bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery
Authors: Battiston Kyle , Parrag Ian , Statham Matthew , Louka Dimitra , Fischer Hans , Mackey Gillian , Daley Adam , Gu Fan , Baldwin Emily , Yang Bingqing , Muirhead Ben , Hicks Emily Anne , Sheardown Heather , Kalachev Leonid , Crean Christopher , Edelman Jeffrey , Santerre J. Paul , Naimark Wendy 
Published: May 2021

AbstractPolymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.
Hox dosage contributes to flight appendage morphology in Drosophila
Authors: Paul Rachel , Giraud Guillaume , Domsch Katrin , Duffraisse Marilyne , Marmigère Frédéric , Khan Soumen , Vanderperre Solene , Lohmann Ingrid , Stoks Robby , Shashidhara L. S. , Merabet Samir 
Published: May 2021

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.
Cells/colony motion of oral keratinocytes determined by non-invasive and quantitative measurement using optical flow predicts epithelial regenerative capacity
Authors: Hoshikawa Emi , Sato Taisuke , Haga Kenta , Suzuki Ayako , Kobayashi Ryota , Tabeta Koichi , Izumi Kenji 
Published: May 2021

AbstractCells/colony motion determined by non-invasive, quantitative measurements using the optical flow (OF) algorithm can indicate the oral keratinocyte proliferative capacity in early-phase primary cultures. This study aimed to determine a threshold for the cells/colony motion index to detect substandard cell populations in a subsequent subculture before manufacturing a tissue-engineered oral mucosa graft and to investigate the correlation with the epithelial regenerative capacity. The distinctive proliferating pattern of first-passage [passage 1 (p1)] cells reveals the motion of p1 cells/colonies, which can be measured in a non-invasive, quantitative manner using OF with fewer full-screen imaging analyses and cell segmentations. Our results demonstrate that the motion index lower than 40 μm/h reflects cellular damages by experimental metabolic challenges although this value shall only apply in case of our culture system. Nonetheless, the motion index can be used as the threshold to determine the quality of cultured cells while it may be affected by any different culture conditions. Because the p1 cells/colony motion index is correlated with epithelial regenerative capacity, it is a reliable index for quality control of oral keratinocytes.
Long-term conservation agriculture and best nutrient management improves productivity and profitability coupled with soil properties of a maize–chickpea rotation
Authors: Pooniya Vijay , Zhiipao R. R. , Biswakarma Niraj , Jat S. L. , Kumar Dinesh , Parihar C. M. , Swarnalakshmi K. , Lama Achal , Verma A. K. , Roy Debasish , Das Kajal , Majumdar K. , Satyanarayana T. , Jat R. D. , Ghasal P. C. , Ram Hardev , Jat Rajkumar , Nath Amlan 
Published: May 2021

AbstractConservation agriculture (CA)-based practices have been promoted and recouped, as they hold the potential to enhance farm profits besides a consistent improvement in soil properties. A 7 years' field experiment consisting of three crop establishment practices viz., zero-till flatbed (ZTFB), permanent beds (PNB), conventional system (CT) along with the three-nutrient management; nutrient expert-based application (NE), recommended fertilization (RDF), and farmers’ fertilizer practice (FFP), was carried out from 2013 to 2020. The CA-based practices (ZTFB/PNB) produced 13.9–17.6% greater maize grain-equivalent yield (MGEY) compared to the CT, while NE and RDF had 10.7–20% greater MGEY than the FFP. PNB and ZTFB gave 28.8% and 24% additional net returns than CT, while NE and RDF had 22.8% and 17.4% greater returns, respectively over FFP. PNB and ZTFB had 2.3–4.1% (0.0–0.20 m soil layers) lower bulk density than the CT. Furthermore, microbial biomass carbon (MBC) increased by 8–19% (0.0–0.50 m soil layers) in ZTFB/PNB over the CT, and by 7.6–11.0% in NE/RDF over FFP. Hence, CA-based crop establishment coupled with the NE or RDF could enhance the yields, farm profits, soil properties of the maize–chickpea rotation, thereby, could sustain production in the long run.
CRISPR-mediated mutations in the ABC transporter gene ABCA2 confer pink bollworm resistance to Bt toxin Cry2Ab
Authors: Fabrick Jeffrey A. , LeRoy Dannialle M. , Mathew Lolita G. , Wu Yidong , Unnithan Gopalan C. , Yelich Alex J. , Carrière Yves , Li Xianchun , Tabashnik Bruce E. 
Published: May 2021

