bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the COVID-19 pandemic with changes in objectively measured sedentary behaviour and adiposity
Authors: Kinoshita Keita , Ozato Naoki , Yamaguchi Tohru , Bushita Hiroto , Sudo Motoki , Yamashiro Yukari , Mori Kenta , Katsuragi Yoshihisa , Sasai Hiroyuki , Murashita Koichi , Takahashi Yoshiko , Ihara Kazushige
Published: February 2023

Background

Several studies have reported that the coronavirus disease (COVID-19) pandemic has increased sedentary behaviour and obesity; however, these analyses used self-reported data, and the association between sedentary behaviour and visceral fat and adipocytokines during the COVID-19 pandemic remains unclear. We aimed to investigate the association of the COVID-19 pandemic with objectively measured sedentary behaviour and these obesity-related factors.

Methods

Longitudinal analysis was conducted on 257 Japanese participants who underwent health check-ups in 2018 before and in 2020 during the COVID-19 pandemic. For both time points, sedentary behaviour was measured using an accelerometer for at least 7 days, visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis, and blood adiponectin level was measured using latex agglutination turbidimetric immunoassay. Multiple linear regression was performed to determine the association between sedentary behaviour and these outcomes.

Results

Compared with data in 2018, sedentary behaviour and VFA were significantly increased (P < 0.001, P = 0.006) whereas adiponectin level was significantly decreased (P < 0.001) in 2020. Increased sedentary behaviour was significantly associated with an increase in VFA (β = 3.85, 95% CI 1.22–6.49, P = 0.004) and a decrease in adiponectin level (β = −0.04, 95% CI −0.06 to −0.01, P = 0.005). However, the association of sedentary behaviour with adiponectin level was not significant after considering the effects of VFA.

Conclusions

The COVID-19 pandemic was associated with objectively measured sedentary behaviour and obesity-related factors in Japanese adults. Additionally, an increase in sedentary behaviour was associated with an increase in VFA, whereas the association of sedentary behaviour with adiponectin was partly mediated by VFA. These results suggest that avoiding increasing sedentary time is important to prevent visceral adiposity thereby ameliorating adiponectin, especially during behavioural limitations such as the COVID-19 pandemic.
RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling
Authors: Yuan Gongsheng , Yang Shuting , Yang Shuying
Published: February 2023

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.
A Phase 1/2 study of the PD-L1 inhibitor, BGB-A333, alone and in combination with the PD-1 inhibitor, tislelizumab, in patients with advanced solid tumours
Authors: Desai Jayesh , Fong Peter , Moreno Victor , Frentzas Sophia , Meniawy Tarek , Markman Ben , Voskoboynik Mark , Rahman Tahmina , Budha Nageshwar , Wu John , Marlow Jin , Yang Silu , Calvo Emiliano , Martin-Liberal Juan
Published: February 2023

Background

Many patients do not respond or eventually relapse on treatment with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors due to secondary or acquired resistance; therefore, there is a need to investigate novel PD-1/PD-L1 inhibitors.

Methods

This open-label, non-randomised study investigated the safety and anti-tumour activity of BGB-A333, a PD-L1 inhibitor, alone and in combination with tislelizumab in patients with advanced solid tumours with progression during/after standard therapy. The primary objectives were to determine the recommended Phase 2 dose (RP2D), safety and tolerability for BGB-A333 alone and in combination with tislelizumab (Phase 1a/1b) and to determine the overall response rate (ORR) with BGB-A333 plus tislelizumab (Phase 2).

Results

Overall, 39 patients across Phase 1a (N = 15), 1b (N = 12) and 2 (N = 12) were enroled. In Phase 1a, an RP2D of 1350 mg was determined. In Phase 1a and 1b/2, serious treatment-emergent adverse events (TEAEs) were reported in five and eight patients, respectively. Two patients experienced TEAEs that led to death. In Phase 2, the ORR was 41.7% (n = 5/12; 95% confidence interval: 15.17%, 72.33%).

Conclusions

TEAEs reported with BGB-A333 were consistent with other PD-L1 inhibitors. Encouraging preliminary anti-tumour activity was observed with BGB-A333 in combination with tislelizumab.

Clinical trial registration

NCT03379259.
Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials
Authors: Loh Jerold , Wu Jiaxuan , Chieng Jenny , Chan Aurora , Yong Wei-Peng , Sundar Raghav , Lee Soo-Chin , Wong Andrea , Lim Joline S. J. , Tan David S. P. , Soo Ross , Goh Boon-Cher , Tai Bee-Choo , Chee Cheng E.
Published: February 2023

Background

Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil–lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population.

Methods

We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020.

Results

The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96–1.70); RMH score 2, HR 2.27 (95% CI: 1.62–3.17); RMH score 3, HR 4.14 (95% CI: 2.62–6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24–2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16–4.35, P < 0.001) were prognostic.

