bluuebunny/crossref_metadata_2025 huggingface dataset:
Mounding treatments set back bryophyte recovery on linear disturbances in treed peatlands
Authors: Echiverri Laureen F. I. , Macdonald S. Ellen , Nielsen Scott E.
Published: October 2022

Treed peatlands are dominated by bryophytes, particularly Sphagnum spp., which create the characteristic hummock‐hollow microtopography. This, in turn, shapes the distribution of bryophyte communities. Disturbances can lead to a loss of this microtopographic variation, impacting the bryophyte community. Seismic lines are deforested linear disturbances (approximately 3–8 m wide) created during oil and gas exploration and very extensive in Alberta, Canada. Loss of microtopographic variation leads to slow tree recovery on seismic lines in treed peatlands. To facilitate tree establishment, mounding is being applied to restore the microtopography on seismic lines. We compared bryophyte communities on unmounded and mounded seismic lines (18 years after seismic line creation, 3 years after mounding), and in adjacent treed fens as the reference, to evaluate how recovery varies with microtopographic position (i.e., top of hummock, slope or side of the hummock, and level ground). We found that recovery on the unmounded seismic lines was underway 18 years after seismic lines were created, while mounding redisturbed the sites and thus set back recovery, at least in the short term (3 years post‐mounding). In unmounded seismic lines, Sphagnum cover was similar to that of reference treatments at all microtopographic positions. In contrast, mounded seismic lines had lower Sphagnum cover and higher cover of true mosses (sans feather mosses) than reference and unmounded treatments. Overall, these results show mounding sets back the recovery of bryophyte communities—the very organisms responsible for the microtopographic variation we are trying to establish. Further monitoring is needed to understand how this changes over time.
The impacts of ecological mowing combined with conventional mechanical or herbicide management on weeds in orange orchards
Authors: Martinelli Rodrigo , Rufino‐Jr. Luiz Renato , Desiderio Daniel Rodrigues , Alcántara‐de la Cruz Ricardo , Monquero Patricia Andrea , Azevedo Fernando Alves de
Published: October 2022

In fruit crops like citrus, weeds coexist throughout their long cycle and can cause several yield losses. Ecological mowing (ECO) is an integrated weed management (IWM) option for citrus, as it produces an in‐situ mulch that suppresses the weeds; however, there is a lack of information on the impacts of tree‐row conventional (CONV) and ECO mechanical weed control when combined with residual or non‐residual herbicides, or standard frequent mechanical (MECH) control. This study aimed to evaluate, for 3 years in a young orange orchard, IWM using ECO and conventional mowing when combined with one of five weed control programmes: pre‐emergent (PRE) herbicides (sulfentrazone [spring], indaziflam [summer]), post‐emergence (POST) herbicides (glyphosate [spring], saflufenacil [summer]), PRE + POST herbicides (sulfentrazone + glyphosate [spring], indaziflam + saflufenacil [summer]) and P/P (pre/post‐emergence duality) herbicides (flumioxazin [spring], diuron [summer]). Impacts on cover crop biomass deposition, weed density, population dynamics, biomass accumulation and seed banks were evaluated. Alternanthera tenella Colla (joyweed), Bidens pilosa L. (hairy beggarticks), Digitaria horizontalis Willd (crabgrass), Galinsoga parviflora Cav. (smallflower galinsoga) and Raphanus raphanistrum L. (wild radish) were the most critical weeds with changes in their population dynamics over time. The ECO treatment promoted greater biomass deposition in the tree‐rows (up to ≈8.0 t ha−1), reducing weed density and biomass accumulation by mulch formation; similarly, MECH resulted in low weed density and a reduction in biomass accumulation. The POST and P/P treatments resulted in low levels of weed control, while ECO + PRE + POST led to almost absolute weed control (>95%). Thus, we suggest ECO + PRE + POST is an efficient IWM option in citrus tree‐row crops with low‐risk herbicide resistance (up to 5 MoA year−1 + mulch).
Analysis and Optimization of Parabolic Trough Solar Collector to Improve Its Optical Performance
Authors: Goel Anubhav , Mahadeva Rajesh , Manik Gaurav
Published: October 2022