AbstractCrops genetically engineered to produce insecticidal proteins from Bacillus thuringiensis (Bt) have many benefits and are important globally for managing insect pests. However, the evolution of pest resistance to Bt crops reduces their benefits. Understanding the genetic basis of such resistance is needed to better monitor, manage, and counter pest resistance to Bt crops. Previous work shows that resistance to Bt toxin Cry2Ab is associated with mutations in the gene encoding the ATP-binding cassette protein ABCA2 in lab- and field-selected populations of the pink bollworm (Pectinophora gossypiella), one of the world’s most destructive pests of cotton. Here we used CRISPR/Cas9 gene editing to test the hypothesis that mutations in the pink bollworm gene encoding ABCA2 (PgABCA2) can cause resistance to Cry2Ab. Consistent with this hypothesis, introduction of disruptive mutations in PgABCA2 in a susceptible strain of pink bollworm increased the frequency of resistance to Cry2Ab and facilitated creation of a Cry2Ab-resistant strain. All Cry2Ab-resistant individuals tested in this study had disruptive mutations in PgABCA2. Overall, we found 17 different disruptive mutations in PgABCA2 gDNA and 26 in PgABCA2 cDNA, including novel mutations corresponding precisely to single-guide (sgRNA) sites used for CRISPR/Cas9. Together with previous results, these findings provide the first case of practical resistance to Cry2Ab where evidence identifies a specific gene in which disruptive mutations can cause resistance and are associated with resistance in field-selected populations.
Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
Authors: He Yingbo , Taylor Natalie , Yao Xiang , Bhattacharya Anindya 
Published: May 2021

AbstractMicroglia, CNS resident innate immune cells, respond strongly to activation of TLR3 and TLR4, which recognize viral dsRNA poly(I:C) and bacterial endotoxin LPS, respectively. However, few studies have thoroughly and parallelly compared functional phenotypes and downstream mechanisms between LPS- and poly(I:C)-exposed primary microglia. Here, we investigated the responses of mouse primary microglia upon LPS and poly(I:C) stimulation by detecting various phenotypes ranging from morphology, proliferation, secretion, chemotaxis, to phagocytosis. Furthermore, we explored their sequential gene expression and the downstream signal cascades. Interestingly, we found that the microglial activation pattern induced by LPS was distinguished from that induced by poly(I:C). Regarding microglial morphology, LPS caused an ameboid-like shape while poly(I:C) induced a bushy shape. Microglial proliferation was also facilitated by LPS but not by poly(I:C). In addition, LPS and poly(I:C) modulated microglial chemotaxis and phagocytosis differently. Furthermore, genome-wide analysis provided gene-level support to these functional differences, which may be associated with NF-κb and type I interferon pathways. Last, LPS- and poly(I:C)-activated microglia mediated neurotoxicity in a co-culture system. This study extends our understanding of TLR roles in microglia and provides insights into selecting proper inflammatory microglial models, which may facilitate identification of new targets for therapeutic application.
A study of the correlations between IVIM-DWI parameters and the histologic differentiation of hepatocellular carcinoma
Authors: Zhou Yi , Yang Gang , Gong Xue-Qin , Tao Yun-Yun , Wang Ran , Zheng Jing , Yang Cui , Peng Juan , Yang Lin , Li Jing-Dong , Zhang Xiao-Ming 
Published: May 2021

AbstractThe present study aimed to investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) in the preoperative prediction of the histologic differentiation of hepatocellular carcinoma (HCC). Seventy HCC patients were scanned with a 3.0 T magnetic resonance scanner. The values of apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and the fraction of the fast apparent diffusion coefficient (f) were measured. Analysis of variance was used to compare the differences in parameters between groups with different degrees of histologic differentiation. p < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were used to analyse the efficacy of IVIM-DWI parameters for predicting the histologic differentiation of HCC. The ADC and D values for well, moderately and poorly differentiated HCC were 1.35 ± 0.17 × 10−3 mm2/s, 1.16 ± 0.17 × 10−3 mm2/s, 0.98 ± 0.21 × 10−3 mm2/s, and 1.06 ± 0.15 × 10−3 mm2/s, 0.88 ± 0.16 × 10−3 mm2/s, 0.76 ± 0.18 × 10−3 mm2/s, respectively, and all differences were significant. The D* and f values of the three groups were 32.87 ± 14.70 × 10−3 mm2/s, 41.68 ± 17.90 × 10−3 mm2/s, 34.54 ± 18.60 × 10−3 mm2/s and 0.22 ± 0.07, 0.23 ± 0.08, 0.18 ± 0.07, respectively, with no significant difference. When the cut-off values of ADC and D were 1.25 × 10−3 mm2/s and 0.97 × 10−3 mm2/s, respectively, their diagnostic sensitivities and specificities for distinguishing well differentiated HCC from moderately differentiated and poorly differentiated HCC were 73.3%, 85.5%, 86.7%, and 78.2%, and their areas under the ROC curve were 0.821 and 0.841, respectively. ADC and D values can be used preoperatively to predict the degree of histologic differentiation in HCC, and the D value has better diagnostic value.
Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
Authors: McMillan Ian A. , Norris Michael H. , Zarzycki-Siek Jan , Heacock-Kang Yun , Sun Zhenxin , Borlee Bradley R. , Hoang Tung T. 
Published: May 2021

AbstractBurkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease endemic to the tropics. Melioidosis manifests in various ways ranging from acute skin lesions to pneumonia and, in rare cases, infection of the central nervous system. Bp is a facultative intracellular pathogen and it can infect various cell types. The Bp intracellular lifecycle has been partially elucidated and is highly complex. Herein, we have identified a transcriptional regulator, BP1026B_II1198, that is differentially expressed as Bp transits through host cells. A deletion mutant of BP1026B_II1198 was attenuated in RAW264.7 cell and BALB/c mouse infection. To further characterize the function of this transcriptional regulator, we endeavored to determine the regulon of BP1026B_II1198. RNA-seq analysis showed the global picture of genes regulated while ChIP-seq analysis identified two specific BP1026B_II1198 binding regions on chromosome II. We investigated the transposon mutants of these genes controlled by BP1026B_II1198 and confirmed that these genes contribute to pathogenesis in RAW264.7 murine macrophage cells. Taken together, the data presented here shed light on the regulon of BP1026B_II1198 and its role during intracellular infection and highlights an integral portion of the highly complex regulation network of Bp during host infection.
Outer membrane and phospholipid composition of the target membrane affect the antimicrobial potential of first- and second-generation lipophosphonoxins
Authors: Látrová Klára , Havlová Noemi , Večeřová Renata , Pinkas Dominik , Bogdanová Kateřina , Kolář Milan , Fišer Radovan , Konopásek Ivo , Do Pham Duy Dinh , Rejman Dominik , Mikušová Gabriela 
Published: May 2021

AbstractLipophosphonoxins (LPPOs) are small modular synthetic antibacterial compounds that target the cytoplasmic membrane. First-generation LPPOs (LPPO I) exhibit an antimicrobial activity against Gram-positive bacteria; however they do not exhibit any activity against Gram-negatives. Second-generation LPPOs (LPPO II) also exhibit broadened activity against Gram-negatives. We investigated the reasons behind this different susceptibility of bacteria to the two generations of LPPOs using model membranes and the living model bacteria Bacillus subtilis and Escherichia coli. We show that both generations of LPPOs form oligomeric conductive pores and permeabilize the bacterial membrane of sensitive cells. LPPO activity is not affected by the value of the target membrane potential, and thus they are also active against persister cells. The insensitivity of Gram-negative bacteria to LPPO I is probably caused by the barrier function of the outer membrane with LPS. LPPO I is almost incapable of overcoming the outer membrane in living cells, and the presence of LPS in liposomes substantially reduces their activity. Further, the antimicrobial activity of LPPO is also influenced by the phospholipid composition of the target membrane. A higher proportion of phospholipids with neutral charge such as phosphatidylethanolamine or phosphatidylcholine reduces the LPPO permeabilizing potential.
The implication of autoantibodies in early diagnosis and monitoring of plasmonic photothermal therapy in the treatment of feline mammary carcinoma
Authors: El-Rasikh Asmaa M. , Farghali Haithem A. M. , Abdelrahman Hisham A. , Elgaffary Mostafa , Abdelmalek Shaymaa , Emam Ibrahim A. , Ghoneim Magdy A. , Selim Salah A. 
Published: May 2021

AbstractFeline mammary carcinoma (FMC) shows great similarities to human breast cancer in the cellular and molecular levels. So, in cats as in humans, the role of immune responses is indicated to detect and follow up the development of tumors. As a new breast cancer therapeutic approach, Plasmonic Photothermal Therapy (PPTT) is an effective localized treatment for canine and feline mammary-carcinoma. Its systemic effect has not been inquired yet and needs many studies to hypothesis how the PPTT eradicates tumor cells. In this study, it is the first time to detect (P53, PCNA, MUC-1, and C-MYC) feline autoantibodies (AAbs), study the relationship between PCNA AAbs and mammary-tumors, and investigate the effect of PPTT on the humoral immune response of cats with mammary-carcinoma through detection of AAbs level before, during, and after the treatment. The four-AAbs panel was evaluated in serum of normal and clinically diagnosed cats with mammary tumors using Enzyme-Linked Immunosorbent Assay. The panel showed 100% specificity and 93.7% sensitivity to mammary tumors. The panel was evaluated in PPTT monotherapy, mastectomy monotherapy, and combination therapy. PPTT monotherapy decreased AAbs level significantly while mastectomy monotherapy and combination therapy had a nonsignificant effect on AAbs level.
Altered mapping of sound frequency to cochlear place in ears with endolymphatic hydrops provide insight into the pitch anomaly of diplacusis
Authors: Guinan J. J. , Lefler S. M. , Buchman C. A. , Goodman S. S. , Lichtenhan J. T. 
Published: May 2021