Conclusions

We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65–0.76]), and validated the RMH model in the largest Asian study to date.
Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis
Authors: Tan Mingyue , Yin Yunfei , Ma Xiao , Zhang Jun , Pan Wanqian , Tan Minghao , Zhao Yongjian , Yang Tianke , Jiang Tingbo , Li Hongxia
Published: February 2023

The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in the cardiovascular system due to its key contribution to detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption of the GSH system is a critical element in the pathogenesis of myocardial injury. Meanwhile, a newly proposed type of cell death, ferroptosis, has been demonstrated to be closely related to the GSH system, which affects the process and outcome of myocardial injury. Moreover, in facing various pathological challenges, the mammalian heart, which possesses high levels of mitochondria and weak antioxidant capacity, is susceptible to oxidant production and oxidative damage. Therefore, targeted enhancement of the GSH system along with prevention of ferroptosis in the myocardium is a promising therapeutic strategy. In this review, we first systematically describe the physiological functions and anabolism of the GSH system, as well as its effects on cardiac injury. Then, we discuss the relationship between the GSH system and ferroptosis in myocardial injury. Moreover, a comprehensive summary of the activation strategies of the GSH system is presented, where we mainly identify several promising herbal monomers, which may provide valuable guidelines for the exploration of new therapeutic approaches.
Evidence for protein leverage in a general population sample of children and adolescents
Authors: Saner Christoph , Senior Alistair M. , Zhang Hanyue , Eloranta Aino-Maija , Magnussen Costan G. , Sabin Matthew A. , Juonala Markus , Janner Marco , Burgner David P. , Schwab Ursula , Haapala Eero A. , Heitmann Berit L. , Simpson Stephen J. , Raubenheimer David , Lakka Timo A.
Published: February 2023

Background/Objectives

The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents.

Subjects/Methods

A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study. Exposures: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates. Outcomes: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure.

Results

Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = −0.36 [−0.47 to −0.25]; L = −0.26 [−0.37 to −0.15]; L = −0.25 [−0.38 to −0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001).

Conclusions

This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity.
Chondrule-like objects and Ca-Al-rich inclusions in Ryugu may potentially be the oldest Solar System materials
Authors: Nakashima Daisuke , Nakamura Tomoki , Zhang Mingming , Kita Noriko T. , Mikouchi Takashi , Yoshida Hideto , Enokido Yuma , Morita Tomoyo , Kikuiri Mizuha , Amano Kana , Kagawa Eiichi , Yada Toru , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Yogata Kasumi , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Yoshikawa Makoto , Saiki Takanao , Tanaka Satoshi , Nakazawa Satoru , Terui Fuyuto , Yurimoto Hisayoshi , Noguchi Takaaki , Yabuta Hikaru , Naraoka Hiroshi , Okazaki Ryuji , Sakamoto Kanako , Watanabe Sei-ichiro , Tachibana Shogo , Tsuda Yuichi
Published: February 2023

Chondrule-like objects and Ca-Al-rich inclusions (CAIs) are discovered in the retuned samples from asteroid Ryugu. Here we report results of oxygen isotope, mineralogical, and compositional analysis of the chondrule-like objects and CAIs. Three chondrule-like objects dominated by Mg-rich olivine are16O-rich and -poor with Δ17O (=δ17O – 0.52 × δ18O) values of ~ –23‰ and ~ –3‰, resembling what has been proposed as early generations of chondrules. The16O-rich objects are likely to be melted amoeboid olivine aggregates that escaped from incorporation into16O-poor chondrule precursor dust. Two CAIs composed of refractory minerals are16O-rich with Δ17O of ~ –23‰ and possibly as old as the oldest CAIs. The discovered objects (<30 µm) are as small as those from comets, suggesting radial transport favoring smaller objects from the inner solar nebula to the formation location of the Ryugu original parent body, which is farther from the Sun and scarce in chondrules. The transported objects may have been mostly destroyed during aqueous alteration in the Ryugu parent body.
The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome
Authors: Goruppi Sandro , Clocchiatti Andrea , Bottoni Giulia , Di Cicco Emery , Ma Min , Tassone Beatrice , Neel Victor , Demehri Shadhmer , Simon Christian , Paolo Dotto G.
Published: February 2023

