bluuebunny/crossref_metadata_2025 huggingface dataset:
Shadow removal method of soil surface image based on GAN used for estimation of farmland soil moisture content
Authors: Meng Chao , Yang Wei , Wang Dong , Hao Ziyuan , Li Minzan
Published: April 2023

It is important to obtain soil moisture content (SMC) in farmland, and soil surface images can be used to rapidly estimate SMC. The objective of this study was to propose a shadow removal algorithm to eliminate the effect of shadows in soil surface images, so as to improve the accuracy of SMC estimation. The structure of the proposed soil shadow generative adversarial networks (SS GAN) was a circulating network, which is an unsupervised method and does not require paired shadow image sets for network training. Four loss functions were defined for the network to effectively remove shadows and ensure texture detail and color consistency. This method is compared with traditional methods, supervised and unsupervised deep learning techniques by comparative experiments. Evaluations were made from visual and quantitative comparisons. Visually, the best shadow removal method was proved, it almost has no shadow boundaries or shadow areas visible for samples. The peak signal to noise ratio (PSNR) and structural similarity (SSIM) were used to quantitatively compare shadow removal images with real non-shadow images. The PSNR and SSIM of SS GAN were 28.46 and 0.95 respectively, which are superior to other methods, indicating that the images processed by SS GAN were closer to the real non-shadow images. Field experiments results shown that SS GAN has excellent shadow removal performance in the self-developed vehicle-mounted detection system. In order to verify the improvement effect of shadow removal image on SMC estimation accuracy, further field test was conducted to estimate SMC. Compared with SMC estimation results before and after shadow removal, R
2 increased from 0.69 to 0.76, and root mean square error decreased from 1.39 to 0.94%. The results show that the proposed method can effectively remove the shadow of soil image and improve the accuracy of SMC estimation in farmland.
Perspective on small mass and force measurements
Authors: Arumugam Kumar , Shaw Gordon
Published: April 2023

The measurement of small mass and force is as pertinent now as it was in 1923 when E M Eden and C G Eden published their article titled ‘Two machines for rapidly weighing loads of a few milligrams’ in the inaugural edition of the Measurement Science and Technology journal (formerly known as the Journal of Scientific Instruments). In the century since, measurement techniques have evolved and become more accurate with current uncertainties of nanograms at the milligram level measurements. This article reviews these advancements as well as the applications for small mass and force measurement that have evolved over the last century.
Enhancing some separability criteria in many-body quantum systems
Authors: Tang Liang , Wu Fan
Published: April 2023

Quantum measurements based on mutually unbiased bases, mutually unbiased measurements and general symmetric informationally complete positive operator valued measurements, which are commonly used in quantum information and quantum computation. In this paper, by a broad class of informationally complete symmetric measurements and correlation matrices, some separability criteria are proposed for different quantum systems that are more robust and comprehensive than the corresponding criteria previously introduced L M Lai, T Li, S M Fei, and Z X Wang, (2018 Quantum Inf. Process., 17, 314); J W Shang, A Asadian, and H J Zhu, (2018 Phys. Rev. A
98, 022309). Furthermore, we extend the separability criteria of tripartite quantum systems to many-body systems. The proposed entanglement criteria may further enrich the relationship between quantum entanglement and measurement.
Impact of QCD uncertainties on antiproton spectra from dark-matter annihilation
Authors: Jueid Adil , Kip Jochem , Ruiz de Austri Roberto , Skands Peter
Published: April 2023

Dark-matter particles that annihilate or decay can undergo complex sequences of processes, including strong and electromagnetic radiation, hadronisation, and hadron decays, before particles that are stable on astrophysical time scales are produced. Antiprotons produced in this way may leave footprints in experiments such as AMS–02. Several groups have reported an excess of events in the antiproton flux in the rigidity range of 10–20 GV. However, the theoretical modeling of baryon production is not straightforward and relies in part on phenomenological models in Monte Carlo event generators.
In this work, we assess the impact of QCD uncertainties on the spectra of antiprotons from dark-matter annihilation. As a proof-of-principle, we show that for a two-parameter model that depends only on the thermally-averaged annihilation cross section (〈σv〉) and the dark-matter mass (Mχ
), QCD uncertainties can affect the best-fit mass
by up to ∼ 14% (with large uncertainties for large DM masses), depending on the choice of Mχ
and the annihilation channel (bb̅ or W
+
W
-),
and 〈σv〉 by up to ∼ 10%. For comparison, changes to the underlying diffusion parameters are found to be within 1%–5%, and the results are also quite resilient to the choice of cosmic-ray propagation model. These findings indicate that QCD uncertainties need to be included in future DM analyses. To facilitate full-fledged analyses, we provide the spectra in tabulated form including QCD uncertainties and code snippets to perform mass interpolations and quick DM fits. The code can be found in this GitHub [1] repository.
Hundred watt level and high energy compact hybrid fiber femtosecond laser with good beam quality
Authors: Li Qianglong , Li Feng , Zhao Wei , Wang Yishan , Wen Wenlong , Yang Yang , Zhao Hualong , Cao Xue , Si Jinhai
Published: April 2023

