bluuebunny/crossref_metadata_2025 huggingface dataset:
Photosynthetic Physiological Basis of Forage Mass Stability in a Progeny of Rhizome-Rooted ‘Qingshui’ Medicago sativa L.
Authors: A Yun , Shi Shangli , Zhang Jinqing , Li Xiaolong , Jing Fang , Zhang Huihui , Ma Ruihong
Published: February 2023

Rhizome-rooted alfalfa (Medicago sativa L.) is an excellent forage for establishing grazing and ecological grasslands, requiring a high and stable yield. Studying the genetic and physiological basis of stable expression of biomass traits is essential for improving production performance in rhizome-rooted alfalfa. We analyzed forage mass and photosynthetic physiological indices of the improved progenies (RSA−01, RSA−02, and RSA−03), parental “Qingshui” (CK1), and “WL168” (CK2) at ages one and five years and their relationships, then revealed heterotic stability. Moreover, we explored the effects of interannual dynamics and genetic differences on tested indices. The results revealed compared with the forage mass of CK1, RSA−03 at ages one and five years increased by 22.17% and 19.72%, respectively, while RSA−01 and RSA−02 varied from 1.40% to 8.65%, indicating obvious heterosis in forage mass of RSA−03. At one year of age, Gs value, Car content and SS content of RSA−03 were higher than those of CK1; SS content of RSA−03 were higher than those of CK2 and RSA−02; Ci, Gs and Tr values of RSA−03 were higher than those of RSA−01. At five years of age, Pn, Gs, and WUE values, and Sta content of RSA−03 were higher than those of CK1; Ci value and Suc content of RSA−03 were higher than those of CK2; Car content and Gs value of RSA−03 were higher than those of other progenies. The forage mass; Chl(a/b) ratio; Pn, Gs, and WUE values; Suc content of RSA−03 at age five years were higher than those at age one year by 9.99%–44.24%. Through path analysis, Gs and NSC were direct factors affecting forage mass at age one year, and both Pn and SP affected forage mass indirectly through Gs; Gs and Chl(a+b) were direct factors affecting forage mass at age five years, and SS affected forage mass indirectly through Gs. Interestingly, Chlb, Chl(a/b), Pn, Tr, Gs, Ci, Suc, SP, and SS were more influenced by age than genetics, while the opposite was true for Car and Sta. Accordingly, RSA−03 showed obvious and stable heterosis in forage mass and photosynthetic physiology, recommending the establishment of grazing pastures and ecological vegetation.
Use of Multivariate Analysis in Screening for Drought Tolerance in Ornamental Asteraceae Species
Authors: Mircea Diana M. , Calone Roberta , Shakya Rashmi , Saavedra Martín Flores , Sestras Radu E. , Boscaiu Monica , Sestras Adriana F. , Vicente Oscar
Published: February 2023

Asteraceae is one of the families with a large number of ornamental plants. Climate change imposes the need to select species that are more tolerant to changing environmental conditions, especially drought. In this study, we compared the performance under water stress of six species belonging to different tribes of Asteraceae with different geographical origins. Young plants obtained after seed germination were subjected to intermediate water stress (irrigation with half the water amount used in control treatments) and severe water stress (no irrigation at all) for one month. Growth variables and biochemical stress markers were determined to assess the effects on the plants of the stress treatments. Multivariate analysis tools were used to rank species according to their tolerance. Three species were relatively more susceptible to water stress, Callistephus chinensis, Xerochrysum bracteatum, and Calendula officinalis, whereas Leucanthemum vulgare, Glebionis carinata, and Ageratum houstonianum were more tolerant. Our study indicated that the last two species, which are registered as invasive in some geographic areas, possess a larger phenotypic plasticity. Principal component analysis (PCA) combined with canonical variation analysis (CVA) proved optimal statistical methods for analysing species of diverse origins and belonging to different genera of a large family, such as the Asteraceae.
Assessing the Efficacy of Living and Dead Cover Crop Mixtures for Weed Suppression in Sweet Corn
Authors: Yurchak Veronica L. , Leslie Alan W. , Hooks Cerruti R. R.
Published: February 2023

Modern vegetable production systems are often characterized by monoculture fields and the intensive use of tillage and/or synthetic agrochemicals for managing weeds. A growing public interest in more sustainable and eco-friendly production practices has resulted in increased demand for crops to be produced with lower inputs. Field studies were conducted over three field seasons to investigate the use of conservation tillage in concert with an interplanted living mulch and/or cover crop residue for managing weeds in sweet corn as compared with the standard practice of using conventional tillage and pre-emergence residual herbicides. Whole plot treatments included: (1) conventional till, (2) no-till with cover crop residue, (3) living mulch + cover crop residue, and (4) living mulch + winter killed residue. The split-plot factor consisted of herbicide treatments: (1) at-planting application of residual herbicides or (2) no herbicide. The cover crop systems suppressed weeds as well as the standard practice throughout the cropping cycle in all three years. In addition, there was no significant improvement in weed suppression with the application of herbicides within the cover crop treatments. Crop development and yield were similar among treatments in year 2. However, reduced yields were encountered in all cover crop treatments during year 3 relative to the conventional tillage treatment.
Castor Plant Adaptation to Salinity Stress during Early Seedling Stage by Physiological and Transcriptomic Methods
Authors: Deng Xiaoxia , Ma Yuwen , Cheng Shuang , Jin Zixuan , Shi Congcong , Liu Junyu , Lin Jixiang , Yan Xiufeng
Published: February 2023

