bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between COVID-19 care and burnout among postgraduate clinical residents in Japan: a nationwide cross-sectional study
Authors: Nishizaki Yuji , Nagasaki Kazuya , Shikino Kiyoshi , Kurihara Masaru , Shinozaki Tomohiro , Kataoka Koshi , Shimizu Taro , Yamamoto Yu , Fukui Sho , Nishiguchi Sho , Katayama Kohta , Kobayashi Hiroyuki , Tokuda Yasuharu
Published: January 2023

Objective

The relationship between the care of patients with COVID-19 and mental health among resident physicians in Japan is imperative for ensuring appropriate care of patients with COVID-19 and should be clarified. We herein assessed the relationship between the care of patients with COVID-19 and mental health among postgraduate year 1 (PGY-1) and PGY-2 resident physicians and factors associated with mental health.

Design

This nationwide cross-sectional study analysed data obtained using the clinical training environment self-reported questionnaire.

Setting

An observational study across Japan among resident physicians (PGY-1 and PGY-2) from 583 teaching hospitals.

Participants

Examinees who took the general medicine in-training examination of academic year 2020.

Primary and secondary outcome measures

The Patient Health Questionnaire and Mini-Z 2.0 were used to assess mental health, and experience of caring for patients with COVID-19 was divided into three groups (none, 1–10 and ≥11). The prevalence of mental conditions in the three groups was compared using the ‘modified’ Poisson generalised estimating equations by adjusting for prefecture-level, hospital-level and resident-level variables.

Results

Of the 5976 participants analysed, 50.9% were PGY-1. The prevalence of burnout was 21.4%. Moreover, 47.0% of all resident physicians had no experience in the care of patients with COVID-19. The well-experienced group accounted for only 7.9% of the total participants. A positive association was found between the number of caring patients with COVID-19 and burnout (prevalence ratio 1.25; 95% CI 1.02 to 1.53). Moreover, the shortage of personal protective equipment was identified as a major contributor to burnout (prevalence ratio 1.60; 95% CI 1.36 to 1.88).

Conclusions

Resident physicians who experienced more care of patients with COVID-19 had slightly greater burnout prevalence than those who did not. Approximately half of resident physicians did not participate in the care of patients with COVID-19, which posed a challenge from an educational perspective.
Precision medicine in laryngeal cancer: protocol of the laryngeal cancer cohort (LARCH)
Authors: Hamilton David Winston , O’Hara James , Rajgor Amarkumar , Selby Gerald , Anderson Mhairi , Keltie Kim , Parker Rosalyn , Teare Dawn , Patterson Joanne , Jones Terry M , Sharp Linda
Published: January 2023

Introduction

Laryngeal cancer disproportionately affects socioeconomically disadvantaged patients. Treatment can render a patient nil by mouth or in need of a permanent tracheostomy. In the past 30 years, survival has remained at best static and at worst it has declined. Currently, there is no method of prognosticating how a patient will respond to treatment.

The LARyngeal Cancer coHort (LARCH) aims to establish how survival and quality-of-life outcomes compare between surgery and (chemo)radiotherapy in early and advanced laryngeal cancer and how the presenting features of laryngeal cancer influence oncological, functional and quality-of-life outcome.

Methods and analysis

This study is the first enhanced laryngeal cancer disease cohort. In the initial phase, we aim to deliver a prospective cohort study of 150 patients in 8 centres over a 3-year period.

Patient, tumour, quality-of-life and laryngeal functional data will be collected from patients with squamous cell carcinoma of the larynx at baseline, 6, 12 and 24 months. Multiple logistic regression analyses will be used to quantify locoregional control and identify factors associated with control overall and by treatment modality and identify factors associated with quality of life overall and by treatment modality.

Ethics and dissemination

Most interventions take place as part of routine care, with LARCH providing a mechanism for recording this data centrally. When successfully recruiting in the North of England, we plan to roll out LARCH nationwide; in the future, LARCH can be used as a trial platform in the disease. The results will be submitted for publication in high-impact international peer-reviewed journals and presented to scientific meetings. Access to the anonymised LARCH dataset by other researchers will be publicised and promoted.

Trial registration number

ISRCTN27819867.
Differences in patient characteristics, clinical practice and outcomes of cardiac implantable electric device therapy between Japan and the USA: a cross-sectional study using data from nationally representative administrative databases
Authors: Tonegawa-Kuji Reina , Inoue Yuko Y , Nakai Michikazu , Kanaoka Koshiro , Sumita Yoko , Miyazaki Yuichiro , Wakamiya Akinori , Shimamoto Keiko , Ueda Nobuhiko , Nakajima Kenzaburo , Wada Mitsuru , Kamakura Tsukasa , Yamagata Kenichiro , Ishibashi Kohei , Miyamoto Koji , Nagase Satoshi , Aiba Takeshi , Miyamoto Yoshihiro , Iwanaga Yoshitaka , Kusano Kengo
Published: January 2023

Objectives

To identify differences in patient characteristics, clinical practice and outcomes of cardiac implantable electronic device (CIED) therapy between Japan and the USA.

Design

A cross-sectional study.

Setting

Nationally representative administrative databases from Japan and the USA containing hospitalisations with first-time implantations of pacemakers, implantable cardioverter-defibrillators (ICD) and cardiac-resynchronisation therapy with or without defibrillators (CRTP/CRTD).

Participants

Patients hospitalised with first-time implantations of CIEDs.