A hundred watt level compact femtosecond laser system comprised of a high gain, low nonlinearity silicate glass fiber amplifier and a highly efficient Yb:YAG single-crystal fiber amplifier is demonstrated. By reducing the harmful thermal lens effect of amplifiers and optical elements, and precisely tuning dispersion of the stretcher, 110 W, 495 fs laser output at 1 MHz repetition rate and 250 μJ, 494 fs laser output at 200 kHz repetition rate are obtained. An optimized beam-quality factor (M
2) of better than 1.3 is obtained by filtering the beam with a small-aperture diaphragm. To our best knowledge, this is the first demonstration of such a hybrid femtosecond laser over 100 W and 100 μJ with good beam quality.
Magnetic and magnetotransport properties of layered TaCoTe2 single crystals
Authors: Mei 梅 Ming 明 , Chen 陈 Zheng 正 , Nie 聂 Yong 勇 , Wang 王 Yuanyuan 园园 , Zhu 朱 Xiangde 相德 , Ning 宁 Wei 伟 , Tian 田 Mingliang 明亮
Published: April 2023

We present the synthesis of TaCoTe2 single crystals and a systematic investigation of the physical properties of bulk crystals and thin flakes. The crystal shows a semiconducting behavior with temperature decreasing from room temperature and turns to a metallic behavior below 38 K. When the magnetic field is applied, the temperature-dependent resistivity curves show an upturn below 10 K. Furthermore, we find that the TaCoTe2 single crystal can be easily exfoliated from the bulk crystal by the micromechanical exfoliation method. Our measurements suggest that the nanoflakes have properties similar to those of the bulk crystal when the thickness is lowered to 18 nm.
Identifying Host Galaxies of Extragalactic Radio Emission Structures using Machine Learning
Authors: Lou Kangzhi , Lake Sean E. , Tsai Chao-Wei
Published: April 2023

This paper presents an automatic multi-band source cross-identification method based on deep learning to identify the hosts of extragalactic radio emission structures. The aim is to satisfy the increased demand for automatic radio source identification and analysis of large-scale survey data from next-generation radio facilities such as the Square Kilometre Array and the Next Generation Very Large Array. We demonstrate a 97% overall accuracy in distinguishing quasi-stellar objects, galaxies and stars using their optical morphologies plus their corresponding mid-infrared information by training and testing a convolutional neural network on Pan-STARRS imaging and WISE photometry. Compared with an expert-evaluated sample, we show that our approach has 95% accuracy at identifying the hosts of extended radio components. We also find that improving radio core localization, for instance by locating its geodesic center, could further increase the accuracy of locating the hosts of systems with a complex radio structure, such as C-shaped radio galaxies. The framework developed in this work can be used for analyzing data from future large-scale radio surveys.
3D-printed hierarchical arrangements of actuators mimicking biological muscular architectures
Authors: De Pascali Corrado , Palagi Stefano , Mazzolai Barbara
Published: April 2023

Being able to imitate the sophisticated muscular architectures that characterize the animal kingdom in biomimetic machines would allow them to perform articulated movements with the same naturalness. In soft robotics, multiple actuation technologies have been developed to mimic the contraction of a single natural muscle, but a few of them can be implemented in complex architectures capable of diversifying deformations and forces. In this work, we present three different biomimetic muscle architectures, i.e. fusiform, parallel, and bipennate, which are based on hierarchical arrangements of multiple pneumatic actuators. These biomimetic architectures are monolithic structures composed of thirty-six pneumatic actuators each, directly 3D printed through low-cost printers and commercial materials without any assembly phase. The considerable number of actuators involved enabled the adoption and consequent comparison of two regulation strategies: one based on input modulation, commonly adopted in pneumatic systems, and one based on fiber recruitment, mimicking the regulation behavior of natural muscles. The straightforward realization through additive manufacturing processes of muscle architectures regulated by fiber recruitment strategies facilitates the development of articulated muscular systems for biomimetics machines increasingly similar to the natural ones.
Generalized polarization measurement and its connection with information energy
Authors: Canturk B , Gedik Z
Published: April 2023

We generalize the polarization measurement to the projective measurements of mutually unbiased bases (MUBs). Based on this result, we reveal a direct connection between polarization measurement and information energy function. We also express the polarization measurement by means of symmetric informationally complete positive operator-valued measures (SIC-POVMs). We present an argument suggesting that polarization measurement by means of SIC-POVMs requires fewer resources than the projective measurements of MUBs.
Infection risk and management strategies for patients with cirrhosis taking proton pump inhibitors
Authors: Zerr Beth , Vazquez Alejandro , Erstad Brian L
Published: April 2023

Purpose

The purpose of this review is to discuss infectious disease–related adverse effects associated with long-term proton pump inhibitor (PPI) therapy in patients with cirrhosis and to provide recommendations for appropriate use and choice of PPI when such therapy is indicated.