The early seedling stage is considered the most vulnerable period for plants, especially under salinity conditions. The castor plant (Ricinus communis) is a well-known oil and energy crop worldwide that can survive under stressful conditions. However, the specific mechanisms of this species during its early seedling stage under salt stress are still not clearly understood. Here, the physiological and transcriptome changes in the cotyledons and roots of the castor plant were evaluated. The results indicated that salt stress (150 mM NaCl, 6 d) increased malondialdehyde (MDA) and proline content, whereas it decreased dry weight (DW) and soluble sugar content. The Illumina Hiseq 2500 platform was used to analyze transcriptome profiles in the cotyledons and roots under salt stress conditions. The results showed that 1580 differentially expressed genes (DEGs) were found in the cotyledons (880 upregulated and 700 downregulated) and 1502 DEGs in the roots (732 upregulated and 770 downregulated). Furthermore, we found that salt stress significantly regulated 22 genes (e.g., 29520.t000005, 29633.t000030, and 29739.t000024) involved in protein processing in the endoplasmic reticulum of the cotyledons. However, salt stress induced the expression of 25 genes (e.g., 30068.t000101, 30076.t000022, 29970.t000022, and 29957.t000027) involved in phenylpropanoid biosynthesis in the roots. In addition, a large number of genes participating in plant hormone signal transduction, starch and sucrose metabolisms, and arginine and proline metabolisms were induced in both cotyledons and roots. In conclusion, this study demonstrated that the different expression patterns in cotyledons and roots as well as their synergic relationship contributed to enhancing the salt tolerance of castor plants.
Climate Projections for Pinot Noir Ripening Potential in the Fort Ross-Seaview, Los Carneros, Petaluma Gap, and Russian River Valley American Viticultural Areas
Authors: Skahill Brian , Berenguer Bryan , Stoll Manfred
Published: February 2023

An unbiased MACA CMIP5 ensemble that optimized calculation of the growing season average temperature (GST) viticulture climate classification index throughout Northern California’s Fort Ross-Seaview (FRS), Los Carneros (LC), Petaluma Gap (PG), and Russian River Valley (RRV) American Viticultural Areas (AVAs) was applied to compute the GST index and Pinot noir specific applications of the grapevine sugar ripeness (GSR) model on a mean decadal basis from the 1950s to the 2090s using RCP4.5 and RCP8.5 projections of minimum and maximum daily temperature. From the 1950s to the 2090s, a 2.1/3.6, 2.4/4.2, 2.3/4.0, 2.3/4.0, and 2.3/4.0 °C increase in the GST index and a rate advance of 1.3/1.9, 1.1/1.8, 1.3/2.0, 1.2/1.9, and 1.2/1.9 days a decade was computed for FRS, LC, PG, RRV, and across all four AVAs while using the RCP4.5/RCP8.5 climate projections, respectively. The GST index and GSR model calculations were highly correlated across both climate projections and their fitted models were used to update the Pinot noir specific upper bound for the GST index throughout each AVA using a published optimal harvest window for the northern hemisphere. At a 220 g/L target sugar concentration, the updated upper bound was 17.6, 17.5, 17.6, 17.5, and 17.6 °C for FRS, LC, PG, RRV, and across all four AVAs. For a 240 g/L sugar concentration, it was 17.9, 17.8, 17.9, 17.8, and 17.9 °C. The results from this study together with comparable results recently reported for the Willamette Valley AVA of Oregon using a different downscaled CMIP5 model archive suggest spatial invariance, albeit sugar concentration dependent, for the updated Pinot noir specific upper bound for the GST climate index.
Clinical Characteristics and Outcomes of Persistent Staphylococcal Bacteremia in a Tertiary Care Hospital
Authors: Kitaya Shiori , Kanamori Hajime , Katori Yukio , Tokuda Koichi
Published: February 2023

Clinical outcomes of persistent staphylococcal bacteremia vary depending on the causative organism. This secondary data analysis study compared the clinical characteristics of persistent Staphylococcus aureus (S. aureus)- and coagulase-negative staphylococci (CoNS)-caused bacteremia, focusing on the methicillin-resistant status. This study used data collected from patients who underwent blood cultures between January 2012 and December 2021 at Tohoku University Hospital, Japan. Patients with persistent staphylococcal bacteremia were divided into groups based on the pathogen and methicillin-resistant status, and their characteristics were analyzed. The primary outcomes were early (30-day), late (30–90 days), and 90-day mortality rates. The early, late, and 90-day mortality rates were similar between the persistent CoNS and S. aureus bacteremia groups. Patients with persistent methicillin-resistant S. aureus (MRSA) bacteremia tended to have higher early, late, and 90-day mortality rates than those with persistent methicillin-susceptible S. aureus bacteremia (not statistically significant). No differences were observed between the methicillin-resistant and-susceptible CoNS groups. In patients with persistent CoNS bacteremia, mortality tended to increase, especially in debilitated or immunocompromised patients with distant metastases, underscoring the importance of infection source control. Mortality tended to be high in patients with persistent MRSA bacteremia, especially when persistent bacteremia clearance was not confirmed, illustrating the need for careful therapeutic management.
A Local Desiccant Antimicrobial Agent as an Alternative to Adjunctive Antibiotics in the Treatment of Periodontitis: A Narrative Review
Authors: Micu Iulia C. , Muntean Alexandrina , Roman Alexandra , Stratul Ștefan I. , Pall Emöke , Ciurea Andreea , Soancă Andrada , Negucioiu Marius , Barbu Tudoran Lucian , Delean Ada G.
Published: February 2023

