bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Albumin Infusion Does not Augment the Response Rate to a Combination of Exclusive Enteral Nutrition and Intravenous Steroids in Acute Severe Ulcerative Colitis: A Randomised Controlled Trial
Authors: Mundhra Sandeep K , Madan Divya , Golla Rithvik , Sahu Pabitra , Vuyyuru Sudheer K , Kante Bhaskar , Kumar Peeyush , Mathew Thomas David , Prasad Shubham , Vaishnav Manas , Verma Mahak , Virmani Shubi , Bajaj Aditya , Markandey Manasvani , Ranjan Mukesh Kumar , Arora Umang , Singh Mukesh Kumar , Makharia Govind K , Ahuja Vineet , Kedia Saurabh
Published: June 2024

Introduction

Overall, 30–40% patients with acute severe ulcerative colitis [ASUC] fail intravenous [IV] steroids, requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition [EEN] has been shown to improve steroid response and albumin levels. Albumin infusion, due to its anti-inflammatory and antioxidant properties, might further improve steroid response in ASUC, which was evaluated in the present study.

Methods

In this open-label, randomised, controlled trial, patients with ASUC were randomised in 1:1 ratio to either albumin + standard of care [SOC] + EEN [Albumin arm] or SOC + EEN [SOC arm], over January 2021–February 2023. Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in the Albumin arm were administered 5 days of 20% weight/volume [w/v] intravenous albumin [100 ml]. Primary outcome was first, steroid failure [need for rescue medical therapy or colectomy] and second, proportion of patients with adverse events.

Results

In all, 61 patients [albumin: 30, SOC: 31][mean age 31.6 ± 0.4 years, male 57.4%], were included. Baseline characteristics were comparable. There was no difference in steroid failure between Albumin and SOC arms (10/30 [33.33%] vs 13/31[41.94%], p = 0.49). No adverse events were reported with albumin infusions. Colectomy rate [10% vs 9.68%, p = 1], response to salvage medical therapy [88.89% vs 76.92%, p = 0.62] and median [interquartile range] duration of hospitalisation [10.5 [7-16] vs 10 [7-20], p = 0.43] were also comparable. The long-term composite outcome of colectomy and re-admission rates was numerically higher in the Albumin than the SOC arm [37.04% vs 17.86%, p > 0.05], although this did not reach statistical significance.

Conclusion

There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.
Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study
Authors: Lu Donghao , Valdimarsdóttir Unnur A , Wei Dang , Chen Yufeng , Andreassen Ole A , Fang Fang , László Krisztina D , Bränn Emma
Published: June 2024

Background and Aims

Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. While major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown.

Methods

A nationwide population-based matched cohort study involving 55 539 women diagnosed with PND during 2001–14 in Sweden and 545 567 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, hazard ratios (HR) of any and type-specific CVD according to PND were estimated.

Results

The mean age at the PND diagnosis was 30.8 [standard deviation (SD) 5.6] years. During the follow-up of up to 20 years (mean 10.4, SD 3.6), 3533 (6.4%) women with PND (expected number 2077) and 20 202 (3.7%) unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD [adjusted HR = 1.36, 95% confidence interval (CI): 1.31–1.42], while compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20, 95% CI 1.07–1.34). The results were most pronounced in women without a history of psychiatric disorder (P for interaction < .001). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50, 95% CI: 1.41–1.60), ischaemic heart disease (HR = 1.37, 95% CI: 1.13–1.65), and heart failure (HR 1.36, 95% CI: 1.06–1.74).

Conclusions

Women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women.
High potential but little success: ungulate browsing increasingly impairs silver fir regeneration in mountain forests in the southern Swiss Alps
Authors: Frei Esther R , Conedera Marco , Bebi Peter , Zürcher Samuel , Bareiss Alena , Ramstein Laura , Giacomelli Nicola , Bottero Alessandra
Published: June 2024

Sustainable regeneration of silver fir (Abies alba Mill.) is important for maintaining and improving the future resilience and protective capacity of mountain forests in the southern Swiss Alps. However, increasing densities of wild ungulates, such as red and roe deer, can hamper the regeneration success of silver fir. A comprehensive understanding of forest–wildlife interactions is essential to plan concrete measures for improving the adaptation potential of mountain forests. Here, we monitored the dynamics of natural silver fir regeneration in mountain protective forests. This study encompassed 30 unfenced permanent plots across two sites, Lostallo and Soazza, located in Valle Mesolcina in the southern Swiss Alps. These sites were selected for their comparable ecological characteristics related to silver fir regeneration, yet contrasting densities of mature, seed-bearing silver fir trees. We recorded the number of seedlings (<10 cm height) and saplings (10–200 cm height), and repeatedly assessed height growth, frequency, and intensity of ungulate browsing on saplings in the summers 2016, 2019, and 2022. In 2022, we additionally recorded the presence of browsing on other tree species in the unfenced plots and the height growth increments of silver fir saplings in pre-existing fences. On average, 509 silver fir seedlings/ha were present in the study area, but there was a lower density of saplings (382 saplings/ha). Between 2016 and 2022, the browsing frequency on silver fir saplings increased from 33 per cent to nearly 100 per cent, accompanied by a significant rise in browsing intensity. Furthermore, sapling height growth from 2019 to 2022 was significantly reduced or even negative in the unfenced plots as compared to the growth of saplings in the fenced plots. The observed seedling density indicated a good potential for natural regeneration of silver fir, irrespective of the differences in the density of seed-bearing trees between the two sites. However, the increased ungulate browsing impaired successful regeneration in the considered mountain forests in the southern Swiss Alps. Thus, without an effective control of ungulate browsing, silver fir may not be able to substantially contribute to the transition to more resilient and future-proof mountain forests.
Tight General Bounds for the Extremal Numbers of 0–1 Matrices
Authors: Janzer Barnabás , Janzer Oliver , Magnan Van , Methuku Abhishek
Published: June 2024

