bluuebunny/crossref_metadata_2025 huggingface dataset:
Listening to the voice of older people: dimensions of loneliness in long-term care facilities
Authors: Jansson Anu H. , Karisto Antti , Pitkälä Kaisu H.
Published: January 2022

Loneliness has proved to be common in long-term care facilities (LTCF) and is associated with adverse health outcomes. Although older residents have expressed their experiences of loneliness in previous studies in various ways, researchers have rarely distinguished or explored the three dimensions of loneliness: social, emotional and existential. Furthermore, descriptions of existential loneliness in LTCF is still a neglected area of research. The aim of this study was to explore how the experiences of loneliness of older people in LTCF are manifested and divided into these dimensions. We used an ethnographic multi-method approach. The analysis leaned on abductive reasoning. In terms of social loneliness, the respondents missed company and lacked peer support, but also felt lonely in a crowd. Emotional loneliness felt miserable and could not be shared with anyone. It was related to a feeling of meaninglessness of life and a lack of meaningful others. Existential loneliness was characterised by waiting and a feeling of emptiness. It reflected the fundamental issues of humanity. The present study is one of the first to explore the dimensions of the experiences of loneliness among frail and cognitively impaired older people in LTCF. According to the voices of the lonely respondents, loneliness has many social, emotional and existential aspects. These features of loneliness should be recognised in studies, care practices and interventions.
Violence against girls during COVID-19 pandemic and associated factors in Gondar city, North West Ethiopia
Authors: Kassie Ayenew , Handebo Simegnew , Adugna Asmamaw , Shitu Kegne
Published: January 2022

In Ethiopia, the magnitude of violence against girls during COVID-19 in the study area is not known. Therefore, this study aimed to assess the violence and associated factors during COVID-19 pandemic among Gondar city secondary school girls in North West Ethiopia. An institution-based cross-sectional study was conducted from January to February 2021. Data were collected from four public and two private Gondar city secondary schools. Investigators used stratified simple random sampling to select participants and the investigators used roster of the students at selected schools. Investigators collected the data using self-reported history of experiencing violence (victimisation). Investigators analysed data using descriptive statistics and multivariable logistic regression. Investigators invited a total of 371 sampled female students to complete self-administered questionnaires. The proportion of girls who experienced violence was 42.05% and psychological violence was the highest form of violence. Having a father who attended informal education (AOR = 1.95, 95% CI 1.08–3.51), ever use of social media 1.65 (AOR = 1.65, 95% CI 1.02–2.69), ever watching sexually explicit material (AOR = 2.04, 95% CI 1.24–3.36) and use of a substance (AOR = 1.92, 95% CI 1.17–3.15) were significantly associated variables with violence. Almost for every five girls, more than two of them experienced violence during the COVID-19 lockdown. The prevalence of violence might be under reported due to desirability bias. Therefore, it is better to create awareness towards violence among substance users, fathers with informal education and social media including user females.
Racial/ethnic differences in maternal feeding practices and beliefs at 6 months postpartum
Authors: von Ash Tayla , Alikhani Anna , Lebron Cynthia , Risica Patricia Markham
Published: January 2022

Objective:

To examine racial/ethnic differences in maternal feeding practices and beliefs in a sample of low-income smoke-exposed women.

Design:

Cross-sectional analysis using data collected during a randomised control trial. Maternal feeding practices and beliefs were assessed using the Infant Feeding Questionnaire (IFQ), which was administered at 6 months postpartum. ANOVA was used to examine differences in IFQ items by race/ethnicity, while multivariable linear regression models were used to examine differences in IFQ factor scores by race/ethnicity adjusting for potential confounders.

Setting:

Participants were recruited from prenatal clinics.

Participants:

343 women (39 % non-Hispanic White, 28 % Hispanic/Latina, 13 % Black, and 20 % other).

Results:

Racial/ethnic minority mothers were more likely than non-Hispanic White mothers to put cereal in their infant’s bottle so that the infant would stay full longer (P = 0·032), state their infant wanted more than just formula or breast milk prior to 4 months (P = 0·019), allow their infant to eat whenever he/she wanted (P = 0·023) and only allow their infant to eat at set times (P < 0·001). Adjusting for potential confounders, racial/ethnic minority mothers had higher scores for factors 1 (concern about infant undereating or becoming underweight), 2 (concern about infant’s hunger), 4 (concern about infant overeating or becoming overweight) and 5 (feeding infant on a schedule), and lower scores for factor 7 (social interaction with the infant during feeding) than White mothers. Racial/ethnic differences were not found for the other two factors.

