bluuebunny/crossref_metadata_2025 huggingface dataset:
A Model for Highly Fluctuating Spatio-Temporal Infection Data, with Applications to the COVID Epidemic
Authors: Congdon Peter
Published: May 2022

Spatio-temporal models need to address specific features of spatio-temporal infection data, such as periods of stable infection levels (endemicity), followed by epidemic phases, as well as infection spread from neighbouring areas. In this paper, we consider a mixture-link model for infection counts that allows alternation between epidemic phases (possibly multiple) and stable endemicity, with higher AR1 coefficients in epidemic phases. This is a form of regime-switching, allowing for non-stationarity in infection levels. We adopt a generalised Poisson model appropriate to the infection count data and avoid transformations (e.g., differencing) to alternative metrics, which have been adopted in many studies. We allow for neighbourhood spillover in infection, which is also governed by adaptive regime-switching. Compared to existing models, the observational (in-sample) model is expected to better reflect the balance between epidemic and endemic tendencies, and short-term extrapolations are likely to be improved. Two case study applications involve COVID area-time data, one for 32 London boroughs (and 96 weeks) since the start of the COVID epidemic, the other for a shorter time span focusing on the epidemic phase in 144 areas of Southeast England associated with the Alpha variant. In both applications, the proposed methods produce a better in-sample fit and out-of-sample short term predictions. The spatial dynamic implications are highlighted in the case studies.
How Does Entrepreneurial Team Relational Governance Promote Social Start-Ups’ Organizational Resilience?
Authors: Mai Yingping , Wu Yenchun Jim , Wang Yu-Min
Published: May 2022

Why are some social entrepreneurial teams able to adapt to challenges and leverage the opportunities that are generated from a crisis, and why can some start-ups achieve sustained growth yet others do not? From the perspective of relational governance, this study unpacked the mechanism of how entrepreneurial teams promote social start-ups’ abilities to deal with crises and the mediating role of team learning through a survey of 396 social entrepreneurial team members. The results showed four key findings. (1) Trust among entrepreneurial team members has a positive effect on organizational resilience, whereas shared vision and communication-cooperation do not. (2) All the dimensions of relational governance positively promote team learning, and team learning is positively associated with organizational resilience. (3) Team learning mediates the effect of entrepreneurial team relational governance on organizational resilience; specifically, team learning plays a complete intermediary effect on shared vision and communication-cooperation to organizational resilience, whereas it plays a partial intermediary effect on trust in organizational resilience. (4) Team learning is the key factor to organizational resilience, whereas communication-cooperation promotes team learning the most. Practically, to strengthen social start-ups’ organizational resilience, entrepreneurial team members must first improve their understanding of environmental adaptability and then engage in productive and creative dialogues to manage issues, improve team members’ capability in information integration, as well as agree upon the action and activities that should be performed.
Exploring the Experiences and Perceptions of Cigar Craving and Addiction among Young Adult Black Cigar Smokers
Authors: Elhabashy Maryam , Phan Lilianna , Hamilton-Moseley Kristen R. , Broun Aaron , Duarte Danielle A. , Ajith Aniruddh , Jewett Bambi , Mead-Morse Erin L. , Choi Kelvin , Chen-Sankey Julia
Published: May 2022

Black young adults have the highest prevalence of cigar smoking in the U.S. Little is known about how this population perceives addiction to cigar smoking, which may influence long-term smoking and cessation outcomes. This study used semi-structured in-depth interviews to understand cravings, triggers, and perceived addiction from cigar smoking among a purposive sample of Black young adult cigar smokers (N = 40; 21–29 years). An iterative process was used to develop the codebook, and thematic analysis was used to capture findings based on the products predominantly used: cigarillos, large cigars, or blunts. Results suggest that while participants may share similar types of cravings and triggers (e.g., stress) across the use of these products, predominant blunt smokers reported more unique triggers related to relieving physical discomforts. While most participants reported cigars could be addictive to people in general, only a few perceived that they themselves were addicted. Participants who predominantly smoked cigarillos reported high perceived addiction to cigars, while those who predominantly smoked blunts reported low addiction. Education messages are needed to inform young Black adult cigar smokers about the risks and health symptoms of cigar addiction. These efforts may help increase cigar cessation seeking and reduce cigar addiction-related health consequences and disparities among Black populations.
Valorization of Livestock Keratin Waste: Application in Agricultural Fields
Authors: Chen Huayi , Gao Shuang , Li Yongtao , Xu Hui-Juan , Li Wenyan , Wang Jinjin , Zhang Yulong
Published: May 2022

Livestock keratin waste is a rich source of protein. However, the unique structure of livestock keratin waste makes its valorization a great challenge. This paper reviews the main methods for the valorization of livestock keratin waste, which include chemical, biological, and other novel methods, and summarizes the main agricultural applications of keratin-based material. Livestock keratin waste is mainly used as animal feed and fertilizer. However, it has promising potential for biosorbents and in other fields. In the future, researchers should focus on the biological extraction and carbonization methods of processing and keratin-based biosorbents for the soil remediation of farmland.
Household Microenvironment and Under-Fives Health Outcomes in Uganda: Focusing on Multidimensional Energy Poverty and Women Empowerment Indices
Authors: Terfa Zelalem G. , Ahmed Sayem , Khan Jahangir , Niessen Louis W. ,   on behalf of the IMPALA Consortium
Published: May 2022