A zero-one matrix $M$ is said to contain another zero-one matrix $A$ if we can delete some rows and columns of $M$ and replace some $1$-entries with $0$-entries such that the resulting matrix is $A$. The extremal number of $A$, denoted $\operatorname{ex}(n,A)$, is the maximum number of $1$-entries that an $n\times n$ zero-one matrix can have without containing $A$. The systematic study of this function for various patterns $A$ goes back to the work of Füredi and Hajnal from 1992, and the field has many connections to other areas of mathematics and theoretical computer science. The problem has been particularly extensively studied for so-called acyclic matrices, but very little is known about the general case (i.e., the case where $A$ is not necessarily acyclic). We prove the first asymptotically tight general result by showing that if $A$ has at most $t$  $1$-entries in every row, then $\operatorname{ex}(n,A)\leq n^{2-1/t+o(1)}$. This verifies a conjecture of Methuku and Tomon. Our result also provides the first tight general bound for the extremal number of vertex-ordered graphs with interval chromatic number $2$, generalizing a celebrated result of Füredi and Alon, Krivelevich, and Sudakov about the (unordered) extremal number of bipartite graphs with maximum degree $t$ in one of the vertex classes.
Prescribing antibiotics for children with dengue infection in Taiwan: who are at risk and who are high prescribers?
Authors: Shen Yi-Jung , Lien Chia-En , Chou Yiing-Jenq , Tsai Theodore , Huang Nicole
Published: June 2024

Inappropriate antibiotic use contributes to antimicrobial resistance, a global public health threat. The non-specific manifestations of dengue, itself a growing public health threat, lead to avoidable empiric antibiotic prescription, particularly in children. In this national pooled population-based cross-sectional study, we evaluated child and physician characteristics associated with antibiotics prescription in confirmed dengue cases in Taiwan. Linking national health care insurance claims and reports of confirmed dengue cases from 2008 to 2015, there were 7086 children with confirmed dengue with 21 744 outpatient visits and 2520 inpatient admissions. We assessed the presence of antibiotic prescription in outpatient and inpatient settings separately a week before or after the confirmation date. Logistic regression models with generalized estimating equations were applied to identify patient, practitioner, and other factors associated with antibiotic prescription. A total of 29.4% of children <18 years old with dengue who did not have a concomitant bacterial infection were prescribed antibiotics during the 14-day assessment period. Antibiotics prescription was reduced from 13.5% to 6.3% and from 43.2% to 19.3% in outpatient and inpatient settings, respectively, after dengue was confirmed. Young children were more likely to receive antibiotics. Significant variations in antibiotic prescribing across physicians were observed only in outpatient settings: physicians ≥60 years old and physicians practicing at clinics and in non-urban facilities were more likely to prescribe antibiotics. Antibiotics were less likely to be prescribed during an exceptional 2-year epidemic than in other years. Antibiotic prescribing for dengue, an arboviral infection affecting half of the global population, was shown to occur in 29% of paediatric cases in Taiwan. That potentially avoidable antibiotic consumption could be reduced by improving antibiotic stewardship, informed by understanding the conditions under which antibiotics are prescribed and the availability of prevention strategies for viral diseases, including dengue. We identified a number of such factors in this national population-based study.
Frost fighters: unveiling the potential of microbial antifreeze proteins in biotech innovation
Authors: Lopes Joana Camila , Kinasz Camila Tomazini , Luiz Alanna Maylle Cararo , Kreusch Marianne Gabi , Duarte Rubens Tadeu Delgado
Published: June 2024

Polar environments pose extreme challenges for life due to low temperatures, limited water, high radiation, and frozen landscapes. Despite these harsh conditions, numerous macro and microorganisms have developed adaptive strategies to reduce the detrimental effects of extreme cold. A primary survival tactic involves avoiding or tolerating intra and extracellular freezing. Many organisms achieve this by maintaining a supercooled state by producing small organic compounds like sugars, glycerol, and amino acids, or through increasing solute concentration. Another approach is the synthesis of ice-binding proteins, specifically antifreeze proteins (AFPs), which hinder ice crystal growth below the melting point. This adaptation is crucial for preventing intracellular ice formation, which could be lethal, and ensuring the presence of liquid water around cells. AFPs have independently evolved in different species, exhibiting distinct thermal hysteresis and ice structuring properties. Beyond their ecological role, AFPs have garnered significant attention in biotechnology for potential applications in the food, agriculture, and pharmaceutical industries. This review aims to offer a thorough insight into the activity and impacts of AFPs on water, examining their significance in cold-adapted organisms, and exploring the diversity of microbial AFPs. Using a meta-analysis from cultivation-based and cultivation-independent data, we evaluate the correlation between AFP-producing microorganisms and cold environments. We also explore small and large-scale biotechnological applications of AFPs, providing a perspective for future research.
Genomic insight of phosphate solubilization and plant growth promotion of two taxonomically distinct winter crops by Enterobacter sp. DRP3
Authors: Saha Kunal Kumar , Mandal Subhrangshu , Barman Anik , Mondal Sangita , Chatterjee Sumit , Mandal Narayan Chandra
Published: June 2024

