bluuebunny/crossref_metadata_2025_split huggingface dataset:
From “footprint” to relationships: Impacts of US military base on Okinawa
Authors: Oshiro Akino 
Published: June 2023

AbstractHow does militarism impact the natural environment? There is a growing body of scholarly work interrogating the intersection of environmental impacts and military activities from what can be referred to as a “footprint” perspective, which documents the tangible environmental impacts. Further, this paper introduces an alternative perspective on militarism's environmental impacts, which emphasizes Indigenous people's relationship to the environment, which this paper calls the relational perspective. This review paper argues that the emerging research concerning the environmental impacts of the US military bases in Okinawa employs the relational perspective, which echoes insights from Indigenous studies that see land as a field of the relationship of things to each other. Overall, this paper acknowledges that there is a reciprocal relationship that bridges humans and nonhuman subjectivity, including the natural environment, animals, and plants, and some places, like Okinawa, prioritize this perspective, which gives us a different angle on how we see the natural environment, the long‐lasting impacts of militarism, and countermeasures to the climate crisis. Military bases necessitate natural resources to exist. However, it is not only those material resources that get affected. Relationships with the natural environment, an essential aspect of Indigenous epistemology, are also impacted.
Dynamic modelling of Renewable Energy Consumption and Production on African Economic Growth and the Environment Using Vector Error Correction Models
Authors: Gwani Alhaji Abdullahi , Sek Siok Kun 
Published: June 2023

Prior research has explored the influence of renewable consumption on economic growth and carbon emissions (CO2), but few studies have examined the impact of both renewable energy consumption (REC) and renewable energy production (REP) on economic growth and CO2 emissions in Africa. The objective of this work is to dynamically estimate the effects of both REC and REP on economic growth and CO2 emissions in Africa, based on empirical evidence and using a data set from the years 1965 to 2020. This research aims to determine how REC and REP affect the economies and ecosystems of Africa. The Error Correction Models (ECMs) were utilized in the analysis, focusing on howREP and REC influence economic growth and environmental carbon dioxide emissions (CO2). Vector Error Correction Models (VECM) and Johansen cointegration methods were used on the data set. The results demonstrated that economic forces existed between the variables and that there was a long run equilibrium relationship between GDP and CO2 emissions in Africa, from REC to REP. Additionally, the outcomes showed that both REC and REP slowed down environmental deterioration while promoting economic growth. Africa can lower the negative impacts of environmental pollution caused by the consumption of nonrenewable energy sources by adopting and aggressively promoting renewable energy production and utilization.
Therapeutic potential of
Bacillus
phage lysin PlyB in ocular infections
Authors: Mursalin Md Huzzatul , Astley Roger , Coburn Phillip S. , Bagaruka Eddy , Hunt Jonathan J. , Fischetti Vincent A. , Callegan Michelle C. 
Published: June 2023

ABSTRACT

Bacteriophage lytic enzymes (i.e., phage lysins) are a trending alternative for general antibiotics to combat growing antimicrobial resistance. Gram-positive
Bacillus cereus
causes one of the most severe forms of intraocular infection, often resulting in complete vision loss. It is an inherently β-lactamase-resistant organism that is highly inflammogenic in the eye, and antibiotics are not often beneficial as the sole therapeutic option for these blinding infections. The use of phage lysins as a treatment for
B. cereus
ocular infection has never been tested or reported. In this study, the phage lysin PlyB was tested
in vitro
, demonstrating rapid killing of vegetative
B. cereus
but not its spores. PlyB was also highly group specific and effectively killed the bacteria in various bacterial growth conditions, including
ex vivo
rabbit vitreous (Vit). Furthermore, PlyB demonstrated no cytotoxic or hemolytic activity toward human retinal cells or erythrocytes and did not trigger innate activation. In
in vivo
therapeutic experiments, PlyB was effective in killing
B. cereus
when administered intravitreally in an experimental endophthalmitis model and topically in an experimental keratitis model. In both models of ocular infection, the effective bactericidal property of PlyB prevented pathological damage to ocular tissues. Thus, PlyB was found to be safe and effective in killing
B. cereus
in the eye, greatly improving an otherwise devastating outcome. Overall, this study demonstrates that PlyB is a promising therapeutic option for
B. cereus
eye infections.