Conclusions:

Differences in maternal feeding practices and beliefs across race/ethnicity are present at 6 months postpartum.
FINITE TWO-DISTANCE-TRANSITIVE DIHEDRANTS
Authors: JIN WEI , TAN LI
Published: January 2022

A noncomplete graph is
$2$
-distance-transitive if, for
$i \in \{1,2\}$
and for any two vertex pairs
$(u_1,v_1)$
and
$(u_2,v_2)$
with the same distance i in the graph, there exists an element of the graph automorphism group that maps
$(u_1,v_1)$
to
$(u_2,v_2)$
. This paper determines the family of
$2$
-distance-transitive Cayley graphs over dihedral groups, and it is shown that if the girth of such a graph is not
$4$
, then either it is a known
$2$
-arc-transitive graph or it is isomorphic to one of the following two graphs:
$ {\mathrm {K}}_{x[y]}$
, where
$x\geq 3,y\geq 2$
, and
$G(2,p,({p-1})/{4})$
, where p is a prime and
$p \equiv 1 \ (\operatorname {mod}\, 8)$
. Then, as an application of the above result, a complete classification is achieved of the family of
$2$
-geodesic-transitive Cayley graphs for dihedral groups.
Nation-Statist Soteriology and Traditions of Defeat: Religious-Zionism, the Ninth of Av, and Jerusalem Day
Authors: Yadgar Yaacov , Hadad Noam
Published: January 2022

We ask how the theopolitics of a nation-state, and especially its soteriology, engage with traditions that preceded the state and relay messages that contradict this theopolitics. To discuss this question, we address the evolving (re-)interpretation of the Ninth of Av—a ritual commemoration of the destruction of Jerusalem and the end of Jewish (Judean) self-rule in ancient times—by Religious-Zionist commentators. We further compare this interpretation to the Religious-Zionist appropriation of Jerusalem Day, a civic holiday celebrating the establishment of Israeli control over East Jerusalem in the June 1967 war. We argue that the statist imperative of the superiority of nation-statist theopolitics suggests that traditions are co-opted to fit in with its soteriology, with varying degrees of resistance or willing accommodation by carriers of these traditions. This co-opting may result in either the de-politicization of what the statist view would see as religion or the religionization of the state's own civic and so-called secular holidays.
Advanced Care Planning
Authors: Georg Jürgen
Published: January 2022

Zusammenfassung. Während mancherorten der Pflegeprozess dem Artensterben anheim zu fallen scheint, gibt es hier und da in der Pflegeszene noch einige gallische Dörfer, die all dem widerstehen und sogar noch einen nächsten Schritt gehen. – Als „Denken heißt überschreiten“ hat Ernst Bloch einmal die zentrale unserer kognitiven Fähigkeiten skizziert. Wo wir bezüglich des Pflegeprozesses stehen und um welche Elemente wir diesen erweitern könnten, um Bestehendes zu überschreiten, skizziert dieser aktualisierte Beitrag von Georg (2017).
ANU GRACE Data Analysis: Characteristics and Benefits of Using Irregularly Shaped Mascons
Authors: Tregoning P. , McGirr R. , Pfeffer J. , Purcell A. , McQueen H. , Allgeyer S. , McClusky S. C.
Published: January 2022

The estimation of mass anomalies using Gravity Recovery and Climate Experiment (GRACE) data involves parameterizing the temporal gravity field using basis functions. In this study, we show that the use of irregularly shaped mass concentration (mascon) tiles that follow land/ocean boundaries reduces the leakage of land signals into ocean regions and vice versa. Leakage of signal from continents to oceans in mascons that cross the coastline affect the integrated mass changes at a regional scale. For example, the calculated mass loss in 2016 is ∼5% greater for Greenland when using mascons that follow coastlines. We describe efficient algorithms for computing the accelerations acting on the satellites caused by mass changes on mascons, along with the partial derivatives relating the mass changes to the inter‐satellite observations. Through simulation, we quantify the impact of different mascon geometries, spatial resolution and regularization. The variations of mass change signals within mascons, which we call “intra‐mascon variability,” contribute to errors in estimates of mass variation from GRACE data. While this can be mitigated through the regularization of the inversions, it cannot be removed entirely. The use of irregularly shaped mascons that follow land/ocean boundaries reduces the “intra‐mascon leakage” of land signals into ocean regions and vice versa. This approach can also be applied to hydrological basins for calculating integrated mass changes on catchment scales.
Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics
Authors: Chen Yu , Yu Zhongzheng , Zheng Kai , Ren Yaguang , Wang Meng , Wu Qiang , Zhou Feifan , Liu Chengbo , Liu Liwei , Song Jun , Qu Junle
Published: January 2022

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics.
Mutations in respiratory complex I promote antibiotic persistence through alterations in intracellular acidity and protein synthesis
Authors: Van den Bergh Bram , Schramke Hannah , Michiels Joran Elie , Kimkes Tom E. P. , Radzikowski Jakub Leszek , Schimpf Johannes , Vedelaar Silke R. , Burschel Sabrina , Dewachter Liselot , Lončar Nikola , Schmidt Alexander , Meijer Tim , Fauvart Maarten , Friedrich Thorsten , Michiels Jan , Heinemann Matthias
Published: January 2022