Long-term PPI therapy in patients with cirrhosis increases the risk of infections, with infections in turn increasing the risk of mortality in this patient population. Expert recommendations include restricting long-term PPI use in cirrhosis to patients with appropriate gastrointestinal indications, using a PPI for the shortest possible duration and at the lowest possible dose, and avoiding PPIs with unfavorable pharmacogenetic properties.

Conclusion

Long-term PPI use in patients with cirrhosis has been associated with increased infections. The risk of adverse effects in observational studies, including decompensation, severe infection (especially spontaneous bacterial peritonitis), and increased mortality, appears to increase as the dose and duration of PPI increase.
Multi-modality attribute learning-based method for drug–protein interaction prediction based on deep neural network
Authors: Dong Weihe , Yang Qiang , Wang Jian , Xu Long , Li Xiaokun , Luo Gongning , Gao Xin
Published: April 2023

Identification of active candidate compounds for target proteins, also called drug–protein interaction (DPI) prediction, is an essential but time-consuming and expensive step, which leads to fostering the development of drug discovery. In recent years, deep network-based learning methods were frequently proposed in DPIs due to their powerful capability of feature representation. However, the performance of existing DPI methods is still limited by insufficiently labeled pharmacological data and neglected intermolecular information. Therefore, overcoming these difficulties to perfect the performance of DPIs is an urgent challenge for researchers. In this article, we designed an innovative ’multi-modality attributes’ learning-based framework for DPIs with molecular transformer and graph convolutional networks, termed, multi-modality attributes (MMA)-DPI. Specifically, intermolecular sub-structural information and chemical semantic representations were extracted through an augmented transformer module from biomedical data. A tri-layer graph convolutional neural network module was applied to associate the neighbor topology information and learn the condensed dimensional features by aggregating a heterogeneous network that contains multiple biological representations of drugs, proteins, diseases and side effects. Then, the learned representations were taken as the input of a fully connected neural network module to further integrate them in molecular and topological space. Finally, the attribute representations were fused with adaptive learning weights to calculate the interaction score for the DPIs tasks. MMA-DPI was evaluated in different experimental conditions and the results demonstrate that the proposed method achieved higher performance than existing state-of-the-art frameworks.
Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model
Authors: Yang Jun-Pu , Ullah Amin , Su Ya-Nan , Otoo Antonia , Adu-Gyamfi Enoch Appiah , Feng Qian , Wang Ying-Xiong , Wang Mei-Jiao , Ding Yu-Bin
Published: April 2023

The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1, on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary syndrome. We generated a polycystic ovary syndrome mouse model by using dehydroepiandrosterone plus high-fat diet. Glycyrrhizin (100 mg/kg) was intraperitoneally injected into the polycystic ovary syndrome mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism, and some molecular mechanisms were investigated. Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance, and decreased insulin sensitivity in the polycystic ovary syndrome mice were reverted by glycyrrhizin. The increased high mobility group box 1 levels in the serum and ovarian tissues of the polycystic ovary syndrome mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor 9, myeloid differentiation factor 88, and nuclear factor kappa B as well as reduced expressions of insulin receptor, phosphorylated protein kinase B, and glucose transporter type 4 were restored by glycyrrhizin in the polycystic ovary syndrome mice. Glycyrrhizin could suppress the polycystic ovary syndrome-induced upregulation of high mobility group box 1, several inflammatory marker genes, and the toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B pathways, while inhibiting the insulin receptor/phosphorylated protein kinase B/glucose transporter type 4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against polycystic ovary syndrome.
Sin as Intellectual Evil: Refusal of Insight in the Contemporary Debate on the Ends of Marriage
Authors: Hogan Margaret Monahan
Published: April 2023

This paper focuses on the possibility of sin as intellectual evil as operative in the contemporaneous culture in the debate over the essential nature of marriage and the accomplishment of the ends of marriage. It presents an account of theology as a science and the application of this understanding and its canons of operation to the issues presented in two recent documents—the Statement of the Wijngaards Institute for Catholic Research and the Affirmation of the Church’s Teaching on the Gift of Sexuality, each of which addresses the encyclical Humanae vitae on the occasion of its 50th anniversary. The paper concludes with an examination of the essential nature of marriage to guide the fulfillment of its ends now described as intrinsic/essential and intrinsic/contingent.
Long-term study into the development of a plenter structure in a forest comprising a mix of European and north American species
Authors: Cameron Andrew , Alexander Ruth
Published: April 2023

