bluuebunny/crossref_metadata_2025 huggingface dataset:
Granivorous ants prefer small and unprotected seeds—implications for restoration in arid ecosystems
Authors: Martyn Trace E. , Kwapich Christina L. , Kline Albert , Gornish Elise S.
Published: July 2022

Successful seed‐based restoration in dryland systems is difficult due to the many limitations associated with germination and establishment. Seed predators, including granivorous ants, can consume or move applied seeds offsite reducing restoration success. Granivorous ants in the U.S. southwest move and store tens of thousands of seeds and show preferences for seeds based on weight, size, nutrient content, and novelty. In this study, we examine which seed traits most influence seed predation rates in a grassland in southwestern Arizona, U.S.A. We presented 24 seed types from native species with restoration value in three cafeteria‐style selection areas installed adjacent to Pogonomyrmex nests. We also installed pitfall traps to assess the diversity of ant species that may have visited the cafeterias. Our results showed that among offered seeds, 3–99% were collected by granivorous ants, with small seeds and those with no structure the most preferred. Across all cafeterias, we had 11 ant species in our pitfall traps, with over half of those being known seed predators. From our study, we found that seed traits do influence ant seed preference and our results can help inform practices that could aid in keeping seed on the ground and increasing the chance of germination and establishment.
Indirect moral governance in prostitution policy: How regulators incorporate stigmatized actors in intermediation processes
Authors: Euchner Eva‐Maria , Zeegers Nicolle
Published: July 2022

Regulatory intermediaries have received attention in the analysis of different policy fields recently. Yet, their role in morality‐based national governance arrangements is hardly addressed, neither is the question of how regulators incorporate stigmatized private actors. The current special issue contributes to closing this research gap by examining the three‐party relationship between public regulators, private intermediaries, and targets in prostitution policy implementation. This introduction presents a typology of indirect moral governance, which is based on two dimensions: (1) the extent to which regulators perceive intermediaries as being trustworthy and (2) their operational capacities. Leveraging examples from the papers in the special issue, we elaborate on how the two dimensions lead to four forms of intermediation. Thus, the typology offers an innovative analytical tool to systematizes regulators' responses to governance and implementation problems in the case of morality policies and value‐laden issues more generally, including the responsibilization of stigmatized actors.
Health professionals' reflections on existential concerns among people with obesity
Authors: Haga Britt Marit , Furnes Bodil , Ueland Venke
Published: July 2022

Purpose

This study aimed to describe health professionals' reflections on existential concerns among people with obesity when attempting to support them in their lifestyle change processes. For many of those affected by obesity, the condition becomes lifelong and causes existential concerns. The health professionals' reflections on existential concerns among people with obesity may influence central aspects of their practice and their patients' well‐being.

Methods

Eighteen health professionals with relevant health education working in three different treatment programmes for people with obesity were recruited for three focus group interviews. The interviews were analysed and interpreted using a model for interpretation of meaning at three levels with a phenomenological–hermeneutical approach.

Findings

The analysis identified three themes. The health professionals reflected on existential concerns among people with obesity in terms of patients' repressed emotional difficulties and lack of self‐respect. In addition, they reflected on their own experiences of powerlessness when presented with people with obesity's existential concerns.

Conclusion

The present study provides valuable insights into reflections on existential concerns among people with obesity, based on health professionals' descriptions. We believe that these insights add to the existing literature and have consequences for how people with obesity are met and cared for.
Coexisting Normative Regimes, Conflict and Urban Inequalities in a Brazilian Favela
Authors: Beraldo Ana , Richmond Matthew A. , Feltran Gabriel
Published: July 2022

This article contributes to debates about the everyday negotiation of difference, inequality and conflict in cities by developing the notion of ‘coexisting normative regimes’. Normative regimes are plausible parameters of action that are sedimented in subjectivities and reproduced in everyday routines. We argue that in many Brazilian favelas and other marginalised urban spaces, distinct and unassimilable normative regimes coexist in space, each providing distinct frameworks and guidelines for dealing with everyday situations. Based on extensive ethnographic research conducted in a favela in the city of Belo Horizonte, the article identifies the everyday ways in which normative regimes operate, how they link to broader urban inequalities, and the ways in which individuals and groups navigate between them and the various threats they pose.
Foreign direct investment and product quality in host economies
Authors: Anwar Sajid , Sun Sizhong
Published: July 2022

We examine, both theoretically and empirically, how the presence of FDI affects product quality of domestic firms through worker mobility. Mobility of more productive workers from foreign‐invested to domestic firms lowers the cost of production and contributes to improvement in the quality of goods produced by domestic firms. Profit maximisation by firms yields a structural relationship between unobserved product quality and observed revenue, which allows us to identify the impact of FDI on product quality. We use the theoretical model to frame empirical estimation, where we propose a novel approach to correct for sample selection bias. Under some mild assumptions, a set of population moments are derived and estimated using firm‐level data from China's beverage manufacturing industry. We find that, on average, (i) working for foreign‐invested firms boosts the skill level of workers by 11.12 per cent and (ii) the probability that an FDI‐trained worker will move to a domestic firm is approximately 0.3. Estimation of the structural parameters shows that a one per cent increase in FDI leads to approximately 1.4 per cent improvement in product quality of domestic firms in China's beverage manufacturing industry.
Design Optimization and Variable Geometries Implementation of a High Bypass Three-Shaft Turbofan Engine for EIS2050
Authors: Mo Da , Roumeliotis Ioannis , Mourouzidis Christos , Kissoon Sajal , Liu Yixiong
Published: July 2022

