bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological and molecular data on a new species of Polygala (Polygalaceae) from Turkey
Authors: Çeçen Ömer , Uğurlu Aydın Zübeyde , Dönmez Ali A.
Published: May 2023

Polygala fadimeana Dönmez and Çeçen is here described as a new species from the inner part of the Taurus mountain range in Turkey based on morphological data and its phylogenetic position is discussed based on molecular data. This new species is confined to limestone rock walls and is morphologically distinguished from P. kurdica and P. peshmenii by smaller plant size, nearly glabrous leaves, enrolled inner sepals, white colour crest, and other minor diagnostic features. However, a multi‐locus chloroplast phylogeny (trnL‐F and rbcL) including accessions of the new species and related taxa of Turkish Polygala revealed a close relationship to P. pruinosa and P. supina. The taxonomic relationship among the new species and P. kurdica, a poorly known species from Zagros Mountain range, and other closely related species such as P. pruinosa, P. peshmenii and P. supina are discussed. The new species is assessed as critically endangered (CR) based on current knowledge and the distribution of the new species and related taxa is mapped.
Pollinators and plants as ecosystem engineers: post‐dispersal fruits provide new habitats for other organisms
Authors: Cardoso João C. F. , Rezende Uiara C. , Caetano Ana P. S. , Oliveira Paulo E.
Published: May 2023

Ecosystem engineering consists of a ubiquitous and fundamental class of interactions where some organisms promote state changes in biotic and abiotic materials which indirectly affect others. Since the concept was created as a counterpoint to traditional flux‐based models, pollinators have never been considered to promote ecosystem engineering because they modulate the supply of resources used by seed/fruit consumers. However, dry fruits may persist in the environment for long periods after seed dispersion as empty structures that are an additional alternative for occupancy. These increase the realized niche of some organisms, being a clear example of biogenic habitats. Here, we demonstrate how pollination may boost ecosystem engineering using an illustrative case study based on a specialized interaction between a bee and an orchid with characteristic capsular fruits. We demonstrate that the orchid is fully dependent on the pollinator to set fruits. Post‐dispersal fruits are voluminous and remain attached to the plant for several years. By investigating the occupation patterns of arthropods, we show that post‐dispersal fruits are highly suitable for occupants when compared to pre‐dispersal and dispersing fruits. Only 13.3% of post‐dispersal fruits were never occupied, 33.3% had organisms inside and 53.3% showed signs of previous occupation. We propose that pollinators are allogenic engineers and plants autogenic, since they promote state changes through their actions and their own physical structure, respectively. Thus, pollination is a case of cooperative ecosystem engineering whereby the effects of the interaction between two or more species expand habitat suitability. Since most plants rely on pollination to set fruits, we suggest that pollination‐mediated engineering constitutes a widespread phenomenon. This offers a new perspective about the effects of pollination in nature, highlighting the importance of pollinators and opening new avenues of investigation of ecosystem dynamics and biodiversity maintenance.
Tropical plant–hummingbird interactions withstand short‐term experimental removal of a common flowering plant
Authors: Leimberger Kara G. , Hadley Adam S. , Frey Sarah J. K. , Betts Matthew G.
Published: May 2023

Theory suggests that species loss can trigger a coextinction cascade within a community, leading to declines in ecosystem function. However, experiments testing this prediction for plant–pollinator interactions remain uncommon. In this study, we simulated the local extinction of a hummingbird‐pollinated understory plant, Heliconia tortuosa, from tropical forest fragments using a replicated before‐after‐control‐impact (BACI) design while quantifying hummingbird abundance and space use (383 hummingbird captures and 36 radio‐tagged individuals), flower visitation rates (> 19 000 observation hours), and pollination success (529 flowers). We expected that H. tortuosa removal would either result in 1) coextinction, in which hummingbirds vacate fragments and compromise the reproductive success of the remaining flowering plants, or 2) increased hummingbird reliance on alternative floral resources, leading to sustained fragment use (persistence). In our experiment, hummingbird behavior and plant–hummingbird interactions were remarkably resistant to loss of H. tortuosa, a locally common plant species representing at least 30–40% of the available nectar resources on average. However, we did not discover evidence that hummingbirds increasingly used alternative floral resources to cope with this temporary resource loss. With the important caution that short‐term experiments may not emulate natural extinction processes, our study suggests that plant–pollinator interactions may be able to withstand single‐species plant losses, but the exact mechanisms enabling hummingbird persistence after resource removal require further research.
Feasibility Analysis of the Bone Cement‐Gelatine Sponge Composite Intravertebral Prefilling Technique for Reducing Bone Cement Leakage in Stage I and II Kümmell's Disease: A Prospective Randomized Controlled Trial
Authors: Zhou Chengqiang , Huang Shaolong , Liao Yifeng , Zhang Feng , Meng Xiao , Tang Zhongjian , Zhang Xu , Li Hua , Zhang Yao , Zhao Shuai , Wang Yunqing
Published: May 2023

Objective

Bone cement leakage is a major complication of percutaneous vertebroplasty (PVP) while treating Kümmell's disease and it is a focus of close attention during the surgical procedure. The study aimed to investigate whether pre‐injecting a composite of bone cement and gelatine sponge (the “bone cement‐gelatine sponge composite”) before injecting bone cement during PVP aids in lowering the leakage rate in stage I and II Kümmell's disease.