Aims

Study of rhizospheric microbiome-mediated plant growth promotional attributes currently highlighted as a key tool for the development of suitable bio-inoculants for sustainable agriculture purposes. In this context, we have conducted a detailed study regarding the characterization of phosphate solubilizing potential by plant growth-promoting bacteria that have been isolated from the rhizosphere of a pteridophyte Dicranopteris sp., growing on the lateritic belt of West Bengal.

Methods and Results

We have isolated three potent bacterial strains, namely DRP1, DRP2, and DRP3 from the rhizoids-region of Dicranopteris sp. Among the isolated strains, DRP3 is found to have the highest phosphate solubilizing potentiality and is able to produce 655.89 and 627.58 µg ml−1 soluble phosphate by solubilizing tricalcium phosphate (TCP) and Jordan rock phosphate, respectively. This strain is also able to solubilize Purulia rock phosphate moderately (133.51 µg ml−1). Whole-genome sequencing and further analysis of the studied strain revealed the presence of pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase gdh gene along with several others that were well known for their role in phosphate solubilization. Further downstream, quantitative reverse transcriptase PCR-based expression study revealed 1.59-fold upregulation of PQQ-dependent gdh gene during the solubilization of TCP. Root colonization potential of the studied strain on two taxonomically distinct winter crops viz. Cicer arietinum and Triticum aestivum has been checked by using scanning electron microscopy. Other biochemical analyses for plant growth promotion traits including indole acetic acid production (132.02 µg ml−1), potassium solubilization (3 mg l−1), biofilm formation, and exopolymeric substances productions (1.88–2.03 µg ml−1) also has been performed.

Conclusion

This study highlighted the active involvement of PQQ-dependent gdh gene during phosphate solubilization from any Enterobacter group. Moreover, our study explored different roadmaps for sustainable farming methods and the preservation of food security without endangering soil health in the future.
Riding Toward Danger: A Scoping Review of Burns Associated With Personal Mobility Devices, Including Electric Bikes (E-Bikes) and Electric Scooters (E-Scooters)
Authors: Warner-Levy John , Herieka Mohammed , Sheikh, Zeeshan
Published: June 2024

Burn injuries related to lithium-ion batteries from personal mobility devices, such as electric bikes and electric scooters, have emerged as a global concern. By examining the literature, this study aims to provide an overview of the demographics, patterns, and outcomes of personal mobility device-associated burns. A Singaporean cohort revealed burns resulting predominantly from fires occurring due to the combustion of unattended personal mobility device batteries during charging. In contrast, an Israeli cohort showed a higher total body surface area and highlighted the vulnerability of limbs to burn injuries in such incidents. A Beijing cohort, consisting of pediatric patients indicated potential child safety concerns regarding personal mobility device usage. Finally, a Shanghai cohort demonstrated the potential dangers of personal mobility device battery chargers. The observed differences between those experiencing burn injuries and the broader population of personal mobility device riders in terms of age and gender suggest that younger males may be at higher risk, perhaps due to risky practices such as leaving personal mobility devices unattended while charging. This review emphasizes the need for safety education, adherence to regulations, and responsible consumer choices to mitigate burn injuries. Recommendations include promoting child safety measures, using certified personal mobility devices, and cautious handling of DIY conversion kits. Further large-scale studies are essential to gain comprehensive insights and develop effective safety strategies to protect personal mobility device riders from burn injuries.
Neighbour effects on plant biomass and its allocation for forbs growing in heterogeneous soils
Authors: Liu Yongjie , Ma Chunyan , Liu Shiting , Liu Mingrui , Li Hui , Wang Mingxia , Li Guoe , De Boeck Hans J , Hou Fujiang , Tang Zhanhui , Li Zhenxin
Published: June 2024