This paper aims to develop an advanced three-shaft turbofan engine with ultrahigh bypass ratio (BPR) for entry-into-service (EIS)2050. The boundary approaching method is utilized to obtain the optimal engine for a series of engines with different fan diameters. Furthermore, the flight mission analysis was carried out to fully consider the engine performance and weight penalty. The optimum engine employs a 3.26 m fan diameter with ultrahigh BPR reaching 21.39. The corresponding specific fuel consumption (SFC) is 11.42 (g/s)/kN, which is 3.88% lower than the 2.95 m fan diameter engine. However, the weight penalty has offset part of the benefits, and the block fuel reduction is 2.5%. Sensitivity analysis results reveal that the low-pressure turbine (LPT) efficiency plays a dominant role in engine performance. Afterwards, the effects of variable geometry are investigated including the blow-off valve (BOV), variable inlet guide vane (VIGV), and bypass variable area nozzle (VAN). Results show that combining the three measures would boost engine performance and save fuel. The designed schedule for the combination of VIGV, BOV, and VAN has generated a reduction in block fuel, NOx, CO2, and H2O reaching 3.36%, 5.55%, 2.47%, and 2.53%, respectively.
Engineering and Characterization of Avian Coronavirus Mutants Expressing Fluorescent Reporter Proteins from the Replicase Gene
Authors: Xing Na , Wang Zhisheng , Wang Jichun , Nascimento Mariana , Jongkaewwattana Anan , Trimpert Jakob , Osterrieder Nikolaus , Kunec Dusan
Published: July 2022

Reverse genetics systems based on bacterial artificial chromosomes (BACs) are the most valuable systems in coronavirus research. Here, we describe the establishment of a reverse genetics system for the avian coronavirus strain Beaudette, the most intensively studied strain.
Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope
Authors: Ratcliff Annette N. , Venner Colin M. , Olabode Abayomi S. , Knapp Jason , Pankrac Joshua , Derecichei Iulian , Gibson Richard M. , Finzi Andrés , Li Yue , Mann Jamie F. S. , Arts Eric J.
Published: July 2022

Typically, a natural amino acid polymorphism is found as the wild-type sequence in the HIV-1 population if it provides a selective advantage to the virus. The natural K425 polymorphism in HIV-1 Env results in higher host cell entry efficiency and greater replicative fitness by virtue of its high binding affinity to CD4.
Draft Genome Sequence of a Serratia marcescens Strain (PIC3611) Proficient at Recalcitrant Polysaccharide Utilization
Authors: Novak Jessica K. , Gardner Jeffrey G.
Published: July 2022

Serratia marcescens
is a Gram-negative bacterium found in terrestrial and aquatic environments and studied for its polysaccharide utilization capabilities as part of larger efforts to discover novel carbohydrate-active enzymes. Here, we announce the genome sequence of an
S. marcescens
strain (PIC3611) that is able to utilize complex polysaccharide substrates.
Impact of Prior Infection on SARS-CoV-2 Antibody Responses in Vaccinated Long-Term Care Facility Staff
Authors: Gallichotte Emily N. , Nehring Mary , Stromberg Sophia , Young Michael C. , Snell Ashley , Daniels Josh , Pabilonia Kristy L. , VandeWoude Sue , Ehrhart Nicole , Ebel Gregory D.
Published: July 2022

Long-term care facilities (LTCFs) have been disproportionately impacted by COVID-19, due to their communal nature, the high-risk profile of residents, and the vulnerability of residents to respiratory pathogens. In this study, we analyzed the role of prior natural immunity to SARS-CoV-2 in postvaccination antibody responses.
Interspecies Transmission of CMY-2-Producing Escherichia coli Sequence Type 963 Isolates between Humans and Gulls in Australia
Authors: Medvecky Matej , Papagiannitsis Costas C. , Wyrsch Ethan R. , Bitar Ibrahim , Cummins Max L. , Djordjevic Steven P. , Dolejska Monika
Published: July 2022

We have provided the first comprehensive genomic study of
E. coli
ST963 by analyzing various genomic and phenotypic data sets of isolates from Australian silver gulls and comparison with genomes from geographically dispersed regions of human and animal origin. Our study suggests the emergence of a specific
bla
CMY-2
-carrying
E. coli
ST963 clone in Australia that is widely spread across the continent by humans and birds.
Methods and Strategies to Uncover Coral-Associated Microbial Dark Matter
Authors: Schultz Júnia , Modolon Flúvio , Rosado Alexandre S. , Voolstra Christian R. , Sweet Michael , Peixoto Raquel S.
Published: July 2022