Methods

This prospective analysis evaluated 74 patients with stage I and II Kümmell's disease who underwent PVP treatment at our hospital from December 2019 to December 2021. The participants were divided randomly into groups based on whether the bone cement‐gelatine sponge composite was used during the surgery. The two groups were the bone cement‐gelatine sponge composite group (GS group, comprising 37 patients) and the no bone cement‐gelatine sponge composite group (N‐GS group, comprising 37 patients). The independent samples t‐test and chi‐square test were employed to compare general information, operative time, cement injection volume, intraoperative bleeding, and bone cement leakage between the two groups. Additionally, the visual analogue scale (VAS) score, Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), and the kyphotic Cobb angle were compared between the two groups at the preoperative, 2 days postoperative, and 6 months postoperative stages using repeated measures analysis of variance.

Results

All patients were followed up for more than 6 months, with an average of (11.19 ± 2.21) months. No significant differences were observed in terms of the operative time, cement injection volume, and intraoperative bleeding between the two groups (P > 0.05). The incidence of bone cement leakage in the N‐GS group (32.43%) was significantly higher than that in the GS group (5.41%), and the difference was statistically significant (P < 0.05). The VAS score and ODI of the two groups at postoperative 2 days and 6 months improved significantly (P < 0.05). The AVHR and kyphotic Cobb angle were corrected to a certain extent (P < 0.05); however, no significant difference was observed between the two groups (P > 0.05).

Conclusion

The bone cement‐gelatine sponge composite intravertebral prefilling technique can lower bone cement leakage in stage I and II Kümmell's disease and can also relieve pain and improve vertebral body height.
Uric acid is a major chemical constituent for the whitish coloration in the medaka leucophores
Authors: Goda Makoto , Miyagi Asuka , Kitamoto Takuya , Kondo Minako , Hashimoto Hisashi
Published: May 2023

In whitish parts of teleost skin, the coloration is attributed to a light scattering phenomenon within light‐reflecting chromatophores, namely leucophores and iridophores, which contain high refractive index materials in their cytoplasmic organelles, leucosomes and light‐reflecting platelets, respectively. Previous chemical examinations revealed that guanine is a major constituent of the materials in the platelets of the iridophores, while, in leucophores, the detailed chemical nature of the materials contained in the leucosomes has not been reported. Here, using liquid chromatography‐tandem mass spectroscopy, we investigated the chemical features of materials eluted from scales, larvae, and single chromatophores of the medaka. Results of the liquid chromatography‐tandem mass spectroscopy suggested that uric acid is a major constituent of the high refractive index materials in medaka leucophores and is a unique marker to investigate the presence of leucophores in the fish. The whitish appearance of the medaka leucophores may be attributed to the light‐scattering phenomenon in leucosomes, which contain highly concentrated uric acid.
Vessel development in compound buds of interspecific hybrid grape induced by artificial deacclimation treatments
Authors: Kasuga Jun , Kawase Ayumi , Kamigaki Rika , Mihara Yuka , Kondoh Daisuke
Published: May 2023

Grape compound buds adapt to subfreezing temperatures in winter by supercooling, but the supercooling ability is thought to be lost upon formation of xylem connections between canes and buds. It was reported that compound buds of the Vitis vinifera variety ‘Chardonnay’ lack xylem cells in mid‐winter, and that vessels differentiate during deacclimation. However, the pattern of vessel formation in compound buds may differ in cold‐hardy Vitis species and interspecific hybrid varieties grown in colder regions. We investigated vessel formation in compound buds of the interspecific hybrid variety ‘Yamasachi’, which were harvested in mid‐winter, during artificial deacclimation treatments. Before these treatments, ‘Yamasachi’ buds had a high supercooling ability (approx. −30°C) and contained cells with characteristics of vessel elements, that is, secondary wall thickening and lignification, at the basal parts. However, the cells still contained organelles and did not have a hydraulic conductivity function. Xylem continuity between the canes and buds was established from day 7 of deacclimation at 20°C. The different pattern of seasonal vessel formation in compound buds of ‘Yamasachi’ from that of V. vinifera may reflect the rapid development traits of Vitis species growing in cold regions with short growing seasons.
Associations between sporting physical activity and cognition in mid and later‐life: Evidence from two cohorts
Authors: Mitchell J. J. , Hamer M. , Blodgett J. M. , Wannamethee G. S. , Jefferis B. J.
Published: May 2023

Evidence has linked sporting leisure time physical activity (sporting‐LTPA) to healthy cognition throughout adulthood. This may be due to the physiological effects of physical activity (PA), or to other, psychosocial facets of sport. We examined associations between sporting‐LTPA and cognition while adjusting for device‐measured PA volume devoid of context, both in midlife (N = 4041) participants from the 1970 British Cohort Study and later‐life (N = 957) participants from the British Regional Heart Study. Independent of device‐measured PA, we identified positive associations between sporting‐LTPA and cognition. Sports with team/partner elements were strongly positively associated with cognition, suggesting LTPA context may be critical to this relationship.
Longitudinal physical activity patterns and the development of cardiometabolic risk factors during adolescence
Authors: Aira Tuula , Kokko Sami Petteri , Heinonen Olli Juhani , Korpelainen Raija , Kotkajuuri Jimi , Parkkari Jari , Savonen Kai , Toivo Kerttu , Uusitalo Arja , Valtonen Maarit , Villberg Jari , Niemelä Onni , Vähä‐Ypyä Henri , Vasankari Tommi
Published: May 2023

Purpose

To examine the associations between longitudinal physical activity (PA) patterns and the development of cardiometabolic risk factors from adolescence to young adulthood.