Outcome measures

In-hospital mortality, in-hospital complication and 30-day readmission rates.

Results

Overall, 107 339 (median age 78 (71–84), 48 415 women) and 295 584 (age 76 (67–83), 127 349 women) records with CIED implantations were included from Japan and the USA, respectively. Proportion of women in defibrillator recipients was lower in Japan than in the USA (ICD, 21% vs 28%, p<0.001; CRTD, 24% vs 29%, p<0.001). Length of stay after CIED implantation was longer in Japan than in the USA for all device types (conventional pacemaker, 8(7–11) vs 1 (1–3) days, p<0.001; leadless pacemaker, 5 (3–9) vs 2 (1–5) days, p<0.001; ICD, 8 (7–11) vs 1 (1–3) days, p<0.001, CRTP, 9 (7–13) vs 2 (1–4) days, p<0.001; CRTD, 9 (8–14) vs 2 (1–4) days, p<0.001). In-hospital mortality after CIED implantation was similar between Japan and the USA ((OR) (95% CI), conventional pacemaker 0.58 (0.83 to 1.004); ICD 0.77 (0.57 to 1.03); CRTP 0.85 (0.51 to 1.44); CRTD 1.11 (0.81 to 1.51)), except that after leadless pacemaker implantation in Japan was lower than that in the USA (0.32 (0.23 to 0.43)). 30-day readmission rates were lower in Japan than in the USA for all device types (conventional pacemaker 0.55 (0.53 to 0.57); leadless pacemaker 0.50 (0.43 to 0.58); ICD 0.54 (0.49 to 0.58); CRTP 0.51 (0.42 to 0.62); CRTD 0.57 (0.51 to 0.64)).

Conclusions

International variations in patient characteristics, practice and outcomes were observed. In-hospital mortality after CIED implantation was similar between Japan and the USA, except in cases of leadless pacemaker recipients.
DirEct versus VIdeo LaryngosCopE (DEVICE): protocol and statistical analysis plan for a randomised clinical trial in critically ill adults undergoing emergency tracheal intubation
Authors: Prekker Matthew E , Driver Brian E , Trent Stacy A , Resnick-Ault Daniel , Seitz Kevin , Russell Derek W , Gandotra Sheetal , Gaillard John P , Gibbs Kevin W , Latimer Andrew , Whitson Micah R , Ghamande Shekhar , Vonderhaar Derek J , Walco Jeremy P , Hansen Sydney J , Douglas Ivor S , Barnes Christopher R , Krishnamoorthy Vijay , Bastman Jill J , Lloyd Bradley Daniel , Robison Sarah W , Palakshappa Jessica A , Mitchell Steven , Page David B , White Heath D , Espinera Alyssa , Hughes Christopher , Joffe Aaron M , Herbert J Taylor , Schauer Steven G , Long Brit J , Imhoff Brant , Wang Li , Rhoads Jillian P , Womack Kelsey N , Janz David , Self Wesley H , Rice Todd W , Ginde Adit A , Casey Jonathan D , Semler Matthew W
Published: January 2023

Introduction

Among critically ill patients undergoing orotracheal intubation in the emergency department (ED) or intensive care unit (ICU), failure to visualise the vocal cords and intubate the trachea on the first attempt is associated with an increased risk of complications. Two types of laryngoscopes are commonly available: direct laryngoscopes and video laryngoscopes. For critically ill adults undergoing emergency tracheal intubation, it remains uncertain whether the use of a video laryngoscope increases the incidence of successful intubation on the first attempt compared with the use of a direct laryngoscope.

Methods and analysis

TheDirEct versusVIdeo LaryngosCopE(DEVICE) trial is a prospective, multicentre, non-blinded, randomised trial being conducted in 7 EDs and 10 ICUs in the USA. The trial plans to enrol up to 2000 critically ill adults undergoing orotracheal intubation with a laryngoscope. Eligible patients are randomised 1:1 to the use of a video laryngoscope or a direct laryngoscope for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is the incidence of severe complications between induction and 2 min after intubation, defined as the occurrence of one or more of the following: severe hypoxaemia (lowest oxygen saturation <80%); severe hypotension (systolic blood pressure <65 mm Hg or new or increased vasopressor administration); cardiac arrest or death. Enrolment began on 19 March 2022 and is expected to be completed in 2023.

Ethics and dissemination

The trial protocol was approved with waiver of informed consent by the single institutional review board at Vanderbilt University Medical Center and the Human Research Protection Office of the Department of Defense. The results will be presented at scientific conferences and submitted for publication in a peer-reviewed journal.

Trial registration number

ClinicalTrials.gov Registry (NCT05239195).
Ultrasensitive electrochemical phosphate detection by pyridine–zinc(II) complex
Authors: Browne Kailey , Pei Yu , Singh Ishwar , Payne Sarah Jane , She Zhe
Published: January 2023