The vast majority of environmental microbes have not yet been cultured, and most of the knowledge on coral-associated microbes (CAMs) has been generated from amplicon sequencing and metagenomes. However, exploring cultured CAMs is key for a detailed and comprehensive characterization of the roles of these microbes in shaping coral health and, ultimately, for their biotechnological use as, for example, coral probiotics and other natural products. Here, the strategies and technologies that have been used to access cultured CAMs are presented, while advantages and disadvantages associated with each of these strategies are discussed.
Novel Organization of the Staphylococcal Cassette Chromosome
mec
Composite Island in Clinical Staphylococcus haemolyticus and Staphylococcus hominis Subspecies
hominis
Isolates from Dogs
Authors: Phumthanakorn Nathita , Wongsurawat Thidathip , Jenjaroenpun Piroon , Kurilung Alongkorn , Prapasarakul Nuvee
Published: July 2022

In Thailand, the staphylococcal cassette chromosome
mec
(SCC
mec
) element, which causes methicillin resistance through acquisition of the
mec
gene, has been studied in clinical coagulase-negative
Staphylococcus
isolates from various companion animals, and
Staphylococcus haemolyticus
and
Staphylococcus hominis
subsp.
hominis
were found to have the most nontypeable (NT)-SCC
mec
elements. These species are more prone to causing illness and more resistant to a variety of antimicrobials than other coagulase-negative staphylococci.
Carbapenemase-Encoding Gene Copy Number Estimator (CCNE): a Tool for Carbapenemase Gene Copy Number Estimation
Authors: Jiang Jianping , Chen Liang , Chen Xin , Li Pei , Xu Xiaogang , Fowler Vance G. , van Duin David , Wang Minggui
Published: July 2022

Globally disseminated carbapenem-resistant
Enterobacterales
is an urgent threat to public health. The most common carbapenem resistance mechanism is the production of carbapenemases.
Limited Correlation between SARS-CoV-2 Serologic Assays for Identification of High-Titer COVID-19 Convalescent Plasma Using FDA Thresholds
Authors: Larkey Nicholas E. , Ewaisha Radwa , Lasho Michael A. , Roforth Matthew M. , Granger Dane , Jerde Calvin R. , Wu Liang , Gorsh Amy , Klassen Stephen A. , Senefeld Jonathon W. , Joyner Michael J. , Baumann Nikola A. , Theel Elitza S. , Mills John R.
Published: July 2022

COVID-19 convalescent plasma (CCP) was one of the first therapeutic options available for the treatment of SARS-CoV-2 infections and continues to be used selectively for immunosuppressed patients. Given the emergence of novel SARS-CoV-2 variants which are resistant to treatment with available monoclonal antibody (MAb) therapy, CCP remains an important therapeutic consideration.
Polyphosphate Kinase Is Required for the Processes of Virulence and Persistence in Acinetobacter baumannii
Authors: Lv Hongfa , Zhou Yonglin , Liu Baichen , Guan Jian , Zhang Peng , Deng Xuming , Li Dan , Wang Jianfeng
Published: July 2022

A. baumannii
was identified as a top-priority pathogen by the WHO due to its antibiotic resistance. Meanwhile, the pathogenicity of
A. baumannii
mediated by several vital virulence factors also cannot be ignored.
Decreased Efficiency of Neutralizing Antibodies from Previously Infected or Vaccinated Individuals against the B.1.617.2 (Delta) SARS-CoV-2 Variant
Authors: Dimeglio Chloé , Herin Fabrice , Da-Silva Isabelle , Gernigon Caroline , Porcheron Marion , Chapuy-Regaud Sabine , Izopet Jacques
Published: July 2022

Recent studies showed that the neutralizing antibody titer is an important contributor to protection against SARS-CoV-2. With the emergence of new variants, the question arises of maintaining the neutralizing capacities of vaccines and/or of a past infection.
There should always be a free lunch: the impact of COVID-19 lockdown suspension of the mid-day meal on nutriture of primary school children in Karnataka, India
Authors: Thankachan Prashanth , Selvam Sumithra , Narendra Agnita R , Mishra Hari N , Sachdev Harshpal S , Thomas Tinku , Kurpad Anura V
Published: July 2022

Background

The COVID-19 pandemic lockdown in 2020 resulted in school closures with eventual suspension of the mid-day meal programme, biannual deworming and iron–folic acid supplements. One year into the lockdown, we evaluated the impact of the withdrawal of these programmes on the nutritional status of rural primary-school children, aged 6–12 years, in Karnataka, India.

Methods

Anthropometry, haemoglobin, serum ferritin and C reactive protein were measured in 290 children at two time points, 1 year apart, starting from just before the lockdown (February 2020 to February 2021).

Results

The prevalence of anaemia doubled from 21% to 40% (p<0.0001) with more pronounced changes in older girls (10%–53%); however, the prevalence of iron deficiency did not change (48.8%–51.9%), despite cessation of deworming and iron/folic acid supplements.