Focal plants are considerably affected by their neighbouring plants, especially when growing in heterogeneous soils. A previous study on grasses demonstrated that soil heterogeneity and species composition affected plant biomass and above- and belowground allocation patterns. We now tested whether these findings were similar for forbs. Three forb species (i.e. Spartina anglica, Limonium bicolor and Suaeda glauca) were grown in pots with three levels of soil heterogeneity, created by alternatively filling resource-rich and resource-poor substrates using small, medium or large patch sizes. Species compositions were created by growing these forbs either in monocultures or in mixtures. Results showed that patch size × species composition significantly impacted shoot biomass, root biomass and total biomass of forbs at different scales. Specifically, at the pot scale, shoot biomass, root biomass and total biomass increased with increasing patch size. At the substrate scale, shoot biomass and total biomass were higher at the large patch size than at the medium patch size, both in resource-rich and resource-poor substrates. Finally, at the community scale, monocultures had more shoot biomass, root biomass and total biomass than those in the two- or three-species mixtures. These results differ from earlier findings on the responses of grasses, where shoot biomass and total biomass decreased with patch size, and more shoot biomass and total biomass were found in resource-rich than resource-poor substrates. To further elucidate the effects of soil heterogeneity on the interactions between neighbour plants, we advise to conduct longer-term experiments featuring a variety of functional groups.
An ecological perspective on Joseph Rock’s (1884–1962) plant collection activities in China
Authors: Luo Jifan , Huang Ruozhi , Yan Hai , Wu Renwu , Liao Shuai , Xiang Zhoubing , Zou Yongxi , Shi Liangchen , Wang Ke , Bao Zhiyi
Published: June 2024

In the early 20th century, numerous western botanists, often referred to as ‘plant hunters’, embarked on ambitious expeditions to China, playing a crucial role in the study of botany and botanical diversity. Despite their contributions, comprehensive assessments of their explorations are lacking. To bridge this gap, this article focuses on the work of Joseph Charles Francis Rock, a notable figure in that era. Our work revisits Rock’s botanical expeditions within the broader context of botanical diversity conservation. It outlines his historical experiences in collecting plants in China and enumerates the species composition and phenotypic traits of the plants he collected. Additionally, it also analyzes the spatial distribution of the species, the completeness of his collection and the α- and β-diversity of the plants he collected. Our findings reveal that Rock led four major botanical expeditions in China between 1922 and 1933, amassing a total of 28 184 sheets and 16 608 numbers across 204 families, 1081 genera and 4231 species. His focus was predominantly on ornamental species, which exhibit a variety of flower colors and inflorescences. His collection work spanned 5 provinces, 35 cities and 72 counties, with a notable concentration in the Hengduan Mountains, a current biodiversity hotspot. This study not only reconstructs Rock’s botanical legacy but also offers valuable historical data and fresh analytical insights for understanding contemporary plant diversity. It contributes to the ongoing discourse on the importance of preserving plant diversity as a cornerstone of environmental sustainability.
Prunus persica leaves aqueous extract mediated biosynthesis of Ag nanoparticles and assessment of its anti-quorum sensing potential against Hafnia species
Authors: Tan Xiqian , Pei Jianbo , Zhang Defu , Cui Fangchao , Wang Dangfeng , Li Xuepeng , Li Jianrong
Published: June 2024

Hafnia sp. was one of the specific spoilage bacteria in aquatic products, and the aim of the study was to investigate the inhibition ability of the silver nanoparticles (AgNPs) biosynthesis by an aqueous extract of Prunus persica leaves toward the spoilage-related virulence factors of Hafnia sp. The synthesized P-AgNPs were spherical, with a mean particle size of 36.3 nm and zeta potential of 21.8 ± 1.33 mV. In addition, the inhibition effects of P-AgNPs on the growth of two Hafnia sp. strains and their quorum sensing regulated virulence factors, such as the formation of biofilm, secretion of N-acetyl-homoserine lactone (AHLs), proteases, and exopolysaccharides, as well as their swarming and swimming motilities were evaluated. P-AgNPs had a minimum inhibitory concentration (MIC) of 64 μg ml−1 against the two Hafnia sp. strains. When the concentration of P-AgNPs was below MIC, it could inhibit the formation of biofilms by Hafnia sp at 8–32 μg ml−1, but it promoted the formation of biofilms by Hafnia sp at 0.5–4 μg ml−1. P-AgNPs exhibited diverse inhibiting effects on AHLs and protease production, swimming, and swarming motilities at various concentrations.
A Methodology for Robust Multislice Ptychography
Authors: Gilgenbach Colin , Chen Xi , LeBeau James M
Published: June 2024

While multislice electron ptychography can provide thermal vibration limited resolution and structural information in 3D, it relies on properly selecting many intertwined acquisition and computational parameters. Here, we outline a methodology for selecting acquisition parameters to enable robust ptychographic reconstructions. We develop two physically informed metrics, areal oversampling and Ronchigram magnification, to describe the selection of these parameters in multislice ptychography. Through simulations, we comprehensively evaluate the validity of these two metrics over a broad range of conditions and show that they accurately guide reconstruction success. Further, we validate these conclusions with experimental ptychographic data and demonstrate close agreement between trends in simulated and experimental data. Using these metrics, we achieve experimental multislice reconstructions at a scan step of 2.1Å/px, enabling large field-of-view, data-efficient reconstructions. These experimental design principles enable the routine and robust use of multislice ptychography for 3D characterization of materials at the atomic scale.
A multitracer analysis for the eBOSS galaxy sample based on the effective field theory of large-scale structure
Authors: Zhao Ruiyang , Mu Xiaoyong , Gsponer Rafaela , Donald-McCann Jamie , Feng Yonghao , Zhang Weibing , Wang Yuting , Zhao Gong-Bo , Koyama Kazuya , Bacon David , Crittenden Robert G
Published: June 2024