Epigenetic mechanisms oversee epidermal homeostasis and oncogenesis. The identification of kinases controlling these processes has direct therapeutic implications. We show that ULK3 is a nuclear kinase with elevated expression levels in squamous cell carcinomas (SCCs) arising in multiple body sites, including skin and Head/Neck. ULK3 loss by gene silencing or deletion reduces proliferation and clonogenicity of human keratinocytes and SCC-derived cells and affects transcription impinging on stem cell-related and metabolism programs. Mechanistically, ULK3 directly binds and regulates the activity of two histone arginine methyltransferases, PRMT1 and PRMT5 (PRMT1/5), with ULK3 loss compromising PRMT1/5 chromatin association to specific genes and overall methylation of histone H4, a shared target of these enzymes. These findings are of translational significance, as downmodulating ULK3 by RNA interference or locked antisense nucleic acids (LNAs) blunts the proliferation and tumorigenic potential of SCC cells and promotes differentiation in two orthotopic models of skin cancer.
Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle
Authors: Rajabian Nika , Ikhapoh Izuagie , Shahini Shahryar , Choudhury Debanik , Thiyagarajan Ramkumar , Shahini Aref , Kulczyk Joseph , Breed Kendall , Saha Shilpashree , Mohamed Mohamed Alaa , Udin Susan B. , Stablewski Aimee , Seldeen Kenneth , Troen Bruce R. , Personius Kirkwood , Andreadis Stelios T.
Published: February 2023

We investigate the age-related metabolic changes that occur in aged and rejuvenated myoblasts using in vitro and in vivo models of aging. Metabolic and signaling experiments reveal that human senescent myoblasts and myoblasts from a mouse model of premature aging suffer from impaired glycolysis, insulin resistance, and generate Adenosine triphosphate by catabolizing methionine via a methionine adenosyl-transferase 2A-dependant mechanism, producing significant levels of ammonium that may further contribute to cellular senescence. Expression of the pluripotency factor NANOG downregulates methionine adenosyltransferase 2 A, decreases ammonium, restores insulin sensitivity, increases glucose uptake, and enhances muscle regeneration post-injury. Similarly, selective inhibition of methionine adenosyltransferase 2 A activates Akt2 signaling, repairs pyruvate kinase, restores glycolysis, and enhances regeneration, which leads to significant enhancement of muscle strength in a mouse model of premature aging. Collectively, our investigation indicates that inhibiting methionine metabolism may restore age-associated impairments with significant gain in muscle function.
North Atlantic oscillation controls multidecadal changes in the North Tropical Atlantic−Pacific connection
Authors: Ding Ruiqiang , Nnamchi Hyacinth C. , Yu Jin-Yi , Li Tim , Sun Cheng , Li Jianping , Tseng Yu‐Heng , Li Xichen , Xie Fei , Feng Juan , Ji Kai , Li Xumin
Published: February 2023

By exciting subtropical teleconnections, sea surface temperature (SST) anomalies in the North Tropical Atlantic (NTA) during boreal spring can trigger El Niño-Southern Oscillation (ENSO) events in the following boreal winter, thereby providing a precursor for ENSO predictability. However, this NTA−ENSO connection is not stationary, and it varies considerably over multidecadal timescales, which cannot be directly explained by the Atlantic multidecadal oscillation or the global warming trend. Here we show that multidecadal changes in the NTA−ENSO connection are principally controlled by multidecadal variability associated with the North Atlantic Oscillation (NAO). During the positive phase of the NAO, the amplification of the NTA impact on ENSO mainly arises from strengthening of the boreal spring mean precipitation over the equatorial Atlantic and enhancement of the persistence of NTA SST anomalies, which enhance the NTA influence by exciting stronger and more persistent subtropical teleconnections. Our findings show that multidecadal variability of the NAO is key to understanding the impacts of the NTA SST on the tropical Pacific Ocean.
Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes
Authors: Citro Antonio , Neroni Alessia , Pignatelli Cataldo , Campo Francesco , Policardi Martina , Monieri Matteo , Pellegrini Silvia , Dugnani Erica , Manenti Fabio , Maffia Maria Chiara , Valla Libera , Kemter Elisabeth , Marzinotto Ilaria , Olgasi Cristina , Cucci Alessia , Follenzi Antonia , Lampasona Vito , Wolf Eckhard , Piemonti Lorenzo
Published: February 2023

Intrahepatic islet transplantation is the standard cell therapy for β cell replacement. However, the shortage of organ donors and an unsatisfactory engraftment limit its application to a selected patients with type 1 diabetes. There is an urgent need to identify alternative strategies based on an unlimited source of insulin producing cells and innovative scaffolds to foster cell interaction and integration to orchestrate physiological endocrine function. We previously proposed the use of decellularized lung as a scaffold for β cell replacement with the final goal of engineering a vascularized endocrine organ. Here, we prototyped this technology with the integration of neonatal porcine islet and healthy subject-derived blood outgrowth endothelial cells to engineer a xenogeneic vascularized endocrine pancreas. We validated ex vivo cell integration and function, its engraftment and performance in a preclinical model of diabetes. Results showed that this technology not only is able to foster neonatal pig islet maturation in vitro, but also to perform in vivo immediately upon transplantation and for over 18 weeks, compared to normal performance within 8 weeks in various state of the art preclinical models. Given the recent progress in donor pig genetic engineering, this technology may enable the assembly of immune-protected functional endocrine organs.
Single-cell atavism reveals an ancient mechanism of cell type diversification in a sea anemone
Authors: Babonis Leslie S. , Enjolras Camille , Reft Abigail J. , Foster Brent M. , Hugosson Fredrik , Ryan Joseph F. , Daly Marymegan , Martindale Mark Q.
Published: February 2023