Conclusion

The increase in anaemia was due to limiting intakes of other erythropoietic nutrients, possibly due to a lower dietary diversity. The mid-day lunch meal at school (MDM) is an important part of daily food intake in rural school children, and it is important to maintain dietary diversity through the delivery of MDM for such vulnerable groups.
Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide: a protocol for a systematic review of observational studies
Authors: Carli Tanja , Locatelli Igor , Košnik Mitja , Kukec Andreja
Published: July 2022

Introduction

Systemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for an SAR is particularly high in beekeepers due to their persistent or seasonal exposure to the stinging Hymenoptera. We aim to provide a critical appraisal and a synthesis of evidence-based data from epidemiological observational studies, focusing on SARs to a Hymenoptera venom and the associated risk factors for SARs in beekeepers worldwide.

Methods and analysis

Searching will include seven electronic databases for published studies without language restrictions, from inception up to 3 August 2021, and it will be rerun for all electronic databases prior publication. Only epidemiological observational studies in beekeepers will be included. The risk of bias in the included studies will be appraised by using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale, adapted for cross-sectional studies. For the certainty of evidence, the Grading of Recommendations Assessment, Development and Evaluation approach will be used. Qualitative synthesis will be presented in a tabulated format with the selected characteristics across primary studies and the main outcome of interest. A meta-analysis is planned to be performed if there will be a sufficient number of homogeneous studies with complete data. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement will guide the reporting of this systematic literature review.

Ethics and dissemination

No ethics approval is needed to conduct the systematic literature review since it will be solely based on the published literature. Findings will be disseminated through the relevant conferences, peer-review and open-access journals.

PROSPERO registration number

CRD42021260922.
Acute pain pathways: protocol for a prospective cohort study
Authors: Jeffery Molly Moore , Ahadpour Mitra , Allen Summer , Araojo Richardae , Bellolio Fernanda , Chang Nancy , Ciaccio Laura , Emanuel Lindsay , Fillmore Jonathan , Gilbert Gregg H , Koussis Patricia , Lee Christine , Lipkind Heather , Mallama Celeste , Meyer Tamra , Moncur Megan , Nuckols Teryl , Pacanowski Michael A , Page David B , Papadopoulos Elektra , Ritchie Jessica D , Ross Joseph S , Shah Nilay D , Soukup Mat , St. Clair Christopher O , Tamang Stephen , Torbati Sam , Wallace Douglas W , Zhao Yueqin , Heckmann Rebekah
Published: July 2022

Introduction

Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses.

Methods and analysis

This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients’ patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids.

Ethics and dissemination

This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public.

Trial registration number

NCT04509115.
Knowledge, attitude and practice of community pharmacy personnel in tuberculosis patient detection: a multicentre cross-sectional study in a high-burden tuberculosis setting
Authors: Pradipta Ivan Surya , Khairunnisa Khairunnisa , Bahar Muh Akbar , Kausar Mersa Nurain , Fitriana Efi , Ruslami Rovina , Aarnoutse Rob E , Abdulah Rizky
Published: July 2022

Introduction

Control of tuberculosis (TB) is hampered by suboptimal case detection and subsequent delays in treatment, which is worsened by the COVID-19 pandemic. The community pharmacy is reported as the place for first aid medication among patients with TB. We, therefore, analysed knowledge, attitude and practice (KAP) on TB patient detection (TBPD) of community pharmacy personnel, aiming to find innovative strategies to engage community pharmacies in TBPD.

Methods

A multicentre cross-sectional study was performed in four areas of Indonesia’s eastern, central and western parts. Pharmacists and pharmacy technicians who worked in community pharmacies were assessed for their characteristics and KAP related to TBPD. Descriptive analysis was used to assess participant characteristics and their KAP, while multivariable regression analyses were used to analyse factors associated with the KAP on TBPD.

Results

A total of 1129 participants from 979 pharmacies, comprising pharmacists (56.6%) and pharmacy technicians (43.4%), were included. Most participants knew about TB. However, knowledge related to TB symptoms, populations at risk and medication for TB were still suboptimal. Most participants showed a positive attitude towards TBPD. They believed in their professional role (75.1%), capacity in TB screening (65.4%) and responsibility for TBPD (67.4%). Nevertheless, a lack of TBPD practice was identified in most participants. Several factors significantly associated with performing the TBPD practice (p<0.05), such as TB training experience (p<0.001), provision of a drug consultation service (p<0.001), male gender (p<0.05), a positive attitude towards TBPD (p<0.001), short working hours (p<0.001) and central city location of the pharmacy (p<0.05).

Conclusions

Most participants had good knowledge and attitude, which did not translate into actual TBPD practice. We identified that TB educational programmes are essential in improving the KAP. A comprehensive assessment is needed to develop effective strategies to engage the community pharmacy in TBPD activities.
Associations between WASH-related violence and depressive symptoms in adolescent girls and young women in South Africa (HPTN 068): a cross-sectional analysis
Authors: Jayaweera Ruvani T , Goin Dana , Twine Rhian , Neilands Torsten B , Wagner Ryan G , Lippman Sheri A , Kahn Kathleen , Pettifor Audrey , Ahern Jennifer
Published: July 2022

Objective

There is a lack of research on experiences of WASH-related violence. This study aims to quantify the association between experience or worry of violence when using the toilet or collecting water and depressive symptoms among a cohort of young women in South Africa.