This article presents a detailed analysis of parameters that affect the optical performance of parabolic trough solar collector (PTSC) and proposes a suitable method to optimize the relevant ones. A mathematical model is drafted and simulated for known geometry and parameters of industrial solar technology (IST) PTSC. The model was evaluated for three different configurations of IST PTSC involving distinct components. A comparison between the experimental results and model estimations indicates a maximum root-mean-square error (RMSE) of 0.7997, confirming the reliability of the proposed model. The influence of variations in absorber diameter (Dao), length (lrc), width (wrc), and focal length of PTSC (frc), along with direct normal incidence (In), dirt factors (ξdm, ξdhc), and angle of incidence (θ) on the optical performance of PTSC has been investigated. It was established that variation in mentioned parameters exhibits both positive and negative impacts on optical performance. After careful analysis, lrc, wrc, frc, Dao, and θ were chosen for optimization as it was perceived that by varying these in a reasonable range, an optimal set of parameters could be obtained that maximize the absorbed solar irradiation for a given PTSC. Genetic algorithm (GA), particle swarm optimization (PSO), and African vultures optimization algorithm (AVOA) are utilized to estimate the optimal values of parameters. Significant improvement in absorbed solar irradiation (∼16%) is registered with optimized parameters, suggesting that benefits can be obtained if a study is performed prior to producing PTSC modules for an application.
Overturning the mechanisms of cochlear amplification via area deformations of the organ of Corti
Authors: Altoè Alessandro , Dewey James B. , Charaziak Karolina K. , Oghalai John S. , Shera Christopher A.
Published: October 2022

The mammalian ear embeds a cellular amplifier that boosts sound-induced hydromechanical waves as they propagate along the cochlea. The operation of this amplifier is not fully understood and is difficult to disentangle experimentally. In the prevailing view, cochlear waves are amplified by the piezo-electric action of the outer hair cells (OHCs), whose cycle-by-cycle elongations and contractions inject power into the local motion of the basilar membrane (BM). Concomitant deformations of the opposing (or “top”) side of the organ of Corti are assumed to play a minor role and are generally neglected. However, analysis of intracochlear motions obtained using optical coherence tomography calls this prevailing view into question. In particular, the analysis suggests that (i) the net local power transfer from the OHCs to the BM is either negative or highly inefficient; and (ii) vibration of the top side of the organ of Corti plays a primary role in traveling-wave amplification. A phenomenological model derived from these observations manifests realistic cochlear responses and suggests that amplification arises almost entirely from OHC-induced deformations of the top side of the organ of Corti. In effect, the model turns classic assumptions about spatial impedance relations and power-flow direction within the sensory epithelium upside down.
Decoupled Control of Grasp and Rotation Constraints During Prehension of Weightless Objects
Authors: Xu Dayuan , Park Jiwon , Lee Jiseop , Lee Sungjune , Park Jaebum
Published: October 2022

Gravity provides critical information for the adjustment of body movement or manipulation of the handheld object. Indeed, the changes in gravity modify the mechanical constraints of prehensile actions, which may be accompanied by the changes in control strategies. The current study examined the effect of the gravitational force of a handheld object on the control strategies for subactions of multidigit prehension. A total of eight subjects performed prehensile tasks while grasping and lifting the handle by about 250 mm along the vertical direction. The experiment consisted of two conditions: lifting gravity-induced (1g) and weightless (0g) handheld objects. The weightless object condition was implemented utilizing a robot arm that produced a constant antigravitational force of the handle. The current analysis was limited to the two-dimensional grasping plane, and the notion of the virtual finger was employed to formulate the cause–effect chain of elemental variables during the prehensile action. The results of correlation analyses confirmed that decoupled organization of two subsets of mechanical variables was observed in both 1g and 0g conditions. While lifting the handle, the two subsets of variables were assumed to contribute to the grasping and rotational equilibrium, respectively. Notably, the normal forces of the thumb and virtual finger had strong positive correlations. In contrast, the normal forces had no significant relationship with the variables as to the moment of force. We conclude that the gravitational force had no detrimental effect on adjustments of the mechanical variables for the rotational action and its decoupling from the grasping equilibrium.
The Mediating Role of Self-Compassion on the Relationship Between Goal Orientation and Sport-Confidence
Authors: Assar Arash , Weinberg Robert , Ward Rose Marie , Vealey Robin S.
Published: October 2022

The purpose of the present investigation was to explore the mediating role of self-compassion on the relation between goal orientation and sport-confidence, as well as exploring whether these factors differed between male and female student-athletes. To that end, a total of 418 National Collegiate Athletic Association Division I student-athletes (M = 20.19, SD = 1.30) completed the Self-Compassion Scale (athlete version), the Task and Ego Orientation in Sport Questionnaire, and the Trait Sport-Confidence Inventory. Structural equation models suggest that task orientation has both a direct effect on sport-confidence and an indirect one through self-compassion. Furthermore, while there was no direct effect between ego orientation and sport-confidence, the results indicated an indirect effect through self-compassion. Moreover, a multigroup analysis indicated that the paths in the mediation model were moderated by gender. Based on these findings, it is recommended that coaches, sport psychologists, and other practitioners consider self-compassion training to enhance confidence among both ego-oriented and female athletes.
Reconstructing codependent cellular cross-talk in lung adenocarcinoma using REMI
Authors: Yu Alice , Li Yuanyuan , Li Irene , Ozawa Michael G. , Yeh Christine , Chiou Aaron E. , Trope Winston L. , Taylor Jonathan , Shrager Joseph , Plevritis Sylvia K.
Published: October 2022