IMPORTANCE

Eye infections from antibiotic-resistant
Bacillus cereus
are devastating and can result in blindness with few available treatment options. Bacteriophage lysins are an alternative to conventional antibiotics with the potential to control antibiotic-resistant bacteria. This study demonstrates that a lysin called PlyB can effectively kill
B. cereus
in two models of
B. cereus
eye infections, thus treating and preventing the blinding effects of these infections.
Rhoptry neck protein 4 plays important roles during
Plasmodium
sporozoite infection of the mammalian liver
Authors: Baba Minami , Nozaki Mamoru , Tachibana Mayumi , Tsuboi Takafumi , Torii Motomi , Ishino Tomoko 
Published: June 2023

ABSTRACT

During invasion,
Plasmodium
parasites secrete proteins from rhoptry and microneme apical end organelles, which have crucial roles in attaching to and invading target cells. A sporozoite stage-specific gene silencing system revealed that rhoptry neck protein 2 (RON2), RON4, and RON5 are important for sporozoite invasion of mosquito salivary glands. Here, we further investigated the roles of RON4 during sporozoite infection of the liver
in vivo
. Following intravenous inoculation of RON4-knockdown sporozoites into mice, we demonstrated that sporozoite RON4 has multiple functions during sporozoite traversal of sinusoidal cells and infection of hepatocytes.
In vitro
infection experiments using a hepatoma cell line revealed that secreted RON4 is involved in sporozoite adhesion to hepatocytes and has an important role in the early steps of hepatocyte infection. In addition,
in vitro
motility assays indicated that RON4 is required for sporozoite attachment to the substrate and the onset of migration. These findings indicate that RON4 is crucial for sporozoite migration toward and invasion of hepatocytes via attachment ability and motility.

IMPORTANCE

Malarial parasite transmission to mammals is established when sporozoites are inoculated by mosquitoes and migrate through the bloodstream to infect hepatocytes. Many aspects of the molecular mechanisms underpinning migration and cellular invasion remain largely unelucidated. By applying a sporozoite stage-specific gene silencing system in the rodent malarial parasite,
Plasmodium berghei
, we demonstrated that rhoptry neck protein 4 (RON4) is crucial for sporozoite infection of the liver
in vivo
. Combined with
in vitro
investigations, it was revealed that RON4 functions during a crossing of the sinusoidal cell layer and invading hepatocytes, at an early stage of liver infection, by mediating the sporozoite capacity for adhesion and the onset of motility. Since RON4 is also expressed in
Plasmodium
merozoites and
Toxoplasma
tachyzoites, our findings contribute to understanding the conserved invasion mechanisms of
Apicomplexa
parasites.
ICD-10 codes for surveillance of non-fatal abusive head trauma in Aotearoa New Zealand: a retrospective cohort study
Authors: Knappstein Joanne , Reed Peter W , Kelly Patrick 
Published: June 2023

ObjectivesTo assess the validity of an International Classification of Diseases (ICD) code based definition of non-fatal head trauma caused by child abuse (abusive head trauma) for population surveillance in New Zealand.DesignA retrospective cohort study of hospital inpatient records.SettingA tertiary children’s hospital in Auckland, New Zealand.Participants1731 children less than 5 years of age who were discharged after a non-fatal head trauma event over a 10-year period from 1 January 2010 to 31 December 2019.Outcome measuresThe outcome of assessment by the hospital’s multidisciplinary child protection team (CPT) was compared with the outcome of ICD, Tenth Revision (ICD-10) discharge coding for non-fatal abusive head trauma (AHT). The ICD-10 code definition of AHT was derived from an ICD, Ninth Revision, Clinical Modification definition developed by the Centers for Disease Control, Atlanta, Georgia, which requires both a clinical diagnosis code and a cause-of-injury code.ResultsThere were 1755 head trauma events with 117 determined as AHT by the CPT. The ICD-10 code definition had a sensitivity of 66.7% (95% CI 57.4 to 75.1) and specificity of 99.8% (95% CI 99.5 to 100). There were only three false positives but 39 false negatives, with 18 of the false negatives coded with X59 (exposure to unspecified factor).ConclusionsThe ICD-10 code broad definition of AHT is a reasonable epidemiological tool for passive surveillance of AHT in New Zealand but it underestimates the incidence. Its performance could be improved by clear documentation of child protection conclusions in clinical notes, clarifying coding practice and removing the exclusion criteria from the definition.
Rapidly building surge capacity within a pandemic response using simulation-based clinical systems testing
Authors: Davis Nichole R , Doughty Cara B , Kerr Tarra , Elegores Gemma , Davis Kasey I , Kaziny Brent D 
Published: June 2023

