bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐world outcomes of pembrolizumab monotherapy in non‐small cell lung cancer in Japan: A post‐marketing surveillance
Authors: Yamamoto Nobuyuki , Kamitani Tetsu , Kanda Kingo , Ito Yuichiro , Hamada Masahiro , Ozaki Masahiko , Takeuchi Noriko , Yamada Tomoko , Kawano Masaki , Maekawa Shinichiroh , Kato Terufumi
Published: May 2022

This post‐marketing surveillance (PMS) was initiated in Japan to identify factors affecting the safety and effectiveness of pembrolizumab monotherapy in patients with advanced non‐small cell lung cancer (NSCLC) with programmed cell death ligand‐1 (PD‐L1) expression. This PMS was conducted from December 2016 to June 2019 at 717 centers across Japan. Patients with unresectable advanced/recurrent NSCLC who received pembrolizumab monotherapy as first‐line (1L) treatment for PD‐L1‐expressing tumors (Tumor Proportion Score [TPS] ≥ 50%) or second‐line or later (2L+) treatment for tumors with PD‐L1 TPS ≥ 1% were enrolled and followed up for 1 year. Of 2805 registered patients, 2740 and 2400 comprised the safety and effectiveness analysis sets, respectively. The median age (range) was 69 (27–92) years; 55.7% and 29.2% of patients experienced treatment‐related adverse events and adverse events of special interest (AEOSIs), respectively. More common AEOSIs included interstitial lung disease, endocrine disorders, liver dysfunction, colitis/severe diarrhea, infusion reactions, and severe skin disorders. The frequency of experiencing ≥2 AEOSIs was low (1L, 6.5%; 2L+, 2.8%). Most AEOSIs occurred within 150 days after initiation of pembrolizumab monotherapy. At 1‐year follow‐up, the objective response rate was 39.2% (1L, 51.5%; 2L+, 30.0%). In conclusion, the 1‐year safety and effectiveness of pembrolizumab monotherapy in patients with unresectable advanced/recurrent NSCLC as 1L treatment for tumors with PD‐L1 TPS ≥ 50% and 2L+ treatment for tumors with PD‐L1 TPS ≥ 1% were similar to those reported in phase 2/3 trials.
Socioeconomic status biases among children and adolescents: The role of school diversity and teacher beliefs in Nepal
Authors: Grütter Jeanine , Dhakal Sandesh , Killen Melanie
Published: May 2022

Investigating socioeconomic status (SES) biases, Nepalese children and adolescents (N = 605, 52% girls, Mage = 13.21, SDage = 1.74) attending schools that varied by SES composition were asked to anticipate whether a peer would include a high or low SES character as a math partner. Novel findings were that students attending mixed SES schools were more likely to expect inclusion of a low SES character than were students attending high SES schools. With age, high SES participants attending mixed SES schools increasingly expected the inclusion of the low SES character. Moreover, teachers' democratic beliefs in high SES schools predicted inclusive expectations. Teacher beliefs and school diversity play a significant role for fostering students' inclusivity in educational contexts.
Infectious keratitis: A review
Authors: Cabrera‐Aguas Maria , Khoo Pauline , Watson Stephanie L.
Published: May 2022

Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.
Residential care as an alternative care option: A review of literature within a global context
Authors: Giraldi Miriana , Mitchell Fiona , Porter Robert Benjamin , Reed Douglas , Jans Valérie , McIver Leanne , Manole Mihaela , McTier Alexander
Published: May 2022

While there is unequivocal agreement on the need to support families and to avoid all unnecessary separation, there are ongoing debates across policy and practitioner communities nationally and internationally, around the place of residential care within the range of alternative care services which should be available to children who need them. This paper presents the findings of a review of evidence looking at the function, quality and outcomes of residential care based on 111 papers identified for inclusion using systematic searches. The review identifies definitional ambiguity in the use of the terms ‘residential’ and ‘institutional’ care in the literature, which, alongside the different cultural, social and economic contexts, makes generalizing challenging. However, we found insufficient evidence to substantiate claims that residential care is inherently unsuitable. We identify research gaps in the literature, including in relation to quality, children's perspectives and factors that impact upon the suitability of residential care for different children, before discussing implications of the findings for research, policy and practice.
Recursive analytic spherical harmonics gradient for spherical lights
Authors: Mézières P. , Mellado N. , Barthe L. , Paulin M.
Published: May 2022