Cellular cross-talk in tissue microenvironments is fundamental to normal and pathological biological processes. Global assessment of cell-cell interactions (CCIs) is not yet technically feasible, but computational efforts to reconstruct these interactions have been proposed. Current computational approaches that identify CCI often make the simplifying assumption that pairwise interactions are independent of one another, which can lead to reduced accuracy. We present REMI (REgularized Microenvironment Interactome), a graph-based algorithm that predicts ligand-receptor (LR) interactions by accounting for LR dependencies on high-dimensional, small–sample size datasets. We apply REMI to reconstruct the human lung adenocarcinoma (LUAD) interactome from a bulk flow-sorted RNA sequencing dataset, then leverage single-cell transcriptomics data to increase the cell type resolution and identify LR prognostic signatures among tumor-stroma-immune subpopulations. We experimentally confirmed colocalization of CTGF:LRP6 among malignant cell subtypes as an interaction predicted to be associated with LUAD progression. Our work presents a computational approach to reconstruct interactomes and identify clinically relevant CCIs.
Distinct fine-scale variations in calcification control revealed by high-resolution 2D boron laser images in the cold-water coral
Lophelia pertusa
Authors: Fietzke Jan , Wall Marlene
Published: October 2022

Coral calcification is a complex biologically controlled process of hard skeleton formation, and it is influenced by environmental conditions. The chemical composition of coral skeletons responds to calcification conditions and can be used to gain insights into both the control asserted by the organism and the environment. Boron and its isotopic composition have been of particular interest because of links to carbon chemistry and pH. In this study, we acquired high-resolution boron images (concentration and isotopes) in a skeleton sample of the azooxanthellate cold-water coral
Lophelia pertusa
. We observed high boron variability at a small spatial scale related to skeletal structure. This implies differences in calcification control during different stages of skeleton formation. Our data point to bicarbonate active transport as a critical pathway during early skeletal growth, and the variable activity rates explain the majority of the observed boron systematic.
Dynamics of an impacting emulsion droplet
Authors: Damak Maher , de Ruiter Jolet , Panat Sreedath , Varanasi Kripa K.
Published: October 2022

Emulsions are widely used in agriculture where oil-based pesticides are sprayed as an emulsion. However, emulsion droplets can bounce off hydrophobic plant surfaces, leading to major health and environmental issues as pesticides pollute water sources and soils. Here, we report an unexpected transition from bouncing to sticking to bouncing as the droplet impact speed increases. We show that the physics are governed by an in situ, self-generated lubrication of the surface leading to a suction force from the nascent oil layer around the droplet. We demonstrate that this phenomenon can be controlled by a careful balance of three time scales: the contact time of the droplet, the impregnation time scale of the oil, and the oil ridge formation time scale. We lastly build a design map to precisely control the bouncing of droplets and the oil coverage of the target surface. These insights have broad applicability in agriculture, cooling sprays, combustion, and additive manufacturing.
Policies to influence perceptions about COVID-19 risk: The case of maps
Authors: Engel Claudia , Rodden Jonathan , Tabellini Marco
Published: October 2022

Choropleth disease maps are often used to inform the public about the risks posed by coronavirus disease 2019 (COVID-19). In a survey conducted in the U.S. state of Georgia in June 2020, we randomly assigned respondents to view either of two maps. The first map reported county-level COVID case counts; the second displayed case rates per 100,000 people. Respondents who saw case rate maps were less likely to perceive COVID as mostly an urban problem and reported higher levels of concerns about the virus. Case rate maps also increased support for policies aimed at mitigating the spread of the virus, although, for this outcome, the effect was quantitatively small and the maps did not change individuals’ self-reported behavior. For several outcomes, the impact of the case rate map was strongest for rural residents and self-identified Republicans, both of whom were less worried about the virus and more skeptical about public health measures to mitigate its spread.
Evaluation of the Characteristics and Infectivity of the Secondary Inoculum Produced by
Plasmopara viticola
on Grapevine Leaves by Means of Flow Cytometry and Fluorescence-Activated Cell Sorting
Authors: Massi Federico , Marcianò Demetrio , Russo Giuseppe , Stuknytė Milda , Arioli Stefania , Mora Diego , Toffolatti Silvia L.
Published: October 2022

P. viticola
secondary infections contribute significantly to the epidemiology of this important plant pathogen. However, the infection dynamics of asexual spores produced by this organism are still poorly investigated.
Draft Genome of
Acidovorax kalamii
Strain JM16, Isolated from Skin Mucus of Zebrafish (Danio rerio)
Authors: Machado-Conteras Jacquelin , Thomas Kayla , Jozwick Anna K. S.
Published: October 2022

