bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial
Authors: Sampson John H , Singh Achrol Achal , Aghi Manish K , Bankiewicz Krystof , Bexon Martin , Brem Steven , Brenner Andrew , Chandhasin Chandtip , Chowdhary Sajeel , Coello Melissa , Ellingson Benjamin M , Floyd John R , Han Seunggu , Kesari Santosh , Mardor Yael , Merchant Fahar , Merchant Nina , Randazzo Dina , Vogelbaum Michael , Vrionis Frank , Wembacher-Schroeder Eva , Zabek Miroslaw , Butowski Nicholas 
Published: January 2023

Abstract

Background
MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes.

Methods
MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10μL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS.

Results
MDNA55 showed an acceptable safety profile at doses up to 240 μg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (&gt;180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26).

Conclusions
MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.
Trial Registration: Clinicaltrials.gov NCT02858895.
Computed tomography scan radiation and brain cancer incidence
Authors: Smoll Nicolas R , Brady Zoe , Scurrah Katrina J , Lee Choonsik , Berrington de González Amy , Mathews John D 
Published: January 2023

Abstract

Background
Computed tomography (CT) scans make substantial contributions to low-dose ionizing radiation exposures, raising concerns about excess cancers caused by diagnostic radiation.

Methods
Deidentified medicare records for all Australians aged 0–19 years between 1985–2005 were linked to national death and cancer registrations to 2012. The National Cancer Institute CT program was used to estimate radiation doses to the brain from CT exposures in 1985–2005, Poisson regression was used to model the dependence of brain cancer incidence on brain radiation dose, which lagged by 2 years to minimize reverse causation bias.

Results
Of 10 524 842 young Australians, 611 544 were CT-exposed before the age of 20 years, with a mean cumulative brain dose of 44 milligrays (mGy) at an average follow-up of 13.5 years after the 2-year lag period. 4472 were diagnosed with brain cancer, of whom only 237 had been CT-exposed. Brain cancer incidence increased with radiation dose to the brain, with an excess relative risk of 0.8 (95% CI 0.57–1.06) per 100 mGy. Approximately 6391 (95% CI 5255, 8155) persons would need to be exposed to cause 1 extra brain cancer.

Conclusions
For brain tumors that follow CT exposures in childhood by more than 2 years, we estimate that 40% (95% CI 29%–50%) are attributable to CT Radiation and not due to reverse causation. However, because of relatively low rates of CT exposure in Australia, only 3.7% (95% CI 2.3%–5.4%) of all brain cancers are attributable to CT scans. The population-attributable fraction will be greater in countries with higher rates of pediatric scanning.
Development and validation of sustainable employability index among older employees
Authors: Neupane S , K C P , Kyrönlahti S , Siukola A , Kosonen H , Lumme-Sandt K , Nikander P , Nygård C H 
Published: January 2023

AbstractBackgroundSustainable employability (SE) has become an important factor for keeping people in the labour market and enabling the extension of working life.AimsWe developed and validated an SE index to predict assured workability in 2 years. Additionally, we developed a scoring tool to use in practice.MethodsA questionnaire survey of postal employees aged ≥50 years was conducted in 2016 and followed up in 2018 (n = 1102). The data were divided into training and validation sets. The outcome was defined as whether the employees had an assured workability after 2 years or not. Multivariable log-binomial regression was used to calculate the SE index. The area under the curve (AUC) was calculated to assess the discriminative power of the index.ResultsThe probability of assured workability increased with increasing quintiles of the SE index. The highest quintiles of the SE index showed the highest observed and expected assured workability in 2 years. The predictive ability, area under the curve (AUC) for training was 0.79 (95% CI 0.75–0.83) and for validation data was 0.76 (95% CI 0.73–0.80). In the scoring tool, the self-rated health, workability, job satisfaction and perceived employment had the highest contribution to the index.ConclusionsThe SE index was able to distinguish the employees based on whether they had assured workability after 2 years. The scoring method could be used to calculate the potentiality of future employability among late midlife postal employees.
Does the depth of informality influence welfare in urban Sub-Saharan Africa?
Authors: Egger Eva-Maria , Poggi Cecilia , Rufrancos Héctor 
Published: January 2023

