bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellulolytic activity at the low temperature of associative bacteria from a seagrass ecosystem
Authors: Simbolon L M , Ismet M S , Ismiati P , Ilham A F , Srimariana E S
Published: February 2023

Cellulase enzymes have been widely used in many industrial activities, such as the production of biofuels, biofertilizers, and bio-decomposers. The usage of cellulase enzymes on an industrial scale usually involves a relatively high temperature. Microorganisms in marine ecosystems are widely known to have the ability to produce cellulase enzymes in various environmental ranges. However, exploring marine cellulolytic bacteria at low temperatures still lacks information. This study aims to determine the cellulolytic activity of bacteria associated with seagrass ecosystems at low temperatures. Cellulolytic activity test used selected bacteria isolates from the seagrass ecosystem (actinobacteria: AA10b, AA11a, AA30a, AB22b; heterotrophic bacterial: HB1.1, HB2.1, HT1.2, HT2.2). The cellulolytic index values were obtained from the clear zone test on CMC 1% medium with congo red staining (actinobacteria) and iodine (heterotrophic bacteria) in different temperature treatments (4°C, 17°C, 20°C, and 40°C). The results showed that all isolates had various cellulolytic index values at different temperatures. There was no bacterial cellulolytic activity at 4°C. However some isolates showed activities at 17°C and increased as the temperature was higher. The highest production of cellulolytic activity occurred at 40°C for both actinobacteria and heterotrophic bacteria isolates. The actinobacteria isolate AA11a had the highest cellulolytic index of 7.00 at 40°C. This study indicates that at low temperatures, associative bacteria from the seagrass ecosystem have considerable cellulolytic activity for further research applications in various industries.
Specifications of bioinspired material structural foam prosoma of Tachpleus gigas and Carcinocorpius rotundicaud using acoustic impulse response
Authors: Riyanto B , Ramadhan W , Putri A I
Published: February 2023

Renewable material innovation has shifted from inorganic materials to biological materials. Especially due to the demands of modern applications in food, biomedicine, and environmental sustainability. The peculiarity of the horseshoe crab is in the prosoma with a hollow structure (foam). The development of structural specifications also leads to non-destructive modern measurements using acoustic response impulse. This study aimed to determine the specifications foam material (shape and size) of the prosoma Tachypleus gigas and Carcinoscorpius rotundicauda using acoustic impulse responses. The research includes the characterization of the components and structure of the foam material prosoma using acoustic impulse response The prosoma components of T. gigas and C. rotundicauda have high protein and crude fiber, as well as functional groups according to chitin. The weight of T. gigas and C. rotundicauda ranges 484.33 ± 5.13 g and 493.33 ±15.28 g and densities of 1206.45 ± 148.01 kg/m3 and 1264.60 ± 120.01 kg/m3, but have differences in pore diameter and strut, 431.39μm ± 166.22 and 153.30μm ± 33.62 for pore diameter and strut, 120.09μm ± 57.83 and 98.0881μm ± 26.75 and compressive strength of 220.68 kPa and 285.88 kPa, and elasticity of 17.85 and 38.12.
Toxicity test of gelatin capsule materials from pangasius skin (Pangasius sp.) on mice (Mus musculus)
Authors: Nurilmala M , Irawan M F , Wientarsih I , Pranata A W , Putri E A W
Published: February 2023

Gelatin is produced from animal skin and bones, which can be used as an ingredient in medicine capsules. There are issues regarding the mad cow disease and certain religious rules that do not allow the consumption of gelatin from pigs and cows, opening up opportunities for developing gelatin derived from fish. This study aims to determine the level of toxicity of pangasius skin gelatin capsules (Pangasius sp.) using the fixed-dose procedure method in mice based on the LD50 value. The 2,000 mg/kg BW dose is determined as the initial dose of the main test after the preliminary test. The test animals were divided into 2 groups, each containing 5 female mice of the DDY strain. The first group was the control group, and the second group was the test animal group which was treated with a dose of 2,000 mg/kg BW. The results showed that the LD50 value of pangasius skin gelatin was > 2,000 mg/kg BW. Pangasius skin gelatin is not toxic, as evidenced by the absence of death and changes in the average body weight of mice. Based on the significant difference in relative weight, only the lungs were affected by pangasius skin gelatin.
Estimation of carbon footprint of longline and lines fisheries in the Indonesia FMA 573-Indian Ocean based at Palabuhanratu Fishing Port
Authors: Anggawangsa R F , Hargiyatno I T , Suryanto  , Widodo A A
Published: February 2023

Being convinced that the fisheries industry produces carbon footprint (CFP), the Center for Fisheries Research carried out research in 2021 to estimate the CFP of longline and lines tuna fisheries based in Palabuhanratu Fishing Port. The port is one of several important bases for tuna longlines and lines fishing fleets operated in the Indonesia FMA 753 (Indian Ocean). The port was selected because of the availability and adequacy of data for estimating the CFP of tuna longline and lines boats. This research aims to estimate the CFP of industrial tuna fisheries represented by both longline fisheries and lines fisheries. The estimate of greenhouse gases was quantified following procedures for the tier II emission factor. The analysis concluded that the average CPF of the two types of tuna fisheries in Palabuhanratu in the last seven years is 603.38 and 508.58 KgCO2eq/Kg of fish, respectively.
Preliminary study of microplastics content in the digestive tract of sea cucumber from Demak Waters
Authors: Hartati R , Widianingsih W , Zainuri M , Supriyo E
Published: February 2023