Young children in low- and middle-income countries (LMICs) are vulnerable to adverse effects of household microenvironments. The UN Sustainable Development Goals (SDGs)—specifically SDG 3 through 7—urge for a comprehensive multi-sector approach to achieve the 2030 goals. This study addresses gaps in understanding the health effects of household microenvironments in resource-poor settings. It studies associations of household microenvironment variables with episodes of acute respiratory infection (ARI) and diarrhoea as well as with stunting among under-fives using logistic regression. Comprehensive data from a nationally representative, cross-sectional demographic and health survey (DHS) in Uganda were analysed. We constructed and applied the multidimensional energy poverty index (MEPI) and the three-dimensional women empowerment index in multi-variate regressions. The multidimensional energy poverty was associated with higher risk of ARI (OR = 1.32, 95% CI 1.10 to 1.58). Social independence of women was associated with lower risk of ARI (OR= 0.91, 95% CI 0.84 to 0.98), diarrhoea (OR = 0.93, 95% CI 0.88 to 0.99), and stunting (OR = 0.83, 95% CI 0.75 to 0.92). Women’s attitude against domestic violence was also significantly associated with episodes of ARI (OR = 0.88, 95% CI 0.82 to 0.93) and diarrhoea (OR = 0.89, 95% CI 0.84 to 0.93) in children. Access to sanitation facilities was associated with lower risk of ARI (OR = 0.55, 95% CI 0.45 to 0.68), diarrhoea (OR = 0.83, 95% CI 0.71 to 0.96), and stunting (OR = 0.64, 95% CI 0.49 to 0.86). Investments targeting synergies in integrated energy and water, sanitation and hygiene, and women empowerment programmes are likely to contribute to the reduction of the burden from early childhood illnesses. Research and development actions in LMICs should address and include multi-sector synergies.
How Anti-Substance Abuse Campaigns Influence Substance Abusers’ Psychological Health in Chinese Communities: The Mediating Role of Perceived Stigma
Authors: Zeng Yonghui , Han Li , Cheng Yu , Jia Cindy Xinshan
Published: May 2022

The current study explored how anti-substance abuse campaigns influence substance abusers’ psychological health through the perception of stigma. The study is based on a sample of substance abusers who received community-based treatments (n = 3457) and used structural equation modeling to estimate the role of perceived stigma in mediating between perceptions of overstatement of harm conveyed in anti-substance abuse campaigns and psychological outcomes. The results revealed that substance abusers’ perception of overstatement of the harm caused by the substances and substance abusers enhanced their perceived stigma and impaired their psychological health in terms of anxiety, depression, and somatization, through both direct and indirect pathways. The results advocate for proper strategies in the design of anti-substance abuse campaigns. Possible initiatives to reduce substance abusers’ perceived stigma are recommended.
The Relationship of Medical Assistants’ Work Engagement with Their Concerns of Having Made an Important Medical Error: A Cross-Sectional Study
Authors: Loerbroks Adrian , Vu-Eickmann Patricia , Dreher Annegret , Mambrey Viola , Scharf Jessica , Angerer Peter
Published: May 2022

Objectives: We aimed to examine associations of work engagement with self-reported concerns of having made medical errors among medical assistants. Methods: We used cross-sectional questionnaire data from 424 medical assistants in Germany (collected between March and May 2021). The nine-item Utrecht Work Engagement Scale assessed the subdimensions vigor, dedication, and absorption. Participants further reported whether they were concerned that they had made an important medical error in the last three months. Work engagement scores were used both as categorized variables (i.e., highest tertile vs. remaining tertiles) and continuous variables (i.e., z-scores) and their associations with concerns to have made an important medical error were examined using multivariable logistic regression to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: High vigor (versus low vigor) and high dedication (versus low dedication) were associated with substantially reduced odds of expressing concerns to have made an important medical error (OR = 0.19, 95%CI = 0.04–0.85 and OR = 0.25, 95%CI = 0.07–0.88, respectively), but absorption was not (OR = 1.10, 95%CI = 0.43–2.86). Analyses with z-scores confirmed this pattern of associations for vigor and absorption, but less so for dedication (OR = 0.72, 95%CI = 0.47–1.11). Conclusions: Vigor and possibly also dedication are inversely related to concerns of having made an important medical error. Our findings may suggest that promotion of these subdimensions of work engagement may improve patient safety.
Reflexive Practice as an Approach to Improve Healthcare Delivery for Indigenous Peoples: A Systematic Critical Synthesis and Exploration of the Cultural Safety Education Literature
Authors: Dawson Jessica , Laccos-Barrett Keera , Hammond Courtney , Rumbold Alice
Published: May 2022