Abstract
We explore the relationship between household welfare and informality, measuring household informality as the share of members’ activities (hours worked or income) without social insurance. We discretize these measures into four bins or portfolios and assess their influence on consumption, as a measure of welfare. Cross-sectional regressions for five urban Sub-Saharan African countries reveal a non-linear relationship between the depth of informality and household welfare. A mixed formality household portfolio has at least the same welfare as a fully formal one. Using panel data for Nigeria, we assess household switches in informality portfolios, accounting for the selection on unobservables, and find it explains most welfare differences. Switching informality portfolios does not change welfare trajectories, with the notable exception of welfare gains for fully informal households becoming fully formal. From a policy perspective, our results suggest that policies incentivizing the formalization of the marginal worker may not result in perceivable welfare effects.
A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients With Metastatic Solid Tumors
Authors: Gatti-Mays Margaret E , Tschernia Nicholas P , Strauss Julius , Madan Ravi A , Karzai Fatima H , Bilusic Marijo , Redman Jason , Sater Houssein Abdul , Floudas Charalampos S , Toney Nicole J , Donahue Renee N , Jochems Caroline , Marté Jennifer L , Francis Deneise , McMahon Sheri , Lamping Elizabeth , Cordes Lisa , Schlom Jeffrey , Gulley James L 
Published: January 2023

AbstractBackgroundNHS-IL12 is a first-in-class, recombinant fusion protein composed of the human monoclonal antibody NHS76 (binds exposed DNA/histones at sites of intratumoral necrosis) fused to 2 IL-12 heterodimers. The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of NHS-IL12 monotherapy given subcutaneously (SC) every 4 weeks was previously reported. The study was expanded to include a high-exposure cohort with NHS-IL12 SC every 2 weeks (q2w).MethodsThis single-arm, phase I trial evaluated NHS-IL12 12 µg/kg SC q2w or 16.8µg/kg SC q2w in patients with metastatic solid tumors. The primary endpoint was safety.ResultsUsing a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. There was 1 DLT (Grade 3 aspartate transaminase/alanine transaminase [AST/ALT] elevation). Other grade 3 toxicities included: flu-like symptoms 1/13 (8%), decreased absolute lymphocyte count (ALC) 1/13 (8%), decreased white blood cell count (WBC) 1/13 (8%), but most adverse events reported were low grade and self-limiting grade. Fifty percent of evaluable patients (6/12) experienced stable disease (SD) with 42% (5/12) developing progressive disease (PD) at the first restaging.ConclusionBiweekly NHS-IL12 was well tolerated in this small phase I study. Additional studies incorporating NHS-IL12 with other immunomodulating agents are underway. (ClinicalTrials.gov Identifier: NCT01417546).
Control of Plant Cell Growth and Proliferation by MO25A, a Conserved Major Component of the Mammalian Sterile 20–Like Kinase Pathway
Authors: Ta Kim Nhung , Yoshida Mari W , Tezuka Takumi , Shimizu-Sato Sae , Nosaka-Takahashi Misuzu , Toyoda Atsushi , Suzuki Takamasa , Goshima Gohta , Sato Yutaka 
Published: January 2023

AbstractThe precise control of cell growth and proliferation underpins the development of plants and animals. These factors affect the development and size of organs and the body. In plants, the growth and proliferation of cells are regulated by environmental stimuli and intrinsic signaling, allowing different cell types to have specific growth and proliferation characteristics. An increasing number of factors that control cell division and growth have been identified. However, the mechanisms underlying cell type–specific cell growth and proliferation characteristics in the normal developmental context are poorly understood. Here, we analyzed the rice mutant osmo25a1, which is defective in the progression of embryogenesis. The osmo25a1 mutant embryo developed incomplete embryonic organs, such as the shoot and root apical meristems. It showed a delayed progression of embryogenesis, associated with the reduced mitotic activity. The causal gene of this mutation encodes a member of the Mouse protein-25A (MO25A) family of proteins that have pivotal functions in a signaling pathway that governs cell proliferation and polarity in animals, yeasts and filamentous fungi. To elucidate the function of plant MO25A at the cellular level, we performed a functional analysis of MO25A in the moss Physcomitrium patens. Physcomitrium patens MO25A was uniformly distributed in the cytoplasm and functioned in cell tip growth and the initiation of cell division in stem cells. Overall, we demonstrated that MO25A proteins are conserved factors that control cell proliferation and growth.
Distribution of squid paralarvae and related oceanographic features in the eastern Campeche Bank, Mexico
Authors: García-Cordova Elton A , De Silva-Dávila Roxana , Velázquez-Abunader Iván , García-Maldonado José Q , Ardisson Pedro-Luis 
Published: January 2023