Phosphorous is an important environmental health parameter as the availability of phosphorus within water systems plays an essential role in the prevalence of harmful algal blooms (cyanobacteria blooms). Currently, phosphates are detected using sensitive chromatographic and colorimetric techniques; however, major disadvantages stem from the lack of anion selectivity in samples with complex matrices, as well as the high cost of analysis. Electrochemical techniques utilizing self-assembled monolayers can provide a cheaper yet sensitive method of detection. This work explores the modification of a gold working electrode using pyridine–zinc(II) complexes. The implementation of self-assembled monolayers allows for an ultrasensitive and selective method of indirect detection of the H2PO4 − species, ranging in concentrations between 0.0 and 1.2 fmol/L phosphate. Electrochemical techniques such as cyclic voltammetry and square-wave voltammetry were explored for their phosphate-detection abilities, with detection limits of 4.0 × 10−16 and 9.0 × 10−17 mol/L H2PO4 −, respectively. X-ray photoelectron spectroscopy measurements were also taken to confirm the modification of the electrode. The selectivity of this sensor towards phosphate anions was successfully explored for this sensor in the presence of potential interfering agents (sulfate, chlorine, carbonate, fluoride, nitrite, and hypochlorite ions), and applicability of sensor was also explored through the detection of phosphate in a tap and lake water sample.
On possible composite structure of scalar fields in expanding universe
Authors: Zheltukhin A. A.
Published: January 2023

Scalar fields in curved backgrounds are assumed to be composite objects. As an example realizing such a possibility we consider a model of the massless tensor field $$l_{\mu \nu }(x)$$

l

μ
ν

(
x
)

in a 4-dim. background $$g_{\mu \nu }(x)$$

g

μ
ν

(
x
)

with spontaneously broken Weyl and scale symmetries. It is shown that the potential of $$l_{\mu \nu }$$

l

μ
ν

, represented by a scalar quartic polynomial, has the degenerate extremal described by the composite Nambu–Goldstone scalar boson $$\phi (x):=g^{\mu \nu }l_{\mu \nu }$$

ϕ

(
x
)

:
=

g

μ
ν

l

μ
ν

. Removal of the degeneracy shows that $$\phi $$
ϕ
acquires a non-zero vev $$\langle \phi \rangle _{0}=\mu $$

⟨
ϕ
⟩

0

=
μ

which, together with the free parameters of the potential, defines the cosmological constant. The latter is zero for a certain choice of the parameters.
Retailer Information Sharing Strategy with Counterfeiter Encroachment
Authors: Yu Mingzhu , Gao Qi , Yi Zelong
Published: January 2023

In this paper, we examine the retailer’s information sharing decision in an authentic supply chain with a single supplier and a single retailer under different counterfeiter encroachment situations. We propose a Stackelberg game model to analyze the optimal wholesale price of the supplier, the optimal order quantity of the retailer and the optimal production quantity of the counterfeiter. We obtain the information sharing strategies of the retailer and analyze the impact of the counterfeiter on the authentic supply chain. It is revealed that: (1) under certain conditions, the retailer will voluntarily share information with the upstream supplier and (2) the existence of the counterfeiter may increase the profit of the authentic supply chain.
The k-Sombor Index of Trees
Authors: Wang Fangxia , Wu Baoyindureng
Published: January 2023

For a positive real number [Formula: see text], the [Formula: see text]-Sombor index of a graph [Formula: see text], introduced by Réti et al, is defined as [Formula: see text] where [Formula: see text] denotes the degree of the vertex [Formula: see text] in [Formula: see text]. By the definition, [Formula: see text] is exactly the Sombor index of [Formula: see text], while [Formula: see text] is the first Zagreb index of [Formula: see text].

In this paper, for [Formula: see text] we present the extremal values of the [Formula: see text]-Sombor index of trees with some given parameters, such as matching number, the number of pendant vertices, diameter. This generalizes the relevant results on Sombor index due to Chen, Li and Wang ((2002). Extremal values on the Sombor index of trees, MATCH Communications in Mathematical and in Computer Chemistry, 87, 23–49).

Handling [Formula: see text] appears to be different for [Formula: see text] in contrast to the case when [Formula: see text]. To demonstrate this, we also characterize the extremal trees with respect to the [Formula: see text] with matching number, the number of pendant vertices and diameter. In addition, three relevant conjectures are proposed.
Radiation reaction on an accelerating point charge
Authors: Franklin Jerrold
Published: January 2023

A point charge accelerating under the influence of an external force emits electromagnetic radiation that reduces the increase in its mechanical energy. This causes a reduction in the particle’s acceleration. We derive the decrease in acceleration due to radiation reaction for a particle accelerating parallel to its velocity, and show that it has a negligible effect.
A brief history of the Jacobian
Authors: Brezis Haïm , Mawhin Jean , Mironescu Petru
Published: January 2023

In his pioneering work, Jacobi discovered two remarkable identities related to the Jacobian. The first one asserts that the Jacobian has a divergence structure. The second one, that some vector fields involving the cofactors of the Jacobian are divergence free. We illustrate the fundamental impact of these properties on research, from the times of Jacobi to our days.
Interpolation of curves on Fano hypersurfaces
Authors: Ran Ziv
Published: January 2023

On a general hypersurface of degree [Formula: see text] in [Formula: see text] or [Formula: see text] itself, we prove the existence of curves of any genus and high enough degree depending on the genus passing through the expected number [Formula: see text] of general points or incident to a general collection of subvarieties of suitable codimensions. In some cases, we also show that the family of curves through [Formula: see text] fixed points has general moduli as family of [Formula: see text]-pointed curves. These results imply positivity of certain intersection numbers on Kontsevich spaces of stable maps. An arithmetical Appendix A by Chang describes the set of numerical characters ([Formula: see text], curve degree, genus) to which our results apply.
Hardware in loop network simulators — An insight overview
Authors: Sushanth G. , Ravish Aradhya H. V.
Published: January 2023