Cnidocytes are the explosive stinging cells unique to cnidarians (corals, jellyfish, etc). Specialized for prey capture and defense, cnidocytes comprise a group of over 30 morphologically and functionally distinct cell types. These unusual cells are iconic examples of biological novelty but the developmental mechanisms driving diversity of the stinging apparatus are poorly characterized, making it challenging to understand the evolutionary history of stinging cells. Using CRISPR/Cas9-mediated genome editing in the sea anemoneNematostella vectensis, we show that a single transcription factor (NvSox2) acts as a binary switch between two alternative stinging cell fates. Knockout ofNvSox2causes a transformation of piercing cells into ensnaring cells, which are common in other species of sea anemone but appear to have been silenced inN. vectensis. These results reveal an unusual case of single-cell atavism and expand our understanding of the diversification of cell type identity.
Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network
Authors: Menon Vinod , Cerri Domenic , Lee Byeongwook , Yuan Rui , Lee Sung-Ho , Shih Yen-Yu Ian
Published: February 2023

The salience network (SN) and default mode network (DMN) play a crucial role in cognitive function. The SN, anchored in the anterior insular cortex (AI), has been hypothesized to modulate DMN activity during stimulus-driven cognition. However, the causal neural mechanisms underlying changes in DMN activity and its functional connectivity with the SN are poorly understood. Here we combine feedforward optogenetic stimulation with fMRI and computational modeling to dissect the causal role of AI neurons in dynamic functional interactions between SN and DMN nodes in the male rat brain. Optogenetic stimulation of Chronos-expressing AI neurons suppressed DMN activity, and decreased AI-DMN and intra-DMN functional connectivity. Our findings demonstrate that feedforward optogenetic stimulation of AI neurons induces dynamic suppression and decoupling of the DMN and elucidates previously unknown features of rodent brain network organization. Our study advances foundational knowledge of causal mechanisms underlying dynamic cross-network interactions and brain network switching.
A sub-wavelength Si LED integrated in a CMOS platform
Authors: Li Zheng , Xue Jin , de Cea Marc , Kim Jaehwan , Nong Hao , Chong Daniel , Lim Khee Yong , Quek Elgin , Ram Rajeev J.
Published: February 2023

A nanoscale on-chip light source with high intensity is desired for various applications in integrated photonics systems. However, it is challenging to realize such an emitter using materials and fabrication processes compatible with the standard integrated circuit technology. In this letter, we report an electrically driven Si light-emitting diode with sub-wavelength emission area fabricated in an open-foundry microelectronics complementary metal-oxide-semiconductor platform. The light-emitting diode emission spectrum is centered around 1100 nm and the emission area is smaller than 0.14 μm2 (~$$\varnothing 400$$
∅
400
nm). This light-emitting diode has high spatial intensity of >50 mW/cm2 which is comparable with state-of-the-art Si-based emitters with much larger emission areas. Due to sub-wavelength confinement, the emission exhibits a high degree of spatial coherence, which is demonstrated by incorporating the light-emitting diode into a compact lensless in-line holographic microscope. This centimeter-scale, all-silicon microscope utilizes a single emitter to simultaneously illuminate ~9.5 million pixels of a complementary metal-oxide-semiconductor imager.
Site-specific encoding of photoactivity and photoreactivity into antibody fragments
Authors: Bridge Thomas , Wegmann Udo , Crack Jason C. , Orman Kate , Shaikh Saher A. , Farndon William , Martins Carlo , Saalbach Gerhard , Sachdeva Amit
Published: February 2023

Design of biomolecules that perform two or more distinct functions in response to light remains challenging. Here, we have introduced concurrent photoactivity and photoreactivity into an epidermal growth factor receptor (EGFR)-targeting antibody fragment, 7D12. This was achieved by site-specific incorporation of photocaged tyrosine (pcY) for photoactivity and p-benzoyl-ʟ-phenylalanine (Bpa) for photoreactivity into 7D12. We identified a position for installing Bpa in 7D12 that has minimal effect on 7D12–EGFR binding affinity in the absence of light. Upon exposure to 365-nm light, this Bpa-containing 7D12 mutant forms a covalent bond with EGFR in an antigen-specific manner. We then developed a method for site-specific incorporation of pcY and Bpa at two distinct sites in 7D12. Finally, we demonstrated that in the absence of light, this pcY- and Bpa-containing mutant of 7D12 does not bind to EGFR, but irradiation with 365-nm light activates (1) specific binding and (2) covalent bond formation with EGFR.
Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice
Authors: Reichart Daniel , Newby Gregory A. , Wakimoto Hiroko , Lun Mingyue , Gorham Joshua M. , Curran Justin J. , Raguram Aditya , DeLaughter Daniel M. , Conner David A. , Marsiglia Júlia D. C. , Kohli Sajeev , Chmatal Lukas , Page David C. , Zabaleta Nerea , Vandenberghe Luk , Liu David R. , Seidman Jonathan G. , Seidman Christine
Published: February 2023