We perform a multitracer full-shape analysis in Fourier space based on the effective field theory of large-scale structure (EFTofLSS) using the complete Sloan Digital Sky Survey IV (SDSS-IV) extended Baryon Oscillation Spectroscopic Survey (eBOSS) DR16 luminous red galaxy (LRG) and emission line galaxy (ELG) samples. We study in detail the impact of the volume projection effect and different prior choices when doing the full-shape analysis based on the EFTofLSS model. We show that adopting a combination of Jeffreys prior and Gaussian prior can mitigate the volume effect and avoid exploring unphysical regions in the parameter space at the same time, which is crucial when jointly analysing the eBOSS LRG and ELG samples. We validate our pipeline using 1000 eBOSS EZmocks. By performing a multitracer analysis on mocks with comparable footprints, we find that cosmological constraints can be improved by $\sim 10-35~{{\ \rm per\ cent}}$ depending on whether we assume zero stochastic terms in the cross power spectrum, which breaks the degeneracy and boosts the constraints on the standard deviation of matter density fluctuation σ8. Combining with the Big Bang Nucleosynthesis (BBN) prior and fixing the spectral tilt ns to Planck value, our multitracer full-shape analysis measures H0 = 70.0 ± 2.3 km s−1Mpc−1, $\Omega _m=0.317^{+0.017}_{-0.021}$, $\sigma _8=0.787_{-0.062}^{+0.055}$, and $S_8=0.809_{-0.078}^{+0.064}$, consistent with the Planck 2018 results. In particular, the constraint on σ8 is improved beyond that obtained from the single tracer analysis by 18 per cent, or by 27 per cent when assuming zero stochastic terms in the cross power spectrum.
Size–mass relations for simulated low-mass galaxies: mock imaging versus intrinsic properties
Authors: Klein Courtney , Bullock James S , Moreno Jorge , Mercado Francisco J , Hopkins Philip F , Cochrane Rachel K , Benavides Jose A
Published: June 2024

The observationally inferred size versus stellar–mass relationship (SMR) for low-mass galaxies provides an important test for galaxy formation models. However, the relationship relies on assumptions that relate observed luminosity profiles to underlying stellar mass profiles. Here we use the Feedback in Realistic Environments simulations of low-mass galaxies to explore how the predicted SMR changes depending on whether one uses star-particle counts directly or mock observations. We reproduce the SMR found in The Exploration of Local Volume Satellites survey remarkably well only when we infer stellar masses and sizes using mock observations. However, when we use star particles to directly infer stellar masses and half-mass radii, we find that our galaxies are too large and obey an SMR with too little scatter compared to observations. This discrepancy between the ‘true’ galaxy size and mass and those derived in the mock observation approach is twofold. First, our simulated galaxies have higher and more varied mass-to-light ratios (MLR) at a fixed colour than those commonly adopted, which tends to underestimate their stellar masses compared to their true, simulated values. Second, our galaxies have radially increasing MLR gradients therefore using a single MLR tends to underpredict the mass in the outer regions. Similarly, the true half-mass radius is larger than the half-light radius because the light is more concentrated than the mass. If our simulations are accurate representations of the real Universe, then the relationship between galaxy size and stellar mass is even tighter for low-mass galaxies than is commonly inferred from observed relations.
Effectiveness of fremanezumab treatment in patients with migraine headache
Authors: Kikui Shoji , Daisuke Danno , Miyahara Junichi , Sugiyama Hanako , Ota Kuniko , Murakata Kenji , Kashiwaya Yoshihiro , Takeshima Takao
Published: June 2024

Objective

To evaluate the efficacy and safety of fremanezumab for migraine prevention.

Design

Retrospective, single-center, real-world study.

Setting

Regional tertiary headache center in Japan.

Subjects

Adult individuals with migraine (n = 165, male = 17, female = 148; average age = 45.5 ± 16.0 years) who received fremanezumab between September 2021 and August 2022.

Methods

Fremanezumab was administered subcutaneously at a monthly dose of 225 mg or quarterly dose of 675 mg based on patient preferences. Patients received fremanezumab treatment for up to 1 year unless it was discontinued. Monthly data were collected on migraine days, headache days, and days requiring acute medication.

Results

Of the 165 patients, 125 (75.7%) received fremanezumab as their first anti-calcitonin gene-related peptide-related antibody drug. Significant reductions in monthly migraine days, headache days, and days requiring acute medication were observed in those with episodic and chronic migraines. The baseline monthly headache days was 8.1 ± 4.0 in the episodic migraine group, which reduced to 6.1 ± 4.8, 5.8 ± 4.4, 4.7 ± 3.6, and 4.6 ± 3.3 days at 1, 3, 6, and 12 months, respectively; in the chronic migraine group, the baseline monthly headache days was 20.9 ± 6.1, which reduced to 17.0 ± 8.9, 15.0 ± 9.2, 13.0 ± 7.7, and 12.0 ± 9.1 days at 1, 3, 6, and 12 months, respectively. Treatment benefits were enhanced after 6 months of administering fremanezumab in the chronic migraine group.