Cultural safety is increasingly being taught in tertiary programmes of study for health professionals. Reflexivity is a key skill required to engage in culturally safe practice, however, there is currently limited literature examining how reflexivity is taught or assessed within cultural safety curricula. A systematic review of the literature up until November 2021 was conducted, examining educational interventions which aimed to produce culturally safe learners. Studies were limited to those with a focus on Indigenous health and delivered in Australia, Aotearoa New Zealand, Canada, and the United States. A total of 46 documents describing 43 different educational interventions were identified. We found that definitions and conceptualisations of reflexivity varied considerably, resulting in a lack of conceptual clarity. Reflexive catalysts were the primary pedagogical approaches used, where objects, people, or Indigenous pedagogies provided a counterpoint to learners’ knowledges and experiences. Information regarding assessment methods was limited but indicates that the focus of existing programmes has been on changes in learner knowledge and attitudes rather than the ability to engage in reflexivity. The results demonstrate a need for greater conceptual clarity regarding reflexivity as it relates to cultural safety, and to develop methods of assessment that focus on process rather than outcomes.
The Impact of Using Different Doses of Biomass Ash on Some Physical Properties of Podzolic Soil under the Cultivation of Winter Oilseed Rape
Authors: Stanek-Tarkowska Jadwiga , Czyż Ewa Antonina , Pastuszczak Miłosz , Skrobacz Karol
Published: May 2022

This two-year study was focused on the effect of the application of different biomass ash doses on selected soil physical properties, i.e., soil moisture (SM), bulk density (BD), penetration resistance (PR), and soil stability in water measured by the content of readily dispersible clay (RDC), following control and mineral NPK fertilization in the cultivation of winter oilseed rape (Brassica napus L. var. napus). A one-factor field experiment conducted on podzolic soil (control, NPK, 100, 200, 300, 400, 500 kg K2O·ha−1) showed that the use of biomass combustion ash significantly improved soil moisture at all depths and variants, and especially at a depth of 30–35 cm in the 500 kg·ha−1 variant, i.e., by 2.99% v/v, compared to NPK. In turn, the moisture content in the 30–35 cm layer increased by 3.19% v/v in all variants in both years compared to the control. In 2020 and 2021, bulk density in the 0–5 cm layer treated with a dose of 500 kg·ha−1 exhibited a positive 0.15 and 0.12 Mg·m−3 decrease, respectively, compared to the control. In both years, the BD values in the 30–35 cm layer were reduced by 0.14 and 0.16 Mg·m−3 compared to the control. The PR values decreased in the treatments with doses of 300, 400, and 500 kg·ha−1, especially in 2021. The RDC content was found to decline in both years, i.e., 2020 and 2021, upon the application of even the lowest dose (100 kg·ha−1) in all the analysed layers. The reduction in the RDC content, especially in the 0–5 cm layer, is very important for soil structure stability and to protect the soil environment. This layer is most susceptible to crusting, which results in poor aeration and weak plant emergence during drought and/or periods of excessive moisture. It may also increase surface runoff and intensify soil erosion processes.
COVID-19 Vaccine Hesitancy in South Africa: Lessons for Future Pandemics
Authors: Engelbrecht Michelle , Heunis Christo , Kigozi Gladys
Published: May 2022

Vaccine hesitancy, long considered a global health threat, poses a major barrier to effective roll-out of COVID-19 vaccination. With less than half (45%) of adult South Africans currently fully vaccinated, we identified factors affecting non-uptake of vaccination and vaccine hesitancy in order to identify key groups to be targeted when embarking upon COVID-19 vaccine promotion campaigns. A cross-sectional, anonymous online survey was undertaken among the South African adult population in September 2021. Our research identified race, interactive–critical vaccine literacy, trust in the government’s ability to roll out the COVID-19 vaccination programme, flu vaccination status and risk perception for COVID-19 infection as key factors influencing the uptake of COVID-19 vaccination. Respondents who did not trust in the government’s ability to roll out vaccination were almost 13 times more likely to be vaccine-hesitant compared to those respondents who did trust the government. Reliable, easy-to-understand information regarding the safety of COVID-19 vaccines is needed, but it is also important that vaccination promotion and communication strategies include broader trust-building measures to enhance South Africans’ trust in the government’s ability to roll out vaccination effectively and safely. This may also be the case in other countries where distrust in governments’ ability prevails.
Improving LST Downscaling Quality on Regional and Field-Scale by Parameterizing the DisTrad Method
Authors: Ibrahim Taha I. M. , Al-Maliki Sadiq , Salameh Omar , Waltner István , Vekerdy Zoltán
Published: May 2022