Acidovorax kalamii
strain JM16 was isolated from the skin mucus of the zebrafish,
Danio rerio
. Its genome is 5.3 Mb with a 65.6% GC content and encodes quorum sensing capabilities, which could contribute to ecosystem functioning within the fish host skin bacterial community.
Draft Genome Sequences of the Vibrio parahaemolyticus Strains VHT1 and VHT2, Pasteurization-Resistant Isolates from Environmental Seafood
Authors: Meza Guadalupe , Majrshi Hussain , Saurabh Singh Kumar , Deole Ratnakar , Tiong Hung King
Published: October 2022

Two pasteurization-resistant strains, VHT1 and VHT2, of environmental, viable but nonculturable, pathogenic
Vibrio parahaemolyticus
were isolated from environmental oysters. Their whole-genome sequences were constructed. The genome sizes for VHT1 and VHT2 are 5.11 Mbp and 5.26 Mbp, respectively.
Draft Genome Sequence of Pseudomonas sp. Strain MWU13-3659, Isolated from Commercial Cranberry Bog Soil in Massachusetts, USA
Authors: Kooner Amritpal , Soby Scott
Published: October 2022

Pseudomonas
sp. strain MWU13-3659 was isolated from cultivated cranberry bog soil in Massachusetts, USA. Its closest known relative is
Pseudomonas entomophila
(digital DNA-DNA hybridization [d4 formula] value of 57.2% and average nucleotide identity based on BLAST value of 93.90), and its genome contains putative gene clusters for the production of polyketides, siderophores, and cyclic lipopeptides that have insecticidal activity in other proteobacteria.
Whole-Genome Sequence of
Sediminibacterium
sp. Strain TEGAF015, Isolated from a Shallow Eutrophic Freshwater Lake in Japan
Authors: Ogata Yusuke , Watanabe Keiji , Takemine Shusuke , Shindo Chie , Kurokawa Rina , Suda Wataru
Published: October 2022

The genus
Sediminibacterium
comprises bacteria representing the ubiquitous taxa of freshwater bacterioplankton. Here, we report the whole-genome sequence of
Sediminibacterium
sp. strain TEGAF015, isolated from a shallow eutrophic freshwater lake in Japan.
Draft Genome Sequences of Pseudomonas sp. Strains MWU 12-2029, MWU 12-3088, and MWU 12-3091, Isolated from Wild and Cultivated Massachusetts Cranberry Bogs
Authors: Manthena Akhila , Pittman Arin , Soby Scott
Published: October 2022

Pseudomonas
sp. strains MWU12-2029, MWU12-3088, and MWU12-3091 were isolated from wild and cultivated cranberry bog soils in southeastern Massachusetts. The three isolates are closely related to
Pseudomonas kribbensis
, a not validly published member of the
P. fluorescens
group, and contain three putative insecticidal protein genes, including the toxin complex A gene (
tcaC
).
In Vitro
Activity of the Sudapyridine (WX-081) against Non-Tuberculous Mycobacteria Isolated in Beijing, China
Authors: Zhu Rui , Shang Yuanyuan , Chen Suting , Xiao Hua , Ren Ruyan , Wang Fen , Xue Yi , Li Lei , Li Yongguo , Chu Naihui , Huang Hairong
Published: October 2022

Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. Over 200 species or subspecies of NTM have been reported, whereas pulmonary diseases in humans are caused mainly by
M. avium
complex (MAC),
M. kansasii
, and
M. abscessus
.
High-Density Lipoprotein Cholesterol as a Potential Medium between Depletion ofLachnospiraceaeGenera and Hypertension under a High-Calorie Diet
Authors: Lan Yongmei , Ning Kang , Ma Yanqing , Zhao Jin , Ci Caihong , Yang Xiao , An Fulong , Zhang Zilong , An Yan , Cheng Mingyue
Published: October 2022

Dietary nutrients can be converted by the gut microbiota into metabolites such as short-chain fatty acids, which may serve as disease-preventing agents in hypertension. Due to the limited population mobility and unique high-calorie dietary habits, the cohort of this study can serve as a representative cohort for elucidating the associations between the gut microbiota and hypertension under a high-calorie diet.
Bilateral atraumatic femoral neck fractures resulting from transient osteoporosis of the hip
Authors: Siva Soorya , Liao Quintin , Abbas Ammar , Periasamy Kumar
Published: October 2022

A woman in her mid-30s presented to the orthopaedic team, unable to mobilise, shortly after her caesarean section. On questioning, she reported 10 weeks of atraumatic right hip pain. A radiograph revealed a displaced right subcapital neck of femur fracture. An MRI confirmed this, as well as identifying a minimally displaced left subcapital neck of femur fracture. She underwent a right total hip replacement and internal fixation of the left hip. A dual energy X-ray absorptiometry (DEXA) scan showed severe osteoporosis, and a diagnosis of transient osteoporosis of the hip was made. She was seen by the bone metabolism team and given calcium and vitamin D medication. Although atraumatic hip fractures are rare in young patients, disproportionate or persisting hip pain in pregnant patients should raise the index of suspicion and prompt further investigation in the form of an MRI. This will allow timely management of hip fractures and improve patient outcomes.
Quantifying antibiotic use in typhoid fever in India: a cross-sectional analysis of private sector medical audit data, 2013–2015
Authors: Fazaludeen Koya Shaffi , Hasan Farooqui Habib , Mehta Aashna , Selvaraj Sakthivel , Galea Sandro
Published: October 2022

Objectives

To estimate the antibiotic prescription rates for typhoid in India.