Antibiotic persistence describes the presence of phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. Perturbations of metabolic homeostasis can promote antibiotic persistence, but the precise mechanisms are not well understood. Here, we use laboratory evolution, population-wide sequencing and biochemical characterizations to identify mutations in respiratory complex I and discover how they promote persistence in Escherichia coli. We show that persistence-inducing perturbations of metabolic homeostasis are associated with cytoplasmic acidification. Such cytoplasmic acidification is further strengthened by compromised proton pumping in the complex I mutants. While RpoS regulon activation induces persistence in the wild type, the aggravated cytoplasmic acidification in the complex I mutants leads to increased persistence via global shutdown of protein synthesis. Thus, we propose that cytoplasmic acidification, amplified by a compromised complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters.
GPCR kinase knockout cells reveal the impact of individual GRKs on arrestin binding and GPCR regulation
Authors: Drube J. , Haider R. S. , Matthees E. S. F. , Reichel M. , Zeiner J. , Fritzwanker S. , Ziegler C. , Barz S. , Klement L. , Filor J. , Weitzel V. , Kliewer A. , Miess-Tanneberg E. , Kostenis E. , Schulz S. , Hoffmann C.
Published: January 2022

G protein-coupled receptors (GPCRs) activate G proteins and undergo a complex regulation by interaction with GPCR kinases (GRKs) and the formation of receptor–arrestin complexes. However, the impact of individual GRKs on arrestin binding is not clear. We report the creation of eleven combinatorial HEK293 knockout cell clones lacking GRK2/3/5/6, including single, double, triple and the quadruple GRK knockout. Analysis of β-arrestin1/2 interactions for twelve GPCRs in our GRK knockout cells enables the differentiation of two main receptor subsets: GRK2/3-regulated and GRK2/3/5/6-regulated receptors. Furthermore, we identify GPCRs that interact with β-arrestins via the overexpression of specific GRKs even in the absence of agonists. Finally, using GRK knockout cells, PKC inhibitors and β-arrestin mutants, we present evidence for differential receptor–β-arrestin1/2 complex configurations mediated by selective engagement of kinases. We anticipate our GRK knockout platform to facilitate the elucidation of previously unappreciated details of GRK-specific GPCR regulation and β-arrestin complex formation.
Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models
Authors: Qiao Wei , Pan Dayu , Zheng Yufeng , Wu Shuilin , Liu Xuanyong , Chen Zhuofan , Wan Mei , Feng Shiqin , Cheung Kenneth M. C. , Yeung Kelvin W. K. , Cao Xu
Published: January 2022

Bone formation induced by divalent metal cations has been widely reported; however, the underlying mechanism is unclear. Here we report that these cations stimulate skeleton interoception by promoting prostaglandin E2 secretion from macrophages. This immune response is accompanied by the sprouting and arborization of calcitonin gene-related polypeptide-α+ nerve fibers, which sense the inflammatory cue with PGE2 receptor 4 and convey the interoceptive signals to the central nervous system. Activating skeleton interoception downregulates sympathetic tone for new bone formation. Moreover, either macrophage depletion or knockout of cyclooxygenase-2 in the macrophage abolishes divalent cation-induced skeleton interoception. Furthermore, sensory denervation or knockout of EP4 in the sensory nerves eliminates the osteogenic effects of divalent cations. Thus, our study reveals that divalent cations promote bone formation through the skeleton interoceptive circuit, a finding which could prompt the development of novel biomaterials to elicit the therapeutic power of these divalent cations.
Deciphering the superior thermoelectric property of post-treatment-free PEDOT:PSS/IL hybrid by X-ray and neutron scattering characterization
Authors: Li Xin , Zou Ruike , Liu Zhen , Mata Jitendra , Storer Ben , Chen Yu , Qi Weiheng , Zhou Zekun , Zhang Peng
Published: January 2022

In this work, a polymer and ionic liquid (IL) hybrid with superior thermoelectric performance is prepared via a system design of the chemical composition, molar ratio of the constituent molecules and manipulating the structure in solution and dried films. The solution-casted hybrid film, consisting of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and 1-ethyl-3-methylimidazolium tricyanomethanide (EMIM:TCM), shows the highest power factor of 175 μW m−1 K−2in the polymer hybrid prepared by a post-treatment-free method. With a set of complementary structure characterization methods, it is found that EMIM:TCM can induce the structure reorganization of PEDOT:PSS in solution from a core-shell model to a rod-like model, during which PEDOT partially separates from PSS that eases the conductive network formation. In addition, the oxidation level of PEDOT:PSS is reduced by adding EMIM:TCM. Based on which, the PEDOT:PSS/IL hybrid shows the best performance in optimizing the conductivity (1163 S cm−1) and Seebeck coefficient (38.8 μV K−1) simultaneously.
Reprocessing seafood waste: challenge to develop aquatic clean meat from fish cells
Authors: Tsuruwaka Yusuke , Shimada Eriko
Published: January 2022