Methods

Data are from visit 3 of the HPTN 068 cohort of adolescent girls in rural Mpumalanga Province, South Africa. Participants (n=1798) included in this analysis were aged 13–21 at baseline. Lifetime experience of violence or fear of violence when using the toilet and collecting water was collected by self-report; depressive symptoms in the past week were measured using the Center for Epidemiological Studies Depression Scale (CES-D). We used G-computation to calculate the prevalence difference (PD) and prevalence ratio of depression (CES-D score >15) associated with each domain of violence, controlling for baseline covariates.

Findings

A total of 15.1% of respondents reported experiencing violence when using the toilet; 17.1% reported experiencing violence when collecting water and 26.7% reported depression. In adjusted models, those who reported experiencing violence when using the toilet had an 18.1% higher prevalence of depression (95% CI: 11.6% to 24.4%) than those who did not experience violence when using the toilet. Adjusted prevalence of depression was also higher among those who reported violence when collecting water (PD 11.9%, 95% CI: 6.7% to 17.2%), and who worried about violence when using the toilet (PD 12.8%, 95% CI: 7.9% to 19.8%), as compared with those who did not report these experiences. Worrying about violence when collecting water was not associated with depression after adjusting for covariates.

Conclusion

Experience of WASH-related violence is common among young women in rural South Africa, and experience or worry of experiencing violence is associated with higher prevalence of depressive symptoms.

Trial registration number

NCT01233531; Post-results.
Comparisons between biopsy-proven versus clinically diagnosed cardiac sarcoidosis
Authors: Kitai Takeshi , Nabeta Takeru , Naruse Yoshihisa , Taniguchi Tatsunori , Yoshioka Kenji , Miyakoshi Chisato , Kurashima Shinichi , Miyoshi Yutaro , Tanaka Hidekazu , Okumura Takahiro , Baba Yuichi , Furukawa Yutaka , Matsue Yuya , Izumi Chisato
Published: July 2022

Objectives

Diagnosis of cardiac sarcoidosis (CS) without histological evidence remains controversial. This study aimed to compare characteristics and outcomes of histologically proven versus clinically diagnosed cases of CS, which were adjudicated using Heart Rhythm Society or Japanese Circulation Society criteria.

Methods

A total of 512 patients with CS (age: 62±11 years, female: 64.3%) enrolled in the multicentre registry were studied. Histologically confirmed patients were classified as ‘biopsy-proven CS’, while those with the presence of strongly suggestive clinical findings of CS without histological evidence were classified as ‘clinical CS’. Primary outcome was a composite of all-cause death, heart failure hospitalisation and ventricular arrhythmia event.

Results

In total, 314 patients (61.3%) were classified as biopsy-proven CS, while 198 (38.7%) were classified as clinical CS. Patients classified under clinical CS were associated with higher prevalence of left ventricular dysfunction, septal thinning, and positive findings in fluorodeoxyglucose-positron emission tomography or Gallium scintigraphy than those under biopsy-proven CS. During median follow-up of 43.7 (23.3–77.3) months, risk of primary outcome was comparable between the groups (adjusted HR: 1.24, 95% CI: 0.88 to 1.75, p=0.22). Similarly, the risks of primary outcome were comparable between patients with clinical isolated CS who did not have other organ/tissue involvement, and biopsy-proven isolated CS (adjusted HR: 1.23, 95% CI: 0.56 to 2.70, p=0.61).

Conclusions

A substantial number of patients were diagnosed with clinical CS without confirmatory biopsy. Considering the worse clinical outcomes irrespective of the histological evidence, the diagnosis of clinical CS is justifiable if imaging findings suggestive of CS are observed.
Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer
Authors: Kwon Minsuk , Kim Gahyun , Kim Ryul , Kim Kyu-Tae , Kim Seung Tae , Smith Simon , Mortimer Peter G S , Hong Jung Yong , Loembé Arsene-Bienvenu , Irurzun-Arana Itziar , Koulai Loumpiana , Kim Kyoung-Mee , Kang Won Ki , Dean Emma , Park Woong-Yang , Lee Jeeyun
Published: July 2022

Background

Targeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination.

Methods

This phase II, open-label, single-center, non-randomized study was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with AGC. The study drug regimen was ceralasertib (240 mg two times a day) days 15–28 in a 28-day cycle in combination with durvalumab (1500 mg) at day 1 every 4 weeks. The primary end point was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (V.1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients.

Results

Among 31 patients, the ORR, disease control rate, median progression-free survival (PFS), and overall survival were 22.6% (95% CI 9.6% to 41.1%), 58.1% (95% CI 39.1% to 75.5%), 3.0 (95% CI 2.1 to 3.9) months, and 6.7 (95% CI 3.8 to 9.6) months, respectively. Common adverse events were manageable with dose modification. A subgroup of patients with a loss of ataxia telangiectasia mutated (ATM) expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated a significantly longer PFS than those with intact ATM and low sig. HRD (5.60 vs 1.65 months; HR 0.13, 95% CI 0.045 to 0.39; long-rank p<0.001). During the study treatment, upregulation of the innate immune response by cytosolic DNA, activation of intratumoral lymphocytes, and expansion of circulating tumor-reactive CD8 +T cell clones were identified in responders. Enrichment of the tumor vasculature signature was associated with treatment resistance.