Design

Cross-sectional study.

Setting

Private sector primary care clinicians in India.

Participants

The data came from prescriptions of a panel of 4600 private sector primary care clinicians selected through a multistage stratified random sampling accounting for the region, specialty type and patient turnover. The data had 671 million prescriptions for antibiotics extracted from the IQVIA database for the years 2013, 2014 and 2015.

Primary and secondary outcome measures

Mean annual antibiotic prescription rates; sex-specific and age-specific prescription rates; distribution of antibiotic class.

Results

There were 8.98 million antibiotic prescriptions per year for typhoid, accounting for 714 prescriptions per 100 000 population. Children 10–19 years of age represented 18.6% of the total burden in the country in absolute numbers, 20–29 year age group had the highest age-specific rate, and males had a higher average rate (844/100 000) compared with females (627/100 000). Ten different antibiotics accounted for 72.4% of all prescriptions. Cefixime–ofloxacin combination was the preferred drug of choice for typhoid across all regions except the south. Combination antibiotics are the preferred choice of prescribers for adult patients, while cephalosporins are the preferred choice for children and young age. Quinolones were prescribed as monotherapy in 23.0% of cases.

Conclusions

Nationally representative private sector antibiotic prescription data during 2013–2015 indicate a higher disease burden of typhoid in India than previously estimated. The total prescription rate shows a declining trend. Young adult patients account for close to one-third of the cases and children less than 10 years account for more than a million cases annually.
Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study
Authors: Jaksa Ashley , Gibbs Liza , Kent Seamus , Rowark Shaun , Duffield Stephen , Sharma Manuj , Kincaid Lynne , Ali Ayad K , Patrick Amanda R , Govil Priya , Jonsson Pall , Gatto Nicolle
Published: October 2022

Objective

To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke.

Study design and setting

A comparative cohort study in UK general practice data from The Health Improvement Network database.

Participants and interventions

Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date.

Primary and secondary outcome measures

The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint.

Results

Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75).

Conclusions

Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.
Factors associated with perceived coercion in adults receiving psychiatric care: a scoping review protocol
Authors: Lessard-Deschênes Clara , Goulet Marie-Hélène , Pariseau-Legault Pierre
Published: October 2022

Introduction

Coercion is inevitably linked to psychiatric and mental healthcare. Though many forms of coercion exist, perceived coercion appears to be a less studied form despite its marked prevalence and negative consequences. In the literature, several factors have been studied for their association with perceived coercion, but few literature reviews have focused on this precise subject. Gaining knowledge of the association between these factors and the degree of perceived coercion is essential to guide future research and develop informed interventions. The purpose of this review will be to identify, in the literature, factors associated with perceived coercion by adults receiving psychiatric care.

Methods and analysis

A scoping review will be conducted by following the Joanna Briggs Institute methodology. A search with descriptors and keywords will be performed in the following databases: CINAHL, MEDLINE, PUBMED, EMBASE and PsycINFO. Then, a search for grey literature will be conducted, psychiatric and mental health journals will be searched, and reference lists will be examined to identify further pertinent literature. All literature on factors (human, health related, organisational, etc) and their association to perceived coercion by adults (18 and older) in inpatient, outpatient and community-based psychiatry will be included. A quality assessment of the literature included will be performed. The extracted data will be analysed with a method of content analysis. An exploratory search was conducted in September 2021 and will be updated in September 2022 once the evidence selection process is planned to begin.

Ethics and dissemination

No ethics approval is required for this review. The results of this scoping review will be submitted to a scientific journal for publication, presented in conferences and shared with clinicians working in psychiatric and mental healthcare.
Self-management programme of activity coping and education—SPACE for COPD(C)—in primary care: a pragmatic randomised trial
Authors: Bourne Claire , Houchen-Wolloff Linzy , Patel Pratiksha , Bankart John , Singh Sally
Published: October 2022

Introduction

We have previously developed a supported self-management programme (SMP): Self-management Programme of Activity, Coping and Education for chronic obstructive pulmonary disease (COPD), which was successfully delivered on an individual basis. Payers expressed an interest in delivering the intervention in groups.

Aim

To explore the feasibility, acceptability and clinical effectiveness of the intervention delivered and supported by healthcare professionals (HCPs) in groups within primary care.