Many scientists have been investigating Land Surface Temperature (LST) because of its relevance in water management science due to its direct influence on the hydrological water cycle. This effect stems from being one of the most significant variables influencing evapotranspiration. One of the most important reasons for the evapotranspiration retrieved from MODIS data’s limited suitability for scheduling and planning irrigation schemes is the lack of spatial resolution. As a result, high-resolution LST is required for estimating evapotranspiration. The goal of this study is to improve the resolution of the available LST data, to improve evapotranspiration (ETa) estimation using statistical downscaling with Normalized Difference Vegetation Index (NDVI) as a predictor. The DisTrad (Disaggregation of Radiometric Surface Temperature) method was used for the LST downscaling procedure, which is based on aggregating the NDVI map to the LST map resolution and then calculating the coefficient of variation of the native NDVI map within the aggregated pixel and classifying the aggregated map into three classes: NDVI < 0.2 for the bare soil, 0.2 ≤ NDVI ≤ 0.5 for the partial vegetation, and NDVI > 0.5 for the full vegetation. DisTrad uses 25% of the pixels with the lowest coefficient of variation from each class to calculate the regression coefficients. In this work, adjustments to the DisTrad method were implemented to enhance downscaling LST and to examine the impacts of that alteration on the evapotranspiration estimation. The linear regression model was tested as an alternative to the original second-order polynomial. In using 10% of the pixels instead of the originally proposed 25% with the lowest coefficient of variation values, it is assumed that a group of pixels with a lower coefficient of variation represents a more homogeneous area, thus it gives more accurate values. The downscaled LST map retrieval was validated using Landsat 8 thermal maps (100 m). Applying the modified DisTrad approach to disaggregate Landsat LST to 30 m (NDVI resolution) yielded an R2 of 0.72 for the 10%, 0.74 for the 25% and 0.61 for the second-order polynomial lowest coefficient of variation compared to native LST Landsat, which means that 10% can be used as an alternative. Applying the downscaled LST map to estimate ETa yielded R2 0.84 in both cases, compared to ETa yielded from the native Landsat LST. These results prove that using the robust linear regression provided better results than using polynomial regression. With the downscaled Land Surface Temperature data, it was possible to create detailed ETa maps of the small agricultural fields in the test area.
Landscape Ecological Risk and Ecological Security Pattern Construction in World Natural Heritage Sites: A Case Study of Bayinbuluke, Xinjiang, China
Authors: Chen Xiaodong , Yang Zhaoping , Wang Tian , Han Fang
Published: May 2022

The evaluation of ecological risk and the construction of ecological security patterns are significant for the conservation of World Natural Heritage sites with high outstanding universal value. This paper constructed a landscape ecological risk evaluation framework for Bayinbuluke using the three aspects of the “nature–society–landscape pattern” and a cumulative resistance surface from the risk evaluation results. The ecological sources were identified based on Morphological Spatial Pattern Analysis (MSPA) and the landscape index. Finally, the Minimum Cumulative Resistance model (MCR) and gravity model were used to obtain both key ecological corridors and general ecological corridors. The results showed that: (1) the influencing factors of landscape ecological risk were, in order of strongest to weakest, landscape pattern factors, natural factors, and social factors; (2) the spatial differences in terms of landscape ecological risk within the study area could be identified. Low-risk areas were mainly concentrated in the core area, high-risk areas were mainly in the outer buffer zone, and the overall ecological risk level at Bayinbuluke was high; and (3) a total of four key corridors and ten general corridors could be constructed. This study provides a reference for decision-making on the ecological security and protection of heritage sites.
APTC-C-SA01: A Novel Bacteriophage Cocktail Targeting Staphylococcus aureus and MRSA Biofilms
Authors: Liu Sha , Hon Karen , Bouras George Spyro , Psaltis Alkis James , Shearwin Keith , Wormald Peter-John , Vreugde Sarah
Published: May 2022

The high infection and mortality rate of methicillin-resistant Staphylococcus aureus (MRSA) necessitates the urgent development of new treatment strategies. Bacteriophages (phages) have several advantages compared to antibiotics for the treatment of multi-drug-resistant bacterial infections, and thus provide a promising alternative to antibiotics. Here, S. aureus phages were isolated from patients and environmental sources. Phages were characterized for stability, morphology and genomic sequence and their bactericidal activity against the biofilm form of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA was investigated. Four S. aureus phages were isolated and tested against 51 MSSA and MRSA clinical isolates and reference strains. The phages had a broad host range of 82–94% individually and of >98% when combined and could significantly reduce the viability of S. aureus biofilms. The phages had a latent period of ≤20 min and burst size of >11 plaque forming units (PFU)/infected cell. Transmission electron microscopy (TEM) identified phages belonging to the family of Myoviridae. Genomic sequencing indicated the lytic nature of all four phages, with no identified resistance or virulence genes. The 4 phages showed a high complementarity with 49/51 strains (96%) sensitive to at least 2/4 phages tested. Furthermore, the frequency of bacteriophage insensitive mutant (BIM) generation was lower when the phages were combined into the phage cocktail APTC-C-SA01 than for bacteria exposed to each of the phages alone. In conclusion, APTC-C-SA01, containing four lytic S. aureus phages has the potential for further development as a treatment against MSSA and MRSA infections.
Energy Deposition around Swift Carbon-Ion Tracks in Liquid Water
Authors: de Vera Pablo , Taioli Simone , Trevisanutto Paolo E. , Dapor Maurizio , Abril Isabel , Simonucci Stefano , Garcia-Molina Rafael
Published: May 2022

Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion’s path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion’s path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak.
Dissecting the Molecular Regulation of Natural Variation in Growth and Senescence of Two Eutrema salsugineum Ecotypes
Authors: Wang Fanhua , Sun Zhibin , Zhu Min , Zhang Qikun , Sun Yufei , Sun Wei , Wu Chunxia , Li Tongtong , Zhao Yiwu , Ma Changle , Zhang Hui , Zhao Yanxiu , Wang Zenglan
Published: May 2022