AbstractThe eastern Campeche Bank is a region where the composition, distribution and abundance of one of its most promising resources, the teuthid cephalopods (squids), need to be better documented, particularly at the paralarval stage. To contribute to its knowledge, we obtained paralarvae from zooplankton samples collected from May 2016 to November 2017, relating and modeling their distribution to sea surface temperature, salinity, dissolved oxygen (DO), chlorophyll-a (Chl-a), zooplankton biomass and depth. The results showed that most paralarvae measured &lt;2.0 mm mantle length. Higher abundances were found during upwelling months. Spatiotemporal segregation of teuthid species was observed, with oceanic paralarvae occurring offshore in May–July, and neritic ones appearing nearshore in September–November, Abralia redfieldi and Doryteuthis plei being the most abundant. Statistical generalized additive model for location, scale and shape showed that A. redfieldi was present in the north (offshore), related to warm Caribbean waters, and increased Chl-a and DO concentration. In contrast, D. plei was present in the south (nearshore), related to Yucatan shelf waters and low Chl-a.
Initial clinical and laboratory parameters triaging non-pharmaceutical acute pediatric poisoned patients for potential adverse outcomes: a three-year retrospective study
Authors: El-Sarnagawy Ghada N , Ghonem Mona M , Helal Nadia E 
Published: January 2023

AbstractIdentifying high-risk pediatric patients with non-pharmaceutical poisoning is crucial to avoid prospective complications and decrease the evident hospital economic burden. Although the preventive strategies have been well studied, determining the early predictors for poor outcomes remains limited. Therefore, this study focused on the initial clinical and laboratory parameters as a triage of non-pharmaceutical poisoned children for potential adverse outcomes taking the causative substance effects into account. This retrospective cohort study included pediatric patients admitted to Tanta University Poison Control Center from January 2018 to December 2020. Sociodemographic, toxicological, clinical, and laboratory data were retrieved from the patient’s files. Adverse outcomes were categorized into mortality, complications, and intensive care unit (ICU) admission. Out of enrolled 1,234 pediatric patients, preschool children constituted the highest percentage of the patients investigated (45.06%), with a female predominance (53.2%). The main non-pharmaceutical agents included pesticides (62.6%), corrosives (19%), and hydrocarbons (8.8%), mainly associated with adverse consequences. The significant determinants for adverse outcomes were pulse, respiratory rate, serum bicarbonate (HCO3), Glasgow Coma Scale, O2 saturation, Poisoning Severity Score (PSS), white blood cells (WBCs), and random blood sugar. The cutoffs of serum HCO3 &lt; 17.55 mmol/l, WBCs &gt;8,650 cells/microliter, and PSS &gt; 2 points were the best discriminators for mortality, complications, and ICU admission, respectively. Thus, monitoring these predictors is essential to prioritize and triage pediatric patients who require high-quality care and follow-up, particularly in aluminum phosphide, sulfuric acid, and benzene intoxications.
Considering developmental neurotoxicityin vitrodata for human health risk assessment using physiologically-based kinetic modeling: deltamethrin case study
Authors: Maass Christian , Schaller Stephan , Dallmann André , Bothe Kathrin , Müller Dennis 
Published: January 2023