Fish consumption has been increasing worldwide as per capita consumption of fish rises along with population growth. At the same time, overfishing is increasing all over the world, causing enormous damage to the ecosystem. There is an urgent need to secure sustainable fishery resources to meet the expanding demand for fish. The present study focused on the cells obtained from fish fins, which were often discarded as food waste, and which had the potential to change their morphology with simple treatments, creating the possibility of processing fish fin cells into clean meat (i.e., meat produced in vitro; artificial, lab-cultured meat using tissue engineering techniques). The fin-derived fibroblast-like cells demonstrated an interesting characteristic; changing the sera or culture media supported differentiation of the fibroblast-like cells to various cell morphologies, such as neurofilaments and adipocytes, etc., without genetic manipulation. Furthermore, it was possible to culture the cells in multi-layered and three-dimensional forms that were suitable for processing and shaping. Taking advantage of the cells’ characteristics, ‘aquatic clean meat’ was produced successfully at the prototype stage. Our results suggest that fish fins, which are often treated as waste material, thus, are easy to procure, simple to process, and could be used to create a sustainable food resource.
Efficacy of an inactivated Zika vaccine against virus infection during pregnancy in mice and marmosets
Authors: Kim In-Jeong , Lanthier Paula A. , Clark Madeline J. , De La Barrera Rafael A. , Tighe Michael P. , Szaba Frank M. , Travis Kelsey L. , Low-Beer Timothy C. , Cookenham Tres S. , Lanzer Kathleen G. , Bernacki Derek T. , Johnson Lawrence L. , Schneck Amanda A. , Ross Corinna N. , Tardif Suzette D. , Layne-Colon Donna , Mdaki Stephanie D. , Dick Edward J. , Chuba Colin , Gonzalez Olga , Brasky Kathleen M. , Dutton John , Rutherford Julienne N. , Coffey Lark L. , Singapuri Anil , Martin Claudia Sanchez San , Chiu Charles Y. , Thomas Stephen J. , Modjarrad Kayvon , Patterson Jean L. , Blackman Marcia A.
Published: January 2022

Zika virus (ZIKV) is a mosquito-borne arbovirus that can cause severe congenital birth defects. The utmost goal of ZIKV vaccines is to prevent both maternal-fetal infection and congenital Zika syndrome. A Zika purified inactivated virus (ZPIV) was previously shown to be protective in non-pregnant mice and rhesus macaques. In this study, we further examined the efficacy of ZPIV against ZIKV infection during pregnancy in immunocompetent C57BL6 mice and common marmoset monkeys (Callithrix jacchus). We showed that, in C57BL/6 mice, ZPIV significantly reduced ZIKV-induced fetal malformations. Protection of fetuses was positively correlated with virus-neutralizing antibody levels. In marmosets, the vaccine prevented vertical transmission of ZIKV and elicited neutralizing antibodies that remained above a previously determined threshold of protection for up to 18 months. These proof-of-concept studies demonstrate ZPIV’s protective efficacy is both potent and durable and has the potential to prevent the harmful consequence of ZIKV infection during pregnancy.
Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: a randomized phase 4 trial
Authors: Li Jingxin , Hou Lihua , Guo Xiling , Jin Pengfei , Wu Shipo , Zhu Jiahong , Pan Hongxing , Wang Xue , Song Zhizhou , Wan Jingxuan , Cui Lunbiao , Li Junqiang , Chen Yin , Wang Xuewen , Jin Lairun , Liu Jingxian , Shi Fengjuan , Xu Xiaoyu , Zhu Tao , Chen Wei , Zhu Fengcai
Published: January 2022

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 (COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial (NCT04892459). Adults who had received two doses of CoronaVac in the past 3–6 months were vaccinated with Convidecia (n = 96) or CoronaVac (n = 102). Adults who had received one dose of CoronaVac in the past 1–3 months were also vaccinated with Convidecia (n = 51) or CoronaVac (n = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting.
A practical approach for continuous in situ characterization of radiation quality factors in space
Authors: Shuryak Igor , Slaba Tony C. , Plante Ianik , Poignant Floriane , Blattnig Steven R. , Brenner David J.
Published: January 2022

The space radiation environment is qualitatively different from Earth, and its radiation hazard is generally quantified relative to photons using quality factors that allow assessment of biologically-effective dose. Two approaches exist for estimating radiation quality factors in complex low/intermediate-dose radiation environments: one is a fluence-based risk cross-section approach, which requires very detailed in silico characterization of the radiation field and biological cross sections, and thus cannot realistically be used for in situ monitoring. By contrast, the microdosimetric approach, using measured (or calculated) distributions of microdosimetric energy deposition together with empirical biological weighting functions, is conceptually and practically simpler. To demonstrate feasibility of the microdosimetric approach, we estimated a biological weighting function for one specific endpoint, heavy-ion-induced tumorigenesis in APC1638N/+ mice, which was unfolded from experimental results after a variety of heavy ion exposures together with corresponding calculated heavy ion microdosimetric energy deposition spectra. Separate biological weighting functions were unfolded for targeted and non-targeted effects, and these differed substantially. We folded these biological weighting functions with microdosimetric energy deposition spectra for different space radiation environments, and conclude that the microdosimetric approach is indeed practical and, in conjunction with in-situ measurements of microdosimetric spectra, can allow continuous readout of biologically-effective dose during space flight.
EEG theta and beta bands as brain oscillations for different knee osteoarthritis phenotypes according to disease severity
Authors: Simis Marcel , Imamura Marta , Pacheco-Barrios Kevin , Marduy Anna , de Melo Paulo S. , Mendes Augusto J. , Teixeira Paulo E. P. , Battistella Linamara , Fregni Felipe
Published: January 2022