Methods

A prospective, single-blinded randomised controlled trial was conducted, with follow-up at 6 and 9 months. Participants were randomly assigned to control (usual care) or intervention (a six-session, group-based SMP delivered over 5 months). The primary outcome was change in COPD Assessment Test (CAT) at 6 months.

Semistructured focus groups were conducted with intervention participants to understand feasibility and acceptability. A focus group was conducted with HCPs who delivered the intervention to gain insight into any potential facilitators/barriers to implementing the intervention in practice. All qualitative data were analysed thematically.

Results

193 participants were recruited, (median Medical Research Council (MRC) grade 2). There was no significant difference between the intervention and control group for the primary outcome (CAT). However, an improvement in self-reported patient activation (at 6 and 9 months), knowledge (at 6 months), mastery (at 6 and 9 months) and fatigue (at 6 months), in the intervention group compared with usual care was demonstrated.

Qualitative results indicated that the intervention was acceptable to patients who took part in the intervention and HCPs valued the intervention, suggesting it might be best delivered early in the disease process.

Conclusions

A supported self-management intervention is feasible and acceptable when delivered as a group-based intervention, by HCPs in the community.
PD-L1/TLR7 dual-targeting nanobody-drug conjugate mediates potent tumor regression via elevating tumor immunogenicity in a host-expressed PD-L1 bias-dependent way
Authors: Yu Xiaolu , Long Yiru , Chen Binfan , Tong Yongliang , Shan Mengwen , Jia Xiaomin , Hu Chao , Liu Meng , Zhou Ji , Tang Feng , Lu Henglei , Chen Runqiu , Xu Pan , Huang Wei , Ren Jin , Wan Yakun , Sun Jianhua , Li Jia , Jin Guangyi , Gong Likun
Published: October 2022

Background

Various tumors are insensitive to immune checkpoint blockade (ICB) therapy. Toll-like receptors (TLRs) establish the link between innate and adaptive immunity, which can assist T-cell activation and serve as promising targets for combination to enhance ICB therapy. Here, we aimed to improve efficacy for anti-programmed death ligand 1 (PD-L1) therapy by developing a PD-L1/TLR7 dual-targeting nanobody-drug conjugate (NDC), based on the PD-L1 nanobodies and TLR7 agonist we developed.

Methods

PD-L1 nanobodies were obtained by phage display screening and identified through T-cell activation bioassay, in vivo imaging and quantitative biodistribution study. Immune activation and PD-L1-inducing of TLR7 agonists were evaluated in diverse innate cell models. We constructed PD-L1/TLR7 dual-targeting NDCs by chemically coupling PD-L1 nanobodies and TLR7 agonists. The antitumor effect was evaluated via several murine or humanized solid tumor models. Immunophenotyping, immune cell depletion, tumor rechallenge, RNA sequencing and PD-L1-deficient models were combined to determine the mechanism for NDCs function. The dynamics of the in vivo behaviors of NDCs were assessed based on multiorgan changes in PD-L1 levels.

Results

The screened PD-L1 nanobodies were characterized as tumor-targeting and alleviated T-cell immunosuppression. The TLR7 agonists induced broad innate immune responses and intratumoral PD-L1 expression on antigen-presenting cells (APCs), and its antitumor effect was dependent on intratumoral delivery. The combination of TLR7 agonists and PD-L1 nanobodies activated both innate and adaptive immunity and upregulated PD-L1-related signaling pathways. After coupling to form dual-targeting NDCs, TLR7 agonists and PD-L1 nanobodies exerted synergistic antitumor effects and safety in either ‘hot’ or ‘cold’ tumor and early or advanced tumor models, reshaped the tumor immune microenvironment and induced antitumor immune memory. CD8+T cells and natural killer cells were the main effector cells for NDCs to function. NDCs can promote PD-L1 expression on intratumoral APCs and tumor cells, and subsequently achieve targeted enrichment in tumors. Moreover, the efficacy of NDCs is biased toward dependence on host expression of PD-L1.

Conclusions

The novel PD-L1/TLR7 dual-targeting NDC exhibited potent efficacy against heterogeneous tumors through orchestrating innate and adaptive immunity, which could act as a promising strategy to improve ICB therapy and shows prospects for clinical development.
Localized ablative immunotherapy drives de novo CD8+T-cell responses to poorly immunogenic tumors
Authors: Hoover Ashley R , Kaabinejadian Saghar , Krawic Jason R , Sun Xiao-Hong , Naqash Abdul Rafeh , Yin Qian , Yang Xinbo , Christopher Garcia K , Davis Mark M , Hildebrand William H , Chen Wei R
Published: October 2022

Background

Localized ablative immunotherapies hold great promise in stimulating antitumor immunity to treat metastatic and poorly immunogenic tumors. Tumor ablation is well known to release tumor antigens and danger-associated molecular patterns to stimulate T-cell immunity, but its immune stimulating effect is limited, particularly against metastatic tumors.