Network simulation is a method of using software or a tool which can be used to mimic the network conditions that exist in pre-defined places. This kind of simulation allows the developers, designers, researchers and the network planners to intelligently plan, design, develop and test their applications or research work in changing network conditions. With varying network conditions either because of wireless nature or because of user mobility, it is very difficult to simulate the exact network conditions with the existing network simulators. These network simulators are flexible, re-usable and reliable. But they have a limitation of not being able to replicate the actual network conditions in the laboratories. This calls for a system in the loop or hardware in the loop concept to be extended to the network simulators. The idea of system in the loop is not new. In this paper, an overview with the fundamental understanding of the hardware-in-loop concept for network simulators, their applications and a review of the existing hardware-in-loop network simulators with their advantages and disadvantages is presented.
Formation of Major Types of Galaxies Based on the Energy Circulation Theory
Authors: Nagao Shigeto
Published: January 2023

The standard cosmology can answer almost nothing about how the structure of a galaxy is formed. It expects a supermassive black hole at the center and dark matter in the halo to explain the circulation of stars and its velocity. However, why the visible matters are distributed in such a thin plane by the interaction with the black hole while dark matter results in a spherical distribution is a critical open question for a disc galaxy. How the elliptical, ring, and long-barred galaxies are formed is unknown either. Here, we repot simulations of structures of galaxies according to our galactic evolution model based on the energy circulation theory. The theory claims the fundamental force to work between momentums, by which various energy circulations are formed. After terminating cyclic decompositions to lower-level circulations and separations to two ones by the space expansion, a resulted circulation (galactic seed) starts to release lower-level circulations (stellar seeds). Linear releases of stellar seeds from an isolated single galactic seed show an elliptical galaxy. Simultaneous releases on the whole circumference result in stellar seeds in a ring, where the seeds continue to circulate even if the ring radius increases. Intermittent ring releases from a single galactic seed provide a disc galaxy. Ring releases from separate binary galactic seeds form a barred ring galaxy, while linear releases from binary ends give a barred arm galaxy. Ring releases from attached two galactic seeds form a double-disc galaxy. If the two seeds rotate, spiral arms come out.
During the COVID-19 Pandemic, Everyone Had a Head-up Display
Authors: Starner Thad
Published: January 2023

A head-up display has been part of my daily life for more than two decades, and people often ask why I wear one. This article makes explicit some of the benefits of video conferencing and shows how a head-worn display provides similar benefits when physically co-present in a conversation.
The Role of Phase-Separated Condensates in Fusion Oncoprotein–Driven Cancers
Authors: Shirnekhi Hazheen K. , Chandra Bappaditya , Kriwacki Richard W.
Published: January 2023

Fusion oncoproteins (FOs) resulting from in-frame chromosomal translocations are associated with many aggressive cancers with poor patient outcomes. Several FOs are now understood to perform their oncogenic functions within biomolecular condensates formed through liquid-liquid phase separation (LLPS). Two classes of phase-separating FOs have emerged, those that form nuclear condensates and alter chromatin biology, including gene expression, and those that form cytoplasmic condensates and promote aberrant signaling, including RAS/MAPK signaling. The amino acid sequences of the FOs within these classes display LLPS-prone intrinsically disordered regions and folded domains that synergistically interact with themselves and other biomolecules to promote condensate formation. This review summarizes the roles of LLPS in the oncogenic functions of these two FO classes, provides examples of FOs that inhibit physiological LLPS in normal cells, and discusses the sequence features commonly associated with LLPS and their enrichment in many FOs.
Rheology and Permeability of Self-Compacting Concretes with Recycled Blue Aggregate
Authors: Al-Kerttani Osamah , Muttar Ammar , Abdulhussain Sana
Published: January 2023

Since the sustainability of concrete became a very important property in the past decades, 15 mixes of self-compacting concrete (SCC), as well as control mixes, were examined to find out the effect of replacing natural aggregates with recycled blue glass (RBG) waste on the rheological properties and permeability of self-compacting concrete. For this purpose, 3 series of SCCs were mixed: the 1st group replaced the natural aggregate (NFA) with fine recycled waste blue glass (RFWBG), the 2nd group replaced the natural coarse aggregate (NCA) with coarse recycled waste blue glass (RCWBG), and the last group replaced the natural aggregate with recycled blue glass (RGA). Each group contains 5 ratios of replacement (0%, 20%, 40%, 60%, 80%, and 100%). The results showed that the torque increased with the increase in recycled green glass replacement; for instance, it increased from 0.95 for control mixes to 1.302, 1.384, and 1.459 Nm for 100% replacement in the 1st, 2nd, and 3rd groups. Meanwhile, the permeability tests include chloride ion permeability (RCPT), a water sorptivity test, and a gas permeability test at 28 days; likewise, this study showed that these characteristics increase with the increase of recycled blue glass.
Correlation between the Severity of Metabolic Dysfunction-Associated Fatty Liver Disease and Serum Uric Acid to Serum Creatinine Ratio
Authors: Liu Jing , Peng Hongye , Wang Che , Wang Yutong , Wang Rongrui , Liu Jixiang , Zhou Tianhui , Yao Shukun
Published: January 2023