Periodontitis is one of the most common oral polymicrobial infectious diseases induced by the complex interplay between the altered subgingival microbiota and the host’s dysregulated immune-inflammatory response, leading to the initiation of progressive and irreversible destruction of the periodontal tissues and eventually to tooth loss. The main goal of cause-related periodontal therapy is to eliminate the dysbiotic subgingival biofilm in order to arrest local inflammation and further periodontal tissue breakdown. Because, in some cases, subgingival mechanical instrumentation has limited efficiency in achieving those goals, various adjunctive therapies, mainly systemic and locally delivered antimicrobials, have been proposed to augment its effectiveness. However, most adjunctive antimicrobials carry side effects; therefore, their administration should be precociously considered. HybenX® (HY) is a commercial therapeutical agent with decontamination properties, which has been studied for its effects in treating various oral pathological conditions, including periodontitis. This review covers the current evidence regarding the treatment outcomes and limitations of conventional periodontal therapies and provides information based on the available experimental and clinical studies related to the HY mechanism of action and effects following its use associated with subgingival instrumentation and other types of dental treatments.
Comparative Assessment of Docking Programs for Docking and Virtual Screening of Ribosomal Oxazolidinone Antibacterial Agents
Authors: Buckley McKenna E. , Ndukwe Audrey R. N. , Nair Pramod C. , Rana Santu , Fairfull-Smith Kathryn E. , Gandhi Neha S.
Published: February 2023

Oxazolidinones are a broad-spectrum class of synthetic antibiotics that bind to the 50S ribosomal subunit of Gram-positive and Gram-negative bacteria. Many crystal structures of the ribosomes with oxazolidinone ligands have been reported in the literature, facilitating structure-based design using methods such as molecular docking. It would be of great interest to know in advance how well docking methods can reproduce the correct ligand binding modes and rank these correctly. We examined the performance of five molecular docking programs (AutoDock 4, AutoDock Vina, DOCK 6, rDock, and RLDock) for their ability to model ribosomal–ligand interactions with oxazolidinones. Eleven ribosomal crystal structures with oxazolidinones as the ligands were docked. The accuracy was evaluated by calculating the docked complexes’ root-mean-square deviation (RMSD) and the program’s internal scoring function. The rankings for each program based on the median RMSD between the native and predicted were DOCK 6 > AD4 > Vina > RDOCK >> RLDOCK. Results demonstrate that the top-performing program, DOCK 6, could accurately replicate the ligand binding in only four of the eleven ribosomes due to the poor electron density of said ribosomal structures. In this study, we have further benchmarked the performance of the DOCK 6 docking algorithm and scoring in improving virtual screening (VS) enrichment using the dataset of 285 oxazolidinone derivatives against oxazolidinone binding sites in the S. aureus ribosome. However, there was no clear trend between the structure and activity of the oxazolidinones in VS. Overall, the docking performance indicates that the RNA pocket’s high flexibility does not allow for accurate docking prediction, highlighting the need to validate VS. protocols for ligand-RNA before future use. Later, we developed a re-scoring method incorporating absolute docking scores and molecular descriptors, and the results indicate that the descriptors greatly improve the correlation of docking scores and pMIC values. Morgan fingerprint analysis was also used, suggesting that DOCK 6 underpredicted molecules with tail modifications with acetamide, n-methylacetamide, or n-ethylacetamide and over-predicted molecule derivatives with methylamino bits. Alternatively, a ligand-based approach similar to a field template was taken, indicating that each derivative’s tail groups have strong positive and negative electrostatic potential contributing to microbial activity. These results indicate that one should perform VS. campaigns of ribosomal antibiotics with care and that more comprehensive strategies, including molecular dynamics simulations and relative free energy calculations, might be necessary in conjunction with VS. and docking.
In Vivo Effect of a Nisin–Biogel on the Antimicrobial and Virulence Signatures of Canine Oral Enterococci
Authors: Cunha Eva , Ferreira Ana Filipa , Valente Sara , Matos Alice , Carreira Luís Miguel , Videira Marta , Chambel Lélia , Tavares Luís , Oliveira Manuela
Published: February 2023