Methods

This cohort study encompassed 250 participants recruited from sports clubs and schools, and examined at mean age 15 and 19. Device‐measured moderate‐to‐vigorous PA was grouped into five patterns (via a data‐driven method, usinginactivity maintainersas a reference). The outcomes were:glucose,insulin,homeostasis model assessment for insulin resistance(HOMA‐IR),total cholesterol,HDL and LDL cholesterol,triglycerides,blood pressure, andbody mass index(BMI). Linear growth curve models were applied with adjustment for sex, age, fruit/vegetable consumption, cigarette/snuff use, and change in the device wear‐time.

Results

Insulin and BMI increased amongdecreasers from moderate to low PA(βfor insulin 0.23, 95% CI 0.03–0.46;βfor BMI 0.90; CI 0.02–1.78). The concentration of HDL cholesterol decreased (β−0.18, CI −0.31 to −0.05) and that of glucose increased (β0.18, CI 0.02–0.35) amongdecreasers from high to moderate PA. By contrast, amongincreasers, blood pressure declined (systolicβ−6.43, CI −12.16 to −0.70; diastolicβ−6.72, CI −11.03 to −2.41).

Conclusions

Already during the transition to young adulthood, changes in PA are associated with changes in cardiometabolic risk factors. Favorable blood pressure changes were found among PAincreasers. Unfavorable changes in BMI, insulin, glucose, and HDL cholesterol were found in groups with decreasing PA. The changes were dependent on the baseline PA and the magnitude of the PA decline.
The soil organic carbon: Clay ratio in North Devon, UK: Implications for marketing soil carbon as an asset class
Authors: Pulley S. , Taylor H. , Prout J. M. , Haefele S. M. , Collins A. L.
Published: May 2023

Building up stocks of agricultural soil organic carbon (SOC) can improve soil conditions as well as contribute to climate change mitigation. As a metric, the ratio of SOC to clay offers a better predictor of soil condition than SOC alone, potentially providing a benchmark for ecosystem service payments. We determined SOC:clay ratios for 50 fields in the North Devon UNESCO World Biosphere Reserve using 30 cm soil cores (divided into 0–10 cm and 10–30 cm depth samples), with soil bulk density, soil moisture and land‐use history recorded for each field. All the arable soils exceeded the minimum desirable SOC:clay ratio threshold, and the ley grassland soils generally exceeded it but were inconsistent at 10–30 cm. Land use was the primary factor driving SOC:clay ratios at 0–10 cm, with permanent pasture fields having the highest ratios followed by ley grass and then arable fields. Approximately half of the fields sampled had potential for building up SOC stock at 10–30 cm. However, at this depth, the effect of land use is significantly reduced. Within‐field variability in SOC and clay was low (coefficient of variation was ~10%) at both 0–10 cm and 10–30 cm, suggesting that SOC:clay ratios precisely characterized the fields. Due to the high SOC:clay ratios found, we conclude that there is limited opportunity to market additional carbon sequestration as an asset class in the North Devon Biosphere or similar areas. Instead, preserving existing SOC stocks would be a more suitable ecosystem service payment basis.
Soil tillage systems and forms of lime application on soil attribute enhancements in ratoon sugarcane
Authors: Pacola Marcela , Guimarães Tiara Moraes , Rigon João Paulo Gonsiorkiewicz , Jacomassi Lucas Moraes , Bossolani João William , Viveiros Josiane , de Siqueira Gabriela Ferraz , Dias Patrícia Pereira , Calonego Juliano Carlos , Crusciol Carlos Alexandre Costa
Published: May 2023

Combining deep tillage (DT) with lime application at greater depths may improve sugarcane yield. The objective of this study was to evaluate the impact of conventional tillage (CT) and DT systems and liming on sugarcane productivity and soil physical attributes. The experiment was conducted in a clayey‐textured Rhodic Hapludox soil cultivated with sugarcane for two growing seasons (first and third ratoons) using a randomized block design with four treatments and four repetitions. The treatments consisted of DT without liming (DT0), DT with liming (DT2), CT without liming (CT0) and CT with liming (CT2). In addition to sugarcane stalk and sugar yields, macroporosity (MA), microporosity (MI), total soil porosity (TP), weighted average diameter (WAD), aggregate stability index (ASI), soil penetration resistance (SPR), pH, potential acidity (H + Al), total soil organic carbon (SOC), particulate organic carbon (POC), mineral‐associated organic carbon (MOC), calcium (Ca) and magnesium (Mg) were analysed. DT2 promoted the best soil conservation effect on sugarcane. In general, DT, regardless of lime application, reduced SOC and POC in soil surface layer. Nevertheless, in the long term, localized lime addition resulted in significant reductions in compaction, reaching values below 2 MPa. The soil fertility improvement provided by DT2 promoted increased sucrose concentrations and stalks yield. Considering that there was an improvement in the physical quality and fertility of soil for better plant development, the deep tillage with localized lime addition can be considered an effective alternative for sugarcane cultivation.
Early onset of Pyrenean collision (97–90 Ma) evidenced by U–Pb dating on calcite (Provence, SE France)
Authors: Bilau Antonin , Rolland Yann , Dumont Thierry , Schwartz Stéphane , Godeau Nicolas , Guihou Abel , Deschamps Pierre
Published: May 2023