IntroductionAs the SARS-CoV-2 virus spread across the globe, hospitals around the USA began preparing for its arrival. Building on previous experience with alternative care sites (ACS) during surge events, Texas Children’s Hospital (TCH) opted to redeploy their mobile paediatric emergency response teams. Simulation-based clinical systems testing (SbCST) uses simulation to test preoccupancy spaces and new processes. We developed rapid SbCST with social distancing for our deployed ACS, with collaboration between emergency management, paediatric emergency medicine and the simulation team.MethodsA two-phased approach included an initial virtual tabletop activity followed by SbCST at each campus, conducted simultaneously in-person and virtually. These activities were completed while also respecting the need for social distancing amidst a pandemic response. Each activity’s discussion was facilitated using Promoting Excellence and Reflective Learning in Simulation (PEARLS) for systems integration debriefing methodology and was followed by compilation of a failure mode and effects analysis (FMEA), which was then disseminated to campus leaders.ResultsWithin a 2-week period, participants from 20 different departments identified 109 latent safety threats (LSTs) across the four activities, with 71 identified as being very high or high priority items. Very high and high priority threats were prioritised in mitigation efforts by hospital leadership.DiscussionSbCST can be rapidly implemented to hone pandemic responses and identify LSTs. We used SbCST to allow for virtual participation and social distancing within a rapidly accelerated timeline. With prioritised FMEA reporting, leadership was able to mitigate concerns surrounding the four Ss of surge capacity: staff, stuff, structure and systems.
Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade
Authors: Randon Giovanni , Aoki Yu , Cohen Romain , Provenzano Leonardo , Nasca Vincenzo , Klempner Samuel J , Maron Steven B , Cerantola Riccardo , Chao Joseph , Fornaro Lorenzo , Ferrari Bravo Walter , Ghelardi Filippo , Ambrosini Margherita , Manca Paolo , Salati Massimiliano , Kawazoe Akihito , Zhu Valerie , Cowzer Darren , Genovesi Virginia , Lonardi Sara , Shitara Kohei , André Thierry , Pietrantonio Filippo 
Published: June 2023

BackgroundSubgroup analyses of randomized trials suggest the superiority of immune checkpoint inhibitor-based therapy over chemotherapy in patients with mismatch-repair deficient (dMMR) and/or microsatellite instability-high (MSI-high) advanced gastric or gastroesophageal junction adenocarcinoma. However, these subgroups are small and studies examining prognostic features within dMMR/MSI-high patients are lacking.MethodsWe conducted an international cohort study at tertiary cancer centers and collected baseline clinicopathologic features of patients with dMMR/MSI-high metastatic or unresectable gastric cancer treated with anti-programmed cell death protein-1 (PD-1)-based therapies. The adjusted HRs of variables significantly associated with overall survival (OS) were used to develop a prognostic score.ResultsOne hundred and thirty patients were included. At a median follow-up of 25.1 months, the median progression-free survival (PFS) was 30.3 months (95% CI: 20.4 to NA) and 2-year PFS rate was 56% (95% CI: 48% to 66%). Median OS was of 62.5 months (95% CI: 28.4 to NA) and 2-year OS rate was 63% (95% CI: 55% to 73%). Among the 103 Response Evaluation Criteria in Solid Tumors-evaluable patients, objective response rate was 66% and disease control rate 87% across lines of therapy. In the multivariable models, Eastern Cooperative Oncology Group Performance Status of 1 or 2, non-resected primary tumor, presence of bone metastases and malignant ascites were independently associated with poorer PFS and OS. These four clinical variables were used to build a three-category (ie, good, intermediate, and poor risk) prognostic score. Compared with patients with good risk, patients with intermediate risk score had numerically inferior PFS and OS (2-year PFS rate: 54.3% versus 74.5%, HR 1.90, 95% CI: 0.99 to 3.66; 2-year OS rate: 66.8% versus 81.2%, HR 1.86, 95% CI: 0.87 to 3.98), whereas patients with poor risk score had significantly inferior PFS and OS (2-year PFS rate: 10.6%, HR 9.65, 95% CI: 4.67 to 19.92; 2-year OS rate: 13.3%, HR 11.93, 95% CI: 5.42 to 26.23).ConclusionsOverall outcomes with anti-PD-1-based therapies are favorable in MSI-high gastroesophageal adenocarcinomas. However, within this overall favorable subgroup a more accurate prognostication using baseline clinical characteristics might identify patients at higher risk of rapid disease progression who may deserve intensified immunotherapy combination strategies.
Quantifying the burden of steroid-related damage in SLE in the Hopkins
Lupus Cohort
Authors: Davidson Julie E , Fu Qinggong , Rao Sapna , Magder Laurence S , Petri Michelle 
Published: June 2023