When rendering images using Spherical Harmonics (SH), the projection of a spherical function on the SH basis remains a computational challenge both for high‐frequency functions and for emission functions from complex light sources. Recent works investigate efficient SH projection of the light field coming from polygonal and spherical lights. To further reduce the rendering time, instead of computing the SH coefficients at each vertex of a mesh or at each fragment on an image, it has been shown, for polygonal area light, that computing both the SH coefficients and their spatial gradients on a grid covering the scene allows the efficient and accurate interpolation of these coefficients at each shaded point. In this paper, we develop analytical recursive formulae to compute the spatial gradients of SH coefficients for spherical light. This requires the efficient computation of the spatial gradients of the SH basis function that we also derive. Compared to existing method for polygonal light, our method is faster, requires less memory and scales better with respect to the SH band limit. We also show how to approximate polygonal lights using spherical lights to benefit from our derivations. To demonstrate the effectiveness of our proposal, we integrate our algorithm in a shading system able to render fully dynamic scenes with several hundreds of spherical lights in real time.
Coverage Axis: Inner Point Selection for 3D Shape Skeletonization
Authors: Dou Zhiyang , Lin Cheng , Xu Rui , Yang Lei , Xin Shiqing , Komura Taku , Wang Wenping
Published: May 2022

In this paper, we present a simple yet effective formulation called Coverage Axis for 3D shape skeletonization. Inspired by the set cover problem, our key idea is to cover all the surface points using as few inside medial balls as possible. This formulation inherently induces a compact and expressive approximation of the Medial Axis Transform (MAT) of a given shape. Different from previous methods that rely on local approximation error, our method allows a global consideration of the overall shape structure, leading to an efficient high‐level abstraction and superior robustness to noise. Another appealing aspect of our method is its capability to handle more generalized input such as point clouds and poor‐quality meshes. Extensive comparisons and evaluations demonstrate the remarkable effectiveness of our method for generating compact and expressive skeletal representation to approximate the MAT.
Z2P: Instant Visualization of Point Clouds
Authors: Metzer G. , Hanocka R. , Giryes R. , Mitra N. J. , Cohen‐Or D.
Published: May 2022

We present a technique for visualizing point clouds using a neural network. Our technique allows for an instant preview of any point cloud, and bypasses the notoriously difficult surface reconstruction problem or the need to estimate oriented normals for splat‐based rendering. We cast the preview problem as a conditional image‐to‐image translation task, and design a neural network that translates point depth‐map directly into an image, where the point cloud is visualized as though a surface was reconstructed from it. Furthermore, the resulting appearance of the visualized point cloud can be, optionally, conditioned on simple control variables (e.g., color and light). We demonstrate that our technique instantly produces plausible images, and can, on‐the‐fly effectively handle noise, non‐uniform sampling, and thin surfaces sheets.
Closed space‐filling curves with controlled orientation for 3D printing
Authors: Bedel A. , Coudert‐Osmont Y. , Martínez J. , Nishat R. I. , Whitesides S. , Lefebvre S.
Published: May 2022

We explore the optimization of closed space‐filling curves under orientation objectives. By solidifying material along the closed curve, solid layers of 3D prints can be manufactured in a single continuous extrusion motion. The control over orientation enables the deposition to align with specific directions in different areas, or to produce a locally uniform distribution of orientations, patterning the solidified volume in a precisely controlled manner.

Our optimization framework proceeds in two steps. First, we cast a combinatorial problem, optimizing Hamiltonian cycles within a specially constructed graph. We rely on a stochastic optimization process based on local operators that modify a cycle while preserving its Hamiltonian property. Second, we use the result to initialize a geometric optimizer that improves the smoothness and uniform coverage of the cycle while further optimizing for alignment and orientation objectives.
A Survey on Reinforcement Learning Methods in Character Animation
Authors: Kwiatkowski Ariel , Alvarado Eduardo , Kalogeiton Vicky , Liu C. Karen , Pettré Julien , van de Panne Michiel , Cani Marie‐Paule
Published: May 2022

Reinforcement Learning is an area of Machine Learning focused on how agents can be trained to make sequential decisions, and achieve a particular goal within an arbitrary environment. While learning, they repeatedly take actions based on their observation of the environment, and receive appropriate rewards which define the objective. This experience is then used to progressively improve the policy controlling the agent's behavior, typically represented by a neural network. This trained module can then be reused for similar problems, which makes this approach promising for the animation of autonomous, yet reactive characters in simulators, video games or virtual reality environments. This paper surveys the modern Deep Reinforcement Learning methods and discusses their possible applications in Character Animation, from skeletal control of a single, physically‐based character to navigation controllers for individual agents and virtual crowds. It also describes the practical side of training DRL systems, comparing the different frameworks available to build such agents.
Promoting resilience to depression among couples during pregnancy: The protective functions of intimate relationship satisfaction and self‐compassion
Authors: Kumar Shaina A. , Franz Molly R. , DiLillo David , Brock Rebecca L.
Published: May 2022