Periodontal disease is a relevant oral disease in dogs and nisin–biogel has been previously proposed to be used in its control. Enterococci, as inhabitants of the oral cavity with a high genetic versatility, are a reliable bacterial model for antimicrobial studies. Our goal was to evaluate the in vivo influence of the long-term dental application of the nisin–biogel on the virulence and antimicrobial signatures of canine oral enterococci. Twenty dogs were randomly allocated to one of two groups (treatment group—TG with nisin–biogel dental application, or control group—CG without treatment) and submitted to dental plaque sampling at day 0 and after 90 days (T90). Samples were processed for Enterococcus spp. isolation, quantification, identification, molecular typing and antimicrobial and virulence characterization. From a total of 140 enterococci, molecular typing allowed us to obtain 70 representative isolates, mostly identified as E. faecalis and E. faecium. No significant differences (p > 0.05) were observed in the virulence index of the isolates obtained from samples collected from the TG and CG at T90. At T90, a statistically significant difference (p = 0.0008) was observed in the antimicrobial resistance index between the isolates from the TC and CG. Oral enterococci were revealed to be reservoirs of high resistant and virulent phenotypes.
Limosilactobacillus fermentum 3872 That Produces Class III Bacteriocin Forms Co-Aggregates with the Antibiotic-Resistant Staphylococcus aureus Strains and Induces Their Lethal Damage
Authors: Abramov Vyacheslav M. , Kosarev Igor V. , Machulin Andrey V. , Priputnevich Tatiana V. , Deryusheva Evgenia I. , Nemashkalova Ekaterina L. , Chikileva Irina O. , Abashina Tatiana N. , Panin Alexander N. , Melnikov Vyacheslav G. , Suzina Nataliya E. , Nikonov Ilia N. , Selina Marina V. , Khlebnikov Valentin S. , Sakulin Vadim K. , Samoilenko Vladimir A. , Gordeev Alexey B. , Sukhikh Gennady T. , Uversky Vladimir N. , Karlyshev Andrey V.
Published: February 2023

LF3872 was isolated from the milk of a healthy lactating and breastfeeding woman. Earlier, the genome of LF3872 was sequenced, and a gene encoding unique bacteriocin was discovered. We have shown here that the LF3872 strain produces a novel thermolabile class III bacteriolysin (BLF3872), exhibiting antimicrobial activity against antibiotic-resistant Staphylococcus aureus strains. Sequence analysis revealed the two-domain structural (lysozyme-like domain and peptidase M23 domain) organization of BLF3872. At least 25% residues of this protein are expected to be intrinsically disordered. Furthermore, BLF3872 is predicted to have a very high liquid-liquid phase separation. According to the electron microscopy data, the bacterial cells of LF3872 strain form co-aggregates with the S. aureus 8325-4 bacterial cells. LF3872 produced bacteriolysin BLF3872 that lyses the cells of the S. aureus 8325-4 mastitis-inducing strain. The sensitivity of the antibiotic-resistant S. aureus collection strains and freshly isolated antibiotic-resistant strains was tested using samples from women with lactation mastitis; the human nasopharynx and oral cavity; the oropharynx of pigs; and the cows with a diagnosis of clinical mastitis sensitive to the lytic action of the LF3872 strain producing BLF3872. The co-cultivation of LF3872 strain with various antibiotic-resistant S. aureus strains for 24 h reduced the level of living cells of these pathogens by six log. The LF3872 strain was found to be able to co-aggregate with all studied S. aureus strains. The cell-free culture supernatant of LF3872 (CSLF3872) induced S. aureus cell damage and ATP leakage. The effectiveness of the bacteriolytic action of LF3872 strain did not depend on the origin of the S. aureus strains. The results reported here are important for the creation of new effective drugs against antibiotic-resistant strains of S. aureus circulating in humans and animals.
Solid–Electrolyte Interface Formation on Si Nanowires in Li-Ion Batteries: The Impact of Electrolyte Additives
Authors: Sarra Angelo , Brutti Sergio , Palumbo Oriele , Capitani Francesco , Borondics Ferenc , Appetecchi Giovanni Battista , Carboni Nicholas , Abdul Ahad Syed , Geaney Hugh , Ryan Kevin , Paolone Annalisa
Published: February 2023

The morphological changes of Si nanowires (Si NWs) cycled in 1:1 ethylene–carbonate (EC)/diethyl–carbonate (DEC) with or without different additives, fluoroethylene carbonate (FEC) or vinylene carbonate (VC), as well as the composition of the deposited solid–electrolyte interphase layer, are investigated by a combination of experimental microscopic and spectroscopic techniques. Scanning electron microscopy and optical spectroscopy highlight that the NW morphology is better preserved in samples cycled in the presence of FEC and VC additives compared to the additive-free electrolyte. However, only the use of FEC is capable of slightly mitigating the amorphization of silicon upon cycling. The solid electrolyte interphase (SEI) formed over the Si NWs cycled in the additive-free electrolyte is richer in organic and inorganic carbonates compared to the SEI grown in the presence of the VC and FEC additives. Furthermore, both additives are able to remarkably limit the degradation of the LiPF6 salt. Overall, the use of the FEC-additive in the carbonate-based electrolyte promotes both morphological and structural resilience of the Si NWs upon cycling thanks to the optimal composition of the SEI layer.
Simple and Powerful PCG Classification Method Based on Selection and Transfer Learning for Precision Medicine Application
Authors: Barnawi Ahmed , Boulares Mehrez , Somai Rim
Published: February 2023

The World Health Organization (WHO) highlights that cardiovascular diseases (CVDs) are one of the leading causes of death globally, with an estimated rise to over 23.6 million deaths by 2030. This alarming trend can be attributed to our unhealthy lifestyles and lack of attention towards early CVD diagnosis. Traditional cardiac auscultation, where a highly qualified cardiologist listens to the heart sounds, is a crucial diagnostic method, but not always feasible or affordable. Therefore, developing accessible and user-friendly CVD recognition solutions can encourage individuals to integrate regular heart screenings into their routine. Although many automatic CVD screening methods have been proposed, most of them rely on complex prepocessing steps and heart cycle segmentation processes. In this work, we introduce a simple and efficient approach for recognizing normal and abnormal PCG signals using Physionet data. We employ data selection techniques such as kernel density estimation (KDE) for signal duration extraction, signal-to-noise Ratio (SNR), and GMM clustering to improve the performance of 17 pretrained Keras CNN models. Our results indicate that using KDE to select the appropriate signal duration and fine-tuning the VGG19 model results in excellent classification performance with an overall accuracy of 0.97, sensitivity of 0.946, precision of 0.944, and specificity of 0.946.
Novel, Blended Polymeric Microspheres for the Controlled Release of Methotrexate: Characterization and In Vivo Antifibrotic Studies
Authors: Nabai Layla , Ghahary Aziz , Jackson John
Published: February 2023