Dominant missense pathogenic variants in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure and sudden cardiac death. In this study, we assessed two different genetic therapies—an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9—to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q. One dose of dual-AAV9 vectors, each carrying one half of RNA-guided ABE8e, corrected the pathogenic variant in ≥70% of ventricular cardiomyocytes and maintained durable, normal cardiac structure and function. An additional dose provided more editing in the atria but also increased bystander editing. AAV9 delivery of RNA-guided Cas9 nuclease effectively inactivated the pathogenic allele, albeit with dose-dependent toxicities, necessitating a narrow therapeutic window to maintain health. These preclinical studies demonstrate considerable potential for single-dose genetic therapies to correct or silence pathogenic variants and prevent the development of HCM.
Radiomics analysis of contrast-enhanced T1W MRI: predicting the recurrence of acute pancreatitis
Authors: Tang Lingling , Ma Lin , Chen Yuying , Hu Yuntao , Chen Xinyue , Huang Xiaohua , Liu Nian
Published: February 2023

To investigate the predictive value of radiomics based on T1-weighted contrast-enhanced MRI (CE-MRI) in forecasting the recurrence of acute pancreatitis (AP). A total of 201 patients with first-episode of acute pancreatitis were enrolled retrospectively (140 in the training cohort and 61 in the testing cohort), with 69 and 30 patients who experienced recurrence in each cohort, respectively. Quantitative image feature extraction was obtained from MR contrast-enhanced late arterial-phase images. The optimal radiomics features retained after dimensionality reduction were used to construct the radiomics model through logistic regression analysis, and the clinical characteristics were collected to construct the clinical model. The nomogram model was established by linearly integrating the clinically independent risk factor with the optimal radiomics signature. The five best radiomics features were determined by dimensionality reduction. The radiomics model had a higher area under the receiver operating characteristic curve (AUC) than the clinical model for estimating the recurrence of acute pancreatitis for both the training cohort (0.915 vs. 0.811, p = 0.020) and testing cohort (0.917 vs. 0.681, p = 0.002). The nomogram model showed good performance, with an AUC of 0.943 in the training cohort and 0.906 in the testing cohort. The radiomics model based on CE-MRI showed good performance for optimizing the individualized prediction of recurrent acute pancreatitis, which provides a reference for the prevention and treatment of recurrent pancreatitis.
Quitting smoking after a cancer diagnosis is associated with high-risk neutrophil-to-lymphocyte ratio among tobacco use-related cancer survivors
Authors: Lu You , Kwong Katherine , Wells James , Edwards Andrea , Chen Zhong , Tseng Tung-Sung , Zhang Kun
Published: February 2023

Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999–2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40–16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.
The importance of cultural tailoring of communicators and media outlets in an influenza vaccination awareness campaign: a digital randomized trial
Authors: Habib G. L. , Yousuf H. , Bredius L. , Bindraban N. R. , Winter M. M. , Scherder E. J. A. , van der Linden S. , Narula J. , Hofstra L.
Published: February 2023

The COVID-19 pandemic has exposed the vulnerability of ethnic minorities again. Health inequity within ethnic minorities has been explained by factors such as higher prevalence of underlying disease, restricted access to care, and lower vaccination rates. In this study, we investigated the effect of cultural tailoring of communicators and media outlets, respectively, on vaccine willingness in an influenza vaccination campaign in the Netherlands. A total of 1226 participants were recruited from two culturally non-tailored media outlets (Dutch newspaper and Facebook), and one media outlet tailored to a large community in the Netherlands with Indian ancestry. The participants from all three media outlets were randomly exposed to a vaccination awareness video delivered by a physician with an Indian or Dutch background, followed by an online survey. Cultural tailoring compared to cultural non-tailoring of communicators showed no difference in improvement of vaccine willingness (13.9% vs. 20.7% increment, respectively, p = 0.083). However, the media outlet tailored to the community with Indian ancestry, resulted in a higher improvement of vaccine willingness compared to non-tailored media outlets (46.7% vs. 14.7% increment, respectively, p < 0.001, unadjusted OR = 5.096). These results suggest that cultural tailoring of media outlets may be critical to effectively reach out to ethnic minorities to help optimize vaccination rates and improve general health.
Exposure to nonnative-accented speech reduces listening effort and improves social judgments of the speaker
Authors: Rovetti Joseph , Sumantry David , Russo Frank A.
Published: February 2023