As a marine delicacy, sea cucumbers were often eaten raw in many part of the world and they have been reported to ingest microplastic. This study aimed to determine the microplastics in the digestive system of sea cucumbers from Demak Waters. The ten samples of Acaudina sp were taken using a bottom dredge from Wulan Estury and put in the glass-bottles samples. In the laboratory, the digestive tract was taken out from the sea cucumber, divided into 7 parts, and pooled in the glass beaker. Microplastics were digested with KOH and incubated at 40 °C for 24 hours. Then, the digestion solution was filtered through a sterile cellulose nitrate filter paper by vacuum filtration. The microplastics obtained were observed for their physical characteristics (density, shape and colour) under the microscope. The density of microplastics were varied among the part of digestive tract. They consisted of fragments, fiber, and pellets. The colour of microplastics were varied but dominated by the blue. As a deposit feeder, the sea cucumber might ingest the microplastics in the sediment they fed on.
Comparative image analysis approaches to assess ecological effects of macroalgal removal on inshore reefs of Magnetic Island, Australia
Authors: Hermanto B , Bourne D G , Smith H
Published: February 2023

Macroalgae removal is a proposed management option in the GBR to reverse declines in inshore coral reef health. Automated image analysis (AIA) is a valuable tool to assess benthic community assemblages. This study compared the accuracy of benthic community assemblages assessed through the AIA program CoralNet to manual image analysis. The ecological effect of macroalgae removal on benthic community composition was also investigated on established permanent quadrats (5x5 m) for reefs at Florence and Arthur Bay, Magnetic Island. Control and treatment quadrats (n=3 respectively) were photographed before and after macroalgae removal over 6 months. The results obtained by AIA and manual approaches were consistent, with macroalgae cover is approximately 77%-87% in all quadrats before macroalgal removal. Through the monitoring period, a small increase in coral cover in the macroalgal removal quadrats was observed in Florence and Arthur Bay (an increase of 1.8% and 0.1%, respectively). CoralNet was demonstrated to be robust for assessing reef benthic cover with no significant difference in recorded benthic categories when compared to the manual approach. CoralNet was accurate for identifying broad benthic categories, but less effective than manual image analyses for lower taxonomic categories (i.e., genus or species level).
Harvesting trend of the pelagic fish resource in North Maluku Province waters (IFMA 715)
Authors: Mahulette R T , Nugroho D
Published: February 2023

Sustainable harvesting of the marine living resources in North Maluku Province would provide employment and economic benefit to broad-scale coastal communities. The pelagic fish resource has been the backbone of marine capture fisheries in this area for years. Mapping the ten years of harvesting would enhance the common baseline to improve the existing instrument for fisheries management. Data limited fisheries approach based on landing records was applied to perform the harvest trend of these typical fisheries. The analysis was performed based on four representative groups of species (skipjack, kawa-kawa, scads, and anchovies) and four main fishing gears regularly recorded (pelagic seiner, beach seine, pole and line, and gillnet) for more than one decade. The result showed that the harvesting system slightly increased since 2002, indicated by 170 % in landing volume and 4 % in the number of gears. The estimated value of landing in 2020 at about 2.6 trillion IDR significantly increased compared to 203 billion IDR in 2002. This multi-scale harvesting trend of pelagic fisheries could increase fishing mortality without regular monitoring and evaluation. It is suggested that improving the existing fisheries management plan for the sustainability of the pelagic fisheries business should be evaluated regularly to provide a long-term beneficiary for coastal community fishery livelihood dependence for the North Moluccas Province.
The definition of small fisher: legal conflicts and their impacts
Authors: Solihin A , Afriansyah A , Bilqis A , Susanto H A
Published: February 2023

The management of small fisher in Indonesia is faced with unclear definition boundaries. Furthermore, the unclear boundaries will have impacts on the rights and obligations of small fisher as regulated in Indonesian laws and regulations. Small Scale Fisher (SSF) has been contributing to poverty alleviation, food security, livelihoods, local economy, and human rights. This is appropriate with fishing activities in Indonesia, where captured fishing fleet is dominated by small scale fisher. This study aims to map the definition of small fisher based on the government regulation, identify the impact of different definition of small fisher, and recommend the arrangement planning of small fisher in fishing activities. Normative juridical and comparative analysis are applied in this study. The result shows that there are various limitations of small fisher definition that impact illegal fishing practices, where small fisher are accused due to the absence of ship registration ownership documents. Therefore, synchronization needs to be implemented in relation with small scale fisher termination boundary to prevent one sided interpretation. Legal clarity is required with regards to the authorization of fishing vessel registration owned by small scale fisher
Social-ecological connectivity and management factors of puerulus (Panulirus spp.) fisheries in the Western Coastal Waters of Lampung Province
Authors: Lestari P A , Adrianto L , Zairion Z , Effendi I
Published: February 2023