Pregnancy, while often marked by joy, may pose considerable risk for depression among parents. Against a backdrop of adverse life events, expectant parents may be even more vulnerable to developing symptoms of depression during the prenatal period. Thus, it is critical to identify sources of resilience that might facilitate a successful transition to parenthood among couples who have a history of adversity. Prior work suggests that interpersonal and intrapersonal factors associated with resilience, such as intimate relationship satisfaction and self‐compassion (i.e., self‐kindness, common humanity, and mindfulness), have the potential to attenuate prenatal depression among couples with a history of stressful life experiences. We tested this possibility in a sample of 159 couples navigating pregnancy. As predicted, a greater number of prior stressful life experiences was associated with increased depression symptom severity for both mothers and fathers. However, moderation analyses revealed the positive link between cumulative stressful life experiences and depression symptom severity was attenuated among mothers who reported greater self‐compassion in the form of feelings of common humanity, and fathers who reported higher levels of intimate relationship satisfaction and self‐compassion in the form of mindfulness. Findings suggest enhancing intimate relationship satisfaction and self‐compassion among expectant couples may be valuable in attenuating prenatal depression among those with a greater history of adversity.
No evidence that conifer biochar impacts soil functioning by serving as microbial refugia in boreal soils
Authors: Pingree Melissa R. A. , Kardol Paul , Nilsson Marie‐Charlotte , Wardle David A. , Maaroufi Nadia I. , Gundale Michael J.
Published: May 2022

It is well established that application of biochar to soils can promote soil fertility, which ultimately may enhance plant growth. While many mechanisms have been proposed to explain this, one specific mechanism, the “microbial refugia hypothesis,” suggests that biochar may provide physical protection for soil microbe from soil microfauna that otherwise exert top‐down control on microbial biomass and activity. We tested the microbial refugia hypothesis by incubating two boreal soils with and without biochar derived from a wood mixture of boreal tree species (Picea abies and Pinus sylvestris), and with and without soil nematodes. We measured phospholipid fatty acids (PLFA) as a relative measure of microbial biomass, and several variables indicative of microbial activity, including extractable nutrient concentrations (NH4+, NO3−, and PO4−), heterotrophic N2‐fixation, and soil respiration. Contrary to our expectations, we found that biochar by itself did not stimulate microbial biomass or activity. Furthermore, we found that nematode addition to soil stimulated rather than depressed the biomass of several bacterial PLFA groups. Finally, interactive effects between the nematode treatment and biochar never worked in a way that supported the microbial refugia hypothesis. Our findings suggest that a typical boreal biochar applied to boreal soils may not have the same stimulatory effect on microbial biomass and activity that has been shown in some other ecosystems, and that enhanced plant growth in response to biochar addition sometimes observed in boreal environments is likely due to other mechanisms, such as direct nutrient supply from biochar or amelioration of soil pH.
CIS and TGF‐β regulatory pathways influence immunity to bacterial infection
Authors: McCulloch Timothy R. , Rossi Gustavo R. , Schreuder Jaring , Belz Gabrielle T. , Wells Timothy J. , Souza‐Fonseca‐Guimaraes Fernando
Published: May 2022

Immunotherapy has revolutionized cancer therapy by reactivating tumour‐resident cytotoxic lymphocytes. More recently, immunotherapy has emerged to restore immunity against infectious agents, including bacterial infections. Immunotherapy primarily targets inhibitory pathways in T cells, however interest in other effector populations, such as natural killer (NK) cells, is growing. We have previously discovered that NK cell metabolism, proliferation and activation can be neutralized through the immunosuppressive transforming growth factor (TGF)‐β pathway by inducing plasticity of NK cells and differentiation into innate lymphoid cell (ILC)1‐like subsets. NK cells are also regulated through cytokine‐inducible SH2‐containing protein (CIS), which is induced by interleukin (IL)‐15 and is a potent intracellular checkpoint suppressing NK cell survival and function. Targeting these two distinct pathways to restore NK cell function has shown promise in cancer models, but their application in bacterial infection remains unknown. Here, we investigate whether enhancement of NK cell function can improve anti‐bacterial immunity, using Salmonella Typhimurium as a model. We identified conversion of NK cells to ILC1‐like for the first time in the context of bacterial infection, where TGF‐β signalling contributed to this plasticity. Future study should focus on identifying further drivers of ILC1 plasticity and its functional implication in bacterial infection model. We further describe that CIS‐deficient mice displayed enhanced pro‐inflammatory function and dramatically enhanced anti‐bacterial immunity. Inhibition of CIS may present as a viable therapeutic option to enhance immunity towards bacterial infection.
Predictors of all‐cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS‐CoV‐2
Authors: Hamilton Mackenzie A. , Liu Ying , Calzavara Andrew , Sundaram Maria E. , Djebli Mohamed , Darvin Dariya , Baral Stefan , Kustra Rafal , Kwong Jeffrey C. , Mishra Sharmistha
Published: May 2022

Background

Shared and divergent predictors of clinical severity across respiratory viruses may support clinical and community responses in the context of a novel respiratory pathogen.

Methods

We conducted a retrospective cohort study to identify predictors of 30‐day all‐cause mortality following hospitalization with influenza (N = 45,749; 2010‐09 to 2019‐05), respiratory syncytial virus (RSV; N = 24 345; 2010‐09 to 2019‐04), or severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; N = 8988; 2020‐03 to 2020‐12; pre‐vaccine) using population‐based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude, and confidence intervals of risk ratios to identify shared and divergent predictors of mortality.