Low dose methotrexate (MTX) is known to effectively decrease type I collagen production in dermal fibroblasts, while increasing the matrix metalloproteinase-1 (MMP-1) production in vitro. For in vivo use as an antifibrotic agent on wounds, a linear and extended controlled release formulation of MTX is required. The objective of this study was to optimize the fabrication of MTX-loaded polymeric microspheres with such properties, and to test the efficacy for the prevention of fibrosis in vivo. Poly lactic-co-glycolic acid (PLGA), Poly (L-lactic acid) (PLLA) and the diblock copolymer, methoxypolyethylene glycol-block-poly (D, L-lactide) (MePEG-b-PDLLA), were used to fabricate microspheres, which were then characterized in terms of size, drug encapsulation efficiency, and in vitro release profiles. The optimized formulation (PLGA with diblock copolymer) showed high drug encapsulation efficiency (>80%), low burst release (~10%) and a gradual release of MTX. The amphipathic diblock copolymer is known to render the microsphere surface more biocompatible. In vivo, these microspheres were effective in reducing fibrotic tissue which was confirmed by quantitative measurement of type I collagen and α-smooth muscle actin expression, demonstrating that MTX can be efficiently encapsulated in PLGA microspheres to provide a delayed, gradual release in wound beds to reduce fibrosis in vivo.
Evaluation of Four Rapid Antigen Tests for the Detection of SARS-CoV-2 Infection with Nasopharyngeal Swabs
Authors: Lim Ho-Jae , Park Min-Young , Baek Young-Hyun , Lee Hyeon-Seo , Kim Inhee , Kwon Youngjin , You Youngshin , Nam Kyoungwoo , Yang Jae-Hyun , Kim Min-Jin , Yu Nae , Sohn Yong-Hak , Park Jung-Eun , Yang Yong-Jin
Published: February 2023

Owing to the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the capacity of testing systems based on the gold standard real-time reverse transcription–polymerase chain reaction (rRT-PCR) is limited. Rapid antigen tests (RATs) can substantially contribute to the prevention of community transmission, but their further assessment is required. Here, using 1503 nasopharyngeal swabs, we compared the diagnostic performance of four RAT kits (Abbott Panbio™ COVID-19 Ag Rapid Test, SD Biosensor Standard™ Q COVID-19 Ag Test, Humasis COVID-19 Ag Test, and SG Medical Acrosis COVID-19 Ag Test) to the cycle threshold (Ct) values obtained from rRT-PCR. The precision values, area under the curve values, SARS-CoV-2 variant detection ability, and non-SARS-CoV-2 specificity of all four kits were similar. An assay using the Acrosis kit had a significantly better positive detection rate with a higher recall value and cut-off value than that using the other three RAT kits. During the current COVID-19 pandemic, the Acrosis kit is an effective tool to prevent the spread of SARS-CoV-2 in communities.
The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population
Authors: Spedicati Beatrice , Santin Aurora , Nardone Giuseppe Giovanni , Rubinato Elisa , Lenarduzzi Stefania , Graziano Claudio , Garavelli Livia , Miccoli Sara , Bigoni Stefania , Morgan Anna , Girotto Giorgia
Published: February 2023

Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50–60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL—70% of cases) or syndromic (SHL—30% of cases). In this study, a multistep and integrative approach aimed at identifying the molecular cause of HHL in 102 patients, whose GJB2 analysis already showed a negative result, is described. In NSHL patients, multiplex ligation probe amplification and long-range PCR analyses of the STRC gene solved 13 cases, while whole exome sequencing (WES) identified the genetic diagnosis in 26 additional ones, with a total detection rate of 47.6%. Concerning SHL, WES detected the molecular cause in 55% of cases. Peculiar findings are represented by the identification of four subjects displaying a dual molecular diagnosis and eight affected by non-syndromic mimics, five of them presenting Usher syndrome type 2. Overall, this study provides a detailed characterisation of the genetic causes of HHL in the Italian population. Furthermore, we highlighted the frequency of Usher syndrome type 2 carriers in the Italian population to pave the way for a more effective implementation of diagnostic and follow-up strategies for this disease.
Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship
Authors: Piccioni Andrea , Rosa Federico , Mannucci Sergio , Manca Federica , Merra Giuseppe , Chiloiro Sabrina , Candelli Marcello , Covino Marcello , Gasbarrini Antonio , Franceschi Francesco
Published: February 2023

There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus type 1 and LADA, in light of the latest evidence. We will then look at both how the role of the gut microbiota appears to be increasingly crucial in the pathogenesis of these disorders and how this aspect may be instrumental in the development of new potential therapeutic strategies that modulate the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation.
Radiation-Induced Nephropathy in the Murine Model Is Ameliorated by Targeting Heparanase
Authors: Abecassis Alexia , Hermano Esther , Sheva Kim , Rubinstein Ariel M. , Elkin Michael , Meirovitz Amichay
Published: February 2023

