bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of sewage sampling for wastewater-based epidemiology through stochastic modeling
Authors: Martin Max , Goethals Paul , Newhart Kathryn , Rhodes Emily , Vogel Jason , Stevenson Bradley 
Published: February 2023

AbstractThe proliferation of the SARS-CoV-2 global pandemic has brought to attention the need for epidemiological tools that can detect diseases in specific geographical areas through non-contact means. Such methods may protect those potentially infected by facilitating early quarantine policies to prevent the spread of the disease. Sampling of municipal wastewater has been studied as a plausible solution to detect pathogen spread, even from asymptomatic patients. However, many challenges exist in wastewater-based epidemiology such as identifying a representative sample for a population, determining the appropriate sample size, and establishing the right time and place for samples. In this work, a new approach to address these questions is assessed using stochastic modeling to represent wastewater sampling given a particular community of interest. Using estimates for various process parameters, inferences on the population infected are generated with Monte Carlo simulation output. A case study at the University of Oklahoma is examined to calibrate and evaluate the model output. Finally, extensions are provided for more efficient wastewater sampling campaigns in the future. This research provides greater insight into the effects of viral load, the percentage of the population infected, and sampling time on mean SARS-CoV-2 concentration through simulation. In doing so, an earlier warning of infection for a given population may be obtained and aid in reducing the spread of viruses.
Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study
Authors: Garassino Marina C. , Gadgeel Shirish , Speranza Giovanna , Felip Enriqueta , Esteban Emilio , Dómine Manuel , Hochmair Maximilian J. , Powell Steven F. , Bischoff Helge G. , Peled Nir , Grossi Francesco , Jennens Ross R. , Reck Martin , Hui Rina , Garon Edward B. , Kurata Takayasu , Gray Jhanelle E. , Schwarzenberger Paul , Jensen Erin , Pietanza M. Catherine , Rodríguez-Abreu Delvys 
Published: February 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present 5-year outcomes from the phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680 ). Eligible patients with previously untreated metastatic nonsquamous non–small-cell lung cancer without EGFR/ALK alterations were randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles with pemetrexed and investigator's choice of carboplatin/cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity. Primary end points were overall survival (OS) and progression-free survival (PFS). Among 616 randomly assigned patients (n = 410, pembrolizumab plus pemetrexed-platinum; n = 206, placebo plus pemetrexed-platinum), median time from random assignment to data cutoff (March 8, 2022) was 64.6 (range, 60.1-72.4) months. Hazard ratio (95% CI) for OS was 0.60 (0.50 to 0.72) and PFS was 0.50 (0.42 to 0.60) for pembrolizumab plus platinum-pemetrexed versus placebo plus platinum-pemetrexed. 5-year OS rates were 19.4% versus 11.3%. Toxicity was manageable. Among 57 patients who completed 35 cycles of pembrolizumab, objective response rate was 86.0% and 3-year OS rate after completing 35 cycles (approximately 5 years after random assignment) was 71.9%. Pembrolizumab plus pemetrexed-platinum maintained OS and PFS benefits versus placebo plus pemetrexed-platinum, regardless of programmed cell death ligand-1 expression. These data continue to support pembrolizumab plus pemetrexed-platinum as a standard of care in previously untreated metastatic non–small-cell lung cancer without EGFR/ALK alterations.
The factory, the antenna and the scaffold: the three-way interplay between the Golgi, cilium and extracellular matrix underlying tissue function
Authors: Stevenson Nicola L. 
Published: February 2023

ABSTRACTThe growth and development of healthy tissues is dependent on the construction of a highly specialised extracellular matrix (ECM) to provide support for cell growth and migration and to determine the biomechanical properties of the tissue. These scaffolds are composed of extensively glycosylated proteins which are secreted and assembled into well-ordered structures that can hydrate, mineralise, and store growth factors as required. The proteolytic processing and glycosylation of ECM components is vital to their function. These modifications are under the control of the Golgi apparatus, an intracellular factory hosting spatially organised, protein-modifying enzymes. Regulation also requires a cellular antenna, the cilium, which integrates extracellular growth signals and mechanical cues to inform ECM production. Consequently, mutations in either Golgi or ciliary genes frequently lead to connective tissue disorders. The individual importance of each of these organelles to ECM function is well-studied. However, emerging evidence points towards a more tightly linked system of interdependence between the Golgi, cilium and ECM. This review examines how the interplay between all three compartments underpins healthy tissue. As an example, it will look at several members of the golgin family of Golgi-resident proteins whose loss is detrimental to connective tissue function. This perspective will be important for many future studies looking to dissect the cause and effect of mutations impacting tissue integrity.
Activation of an actin signaling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation
Authors: Faria Lídia , Canato Sara , Jesus Tito T. , Gonçalves Margarida , Guerreiro Patrícia S. , Lopes Carla S. , Meireles Isabel , Morais-de-Sá Eurico , Paredes Joana , Janody Florence 
Published: February 2023