This study aims to investigate the multivariate relationship between different sociodemographic, clinical, and neurophysiological variables with resting-state, high-definition, EEG spectral power in subjects with chronic knee osteoarthritis (OA) pain. This was a cross-sectional study. Sociodemographic and clinical data were collected from 66 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models by frequency bands (delta, theta, alpha, beta, low-beta, and high-beta) and by pre-defined regions (frontal, central, and parietal). From adjusted multivariate models, we found that: (1) increased frontocentral high-beta power and reduced central theta activity are positively correlated with pain intensity (β = 0.012, 95% CI 0.004–0.020; and β = − 0.008; 95% CI 0.014 to − 0.003; respectively); (2) delta and alpha oscillations have a direct relationship with higher cortical inhibition; (3) diffuse increased power at low frequencies (delta and theta) are associated with poor cognition, aging, and depressive symptoms; and (4) higher alpha and beta power over sensorimotor areas seem to be a maladaptive compensatory mechanism to poor motor function and severe joint degeneration. Subjects with higher pain intensity and higher OA severity (likely subjects with maladaptive compensatory mechanisms to severe OA) have higher frontocentral beta power and lower theta activity. On the other hand, subjects with less OA severity and less pain have higher theta oscillations power. These associations showed the potential role of brain oscillations as a marker of pain intensity and clinical phenotypes in chronic knee OA patients. Besides, they suggest a potential compensatory mechanism of these two brain oscillators according to OA severity.
Graphene optical modulators using bound states in the continuum
Authors: Kim Myunghwan , Kim Sangin , Kim Soeun
Published: January 2022

Graphene-based optical modulators have been widely investigated due to the high mobility and tunable permittivity of graphene. However, achieving a high modulation depth with a low insertion loss is challenging owing to low graphene-light interaction. To date, only waveguide-type modulators have been extensively studied to improve light-graphene interaction, and few free-space type modulators have been demonstrated in the optical communication wavelength range. In this study, we propose two graphene-based optical free-space type modulators in a simple silicon photonic crystal structure that supports bound states in the continuum. The designed modulator with an ultra-high quality factor from the bound states in the continuum achieves a high modulation depth (MD = 0.9972) and low insertion loss (IL = 0.0034) with a small Fermi level change at the optical communication wavelength. In addition, the proposed modulators support outstanding modulation performance in the normal chemical vapor deposition (CVD) graphene (mobility = 0.5 m2/Vs). We believe the scheme may pave the way for graphene-based optical active devices.
Association between the CYP1A1 MspI polymorphism and risk of head and neck cancer: a meta-analysis
Authors: Mohammadi Hady , Momeni Roochi Mehrnoush , Rezaei Farzad , Garajei Ata , Heidar Hosein , Ghaderi Bayazid , Sadeghi Masoud
Published: January 2022

The studies recommended the relationship between lots of polymorphisms with the head and neck cancers (HNCs) risk. Herein, we reported the association between the CYP1A1 MspI polymorphism and the risk of HNC in an updated meta-analysis. The PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until March 31, 2021, without any restrictions. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between CYP1A1 MspI polymorphism and the HNC risk based on five applied genetic models by RevMan 5.3 software. Other analyses (sensitivity analysis, meta-regression, and bias analysis) were performed by CMA 2.0 software. Trial sequential analysis (TSA) was done by TSA software (version 0.9.5.10 beta). Among the databases and other sources, 501 recorded were identified that at last, 29 studies were obtained for the analysis. The pooled ORs were 1.28 (95%CI 1.09, 1.51; P = 0.003), 1.68 (95%CI 1.16, 2.45; P = 0.007), 1.24 (95%CI 1.03, 1.50; P = 0.02), 1.26 (95%CI 1.07, 1.48; P = 0.005), and 1.66 (95%CI 1.27, 2.16; P = 0.0002) for allelic, homozygous, heterozygous, recessive, and dominant models, respectively. Therefore, the m2 allele and m1/m2 and m2/m2 genotypes had significantly increased risks in HNC patients. With regards to stable results and enough samples, the findings of the present meta-analysis recommended that there was an association between CYP1A1 MspI polymorphism and the HNC risk.
Phasic firing of dopaminergic neurons in the ventral tegmental area triggers peripheral immune responses
Authors: Kayama Tasuku , Ikegaya Yuji , Sasaki Takuya
Published: January 2022

Dopaminergic neurons in the ventral tegmental area (VTA) play a crucial role in the processing of reward-related information. Recent studies with pharmacological manipulations of VTA neuronal activity demonstrated a VTA-induced immunoenhancement in peripheral organs. Here, to examine the detailed physiological dynamics, we took an optogenetic approach in which VTA dopaminergic neurons were selectively activated with millisecond precision. Optogenetic phasic, rather than tonic, stimulation of VTA dopaminergic neurons increased serum cytokine levels, such as IL-2, IL-4 and TNF-α. These results provide direct evidence to link dopaminergic neuronal phasic firing to peripheral immunity. Next, we tested whether cytokine induction in male mice was boosted by female encounters, a natural condition that induces increased active VTA neurons and gamma power. Female encounters increased serum IL-2 levels, which were abolished by pharmacological inhibition of VTA neuronal activity. Taken together, our results highlight the importance of the brain reward system in the treatment and management of immune-related disorders.
One-step visualization of natural cell activities in non-labeled living spheroids
Authors: Tanaka Shotaro , Takizawa Kotaro , Nakamura Fumio
Published: January 2022