Conclusions

Ceralasertib plus durvalumab has promising antitumor activity, with durable responses in patients with refractory AGC. Thus, a biomarker-driven trial is required.

Trial registration

NCT03780608.
Quantum gravity on a manifold with boundaries: Schrödinger evolution and constraints
Authors: Rosabal J. A.
Published: July 2022

In this work, we derive the boundary Schrödinger (functional) equation for the wave function of a quantum gravity system on a manifold with boundaries together with a new constraint equation defined on the timelike boundary. From a detailed analysis of the gravity boundary condition on the spatial boundary, we find that while the lapse and the shift functions are independent Lagrange multipliers on the bulk, on the spatial boundary, these two are related; namely, they are not independent. In the Hamiltonian ADM formalism, a new Lagrange multiplier, solving the boundary conditions involving the lapse and the shift functions evaluated on the spatial boundary, is introduced. The classical equation of motion associated with this Lagrange multiplier turns out to be an identity when evaluated on a classical solution of Einstein’s equations. On the other hand, its quantum counterpart is a constraint equation involving the gravitational degrees of freedom defined only on the boundary. This constraint has not been taken into account before when studying the quantum gravity Schrödinger evolution on manifolds with boundaries.
On Finslerian extension of special relativity
Authors: Sagaydak Alina E. , Silagadze Zurab K.
Published: July 2022

In this paper, we demonstrate that Robb-Geroch’s definition of a relativistic interval admits a simple and fairly natural generalization leading to a Finsler extension of special relativity. Another justification for such an extension goes back to the works of Lalan and Alway and, finally, was put on a solid basis and systematically investigated by Bogoslovsky under the name “Special-relativistic theory of locally anisotropic spacetime”. The isometry group of this spacetime, DISIM[Formula: see text], is a deformation of the Cohen and Glashow’s very special relativity symmetry group ISIM(2). Thus, the deformation parameter [Formula: see text] can be regarded as an analog of the cosmological constant characterizing the deformation of the Poincaré group into the de Sitter (anti-de Sitter) group. The simplicity and naturalness of Finslerian extension in the context of this paper adds weight to the argument that the possibility of a nonzero value of [Formula: see text] should be carefully considered.
AN ADAPTIVE PHARMACOKINETIC OPTIMAL CONTROL APPROACH IN CHEMOTHERAPY FOR HETEROGENEOUS TUMOR
Authors: NANDITHA C. K. , RAJAN M. P.
Published: July 2022

The mathematical study of cancer received great attention in recent years. The theoretical and numerical investigations of models employed for studying the growth of cancer cells and treatment of cancer can help the clinical practitioners in adapting new strategies to face the challenges posed by the deadly disease. Chemotherapy is the most common method of treatment for cancer. The resistance of tumor cells toward the administered drug and the toxic effect of anti-cancer agents on healthy cells are major hurdles to the success of therapy. In this paper, we study this as an optimal control problem in which the amount of drug injected is taken as control. The evolution of different types of cells — sensitive tumor cells, resistant tumor cells and normal cells — under treatment are analyzed. The pharmacokinetics of the drug is also incorporated into the mathematical model. We propose a treatment protocol that assures the death of a maximum number of tumor cells but also manages to keep the normal cells at a sufficient level. We also validated our theoretical results numerically.
Dynamic Buckling Characteristics of Drill String in Inclined Straight Well with Friction Effect
Authors: Tian Jialin , Liu Chenghang , Yang Yinglin
Published: July 2022

The buckling behaviors of drill string may cause serious down-hole problems, such as high friction during drilling, loss of weight on bit (WOB), and even drill string failure. This paper analyzes the dynamic buckling characteristics of drill string, considering the friction between drill string and wellbore. In the theoretical research, the key parameter expressions are determined, especially the contact behaviors of drill string and mathematical models are proposed, which include axial displacement, angular displacement and contact force. The numerical calculation results show that the influence of friction on the drill string buckling is mainly reflected in angular displacement. The influences of friction effect on the dynamic characteristics of drill string become greater with the increase of inclination angle, while become lower with the increase of drill string length. The friction effect appears to have insignificant influence on drill string condition with the accumulation of time. The comparison results indicate that the friction affects the action of axial load on drill string and delays the onset of buckling. On the other hand, the angular displacements decrease with drill string length increasing, while the axial displacements have an opposite effect. The research results provide theoretical references for studying dynamic buckling characteristics; furthermore, we can determine the methods and solutions to prevent drill string buckling based on this, and improve the safety of downhole drilling.
Behavior of Pre-Stressed Arch Subjected to Sliding Load
Authors: Musiket Kamtornkiat , Phungpaingam Boonchai , Chucheepsakul Somchai
Published: July 2022