Results

A total of 3186 (7.0%), 697 (2.9%), and 1880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS‐CoV‐2, respectively. Shared predictors of increased mortality included older age, male sex, residence in a long‐term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS‐CoV‐2. Few comorbidities were associated with mortality among patients with SARS‐CoV‐2 as compared with those with influenza or RSV.

Conclusions

Our findings may help identify patients at greatest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local prevention and therapeutic strategies to communities with higher prevalence of risk factors.
Improvement in desulfurization of dibenzothiophene and dibenzothiophene sulfone by Paenibacillus strains using immobilization or nanoparticle coating
Authors: Sar Taner , Ozturk Murat , Stark Benjamin C. , Akbas Meltem Yesilcimen
Published: May 2022

Aims

Biodesulfurization of fossil fuels is a promising technology for deep desulfurization. Previously, we have shown that Paenibacillus strains 32O-W and 32O-Y can desulfurize dibenzothiophene (DBT) and DBT sulfone (DBTS) effectively. In this work, improvements in DBT and DBTS desulfurization by these strains were investigated through immobilization and nanoparticle coating of cells.

Methods and Results

Paenibacillus strains 32O-W and 32O-Y immobilized in alginate gel beads or coated with Fe3O4 magnetite nanoparticles were grown at various concentrations (0.1–2 mmol l−1) of DBT or DBTS for 96 h. The production of 2-hydroxybiphenyl (2-HBP) from the 4S pathway biotransformation of DBT or DBTS was measured. The highest amounts of 2-HBP production occurred at concentrations of 0.1 and 0.5 mmol l−1. Compared to planktonic cultures maximum 2-HBP production increased by 54% for DBT and 90% for DBTS desulfurization with immobilized strains, and 44% for DBT and 66% for DBTS desulfurization by nanoparticle-coated strains.

Conclusions

Nanoparticle-coated and immobilized cells may be of use in efforts to increase the efficiency of biodesulfurization.

Significance and Impact of the Study

Alginate immobilization or nanoparticle coating of bacterial cells may be useful approaches for the enhancement of biodesulfurization for eventual use on an industrial scale.
Hidden island endemic species and their implications for cryptic speciation within soil arthropods
Authors: Pérez‐Delgado Antonio J. , Arribas Paula , Hernando Carles , López Heriberto , Arjona Yurena , Suárez‐Ramos Daniel , Emerson Brent C. , Andújar Carmelo
Published: May 2022

Aim

Specialisation to the soil environment is expected to constrain the spatial scale of diversification within animal lineages. In this context, flightless arthropod lineages, adapted to soil environments, but with broad geographical ranges, represent something of an anomaly. Here we investigate the diversification process within one such ‘anomalous’ soil specialist, an eyeless and flightless beetle species strongly adapted to the endogean environment but distributed across several oceanic islands.

Location

Canary Islands.

Taxon

Geomitopsis franzi Coiffait, 1978 (Coleoptera, Staphylinidae).

Methods

We performed an integrative study, including molecular phylogenetics, population genomics and morphometry. Four DNA regions (two mitochondrial and two nuclear) were amplified and sequenced for 159 specimens from 58 localities sampled across five islands for phylogenetic analyses, and a dated phylogenetic tree was obtained using a mitogenome dataset. ddRAD‐seq data were generated to evaluate mtDNA lineages in sympatry against the biological species concept.

Results

We found high levels of genetic differentiation (>8% COI gene divergence) among populations from different islands and among geographically coherent lineages within single islands. Lineages within Tenerife presented significant patterns of isolation by distance, with ddRAD‐seq providing evidence that lineages represent biological species. Morphometric analyses revealed limited variation.

Main conclusions

Geomitopsis franzi is comprised of at least seven lineages that merit consideration as biological species, and is best considered as a complex of cryptic species. The limited morphological variation across these lineages is consistent with adaptation to the endogean environment placing strong constraints on morphological change. The evolution of cryptic species should be favoured when such constraints are coupled with limited dispersal ability, a trait that broadly characterises the soil mesofauna.
Emergency and post‐emergency care of older adults with Alzheimer's disease/Alzheimer's disease related dementias
Authors: Hill Jacob D. , Schmucker Abigail M. , Siman Nina , Goldfeld Keith S. , Cuthel Allison M. , Chodosh Joshua , Bouillon‐Minois Jean‐Baptiste , Grudzen Corita R.
Published: May 2022

Background

The emergency department (ED) is a critical juncture in the care of persons living with dementia (PLwD), as they have a high rate of hospital admission, ED revisits, and subsequent inpatient stays. We examine ED disposition of PLwD compared with older adults with non‐dementia chronic disease as well as healthcare utilization and survival.

Methods

Medicare claims data were used to identify community‐dwelling older adults 66+ years old from 34 hospitals with either Alzheimer's disease/Alzheimer's disease related dementias (AD/ADRD) or a non‐AD/ADRD chronic condition between January 1, 2014, and December 31, 2018. We compared ED disposition at the index visit, as well as healthcare utilization and mortality in the 12 months following an index ED visit, and adjusted for age, gender, and risk of mortality.