Salt cress (Eutrema salsugineum, aka Thellungiella salsuginea) is an extremophile and a close relative of Arabidopsis thaliana. To understand the mechanism of selection of complex traits under natural variation, we analyzed the physiological and proteomic differences between Shandong (SD) and Xinjiang (XJ) ecotypes. The SD ecotype has dark green leaves, short and flat leaves, and more conspicuous taproots, and the XJ ecotype had greater biomass and showed clear signs of senescence or leaf shedding with age. After 2-DE separation and ESI-MS/MS identification, between 25 and 28 differentially expressed protein spots were identified in shoots and roots, respectively. The proteins identified in shoots are mainly involved in cellular metabolic processes, stress responses, responses to abiotic stimuli, and aging responses, while those identified in roots are mainly involved in small-molecule metabolic processes, oxidation-reduction processes, and responses to abiotic stimuli. Our data revealed the evolutionary differences at the protein level between these two ecotypes. Namely, in the evolution of salt tolerance, the SD ecotype highly expressed some stress-related proteins to structurally adapt to the high salt environment in the Yellow River Delta, whereas the XJ ecotype utilizes the specialized energy metabolism to support this evolution of the short-lived xerophytes in the Xinjiang region.
Time-Course Transcriptomic Profiling of Floral Induction in Cultivated Strawberry
Authors: Liang Jiahui , Zheng Jing , Wu Ze , Wang Hongqing
Published: May 2022

The initiation and quality of flowering directly affect the time to market and economic benefit of cultivated strawberries, but the underlying mechanisms of these processes are largely unknown. To investigate the gene activity during the key period of floral induction in strawberries, time-course transcriptome analysis was performed on the shoot apex of the strawberry cultivar ‘Benihoppe.’ A total of 7177 differentially expressed genes (DEGs) were identified through pairwise comparisons. These DEGs were grouped into four clusters with dynamic expression patterns. By analyzing the key genes in the potential flowering pathways and the development of the leaf and flower, at least 73 DEGs that may be involved in the regulatory network of floral induction in strawberries were identified, some of which belong to the NAC, MYB, MADS, and SEB families. A variety of eight hormone signaling pathway genes that might play important roles in floral induction were analyzed. In particular, the gene encoding DELLA, a key inhibitor of the gibberellin signaling pathway, was found to be significantly differentially expressed during the floral induction. Furthermore, the differential expression of some important candidate genes, such as TFL1, SOC1, and GAI-like, was further verified by qRT-PCR. Therefore, we used this time-course transcriptome data for a preliminary exploration of the regulatory network of floral induction and to provide potential candidate genes for future studies of flowering in strawberries.
Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector
Authors: Ju Zhenlin , Thomas Tamlyn N. , Chiu Yi-Jen , Yamanouchi Sakuya , Yoshida Yukari , Abe Jun-ichi , Takahashi Akihisa , Wang Jing , Fujiwara Keigi , Hada Megumi
Published: May 2022

Cultured mammalian cells have been shown to respond to microgravity (μG), but the molecular mechanism is still unknown. The study we report here is focused on molecular and cellular events that occur within a short period of time, which may be related to gravity sensing by cells. Our assumption is that the gravity-sensing mechanism is activated as soon as cells are exposed to any new gravitational environment. To study the molecular events, we exposed cells to simulated μG (SμG) for 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h using a three-dimensional clinostat and made cell lysates, which were then analyzed by reverse phase protein arrays (RPPAs) using a panel of 453 different antibodies. By comparing the RPPA data from cells cultured at 1G with those of cells under SμG, we identified a total of 35 proteomic changes in the SμG samples and found that 20 of these changes took place, mostly transiently, within 30 min. In the 4 h and 8 h samples, there were only two RPPA changes, suggesting that the physiology of these cells is practically indistinguishable from that of cells cultured at 1 G. Among the proteins involved in the early proteomic changes were those that regulate cell motility and cytoskeletal organization. To see whether changes in gravitational environment indeed activate cell motility, we flipped the culture dish upside down (directional change in gravity vector) and studied cell migration and actin cytoskeletal organization. We found that compared with cells grown right-side up, upside-down cells transiently lost stress fibers and rapidly developed lamellipodia, which was supported by increased activity of Ras-related C3 botulinum toxin substrate 1 (Rac1). The upside-down cells also increased their migratory activity. It is possible that these early molecular and cellular events play roles in gravity sensing by mammalian cells. Our study also indicated that these early responses are transient, suggesting that cells appear to adapt physiologically to a new gravitational environment.
The Establishment of a Mouse Model of Recurrent Primary Dysmenorrhea
Authors: Hong Fang , He Guiyan , Zhang Manqi , Yu Boyang , Chai Chengzhi
Published: May 2022

Primary dysmenorrhea is one of the most common reasons for gynecologic visits, but due to the lack of suitable animal models, the pathologic mechanisms and related drug development are limited. Herein, we establish a new mouse model which can mimic the periodic occurrence of primary dysmenorrhea to solve this problem. Non-pregnant female mice were pretreated with estradiol benzoate for 3 consecutive days. After that, mice were injected with oxytocin to simulate menstrual pain on the 4th, 8th, 12th, and 16th days (four estrus cycles). Assessment of the cumulative writhing score, uterine tissue morphology, and uterine artery blood flow and biochemical analysis were performed at each time point. Oxytocin injection induced an equally severe writhing reaction and increased PGF2α accompanied with upregulated expression of COX-2 on the 4th and 8th days. In addition, decreased uterine artery blood flow but increased resistive index (RI) and pulsatility index (PI) were also observed. Furthermore, the metabolomics analysis results indicated that arachidonic acid metabolism; linoleic acid metabolism; glycerophospholipid metabolism; valine, leucine, and isoleucine biosynthesis; alpha-linolenic acid metabolism; and biosynthesis of unsaturated fatty acids might play important roles in the recurrence of primary dysmenorrhea. This new mouse model is able to mimic the clinical characteristics of primary dysmenorrhea for up to two estrous cycles.
Tissue Sampling and Homogenization with NIRL Enables Spatially Resolved Cell Layer Specific Proteomic Analysis of the Murine Intestine
Authors: Voß Hannah , Moritz Manuela , Pelczar Penelope , Gagliani Nicola , Huber Samuel , Nippert Vivien , Schlüter Hartmut , Hahn Jan
Published: May 2022