Access limitation to capture lobster puerulus needs to be done to sustain the utilization of the resources, increase fishermen’s income and preserve the abundance of puerulus in the Western Coastal Waters of Lampung Province. The management of puerulus resources in these waters does not seem to have been well integrated within the framework of the social-ecological system (SES) of fishery resources. This study aims to analyze SES components and connectivity of lobster puerulus and identify strategic factors to be used in the context of fisheries management of lobster (Panulirus spp.). The research was conducted between October until November 2021 in West Coast Regency, Lampung Province, using SES approach. From the results, we have been revealed that there is a strong interaction and influence between the resources actor component (RA) and the resources unit (RU) in the context of the dynamics of the resources system (RS), but tends to be weak in the framework of the governance of the resource (RG). The management strategy is carried out through good collaboration between the government and resources actor to maintain puerulus abundance.
Numerical analysis of shock characteristics control based on bump
Authors: Li Dawei , Yu Kaibo , Wang Xiao , Gao Yuanbo
Published: February 2023

The effects of bump control on shock aerodynamic characteristics have been investigated by simulations. A bump control that based on the changes of local upper surface of two-dimensional (2D) airfoil or three-dimensional (3D) wing model has been applied to affect the shock intensity and position. The simulation results are close of other experiment when the calculate parameters are same with each other. The simulations show that the drag and lift characteristics can be improved with the bump control, and the results of improvement strongly depend on control parameters. For the 2D RAE2822 airfoil, the optimal control position of the bump control must keep close to the position of the shock wave. The 3D local bump that located on 80% wing span wise and closed to the tip can acquire a batter control results for the 3D RAE2822 wing model.
A facile method to pattern silver nanowires on sandpaper and its application in pressure sensors
Authors: Wang Li , Geng Yang
Published: February 2023

A conductive layer deposited on a rough surface can effectively improve the performance of a pressure sensor; however, its further application requires patterning of the conductive layer to obtain the corresponding electrical layout. In this paper, a facile patterning method with few steps was proposed for patterning silver nanowires on sandpaper. This method employed a photocurable resin as the key material to define the pattern using a photomask under UV exposure. It was found that greater cure depths and narrower light-transmitting areas require longer exposure times. A pattern with linewidth of approximately 40 μm was obtained on M-400 sandpaper (M-400 stands for the mesh number). Based on this method, pressure sensors consisting of interdigital electrodes with rough surfaces and sponge-sensing layers were fabricated. The best resulting sensor exhibited a high-pressure sensitivity of 21.89 kPa−11 for less than 2 kPa, a low detection limit (24.5 Pa), low operating voltage (0.01 V), and short response time (84 ms). Moreover, this patterning method has no special requirements for materials and substrates and thus can be applied to pattern other materials on rough or smooth surface substrates.
Structural dynamics of Schottky and Frenkel defects in CeO2: a density-functional theory study
Authors: Smith Thomas , Moxon Samuel , Tse Joshua S , Skelton Jonathan M , Cooke David J , Gillie Lisa J , da Silva E Lora , Harker Robert M , Storr Mark T , Parker Stephen C , Molinari Marco
Published: February 2023

Cerium dioxide CeO2 (ceria) is an important material in catalysis and energy applications. The intrinsic Frenkel and Schottky defects can impact a wide range of material properties including the oxygen storage capacity, the redox cycle, and the ionic and thermal transport. Here, we study the impact of Frenkel and Schottky defects on the structural dynamics and thermal properties of ceria using density functional theory. The phonon contributions to the free energy are found to reduce the defect formation free energies at elevated temperature. The phonon dispersions of defective CeO2 show significant broadening of the main branches compared to stoichiometric ceria. Phonon modes associated with the defects are identifiable in the infrared spectra through characteristic shoulders on the main features of the stoichiometric fluorite structure. Finally, the presence of Frenkel and Schottky defects are also found to reduce the thermal conductivity by up to 88% compared to stoichiometric CeO2.
Cobalt nickel boride as electrocatalyst for the oxidation of alcohols in alkaline media
Authors: Braun Michael , Chatwani Mohit , Kumar Piyush , Hao Yun , Sanjuán Ignacio , Apostoleri Ariadni-Aikaterini , Brix Ann Cathrin , Morales Dulce M , Hagemann Ulrich , Heidelmann Markus , Masa Justus , Schuhmann Wolfgang , Andronescu Corina
Published: February 2023