Prior research has revealed a native-accent advantage, whereby nonnative-accented speech is more difficult to process than native-accented speech. Nonnative-accented speakers also experience more negative social judgments. In the current study, we asked three questions. First, does exposure to nonnative-accented speech increase speech intelligibility or decrease listening effort, thereby narrowing the native-accent advantage? Second, does lower intelligibility or higher listening effort contribute to listeners’ negative social judgments of speakers? Third and finally, does increased intelligibility or decreased listening effort with exposure to speech bring about more positive social judgments of speakers? To address these questions, normal-hearing adults listened to a block of English sentences with a native accent and a block with nonnative accent. We found that once participants were accustomed to the task, intelligibility was greater for nonnative-accented speech and increased similarly with exposure for both accents. However, listening effort decreased only for nonnative-accented speech, soon reaching the level of native-accented speech. In addition, lower intelligibility and higher listening effort was associated with lower ratings of speaker warmth, speaker competence, and willingness to interact with the speaker. Finally, competence ratings increased over time to a similar extent for both accents, with this relationship fully mediated by intelligibility and listening effort. These results offer insight into how listeners process and judge unfamiliar speakers.
Discrete optimal quadratic AGC based cost functional minimization for interconnected power systems
Authors: Esmail M. , Krishnamurthy S.
Published: February 2023

The increasing complexity and difficulty of the Automatic generation control (AGC) problem has resulted from the increasing scale of interconnected power networks and changing daily demands. The primary goals of AGC are to control frequency variations at nominal levels and tie-line power variances at planned levels. To effectively deal with AGC control difficulties, this study introduces Discrete Optimal Quadratic Automatic Generation Control (OQAGC). One advantages of this method is the differentiation of quadratic cost function results into linear terms while minimizing control actions and minimizing state deviations. This developed control method leads to a simple and easy discrete control law that can be implemented for both linear and nonlinear systems. For optimizing the controller, this research work utilized an optimum control theorem using Lagrangian multipliers, while the functional minimization technique is used for systematically selecting the state and control weighting matrices in discrete form for N control regions (where N is the number of interconnected power systems). The discrete cost function needs are derived using this technique in terms of area control errors, integral area control errors, and control energy expenditure. Four interconnected power systems were analyzed with/without disturbances and area control errors, each with one thermal, hydro, and gas-generating unit. A two-area multi-source power system with renewable energy in control area 2 is analyzed for the performance of the proposed controller with generation rate constraints (GRCs). The functional minimization technique simplifies and eases the choosing of weighting matrices. Furthermore, the simulation findings suggest that the developed discrete optimum quadratic AGC control-based cost functional minimization approach enhances power system dynamics in terms of stability, steady-state performance, and the closed-loop control system's robustness to input load disturbances. As a result, the newly developed OQAGC approach demonstrates the significance of the discrete LQR controller for N multi-area power systems.
Association between knee osteoarthritis and the risk of cardiovascular disease and the synergistic adverse effects of lack of exercise
Authors: Park Dojoon , Park Yong-Moon , Ko Seung-Hyun , Choi Youn-Ho , Min Dong-Uk , Ahn Jae-Hyun , Kim Bongseong , Koh Hae-Seok , Han Kyungdo
Published: February 2023

We aimed to determine whether knee OA is associated with CVD risk and all-cause death and to evaluate whether the association differs by exercise behavior. We used Korea National Health Insurance Service (KNHIS) database and included 201,466 participants (7572 subjects diagnosed with knee OA) who underwent health screening between 2009 and 2015. Those who had been diagnosed with knee OA or CVD before the index year were excluded. Cox proportional hazard models were used after adjusting for sociodemographic and CVD risk factors to evaluate the association between knee OA and CVD risk and all-cause death. Stratification analysis was further performed to determine the effect of exercise behavior on this relationship. During a median follow-up of 7.06 ± 2.24 years, 8743 CVD (2510 MI and 6553 stroke) cases developed. Individuals with knee OA had increased risks of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.15–1.38], myocardial infarction (MI) (HR 1.20, 95% CI 1.00–1.44), and stroke (HR 1.29, 95% CI 1.16–1.43) compared with those without knee OA. Those with knee OA who did not exercise had an increased risk of CVD (HR 1.25, 95% CI 1.11–1.40), whereas no significant increased CVD risk was observed in those with knee OA who exercised at least once a week (HR 1.11, 95% CI 0.96–1.28). There was no association between knee osteoarthritis and all-cause death. Knee OA was independently associated with an increased risk of CVD. Lack of exercise might have a synergistic adverse effect on the association between knee OA and CVD.
Risk of gout attack not increased in patients with thalassemia: a population-based cohort study
Authors: Chen Jing-Wen , Xu Qiang , Yang Pei-Dan , Huang Jing-Yang , Wei James Cheng-Chung
Published: February 2023