AbstractDevelopmental neurotoxicity (DNT) is a potential hazard of chemicals. Recently, an in vitro testing battery (DNT IVB) was established to complement existing rodent in vivo approaches. Deltamethrin (DLT), a pyrethroid with a well-characterized neurotoxic mode of action, has been selected as a reference chemical to evaluate the performance of the DNT IVB. The present study provides context for evaluating the relevance of these DNT IVB results for the human health risk assessment of DLT by estimating potential human fetal brain concentrations after maternal exposure to DLT. We developed a physiologically based kinetic (PBK) model for rats which was then translated to humans considering realistic in vivo exposure conditions (acceptable daily intake [ADI] for DLT). To address existing uncertainties, we designed case studies considering the most relevant drivers of DLT uptake and distribution. Calculated human fetal brain concentrations were then compared with the lowest benchmark concentration achieved in the DNT IVB. The developed rat PBK model was validated on in vivo rat toxicokinetic data of DLT over a broad range of doses. The uncertainty based case study evaluation confirmed that repeated exposure to DLT at an ADI level would likely result in human fetal brain concentrations far below the in vitro benchmark. The presented results indicate that DLT concentrations in the human fetal brain are highly unlikely to reach concentrations associated with in vitro findings under realistic exposure conditions. Therefore, the new in vitro DNT results are considered to have no impact on the current risk assessment approach.
Pneumoperitoneum caused by pneumatosis cystoides coli
Authors: Chang Ting-Wei , Tsai Feng-Chi 
Published: January 2023

Abstract
Pneumatosis cystoides intestinalis (PCI) is a rare disease with the incidence of 0.03% in the general population, and the symptoms are diverse, ranging from asymptomatic to life-threatening scenario. Herein, we present a case of pneumatosis cystoides coli with pneumoperitoneum and an unknown origin of septic shock undergoing exploratory laparotomy. A 70-year-old woman with a history of Bechet disease was admitted to the internal medicine department because of Bechet disease with acute exacerbation, and she received high-dose steroid therapy. Emergency computed tomography of the abdomen disclosed diffuse pneumatosis coli with pneumoperitoneum and mild ascites. Ischemic bowel disease was highly suspected. Exploratory laparotomy was done with intraoperative findings of an intact gastrointestinal tract without ischemic change and gas within the wall of the colon. Pneumoperitoneum could be a life-threatening condition and also be a nonsurgical scenario. Arterial gas examination could be a considerable clue to distinguish pneumatosis cystoides coli–related pneumoperitoneum from surgical pneumoperitoneum. Close and serial observation of clinical presentation, laboratory examination, and image study would be helpful to identify the possible etiologies of pneumoperitoneum. Laparoscopic exploration may also be a safe and feasible option to examine the integrity of the gastrointestinal tract.
Serratia Infection Epidemiology Among Very Preterm Infants in the Neonatal Intensive Care Unit
Authors: Coggins Sarah A. , Edwards Erika M. , Flannery Dustin D. , Gerber Jeffrey S. , Horbar Jeffrey D. , Puopolo Karen M. 
Published: January 2023

Background:

Serratia spp. are opportunistic, multidrug resistant, Gram-negative pathogens, previously described among preterm infants in case reports or outbreaks of infection. We describe Serratia late-onset infection (LOI) in very preterm infants in a large, contemporary, nationally representative cohort.

Methods:
In this secondary analysis of prospectively collected data of preterm infants born 401–1500 grams and/or 22–29 weeks gestational age from 2018 to 2020 at 774 Vermont Oxford Network members, LOI was defined as culture-confirmed blood and/or cerebrospinal fluid infection > 3 days after birth. The primary outcome was incidence of Serratia LOI. Secondary outcomes compared rates of survival and discharge morbidities between infants with Serratia and non-Serratia LOI.

Results:
Among 119,565 infants, LOI occurred in 10,687 (8.9%). Serratia was isolated in 279 cases (2.6% of all LOI; 2.3 Serratia infections per 1000 infants). Of 774 hospitals, 161 (21%) reported at least one Serratia LOI; 170 of 271 (63%) cases occurred at hospitals reporting 1 or 2 Serratia infections, and 53 of 271 (20%) occurred at hospitals reporting ≥5 Serratia infections. Serratia LOI was associated with a lower rate of survival to discharge compared with those with non-Serratia LOI (adjusted relative risk 0.88, 95% CI: 0.82–0.95). Among survivors, infants with Serratia LOI had higher rates of tracheostomy, gastrostomy and home oxygen use compared with those with non-Serratia LOI.

Conclusions:
The incidence of Serratia LOI was 2.3 infections per 1000 very preterm infants in this cohort. Lower survival and significant morbidity among Serratia LOI survivors highlight the need for recognition and targeted prevention strategies for this opportunistic nosocomial infection.
Pneumonia in Children During the 2019 Outbreak in Xiamen, China
Authors: Zhang Jinqiang , Zhuo Zhiqiang , Xu Yongjun , Bai Dingzhen , Wang Chuning , Cai Jiehao , Zeng Mei 
Published: January 2023

Background:
To understand the regional epidemiology and clinical characteristics of adenovirus pneumonia in hospitalized children during the 2019 outbreak of respiratory adenoviruses in China.