ABSTRACT
Alterations in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression. Among those, P-cadherin is highly enriched in basal-like breast carcinomas, playing a central role in cancer cell self-renewal, collective cell migration and invasion. To establish a clinically relevant platform for functional exploration of P-cadherin effectors in vivo, we generated a humanized P-cadherin Drosophila model. We report that actin nucleators, Mrtf and Srf, are main P-cadherin effectors in fly. We validated these findings in a human mammary epithelial cell line with conditional activation of the SRC oncogene. We show that, prior to promoting malignant phenotypes, SRC induces a transient increase in P-cadherin expression, which correlates with MRTF-A accumulation, its nuclear translocation and the upregulation of SRF target genes. Moreover, knocking down P-cadherin, or preventing F-actin polymerization, impairs SRF transcriptional activity. Furthermore, blocking MRTF-A nuclear translocation hampers proliferation, self-renewal and invasion. Thus, in addition to sustaining malignant phenotypes, P-cadherin can also play a major role in the early stages of breast carcinogenesis by promoting a transient boost of MRTF-A–SRF signaling through actin regulation.
Nonsentinel Axillary Lymph Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph Node: A Predictive Model Proposal
Authors: Cebrecos Isaac , Mension Eduard , Alonso Inmaculada , Castillo Helena , Sanfeliu Esther , Vidal-Sicart Sergi , Ganau Sergi , Vidal Maria , Schettini Francesco 
Published: February 2023

Abstract
Background
In clinically node-negative (cN0) early stage breast cancer (EBC) undergoing primary systemic treatment (PST), post-treatment positive sentinel lymph node (SLN+) directs axillary lymph node dissection (ALND), with uncertain impacts on outcomes and increased morbidities.

Patients and Methods
We conducted an observational study on imaging-confirmed cN0 EBC, who underwent PST and breast surgery that resulted in SLN+ and underwent ALND. The association among baseline/postsurgical clinic–pathological factors and positive nonsentinel additional axillary lymph nodes (non-SLN+) was analyzed with logistic regression. LASSO regression (LR) identified variables to include in a predictive score of non-SLN+ (ALND-predict). The accuracy and calibration were assessed, an optimal cut-point was then identified, and in silico validation with bootstrap was undertaken.

Results
Non-SLN+ were detected in 22.2% cases after ALND. Only progesterone receptor (PR) levels and macrometastatic SLN+ were independently associated to non-SLN+. LR identified PR, Ki67, and type and number of SLN+ as the most efficient covariates. The ALND-predict score was built based on their LR coefficients, showing an area under the curve (AUC) of 0.83 and an optimal cut-off of 63, with a negative predictive value (NPV) of 0.925. Continuous and dichotomic scores had a good fit (p = 0.876 and p = 1.00, respectively) and were independently associated to non-SLN+ [adjusted odds ratio (aOR): 1.06, p = 0.002 and aOR: 23.77, p < 0.001, respectively]. After 5000 bootstrap-adjusted retesting, the estimated bias-corrected and accelerated 95%CI included the aOR.