A mixed Co and Ni boride precursor was synthesized via chemical reduction and subsequently annealed at 400 or 500 °C with or without prior addition of the monomer benzoxazine (BO). The resulting mixed CoNiB materials were investigated as electrocatalysts for three alcohol oxidation reactions (AOR) in alkaline electrolyte: the oxidation of glycerol (GOR), ethylene glycol (EGOR) and ethanol (EOR). Comparison of the rotating disk electrode (RDE) cyclic voltammograms for the different catalysts revealed that CoNiB annealed at 500 °C without the addition of BO exhibited the lowest overpotentials in AORs at 10 mA cm−2, promoting GOR at 224 ± 6 mV lower potential compared to OER. When pyrolysis was conducted at 400 °C, the BO-containing catalyst showed a significant increase in the electrocatalytic activity for the AORs compared to the CoNiB catalyst only. The product selectivity on the different catalysts was investigated in a batch-type reactor with flow recirculation revealing formate as the main oxidation product during GOR and EGOR with faradaic efficiencies (FE) in a range of 60%–80%, while acetate was obtained during EOR (FE ∼ 85%–90%). The electrode potential, electrolyte composition and the type of ionomer were explored with respect to their influence on the GOR selectivity. The use of different ionomers resulted in significant differences in the activity trends between RDE and the batch-type reactor with flow recirculation measurements, indicating a strong influence of the two different substrates used, namely glassy carbon and carbon paper on the catalyst formation and thus on the recorded electrochemical activity.
Machine-learning approach for quantified resolvability enhancement of low-dose STEM data
Authors: Gambini Laura , Mullarkey Tiarnan , Jones Lewys , Sanvito Stefano
Published: February 2023

High-resolution electron microscopy is achievable only when a high electron dose is employed, a practice that may cause damage to the specimen and, in general, affects the observation. This drawback sets some limitations on the range of applications of high-resolution electron microscopy. Our work proposes a strategy, based on machine learning, which enables a significant improvement in the quality of Scanning Transmission Electron Microscope images generated at low electron dose, strongly affected by Poisson noise. In particular, we develop an autoencoder, trained on a large database of images, which is thoroughly tested on both synthetic and actual microscopy data. The algorithm is demonstrated to drastically reduce the noise level and approach ground-truth precision over a broad range of electron beam intensities. Importantly, it does not require human data pre-processing or the explicit knowledge of the dose level employed and can run at a speed compatible with live data acquisition. Furthermore, a quantitative unbiased benchmarking protocol is proposed to compare different denoising workflows.
Conformal capacity of hedgehogs
Authors: Betsakos Dimitrios , Solynin Alexander , Vuorinen Matti
Published: February 2023

We discuss problems concerning the conformal condenser capacity of “hedgehogs”, which are compact sets

E
E

in the unit disk

D

=
{
z
:

|

z

|

>
1
}

\mathbb {D}=\{z:\,|z|>1\}

consisting of a central body

E
0

E_0

that is typically a smaller disk

D

¯

r

=
{
z
:

|

z

|

≤
r
}

\overline {\mathbb {D}}_r=\{z:\,|z|\le r\}

,

0
>
r
>
1

0>r>1

, and several spikes

E
k

E_k

that are compact sets lying on radial intervals

I
(

α
k

)
=
{
t

e

i

α
k

:

0
≤
t
>
1
}

I(\alpha _k)=\{te^{i\alpha _k}:\,0\le t>1\}

. The main questions we are concerned with are the following: (1) How does the conformal capacity

c
a
p

(
E
)

\mathrm {cap}(E)

of

E
=

∪

k
=
0

n

E
k

E=\cup _{k=0}^n E_k

behave when the spikes

E
k

E_k

,

k
=
1

k=1

, …,

n
n

, move along the intervals

I
(

α
k

)

I(\alpha _k)

toward the central body if their hyperbolic lengths are preserved during the motion? (2) How does the capacity

c
a
p

(
E
)

\mathrm {cap}(E)

depend on the distribution of angles between the spikes

E
k

E_k

? We prove several results related to these questions and discuss methods of applying symmetrization type transformations to study the capacity of hedgehogs. Several open problems, including problems on the capacity of hedgehogs in the three-dimensional hyperbolic space, will also be suggested.
Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections
Authors: Goodman Greg J , McDonald Cara B , Lim Adrian , Porter Catherine E , Deva Anand K , Magnusson Mark , Patel Anita , Hart Sarah , Callan Peter , Rudd Alice , Roberts Stefania , Wallace Katy , Bekhor Philip , Clague Michael , Williams Linda , Corduff Niamh , Wines Nina , Al-Niaimi Firas , Fabi Sabrina G , Studniberg Howard M , Smith Saxon , Tsirbas Angelo , Arendse Sean , Ciconte Antoinette , Poon Terence
Published: February 2023

Background

The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain.

Objectives

To formulate a rational theory for DTN development and their avoidance and treatment.

Methods

A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement.

Results

Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide.

Conclusions

The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors—filler, inflammation, and infection—separately.

Level of Evidence: 4
Efficacy of downtitration or treatment withdrawal compared with continuous dosing after successful treatment with baricitinib in patients with moderate-to-severe atopic dermatitis in a randomized substudy from the long-term extension study BREEZE-AD3
Authors: Reich Kristian , Simpson Eric , Wollenberg Andreas , Bissonnette Robert , Abe Masatoshi , Cardillo Tracy , Janes Jonathan , Sun Luna , Chen Sherry , Silverberg Jonathan I
Published: February 2023

Background

Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435).