Early Late Cretaceous uplift of Provence gave rise to the Durance Isthmus. In the present study, U–Pb dating on calcite of compressional structures related to Pyrenean foreland compressional deformation in Provence shows that N‐S shortening occurred coeval with emersion of the Durance Isthmus, through the development of combined top‐to‐the‐North to NW thrusts between 97 and 90 Ma. This large‐scale event, recorded from the Pyrenees to the Middle‐East regions is interpreted as a far‐field internal plate precursor of the Africa‐Europe plates reorganization. Furthermore, the change in tectonic style and amount of shortening between Provence and Pyrenees was accommodated by sinistral reactivation of the NE–SW Cevennes and Nimes faults, acting as transform boundaries in this incipient collisional context.
Motor potentials evoked by transcranial magnetic stimulation: interpreting a simple measure of a complex system
Authors: Spampinato Danny Adrian , Ibanez Jaime , Rocchi Lorenzo , Rothwell John
Published: May 2023

Transcranial magnetic stimulation (TMS) is a non‐invasive technique that is increasingly used to study the human brain. One of the principal outcome measures is the motor‐evoked potential (MEP) elicited in a muscle following TMS over the primary motor cortex (M1), where it is used to estimate changes in corticospinal excitability. However, multiple elements play a role in MEP generation, so even apparently simple measures such as peak‐to‐peak amplitude have a complex interpretation. Here, we summarize what is currently known regarding the neural pathways and circuits that contribute to the MEP and discuss the factors that should be considered when interpreting MEP amplitude measured at rest in the context of motor processing and patients with neurological conditions. In the last part of this work, we also discuss how emerging technological approaches can be combined with TMS to improve our understanding of neural substrates that can influence MEPs. Overall, this review aims to highlight the capabilities and limitations of TMS that are important to recognize when attempting to disentangle sources that contribute to the physiological state‐related changes in corticomotor excitability.

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Identification of Pseudomonas aeruginosa exopolysaccharide Psl in biofilms using 3D OrbiSIMS
Authors: Khateb Heba , Hook Andrew L. , Kern Stefanie , Watts Julie A. , Singh Sonali , Jackson Darryl , Marinez-Pomares Luisa , Williams Paul , Alexander Morgan R.
Published: May 2023

Secondary ion mass spectrometry (SIMS) offers advantages over both liquid extraction mass spectrometry and matrix assisted laser desorption mass spectrometry in that it provides the direct in situ analysis of molecules and has the potential to preserve the 3D location of an analyte in a sample. Polysaccharides are recognized as challenging analytes in the mass spectrometry of liquids and are also difficult to identify and assign using SIMS. Psl is an exopolysaccharide produced by Pseudomonas aeruginosa, which plays a key role in biofilm formation and maturation. In this Letter, we describe the use of the OrbiTrap analyzer with SIMS (3D OrbiSIMS) for the label-free mass spectrometry of Psl, taking advantage of its high mass resolving power for accurate secondary ion assignment. We study a P. aeruginosa biofilm and compare it with purified Psl to enable the assignment of secondary ions specific to the Psl structure. This resulted in the identification of 17 peaks that could confidently be ascribed to Psl fragments within the biofilm matrix. The complementary approach of the following neutral loss sequences is also shown to identify multiple oligosaccharide fragments without the requirement of a biological reference sample.
Nonlinear two-photon pumped vortex lasing based on quasi-bound states in the continuum from perovskite metasurface
Authors: Liu Chi-Ching , Hsiao Hui-Hsin , Chang Yun-Chorng
Published: May 2023

The experimental observation of nonlinear two-photon pumped vortex lasing from perovskite metasurfaces is demonstrated. The vortex lasing beam is based on symmetry-protected quasi-bound states in the continuum (QBICs). The topological charge is estimated to be +1 according to the simulation result. The quality factor and lasing threshold are around 1100 and 4.28 mJ/cm
2
, respectively. Theoretical analysis reveals that the QBIC mode originates from the magnetic dipole mode. The lasing wavelength can be experimentally designed within a broad spectral range by changing the diameter and periodicity of the metasurface. The finite array size effect of QBIC can affect the quality factor of the lasing and be used to modulate the lasing. Results shown in this study can lead to more complex vortex beam lasing from a single chip and previously unidentified ways to obtain ultrafast modulation of the QBIC lasing via the finite array size effect.
PAXX binding to the NHEJ machinery explains functional redundancy with XLF
Authors: Seif-El-Dahan Murielle , Kefala-Stavridi Antonia , Frit Philippe , Hardwick Steven W. , Chirgadze Dima Y. , Maia De Oliviera Taiana , Andreani Jessica , Britton Sébastien , Barboule Nadia , Bossaert Madeleine , Pandurangan Arun Prasad , Meek Katheryn , Blundell Tom L. , Ropars Virginie , Calsou Patrick , Charbonnier Jean-Baptiste , Chaplin Amanda K.
Published: May 2023

Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo–electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF. We identify residues critical for the Ku70/PAXX interaction in vitro and in cells. We demonstrate that PAXX and XLF can bind simultaneously to the Ku heterodimer and act as structural bridges in alternate forms of DNA-PK dimers. Last, we show that engagement of both proteins provides a complementary advantage for DNA end synapsis and end joining in cells.
Structural basis of purine nucleotide inhibition of human uncoupling protein 1
Authors: Jones Scott A. , Gogoi Prerana , Ruprecht Jonathan J. , King Martin S. , Lee Yang , Zögg Thomas , Pardon Els , Chand Deepak , Steimle Stefan , Copeman Danielle M. , Cotrim Camila A. , Steyaert Jan , Crichton Paul G. , Moiseenkova-Bell Vera , Kunji Edmund R. S.
Published: May 2023

Mitochondrial uncoupling protein 1 (UCP1) gives brown adipose tissue of mammals its specialized ability to burn calories as heat for thermoregulation. When activated by fatty acids, UCP1 catalyzes the leak of protons across the mitochondrial inner membrane, short-circuiting the mitochondrion to generate heat, bypassing ATP synthesis. In contrast, purine nucleotides bind and inhibit UCP1, regulating proton leak by a molecular mechanism that is unclear. We present the cryo–electron microscopy structure of the GTP-inhibited state of UCP1, which is consistent with its nonconducting state. The purine nucleotide cross-links the transmembrane helices of UCP1 with an extensive interaction network. Our results provide a structural basis for understanding the specificity and pH dependency of the regulatory mechanism. UCP1 has retained all of the key functional and structural features required for a mitochondrial carrier–like transport mechanism. The analysis shows that inhibitor binding prevents the conformational changes that UCP1 uses to facilitate proton leak.
Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis
Authors: O’Sullivan Eoin D. , Mylonas Katie J. , Xin Cuiyan , Baird David P. , Carvalho Cyril , Docherty Marie-Helena , Campbell Ross , Matchett Kylie P. , Waddell Scott H. , Walker Alexander D. , Gallagher Kevin M. , Jia Siyang , Leung Steve , Laird Alexander , Wilflingseder Julia , Willi Michaela , Reck Maximilian , Finnie Sarah , Pisco Angela , Gordon-Keylock Sabrina , Medvinsky Alexander , Boulter Luke , Henderson Neil C. , Kirschner Kristina , Chandra Tamir , Conway Bryan R. , Hughes Jeremy , Denby Laura , Bonventre Joseph V. , Ferenbach David A.
Published: May 2023

Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1
+
) cells are a major source of activated fibroblasts in multiple organs, but the links between injury, inflammation, and Gli1
+
cell expansion and tissue fibrosis remain incompletely understood. We demonstrated that leukocyte-derived tumor necrosis factor (TNF) promoted Gli1
+
cell proliferation and cardiorenal fibrosis through induction and release of Indian Hedgehog (IHH) from renal epithelial cells. Using single-cell–resolution transcriptomic analysis, we identified an “inflammatory” proximal tubular epithelial (iPT) population contributing to TNF- and nuclear factor κB (NF-κB)–induced IHH production in vivo. TNF-induced Ubiquitin D (
Ubd
) expression was observed in human proximal tubular cells in vitro and during murine and human renal disease and aging. Studies using pharmacological and conditional genetic ablation of TNF-induced IHH signaling revealed that IHH activated canonical Hedgehog signaling in Gli1
+
cells, which led to their activation, proliferation, and fibrosis within the injured and aging kidney and heart. These changes were inhibited in mice by
Ihh
deletion in
Pax8
-expressing cells or by pharmacological blockade of TNF, NF-κB, or Gli1 signaling. Increased amounts of circulating IHH were associated with loss of renal function and higher rates of cardiovascular disease in patients with chronic kidney disease. Thus, IHH connects leukocyte activation to Gli1
+
cell expansion and represents a potential target for therapies to inhibit inflammation-induced fibrosis.
Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas
Authors: Kanaya Nobuhiko , Kitamura Yohei , Lopez Vazquez Maria , Franco Arnaldo , Chen Kok-Siong , van Schaik Thijs A. , Farzani Touraj Aligholipour , Borges Paulo , Ichinose Toru , Seddiq Waleed , Kuroda Shinji , Boland Genevieve , Jahan Nusrat , Fisher David , Wakimoto Hiroaki , Shah Khalid
Published: May 2023

Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1
KO
) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). Using mouse models of brain metastatic BRAF
V600E
/PTEN
−/−
and BRAF
V600E/wt
/PTEN
−/−
mutant melanomas, we show that locoregional delivery of TSCs releasing oHSV and GM-CSF (TSC-G) activated dendritic cell– and T cell–mediated immune responses. In addition, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the TSCs composed of SC-oHSV and SC
N1KO
–releasing GM-CSF and single-chain variable fragment anti–PD-1 (TSC-G/P) had therapeutic efficacy in both syngeneic and patient-derived humanized mouse models of leptomeningeal metastasis. Our findings provide a promising allogeneic SC-based immunotherapeutic strategy against melanomas in the CNS and a road map toward clinical translation.
Impact of Acquired Broad Spectrum β-Lactamases on Susceptibility to Novel Combinations Made of β-Lactams (Aztreonam, Cefepime, Meropenem, and Imipenem) and Novel β-Lactamase Inhibitors in Escherichia coli and Pseudomonas aeruginosa
Authors: Le Terrier Christophe , Nordmann Patrice , Freret Charlotte , Seigneur Marion , POIREL Laurent
Published: May 2023

The impact of broad-spectrum β-lactamases on the susceptibility to novel β-lactamase/β-lactamase inhibitor combinations was evaluated both in
Pseudomonas aeruginosa
and
Escherichia coli
using isogenic backgrounds. Cefepime-zidebactam displayed low MICs, mainly due to the significant intrinsic antibacterial activity of zidebactam.
Bedquiline Resistance Mutations: Correlations with Drug Exposures and Impact on the Proteome in M. tuberculosis
Authors: Xu Jian , Li Dongshuo , Shi Jinghua , Wang Bin , Ge Fei , Guo Zhenyong , Mu Xiaopan , Nuermberger Eric , Lu Yu
Published: May 2023

Bedaquiline (BDQ) is an effective drug for the treatment of drug-resistant tuberculosis. Mutations in
atpE
, which encodes the target of BDQ, are associated with large increases in MICs. Mutations in
Rv0678
that derepress the transcription of the MmpL5-MmpS5 efflux transporter are associated with smaller increases in MICs. However,
Rv0678
mutations are the most common mutations that are associated with BDQ resistance in clinical isolates, and they also confer cross-resistance to clofazimine (CFZ).
Preharvest Maize Fungal Microbiome and Mycotoxin Contamination: Case of Zambia’s Different Rainfall Patterns
Authors: Katati Bwalya , Schoenmakers Pierre , Njapau Henry , Kachapulula Paul W. , Zwaan Bas J. , van Diepeningen Anne D. , Schoustra Sijmen E.
Published: May 2023

Fungi contaminate various crops worldwide. Maize, an important human staple and livestock cereal, is susceptible to contamination with fungi in the field.
A (
S
)-3-Hydroxybutyrate Dehydrogenase Belonging to the 3-Hydroxyacyl-CoA Dehydrogenase Family Facilitates Hydroxyacid Degradation in Anaerobic Bacteria
Authors: Zhou Yan , Wei Yifeng , Jiang Li , Zhang Yan , Jiao Xinan
Published: May 2023

(
R
)-3-hydroxybutyrate is well studied as a component of ketone bodies produced by the liver and of bacterial polyesters. However, the biochemistry of its enantiomer (
S
)-3-hydroxybutyrate is poorly understood.
Ring Finger Protein 34 Facilitates Nervous Necrosis Virus Evasion of Antiviral Innate Immunity by Targeting TBK1 and IRF3 for Ubiquitination and Degradation in Teleost Fish
Authors: Zhang Wanwan , Yao Lan , Chen Leshi , Jia Peng , Xiang Yangxi , Yi Meisheng , Jia Kuntong
Published: May 2023

Ubiquitination plays an essential role in the regulation of innate immune responses to pathogens. NNV, a type of RNA virus, is the causal agent of a highly destructive disease in a variety of marine and freshwater fish.
Activation of the NLRP1 Inflammasome and Its Role in Transmissible Gastroenteritis Coronavirus Infection
Authors: He Haojie , Wang Wenzhe , Li Liang , Zhang Xin , Shi Hongyan , Chen Jianfei , Shi Da , Xue Mei , Feng Li
Published: May 2023

Coronavirus primarily targets the epithelial cells of the respiratory and gastrointestinal tracts, leading to damage in both humans and animals. NLRP1 is a direct sensor for RNA virus infection which is highly expressed in epithelial barrier tissues.
Detection of influenza virus and
Streptococcus pneumoniae
in air sampled from co-infected ferrets and analysis of their influence on pathogen stability
Authors: French Andrea J. , Rockey Nicole C. , Le Sage Valerie , Mueller Brown Karina , Shephard Meredith J. , Frizzell Sheila , Myerburg Mike M. , Hiller N. Luisa , Lakdawala Seema S.
Published: May 2023

Secondary infection with
Streptococcus pneumoniae
has contributed significantly to morbidity and mortality during multiple influenza virus pandemics and remains a common threat today. During a concurrent infection, both pathogens can influence the transmission of each other, but the mechanisms behind this are unclear. In this study, condensation air sampling and cyclone bioaerosol sampling were performed using ferrets first infected with the 2009 H1N1 pandemic influenza virus (H1N1pdm09) and secondarily infected with
S. pneumoniae
strain D39 (Spn). We detected viable pathogens and microbial nucleic acid in expelled aerosols from co-infected ferrets, suggesting that these microbes could be present in the same respiratory expulsions. To assess whether microbial communities impact pathogen stability within an expelled droplet, we performed experiments measuring viral and bacterial persistence in 1 µL droplets. We observed that H1N1pdm09 stability was unchanged in the presence of Spn. Further, Spn stability was moderately increased in the presence of H1N1pdm09, although the degree of stabilization differed between airway surface liquid collected from individual patient cultures. These findings are the first to collect both pathogens from the air and in doing so, they provide insight into the interplay between these pathogens and their hosts.