Results

There were 29,626 patients in the AD/ADRD sample, and 317,046 in the comparison sample. The AD/ADRD sample was older (82.4 years old [SD: 8.2] vs. 76.0 years old [SD: 7.7]) and had more female patients (59.9% vs. 54.7%). The AD/ADRD sample was more likely to experience ED disposition to acute care (OR 1.039, p < 0.001, 95% CI 1.029–1.050), to have an ED revisit (OR 1.077, p < 0.001, 95% CI 1.066–1.087), and an inpatient stay in the subsequent 12 months (OR 1.085, p < 0.001, 95% CI 1.075–1.095). ED disposition to hospice was low in both samples (0.2%). AD/ADRD patients had a higher risk of mortality (OR 1.099, p < 0.001, 95% CI 1.091–1.107) and high short‐term mortality (31.9% within 12 months) than those without AD/ADRD (15.3% within 12 months).

Conclusions

PLwD who visit the ED have high short‐term mortality. Despite this, disposition to acute care, ED revisits, and inpatient stays, rather than hospice, remain the predominant mode of care delivery. Transition directly from the ED to hospice for PLwD is rare.
An update on polymyalgia rheumatica
Authors: Lundberg Ingrid E. , Sharma Ankita , Turesson Carl , Mohammad Aladdin J.
Published: May 2022

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2–3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL‐6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15–25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC‐related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease‐modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment.
Molecular pathways and possible therapies for head and neck vascular anomalies
Authors: Coulie Julien , Boon Laurence , Vikkula Miikka
Published: May 2022

Vascular anomalies are a heterogenous group of vascular lesions that can be divided, according to the International Society for the Study of Vascular Anomalies Classification, into two main groups: vascular tumors and vascular malformations. Vascular malformations can be further subdivided into slow‐flow and fast‐flow malformations. This clinical and radiological classification allows for a better understanding of vascular anomalies and aims to offer a more precise final diagnosis. Correct diagnosis is essential to propose the best treatment, which traditionally consists of surgery, embolization, or sclerotherapy. Since a few years, medical treatment has become an important part of multidisciplinary treatment. Genetic and molecular knowledge of vascular anomalies are increasing rapidly and opens the door for a molecular classification of vascular anomalies according to the underlying pathways involved. The main pathways seem to be PI3K/AKT/mTOR and RAS/RAF/MEK/ERK. Knowing the underlying molecular cascades allows us to use targeted medical therapies. The first part of this article aims to review the vascular anomalies seen in the head and neck region and their underlying molecular causes and involved pathways. The second part will propose an overview of the available targeted therapies based on the affected molecular cascade. This article summarizes theragnostic treatments available in vascular anomalies.
A validated UPLC‐MS/MS method for quantification of glutamine in plasma and pharmacokinetic study of oral glutamine tablets in healthy Beagles
Authors: Liu Dongying , Guo Fanxi , Yu Yuanqian , Zhou Yuqing , Xu Yidan , Zou Yuanpeng , Li Chongyang , Zhang Fengyichi , Yu Zugong
Published: May 2022

This study aimed to clarify the laws of glutamine tablets absorption, distribution, and metabolism in Beagles and to provide a basis for formulating dosing regimens. Twelve healthy Beagles were enrolled the absolute bioavailability study with a crossover design . Glutamine tablets (240 mg/kg b.w.) or glutamine sterile solution (60 mg/kg b.w.) were administered. A method for the determination of glutamine in Beagles' plasma by UPLC‐MS/MS was established, with high sensitivity, specificity, and simplicity. Based on the study of endogenous glutamine concentration, the mean concentration of the four time points before drug administration was selected as the background concentration of glutamine. Pharmacokinetic parameters were calculated by non‐compartment model. The Cmax of glutamine was 136.11 ± 72.51 μg/ml, Tmax was 0.85 ± 0.29 h, and t1/2λz was 0.42 ± 0.27 h after oral administration. The AUC0−t of glutamine was 116.30 ± 75.15 h·μg/ml vs. 44.55 ± 22.48 h·μg/ml following oral and IV administration, respectively, with an absolute bioavailability of 64.74% ± 19.18%. The results showed glutamine was quickly absorbed and eliminated in Beagles with high bioavailability. Therefore, glutamine is suitable to be prepared as oral tablets and recommended to shorten the dosing interval.
Medium optimization for submerged fermentative production of β-cyclodextrin glucosyltransferase by isolated novel alkalihalophilic Bacillus sp. NCIM 5799 using statistical approach
Authors: Solanki P. , Banerjee T.
Published: May 2022