Objectives

To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3.

Methods

The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose).

Results

For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively.

Conclusions

Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose.
The concomitant use of proton pump inhibitors and BRAF/MEK inhibitors in metastatic melanoma
Authors: Poizeau Florence , Balusson Frédéric , Lemaitre Florian , Tron Camille , Pracht Marc , Russo David , Dinulescu Monica , Lesimple Thierry , Oger Emmanuel , Dupuy Alain
Published: February 2023

Background

Proton-pump inhibitors (PPIs) are commonly used by patients with cancer, although they could reduce the absorption of oral anticancer targeted therapies. The US Food and Drug Administration states that the effect of PPIs on the efficacy of dabrafenib use by patients with metastatic melanoma is unknown. As a precautionary measure, the European Society for Medical Oncology recommends avoiding PPIs for patients receiving dabrafenib.

Objectives

To determine the effect of the concomitant use of PPIs and BRAF/MEK inhibitors in patients with metastatic melanoma.

Methods

Patients with advanced melanoma receiving BRAF/MEK inhibitors as first-line treatments between 2015 and 2017 in France were selected using the French National Health Insurance database. We compared time-to-treatment discontinuation (TTD) and overall survival (OS) according to concomitant PPI exposure. We balanced the baseline characteristics of patients exposed and nonexposed to PPIs using an overlap weighting method based on a propensity score.

Results

The metastatic melanoma cohort comprised 1028 patients receiving BRAF/MEK inhibitors, including 361 (35.1%) patients using PPIs. PPI users had more comorbidities and a more severe metastatic disease. After having equally distributed metastatic sites and comorbidities across patients exposed and nonexposed to PPIs, concomitant PPI use was not associated with shorter TTD [weighted hazard ratio (wHR) 1.03, 95% confidence interval (CI) 0.86–1.24] or OS (wHR 1.11, 95% CI 0.88–1.39). Consistent results were observed when restricting the population to patients receiving dabrafenib, or when narrowing exposure to PPIs with stronger inhibition of cytochromes.

Conclusions

In a population-based cohort of patients with advanced melanoma, the concomitant use of PPIs and BRAF/MEK inhibitors was not associated with worse outcome.
Conventional therapy in psoriasis. Lost in translation?
Authors: Carrascosa Jose-Manuel
Published: February 2023

As no more than one out of every 3 patients receiving a first course of acitretin, cyclosporin or fumaric acid esters achieved contemporary therapeutic objectives in psoriasis, biosimilars could be positioned as the first line of treatment in patients with moderate to severe psoriasis.
Hyperosmolar environment and salivary gland epithelial cells increase extra-cellular matrix remodeling and lymphocytic infiltration in Sjögren’s syndrome
Authors: Rivière Elodie , Chivasso Clara , Pascaud Juliette , Bechara Rami , Ly Bineta , Delporte Christine , Mariette Xavier , Nocturne Gaetane
Published: February 2023

Salivary gland epithelial cells (SGECs) play an active role in primary Sjogren’s syndrome (pSS) pathogenesis. Quantitative and qualitative abnormalities of saliva might expose SGECs to chronic hyperosmolarity. We aimed to decipher the links between hyperosmolar stimulation of SGECs and lymphocytic infiltration of the salivary glands (SG) observed in pSS. RNAseq was performed on NS-SV-AC cells stimulated with hyperosmolar media containing NaCl (100 mM) or sucrose (200 mM), or with iso-osmolar (Iso) medium. RNAseq was performed on primary cultured SGECs from pSS and controls, in the presence or not of B cells. Hyperosmolar stimulation of NS-SV-AC-cells identified an upregulation of interferon-induced (MX1, IFIT2) and MMPs genes. Enrichment analysis revealed an over-representation of fibrosis pathway. In parallel, RNAseq of SGECs comparing pSS to controls identified an over-representation of a pathway involving MMPs. Given the unexpected upregulation of collagen (COL3A1, COL1A2) and ADAMTS genes in pSS SGECs, we hypothesized that SGECs might undergo epithelial–mesenchymal transition. ZEB2 was upregulated and SLUG was down regulated in SGECs from pSS versus controls. MMP24 and ZEB2 were higher in SGECs from pSS with a focus score ≥1 versus <1. Lastly, SGECs cocultured with B cells expressed higher levels of COL1A2. These results suggest the existence of a vicious circle. Alteration of SGECs in pSS participates in the establishment of a hyperosmolar microenvironment, which in turn promotes SGECs transcriptomic modifications. These modifications include extracellular matrix remodeling and promote SG lymphocytic infiltration.
Examination of common and unique brain regions for atypical reading and math: a meta-analysis
Authors: Martinez-Lincoln Amanda , Fotidzis Tess S , Cutting Laurie E , Price Gavin R , Barquero Laura A
Published: February 2023