Conclusions
In cN0 EBC with post-PST SLN+, non-SLN+ at ALND are infrequent (~22%) and independently associated to PR levels and macrometastatic SLN. ALND-predict multiparametric score accurately predicted absence of non-SLN involvement, identifying most patients who could be safely spared unnecessary ALND. Prospective validation is required.
Highly Luminescent Aluminum Complex with β-Diketone Ligands Exhibiting Near-Unity Photoluminescence Quantum Yield, Thermally Activated Delayed Fluorescence, and Rapid Radiative Decay Rate Properties in Solution-Processed Organic Light-Emitting Devices
Authors: Matsuya Misaki , Sasabe Hisahiro , Sumikoshi Shunsuke , Hoshi Keigo , Nakao Kohei , Kumada Kengo , Sugiyama Ryo , Sato Ryoma , Kido Junji 
Published: February 2023

Abstract
A highly luminescent mononuclear Al complex with β-diketone ligands exhibiting superior thermally activated delayed fluorescence (TADF) properties was developed in this work. The complex showed yellow emission with promising photofunctions, including a near-unity photoluminescence quantum yield (PLQY), a rapid radiative decay rate, and a short delayed fluorescence lifetime in the solid state. When applied in a solution-processed organic light-emitting device, an external quantum efficiency (EQE) exceeding 18% and a low turn-on voltage of 2.9 V at 1 cd/m2 were obtained, surpassing those of the corresponding β-diketone ligand. Metal complexation with Al generated unique electronic structures that significantly strengthened the photofunctions of the original β-diketone ligand in the solid state.
The added value of brain MR spectroscopy in children with Crigler-Najjar syndrome type-I: correlation with demographic, neurodevelopmental, and laboratory findings
Authors: Alnaghy Eman , Taman Saher , Abdelhalim Ebrahim , Abdel Razek Ahmed , El-Shabrawi Mortada , Ezz El Regal Mohamed , Megahed Ahmed , Elzeny Sherine , El Tantawi Noha 
Published: February 2023

Objective The aim of this study is to demonstrate the role of proton magnetic resonance spectroscopy (1H-MRS) in the detection of brain microstructural changes in patients with Crigler-Najjar syndrome type-I (CNs-I), and its correlation with demographic, neurodevelopmental and laboratory findings. Methods Prospective study was conducted on 25 children with CNs-I and 25 age and sex-matched children, who served as control. They underwent multivoxel 1H-MRS of basal ganglion at echo time 135–144 ms. N-acetyl aspartate/Creatine (NAA/Cr) and Choline (Ch)/Cr were calculated and correlated with demographic, clinical, and laboratory findings of patients with CNs-I. Results There was a significant difference in NAA/Cr and Ch/Cr between patients and controls. The cut-off value for NAA/Cr and Ch/Cr used to differentiate patients from controls were 1.8 and 1.2 with an area under the curve (AUC) of 0.91 and 0.84 respectively. There was a significant difference in MRS ratios between patients with neurodevelopmental delay (NDD) and patients without NDD. The cut-off values for NAA/Cr and Ch/Cr used to differentiate between patients with NDD and patients without NDD were 1.47 and 0.99, with AUC of 0.87 and 0.8 respectively. The NAA/Cr and Ch/Cr were well correlated with family history (p = 0.006 and p < 0.001) respectively, consanguinity (p < 0.001 and p = 0.001), neurodevelopmental delay (p = 0.001 and p = 0.004), serum bilirubin level (r = −0.77, p < 0.001), (r = −0.49, p = 0.014), phototherapy (p < 0.001 and p = 0.32), blood transfusion (p < 0.001 and p = 0.001) respectively. Conclusion 1H-MRS can be a useful tool in the detection of neurological changes in patients with CNs-I; NAA/Cr and Ch/Cr parameters are well correlated with demographic, clinical, and laboratory findings. Advances in knowledge Our study is the first report on using MRS in assessing neurological manifestations in CNs. 1H-MRS can be a useful tool in the detection of neurological changes in patients with CNs-I.
T1 based oxygen-enhanced MRI in tumours; a scoping review of current research
Authors: McCabe Alastair , Martin Stewart , Shah Jagrit , Morgan Paul S , Panek Rafal 
Published: February 2023