Irregular or plenter forestry evolved in Central Europe around a small number of shade-tolerating species; however, increasing interest in developing more climatically resilient, diverse forest structures has seen a greater range of species being studied. A critical question is whether stands comprising a wide geographic mix of species can form irregular structures in the long term. Using data from a unique experimental site established in 1953 at Faskally Forest, North Scotland, temporal changes in structure, density, growth and species diversity were studied in a stand comprising a mix of European and North American species undergoing the latter stages of transformation. A 1-ha permanent sample plot was established in 1997 and data evaluated from five complete inventories carried out at six-yearly intervals (latest in 2021). Metrics describing the irregular structure – defined by negative exponential diameter distributions, q values, Lorenz curves, Gini coefficients and stand density indices – have stabilized over the last three inventories suggesting a relative balance has been achieved between recruitment and harvesting/mortality losses. Whilst shade tolerating species dominate regeneration and recruitment, species diversity has increased since the start of the study. Analyses of transition periods (average time required for all trees to progress from one diameter class into the next) and annual recruitment (average number of trees moving from each diameter class into the next higher class) highlight a growth advantage of shade tolerating species. The range of values defining the irregular stand at Faskally compare well with those from long-term plenter forests in Continental Europe highlighting the potential of forming irregular stand structures comprising geographically diverse species. The study also indicates that the silvicultural characteristics of species are more important than whether they are native or non-native. Stand characteristics reported here could aid managers of irregular/plenter forests by indicating values of such characteristics to guide the transformation of similar mixed-species stands.
Association of Night Shifts and Lifestyle Risks With Incident Dementia
Authors: Ren Jiao-Jiao , Zhang Pei-Dong , Li Zhi-Hao , Zhang Xi-Ru , Zhong Wen-Fang , Chen Pei-Liang , Huang Qing-Mei , Wang Xiao-Meng , Gao Ping-Ming , Mao Chen
Published: April 2023

Background

Little is known about the combined relationship between night shifts and lifestyle risks with incident dementia or their potential interactions. To evaluate the association of night shifts and lifestyle risks with incident dementia and further analyze their interactions.

Methods

A total of 276 059 participants were included in this study from the UK Biobank cohort. Cox proportional hazards models were used to investigate the combined association of night shifts and lifestyle risks with incident dementia.

Results

Participants with always night shifts and 3 or 4 unhealthy lifestyle factors had the highest risk of incident all-cause dementia (hazard ratio: 3.15, 95% confidence interval [CI]: 1.74–5.69). An additive interaction was found between night shifts and lifestyle risks for incident all-cause dementia (p < .001), with a relative excess risk due to the interaction of 0.14 (95% CI: 0.11–0.45). The attributable proportions of the combined effect on the incidence of all-cause dementia were 22.6% (95% CI: 20.91%–26.75%) for night shift work, 65.0% (95% CI: 63.12%–69.80%) for unhealthy lifestyle factors, and 12.1% (95% CI: 8.67%–18.04%) for their interaction.

Conclusions

Both night shifts and lifestyle risks were associated with a higher risk of incident dementia. The combined impact was higher than the increase in the risks related to each single factor. Our results indicated that most incident dementia cases might be prevented by a healthy lifestyle, and the benefits would be greater among night shift workers. Further studies are needed to confirm our results and explore the underlying mechanisms.
Habitat openness and predator abundance determine predation risk of warningly colored longhorn beetles (Cerambycidae) in temperate forest
Authors: Goßmann Anika , Ambrožová Lucie , Cizek Lukas , Drag Lukas , Georgiev Kostadin , Neudam Liane , Perlík Michal , Seidel Dominik , Thorn Simon
Published: April 2023

Organisms have evolved different defense mechanisms, such as crypsis and mimicry, to avoid detection and recognition by predators. A prominent example is Batesian mimicry, where palatable species mimic unpalatable or toxic ones, such as Clytini (Coleoptera: Cerambycidae) that mimic wasps. However, scientific evidence for the effectiveness of Batesian mimicry in Cerambycids in natural habitats is scarce. We investigated predation of warningly and nonwarningly colored Cerambycids by birds in a temperate forest using beetle dummies. Dummies mimicking Tetropium castaneum, Leptura aethiops, Clytus arietis, and Leptura quadrifasciata were exposed on standing and laying deadwood and monitored predation events by birds over one season. The 20 surveyed plots differed in their structural complexity and canopy openness due to different postdisturbance logging strategies. A total of 88 predation events on warningly colored beetle dummies and 89 predation events on nonwarningly colored beetle dummies did not reveal the difference in predation risk by birds. However, predation risk increased with canopy openness, bird abundance, and exposure time, which peaked in July. This suggests that environmental factors have a higher importance in determining predation risk of warningly and nonwarningly colored Cerambycidae than the actual coloration of the beetles. Our study showed that canopy openness might be important in determining the predation risk of beetles by birds regardless of beetles’ warning coloration. Different forest management strategies that often modify canopy openness may thus alter predator–prey interactions.
Sex-Biased Expression Is Associated With Chromatin State in DrosophilamelanogasterandDrosophila simulans
Authors: Nanni Adalena V , Martinez Natalie , Graze Rita , Morse Alison , Newman Jeremy R B , Jain Vaibhav , Vlaho Srna , Signor Sarah , Nuzhdin Sergey V , Renne Rolf , McIntyre Lauren M
Published: April 2023