Methods:
We analyzed the epidemiologic trend of adenovirus in children hospitalized for acute lower respiratory tract infections in Xiamen in 2019. Adenovirus was identified using direct fluorescent antibody detection. During the peak seasons of adenovirus epidemic, 170 adenovirus-positive specimens were obtained for molecular typing, and the clinical data were collected.

Results:
Among the 9890 children hospitalized for acute lower respiratory tract infection, 609 (6.2%) were tested positive for adenovirus. The detection rate of adenovirus was significantly higher in boys than in grils (9.5% vs. 4.6%, P < 0.05). Adenovirus activity increased markedly between April and August with the prevalence of 7.3%–12.4%. During the outbreak season, type 7 accounted for 70.6%, followed by type 3 (28.8%) and type 4 (0.6%). Of the 155 cases of adenovirus pneumonia, the median age was 3.0 years (range: 4 month to 9 years), 153 (98.7%) had fever with a mean fever duration of 9.04 ± 5.52 days, 28 (16.5%) had wheezing, 93 (60%) showed segmental or lobar consolidation with atelectasis and 13 (8.4%) showed pleural effusion. Forty-six (29.6%) cases developed severe pneumonia, 7 (4.1%) required mechanical ventilation and 2 (1.2%) died. Younger age, longer duration of fever and higher fever spike were more frequently seen in severe cases (P < 0.05). Twenty-five (16.2%) had C-reactive protein ≥ 40 mg/L, and 91 (58.7%) had procalcitonin ≥ 0.25 mg/L.

Conclusions:
Adenovirus types 7 and 3 caused the outbreak of adenovirus pneumonia in community children during late spring to summer in 2019 in Xiamen. The majority of adenovirus pneumonia resembles bacterial pneumonia. The incidence of severe pneumonia was high when type 7 predominantly prevailed. Adenovirus type 7 was more common in severe cases than in nonsevere cases.
Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series
Authors: Rau Cornelius , Auer-Hackenberg Lorenz , Deubzer Hedwig E. , Schwabel Elisabeth , Jaros Maria , Diederichs Antonia , Lehrnbecher Thomas , Holm Mette , von Linstow Marie-Louise , Martin Luise , Dinges Sarah Svenja , Rothensteiner Maria , Siepermann Meinolf , Strenger Volker , von Both Ulrich , Teig Norbert , Brinkmann Folke , Leeb Franziska , Zeitlinger Markus , Kobbe Robin , Götzinger Florian 
Published: January 2023

Background:
Although severe COVID-19 in children is rare, those with certain pre-existing health conditions are more prone to severe disease. Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potent antiviral agents that reduce adverse clinical outcomes in adults, but are commonly not approved for use in pediatric patients.

Methods:
We retrospectively evaluated mAb treatment in children <12 years of age or <40kg with SARS-CoV-2 infection between January 1, 2021, and March 7, 2022, in 12 tertiary care centers in 3 European countries.

Results:
We received data from 53 patients from Austria, Denmark and Germany. Median age was 5.4 years [0–13.8, interquartile range (IQR) = 6.2], and median body weight was 20 kg (3–50.1, IQR = 13). The most frequent SARS-CoV-2 variant in this study, if known, was Omicron, followed by Delta and Alpha. Pre-existing conditions included immunodeficiency, malignancy, hematologic disease, cardiac disease, chronic lung disease, chronic liver disease, kidney disease and diabetes. Forty-two patients received sotrovimab (79%), 9 casirivimab/imdevimab (17%) and 2 bamlanivimab (4%). All but 1 patient survived. Median duration of hospital stay was 3 days (0–56, IQR = 6). Seven patients required treatment in an intensive care unit, and 5 required high-flow nasal cannula treatment. Potential side effects included neutropenia (6/53, 11%), lymphopenia (3/53, 6%), nausea or vomiting (2/53, 4%), rise of alanine transaminase (1/53, 2%) and hypotonia (1/53, 2%).

Conclusions:
MAb treatment was well tolerated by children in this cohort.