Agents used to reduce adverse effects common in cancer treatment modalities do not typically possess tumor-suppressing properties. We report that heparanase, an extracellular matrix-degrading enzyme, is a promising candidate for preventing radiation nephropathy. Heparanase promotes tumor development and progression and is upregulated in tumors found in the abdominal/pelvic cavity, whose radiation treatment may result in radiation nephropathy. Additionally, heparan sulfate degradation by heparanase has been linked to glomerular and tubular/interstitial injury in several kidney disorders. In this study, heparanase mRNA levels were measured in HK-2- and HEK-293-irradiated kidney cells and in a murine radiation nephropathy model by qRT-PCR. Roneparstat (specific heparanase inhibitor) was administered to irradiated mice, and 24 h urinary albumin was measured. Kidneys were harvested and weighed 30 weeks post-irradiation. Clinically relevant doses of ionizing radiation upregulated heparanase expression in both renal cells and mice kidneys. A murine model of abdominal radiation therapy revealed that Roneparstat abolished radiation-induced albuminuria—the hallmark of radiation nephropathy. Given the well-documented anti-cancer effects of heparanase inhibition, our findings attest this enzyme to be a unique target in cancer therapy due to its dual action. Targeting heparanase exerts not only direct anti-tumor effects but protects against radiation-induced kidney damage—the backbone of cancer therapy across a range of malignancies.
On the Mechanical Behaviour of Biomimetic Cornstalk-Inspired Lightweight Structures
Authors: Siddique Shakib Hyder , Hazell Paul J. , Pereira Gerald G. , Wang Hongxu , Escobedo Juan P. , Ameri Ali A. H.
Published: February 2023

This paper presents an investigation on the stiffness and energy absorption capabilities of three proposed biomimetic structures based on the internal architecture of a cornstalk. 3D printing was used to manufacture specimens using a tough and impact-resistant thermoplastic material, acrylonitrile butadiene styrene (ABS). The structural stiffness, maximum stress, densification strain, and energy absorption were extracted from the compression tests performed at a strain rate of 10−3 s−1. A numerical model was developed to analyse the behaviour of the biomimetic structures under compression loading. Further, a damage examination was conducted through optical microscopy and profilometry. The results showed that the cornstalk-inspired biomimetic structure exhibited a superior specific energy absorption (SEA) capability that was three times higher than that of the other core designs as reported in the literature.
Osseointegration of Titanium Implants in a Botox-Induced Muscle Paralysis Rat Model Is Sensitive to Surface Topography and Semaphorin 3A Treatment
Authors: Deng Jingyao , Cohen D. Joshua , Berger Michael B. , Sabalewski Eleanor L. , McClure Michael J. , Boyan Barbara D. , Schwartz Zvi
Published: February 2023

Reduced skeletal loading associated with many conditions, such as neuromuscular injuries, can lead to bone fragility and may threaten the success of implant therapy. Our group has developed a botulinum toxin A (botox) injection model to imitate disease-reduced skeletal loading and reported that botox dramatically impaired the bone formation and osseointegration of titanium implants. Semaphorin 3A (sema3A) is an osteoprotective factor that increases bone formation and inhibits bone resorption, indicating its potential therapeutic role in improving osseointegration in vivo. We first evaluated the sema3A effect on whole bone morphology following botox injections by delivering sema3A via injection. We then evaluated the sema3A effect on the osseointegration of titanium implants with two different surface topographies by delivering sema3A to cortical bone defect sites prepared for implant insertion and above the implants after insertion using a copper-free click hydrogel that polymerizes rapidly in situ. Implants had hydrophobic smooth surfaces (PT) or multiscale biomimetic micro/nano topography (SLAnano). Sema3A rescued the botox-impaired bone formation. Furthermore, biomimetic Ti implants improved the bone-to-implant contact (BIC) and mechanical properties of the integrated bone in the botox-treated rats, which sema3A enhanced. This study demonstrated the value of biomimetic approaches combining multiscale topography and biologics in improving the clinical outcomes of implant therapy.
The Prosocial-Culture-Work Nexus: An Integrative Literature Review and Future Research Agenda
Authors: Gibb Stephen
Published: February 2023

Organization culture is a potential antecedent and moderator of prosocial behaviors at work. So, what is currently known about the prosocial-culture-work nexus? Studies of this nexus may be predicted to exist in the form of research on organization cultures of three types. One would be studies of specific organization cultures representing espoused Employer Value Propositions (EVPs). One would be etic studies using constructs of organization culture. The other would be emic studies, with the ‘thick description’ associated with ethnography/anthropology. An integrative literature review on the prosocial-organization culture-work nexus located 22 studies. Most studies are of the etic type, while others are mainly concerned with theory development. There is no evidence of a clear concept of organization culture being used in any study. The future research agenda for the prosocial-culture-work nexus follow from this. Constructs of organization culture need to be adopted and used. There is huge scope for EVP studies to explicitly and critically explore the breadth of the prosocial themes these often contain. Etic studies are the ones where the lack of organization culture constructs is most striking, given their methodologies. More emic studies with ethnographic/anthropological depth to explore, both work organizations in single countries, and in comparative studies across countries, are needed. Better clarified prosocial constructs will not in themselves advance knowledge if the organizational culture contexts in which prosociality exists remain under-appreciated.
Effects of Volume Ratio, Layout and Leave Size of Indoor Plants on Workers’ Attention Recovery in Factory Staff Break Area
Authors: Fang Zirui , Xu Hongpeng , Tao Lulu , Tan Yichen , Li Yuqing , Wu Jianmei
Published: February 2023