In Drosophila melanogaster and D. simulans head tissue, 60% of orthologous genes show evidence of sex-biased expression in at least one species. Of these, ∼39% (2,192) are conserved in direction. We hypothesize enrichment of open chromatin in the sex where we see expression bias and closed chromatin in the opposite sex. Male-biased orthologs are significantly enriched for H3K4me3 marks in males of both species (∼89% of male-biased orthologs vs. ∼76% of unbiased orthologs). Similarly, female-biased orthologs are significantly enriched for H3K4me3 marks in females of both species (∼90% of female-biased orthologs vs. ∼73% of unbiased orthologs). The sex-bias ratio in female-biased orthologs was similar in magnitude between the two species, regardless of the closed chromatin (H3K27me2me3) marks in males. However, in male-biased orthologs, the presence of H3K27me2me3 in both species significantly reduced the correlation between D. melanogaster sex-bias ratio and the D. simulans sex-bias ratio. Male-biased orthologs are enriched for evidence of positive selection in the D. melanogaster group. There are more male-biased genes than female-biased genes in both species. For orthologs with gains/losses of sex-bias between the two species, there is an excess of male-bias compared to female-bias, but there is no consistent pattern in the relationship between H3K4me3 or H3K27me2me3 chromatin marks and expression. These data suggest chromatin state is a component of the maintenance of sex-biased expression and divergence of sex-bias between species is reflected in the complexity of the chromatin status.
Induced Immune Reaction in the Acorn Worm, Saccoglossus kowalevskii, Informs the Evolution of Antiviral Immunity
Authors: Tassia Michael G , Hallowell Haley A , Waits Damien S , Range Ryan C , Lowe Christopher J , Graze Rita M , Schwartz Elizabeth Hiltbold , Halanych Kenneth M
Published: April 2023

Evolutionary perspectives on the deployment of immune factors following infection have been shaped by studies on a limited number of biomedical model systems with a heavy emphasis on vertebrate species. Although their contributions to contemporary immunology cannot be understated, a broader phylogenetic perspective is needed to understand the evolution of immune systems across Metazoa. In our study, we leverage differential gene expression analyses to identify genes implicated in the antiviral immune response of the acorn worm hemichordate, Saccoglossus kowalevskii, and place them in the context of immunity evolution within deuterostomes—the animal clade composed of chordates, hemichordates, and echinoderms. Following acute exposure to the synthetic viral double-stranded RNA analog, poly(I:C), we show that S. kowalevskii responds by regulating the transcription of genes associated with canonical innate immunity signaling pathways (e.g., nuclear factor κB and interferon regulatory factor signaling) and metabolic processes (e.g., lipid metabolism), as well as many genes without clear evidence of orthology with those of model species. Aggregated across all experimental time point contrasts, we identify 423 genes that are differentially expressed in response to poly(I:C). We also identify 147 genes with altered temporal patterns of expression in response to immune challenge. By characterizing the molecular toolkit involved in hemichordate antiviral immunity, our findings provide vital evolutionary context for understanding the origins of immune systems within Deuterostomia.
Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction
Authors: Koenekoop Lucien , Åqvist Johan
Published: April 2023

Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by a higher catalytic activity at low temperature than their mesophilic orthologs and are also usually found to be more thermolabile. Computer simulations of the catalytic reactions have been shown to be a very powerful tool for analyzing the structural and energetic origins of these effects. Here, we examine the cold adaptation of lactate dehydrogenases from two Antarctic and sub-Antarctic fish species using this approach and compare our results with those obtained for the orthologous dogfish enzyme. Direct calculations of thermodynamic activation parameters show that the cold-adapted fish enzymes are characterized by a lower activation enthalpy and a more negative entropy term. This appears to be a universal feature of psychrophilic enzymes, and it is found to originate from a higher flexibility of certain parts of the protein surface. We also carry out free energy simulations that address the differences in thermal stability and substrate binding affinity between the two cold-adapted enzymes, which only differ by a single mutation. These calculations capture the effects previously seen in in vitro studies and provide straightforward explanations of these experimental results.
Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas
Authors: Gross Andrea M , Dombi Eva , Wolters Pamela L , Baldwin Andrea , Dufek Anne , Herrera Kailey , Martin Staci , Derdak Joanne , Heisey Kara S , Whitcomb Patricia M , Steinberg Seth M , Venzon David J , Fisher Michael J , Kim AeRang , Bornhorst Miriam , Weiss Brian D , Blakeley Jaishri O , Smith Malcolm A , Widemann Brigitte C
Published: April 2023

Background

Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies.

Methods

This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index).

Results

For the 74 children (median age 10.3 years; range 3–18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1–100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment.