The purpose of this study is to identify consistencies across functional neuroimaging studies regarding common and unique brain regions/networks for individuals with reading difficulties (RD) and math difficulties (MD) compared to typically developing (TD) individuals. A systematic search of the literature, utilizing multiple databases, yielded 116 functional magnetic resonance imaging and positron emission tomography studies that met the criteria. Coordinates that directly compared TD with either RD or MD were entered into GingerALE (Brainmap.org). An activation likelihood estimate (ALE) meta-analysis was conducted to examine common and unique brain regions for RD and MD. Overall, more studies examined RD (n = 96) than MD (n = 20). Across studies, overactivation for reading and math occurred in the right insula and inferior frontal gyrus for atypically developing (AD) > TD comparisons, albeit in slightly different areas of these regions; however, inherent threshold variability across imaging studies could diminish overlying regions. For TD > AD comparisons, there were no similar or overlapping brain regions. Results indicate there were domain-specific differences for RD and MD; however, there were some similarities in the ancillary recruitment of executive functioning skills. Theoretical and practical implications for researchers and educators are discussed.
Value of screening for the risk of sudden cardiac death in young competitive athletes
Authors: Sarto Patrizio , Zorzi Alessandro , Merlo Laura , Vessella Teresina , Pegoraro Cinzia , Giorgiano Flaviano , Graziano Francesca , Basso Cristina , Drezner Jonathan A , Corrado Domenico
Published: February 2023

Aims

This study aimed to report the long-term findings of the Italian programme of cardiovascular preparticipation screening (PPS) in young, competitive athletes.

Methods and results

The study assessed the diagnostic yield for diseases at risk of sudden cardiac death (SCD), the costs of serial evaluations, and the long-term outcomes of PPS in a large population of Italian children (age range, 7–18 years). The PPS was repeated annually and included medical history, physical examination, resting electrocardiogram, and stress testing; additional tests were reserved for athletes with abnormal findings. Over an 11-year study period, 22 324 consecutive children [62% males; mean age, 12 (interquartile range, 10–14) years at first screening] underwent a total of 65 397 annual evaluations (median 2.9/child). Cardiovascular diseases at risk of SCD were identified in 69 children (0.3%) and included congenital heart diseases (n = 17), channelopathies (n = 14), cardiomyopathies (n = 15), non-ischaemic left ventricular scar with ventricular arrhythmias (n = 18), and others (n = 5). At-risk cardiovascular diseases were identified over the entire age range and more frequently in children ≥12 years old (n = 63, 91%) and on repeat evaluation (n = 44, 64%). The estimated cost per diagnosis was 73 312€. During a follow-up of 7.5 ± 3.7 years, one child with normal PPS findings experienced an episode of resuscitated cardiac arrest during sports activity (event rate of 0.6/100.000 athletes/year).

Conclusion

The PPS programme led to the identification of cardiovascular diseases at risk of SCD over the whole study age range of children and more often on repeat evaluations. Among screened children, the incidence of sport-related cardiac arrest during long-term follow-up was low.
Public perceptions of responsibility for recommended food policies in seven countries
Authors: Pinho-Gomes Ana-Catarina , Booth Leon , Pettigrew Simone
Published: February 2023

Background

Food policy is important to promote healthy and sustainable diets. However, who is responsible for developing and implementing food policy remains contentious. Therefore, this study aimed to investigate how the public attributes responsibility for food policy to governments, individuals and the private sector.

Methods

A total of 7559 respondents from seven countries [Australia (n = 1033), Canada (n = 1079), China (n = 1099), India (n = 1086), New Zealand (n = 1090), the UK (n = 1079) and the USA (n = 1093)] completed an online survey assessing perceived responsibility for 11 recommended food policies.

Results

Overall, preferred responsibility for the assessed food policies was primarily attributed to governments (62%), followed by the private sector (49%) and individuals (31%). Respondents from New Zealand expressed the highest support for government responsibility (70%) and those from the USA the lowest (50%). Respondents from the USA and India were most likely to nominate individuals as responsible (both 37%), while those from China were least likely (23%). The private sector had the highest attributed responsibility in New Zealand (55%) and the lowest in China and the USA (both 47%). Support for government responsibility declined with age and was higher among those on higher incomes, with a university degree, and who perceived themselves to consume a healthy diet or be in poor health.

Conclusions

Across seven diverse countries, results indicate the public considers government should take primary responsibility for the assessed food policies, with modest contribution from the private sector and minority support for individual responsibility.
Regulation of trehalose metabolism in insects: from genes to the metabolite window
Authors: Tellis Meenakshi B , Kotkar Hemlata M , Joshi Rakesh S
Published: February 2023