A more efficient attention recovery of workers during their break time is essential for achieving higher productivity and wellness. In recent years, the biophilic design that introduces indoor plants has become one of the solutions to these problems. This study aims to determine the impact factors and corresponding levels related to indoor planting design concerning workers’ attention recovery. Firstly, the volume ratio, layout, and leaf size of indoor plants and the corresponding levels were put forward by a focus group study with ten participants. Secondly, the orthogonal experiment method established nine virtual recovery scenarios based on characteristics extraction of staff break areas in the factory. Thirdly, eighteen participants were guided to feel fatigued by experiencing the sustained attention to response test to measure the baseline attention level of participants. Then, participants rested in the virtual scenarios. Lastly, the attention test was conducted again to observe participants’ attention recovery degree. The difference values of participants’ sensitivity, reaction times, and the number of correct responses between the two detection targets were applied to evaluate the attention recovery. Results showed that the volume ratio of indoor plants had the most significant effect on workers’ attention recovery; 3% by volume ratio, mixed floor and wall plants and floor planting with large leaves were demonstrated as the optimal indoor planting design for attention recovery.
Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review
Authors: Fernandez-Pombo Antia , Diaz-Lopez Everardo Josue , Castro Ana I. , Sanchez-Iglesias Sofia , Cobelo-Gomez Silvia , Prado-Moraña Teresa , Araujo-Vilar David
Published: February 2023

Type 2 familial partial lipodystrophy (FPLD2) is a laminopathic lipodystrophy due to pathogenic variants in the LMNA gene. Its rarity implies that it is not well-known. The aim of this review was to explore the published data regarding the clinical characterisation of this syndrome in order to better describe FPLD2. For this purpose, a systematic review through a search on PubMed until December 2022 was conducted and the references of the retrieved articles were also screened. A total of 113 articles were included. FPLD2 is characterised by the loss of fat starting around puberty in women, affecting limbs and trunk, and its accumulation in the face, neck and abdominal viscera. This adipose tissue dysfunction conditions the development of metabolic complications associated with insulin resistance, such as diabetes, dyslipidaemia, fatty liver disease, cardiovascular disease, and reproductive disorders. However, a great degree of phenotypical variability has been described. Therapeutic approaches are directed towards the associated comorbidities, and recent treatment modalities have been explored. A comprehensive comparison between FPLD2 and other FPLD subtypes can also be found in the present review. This review aimed to contribute towards augmenting knowledge of the natural history of FPLD2 by bringing together the main clinical research in this field.
Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period
Authors: Shimizu Yo , Sakata-Haga Hiromi , Saikawa Yutaka , Hatta Toshihisa
Published: February 2023

The developmental origins of health and disease (DOHaD) indicate that fetal tissues and organs in critical and sensitive periods of development are susceptible to structural and functional changes due to the adverse environment in utero. Maternal immune activation (MIA) is one of the phenomena in DOHaD. Exposure to maternal immune activation is a risk factor for neurodevelopmental disorders, psychosis, cardiovascular diseases, metabolic diseases, and human immune disorders. It has been associated with increased levels of proinflammatory cytokines transferred from mother to fetus in the prenatal period. Abnormal immunity induced by MIA includes immune overreaction or immune response failure in offspring. Immune overreaction is a hypersensitivity response of the immune system to pathogens or allergic factor. Immune response failure could not properly fight off various pathogens. The clinical features in offspring depend on the gestation period, inflammatory magnitude, inflammatory type of MIA in the prenatal period, and exposure to prenatal inflammatory stimulation, which might induce epigenetic modifications in the immune system. An analysis of epigenetic modifications caused by adverse intrauterine environments might allow clinicians to predict the onset of diseases and disorders before or after birth.
Solvatochromic Behavior of 2,7-Disubstituted Sila- and Germafluorenes
Authors: Jarrett-Noland Shelby J. , McConnell William , Braddock-Wilking Janet , Dupureur Cynthia M.
Published: February 2023

Push–pull dyes exhibit intramolecular charge transfer behavior, which due to changes in the dipole moment upon excitation, is the origin of their sensitivity to the environment. Such compounds are of interest as probes for bioimaging and as biosensors to monitor cellular dynamics and molecular interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Fluorophores with scaffolding that can be used to tune and optimize solvatochromic behavior are of particular interest. Here, we investigate the environmental sensitivity of a small library of highly fluorescent 2,7-disubstituted sila- and germafluorenes. Density functional theory (DFT) calculations show that charge transfer occurs from the alkyne core out to the 2,7-substitutents and 3,6-methoxy substituents, the hallmark of push–pull behavior. They exhibit HOMO–LUMO energy gaps of about 3 eV with desirable dipole moments ranging from 2 to 9 D. These compounds exhibit desirable Stokes shifts in various solvents (25 to 102 nm). Interestingly, silafluorene with a benzaldehyde substituent exhibits competitive solvatochromic behavior. With the ability to tune push–pull properties via the 2,7-substituent, these disubstituted sila- and germafluorenes have excellent potential as biological probes.
Effectiveness and Tolerability of a New Formulation of a Topical Anesthetic in Reduction of Pain and Parents’ Satisfaction in Pediatric Dentistry
Authors: Ferrazzano Gianmaria Fabrizio , Di Fabio Giuseppe , Gatto Roberto , Caruso Sara , Botticelli Gianluca , Caruso Silvia
Published: February 2023