AbstractA fundamental property of mammalian hearing is the conversion of sound pressure into a frequency-specific place of maximum vibration along the cochlear length, thereby creating a tonotopic map. The tonotopic map makes possible systematic frequency tuning across auditory-nerve fibers, which enables the brain to use pitch to separate sounds from different environmental sources and process the speech and music that connects us to people and the world. Sometimes a tone has a different pitch in the left and right ears, a perceptual anomaly known as diplacusis. Diplacusis has been attributed to a change in the cochlear frequency-place map, but the hypothesized abnormal cochlear map has never been demonstrated. Here we assess cochlear frequency-place maps in guinea-pig ears with experimentally-induced endolymphatic hydrops, a hallmark of Ménière’s disease. Our findings are consistent with the hypothesis that diplacusis is due to an altered cochlear map. Map changes can lead to altered pitch, but the size of the pitch change is also affected by neural synchrony. Our data show that the cochlear frequency-place map is not fixed but can be altered by endolymphatic hydrops. Map changes should be considered in assessing hearing pathologies and treatments.
Effect of physical activity levels on oncological breast surgery recovery: a prospective cohort study
Authors: Klein Ifat , Kalichman Leonid , Chen Noy , Susmallian Sergio 
Published: May 2021

AbstractAfter breast cancer (BC) surgery, women may experience a physical decline. The effect of physical activity (PA) on the course of recovery after BC surgery has not yet been thoroughly examined. To analyze the impact of physical activity performed by women undergoing breast cancer surgery on measures of function, range of motion, and self-efficacy. A prospective study was carried out in 157 patients who underwent surgery for BC between October 2018 and April 2019, divided into four groups according to the intensity of PA with 6 months follow-up. 50 sedentary patients and 107 active patients were enrolled; the mean age was 52.6. Women who performed physical activity, moderate to vigorous, demonstrated lower function disabilities (QuickDASH 2.22) compared with inactivity or light physical activity (QuickDASH 7.0, p < 0.001), with better shoulder flexion (159.0° vs. 150.7°, p = 0.007) and abduction (159.5° vs. 152.2°, p = 0.008). Higher PA levels, displayed in higher self-efficacy reports (9.5 vs. 8.8, p = 0.002), and return to prior job status (0.005). The PA level does not influence pain at one, three and 6 months postoperatively (p = 0.278, p = 0.304 and p = 0.304 respectively). High PA levels increase the risk of axillary web syndrome (p = 0.041), although, it reduces the incidence of chronic pain (p = 0.007). Women who practice physical activity recover better from BC surgery than sedentary women. The higher the intensity and frequency of training, the better the results. Vigorous activity cause axillary web syndrome, despite, it has a beneficial effect on lowering the rate of chronic pain.
The effect of increased channel interaction on speech perception with cochlear implants
Authors: Goehring Tobias , Archer-Boyd Alan W. , Arenberg Julie G. , Carlyon Robert P. 
Published: May 2021

AbstractCochlear implants (CIs) are neuroprostheses that partially restore hearing for people with severe-to-profound hearing loss. While CIs can provide good speech perception in quiet listening situations for many, they fail to do so in environments with interfering sounds for most listeners. Previous research suggests that this is due to detrimental interaction effects between CI electrode channels, limiting their function to convey frequency-specific information, but evidence is still scarce. In this study, an experimental manipulation called spectral blurring was used to increase channel interaction in CI listeners using Advanced Bionics devices with HiFocus 1J and MS electrode arrays to directly investigate its causal effect on speech perception. Instead of using a single electrode per channel as in standard CI processing, spectral blurring used up to 6 electrodes per channel simultaneously to increase the overlap between adjacent frequency channels as would occur in cases with severe channel interaction. Results demonstrated that this manipulation significantly degraded CI speech perception in quiet by 15% and speech reception thresholds in babble noise by 5 dB when all channels were blurred by a factor of 6. Importantly, when channel interaction was increased just on a subset of electrodes, speech scores were mostly unaffected and were only significantly degraded when the 5 most apical channels were blurred. These apical channels convey information up to 1 kHz at the apical end of the electrode array and are typically located at angular insertion depths of about 250 up to 500°. These results confirm and extend earlier findings indicating that CI speech perception may not benefit from deactivating individual channels along the array and that efforts should instead be directed towards reducing channel interaction per se and in particular for the most-apical electrodes. Hereby, causal methods such as spectral blurring could be used in future research to control channel interaction effects within listeners for evaluating compensation strategies.