Methods

In this study, we combined photothermal therapy with a potent immune stimulant, N-dihydrogalactochitosan, to create a local ablative immunotherapy which we refer to as laser immunotherapy (LIT). Mice bearing B16-F10 tumors were treated with LIT when the tumors reached 0.5 cm3and were monitored for survival, T-cell activation, and the ability to resist tumor rechallenge.

Results

We found that LIT stimulated a stronger and more consistent antitumor T-cell response to the immunologically ‘cold’ B16-F10 melanoma tumors and conferred a long-term antitumor memory on tumor rechallenge. Furthermore, we discovered that LIT generated de novo CD8+T-cell responses that strongly correlated with animal survival and tumor rejection.

Conclusion

In summary, our findings demonstrate that LIT enhances the activation of T cells and drives de novo antitumor T-cell responses. The data presented herein suggests that localized ablative immunotherapies have great potential to synergize with immune checkpoint therapies to enhance its efficacy, resulting in improved antitumor immunity.
Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Authors: Waks Adrienne G , Keenan Tanya E , Li Tianyu , Tayob Nabihah , Wulf Gerburg M , Richardson Edward T , Attaya Victoria , Anderson Leilani , Mittendorf Elizabeth A , Overmoyer Beth , Winer Eric P , Krop Ian E , Agudo Judith , Van Allen Eliezer M , Tolaney Sara M
Published: October 2022

Background

Preclinical and clinical data support potential synergy between anti-HER2 therapy plus immune checkpoint blockade. The safety and tolerability of trastuzumab emtansine (T-DM1) combined with pembrolizumab is unknown.

Methods

This was a single-arm phase Ib trial (registration date January 26, 2017) of T-DM1 plus pembrolizumab in metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Eligible patients had HER2-positive, metastatic breast cancer previously treated with taxane, trastuzumab, and pertuzumab, and were T-DM1-naïve. A dose de-escalation design was used, with a dose-finding cohort followed by an expansion cohort at the recommended phase 2 dose (RP2D), with mandatory baseline biopsies. The primary endpoint was safety and tolerability. Secondary endpoints included objective response rate (ORR) and progression-free survival (PFS). Immune biomarkers were assessed using histology, protein/RNA expression, and whole exome sequencing. Associations between immune biomarkers and treatment response, and biomarker changes before and during treatment, were explored.

Results

20 patients received protocol therapy. There were no dose-limiting toxicities. The RP2D was 3.6 mg/kg T-DM1 every 21 days plus 200 mg pembrolizumab every 21 days. 85% of patients experienced treatment-related adverse events (AEs) ≥grade 2, 20% of patients experienced grade 3 AEs, and no patients experienced grade >4 AEs. Four patients (20%) experienced pneumonitis (three grade 2 events; one grade 3 event). ORR was 20% (95% CI 5.7% to 43.7%), and median PFS was 9.6 months (95% CI 2.8 to 16.0 months). Programmed cell death ligand-1 and tumor infiltrating lymphocytes did not correlate with response in this small cohort.

Conclusions

T-DM1 plus pembrolizumab was a safe and tolerable regimen. Ongoing trials will define if there is a role for checkpoint inhibition in the management of HER2-positive metastatic breast cancer.

Trial registration number

NCT03032107.
Tumor microenvironment shows an immunological abscopal effect in patients with NSCLC treated with pembrolizumab-radiotherapy combination
Authors: van der Woude Lieke L , Gorris Mark A J , Wortel Inge M N , Creemers Jeroen H A , Verrijp Kiek , Monkhorst Kim , Grünberg Katrien , van den Heuvel Michel M , Textor Johannes , Figdor Carl G , Piet Berber , Theelen Willemijn S M E , de Vries I Jolanda M
Published: October 2022

Background

Immunotherapy is currently part of the standard of care for patients with advanced-stage non-small cell lung cancer (NSCLC). However, many patients do not respond to this treatment, therefore combination strategies are being explored to increase clinical benefit. The PEMBRO-RT trial combined the therapeutic programmed cell death 1 (PD-1) antibody pembrolizumab with stereotactic body radiation therapy (SBRT) to increase the overall response rate and study the effects on the tumor microenvironment (TME).

Methods

Here, immune infiltrates in the TME of patients included in the PEMBRO-RT trial were investigated. Tumor biopsies of patients treated with pembrolizumab alone or combined with SBRT (a biopsy of the non-irradiated site) at baseline and during treatment were stained with multiplex immunofluorescence for CD3, CD8, CD20, CD103 and FoxP3 for lymphocytes, pan-cytokeratin for tumors, and HLA-ABC expression was determined.