3D cultured cell aggregates, including spheroids, reflect the gene expression patterns of living tissues/organs. Mass preparation of spheroids enables high-throughput drug screening (HTS). However, conventional optical imaging of spheroids makes it difficult to obtain sufficient resolution of individual living cells in the thick cellular stack. Rapid and accurate assessment of cellular responses in spheroids is required for effective drug screening. Here, we show that negative contrast imaging (NCI) of spheroids overcomes this issue. Hydrophilic fluorescent dye added into the culture medium rapidly diffused into the intercellular space of living spheroids within a few minutes. Confocal microscopy showed the NCI of individual cells as dark and detailed contours clearly separated with fluorescence signals in the intercellular space. NCI enables the visualization of the alteration of cell morphology after anti-tumor drug application to living spheroids and the measurement of the fluorescent dye diffusion rate without any complicated pretreatments. Using this system, we found that the antitumor drug doxorubicin reduced the intercellular space of spheroids consisting of the human hepatocyte carcinoma cell line HepG2, through the activation of TGF-β signaling and upregulation of ECM protein expression, implicating a drug resistance mechanism. Collectively, the combination of NCI of spheroids and HTS may enhance the efficiency of drug discovery.
Microporous hierarchically Zn-MOF as an efficient catalyst for the Hantzsch synthesis of polyhydroquinolines
Authors: Ramish Sayed Mohammad , Ghorbani-Choghamarani Arash , Mohammadi Masoud
Published: January 2022

A three-dimensional walnut-like Zn-based MOF microsphere system was designed and synthesized via hydrothermal reaction of zinc salt with 4,6-diamino-2-pyrimidinethiol as a tridentate ligand. Besides, Zn ions were coordinated to the functional groups of the ligand to give a novel Zn-MOF microsphere material. Afterward, the resultant material was thoroughly characterized using various analysis and physico-chemical methods; including, FT-IR, XRD, TGA, EDX, X-ray mapping, SEM, TEM, and BET analysis. The Zn-MOF microspheres were utilized in the Hantzsch reaction for a selective synthesis of asymmetric polyhydroquinolines, using various aromatic aldehydes. Our strategy aims at providing a controlled synthesis of hierarchically nanoporous Zn-MOF microspheres with a well-defined morphology, structure, and excellent catalytic properties. Besides, it would result in having a promising heterogeneous catalyst for a selective synthesis with good yields, short reaction time, a low limit of steric hindrance and electronic effects. Moreover, the heterogeneity of the catalyst is further tested with hot filtration and also the reusability results point.
Investigation of the occupational exposure to blood-borne pathogens of staff at a third-class specialist hospital in 2015–2018: a retrospective study
Authors: Ji Yuanyi , Huang Junbo , Jiang Guoguo , Liu Qiaolan , Xiao Dalei , Deng Jianjun
Published: January 2022

To understand the current situation of occupational exposure to blood-borne pathogens in a women's and children's hospital and analyze the causes to provide a scientific basis for improving occupational exposure prevention and control measures. We analyzed occupational exposure to blood-borne pathogens in a third-class women's and children's hospital from 2015 to 2018, considering the workers’ occupational categories and length of service; the sites, types, and causes of exposure; and the pathogens of the source patients. From 2015 to 2018, there were 146 cases of occupational exposure to blood-borne pathogens, mainly from sharp-instrument injuries (81.5%; 119/146). Trainees represented the highest proportion of occupational exposure (30.1%; 44/146), followed by nurses (29.5%; 43/146). Occupational exposure among staff with less than one year of service accounted for 43.2% (63/146) of cases. Fisher's exact test showed that different occupational groups had different types of occupational exposure, and among the occupationally exposed populations, the proportion of sharp injuries is higher than that of blood and body fluid exposure, and the difference is statistically significant (χ2 = 12.937, P = 0.008). Different occupational groups faced exposure to different types of pathogens: medical staff were more likely than workmen to be exposed to hepatitis B, while workmen were more likely than medical staff to be exposed to unknown pathogens; these differences were statistically significant (χ2 = 55.344, P < 0.001). Health records were established for all cases of occupational exposure to blood-borne pathogens, and no staff members contracted a blood-borne disease due to occupational exposure. In order to reduce occupational exposure, regular training in occupational protection for junior medical staff and workers should be strengthened, the monitoring and protection system of occupational exposure to blood-borne pathogens improved, standard prevention measures strengthened, operations standardized, safe injection equipment provided, and comprehensive measures taken.
A medium composition containing normal resting glucose that supports differentiation of primary human airway cells
Authors: Morgan Rachel , Manfredi Candela , Easley Kristen F. , Watkins Lionel D. , Hunt William R. , Goudy Steven L. , Sorscher Eric J. , Koval Michael , Molina Samuel A.
Published: January 2022