This paper investigates the behavior of a pre-stressed arch under a sliding load, where the initial configuration can be obtained from the buckling of a straight column. The shape of the pre-stressed arch can be varied by increasing the end shortening. Subsequently, a sliding load is applied at a certain height level. The orientation of the applied load maintains the right angle with respect to the tangential line of the arch. By moving the load horizontally, the behavior of the arch can be explored. The governing differential equations of the problem can be obtained by equilibrium equations, constitutive relation, and nonlinear geometric expressions. The exact closed-form solutions can be derived in terms of elliptic integrals of the first and second kinds. In this problem, the arch can be divided into two segments where each segment is a part of a buckled hinged-hinged column mounted on an inclined support. The shooting method is employed to solve the numerical solutions for comparing with the elliptic integral method. The stability of the pre-stressed arch is evaluated from vibration analysis, where the shooting method is again utilized for solving the natural frequencies in terms of a square function. A simple experiment is set up to explore the equilibrium shapes. Poly-carbonate sheet is utilized as the pre-stressed arch. From the results, it is found that the results obtained from elliptic integral method are in excellent agreement with those obtained from shooting method. The equilibrium shapes from the theoretical results can also compare with those from the experiment. The pre-stressed arch can lose its stability and snap into an upside-down (inverted) configuration depending on the ratio of rise to span-length and loading height. The instability of the arch is not only detected during the pushing of the sliding load but a pulling load can also cause unstable behavior of the arch.
On the Dynamics of Euclidean Space–Time at the Planck Scale
Authors: Nash Lewis
Published: July 2022

In this study, a radical hypothesis concerning the wave-particle duality exhibited by extremely small objects in nature is explored by developing a Planck lattice model of space–time that grapples with the uncertain dynamic quantum structure of space–time at the Planck scale. Upon applying the Planck lattice model to two notable experiments that most clearly demonstrate the essence of wave-particle duality, one immediately finds that it successfully shows in a relatively straightforward and physically consistent manner how parcels of matter and energy, i.e., electrons and photons, respectively, can behave like waves. The heuristic concepts regarding the underlying structure of space–time contained herein are intended to show the classical particle description of matter and energy as fundamental, while at the same time doing away with the widely held notion of a continuous space–time.
Fairness-aware Data Integration
Authors: Mazilu Lacramioara , Paton Norman W. , Konstantinou Nikolaos , Fernandes Alvaro A. A.
Published: July 2022

Machine learning can be applied in applications that take decisions that impact people’s lives. Such techniques have the potential to make decision making more objective, but there also is a risk that the decisions can discriminate against certain groups as a result of bias in the underlying data. Reducing bias, or promoting fairness, has been a focus of significant investigation in machine learning, for example, based on pre-processing the training data, changing the learning algorithm, or post-processing the results of the learning. However, prior to these activities, data integration discovers and integrates the data that is used for training, and data integration processes have the potential to produce data that leads to biased conclusions. In this article, we propose an approach that generates schema mappings in ways that take into account: (i) properties that are intrinsic to mapping results that may give rise to bias in analyses; and (ii) bias observed in classifiers trained on the results of different sets of mappings. The approach explores a space of different ways of integrating the data, using a Tabu search algorithm, guided by bias-aware objective functions that represent different types of bias.The resulting approach is evaluated using Adult Census and German Credit datasets to explore the extent to which and the circumstances in which the approach can increase the fairness of the results of the data integration process.
How Ionic Structure Governs Bulk Properties: Charge Lever Moments of Alicyclic Ionic Liquids utilized in Lithium Metal Batteries
Authors: Sadeghian H. , Maftoon-azad L. , Jalali T.
Published: July 2022

In this study, the effect of ionic symmetry and liberational motion on macroscopic properties of some lithium cell electrolytes was investigated. We utilized the charge lever moment (CLM) concept to establish the dynamical behavior of ionic liquids. The CLM value was specified using density functional theory and characterized for each ionic liquid using the electronic structure. In particular, we surveyed the impact of the basis set, method, lithium presence and ions shapes, sizes, and the heteroatom type on CLM.
Electrochemical Protocols to Assess the Effects of Dissolved Transition Metal in Graphite/LiNiO2 Cells Performance
Authors: Meunier Valentin , De Souza Matheus Leal , Morcrette Mathieu , Grimaud Alexis
Published: July 2022

The deployment of energy dense positive electrode materials such as Ni-rich NMC (LiNixMnyCozO2 with 0 < x, y, z < 1 and x + y + z = 1) for Li-ion batteries is plagued by numerous interfacial limitations. Among them, dissolution of transition metals (TMs) was shown to trigger deleterious growth of solid electrolyte interphase (SEI) and/or lithium plating at the anode. Although numerous post-mortem analysis and cycling data showed a causal relationship between TMs deposition and capacity fading, quantifying and discriminating the major source of degradation proves tedious. Herein, using graphite/LiNiO2 chemistry, we quantitatively demonstrate that TMs in solution permeate inside the SEI to be reduced, which precipitates cell aging following a loss of lithium inventory at the anode. This loss induces a change in intercalation staging at the graphite anode, allowing the recovery of LiNiO2 intercalation plateau at high potential, thus leading to a “S”-shape evolution of capacity as function of cycling. Furthermore, aging study in temperature show that TMs do not favor lithium plating but rather destabilize the SEI, especially at high temperature. Beyond the sole understanding of the graphite/LiNiO2 chemistry, this work offers practical routes towards evaluating LIBs degradations using electrochemical diagnosis methods.
Immunomodulatory Effects of Lepidium meyenii Walp. Polysaccharides on an Immunosuppression Model Induced by Cyclophosphamide
Authors: Fei Wen-ting , Yue Na , Li Ai-min , Yu Shu-hui , Zhao Dan-ping , Zhu Ying-li , Wang Chun , Zhang Jian-jun , Wang Lin-yuan
Published: July 2022