Purpose. As one of the most common chronic liver diseases, metabolic dysfunction-associated fatty liver disease (MAFLD) had different prognoses between mild and moderate-severe levels. Serum uric acid to serum creatinine ratio (sUA/Cr) can reflect the overall metabolic status of the body. To explore a convenient indicator to screen MAFLD and distinguish the severity of the disease, this study analyzed the correlation between sUA/Cr and the severity of MAFLD. Methods. 228 participants were enrolled and divided into 2 groups, including mild MAFLD and non-MAFLD group and moderate-severe MAFLD group, based on liver/spleen computed tomography (CT) ratios. The correlations between sUA/Cr and the severity of MAFLD were analyzed by logistic and linear regression. Receiver operating characteristics (ROCs) analyzed the predictive ability of sUA/Cr for the severity of MAFLD expressed by the area under curve (AUC). Results. The level of sUA/Cr was higher in themoderate-severe MAFLD group than mild MAFLD and non-MAFLD group (6.14 ± 1.55 vs. 5.51 ± 1.19,

P
=
0.008

). After adjustment for confounders, the correlation analysis showed that patients with elevated sUA/Cr had a higher risk of moderate-severe MAFLD (OR: 1.350,

P
=
0.036

). A higher sUA/Cr level was associated with lower liver CT values (β = −0.133,

P
=
0.039

) and liver/spleen CT ratio (β = −0.154,

P
=
0.016

). sUA/Cr had the ability to discriminate the severity of MAFLD (AUC: 0.623). Conclusion. sUA/Cr was positively associated with the risk of moderate-severe MAFLD and had the predictive ability to discriminate the moderate-severe MAFLD from mild MAFLD and non-MAFLD. The sUA/Cr level was suggested to be monitored and controlled in the screening and treatment of MAFLD.
Green Synthesis Method of ZnO Nanoparticles using Extracts of Zingiber officinale and Garlic Bulb (Allium sativum) and Their Synergetic Effect for Antibacterial Activities
Authors: Kebede Urge Solomon , Tiruneh Dibaba Solomon , Belay Gemta Abebe
Published: January 2023

In this paper, antibacterial activities of zinc oxide (ZnO) nanoparticles synthesized through green method using garlic bulb (Allium sativum), ginger (Zingiber officinale) extracts, and their mixture are reported. The synthesized ZnO NPs were characterized by X-ray diffraction (XRD), ultraviolet visible (UV–vis), photoluminescence (PL), spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The crystalline sizes of ZnO NPs synthesized using garlic bulb (Allium sativum) extract, ginger (Zingiber officinale) root extract, and their mixture were 19.8, 21.94, and 23.86 nm, respectively. Similarly, the corresponding peak absorbances were 369.5, 377.5, and 374 nm, respectively. The antibacterial activities of synthesized ZnO NPs were tested against gram-negative bacteria Escherichia coli (E. coli) and Pseudomonas putida (P. putida) and gram-positive bacteria Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes). The ZnO NPs synthesized using the mixture of garlic bulb (Allium sativum) and ginger (Z. officinale) root extract have shown maximum inhibition zone against gram-negative bacteria (P. putida: 28.67 ± 0.82 mm) and gram-positive bacteria (S. pyogenes: 10.67 ± 0.47 mm) as compared to ZnO NPs synthesized using the two extracts separately. On the other hand, ZnO NPs obtained from garlic bulb and Z. officinale root extracts exhibited maximum inhibition zone against E. coli (19 ± 0.82 mm) and S. aureus (16.4 ± 0.47 mm), respectively.
SPRR3 Contributes to Aggressiveness of Pancreatic Cancer Cells via NF‐κB Signaling Pathway
Authors: Xie Yuankang , Li Heping , Zhong Baiyin , Zhu Xiansen , Ye Rong , Xie Binhui , Zhang Jianhong
Published: January 2023

Pancreatic cancer remains a deadly solid tumor with worst survival, and a better understanding of the mechanisms of carcinogenesis of pancreatic cancer is critical to promote the survival of patients with pancreatic cancer. qPCR and western blot assay were used to determine the expression of SPRR3 in pancreatic cancer. Anchorage‐independent growth ability, BrdU labeling, Transwell assay, and in vivo experiment were used to examine the functions of SPRR3 in aggressiveness of pancreatic cancer. Luciferase reporter assay, nucleoplasmic‐separation technique, qPCR, and western blot assay were used to investigate the mechanism of SPRR3 regulating aggressiveness of pancreatic cancer. Our results showed that SPRR3 was significantly increased in pancreatic cancer, which resulted in poor survival for patients with pancreatic cancer. Further analysis showed that overexpression of SPRR3 contributed to anchorage‐independent growth ability, growth rate, and invasion ability of pancreatic cancer cells. While, knockdown of SPRR3 showed the reverse results. Mechanistically, overexpression of SPRR3 can promote the transcription of NF‐κB pathway, nuclear accumulation of p65, and mRNA levels of NF‐κB pathway downstream genes. But, knockdown of SPRR3 induced the reverse results. The above findings clarified the important roles of SPRR3 in the progression of pancreatic cancer through NF‐κB pathway. And targeting SPRR3 might be an effective strategy to therapy pancreatic cancer.
SETDB1 Modulates Degradation of Phosphorylated RB and Anticancer Efficacy of CDK4/6 Inhibitors
Authors: Huang Zhenlin , Li Xiang , Tang Bo , Li Hao , Zhang Jianong , Sun Rui , Ma Jian , Pan Yunqian , Yan Binyuan , Zhou Yingke , Ding Donglin , Yan Yuqian , Jimenez Rafael , Orme Jacob J. , Jin Xin , Yang Jinjian , Huang Haojie , Jia Zhankui
Published: January 2023