IMPORTANCE

The impact of microbial communities on transmission fitness and environmental persistence is under-studied. Environmental stability of microbes is crucial to identifying transmission risks and mitigation strategies, such as removal of contaminated aerosols and decontamination of surfaces. Co-infection with
S. pneumoniae
is very common during influenza virus infection, but little work has been done to understand whether
S. pneumoniae
alters stability of influenza virus, or vice versa, in a relevant system. Here, we demonstrate that influenza virus and
S. pneumoniae
are expelled by co-infected hosts. Our stability assays did not reveal any impact of
S. pneumoniae
on influenza virus stability, but did show a trend towards increased stability of
S. pneumoniae
in the presence of influenza viruses. Future work characterizing environmental persistence of viruses and bacteria should include microbially complex solutions to better mimic physiologically relevant conditions.
Mangiferin and Taurine Ameliorate MSRV Infection by Suppressing NF-κB Signaling
Authors: Dai Caijiao , Yu Li , Wang Zhiwen , Deng Peng , Li Lijuan , Gu Zemao , He Xugang , Wang Jianghua , Yuan Junfa
Published: May 2023

Aquaculture now provides almost half of all fish for human food in 2021 and plays a significant role in eliminating hunger, promoting health, and reducing poverty. There are diverse viral pathogens that decrease production in aquaculture.
Youngest en-bloc kidney transplant recipient in India: defying the barriers and challenges with teamwork
Authors: Ajmera Jagadeep , Pol Manjunath Maruti , Bagga Arvind , Sinha Aditi
Published: May 2023

We received a call from a transplant coordinator about the availability of a consented deceased donor. En-bloc kidneys with the aorta and IVC (inferior vena cava) were harvested from a toddler weighing 8 kg. The recipient was of early childhood weighing 14 kg who had been on haemodialysis for the last 3 years for end-stage kidney disease. He received anti-thymocyte globulin as an induction immunosuppressant. The kidneys were transplanted en bloc in the right lower quadrant retroperitoneal region; an anastomosis was performed to the recipient’s aorta and IVC, and two separate neocystoureterostomies were created. His serum creatinine reached 0.5 mg/dL on the seventh postoperative day, following a few days of delayed graft function. In this study, we describe the surgical and non-surgical challenges that we faced while performing en-bloc kidney transplant to the youngest recipient and how a multidisciplinary team approach helped us overcome them.
Early recurrence of focal segmental glomerulosclerosis in a kidney transplant recipient withAPOL1one risk variant
Authors: Acharya Ratna , Upadhyay Kiran
Published: May 2023

Apolipoprotein 1(APOL1) risk variants (G1 and G2) are associated with focal segmental glomerulosclerosis (FSGS) in patients of African ancestry. The prevalence ofAPOL1two risk variants is lower in Hispanics and very rare in European and Asian populations.APOL1two risk variants in donor kidneys is associated with recipient kidney graft loss, however the effect of recipient risk variant in the kidney transplant outcome is unclear. Here, we present a late adolescent male with FSGS and end stage renal disease with oneAPOL1risk variant (G2) who had immediate recurrence of FSGS in the post-KT period. There was an excellent response to few sessions of plasmapheresis and Rituximab with no further recurrence of FSGS in the 1 year follow-up period. It needs to be seen whether the recipientAPOL1single risk variant causes increased susceptibility to kidney graft loss on a long run via recurrent or de novo pathologies.
Rifampicin-induced hypertensive urgency: eyes see what the mind knows
Authors: Gaba Manish , Kumar Naveen , Pandey Ankita , Dewan Arun
Published: May 2023

A man had poor control of hypertension throughout 9 months of antituberculosis treatment. He consulted multiple physicians, who kept increasing this blood pressure medicine. Despite that, it was not controlled and he visited emergency many times with hypertensive urgency. When admitted in our care, he was off antituberculosis treatment for 5 days and his blood pressure was back to normal. We attributed it secondary to rifamipicin-induced enzyme induction. Tuberculosis and hypertension both being very common diseases, we report this case to highlight lack of awareness about these important and easily preventable drug interactions.
Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol
Authors: Guerra-Alejos B Carolina , Kurz Megan , Min Jeong Eun , Dale Laura M , Piske Micah , Bach Paxton , Bruneau Julie , Gustafson Paul , Hu X Joan , Kampman Kyle , Korthuis P Todd , Loughin Tom , Maclure Malcolm , Platt Robert W , Siebert U , Socías M Eugenia , Wood Evan , Nosyk Bohdan
Published: May 2023

Introduction

Urine drug tests (UDTs) are commonly used for monitoring opioid agonist treatment (OAT) responses, supporting the clinical decision for take-home doses and monitoring potential diversion. However, there is limited evidence supporting the utility of mandatory UDTs—particularly the impact of UDT frequency on OAT retention. Real-world evidence can inform patient-centred approaches to OAT and improve current strategies to address the ongoing opioid public health emergency. Our objective is to determine the safety and comparative effectiveness of alternative UDT monitoring strategies as observed in clinical practice among OAT clients in British Columbia, Canada from 2010 to 2020.