The incidence of gout arthritis in patients with thalassemia and the association between them was indefinite. We aimed to give epidemiological evidence regarding the association between thalassemia and gout arthritis. This retrospective cohort study extracted data relating to the risk of gout arthritis from patients diagnosed with thalassemia between 2000 and 2013. We selected the control group at a ratio of 1:4 by propensity score matching (PSM). Univariable and multivariable Cox proportional hazard regression models were performed to analyze the association between thalassemia and gout arthritis and to evaluate the hazard ratio (HR) of gout arthritis after exposure with thalassemia. The sensitivity analysis was performed to avoid the mislabeled thalassemia disease, the transfusion-dependent thalassemia was classified to compare the risk of gout arthritis. The secondary outcome for the risk of gout arthritis with antigout drugs treatment was also evaluated between study groups. In the age and sex matched cohort, the majority of thalassemia patients were women (62.03%) and aged younger than 30 years old (44.79%). There were 138 (4.2%) and 500 (3.8%) incident cases of gout arthritis in the thalassemia and non-thalassemia group. After PSM, the incidence rate, per 100 person-years, of gout arthritis was 0.48 (95% CI 0.42 to 0.56) and 0.60 (95% CI 0.51 to 0.72) in non-thalassemia individuals and patients with thalassemia, respectively. In the Cox proportional hazard regression, patients with thalassemia had no significant increase in the risk of gout arthritis (adjusted HR, 1.00; 95%CI: 0.80 to 1.25) after adjusting demographic variables and comorbidities. The Kaplan–Meier curve showed that the cumulative incidence of gout arthritis was not a significant difference in the thalassemia group than in the comparison group (p > 0.05). The sensitivity analysis showed the consistent results about the risk of gout arthritis in patients with thalassemia. Our study indicated that there was no significant increase in the risk of gout arthritis in subjects with thalassemia.Future research needs to clarify the biological mechanisms behind this connection.
The impact of feeding supplemental minerals to sheep on the return of micronutrients to pasture via urine and faeces
Authors: Kao P.-T. , Fleming H. , Warren H. , Darch T. , McGrath S. P. , Buss H. L. , Lee M. R. F.
Published: February 2023

The form (organic versus inorganic) of minerals (Se, Zn, Cu and Mn), supplemented to sheep (Charolais × Suffolk-Mule (mean weight = 57 ± 2.9 kg) at two European industrial doses, on the return of micronutrients to pasture via nutrient partitioning and composition in sheep urine and faeces was investigated. This gave four treatments in total with 6 animals per treatment (n = 24). The form of the supplemented minerals did not influence the excretory partitioning of micronutrients (Se, Zn, Cu and Mn) between urine and faeces, nor on their concentrations in the excreta. The two doses trialed however, may influence the Se flux in the environment through altering the ratios of Se:P and Se:S ratios in the faeces and Se:S ratio in the urine. Administration of the mineral supplements also improved the retention of P in sheep reducing its excretion via urine. Although the concentrations of readily bioavailable micronutrients in the faeces were not affected by the mineral forms, there were differences in the more recalcitrant fractions of Se, Zn and Cu (as inferred via a sequential extraction) in faeces when different forms of supplemental minerals were offered. The potential impact of these differences on micronutrient flux in pasture requires further investigation.
An insight into synthesis and antitumor activity of citrate and gallate stabilizing gold nanospheres
Authors: Fathy Mohamed M. , Elfiky Abdo A. , Bashandy Yousef S. , Hamdy Mayar M. , Elgharib Ahmed M. , Ibrahim Ibrahim M. , Kamal Rana T. , Mohamed Ahmed S. , Rashad Anan M. , Ahmed Ola S. , Elkaramany Yomna , Abdelaziz Youssef S. , Amin Fatma G. , Eid Jehane I.
Published: February 2023

Both gallic and citrate are well-established antioxidants that show promise as new selective anti-cancer drugs. Gold nanoparticles (AuNPs) as well can be developed as flexible and nontoxic nano-carriers for anti-cancer drugs. This article evaluating the efficiency and biocompatibility of gallic acid and citrate capping gold nanoparticles to be used as anti-cancer drug. The biosafety and therapeutic efficiency of prepared nano-formulations were tested on Hela and normal BHK cell line. Gold nanospheres coated with citrate and gallate were synthesized via wet chemical reduction method. The prepared nano-formulations, citrate and gallate coated gold nanospheres (Cit-AuNPs and Ga-AuNPs), were characterized with respect to their morphology, FTIR spectra, and physical properties. In addition, to assess their cytotoxicity, cell cycle arrest and flow cytometry to measure biological response were performed. Cit-Au NPs and Ga-Au NPs were shown to significantly reduce the viability of Hela cancer cells. Both G0/G cell cycle arrest and comet assay results showed that genotoxic effect was induced in Hela cells by Cit-Au NPs and Ga-Au NPs. The results of this study showed that Cit-Au NPs and Ga-AuNPs inhibit the growth of metastatic cervical cancer cells, which could have therapeutic implications.
Direct observation of electric field-induced magnetism in a molecular magnet
Authors: Lewkowitz M. , Adams J. , Sullivan N. S. , Wang Ping , Shatruk M. , Zapf V. , Arvij Ali Sirusi
Published: February 2023