Retinoblastoma (RB) protein can exert tumor suppressor functions even when it becomes phosphorylated. It is thus essential to understand how phosphorylated RB (p-RB) expression and function are regulated. Here, we demonstrated that RING finger domain protein TRIM28 bound and promoted ubiquitination and degradation of CDK4/6-phosphorylated RB protein. SETDB1, a known TRIM28 binding partner, protected p-RB from degradation through the binding of methylated RB by its Tudor domain independent of its methyltransferase activity. SETDB1 was found to be frequently overexpressed due to gene amplification and positively correlated with p-RB in prostate cancer patient specimens. Inhibition of SETDB1 expression using a gene-specific antisense oligonucleotide (ASO) reduced tumor growth but accelerated RB protein degradation, limiting the therapeutic efficacy. However, coadministration of the CDK4/6 inhibitor palbociclib blocked ASO-induced RB degradation and resulted in a much greater cancer-inhibitory effect than each inhibitor alone both in vitro and in vivo. This study identified CDK4/6-dependent, TRIM28-mediated proteasomal degradation as a mechanism of RB inactivation and reveals SETDB1 as a key inhibitor of this process. Our findings suggest that combined targeting of SETDB1 and CDK4/6 represents a viable approach for the treatment of cancers with SETDB1 gene amplification or overexpression.

Significance:

The identification of a role for TRIM28 and SETDB1 in regulating CDK4/6-phosphorylated RB stability uncovers a combination strategy using CDK4/6 and SETDB1 inhibition to decrease RB degradation and inhibit cancer growth.
New Life of Topoisomerase I Inhibitors as Antibody–Drug Conjugate Warheads
Authors: Pommier Yves , Thomas Anish
Published: January 2023

Antibody–drug conjugates (ADC) allow the delivery of cytotoxic chemotherapeutic agents to tumors. Two ADC delivering topoisomerase I (TOP1) poisons (Enhertu and Trodelvy) have recently been FDA-approved for Her2- and Trop2-expressing solid tumors. In a recent study, a TOP1-anti B7-H4 ADC was described and shown to be synergistic with a novel PARP1-selective inhibitor.

See related article by Kinneer et al., p. 1086
Malignant Progression of an Ancestral Bone Marrow Clone Harboring aCIC-NUTM2AFusion in Isolated Myeloid Sarcoma
Authors: Kamens Jennifer L. , Dang Jinjun , Shaw Timothy I. , Gout Alexander M. , Newman Scott , Hagiwara Kohei , Smith Amelia M.R. , Obermayer Alyssa N. , Aldridge Sarah , Ma Jing , Zhang Yang , Wu Gang , Leventaki Vasiliki , Santiago Teresa , Raimondi Susana , Nakitandwe Joy , Pappo Alberto , Li Chunliang , Zhang Jinghui , Gruber Tanja A.
Published: January 2023

Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow, which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase (RTK) signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis.

Implications:

This study illustrates molecular involvement of phenotypically normal bone marrow in myeloid sarcoma, which has significant implications in clinical care. Further, it extends the definition of CIC-rearrangements to include hematologic malignancies and shows evidence of RTK activation that may be exploited therapeutically in cancer(s) driven by these fusions.
Identification of a Novel IQCE Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7
Authors: Tilemis Faidon-Nikolaos , Marinakis Nikolaos M. , Kosma Konstantina , Fostira Florentia , Traeger-Synodinos Joanne
Published: January 2023

Introduction: Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including IQCE gene. More precisely, loss-of-function of IQCE is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642). Case Presentation: A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth. Through whole-exome sequencing (WES), a pathogenic IQCE variant was identified (c.895_904del) in the homozygous state, which adequately explained the disease phenotype of our patient. However, copy number variant (CNV) analysis from WES data, using ExomeDepth, revealed a novel, likely pathogenic large deletion involving IQCE genomic regions (DEL:chr7:2606751_2641098) encompassing exons 2–18 of the gene. Conclusion: IQCE gene codes for a 695-amino acid protein located at the base of the primary cilia that positively regulates the Hedgehog signaling pathway. This case report represents the first description of a large deletion in IQCE and indicates that implementation of ExomeDepth in routine WES analysis can contribute valuable information toward elucidating the correct etiology of rare genetic diseases, increasing the diagnostic yield, and minimizing the need for additional tests.
Biomarkers of Covert Acid Stress in Patients with Chronic Kidney Disease: A Cross-Sectional Study
Authors: Goraya Nimrit , Madias Nicolaos E. , Mamun Abdullah , Simoni Jan , Wesson Donald E.
Published: January 2023