Trehalose is a major circulatory sugar in the haemolymph of insects. It provides instant energy and protection against stress. Trehalose metabolism is associated with insect growth and development. The architecture and spatio-temporal expression dynamics of trehalose metabolism and transport genes are key for regulation. These genes are controlled by various transcription factors, largely linked to nutrition, insect development, and metamorphosis. Also, trehalose levels are affected by substrate affinities and modifications of enzymes involved in the pathway. A feedback mechanism involving the precursors and products can regulate trehalose metabolism. Further, the neuroendocrine system controls trehalose levels under normal and stressed conditions by producing different hormones. Hypotrehalosemic hormones work under surplus energy conditions to activate haemolymph trehalose uptake and degradation. In contrast, hypertrehalosemic hormones stimulate trehalose production in the fat body and its transport to the haemolymph. However, trehalose metabolism regulation in insects needs to be studied in detail. This review discusses aspects of trehalose synthesis, transport, and degradation dynamics in developmental transition and stress response. Unraveling the epigenetic factors, transcriptional control and chemical or genetic modulators can provide further insights into the intricate regulation of trehalose in a development- and tissue-specific manner. This molecular information about effectors and regulators of trehalose metabolism can be applied in developing diverse biotechnological applications.
Varied Patterns of Decay of Intact Human Immunodeficiency Virus Type 1 Proviruses Over 2 Decades of Antiretroviral Therapy
Authors: Gandhi Rajesh T , Bosch Ronald J , Mar Hanna , Laird Gregory M , Halvas Elias K , Hovind Laura , Collier Ann C , Riddler Sharon A , Martin Albine , Ritter Kristen , McMahon Deborah K , Eron Joseph J , Cyktor Joshua C , Mellors John W ,   AIDS Clinical Trials Group A5321 Team, Hogg Evelyn , LeBlanc Rebecca , Scello Christine , Palm David , Gandhi Monica , Fletcher Courtney , Podany Anthony , Aweeka Fran , Joseph Jeymohan , Pederson Susan , Rubin Leah , Smith Davey , Spudich Serena , Tsibris Athe
Published: February 2023

Fourteen people with human immunodeficiency virus type 1 had longitudinal measurements of intact, defective, and total proviral DNA over the course of two decades of antiretroviral therapy. Three patterns of intact proviral DNA decay were revealed: (1) biphasic decline with markedly slower second-phase decline, (2) initial decline that transitions to a zero-slope plateau, and (3) initial decline followed by later increases in intact proviral DNA. Defective proviral DNA levels were essentially stable. Mechanisms of slowing or reversal of second-phase decay of intact proviral DNA may include the inability to clear cells with intact but transcriptionally silent proviruses and clonal expansion of cells with intact proviruses.
The (Dis-)Appearance of Race in the United Kingdom’s Institutionalization and Implementation of the Women, Peace and Security Agenda
Authors: Achilleos-Sarll Columba
Published: February 2023

In contrast to earlier, more celebratory accounts, more recent scholarship on the United Nations Security Council's Women, Peace and Security (WPS) agenda reveals the racial–colonial logics deeply woven into the very fabric of the agenda that contribute to reproducing hierarchies, inequalities, and exclusions. Building on this body of literature, this article investigates in more detail how race shapes the United Kingdom's engagement with and institutionalization of the WPS agenda, reinforcing particular domestic identities. Drawing from a rich body of new empirical material, including documentary sources and interview data, the analysis excavates four interlinked racial–colonial practices: (1) the erasure of Britain's imperial and colonial history; (2) the production of new geographies of empire; (3) the construction of cultural inferiority of the “other”; and (4) nation branding efforts that construct the UK as the repository of leadership and expertise. I argue that the UK serves as an illustrative case that yields significant empirical and theoretical insights regarding how race is central to the institutionalization and implementation of the WPS agenda by national governments in the Global North and how, in turn, the WPS agenda enables those governments to identify as morally and culturally superior, thereby justifying racialized hierarchies in international relations.
Development and validation of a dosing nomogram for continuous infusion cloxacillin in infective endocarditis
Authors: Bellouard Ronan , Rambaud Antoine , Delaunay Clarisse , Dailly Éric , Lecomte Raphaël , Deschanvres Colin , Leroy Anne-Gaëlle , Boutoille David , Le Turnier Paul , Grégoire Matthieu ,   the Nantes Anti-Microbial Agents PK/PD (NAMAP) study group, Boutoille David , Gaborit Benjamin Jean , Le Turnier Paul , Deschanvres Colin , Lecomte Raphaël , Grégoire Matthieu , Bellouard Ronan , Deslandes Guillaume , Dailly Eric , Leroy Anne-Gaëlle , Corvec Stéphane , Morio Florent , Huon Jean-François , Navas Dominique
Published: February 2023

Background

Cloxacillin is the first-line treatment for methicillin-susceptible staphylococcal infective endocarditis (IE). The recommended dose is 12 g per day regardless of the patient characteristics, despite the importance of renal function on its pharmacokinetics.

Objectives

We sought to build a population pharmacokinetics model of continuous infusion cloxacillin in IE patients to evaluate the influence of multiple covariates and then develop a nomogram based on significant covariates for individual adaptation.

Patients and methods

We included patients of a local IE cohort who were treated with cloxacillin administered by continuous infusion, excluding those who received intermittent or continuous dialysis, extracorporeal membrane oxygenation or extracorporeal circulation. The population pharmacokinetic analysis was performed using Pmetrics. The influence of weight, ideal weight, height, body mass index, body surface area, glomerular filtration rate (GFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration formula (both expressed in mL/min/1.73 m² and in mL/min) and serum protein level on cloxacillin pharmacokinetics was assessed. Accounting for relevant covariates, a dosing nomogram was developed to determine the optimal daily dose required to achieve a steady-state plasma concentration range of 20–50 mg/L with a probability ≥0.9.