β-cyclodextrin glucosyltransferase (β-CGTase) is an essential enzyme to catalyse the biotransformation of starch into β-cyclodextrins (β-CD). β-CD has widespread applications in the biomedical, pharmaceutical and food industries. The present study focused on β-CGTase production using an efficient natural microbial strain and statistical production optimization for enhanced production. The isolated organism Bacillus sp. NCIM 5799 was found to be 5 μm short bacilli under FE-SEM and alkalihalophilic in nature. The β-CGTase production was optimized using a combination of Plackett–Burman design (PBD) and Central Composite Design—Response Surface Methodology (CCD-RSM). On PBD screening Na2CO3, peptone and MgSO4.7H2O were found to be significant for optimal β-CGTase production, whereas the soluble starch and K2HPO4 concentrations were found to be nonsignificant for β-CGTase production. The significant factors obtained after PBD were further optimized using CCD-RSM design. Peptone was found to have a significant interaction effect with Na2CO3, and MgSO4·7H2O and Na2CO3 exhibited a significant effect on the production of CGTase. The production of β-CGTase was enhanced in the presence of peptone (3%) and Na2CO3 (0·8%). CGTase production obtained was 156·76 U/ml when optimized using CCD-RSM. The final optimized medium (RSM) shows 7·7- and 5·4-fold high productions as compared to un-optimized and one factor at a time production media.
Antibacterial and antibiofilm activities of some plant essential oils and synergistic effects of cinnamon essential oil with vancomycin against Clostridioides difficile: in vitro study
Authors: Tosun M.N. , Taylan G. , Demirel Zorba N.N.
Published: May 2022

The detection of resistant strains of Clostridioides difficile against existing antibiotics and the side effects led to the investigation of alternative agents. Inhibition zones of various essential oils to four strains of C.difficile and other Clostridium species ranged from 8·32 to 44·18 mm. The highest zone was observed in cinnamon and tea tree essential oils. and The MIC values varied between 0·39–25 (%, v/v). The main components were cinnamaldehyde (85·64%) in cinnamon essential oil, 4-terpineol (83·6%) was determined in tea tree essential oil. Additive effects were found between cinnamon essential oil and vancomycin and between cinnamon and tea tree essential oils, and the FICI values were 0·512 and 0·517, respectively. Both cinnamon and tea tree essential oils showed antibiofilm activities against all tested C. difficile strains at all tested concentrations. Essential oils may be used as a supplement in addition to treatment in the control of C. difficile-related diseases.
High level of calcium carbonate precipitation achieved by mixed culture containing ureolytic and nonureolytic bacterial strains
Authors: Harnpicharnchai P. , Mayteeworakoon S. , Kitikhun S. , Chunhametha S. , Likhitrattanapisal S. , Eurwilaichitr L. , Ingsriswang S.
Published: May 2022

This study demonstrates a remarkably high level of microbial-induced calcium carbonate precipitation (MICP) using a mixed culture containing TBRC 1396 (Priestia megaterium), TBRC 8147 (Neobacillus drentensis) and ATCC 11859 (Sporosarcina pasteurii) bacterial strains. The mixed culture produced CaCO3 weights 1·4 times higher than those obtained from S. pasteurii, the gold standard for efficient MICP processes. The three strains were selected after characterization of various Bacillus spp. and related species for their ability to induce the MICP process, especially in an alkaline and high-temperature environment. Results showed that the TBRC 1396 and TBRC 8147 strains, as well as TBRC 5949 (Bacillus subtilis) and TBRC 8986 (Priestia aryabhattai) strains, could generate calcium carbonate at pH 9–12 and temperature 30–40°C, which is suitable for construction and consolidation purposes. The TBRC 8147 strain also exhibited CaCO3 precipitation at 45°C. The TBRC 8986 and TBRC 8147 strains are nonureolytic bacteria capable of MICP in the absence of urea, which can be used to avoid the generation of undesirable ammonia associated with the ureolytic MICP process. These findings facilitate the successful use of MICP as a sustainable and environmentally friendly technology for the development of various materials, including self-healing concrete and soil consolidation.
Acidic dileucine motifs in the cylindrical inclusion protein of turnip mosaic virus are crucial for endosomal targeting and viral replication
Authors: Wu Guanwei , Jia Zhaoxing , Rui Penghuan , Zheng Hongying , Lu Yuwen , Lin Lin , Peng Jiejun , Rao Shaofei , Wang Aiming , Chen Jianping , Yan Fei
Published: May 2022

Previously we reported that the multifunctional cylindrical inclusion (CI) protein of turnip mosaic virus (TuMV) is targeted to endosomes through the interaction with the medium subunit of adaptor protein complex 2 (AP2β), which is essential for viral infection. Although several functionally important regions in the CI have been identified, little is known about the determinant(s) for endosomal trafficking. The CI protein contains seven conserved acidic dileucine motifs [(D/E)XXXL(L/I)] typical of endocytic sorting signals recognized by AP2β. Here, we selected five motifs for further study and identified that they all were located in the regions of CI interacting with AP2β. Coimmunoprecipitation assays revealed that alanine substitutions in the each of these acidic dileucine motifs decreased binding with AP2β. Moreover, these CI mutants also showed decreased accumulation of punctate bodies, which enter endocytic‐tracking styryl‐stained endosomes. The mutations were then introduced into a full‐length infectious clone of TuMV, and each mutant had reduced viral replication and systemic infection. The data suggest that the acidic dileucine motifs in CI are indispensable for interacting with AP2β for efficient viral replication. This study provides new insights into the role of endocytic sorting motifs in the intracellular movement of viral proteins for replication.
Skin patterning and internal anatomy in a fossil moonfish from the Eocene Bolca Lagerstätte illuminate the ecology of ancient reef fish communities
Authors: Rossi Valentina , Unitt Richard , McNamara Maria , Zorzin Roberto , Carnevale Giorgio
Published: May 2022