Conclusions

With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.
Canker Disease Intensifies Cross-Kingdom Microbial Interactions in the Endophytic Microbiota of Citrus Phyllosphere
Authors: Huang Feng , Ling Jinfeng , Zhu Congyi , Cheng Baoping , Song Xiaobing , Peng Aitian
Published: April 2023

Plant disease is an important factor that affects the plant microbiome. However, for many plant–pathogen–microbiome interactions, the influences are unknown. Citrus, comprising abundant varieties of mandarin, sweet orange, pomelo, and lemon, is widely cultivated in different production areas in China. Most of these varieties are vulnerable to citrus canker, which is caused by Xanthomonas spp. In this study, asymptomatic and cankered leaves from asymptomatic and canker-infected trees, respectively, were collected from 17 orchards in six citrus production areas and their endophytic microbiomes were compared. The effects of canker on the microbial community richness and diversity were dependent on whether the interaction type was intrakingdom (for bacteria, positive) and interkingdom (for fungi, negative), respectively. The negative effects of canker on the fungal communities might be affected by the strong correlation between Xanthomonas and Fusarium/ Gibberella species. The occurrence of canker significantly affected the composition and structure of both the endophytic fungal and bacterial communities, and altered the dominant genera of each community. In addition, canker occurrence intensified the cross-kingdom microbial interaction network, in which species of Enterobacter, Xanthomonas, Pseudomonas, and Pantoea were detected with increased roles in the network and responsible for the predominant functional genes involved in nutritional metabolism, the bacterial secretion system, and biotin metabolism. The results provide insights into the responses of the endophytic microbiome to citrus canker disease.
Real-world Outcomes Associated With Poly(ADP-ribose) Polymerase Inhibitor Monotherapy Maintenance in Patients With Primary Advanced Ovarian Cancer
Authors: Chan John K. , Liu Jinan , Song Jinlin , Xiang Cheryl , Wu Eric , Kalilani Linda , Hurteau Jean A. , Thaker Premal H.
Published: April 2023

Objective:

This study used real-world population data to assess the trends of first-line (1L) poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment uptake and outcomes in patients with primary advanced ovarian cancer (AOC).

Methods:

Patients diagnosed with AOC between January 1, 2017, and June 30, 2021, who completed 1L chemotherapy were selected from a real-world database. Descriptive analyses were performed to evaluate patient demographics, clinicopathological characteristics, and 1L treatment patterns. Time to next treatment or death was used as a proxy for real-world progression-free survival (rwPFS). Kaplan-Meier methods and Cox models were used for statistical analyses.

Results:

Of 705 patients who completed 1L chemotherapy, 166 received PARPi monotherapy and 539 underwent active surveillance (AS). Median follow-up was 10.9 months for PARPi monotherapy and 20.6 months for AS. PARPi monotherapy use increased from 6% in 2017 to 53% in 2021. Overall, patients receiving PARPi monotherapy had longer rwPFS than those who underwent AS (not reached vs 9.53 mo) respectively. rwPFS was also longer in patients who received PARPi monotherapy compared with AS in patients with BRCA-mutated disease (not reached vs 11.4 mo), BRCA–wild-type disease (13.5 vs 9.1 mo), homologous recombination-deficient tumors (not reached vs 10.2 mo), and homologous recombination-proficient or unknown status tumors (13.5 vs 9.3 mo).

Conclusions:

Our real-world analysis suggested that 47% of patients with primary AOC did not receive PARPi maintenance in the year 2021. PARPi use was associated with significantly improved outcomes compared with AS.
Quality of Life in Patients with Acne Vulgaris: an observational study.
Authors: Ruilian Ding , He Yizhen , Wu Qiuju , Lin Tong
Published: April 2023

Objective:

To investigate the quality of life of patients with acne vulgaris of various degrees of severity, and to provide evidence for establishing effective clinical treatment strategies.

Methods:

We used a self-made questionnaire to assess the demographics, symptoms, and physical signs of patients with acne vulgaris, as well as the acne severity, treatment efficacy, impact of acne on mental health, and effect of acne on daily life. The severity of acne was classified into four grades based on the latest acne grading guideline. Quantitative variables were described as ranges, percentages, and means ± standard deviations. The chi-squared test, linear-by-linear association, and Spearman’s correlation analysis were used to analyze the correlations between categorical variables. Data were analyzed using the Statistical Package for the Social Sciences program (version 22.00; SPSS Inc.). A two-tailed probability value of less than 0.05 was considered statistically significant.

Results:

Of the 94 patients who responded to the questionnaire, the responses of nine patients were excluded because of incomplete data. As the acne severity grading increased and the self-assessed appearance rating decreased, the impacts on daily life, social activity, and mental health increased. There was a weak correlation between the acne severity grading and self-assessed appearance rating (P=0.020, rs=-0.253). The impact of acne severity on the quality of life was mainly reflected as influences on personal reputation (P=0.016) and recreation and leisure activities (P=0.042); the self-assessed appearance mainly affected the patients’ professional careers (P=0.010). The severity of acne (P=0.005) and the effects of acne on attention (P=0.010) and intimacy (P=0.024) varied by sex. Females were less tolerant of appearance blemishes, while males were more troubled by the physical discomforts caused by acne.