For investigating the molecular physiology and pathophysiology in organs, the most exact data should be obtained; if not, organ-specific cell lines are analyzed, or the whole organ is homogenized, followed by the analysis of its biomolecules. However, if the morphological organization of the organ can be addressed, then, in the best case, the composition of molecules in single cells of the target organ can be analyzed. Laser capture microdissection (LCM) is a technique which enables the selection of specific cells of a tissue for further analysis of their molecules. However, LCM is a time-consuming two-dimensional technique, and optimal results are only obtained if the tissue is fixed, e.g., by formalin. Especially for proteome analysis, formalin fixation reduced the number of identifiable proteins, and this is an additional drawback. Recently, it was demonstrated that sampling of fresh-frozen (non-fixed) tissue with an infrared-laser is giving higher yields with respect to the absolute protein amount and number of identifiable proteins than conventional mechanical homogenization of tissues. In this study, the applicability of the infrared laser tissue sampling for the proteome analysis of different cell layers of murine intestine was investigated, using LC–MS/MS-based differential quantitative bottom-up proteomics. By laser ablation, eight consecutive layers of colon tissue were obtained and analyzed. However, a clear distinguishability of protein profiles between ascending, descending, and transversal colon was made, and we identified the different intestinal-cell-layer proteins, which are cell-specific, as confirmed by data from the Human Protein Atlas. Thus, for the first time, sampling directly from intact fresh-frozen tissue with three-dimensional resolution is giving access to the different proteomes of different cell layers of colon tissue.
Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange
Authors: Eugenin Eliseo , Camporesi Enrico , Peracchia Camillo
Published: May 2022

The history of direct cell-cell communication has evolved in several small steps. First discovered in the 1930s in invertebrate nervous systems, it was thought at first to be an exception to the “cell theory”, restricted to invertebrates. Surprisingly, however, in the 1950s, electrical cell-cell communication was also reported in vertebrates. Once more, it was thought to be an exception restricted to excitable cells. In contrast, in the mid-1960s, two startling publications proved that virtually all cells freely exchange small neutral and charged molecules. Soon after, cell-cell communication by gap junction channels was reported. While gap junctions are the major means of cell-cell communication, in the early 1980s, evidence surfaced that some cells might also communicate via membrane pores. Questions were raised about the possible artifactual nature of the pores. However, early in this century, we learned that communication via membrane pores exists and plays a major role in medicine, as the structures involved, “tunneling nanotubes”, can rescue diseased cells by directly transferring healthy mitochondria into compromised cells and tissues. On the other hand, pathogens/cancer could also use these communication systems to amplify pathogenesis. Here, we describe the evolution of the discovery of these new communication systems and the potential therapeutic impact on several uncurable diseases.
Synthesis, Structure and Bonding in Pentagonal Bipyramidal Cluster Compounds Containing a cyclo-Sn5 Ring, [(CO)3MSn5M(CO)3]4− (M = Cr, Mo)
Authors: Mondal Sourav , Chen Wei-Xing , Sun Zhong-Ming , McGrady John E.
Published: May 2022

In this paper, we report the synthesis and structural characterisation of two hetero-metallic clusters, [(CO)3CrSn5Cr(CO)3]4− and [(CO)3MoSn5Mo(CO)3]4−, both of which have a pentagonal bipyramidal core. The structures are similar to that of previously reported [(CO)3MoPb5Mo(CO)3]4− and our analysis of the bonding suggests that they are best formulated as containing Sn54− rings bridging two zerovalent M(CO)3 fragments. The electronic structure is compared to two isolobal M2E5 clusters, [CpCrP5CrCp]− and Tl77−, both of which show clear evidence for trans-annular bonds between the apical atoms that is not immediately obvious in the title clusters. Our analysis shows that the balance between E-E and M-M bonding is a delicate one, and shifts in the relative energies of the orbitals on the E5 and M2 fragments generate a continuum of bonding situations linked by the degree of localisation of the cluster LUMO.
Association between Low Ankle-Brachial Index and Poor Outcomes in Patients with Embolic Stroke of Undetermined Source
Authors: Han Minho , Heo JoonNyung , Jung Jae Wook , Lee Il Hyung , Kim Joon Ho , Lee Hyungwoo , Kim Young Dae , Nam Hyo Suk
Published: May 2022

