.

Methods:

Five databases (Embase, MEDLINE, web of science, and Cochrane Central) were searched. Studies that reported either numerical (VAS/NRS) or non-numerical postoperative pain scores after surgical treatment of peripheral neuroma were identified.

Results:

Thirty-two articles met the eligibility criteria and were analyzed for qualitative review. Thirty studies were included in qualitative analysis for a total of 1150 neuromas. Surgical treatment of peripheral neuroma achieved good postoperative results in 70% of treated neuromas (95% CI; 64-77). Proportions between techniques ranged between 60%-92%. In a post-hoc analysis, Targeted Muscle Reinnervation (82%, 95% CI; 73-92) performed significantly better than neurectomy (p = 0.024).

Conclusions:

The choice of surgical management in treating symptomatic peripheral neuroma is challenging, yet surgical intervention achieves significant pain relief in the majority of cases. Targeted Muscle Reinnervation is promising for the management of painful neuromas.