Primary cells isolated from the human respiratory tract are the state-of-the-art for in vitro airway epithelial cell research. Airway cell isolates require media that support expansion of cells in a basal state to maintain the capacity for differentiation as well as proper cellular function. By contrast, airway cell differentiation at an air–liquid interface (ALI) requires a distinct medium formulation that typically contains high levels of glucose. Here, we expanded and differentiated human basal cells isolated from the nasal and conducting airway to a mature mucociliary epithelial cell layer at ALI using a medium formulation containing normal resting glucose levels. Of note, bronchial epithelial cells expanded and differentiated in normal resting glucose medium showed insulin-stimulated glucose uptake which was inhibited by high glucose concentrations. Normal glucose containing ALI also enabled differentiation of nasal and tracheal cells that showed comparable electrophysiological profiles when assessed for cystic fibrosis transmembrane conductance regulator (CFTR) function and that remained responsive for up to 7 weeks in culture. These data demonstrate that normal glucose containing medium supports differentiation of primary nasal and lung epithelial cells at ALI, is well suited for metabolic studies, and avoids pitfalls associated with exposure to high glucose.
Evaluation of robustness in hybrid intensity-modulated radiation therapy plans generated by commercial software for automated breast planning
Authors: Mizuno Norifumi , Yamauchi Ryouhei , Kawamori Jiro , Itazawa Tomoko , Shimbo Munefumi , Nishimura Keiichiro , Yamano Takafumi , Hatanaka Shogo , Hariu Masatsugu , Takahashi Takeo
Published: January 2022

This study aimed to evaluate the robustness against geometric uncertainties in the hybrid intensity-modulated radiation therapy (IMRT) plans generated by commercially available software for automated breast planning (ABP). The ABP plans were compared with commonly used forward-planned field-in-field (FIF) technique plans. The planning computed tomography datasets of 20 patients who received left-sided breast-conserving surgery were used for both the ABP and FIF plans. Geometric uncertainties were simulated by shifting beam isocenters by 2, 3, 5, and 10 mm in the six directions: anterior/posterior, left/right, and superior/inferior. A total of 500 plans (20 patients and 25 scenarios, including the original plan) were created for each of the ABP and FIF plans. The homogeneity index of the target volume in the ABP plans was significantly better (p < 0.001) than the value in the FIF plans in the scenarios of shifting beam isocenters by 2, 3, and 5 mm. Mean heart dose and percentage volume of lungs receiving a dose more than 20 Gy were clinically acceptable in all scenarios. The hybrid IMRT plans generated by commercially available ABP software provided better robustness against geometric uncertainties than forward-planned FIF plans.
Synthesis and in vitro assay of hydroxyxanthones as antioxidant and anticancer agents
Authors: Fatmasari Nela , Kurniawan Yehezkiel Steven , Jumina Jumina , Anwar Chairil , Priastomo Yoga , Pranowo Harno Dwi , Zulkarnain Abdul Karim , Sholikhah Eti Nurwening
Published: January 2022

In the present work, three hydroxyxanthones were synthesized in 11.15–33.42% yield from 2,6-dihydroxybenzoic acid as the starting material. The chemical structures of prepared hydroxyxanthones have been elucidated by using spectroscopic techniques. Afterward, the hydroxyxanthones were evaluated as antioxidant agents through radical scavenging assay; and anticancer agents through in vitro assays against WiDr, MCF-7, and HeLa cancer cell lines. Hydroxyxanthone 3b was categorized as a strong antioxidant agent (IC50 = 349 ± 68 µM), while the other compounds were categorized as moderate antioxidant agents (IC50 > 500 µM). On the other hand, hydroxyxanthone 3a exhibited the highest anticancer activity (IC50 = 184 ± 15 µM) and the highest selectivity (SI = 18.42) against MCF-7 cancer cells. From the molecular docking study, it was found that hydroxyxanthone 3a interacted with the active sites of Topoisomerase II protein through Hydrogen bonding with DG13 and π–π stacking interactions with DA12 and DC8. These findings revealed that hydroxyxanthones are potential candidates to be developed as antioxidant and anticancer agents in the future.
Bioinformatics approaches identified dasatinib and bortezomib inhibit the activity of MCM7 protein as a potential treatment against human cancer
Authors: Samad Abdus , Huq Md. Amdadul , Rahman Md. Shahedur
Published: January 2022