We investigated the association of low ankle-brachial index (ABI < 0.9) with major adverse cardiovascular events (MACE) and all-cause mortality in patients with embolic stroke of undetermined source (ESUS) as well as whether the association differed by ESUS subtype. This retrospective single-center study included ESUS patients who underwent transesophageal echocardiography and ABI during hospitalization. ESUS was classified as ESUS with minor cardioembolic source, arteriogenic embolism, two or more causes, or no cause. Arteriogenic embolism was defined and classified as complex aortic or non-stenotic relevant artery plaque. MACE was defined as stroke recurrence, acute coronary syndrome, hospitalization for heart failure, or death. Overall, 829 patients were included, with a median follow-up of 45.8 months. Of these, 42 (5.1%) and 370 (44.6%) had low ABI and arteriogenic embolism, respectively. ABI < 0.9 was independently associated with MACE (hazard ratio [HR]: 2.038, 95% confidence interval [CI]: 1.093–3.801) and all-cause mortality (HR: 3.608, 95% CI: 1.538–8.465) according to the multivariable Cox regression analysis. Between ESUS subtypes, low ABI was independently associated with MACE (HR: 2.513, 95% CI: 1.257–5.023) and all-cause mortality (HR: 5.681, 95% CI: 2.151–15.008) in arteriogenic embolism patients, especially in those with complex aortic plaque. However, in non-arteriogenic embolism patients, low ABI was not related to MACE and mortality. In ESUS patients, low ABI was linked to MACE and all-cause mortality, especially in those with arteriogenic embolisms from complex aortic plaque.
Correction: Di Micco et al. Clinical Differences between COVID-19 and a COVID-like Syndrome. J. Clin. Med. 2021, 10, 2519
Authors: Di Micco Pierpaolo , Camporese Giuseppe , Russo Vincenzo , Cardillo Giuseppe , Imbalzano Egidio , Tufano Antonella , Bernardi Enrico , Fontanella Andrea
Published: May 2022

Incorrect Affiliation [...]
Sclerobanding Is a Novel Technique for the Treatment of Second- and Third-Degree Hemorrhoidal Disease. Reply to Jongen et al. Comment on “Pata et al. Sclerobanding (Combined Rubber Band Ligation with 3% Polidocanol Foam Sclerotherapy) for the Treatment of Second- and Third-Degree Hemorrhoidal Disease: Feasibility and Short-Term Outcomes. J. Clin. Med. 2022, 11, 218”
Authors: Pata Francesco , Bracchitta Luigi Maria , D’Ambrosio Giancarlo , Bracchitta Salvatore
Published: May 2022

We thank Johannes Jongen and colleagues for their correspondence [...]
Safety and Feasibility of Low Fluence Intense Pulsed Light for Treating Pediatric Patients with Moderate-to-Severe Blepharitis
Authors: Zhai Zimeng , Jiang Hao , Wu Yuqing , Yang Pei , Zhou Shuyun , Hong Jiaxu
Published: May 2022

To explore the safety and feasibility of low fluence intense pulsed light (IPL) for treating pediatric patients with moderate-to-severe blepharitis and to analyze potential factors associated with the recovery of meibomian glands (MG) dropout, a retrospective, noncomparative study, including 17 blepharitis patients (33 eyes) aged between 5 and 16 years old was conducted. All of the participants were given 4 continuous sessions of low-fluence (9–12 J/cm2) IPL at 3–4 week intervals. Corneal fluorescein staining (CFS), tear breakup time (BUT), inferior tear meniscus height, Demodex presence, and MG morphology were examined before and after the treatment. Results indicated that CFS, BUT and MG morphology (central/total gland area ratio and gland signal index) had significantly improved (p < 0.05). Symptoms and signs such as severe corneal neovascularization, limbal pannus and conjunctival congestion also subsided. Among age, gender, presence of Demodex and interval before diagnosis, age initiating the formal treatment was confirmed as a negatively correlated factor of the recovery of MG dropout (p = 0.032, B = −1.755). No notable adverse events were reported. In conclusion, low fluence IPL seems to be a safe and effective alternative for moderate-to-severe pediatric blepharitis, and MG dropout is prone to recover in younger patients.
Special Issue “New Frontiers in Facial Surgery”
Authors: Dell’Aversana Orabona Giovanni , Maglitto Fabio , Abbate Vincenzo , Romano Antonio , Bonavolontà Paola , Califano Luigi
Published: May 2022

Facial surgery remains a challenge for surgeons in order to achieve the best results, both functionally and aesthetically [...]
Reply to Kielb et al. Untapped Potential for Female Patients? Comment on “Lucà et al. Update on Management of Cardiovascular Diseases in Women. J. Clin. Med. 2022, 11, 1176”
Authors: Lucà Fabiana , Colivicchi Furio , Rossini Roberta , Riccio Carmine , Gelsomino Sandro , Gulizia Michele Massimo
Published: May 2022

We would like to thank the authors of this letter for their comments [...]
Association between Masseter Muscle Area and Thickness and Outcome after Carotid Endarterectomy: A Retrospective Cohort Study
Authors: Hogenbirk Rianne N. M. , Banning Louise B. D. , Visser Anita , Jager-Wittenaar Harriet , Pol Robert A. , Zeebregts Clark J. , Klaase Joost M.
Published: May 2022