Objective
Corticosteroids are a mainstay of SLE treatment; however, cumulative
steroid exposure may lead to organ damage. This study aimed to quantify
the risk of new diabetes, hypertension, cataracts, osteoporosis and
avascular necrosis that is attributable to cumulative corticosteroid
exposure in SLE.

Methods
Using data from the Hopkins Lupus Cohort, a longitudinal study of
lupus activity, organ damage and quality of life in patients with SLE,
five matched case–control analyses nested within a prospectively
enrolled SLE cohort were performed. Two randomly selected controls were
matched to each case using incidence-density sampling from defined risk
sets. Attributable risk was calculated for steroid exposure (dose and
duration, separately). Cumulative steroid dose was modelled as a
four-level categorical variable using clinically relevant thresholds:
0 g (no exposure); >0 and <3.65 g (<10 mg/day for a year);
≥3.65 g and <18.25 g (1–5 years at 10 mg/day); and ≥18.25 g (>5
years at 10 mg/day).

Results
Eligible cases were identified for diabetes (n=42), hypertension
(n=79), cataract (n=132), osteoporosis (n=118) and avascular necrosis
(n=38). The unadjusted OR for a one-category increase in cumulative
steroid exposure ranged from 1.157 (cataract (0.889 to 1.506); p=0.2779)
to 2.183 (avascular necrosis (1.162 to 4.103); p=0.0153). After
adjusting for confounding variables, a one-category increase in the
cumulative steroid dose was significantly associated with risk of
cataract (OR (95% CI) 1.855 (1.190 to 2.892); p=0.0064) and osteoporosis
(OR (95% CI) 1.604 (1.067 to 2.412); p=0.0232). ORs for avascular
necrosis, diabetes and hypertension suggested a moderately increased
risk (not significant). Duration of steroid exposure was not associated
with any of the outcomes. The proportion of risk attributable to steroid
exposure after adjustment for covariates was 0.711 for cataract and
0.540 for osteoporosis.

Conclusions
Cumulative steroid exposure was associated with an increased risk of
cataract and osteoporosis in patients with SLE.

Trial registration number
NCT01616472.
Type I interferon receptor blockade with anifrolumab corrects innate and
adaptive immune perturbations of SLE
Authors: Casey Kerry A , Guo Xiang , Smith Michael A , Wang Shiliang , Sinibaldi Dominic , Sanjuan Miguel A , Wang Liangwei , Illei Gabor G , White Wendy I 
Published: June 2023

Objective
Anifrolumab is a fully human immunoglobulin G1κ
monoclonal antibody specific for subunit 1 of the type I interferon
(IFN) α receptor. In a phase IIb study of adults with moderate to severe
SLE, anifrolumab treatment demonstrated substantial reductions in
multiple clinical endpoints. Here, we evaluated serum proteins and
immune cells associated with SLE pathogenesis, type I interferon gene
signature (IFNGS) test status and disease activity, and how anifrolumab
affected these components.