Background. Lepidium meyenii Walp. (Maca) has emerged as a functional plant food and traditional herb owing to its biological activities; Maca polysaccharides as an important active component of Maca have good immunomodulatory effect; however, studies on the immunomodulatory effect of Maca polysaccharides are mainly focused on macrophages; little attention has been devoted to the mechanisms and other immune cells. This study is aimed at investigating the immunomodulatory effects and mechanisms of Maca polysaccharides. Methods. Sixty mice were divided into five groups, and the mice were injected with cyclophosphamide to establish an immunosuppression model except for those in the common group. The body weights were measured, as well as immune-related indices, such as organ indices, haematological parameters, lymphocyte cycle, and proliferation, cytokine, and protein expression levels. Results. The weight loss and immune organ index decline caused by cyclophosphamide could be reversed by MP. Furthermore, MP increased WBC and HGB counts and reduced the ratio of G0/G1 phase obviously, increased the proportion of S phase and G2/M phase in peripheral blood lymphocytes, increased the counts of CD4+ T cells and the ratio of CD4+/CD8+, and reduced the inhibition rate of splenic lymphocytes. MP affected the production of cytokines by increasing IFN-γ, TNF-α, and IL-2 levels and by decreasing IL-4 levels. MP increased the mRNA expression of T-bet and the protein expression of Bcl-2 in the spleen and decreased the protein expression of caspase-3 and Bax. Conclusions. Maca polysaccharides might be the basic material for Maca’s immunomodulatory effect. The mechanism was perhaps related to inhibiting lymphocyte apoptosis and promoting the balance of Th1/Th2 cell subsets.
Flavonoid Extract from Propolis Provides Cardioprotection following Myocardial Infarction by Activating PPAR-γ
Authors: Wang Qian , Chen Rui , Tang Qian , Chen Jin-ying , Wang Yan , Sui Dian-jun , Liu Ai-dong
Published: July 2022

We have previously reported that flavonoid extract from propolis (FP) can improve cardiac function in rats following myocardial infarction (MI). However, the mechanisms responsible for the cardioprotective effects of FP have not been fully elucidated. In the current study, we explored whether FP can reduce inflammatory cytokines and attenuate sympathetic nerve system activity and antiendoplasmic reticulum (ER) stress and whether the cardioprotective effects are related to peroxisome proliferator-activated receptor gamma (PPAR-γ) activation. Sprague Dawley rats were randomly divided into six groups: Sham group received the surgical procedure but no artery was ligated; MI group received ligation of the left anterior descending (LAD) branch of the coronary artery; MI + FP group received FP (12.5 mg/kg/d, intragastrically) seven days prior to LAD ligation; FP group (Sham group + 12.5 mg/kg/d, intragastrically); MI + FP + GW9662 group received FP prior to LAD ligation with the addition of a specific PPAR-γ inhibitor (GW9662), 1 mg/kg/d, orally); and MI + GW9662 group received the PPAR-γ inhibitor and LAD ligation. The results demonstrated that the following inflammatory markers were significantly elevated following MI as compared with expression in sham animals: IL-1β, TNF-α, CRP; markers of sympathetic activation: plasma norepinephrine, epinephrine and GAP43, nerve growth factor, thyroid hormone; and ER stress response markers GRP78 and CHOP. Notably, the above changes were attenuated by FP, and GW9662 was able to alleviate the effect of FP. In conclusion, FP induces a cardioprotective effect following myocardial infarction by activating PPAR-γ, leading to less inflammation, cardiac sympathetic activity, and ER stress.
Synchronization in Finite Time of Fuzzy Neural Networks with Hybrid Delays and Uncertain Nonlinear Perturbations
Authors: Zhao Shuyue , Li Kelin , Hu Weiyi
Published: July 2022

This paper deals with the finite-time synchronization problem of a class of fuzzy neural networks with hybrid delays and uncertain nonlinear perturbations. By applying the famous finite-time stability theory, combining differential inequality techniques, and the analysis approach, several new algebraic sufficient criteria are obtained to realize finite-time synchronization between the drive system and the response system by designing a state feedback controller and an adaptive controller. Taking discrete delays, distributed delays, and uncertain nonlinear perturbations into account in fuzzy cellular neural networks makes the neural system more general than most existing cellular neural networks. Two different novel types of controllers designed to achieve finite-time synchronization can not only effectively overcome the influence of time delays and perturbations but also change their form according to the change of system state or perturbation to achieve a better control effect. Meanwhile, some algebraic sufficient criteria obtained in this paper can be proved by the parameters of the system itself, and the complex calculation of matrix inequality is avoided. Finally, the validity of our proposed results is confirmed by several examples and simulations. Furthermore, a secure communication problem is presented to further illustrate the fact of the obtained results.