Low muscle mass is associated with adverse outcomes after surgery. This study examined whether facial muscles, such as the masseter muscle, could be used as a proxy for generalized low muscle mass and could be associated with deviant outcomes after carotid endarterectomy (CEA). As a part of the Vascular Ageing study, patients with an available preoperative CT-scan, who underwent an elective CEA between December 2009 and May 2018, were included. Bilateral masseter muscle area and thickness were measured on preoperative CT scans. A masseter muscle area or thickness of one standard deviation below the sex-based mean was considered low masseter muscle area (LMA) or low masseter muscle thickness (LMT). Of the 123 included patients (73.3% men; mean age 68 (9.7) years), 22 (17.9%) patients had LMA, and 18 (14.6%) patients had LMT. A total of 41 (33.3%) patients had a complicated postoperative course and median length of hospital stay was four (4–5) days. Recurrent stroke within 5 years occurred in eight (6.6%) patients. Univariable analysis showed an association between LMA, complications and prolonged hospital stay. LMT was associated with a prolonged hospital stay (OR 8.78 [1.15–66.85]; p = 0.036) and recurrent stroke within 5 years (HR 12.40 [1.83–84.09]; p = 0.010) in multivariable logistic regression analysis. Masseter muscle might be useful in preoperative risk assessment for adverse short- and long-term postoperative outcomes.
Evolving Indications of Transcatheter Aortic Valve Replacement—Where Are We Now, and Where Are We Going
Authors: Mesnier Jules , Panagides Vassili , Nuche Jorge , Rodés-Cabau Josep
Published: May 2022

Indications for transcatheter aortic valve replacement (TAVR) have steadily increased over the last decade since the first trials including inoperable or very high risk patients. Thus, TAVR is now the most common treatment of aortic valve stenosis in elderly patients (vs. surgical aortic valve replacement -SAVR-). In this review, we summarize the current indications of TAVR and explore future directions in which TAVR indications can expand.
Safety and Efficacy of a Large-Bore Biliary Metallic Stent for Malignant Biliary Obstruction
Authors: Do Min Young , Jang Sung Ill , Cho Jae Hee , Kim Yonsoo , Kim In-Jung , Lee Kwang-Hun , Joo Seung-Moon , Lee Dong Ki
Published: May 2022

Self-expandable metallic stents (SEMSs) are typically inserted in patients with unresectable malignant biliary obstruction. However, SEMSs are susceptible to occlusion. To overcome this issue, we developed a large-bore, dumbbell-shaped, fully covered SEMS (FCSEMS-L) and compared its efficacy and safety with those of a conventional FCSEMS (FCSEMS-C) in patients with malignant biliary obstruction. Methods: Patients with unresectable distal malignant biliary obstruction were retrospectively enrolled between January 2011 and February 2021. All patients underwent endoscopic insertion of FCSEMSs. Recurrent biliary obstruction (RBO), patient survival time, complications, and prognosis were analyzed. Results: RBO occurred in 31 patients (35.6%) who received an FCSEMS-L, and in 34 (45.9%) who received an FCSEMS-C. Stent occlusion occurred in 19 patients (21.8%) who received an FCSEMS-L, and in 22 (29.7%) who received an FCSEMS-C. Stent migration occurred in 12 patients (13.8%) with an FCSEMS-L and 12 (16.2%) with an FCSEMS-C. The median time to RBO (TRBO) was 301 days with an FCSEMS-L and 203 days with an FCSEMS-C. The median survival time was 479 days with an FCSEMS-L and 523 days with an FCSEMS-C. The TRBO and patient survival time did not significantly differ between the two groups. Conclusions: There were no significant differences in efficacy and complication rates between the fully covered large bore SEMSs and conventional fully covered SEMSs.
Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland
Authors: Glińska Marta , Walczak Mieczysław , Wikiera Beata , Pyrżak Beata , Majcher Anna , Paluchowska Monika , Gawlik Aneta , Antosz Aleksandra , Kusz Marcin , Bossowski Artur , Stożek Karolina , Wędrychowicz Anna , Starzyk Jerzy , Petriczko Elżbieta
Published: May 2022

Short stature resulting from SGA is an obligatory indication for treatment with rhGH. The aim of the study was to assess the response to rhGH treatment in patients treated in the years 2016–2020 in six clinical centers in Poland. During the analysis, auxological data were collected, and anthropometrical parameters (Ht, SDS Ht, HV and ΔHV) were reassessed. Subgroups of patients with dysmorphic features (DYSM), fetal alcohol syndrome (FAS) and Silver-Russel syndrome (SRS) were selected. The study group consisted of 235 children (137 boys). The medium initial age was 9.08 years, and 190 patients were in the prepubertal stage. The poor response to treatment was defined as ΔHt SDS < 0.3 and/or ΔHV < 3 cm/year. Seventeen per cent of all patients after the first year and 44% after the second year met the ΔHt SDS < 0.3 criterion, and 56% during the first and 73% during the second year met the ΔHV < 3 cm/year criterion. Our data suggest that patients with SRS may show the best response to treatment, which was sustained throughout the follow-up period. The best response in all subgroups was observed during the first 12 months of therapy. Although the proportion of patients meeting the poor response criteria was high, only a few patients exceeded the 97th percentile for IGF-1 concentration during the first year of treatment. This might suggest that increasing the dose of rhGH in the second treatment year in order to sustain accelerated HV would be safe in these patients.