Colour patterning in extant animals can be used as a reliable indicator of their biology and, in extant fish, can inform on feeding strategy. Fossil fish with preserved colour patterns may thus illuminate the evolution of fish behaviour and community structure, but are understudied. Here we report preserved melanin‐based integumentary colour patterning and internal anatomy of the fossil moonfish Mene rhombea (Menidae) from the Bolca Lagerstätte (Eocene (Ypresian), north‐east Italy). The melanosome‐based longitudinal stripes of M. rhombea differ from the dorsal rows of black spots in its extant relative M. maculata, suggesting that the ecology of moonfish has changed during the Cenozoic. Extant moonfish are coastal schooling fish that feed on benthic invertebrates, but the longitudinal stripes and stomach contents with fish remains in M. rhombea suggest unstructured open marine ecologies and a piscivorous diet. The localized distribution of extant moonfish species in the Indo‐Pacific Ocean may reflect, at least in part, tectonically‐driven reorganization of global oceanographic patterns during the Cenozoic. It is likely that shifts in habitat and colour patterning genes promoted colour pattern evolution in the menid lineage.
Plant metabolism and defence strategies in the flowering stage: Time‐dependent responses of leaves and flowers under attack
Authors: Chrétien Lucille T. S. , Khalil Alix , Gershenzon Jonathan , Lucas‐Barbosa Dani , Dicke Marcel , Giron David
Published: May 2022

Plants developing into the flowering stage undergo major physiological changes. Because flowers are reproductive tissues and resource sinks, strategies to defend them may differ from those for leaves. Thus, this study investigates the defences of flowering plants by assessing processes that sustain resistance (constitutive and induced) and tolerance to attack. We exposed the annual plant Brassica nigra to three distinct floral attackers (caterpillar, aphid and bacterial pathogen) and measured whole‐plant responses at 4, 8 and 12 days after the attack. We simultaneously analysed profiles of primary and secondary metabolites in leaves and inflorescences and measured dry biomass of roots, leaves and inflorescences as proxies of resource allocation and regrowth. Regardless of treatments, inflorescences contained 1.2 to 4 times higher concentrations of primary metabolites than leaves, and up to 7 times higher concentrations of glucosinolates, which highlights the plant's high investment of resources into inflorescences. No induction of glucosinolates was detected in inflorescences, but the attack transiently affected the total concentration of soluble sugars in both leaves and inflorescences. We conclude that B. nigra evolved high constitutive rather than inducible resistance to protect their flowers; plants additionally compensated for damage by attackers via the regrowth of reproductive parts. This strategy may be typical of annual plants.
The co‐chaperone HOP participates in TIR1 stabilisation and in auxin response in plants
Authors: Muñoz Alfonso , Mangano Silvina , Toribio René , Fernández‐Calvino Lourdes , del Pozo Juan C. , Castellano M. Mar
Published: May 2022

HOP (HSP70‐HSP90 organising protein) is a conserved family of co‐chaperones well known in mammals for its role in the folding of signalling proteins associated with development. In plants, HOP proteins have been involved in the response to multiple stresses, but their role in plant development remains elusive. Herein, we describe that the members of the HOP family participate in different aspects of plant development as well as in the response to warm temperatures through the regulation of auxin signalling. Arabidopsis hop1 hop2 hop3 triple mutant shows different auxin‐related phenotypes and a reduced auxin sensitivity. HOP interacts with TIR1 auxin coreceptor in vivo. Furthermore, TIR1 accumulation and auxin transcriptional response are reduced in the hop1 hop2 hop3 triple mutant, suggesting that HOP's function in auxin signalling is related, at least, to TIR1 interaction and stabilisation. Interestingly, HOP proteins form part of the same complexes as SGT1b (a different HSP90 co‐chaperone) and these co‐chaperones synergistically cooperate in auxin signalling. This study provides relevant data about the role of HOP in auxin regulation in plants and uncovers that both co‐chaperones, SGT1b and HOP, cooperate in the stabilisation of common targets involved in plant development.
Fillable and unfillable gaps in plant transcriptome under field and controlled environments
Authors: Hashida Yoichi , Tezuka Ayumi , Nomura Yasuyuki , Kamitani Mari , Kashima Makoto , Kurita Yuko , Nagano Atsushi J.
Published: May 2022