Minichromosome Maintenance Complex Component 7 (MCM7) is a key component of the DNA replication licensing factor and hexamer MCM (MCM2–7) complex that regulates the DNA replication process. The MCM7 protein is associated with tumor cell proliferation that plays an important role in different human cancer progression. As the protein is highly expressed during the cancer development process, therefore, inhibition of the protein can be utilized as a treatment option for different human cancer. However, the study aimed to identify potential small molecular drug candidates against the MCM7 protein that can utilize treatment options for human cancer. Initially, the compounds identified from protein-drugs network analysis have been retrieved from NetworkAnalyst v3.0 server and screened through molecular docking, MM-GBSA, DFT, pharmacokinetics, toxicity, and molecular dynamics (MD) simulation approach. Two compounds namely Dasatinib (CID_3062316) and Bortezomib (CID_387447) have been identified throughout the screening process, which have the highest negative binding affinity (Kcal/mol) and binding free energy (Kcal/mol). The pharmacokinetics and toxicity analysis identified drug-like properties and no toxicity properties of the compounds, where 500 ns MD simulation confirmed structural stability of the two compounds to the targeted proteins. Therefore, we can conclude that the compounds dasatinib and bortezomib can inhibit the activity of the MCM7 and can be developed as a treatment option against human cancer.
Decidualization of endometriosis in a cohort of IVF-mediated pregnancies
Authors: Filippi Francesca , Benaglia Laura , Alagna Federica , La Vecchia Irene , Biancardi Rossella , Reschini Marco , Somigliana Edgardo , Vercellini Paolo
Published: January 2022

Decidualization is the process of endometrial change in pregnancy, a phenomenon that can involve also ovarian endometriomas. However, the frequency of this event remains unknown. In addition, there is no evidence on the decidualization of deep invasive endometriosis (DIE). To shed more light on this issue, we prospectively recruited women with ovarian endometriomas or DIE who underwent IVF. They were subsequently excluded if they did not become pregnant or if they had a miscarriage. The evaluation was repeated in five time points during pregnancy and post-partum. The primary outcome was the rate of decidualized endometriomas at 11–13 weeks’ gestation. Data from 45 endometriomas and 15 nodules were available for data analyses. At the 11–13 weeks’ ultrasound, endometriomas’ decidualization was observed in seven cases, corresponding to 16% (95% CI 8–29%). Subsequent assessments in pregnancy failed to identify any additional case. DIE also underwent significant changes during pregnancy. At the 11–13 weeks’ ultrasound, lesions were increased in size and more vascularized. In conclusion, decidualization of ovarian endometriomas in IVF pregnancies is not rare. DIE may also undergo decidualization, but further evidence is needed for a robust and shared definition of this process.
Quality assessment standards in artificial intelligence diagnostic accuracy systematic reviews: a meta-research study
Authors: Jayakumar Shruti , Sounderajah Viknesh , Normahani Pasha , Harling Leanne , Markar Sheraz R. , Ashrafian Hutan , Darzi Ara
Published: January 2022

Artificial intelligence (AI) centred diagnostic systems are increasingly recognised as robust solutions in healthcare delivery pathways. In turn, there has been a concurrent rise in secondary research studies regarding these technologies in order to influence key clinical and policymaking decisions. It is therefore essential that these studies accurately appraise methodological quality and risk of bias within shortlisted trials and reports. In order to assess whether this critical step is performed, we undertook a meta-research study evaluating adherence to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool within AI diagnostic accuracy systematic reviews. A literature search was conducted on all studies published from 2000 to December 2020. Of 50 included reviews, 36 performed the quality assessment, of which 27 utilised the QUADAS-2 tool. Bias was reported across all four domains of QUADAS-2. Two hundred forty-three of 423 studies (57.5%) across all systematic reviews utilising QUADAS-2 reported a high or unclear risk of bias in the patient selection domain, 110 (26%) reported a high or unclear risk of bias in the index test domain, 121 (28.6%) in the reference standard domain and 157 (37.1%) in the flow and timing domain. This study demonstrates the incomplete uptake of quality assessment tools in reviews of AI-based diagnostic accuracy studies and highlights inconsistent reporting across all domains of quality assessment. Poor standards of reporting act as barriers to clinical implementation. The creation of an AI-specific extension for quality assessment tools of diagnostic accuracy AI studies may facilitate the safe translation of AI tools into clinical practice.
Differential toxicity to murine small and large intestinal epithelium induced by oncology drugs
Authors: Bieber Jake M. , Sanman Laura E. , Sun Xiaoxiao , Hammerlindl Heinz , Bao Feng , Roth Maike A. , Koleske Megan L. , Huang Liusheng , Aweeka Fran , Wu Lani F. , Altschuler Steven J.
Published: January 2022

Gastrointestinal toxicity is a major concern in the development of drugs. Here, we establish the ability to use murine small and large intestine-derived monolayers to screen drugs for toxicity. As a proof-of-concept, we applied this system to assess gastrointestinal toxicity of ~50 clinically used oncology drugs, encompassing diverse mechanisms of action. Nearly all tested drugs had a deleterious effect on the gut, with increased sensitivity in the small intestine. The identification of differential toxicity between the small and large intestine enabled us to pinpoint differences in drug uptake (antifolates), drug metabolism (cyclophosphamide) and cell signaling (EGFR inhibitors) across the gut. These results highlight an under-appreciated distinction between small and large intestine toxicity and suggest distinct tissue properties important for modulating drug-induced gastrointestinal toxicity. The ability to accurately predict where and how drugs affect the murine gut will accelerate preclinical drug development.