Results

A total of 114 patients (331 plasma concentrations) were included. A one-compartment model including GFR expressed in mL/min as a covariate was chosen. Using the nomogram, achieving the cloxacillin concentration target requires a daily dose ranging from 3.5 to 13.1 g for a GFR ranging from 20 to 125 mL/min.

Conclusions

This work provided a practical tool for cloxacillin dose adjustment in IE according to renal function.
A platform for phenotyping disease progression and associated longitudinal risk factors in large-scale EHRs, with application to incident diabetes complications in the UK Biobank
Authors: Kim Do Hyun , Jensen Aubrey , Jones Kelly , Raghavan Sridharan , Phillips Lawrence S , Hung Adriana , Sun Yan V , Li Gang , Reaven Peter , Zhou Hua , Zhou Jin J
Published: February 2023

Objective

Modern healthcare data reflect massive multi-level and multi-scale information collected over many years. The majority of the existing phenotyping algorithms use case–control definitions of disease. This paper aims to study the time to disease onset and progression and identify the time-varying risk factors that drive them.

Materials and Methods

We developed an algorithmic approach to phenotyping the incidence of diseases by consolidating data sources from the UK Biobank (UKB), including primary care electronic health records (EHRs). We focused on defining events, event dates, and their censoring time, including relevant terms and existing phenotypes, excluding generic, rare, or semantically distant terms, forward-mapping terminology terms, and expert review. We applied our approach to phenotyping diabetes complications, including a composite cardiovascular disease (CVD) outcome, diabetic kidney disease (DKD), and diabetic retinopathy (DR), in the UKB study.

Results

We identified 49 049 participants with diabetes. Among them, 1023 had type 1 diabetes (T1D), and 40 193 had type 2 diabetes (T2D). A total of 23 833 diabetes subjects had linked primary care records. There were 3237, 3113, and 4922 patients with CVD, DKD, and DR events, respectively. The risk prediction performance for each outcome was assessed, and our results are consistent with the prediction area under the ROC (receiver operating characteristic) curve (AUC) of standard risk prediction models using cohort studies.

Discussion and Conclusion

Our publicly available pipeline and platform enable streamlined curation of incidence events, identification of time-varying risk factors underlying disease progression, and the definition of a relevant cohort for time-to-event analyses. These important steps need to be considered simultaneously to study disease progression.
Inhibitory machinery for the functional dystroglycan glycosylation
Authors: Kondo Yuji , Okajima Tetsuya
Published: February 2023

Dystroglycan (DG), a muscular transmembrane protein, plays a critical role in transducing extracellular matrix-derived signals to the cytoskeleton and provides physical strength to skeletal muscle cell membranes. The extracellular domain of DG, α-DG, displays unique glycosylation patterns. Fully functional glycosylation is required for this domain to interact with components of extracellular matrices, including laminin. One of the unique sugar compositions found in such functional glycans on DG is two ribitol phosphates that are transferred by the sequential actions of fukutin (FKTN) and fukutin-related protein (FKRP), which use CDP-ribitol as a donor substrate. These are then further primed for matriglycan biosynthesis. A recent in vitro study reported that glycerol phosphate could be similarly added to α-DG by FKTN and FKRP if they used CDP-glycerol (CDP-Gro) as a donor substrate. However, the physiological relevance of these findings remains elusive. Imae et al. addressed the knowledge gap regarding whether CDP-Gro is present in mammals and how CDP-Gro is synthesized and functions in mammals.
Thermodynamic stability of human lipocalin-type prostaglandin D synthase under various pH conditions
Authors: Iida Tsukimi , Nakatsuji Masatoshi , Teraoka Yoshiaki , Goto Yuji , Yamamura Takaki , Inui Takashi
Published: February 2023

Lipocalin-type prostaglandin D synthase (L-PGDS) binds various hydrophobic small molecules. Since we aim to use human L-PGDS as a carrier in a drug delivery system (DDS) for poorly water-soluble drugs, quality control of the protein is indispensable. In this study, we investigated the thermodynamic stability of human L-PGDS under various pH conditions. Differential scanning calorimetry revealed that the thermal unfolding of L-PGDS was an almost-reversible two-state transition between the native and unfolded states over the pH range from 2.5 to 7.4. The linear relationship of ΔH(Tm) to Tm in this pH range gave a heat capacity change (ΔCp) of 4.76 kJ/(K·mol), which was small compared to those commonly found in globular proteins. The temperature-dependent free energy of unfolding, ΔG(T), specified by Tm, ΔH(Tm) and ΔCp, showed a pH dependence with the highest value at pH 7.4 closest to the isoelectric point of 8.3. The small value of Cp resulted in a large value of ΔG(T), which contributed to the stability of the protein. Taken together, these results demonstrated that human L-PGDS is sufficiently thermostable for storage and practical use and can be useful as a delivery vehicle of protein-based DDS.