Objective: Oxygen-enhanced MRI (OE-MRI) or tissue oxygen-level dependent (TOLD) MRI is an imaging technique under investigation for its ability to quantify and map oxygen distributions within tumours. The aim of this study was to identify and characterise the research into OE-MRI for characterising hypoxia in solid tumours. Methods: A scoping review of published literature was performed on the PubMed and Web of Science databases for articles published before 27 May 2022. Studies imaging solid tumours using proton-MRI to measure oxygen-induced T1/R1 relaxation time/rate changes were included. Grey literature was searched from conference abstracts and active clinical trials. Results: 49 unique records met the inclusion criteria consisting of 34 journal articles and 15 conference abstracts. The majority of articles were pre-clinical studies (31 articles) with 15 human only studies. Pre-clinical studies in a range of tumour types demonstrated consistent correlation of OE-MRI with alternative hypoxia measurements. No clear consensus on optimal acquisition technique or analysis methodology was found. No prospective, adequately powered, multicentre clinical studies relating OE-MRI hypoxia markers to patient outcomes were identified. Conclusion: There is good pre-clinical evidence of the utility of OE-MRI in tumour hypoxia assessment; however, there are significant gaps in clinical research that need to be addressed to develop OE-MRI into a clinically applicable tumour hypoxia imaging technique. Advances in knowledge: The evidence base of OE-MRI in tumour hypoxia assessment is presented along with a summary of the research gaps to be addressed to transform OE-MRI derived parameters into tumour hypoxia biomarkers.
MRI-based cephalometrics: a scoping review of current insights and future perspectives
Authors: Sennimalai Karthik , Selvaraj Madhanraj , Kharbanda Om Prakash , Kandasamy Devasenathipathy , Mohaideen Kaja 
Published: February 2023

Objective: This review aims to explore the current status of magnetic resonance imaging (MRI) as a cephalometric tool, summarize the equipment design and methods, and propose recommendations for future research. Methods: A systematic search was conducted in electronic databases, including PubMed, Ovid MEDLINE, Scopus, Embase, Web of Science, EBSCOhost, LILACS, and Cochrane Library, using broad search terms. The articles published in any language till June 2022 were considered. Cephalometric studies conducted using the MRI dataset on human participants, phantom or cadaver were included. Two independent reviewers assessed the final eligible articles using the quality assessment score (QAS). Results: Nine studies were included in the final assessment. Studies used various methods, including 1.5 T or 3 T MRI systems and 3D or 2D MRI datasets. Among the imaging sequences, T1-weighted, T2-weighted and black bone MR images were used for cephalometric analysis. In addition, the reference standards varied among studies, such as traditional 2D cephalogram, cone-beam CT and phantom measurements. The mean QAS of all the included studies was 79% (± 14.4%). The main limitation of most studies was the small sample size and the heterogeneity of the methods, statistical tools used, and metric outcomes assessed. Conclusions: Despite the heterogeneity and lack of metrological evidence on the effectiveness of MRI-based cephalometric analysis, the preliminary results demonstrated by in vivo and in vitro studies are encouraging. However, future studies exploring MRI sequences specific to cephalometric diagnosis are required for wider adoption of this technique in routine orthodontic practice.
Personal exposures to fine particulate matter and carbon monoxide in relation to cooking activities in rural Malawi
Authors: Saleh Sepeedeh , Sambakunsi Henry , Makina Debora , Chinouya Martha , Kumwenda Moses , Chirombo James , Semple Sean , Mortimer Kevin , Rylance Jamie 
Published: February 2023

Background: Air pollution is a major environmental risk factor for cardiorespiratory disease. Exposures to household air pollution from cooking and other activities, are particularly high in Southern Africa. Following an extended period of participant observation in a village in Malawi, we aimed to assess individuals’ exposures to fine particulate matter (PM2.5) and carbon monoxide (CO) and to investigate the different sources of exposure, including different cooking methods. Methods: Adult residents of a village in Malawi wore personal PM2.5 and CO monitors for 24-48 hours, sampling every 1 (CO) or 2 minutes (PM2.5). Subsequent in-person interviews recorded potential exposure details over the time periods. We present means and interquartile ranges for overall exposures and summaries stratified by time and activity (exposure). We employed multivariate regression to further explore these characteristics, and Spearman rank correlation to examine the relationship between paired PM2.5 and CO exposures. Results: Twenty participants (17 female; median age 40 years, IQR: 37–56) provided 831 hours of paired PM2.5 and CO data. Concentrations of PM2.5 during combustion activity, usually cooking, far exceeded background levels (no combustion activity): 97.9μg/m3 (IQR: 22.9–482.0), vs 7.6μg/m3, IQR: 2.5–20.6 respectively. Background PM2.5 concentrations were higher during daytime hours (11.7μg/m3 [IQR: 5.2–30.0] vs 3.3μg/m3 at night [IQR: 0.7–8.2]). Highest exposures were influenced by cooking location but associated with charcoal use (for CO) and firewood on a three-stone fire (for PM2.5). Cooking-related exposures were higher in more ventilated places, such as outside the household or on a walled veranda, than during indoor cooking. Conclusions: The study demonstrates the value of combining personal PM2.5 exposure data with detailed contextual information for providing deeper insights into pollution sources and influences. The finding of similar/lower exposures during cooking in seemingly less-ventilated places should prompt a re-evaluation of proposed clean air interventions in these settings.
The Effect of Managers on Systematic Risk
Authors: Schoar Antoinette , Yeung Kelvin , Zuo Luo 
Published: February 2023