Results

The total number of lymphocytes increased significantly after 6 weeks of treatment in the anti-PD-1 group (fold change: 1.87, 95% CI: 1.06 to 3.29) and the anti-PD-1+SBRT group (fold change: 2.29, 95% CI: 1.46 to 3.60). The combination of SBRT and anti-PD-1 induced a 4.87-fold increase (95% CI: 2.45 to 9.68) in CD103+cytotoxic T-cells 6 weeks on treatment and a 2.56-fold increase (95% CI: 1.03 to 6.36) after anti-PD-1 therapy alone. Responders had a significantly higher number of lymphocytes at baseline than non-responders (fold difference 1.85, 95% CI: 1.04 to 3.29 for anti-PD-1 and fold change 1.93, 95% CI: 1.08 to 3.44 for anti-PD-1+SBRT).

Conclusion

This explorative study shows that that lymphocyte infiltration in general, instead of the infiltration of a specific lymphocyte subset, is associated with response to therapy in patients with NSCLC.

Furthermore, anti-PD-1+SBRT combination therapy induces an immunological abscopal effect in the TME represented by a superior infiltration of cytotoxic T cells as compared with anti-PD-1 monotherapy.
Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations
Authors: Bourke John , Turner Cathy , Bradlow William , Chikermane Ashish , Coats Caroline , Fenton Matthew , Ilina Maria , Johnson Alexandra , Kapetanakis Stam , Kuhwald Lisa , Morley-Davies Adrian , Quinlivan Ros , Savvatis Konstantinos , Schiava Marianela , Yousef Zaheer , Guglieri Michela
Published: October 2022

Objective

We provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in theDMD-gene.

Methods

Initiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD.

Results

The resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivanet aland are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society.

Conclusion

These guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.
Regeneration enhancers: a field in development
Authors: Harris Robin E.
Published: October 2022

The ability to regenerate tissues and organs following damage is not equally distributed across metazoans, and even highly related species can vary considerably in their regenerative capacity. Studies of animals with high regenerative potential have shown that factors expressed during normal development are often reactivated upon damage and required for successful regeneration. As such, regenerative potential may not be dictated by the presence or absence of the necessary genes, but whether such genes are appropriately activated following injury. The identification of damage-responsive enhancers that regulate regenerative gene expression in multiple species and tissues provides possible mechanistic insight into this phenomenon. Enhancers that are reused from developmental programs, and those that are potentially unique to regeneration, have been characterized individually and at a genome-wide scale. A better understanding of the regulatory events that, direct and in some cases limit, regenerative capacity is an important step in developing new methods to manipulate and augment regeneration, particularly in tissues that do not have this ability, including those of humans.
Method for Controlling Economic Management Cost in Enterprises Based on Coase Theorem
Authors: Li Zilian , Hu Qiumei , Huo Jie
Published: October 2022

In today’s integrated economy, no country’s economic development can be outside the international economic environment. After continuous and rapid development, China’s economy has surpassed Japan’s overall economic level and has become the second largest economic power in the world. But with the advent of the new normal economy in China, the economy has entered a stage of medium- and high-speed development, and business management and cost management of enterprises are also facing the transformation of strategies and systems. Every enterprise and company is trying its best to improve its own cost management system, business model, and cost management strategy. The development of science and technology and the advent of the era of information technology have gradually brought China’s economic development into a green development track, which has put forward greater research topics for enterprise cost management. Therefore, the method for controlling economic management cost in enterprises based on the Coase theorem was proposed.
Optimal Deep Learning-Based Vocal Fold Disorder Detection and Classification Model on High-Speed Video Endoscopy
Authors: Sakthivel S. , Prabhu V.
Published: October 2022

The use of high-speed video-endoscopy (HSV) in the study of phonatory processes linked to speech needs the precise identification of vocal fold boundaries at the time of vibration. The HSV is a unique laryngeal imaging technology that captures intracycle vocal fold vibrations at a higher frame rate without the need for auditory inputs. The HSV is also effective in identifying the vibrational characteristics of the vocal folds with an increased temporal resolution during retained phonation and flowing speech. Clinically significant vocal fold vibratory characteristics in running speech can be retrieved by creating automated algorithms for extracting HSV-based vocal fold vibration data. The best deep learning-based diagnosis and categorization of vocal fold abnormalities is due to the usage of HSV (ODL-VFDDC). The suggested ODL-VFDDC technique starts with temporal segmentation and motion correction to identify vocalized regions from the HSV recording and gathers the position of movable vocal folds across frames. The attributes gathered are fed into the deep belief network (DBN) model. Furthermore, the agricultural fertility algorithm (AFA) is used to optimize the hyperparameter tuning of the DBN model, which improves classification results. In terms of vocal fold disorder classification, the testing results demonstrated that the ODL-VFDDC technique beats the other existing methodologies. The farmland fertility algorithm (FFA) is then used to accurately determine the glottal limits of vibrating vocal folds. The suggested method has successfully tracked the speech fold boundaries across frames with minimum processing cost and high resilience to picture noise. This method gives a way to look at how the vocal folds move during a connected speech that is completely done by itself.