Introduction: Like metabolic acidosis, earlier stages of acid (H+) stress, including an ongoing H+ challenge in the form of dietary H+, without or with steady-state H+ accumulation but with normal plasma total CO2 (PTCO2) (the latter state known as eubicarbonatemic acidosis), are associated with augmented progression of chronic kidney disease (CKD), but diagnosis of this covert H+ stress is clinically problematic. Prior published studies to identify clinically practical biomarkers of covert H+ stress did not include assessments of either dietary H+ or H+ retention. Methods: We tested plasma pH (PpH), 8-h urine excretion of citrate (UcitV) or ammonium (UNH4+V) as biomarkers of dietary H+ assessed as potential renal acid load (PRAL), and of steady-state H+ retention by comparing observed to expected PTCO2 increase 2 h after an oral NaHCO3 bolus. We recruited 313 non-diabetic participants with PTCO2 ≥ 22 mM to exclude participants with metabolic acidosis and with eGFR (mean [SD], mL/min/1.73 m2) stages G1 (n = 62, 99.2 [7.3]), G2 (n = 167, 73.8 [6.3]), and G3 (n = 84, 39.9 [6.7]). We performed linear regressions (LR) between H+ retention or PRAL (dependent variables) and PpH, UcitV, or UNH4+V (independent variables) after adjusting for eGFR. Results: Steady-state H+ retention (mean [SD], mmol) increased with stage (G1 = 3.8 [12.5], G2 = 18.2 [12.4], and G3 = 25.6 [9.0]). PpH was not significantly associated with PRAL in any group, and its association with H+ retention was significant only for G3 (p < 0.01). UcitV association with PRAL was significant only for G1 (p < 0.01) but not for G2 (p = 0.65) or G3 (p = 0.11). UcitV association with H+ retention was negative for both G2 (p < 0.01) and G3 (p < 0.01) but was not significant for G1 (p = 0.50). Adding UNH4+V to UcitV as a regressor for H+ retention increased r2 only marginally for G2 (0.61–0.63) and G3 (0.75–0.79). UNH4+V association with PRAL was positive (p < 0.01) for G1 and G2 but was not significant for G3 (p = 0.46). UNH4+V association with H+ retention was significant for both G2 (p < 0.04) and G3 (p < 0.01) but diverged directionally, being positive for G2 but negative for G3. Discussion: Among patients with CKD at risk for covert H+ stress, lower UcitV better identified eubicarbonatemic acidosis than UNH4+V because the UNH4+V versus H+ retention relationship diverged between G2 and G3. Neither test identified eubicarbonatemic acidosis with certainty, indicating need for further work to establish a clinically useful test. On the other hand, UNH4+V had better utility identifying increased dietary H+ assessed as PRAL in G1 and G2.
Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection
Authors: Carnevale Roberto , Cammisotto Vittoria , Bartimoccia Simona , Nocella Cristina , Castellani Valentina , Bufano Marianna , Loffredo Lorenzo , Sciarretta Sebastiano , Frati Giacomo , Coluccia Antonio , Silvestri Romano , Ceccarelli Giancarlo , Oliva Alessandra , Venditti Mario , Pugliese Francesco , Maria Mastroianni Claudio , Turriziani Ombretta , Leopizzi Martina , D’Amati Giulia , Pignatelli Pasquale , Violi Francesco
Published: January 2023

Background:

SARS-CoV-2 is associated with an increased risk of venous and arterial thrombosis, but the underlying mechanism is still unclear.

Methods:

We performed a cross-sectional analysis of platelet function in 25 SARS-CoV-2 and 10 healthy subjects by measuring Nox2 (NADPH oxidase 2)-derived oxidative stress and thromboxane B
2
, and investigated if administration of monoclonal antibodies against the S protein (Spike protein) of SARS-CoV-2 affects platelet activation. Furthermore, we investigated in vitro if the S protein of SARS-CoV-2 or plasma from SARS-CoV-2 enhanced platelet activation.

Results:

Ex vivo studies showed enhanced platelet Nox2-derived oxidative stress and thromboxane B
2
biosynthesis and under laminar flow platelet-dependent thrombus growth in SARS-CoV-2 compared with controls; both effects were lowered by Nox2 and TLR4 (Toll-like receptor 4) inhibitors. Two hours after administration of monoclonal antibodies, a significant inhibition of platelet activation was observed in patients with SARS-CoV-2 compared with untreated ones. In vitro study showed that S protein per se did not elicit platelet activation but amplified the platelet response to subthreshold concentrations of agonists and functionally interacted with platelet TLR4. A docking simulation analysis suggested that TLR4 binds to S protein via three receptor-binding domains; furthermore, immunoprecipitation and immunofluorescence showed S protein-TLR4 colocalization in platelets from SARS-CoV-2. Plasma from patients with SARS-CoV-2 enhanced platelet activation and Nox2-related oxidative stress, an effect blunted by TNF (tumor necrosis factor) α inhibitor; this effect was recapitulated by an in vitro study documenting that TNFα alone promoted platelet activation and amplified the platelet response to S protein via p47phox (phagocyte oxidase) upregulation.

Conclusions:

The study identifies 2 TLR4-dependent and independent pathways promoting platelet-dependent thrombus growth and suggests inhibition of TLR4. or p47phox as a tool to counteract thrombosis in SARS-CoV-2.
The Emergence of the Bissau-Guinean Fula Cernos
Authors: Boiro Hamadou , Einarsdóttir Jónína
Published: January 2023

International agencies and non-governmental organisations classify Quranic schoolboys who beg on behalf of their teachers as victims of child trafficking. The aim here is to understand why no Bissau-Guinean Fula religious leader, referred to as cerno, has been sentenced to prison, despite accusations of child trafficking. The findings show that community members hold religious leaders in high esteem for their role within the spiritual, educative, and social spheres. Community members, entrenched in complex discriminatory relations within their ethnic group and beyond, perceive them as their saviours, while politicians, high-ranking officers and traders compete for their endorsement. Criminalising the cernos is unsuccessful; to safeguard the interests of children, the children and their community members, including the cernos, should be put at the heart of the safeguarding measures. Despite complex layers of coloniality, the religious leaders are the masters of the game, and their imprisonment is challenging.
Integration and Special Rights
Authors: Malloy Tove H.
Published: January 2023