Conclusions

In this real-world study of patients with migraine, fremanezumab appears to be effective and safe. Further studies are required to identify additional predictors of treatment success and failure with fremanezumab.
Simple Design Criterion for High-Intensity Hadron Linacs
Authors: Kasagaki Asuto , Okamoto Hiromi
Published: June 2024

A simple procedure is established to optimize fundamental design parameters of a high-intensity hadron linac where interparticle Coulomb interaction plays a crucial role. Based on the recently proposed semi-empirical resonance condition, a stability map is constructed which reveals potentially dangerous operating regions in tune space. The map is shown to be consistent with numerical data obtained from more complicated approaches. The effectiveness of the new design scheme is demonstrated through systematic particle-in-cell simulations assuming the most typical structure of an Alvarez-type drift tube linac. The present results suggest that the so-called equipartitioning condition, which has often been taken very seriously in high-intensity linac designs, does not need to be met to guarantee the best machine performance. The basic design concept described here can be applied not only to linacs but also to circular machines.
Blurring the Boundaries Between Medicine and Food: The Canny Marketing of Läkerol in Early Twentieth-Century Sweden
Authors: O’Hagan Lauren Alex , Eriksson Göran
Published: June 2024

This paper explores the early marketing practices (1910–1940) of the Swedish cough drop brand Läkerol, demonstrating how it capitalised on the ‘spaces of confusion’ posed by the product’s liminality between food and medicine to create a slick marketing campaign inspired by the tried-and-tested formulas of the food industry. Advertisements used a range of strategies, such as expert and role model testimonials, humorous and serious newsjacking and the introduction of a friend-physician brand mascot to extend Läkerol from a cold remedy to an everyday product necessary for fun and excitement. By telling consumers not just about its benefits, but also connoting that it was part of a contemporary way of living, Läkerol was able to incorporate itself into a daily consumerist lifestyle, growing into a trendy and popular brand consumed daily by Swedes as part of a ritualised practice.
When to sleep and consume caffeine to boost alertness
Authors: Vital-Lopez Francisco G , Doty Tracy J , Reifman Jaques
Published: June 2024

Study Objectives

Sleep loss can cause cognitive impairments that increase the risk of mistakes and accidents. However, existing guidelines to counteract the effects of sleep loss are generic and are not designed to address individual-specific conditions, leading to suboptimal alertness levels. Here, we developed an optimization algorithm that automatically identifies sleep schedules and caffeine-dosing strategies to minimize alertness impairment due to sleep loss for desired times of the day.

Methods

We combined our previous algorithms that separately optimize sleep or caffeine to simultaneously identify the best sleep schedules and caffeine doses that minimize alertness impairment at desired times. The optimization algorithm uses the predictions of the well-validated Unified Model of Performance to estimate the effectiveness and physiological feasibility of a large number of possible solutions and identify the best one. To assess the optimization algorithm, we used it to identify the best sleep schedules and caffeine-dosing strategies for four studies that exemplify common sleep-loss conditions and compared the predicted alertness-impairment reduction achieved by using the algorithm’s recommendations against that achieved by following the U.S. Army caffeine guidelines.

Results

Compared to the alertness-impairment levels in the original studies, the algorithm’s recommendations reduced alertness impairment on average by 63%, an improvement of 24 percentage points over the U.S. Army caffeine guidelines.

Conclusions

We provide an optimization algorithm that simultaneously identifies effective and safe sleep schedules and caffeine-dosing strategies to minimize alertness impairment at user-specified times.
Adipose Kiss1 controls aerobic exercise‐related adaptive responses in adipose tissue energy homeostasis
Authors: Liang Chunyu , Li Xuehan , Song Ge , Schmidt Søren Fisker , Sun Lingyu , Chen Jianhao , Pan Xinliang , Zhao Haotian , Yan Yi
Published: June 2024

Kisspeptin signaling regulates energy homeostasis. Adiposity is the principal source and receiver of peripheral Kisspeptin, and adipose Kiss1 metastasis suppressor (Kiss1) gene expression is stimulated by exercise. However, whether the adipose Kiss1 gene regulates energy homeostasis and plays a role in adaptive alterations during prolonged exercise remains unknown. Here, we investigated the role of Kiss1 role in mice and adipose tissues and the adaptive changes it induces after exercise, using adipose‐specific Kiss1 knockout (Kiss1adipoq−/−) and adeno‐associated virus‐induced adipose tissue Kiss1‐overexpressing (Kiss1adipoq over) mice. We found that adipose‐derived kisspeptin signal regulates lipid and glucose homeostasis to maintain systemic energy homeostasis, but in a sex‐dependent manner, with more pronounced metabolic changes in female mice. Kiss1 regulated adaptive alterations of genes and proteins in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OxPhos) pathways in female gWAT following prolonged aerobic exercise. We could further show that adipose Kiss1 deficiency leads to reduced peroxisome proliferator‐activated receptor gamma co‐activator 1 alpha (PGC‐1α) protein content of soleus muscle and maximum oxygen uptake (VO2 max) of female mice after prolonged exercise. Therefore, adipose Kisspeptin may be a novel adipokine that increases organ sensitivity to glucose, lipids, and oxygen following exercise.
The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila
Authors: Dai Yuting , Wang Yixuan , Kang Qian , Wu Yifan , Liu Yongqi , Su Yun , Wang Xinhua , Xiu Minghui , He Jianzheng
Published: June 2024