Conclusion:

The impact of facial acne on quality of life is related to the acne severity grading, patients’ self-assessed appearance rating, and sex. In clinical practice, therapeutic regimes should be formulated in accordance with the different needs of each patient.
Effectiveness and health benefits of a nutritional, chronobiological and physical exercise primary care intervention in fibromyalgia and chronic fatigue syndrome: SYNCHRONIZE + mixed-methods study protocol
Authors: Carrasco-Querol Noèlia , González Serra Gemma , Bueno Hernández Nerea , Gonçalves Alessandra Queiroga , Pastor Cazalla Marta , Bestratén del Pino Pau , Montesó Curto Pilar , Caballol Angelats Rosa , Fusté Anguera Immaculada , Sancho Sol Mª Cinta , Castro Blanco Elisabet , Vila-Martí Anna , Medina-Perucha Laura , Fernández-Sáez José , Dalmau Llorca M. Rosa , Aguilar Martín Carina
Published: April 2023

Introduction:

Chronic pain, fatigue and insomnia are classic symptoms of fibromyalgia (FM) and chronic fatigue syndrome (CFS) and seriously affect quality of life. Nutrition and chronobiology are often overlooked in multicomponent approach despite their potential. This study aims to evaluate the effectiveness of a multidisciplinary group intervention based on nutrition, chronobiology, and physical exercise in the improvement of lifestyle and quality of life in FM and CFS.

Methods:

Mixed-methods study based on a randomized clinical trial and qualitative analysis with a descriptive phenomenological approach. The study will be conducted in primary care in Catalonia. The control group will follow the usual clinical practice and the intervention group the usual practice plus the studied intervention (12 hours over 4 days). The intervention based on nutrition, chronobiology and physical exercise will be designed considering participants’ opinions as collected in 4 focus groups. To evaluate effectiveness, EuroQol-5D, multidimensional fatigue inventory, VAS pain, Pittsburgh Sleep Quality Index, erMEDAS-17, biological rhythms interview of assessment in neuropsychiatry, REGICOR-Short, FIQR and Hospital Anxiety and Depression Scale questionnaires will be collected at baseline, and at 1, 3, 6, and 12 months post-intervention. Food intake, body composition, resistance and, strength will also be evaluated. The effect size will be calculated using Cohen d and logistic regression models will be used to quantify the impact of the intervention by adjusting for different variables.

Discussion:

It expected that the intervention will improve the patients’ quality of life, fatigue, pain and insomnia, as well as food and physical exercise habits, providing effectiveness evidence of a new therapy in addressing these syndromes in Primary Heath Care. Improvements in the quality of life will have a positive socioeconomic impact by reducing health expenditure on recurrent medical consultation, medication, complementary medical tests, etc and favor the maintenance of an active working life and productivity.
Network meta-analysis: efficacy and safety of treatments for fistulising Crohn’s disease
Authors: Chahal Jacinder K. , Sriranganathan Danujan , Poo Stephanie , Lo Sheng Wei , Kashkooli Soleiman , Garg Mayur , Segal Jonathan P.
Published: April 2023

Introduction

Fistulas are a debilitating complication of Crohn’s disease and treatment options remain limited. There is a lack of head-to-head comparisons between treatments. To our knowledge, this is the first network meta-analysis on the efficacy of medical therapies in achieving fistula remission and maintenance of fistula closure in Crohn’s disease.

Methods

Biomedical databases and the Cochrane Central Registry were searched between 1978 and 2022 for randomized controlled trials (RCTs) reporting on treatments. A network meta-analysis was performed using the frequentist model with pooled relative risks (RRs) and P-scores used to rank treatments.

Results

Twenty-five RCTs were included for analysis with 2239 patients included. At the 16–24 week time point, infliximab produced the only statistically significant result with the 5 mg/kg dose proving the most effective [RR, 2.30; 95% confidence interval (CI), 1.40–3.77]. At 44 weeks, ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24–4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06–3.99) and infliximab 5 mg/kg (RR, 1.68; 95% CI, 1.03–2.75) also producing a statistically significant result.

Conclusion

Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising Crohn’s disease, biologics such as ustekinumab, vedolizumab and adalimumab show promising results.
Implications of COVID-19 on hip fracture care discharge locations during the early stages of the pandemic
Authors: Konda Sanjit R. , Esper Garrett W. , Meltzer-Bruhn Ariana T. , Ganta Abhishek , Leucht Philipp , Tejwani Nirmal C. , Egol Kenneth A.
Published: April 2023

Objectives:

To document discharge locations for geriatric patients treated for a hip fracture before and during the COVID pandemic and subsequent changes in outcomes seen between each cohort.

Design:

Retrospective cohort study.

Setting:

Academic medical center.

Patients/Participants:

Two matched cohorts of 100 patients with hip fracture treated pre-COVID (February–May 2019) and during COVID (February–May 2020).

Intervention:

Discharge location and COVID status on admission. Discharge locations were home (home independently or home with health services) versus facility [subacute nursing facility (SNF) or acute rehabilitation facility].

Main Outcome Measurements:

Readmissions, inpatient and 1-year mortality, and 1-year functional outcomes (EQ5D-3L).