We report the direct observation of an electrically-induced magnetic susceptibility in the molecular nano- magnet [Fe3O(O2CPh)6(py)3]ClO4·py, an Fe3 trimer. This magnetoelectric effect results from the breaking of spatial inversion symmetry due to the spin configurations of the antiferromagnetic trimer. Both static and very low frequency electric fields were used. Fractional changes of the magnetic susceptibility of 11 ppb$$\pm 2$$

±
2

per kVm-1 for the temperature range 8.5 < T < 13.5 K were observed for applied electric fields up to 62 kV m−1. The changes in susceptibility were measured using a tunnel diode oscillator operating at liquid helium temperatures while the sample is held at a higher regulated temperature.
Calculation of active earth pressure on external corners with equal length on both sides in excavation engineering
Authors: Long Zhao , Zeng Hao , Ye Shuaihua , Li Weili
Published: February 2023

Taking the external corner with equal lengths as the research object, two failure modes of the equilateral external corner are established, and the active earth pressure calculation formula of the equilateral external corner in the limit state is further deduced when the external angle is 90°. The comparison between the theoretical calculation results and Midas/GTS simulation results shows that when the ratio of the side length B to the depth H is large, the sliding wedge failure will occur at the external corner, and the active earth pressure of the external corner in the range of wedge-shaped slider will not change with the change of size B. When the ratio of the side length B to the depth H is small, the displaced soil is composed of two parts, and the earth pressure varies with the change of size B. In this paper, the magnitude and distribution law of the active earth pressure obtained by the horizontal micro-layered limit equilibrium analysis method is similar to the three-dimensional simulation value of the Midas/GTS software, which can prove the feasibility and rationality of the theoretical calculation.
Combination of treatments with transoral endoscopic thyroidectomy vestibular approach (TOETVA) for Graves’ disease
Authors: Wu Yi-Ju , Chang Yen-Hsiang , Tsai Chiajen , Chan Yi-Chia , Chi Shun-Yu , Chou Fong-Fu , Lin Wei-Che , Yang Yi Ting
Published: February 2023

Although the success rates of non-surgical treatments for Graves’ disease such as antithyroid medication and radioiodine ablation were good, there were still failure of treatments or intolerance for some patients. Traditional thyroid surgery could treat these patients but result in unaesthetic neck scars. Herein, we report the preliminary results of our combination of treatments with the transoral endoscopic thyroidectomy vestibular approach for Graves’ disease. A retrospective review of patients who underwent the transoral endoscopic thyroidectomy vestibular approach for the treatment of different sizes of goiters between January 2019 and December 2020 was performed. The demographic and clinical data of patients were collected. All patients were followed up for > 12 months. Each patient’s goiter size was determined using four grades—from 0 to 3. In total, 14 female patients receiving the combination treatment with > 1 year of follow-up and a median (range) age of 35 (20–48) years at surgery were included. There were two, three, four, and five patients with grade 0, 1, 2, and 3 goiters, respectively. The median (range) intraoperative blood loss was higher in grade 3 patients (100 [20–850] mL) than in grade 2 patients (20 [10–200] mL) and grade 1 and 0 patients (both < 10 mL) (p = 0.033). All patients had normal-looking necks with a euthyroid or hypothyroid status within 1 year. There were no complications, including re-operation for bleeding, hypoparathyroidism, vocal cord palsy, or infections. The designed combination treatment with the transoral endoscopic thyroidectomy vestibular approach for Graves’ disease provides optimal cosmetic results with a high success rate.
Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway
Authors: Ji Wanli , Ren Yaoxin , Wei Xiaolian , Ding Xiangxiang , Dong Yihan , Yuan Bin
Published: February 2023

Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect neurons by reducing the permeability of blood brain barrier (BBB). In this study, we investigated the role of ISO-1 in cerebral ischemia/reperfusion injury by establishing a model of middle cerebral artery occlusion/reperfusion in rats. Rats were randomly divided into four groups: the sham operation group, the ISO-1group, the cerebral I/R group, and the ISO-1 + I/R group. We assessed the degree of neurological deficit in each group and measured the volume of cerebral infarction. We detected the expression of MIF in the core necrotic area and penumbra. We detected the expression of apoptosis-related proteins, apoptosis-inducing factor (AIF), endonuclease G (EndoG) and cytochrome c oxidase-IV (COX-IV) in the ischemic penumbra region. The results showed that MIF was expressed in the ischemic penumbra, while the injection of ISO-1 was able to alleviate neurological damage and reduce the infarction volume. In the cerebral ischemic penumbra region, ISO-1 could reduce the expression of Bax and Caspase3 and inhibit the displacement of AIF and EndoG to the nucleus simultaneously. Besides, ISO-1 also exhibited the ability to reduce apoptosis. In summary, ISO-1 may inhibit neuronal apoptosis through the endogenous mitochondrial pathway and reduce the injury of brain I/R after ischemic stroke.