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1‐GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative‐related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aβ42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aβ‐induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.
Andragogic Improvements in Radiation Safety Training
Authors: Cotton Chandler , Wilson Charles , Heath Robert , Caffrey Emily
Published: June 2024

At the University of Alabama at Birmingham (UAB), many diagnostic and therapeutic procedures involving radioactive materials or radiation-producing machines are performed daily. A growing number of minor but preventable incidents related to radiation safety have brought up concerns related to the effectiveness of the training program. A comprehensive literature review was performed to summarize post-COVID insights into andragogic online training practices, statistical analyses, and overall retention competencies in radiation safety. Andragogic research shows that the best method of training adult learners is controlled simulation that tests critical thinking and problem-solving capabilities, drawing upon previous knowledge or experiences. A new training curriculum based on these andragogic principles was designed and administered to a subgroup of UAB radiation workers. Scores from pre-testing and post-testing were collected and analyzed. An ANCOVA was used to account for differences in the pre-test scores between the control and experimental groups, which was found to be statistically significant (p = 0.018), suggesting that small changes in a radiation safety training program can have significant impacts in retention of key information.
The Effect of Medicare Annual Wellness Visits on Breast Cancer Screening and Diagnosis
Authors: Hamer Mika K. , Bradley Cathy J. , Lindrooth Richard , Perraillon Marcelo C.
Published: June 2024

Objective:

The Medicare Annual Wellness Visit (AWV)—a prevention-focused annual check-up—has been available to beneficiaries with Part B coverage since 2011. The objective of this study was to estimate the effect of Medicare AWVs on breast cancer screening and diagnosis.

Data Sources and Study Setting:

The National Cancer Institute’s Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims (SEER-Medicare), HRSA’s Area Health Resources Files, the FDA’s Mammography Facilities database, and CMS “Mapping Medicare Disparities” utilization data from 2013 to 2015.

Study Design:

Using an instrumental variables approach, we estimated the effect of AWV utilization on breast cancer screening and diagnosis, using county Welcome to Medicare Visit (WMV) rates as the instrument.

Data Collection/Extraction Methods:

66,088 person-year observations from 49,769 unique female beneficiaries.

Principal Findings:

For every 1-percentage point increase in county WMV rate, the probability of AWV increased by 1.7 percentage points. Having an AWV was associated with a 22.4-percentage point increase in the probability of receiving a screening mammogram within 6 months (P<0.001). There was no statistically significant increase in the probability of breast cancer diagnosis (overall or early stage) within 6 months of an AWV. Findings were robust to multiple model specifications.

Conclusions:

Performing routine cancer screening is an evidence-based practice for diagnosing earlier-stage, more treatable cancers. The AWV effectively increases breast cancer screening and may lead to more timely screening. Continued investment in Annual Wellness Visits supports breast cancer screening completion by women who are most likely to benefit, thus reducing the risk of overscreening and overdiagnosis.
Clinical Relevance of Cancerization of Ducts in Resected Pancreatic Ductal Adenocarcinoma
Authors: Kinny-Köster Benedict , Ahmad Yembur , Pflüger Michael J. , Habib Joseph R. , Fujikura Kohei , Hutchings Danielle , Cameron John L. , Shubert Christopher R. , Lafaro Kelly J. , Burkhart Richard A. , Burns William R. , Javed Ammar A. , Yu Jun , Hruban Ralph H. , Wood Laura D. , Thompson Elizabeth D. , He Jin
Published: June 2024

Objectives

Although prevalent in 50%–90% of pancreatic ductal adenocarcinomas, the clinical relevance of “cancerization of ducts” (COD) remains unknown.

Methods

Pathologists retrospectively reviewed slides classifying prevalence of COD. Histopathological parameters, location of first recurrence, recurrence-free survival (RFS), and overall survival (OS) were collected from the institutional pancreatectomy registry.

Results

Among 311 pancreatic ductal adenocarcinomas, COD was present in 216 (69.5%) and more prevalent in the cohort that underwent upfront surgery (75.3% vs 63.1%, P = 0.019). Furthermore, COD was associated with female gender (P = 0.040), advanced T stage (P = 0.007), perineural invasion (P = 0.014), lymphovascular invasion (P = 0.025), and R1 margin (P = 0.009), but not N stage (P = 0.401) or tumor differentiation (P = 0.717). In multivariable regression, COD was associated with less liver recurrence (odds ratio, 0.44; P < 0.005). This association was driven by the cohort of patients who had received preoperative treatment (odds ratio, 0.18; P < 0.001). COD was not predictive for RFS or OS.