Results:

In COVID+ patients, 93% (13/14) were discharged to a facility, 62% (8/13) of whom passed away within 1 year of discharge. Of COVID+ patients discharged to an SNF, 80% (8/10) died within 1 year. Patients discharged to an SNF in 2020 were 1.8x more likely to die within 1 year compared with 2019 (P = 0.029). COVID− patients discharged to an SNF in 2020 had a 3x increased 30-day mortality rate and 1.5x increased 1-year mortality rate compared with 2019. Patients discharged to an acute rehabilitation facility in 2020 had higher rates of 90-day readmission. There was no difference in functional outcomes.

Conclusions:

All patients, including COVID− patients, discharged to all discharge locations during the onset of the pandemic experienced a higher mortality rate as compared with prepandemic. This was most pronounced in patients discharged to a skilled nursing facility in 2020 during the early stages of the pandemic. If this trend continues, it suggests that during COVID waves, discharge planning should be conducted with the understanding that no options eliminate the increased risks associated with the pandemic.

Level of Evidence:

III
Optimizing and validating a pediatric screening tool to more efficiently test and identify children living with HIV
Authors: Joseph Jessica T. , Mpasela Felton , Dowling Stephanie , Banda Isaac , Bobo Patricia M. , Carmone Andy E. , Haimbe Prudence , Hasweeka Pamfred , Kampekete Gertrude S. , Mumba Fredrick , Mwanza Felix , Sakulanda Charles , Simasiku Mwanei , Suggu Kanchana , Shakwelele Hilda , Munthali Gloria
Published: April 2023

Objective:

To develop and validate a screening tool to improve testing efficiency and increase case finding of children living with HIV.

Design:

Cross-sectional study.

Methods:

Between November 2020 and September 2021, children 18 months to 14 years presenting at outpatient departments in 30 health facilities in Zambia were administered a 14-question pediatric HIV screening tool and then tested for HIV. Data were analyzed using a randomly extracted ‘validation’ dataset and multivariable logistic regression to determine the highest performing and optimal number of screening questions. The final tool was then evaluated in the ‘test’ dataset. Sensitivity and specificity were calculated for both datasets. The final tool was then also implemented in 12 additional facilities to determine operational feasibility and uptake.

Results:

A total of 9,902 children were included in the final analysis. HIV prevalence was 1.3%. Six questions were significantly associated with HIV-positivity. The optimal screening cutoff score was to answer ‘yes’ to one or more of the six questions; using this cutoff sensitivity was 92.5% [95% confidence interval (CI): 85.7%-96.7%] and specificity was 62.9% (95% CI: 61.9%-64.0%). In the test dataset, the same tool had a sensitivity of 84.6% (95% CI: 65.1%-95.6%) and specificity of 64.6% (95% CI: 62.4%-66.7%). Uptake was 89%.

Conclusions:

The results of this study show sensitivity and acceptable specificity in a six-question validated HIV screening tool. Implementing this screening tool in settings where universal testing is not feasible should more efficiently accelerate identification of children living with HIV and their timely initiation onto life-saving drugs.
HIV DNA positively correlates with HLA-DR+CD8+ T lymphocytes over 8-year suppressive ART
Authors: Zhu Tianyuan , Cao Wei , Li Taisheng
Published: April 2023

Objective:

Despite long-term suppressive cART, the activation level of T lymphocytes remains significantly high HIV-infected individuals. This study aims to unravel the relationship between CD8+ T cell activation and HIV DNA reservoir.

Design/methods:

In this retrospective study, 82 HIV-infected patients receiving suppressive cART for ≥8 years were included. Total HIV-1 DNA and expression of CD38 and HLA-DR in CD8+ T cell were quantified repeatedly during long-term follow-up. Longitudinal correlation between HIV-1 DNA and CD8+ T cell activation level was analysed using generalized estimating equation (GEE) model.

Results:

Significant decrease of both total HIV-1 DNA and CD8+ T cell activation level were observed after combined antiretroviral therapy (cART) initiation. However, the expression level of HLA-DR in CD8+ T cells remained abnormally higher than normal range. GEE analysis revealed that HLA-DR expression was positively correlated with total HIV-1 DNA over long-term suppressive cART.

Conclusions:

HIV DNA reservoir may be closely related to CD8+ T cell activation and the inflammatory state in HIV-infected patients despite long-term cART.
Emergency Medicine Case Study on Giant Cell Arteritis
Authors: Vea Davina L. , Hill April T.
Published: April 2023

The purpose of this case study on giant cell arteritis (GCA) is to ensure that emergency nurse practitioners (ENPs) are knowledgeable on this disease process to prevent serious complications such as permanent blindness in patients presenting to the emergency department (ED). The case study reviews emergency management of GCA, which includes diagnostic workup, pharmacological treatment, consults, disposition, follow-up care, and when to return to the ED. The classification criteria will be discussed for GCA from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. In addition, risk assessment, clinical presentation, and physical examination findings will be listed. After reviewing this case study, ENPs should be able to identify GCA and manage care to reduce complications and recurrence of GCA in a patient presenting to the ED.