Methods
Whole blood samples were collected from patients enrolled in MUSE
(NCT01438489) for serum protein and cellular
assessments at baseline and subsequent time points. Data were parsed by
IFNGS test status (high/low) and disease activity. Protein expression
and immune cell subsets were measured using multiplex immunoassay and
flow cytometry, respectively. Blood samples from healthy donors were
analysed for comparison.

Results
Baseline protein expression differed between patients with SLE and
healthy donors, IFNGS test-high and -low patients, and patients with
moderate and severe disease. Anifrolumab treatment lowered
concentrations of IFN-induced chemokines associated with B, T and other
immune cell migration in addition to proteins associated with
endothelial activation that were dysregulated at baseline. IFNGS
test-high patients and those with high disease activity were
characterised by low baseline numbers of lymphocytes, circulating memory
T-cell subsets and neutrophils. Anifrolumab treatment reversed
lymphopenia and neutropenia in the total population, and normalised
multiple T-cell subset counts in IFNGS test-high patients compared with
placebo.

Conclusions
Anifrolumab treatment reversed IFN-associated changes at the protein
and cellular level, indicating multiple modes of activity.

Trial registration number
NCT01438489.
Pharmacodynamic and pharmacokinetic effects and safety of verinurad in
combination with febuxostat in adults with gout: a phase IIa, open-label
study
Authors: Fleischmann Roy , Winkle Peter , Hall Jesse , Valdez Shakti , Liu Sha , Yan Xiaohong , Hicks Liz , Lee Caroline , Miner Jeffrey N , Gillen Michael , Hernandez-Illas Martha 
Published: June 2023

Objective
Verinurad (RDEA3170) is a high-affinity, selective URAT1 inhibitor
in development for treating gout and asymptomatic hyperuricaemia. This
study evaluated the pharmacodynamics, pharmacokinetics and safety of
verinurad in combination with febuxostat in adults with gout.

Methods
The phase IIa, open-label, multicentre study randomised 64 subjects
into one of five cohorts to receive febuxostat (40 or 80 mg) alone or in
combination with verinurad 2.5–20 mg. Serial plasma/serum and urine
samples were assayed for verinurad and uric acid. Safety was assessed by
adverse events, chemistry panels, ECGs and physical
examinations.

Results
Serum pharmacodynamic data demonstrated the maximum percent decrease
in serum urate (sUA) from baseline (Emax) at
8–12 hours after dosing. Verinurad with febuxostat decreased sUA in a
dose-dependent manner. Emaxfor verinurad with
febuxostat 40 mg ranged from 52% to 77% vs 42% for febuxostat 40 mg
alone; Emaxfor verinurad with febuxostat 80 mg was
62%–82% vs 55% for febuxostat 80 mg alone. Urinary uric acid excretion
rate was reduced below baseline by febuxostat alone and was comparable
to baseline for verinurad with febuxostat. Verinurad plasma exposure
increased with dose and was comparable when combined with febuxostat. No
drug-drug interactions were observed. Verinurad was well tolerated with
no clinically meaningful changes in laboratory values.

Conclusion
Verinurad administered with febuxostat produced dose-dependent
decreases in sUA while maintaining urinary uric acid levels comparable
to baseline. These dose combinations of verinurad and febuxostat were
generally well tolerated. These data support continued investigation of
oral verinurad in patients with gout.

Trial registration number
NCT02246673
Efficiency of a self-organizing Ising model of financial markets
Authors: Antenorcruz Jude Maria V. , Batac Rene C. 
Published: June 2023

Individual agents in financial markets decide based on market conditions, external news and information, and personal idiosyncrasies; from the collective action of such agents arise the unpredictable market dynamics. These actions affect the overall market efficiency, which measures how well the price reflects all available information. Here, we implement the self-organizing Ising model of Zhou and Sornette [Eur. Phys. J. B 55, 175 (2007)] to probe the efficiency of simulated financial markets under various conditions. Efficiency is parametrized by the dispersion of the generalized Hurst exponents obtained from multifractal detrended fluctuation analysis. Scanning different model parameter sets reveals the regimes of efficiency values in simulated markets that compare with those obtained from real-world data.