Tracking the movement of top managers across firms, we document the importance of manager-specific fixed effects in explaining heterogeneity in firm exposures to systematic risk. In equilibrium, manager fixed effects on systematic risk are positively related with manager fixed effects on stock returns. These differences in systematic risk are partially explained by managers’ corporate strategies, such as their preferences for internal growth and financial conservatism. The early career experiences of managers starting their first job in a recession also contribute to differential loadings on systematic risk. These effects are more pronounced when managers wield more influence, as in smaller firms and firms that do not have an independent board. Overall, our results suggest that managers play an important role in shaping a firm’s systematic risk. This paper was accepted by Victoria Ivashina, finance. Funding: A. Schoar acknowledges financial support from the MIT Sloan School of Management. K. Yeung acknowledges financial support from City University of Hong Kong and the Cornell SC Johnson College of Business. L. Zuo acknowledges financial support from the Cornell SC Johnson College of Business and the University of Toronto Roger Martin Award for Emerging Leaders. Supplemental Material: Data and the online appendix are available at https://doi.org/10.1287/mnsc.2023.4710 .
Chitosan from crab shell waste for soft lithography of bioplastic diffraction gratings
Authors: Gumayan Efren G. , Dimzon Ian Ken D. , Guerrero Raphael A. 
Published: February 2023

Bioplastic diffraction gratings are fabricated from chitosan prepared from crab shells through a soft lithography replication process. Atomic force microscopy and diffraction experiments with the chitosan grating replicas indicate the successful copying of periodic nanoscale groove structures corresponding to densities of 600 and 1200 lines/mm. First-order efficiency of bioplastic gratings is comparable to the output of elastomeric grating replicas.
Nanosensor and slow light based on quintuple Fano resonances in a metal–insulator–metal waveguide coupled with a concentric-ring resonator
Authors: Chen F. , Yang W. X. 
Published: February 2023

In this paper, quintuple Fano resonances are produced and numerically analyzed based on
a plasmonic resonator system. The system is composed of an optical
metal–insulator–metal (MIM) waveguide, a side-coupled
disk, and a concentric-ring resonator. Five Fano resonances can be
seen, which originate from the interaction of the cavity mode between
the disk resonator and the concentric-ring resonator. The transmission
spectrum shows that the Fano resonance can be independently tuned by
changing different geometrical parameters, such as the outer radius or
inner radius of the concentric-ring resonator. The refractive index
sensitivity is 1250nm/RIU for FR5, and the figure of merit is
138.9 (RIU is a refractive index unit). It can also serve as a
temperature sensor with a maximum sensitivity of about 0.4nm/∘C. Moreover, for slow light, the
maximum delay time is about 0.12 ps at FR3. The proposed
nano-scale structure has a sharp Fano line shape and effective ways of
tuning independently, which may have applications in slow light and
nano-biosensing; for example, we show the application of the detection
of different human blood types.
Instabilities in a CO2Laser with Feedback on Intracavity E-O Modulator
Authors: Gadomski W. , Salieri P. , Arecchi F.T. , Meucci R. 
Published: February 2023

In a homogeneously broadened CO2laser [1] only the polarization can be adiabatically eliminated (class B lasers), so that the dynamics is ruled by two rate equations for the field and population inversion (

I
=

E
2

/

E
s
2

is the field squared and normalized to saturation intensity

E
S
2

=

γ
⊥

γ

IL

4

g
2

,
G
=
2

g
2

/

γ
1

is the coupling factor, d is the population inversion normalized to the pump value Δo, with g = wµ2/ħϵoV and γ1, γILfor the polarization and population inversion decay rates).