For almost 25 years, the Council of Europe and the Danish authorities have entertained a fruitless and stalled dialogue on an option to apply the Council’s Framework Convention for the Protection of National Minorities in the societal integration of Greenlanders living in Denmark. So far, the Danish authorities have not been willing to award the Greenlanders any special rights citing their individual and universal rights to non-discrimination and equal civil rights as sufficient for integration. The refusal is based on the authorities’ specific interpretation of the status of Greenland and Greenlanders under international conventions. A review of the dialogue from 1999 till today set against a short Nordic-Canadian perspective reveals that a combination of special rights and universal equal civil rights puts the view of the Danish authorities in question. This seems, therefore, to indicate an unwillingness on behalf of the authorities to consider feasible alternatives.
Macao’s Split Labour Market
Authors: Kerswell Timothy , Hang Leong Sin , Chan William
Published: January 2023

Edna Bonacich’s split labour market states that socio-political factors generate differential outcomes for workers in a region, generally as the result of ethnic antagonism. This ethnic antagonism, Bonacich argues, does not require open violence or even verbal confrontation but can operate through exclusion movements and “caste” systems. In this paper, we use Bonacich’s framework to analyse the production of a split labour market in the Macao, Special Administrative Region of China. Macao depends on an abundant supply of low-skilled migrant workers to remunerate the workforce. While many migrant workers are foreigners, most are ‘internal’ migrants from Mainland China, meaning that a conventional explanation of ethnic differences is insufficient. Bonacich had observed that “exclusion attempts and caste-like arrangements are found among national groupings within a racial category” giving the example of ‘whites’ in the United States excluding other ‘whites’ from different parts of Europe. However, Macao as a part of China constitutes a unique example in that an exclusion attempt and caste-like arrangement is to be found within the same national grouping of the same racial category in the same country. As this research considers how ethnic and quasi-ethnic differences are produced and sustained in Macao through government policy; social attitudes and the social practices of workers and businesses, we find that permanent Macao id card holders, which gives out numerous benefits and rights, is as a form of exclusion movement. Moreover, local workers act as a labour aristocracy: they extract concessions from businesses and suppress migrant workers economically, politically and socially. Edna Bonacich’s split labour market helps explain how a labour aristocracy is maintained subtly at the interest of local workers through concessions from the businesses.
Breaching Protocol and Flouting Norms on the European Parliament Floor
Authors: Bendazzoli Claudio
Published: January 2023

In the plenary sittings of the European Parliament (EP), institutional discourse is regulated by pre-established procedures and multilingualism is guaranteed thanks to simultaneous interpreting into each official EU language. In this setting, political leaders speak in their native language when addressing other Members of the EP and are allowed to hold the floor for a specific amount of time. What happens when such rules and procedures are disrupted? This study analyses a particular breach of protocol, which triggered a number of reactions at different levels of re-contextualisation. These are discussed by considering both the micro- and the macro-context, including the interpreters’ output in 21 different languages along with the official verbatim report of proceedings and its translation into English. The results point to variability in terms of editing standards in the verbatim reports and professional practices among the interpreting booths, with potential differences in accessibility by target recipients.
Theranostic Ruthenium Polypyridine Nanoparticles for Targeted Chimera Delivery into Ovarian Cancer Cells
Authors: Li Xia , Mei Wenjie , Wu Qiong , Wang Jianjun , Qi Lifeng
Published: January 2023

Efficient in vivo delivery of small interfering RNAs (siRNAs) to target cells is challenging in clinical applications. Ruthenium (II) polypyridyl complexes have been discovered as imaging theranostic and anticancer agents due to their photophysical and biological properties.
However, the clinical implementation of ruthenium complexes is limited by cancer cell selectivity. This study presents a novel siRNA delivery nanoplatform by ruthenium polypyridine complex nanoparticles (RPNs). The EGFR RNA aptamer and Notch3 siRNA chimera-loaded RPNs showed
superior RNAi effects against Notch3 gene compared to Lipofectamine. Also, RPN-chimera complexes exhibited significant in vivo antitumor effects against ovarian cancer, which exhibited much potential in future cancer imaging guided gene therapy.
Wear and surface roughness of commercially available computer-aided design/computer-aided manufacturing dental ceramic materials
Authors: AlSunbul Hanan , AlAhdal Khold , AlMashhaf Arwa , AlHaidry Hind , AlAmeel Alhanouf
Published: January 2023

The study evaluated in vitro two-body wear and surface roughness of the recently introduced CAD/CAM dental materials. Pin-on-disk design was set against each other horizontally at a fixed distance with 5 kg (49 N) in distilled water. CAD/CAM materials used were: Feldspathic ceramic
(Vitablocks Mark II), lithium disilicate (IPS e.max CAD), hybrid ceramic (Vita Enamic) and zirconia-reinforced glass ceramic (Vita Suprinity PC). Wear evaluation before and after the chewing cycles were performed by two approaches: weight and vertical height measurements. The surface roughness
of the tested materials was further evaluated after chewing cycles. One-way ANOVA showed significant differences among the mean values of the materials’ vertical height loss and surface roughness (P < 0.05). However, in weight loss, no statistical differences were observed.
The highest vertical height loss was observed in feldspathic ceramic while the lowest vertical height loss was recorded in zirconia-reinforced glass ceramic. Feldspathetic ceramic demonstrated the least surface roughness among all the groups. Feldspathic ceramic had a significantly least wear
resistance and surface roughness, while Zirconia reinforced glass ceramic (VITA Suprinity PC) had a significantly higher wear resistance and acceptable surface roughness among tested groups.