The aim of the present study was to test a new topical anesthetic gel with a different formulation (10% lidocaine, 10% prilocaine) to analyze its effectiveness in pain control, during the subsequent injection of local anesthetic, and the presence of any side effects. Methods: The study’s research design was a randomized controlled clinical trial on 300 children, aged 5–8 years, divided into two groups, each of 150 patients, according to pre-injection procedures (presence or absence of topical anesthesia). The injection pain was analyzed using the Wong-Baker Faces Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability Scale (FLACC). At the end of the procedures, patients’ parents’ satisfaction was recorded. The data were analyzed using the Student’s T test, Mann–Whitney U test and Chi-square test. Results: There were statistically significant differences between the two groups both in the PRS and FLACC ratings. Both in subjective and objective pain evaluations, significantly higher pain ratings were observed in the group without topical anesthesia. There was also a statistically significant difference in terms of patients’ parents’ judgment, as in the group with the use of topical anesthetic the level of parental satisfaction is statistically higher. Conclusion: The experimental anesthetic has proved very effective in its use as a topical gel in both pain measurement scales, thus validating its use on the oral mucosa, for its pharmacological and psychological effect, in the total absence of local and systemic side effects.
Novel Indices to Improve the Diagnostic Ability of Nocturnal Oximetry in Children with OSAS
Authors: Pappa Panagiota , Kourelis Konstantinos , Goulioumis Anastasios , Tsiakou Magdalene , Plotas Panagiotis , Bertzouanis Aris , Theodorakopoulos Ilias , Mourtzouchos Konstantinos , Anthracopoulos Michael B. , Asimakopoulos Athanasios , Fouzas Sotirios
Published: February 2023

Nocturnal pulse oximetry (NOx) is an alternative diagnostic test for obstructive sleep apnea syndrome (OSAS) in childhood yet with variable diagnostic performance. Our aim was to apply advanced signal analysis to develop novel and more accurate NOx indices. We studied 45 children aged 3–10 years who underwent adenotonsillectomy for adenotonsillar hypertrophy and OSAS symptoms. Participants performed NOx before and three months after surgery, and the changes in McGill oximetry score (MOS), oxygen desaturation ≥3% index (ODI3), and the novel parameters—cumulative saturation area (CSA) and oxygen saturation sample entropy (SSE)—were assessed. There was a significant improvement (p < 0.001) in all NOx indices. When pre- and post-adenotonsillectomy NOx recordings were compared, the MOS had an area under the curve (AUC) of 0.811 with 63.2% sensitivity and 100% specificity at a cutoff >1. The AUC of ODI3 was 0.994, with 97.8% sensitivity and 91.1% specificity at a cutoff of >3.6 events per hour. The CSA and SSE had an AUC of 1.00, with 100% sensitivity and specificity at a cutoff of >293 and >0.99, respectively. We conclude that the herein-introduced indices—CSA and SSE—hold promise in improving the diagnostic ability of NOx in children suspected of OSAS.
Use of Cardio-Pulmonary Ultrasound in the Neonatal Intensive Care Unit
Authors: Ciarmoli Elena , Storti Enrico , Cangemi Jessica , Leone Arianna , Pierro Maria
Published: February 2023

Cardiopulmonary ultrasound (CPUS), the combination of lung ultrasound (LUS) and targeted neonatal echocardiography (TnECHO)AA, may offer a more appropriate approach to the challenging neonatal cardiovascular and respiratory disorders. This paper reviews the possible use of CPUS in the neonatal intensive care unit (NICU).
Considering Risks to Researchers and Staff in Low-Resource Settings during Public Health Crises: A Proposed Conceptual Model
Authors: Perez Krystle M. , Asim Muhammad , Weiss Elliott M. , Valentine Gregory C. , Kavi Avinash , Somannavar Manjunath S. , Iwuh Ibezimako , Chiweza Chikondi , Tickell Kirkby D. , Singa Benson O. , Beima-Sofie Kristin , Batra Maneesh , Walson Judd L. , Umoren Rachel , Kelley Maureen , Saleem Sarah
Published: February 2023

Human subjects research protections have historically focused on mitigating risk of harm and promoting benefits for research participants. In many low-resource settings (LRS), complex and often severe challenges in daily living, poverty, geopolitical uprisings, sociopolitical, economic, and climate crises increase the burdens of even minimal risk research. While there has been important work to explore the scope of ethical responsibilities of researchers and research teams to respond to these wider challenges and hidden burdens in global health research, less attention has been given to the ethical dilemmas and risk experienced by frontline researcher staff as they perform research-related activities in LRS. Risks such as job insecurity, moral distress, infection, or physical harm can be exacerbated during public health crises, as recently highlighted by the COVID-19 pandemic. We highlight the layers of risk research staff face in LRS and present a conceptual model to characterize drivers of this risk, with particular attention to public health crises. A framework by which funders, institutions, principal investigators, and/or research team leaders can systematically consider these additional layers of risk to researchers and frontline staff is an important and needed addition to routine research proposals and protocol review.