Methods and analysis

We propose a population-level retrospective cohort study of all individuals 18 years of age or older who initiated OAT from 1 January 2010 to 17 March 2020. The study will draw on eight linked health administrative databases from British Columbia. Our primary outcomes include OAT discontinuation and all-cause mortality. To determine the effectiveness of the intervention, we will emulate a ‘per-protocol’ target trial using a clone censoring approach to compare fixed and dynamic UDT monitoring strategies. A range of sensitivity analyses will be executed to determine the robustness of our results.

Ethics and dissemination

The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.
Is our public research money well spent? Publication of research outputs from Health Research Council of New Zealand-funded studies: a cross-sectional study
Authors: Showell Marian , Farquhar Cynthia M , Greenwood Grace , Jordan Vanessa M B
Published: May 2023

Objective

To evaluate the reporting of results from the projects and programmes funded by the Health Research Council (HRC) New Zealand.

Design

A cross-sectional analysis.

Setting

Research projects and programmes funded by the HRC New Zealand from 2006 to 2014.

Participants

Publicly available data provided by the HRC.

Main outcome measures

The number and proportion with evidence of publication and dissemination of a research output from HRC grants and the time taken to disseminate the results.

Results

Of the 374 HRC grants from 2006 to 2014, there was no evidence of publication or reporting of any research output for 48 studies (13%). Of the 326 (87%) grants with research outputs, there was a mean dissemination time of 4.73 years (SD 2.37). The total funding provided by the HRC was NZ$471 663 336, while the 48 grants with no evidence of dissemination represented NZ$47 095 727 (10%).

Conclusions

Thirteen per cent of the HRC projects and programmes from 2006 to 2014 have not contributed to the healthcare evidence as their results remain unknown.
Now that the door is open: an update on ischemic stroke pharmacotherapeutics for the neurointerventionalist
Authors: Fraser Justin F , Pahwa Shivani , Maniskas Michael , Michas Christopher , Martinez Mesha , Pennypacker Keith R , Dornbos David
Published: May 2023

The last 10 years have seen a major shift in management of large vessel ischemic stroke with changes towards ever-expanding use of reperfusion therapies (intravenous thrombolysis and mechanical thrombectomy). These strategies ‘open the door’ to acute therapeutics for ischemic tissue, and we should investigate novel therapeutic approaches to enhance survival of recently reperfused brain. Key insights into new approaches have been provided through translational research models and preclinical paradigms, and through detailed research on ischemic mechanisms. Additional recent clinical trials offer exciting salvos into this new strategy of pairing reperfusion with neuroprotective therapy. This pairing strategy can be employed using drugs that have shown neuroprotective efficacy; neurointerventionalists can administer these during or immediately after reperfusion therapy. This represents a crucial moment when we emphasize reperfusion, and have the technological capability along with the clinical trial experience to lead the way in multiprong approaches to stroke treatment.
Effects of intravenous thrombolysis on stent retriever and aspiration thrombectomy outcomes: a systematic review and meta-analysis of the randomized controlled trials
Authors: Bilgin Cem , Tolba Hatem , Ghozy Sherief , Kobeissi Hassan , Hassankhani Amir , Senol Yigit Can , Arul Santhosh , Kadirvel Ramanathan , Kallmes David F
Published: May 2023

Background

Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT’s specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes.

Methods

In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT).

Results

Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0–2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0–2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy.

Conclusions

Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.
Total reflectivity for infrared radiation based on one-dimensional gyroidal metallic photonic crystals
Authors: Almawgani Abdulkarem H. M. , Elsayed Hussein A. , Mehaney Ahmed , Sharma Arvind , Ahmed Ashour M. , Ahmed Ali Ghassan , Sabra Walied
Published: May 2023

In this research, a one-dimensional photonic crystal with such a novel and simple design is introduced to serve as an efficient reflector for infrared (IR) wavelengths. The construction of the proposed photonic crystal design based on the gyroidal geometry is the mainstay of this research to investigate the total reflectivity through a wide band of IR wavelengths. In this regard, [Air/(A/B)10/substrate] is indeed the configuration of the suggested photonic crystal structure. The layer symbols, A and B represent two layers of silver with a gyroidal configuration in host materials of titanium dioxide and silicon, respectively. Meanwhile, our numerical findings demonstrate the existence of a cutoff feature at a wavelength of 1[Formula: see text][Formula: see text]m of the propagating electromagnetic waves. Moreover, the filling fraction of sliver through layers (A) and (B) provides a substantial role in the tunability of the cutoff frequency and the reflectivity of the structure as well. Then, we have taken into account how the host material’s thicknesses and refractive indices will affect the proposed structure’s reflectance. In particular, the refractive index of the host material could lead to a significant variation of the permittivities of the considered materials. Finally, we think that the proposed structure may be of a great interest in a variety of physical and engineering applications including the optical reflectors, smart windows and solar cells applications as well.