Conclusions

Cancerization of ducts was not associated with RFS or OS. Currently underrecognized, standardized implementation into histopathological reports may have merit, and further mechanistic scientific experiments need to illuminate its clinical and biologic impact.
Mandibular third-molar germectomy: case report
Authors: Ouaabbou Hajar , Hakkou Fouzia , Chbicheb Saliha
Published: June 2024

Introduction and importance:

Third molars are often removed in order to prevent complications and various other problems associated with impacted teeth.

Case presentation:

A healthy 17-year-old girl with no history was referred to the Department of Oral Surgery by her orthodontist to remove mandibular third-molar germs. Panoramic radiography showed the presence of impacted mandibular third-molar germs, vertically positioned, with incomplete root formation. The tooth germs (48, 38) were extracted under local-regional anesthesia. The postoperative period was uneventful.

Clinical discussion:

Germectomy is still relevant in the management of mandibular third molars (MTM). It is a surgical removal of the dental germ at a particularly specific developmental period. However, the need to extract the MTM germs is still controversial.

Conclusion:

Germectomy is well justified in light of clinical symptomatology and/or a suspicious radiographic image. Nonetheless, in asymptomatic MTM, it is important to assess the procedure’s cost-benefit ratio.
Electrocardiogram (EKG) knowledge and interpretation proficiency among healthcare professionals in Pakistan: a prospective cross-sectional study
Authors: Hassan Zair , Kumari Usha , Waseem Maria , Yaqoob Uzair , Sahito Moiz , Zehra Syeda Arshia , Reddy Nikhil , Jan Muneeb Ullah , Surani Salim , Khan Aarash
Published: June 2024

Background:

Electrocardiogram (EKG) is a commonly used diagnostic tool for the evaluation of the electrical activity of the heart. The purpose of this study was to assess the knowledge and interpretation proficiency of EKG among healthcare professionals (HCPs) in Pakistan.

Methods:

This prospective cross-sectional study was conducted among HCPs working in different healthcare settings. A structured questionnaire was used to assess the participants’ theoretical knowledge and ability to interpret EKG findings. The data were analyzed using descriptive statistics and χ2 tests. The study indicates that EKG knowledge and interpretation proficiency among HCPs in Pakistan is unsatisfactory. The inadequacy of training periods of EKG training sessions and insufficient participation of HCPs in offered training opportunities put forward the need for the formation and introduction of better structured and efficient EKG training programmes.

Results:

A total of 511 HCPs participated in the study, 28% of whom reportedly had received formal training for EKG interpretation. About 80% of the participants correctly identified theoretical questions pertaining to EKG, while 58% of the participants were able to accurately interpret EKG findings, and most HCPs (69.9%) read fewer than ten EKGs per week.

Conclusion:

This study demonstrates a lack of expertise and a poor understanding of EKG in HCPs of Pakistan. The low level of EKG knowledge and interpretation proficiency among HCPs may lead to diagnostic errors and poor patient outcomes. Therefore, efforts should be made to improve EKG education and training among HCPs in Pakistan.
Specificity and tunability of efflux pumps: a new role for the proton gradient?
Authors: Gerry Matthew , Kirby Duncan , Alexandrov Boian S. , Segal Dvira , Zilman Anton
Published: June 2024

Bacterial efflux pumps that transport antibacterial drugs out of the bacterial cells have broad specificity, commonly leading to broad spectrum resistance and limiting treatment strategies for infections. It remains unclear how efflux pumps can maintain this broad spectrum specificity to diverse drug molecules while limiting the efflux of other cytoplasmic content. We investigate the origins of this broad specificity using theoretical models informed by the experimentally determined structural and kinetic properties of efflux pumps. We develop a set of mathematical models describing operation of efflux pumps as a discrete cyclic stochastic process across a network of states characterizing pump conformations and the presence/absence of bound ligands and protons. We find that the pump specificity is determined not solely by the drug affinity to the pump–as is commonly assumed–but it is also directly affected by the periplasmic pH and the transmembrane potential. Therefore, the pump effectiveness in removing a particular drug molecule from the cell can be tuned by modifying the proton concentration gradient and the voltage drop across the membrane. Furthermore, we find that while both the proton concentration gradient across the membrane and the transmembrane potential contribute to the thermodynamic force driving the pump, their effects on the efflux enter not strictly in a combined proton motive force, but rather they have two distinguishable effects on the overall throughput. These results potentially explain the broad specificity of efflux pumps and suggest ways to overcome bacterial resistance, while highlighting unexpected effects of thermodynamic driving forces out of equilibrium.
Deconvoluted methylation profiles discriminate between closely related melanocytic nevi
Authors: Aldea Daniel , Macagno Nicolas , Marechal Elise , Moreno Mathias , Romanet Pauline , Pertuit Morgane , Garcia Jérémy , Degardin Nathalie , Mallet Stéphanie , James Isabelle , Captier Guillaume , Barlier Anne , Etchevers Heather C.
Published: June 2024

Congenital melanocytic nevi (CMN) and common acquired melanocytic nevi (AMN) are melanoma-predisposing skin conditions presenting excessive numbers of melanocytes but arising at different times in life. Appropriately weighted whole-genome methylation analysis can be used as a basis for further research in dermatopathology and as applied here provides new insights into nevus biology.