The differences between plants grown in field and in controlled environments have long been recognized. However, few studies have addressed the underlying molecular mechanisms. To evaluate plant responses to fluctuating environments using laboratory equipment, we developed SmartGC, a high‐performance growth chamber that reproduces the fluctuating irradiance, temperature and humidity of field environments. We analysed massive transcriptome data of rice plants grown under field and SmartGC conditions to clarify the differences in plant responses to field and controlled environments. Rice transcriptome dynamics in SmartGC mimicked those in the field, particularly during the morning and evening but those in conventional growth chamber conditions did not. Further analysis revealed that fluctuation of irradiance affects transcriptome dynamics in the morning and evening, while fluctuation of temperature affects transcriptome dynamics only in the morning. We found upregulation of genes related to biotic and abiotic stress, and their expression was affected by environmental factors that cannot be mimicked by SmartGC. Our results reveal fillable and unfillable gaps in the transcriptomes of rice grown in field and controlled environments and can accelerate the understanding of plant responses to field environments for both basic biology and agricultural applications.
Recovery after long‐term summer drought: Hydraulic measurements reveal legacy effects in trunks of Picea abies but not in Fagus sylvatica
Authors: Knüver T. , Bär A. , Ganthaler A. , Gebhardt T. , Grams T. E. E. , Häberle K.‐H. , Hesse B. D. , Losso A. , Tomedi I. , Mayr S. , Beikircher B.
Published: May 2022

Climate change is expected to increase the frequency and intensity of summer droughts. Sufficient drought resistance, the ability to acclimate to and/or recover after drought, is thus crucial for forest tree species. However, studies on the hydraulics of mature trees during and after drought in natura are scarce.

In this study, we analysed trunk water content (electrical resistivity: ER) and further hydraulic (water potential, sap flow density, specific hydraulic conductivity, vulnerability to embolism) as well as wood anatomical traits (tree ring width, conduit diameter, conduit wall reinforcement) of drought‐stressed (artificially induced summer drought via throughfall‐exclusion) and unstressed Picea abies and Fagus sylvatica trees.

In P. abies, ER indicated a strong reduction in trunk water content after 5 years of summer drought, corresponding to significantly lower pre‐dawn leaf water potential and xylem sap flow density. Vulnerability to embolism tended to be higher in drought‐stressed trees. In F. sylvatica, only small differences between drought‐stressed and control trees were observed.

Re‐watering led to a rapid increase in water potentials and xylem sap flow of both drought‐stressed trees, and to increased growth rates in the next growing season. ER analyses revealed lower trunk water content in P. abies trees growing on throughfall‐exclusion plots even 1 year after re‐watering, indicating a limited capacity to restore internal water reserves. Results demonstrated that P. abies is more susceptible to recurrent summer drought than F. sylvatica, and can exhibit long‐lasting and pronounced legacy effects in trunk water reserves.
Exogenous melatonin improves the resistance to cucumber bacterial angular leaf spot caused by Pseudomonas syringae pv. Lachrymans
Authors: Li Lele , Du Changxia , Wang Lu , Lai Mengxia , Fan Huaifu
Published: May 2022

Pseudomonas syringae pv. Lachrymans (Psl) is a bacterial pathogen that causes cucumber bacterial angular leaf spot (BALS). It is known that melatonin (MT), as a pleiotropic signal molecule, can improve plant stress tolerance, but less information is available about the function of MT on plant resistance to bacteria disease. Here, we investigated the effect of MT on cucumber BALS. Our results show that MT inhibited the bacteria Psl growth significantly in vitro and attenuated cucumber BALS remarkably in vivo. The concentration of bacteria in leaves treated with 0.1 mM MT was approximately 10,000 times reduced at 5 days‐post‐inoculation (dpi), compared to the control without MT. Transcriptomic analysis showed that 225 differentially expressed genes (DEGs) were induced in leaves after just MT treatment for 3 h. The functions of these DEGs were mainly associated with hormone signal transduction, mitogen‐activated protein kinase (MAPK) signaling pathway, and photosynthesis, suggesting that MT could regulate plant growth and induce plant immunity. Moreover, 665 DEGs were induced when leaves were treated with exogenous MT in combination with the bacteria inoculation for 12 h. The functions of these DEGs were much related to plant–pathogen interaction, hormone signal transduction, and amino acids biosynthesis pathways. Many MT‐induced DEGs were involved in some distinct signal transduction pathways, such as calmodulin (CaM), polyamines (PAs), nitric oxide (NO), and salicylic acid (SA). The physiological analysis shows that exogenous MT spray reduced the stomatal aperture and enhanced the activities of antioxidant and defense enzymes, which were in consistent with the results of the transcriptome analysis. In addition, MT may function in regulating the metabolic balance between plant growth and defense. In conclusion, our results demonstrate that MT could alleviate the cucumber BALS via inhibiting propagation and invasion of Psl, activating plant signaling, enhancing antioxidative and defense systems, inducing stress‐related genes expression, and regulating the plant growth‐defense balance.