bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and impact of brain metastasis in patients with hereditary BRCA1 or BRCA2 mutated invasive breast cancer
Authors: Garber Haven R. , Raghavendra Akshara Singareeka , Lehner Michael , Qiao Wei , Gutierrez-Barrera Angelica M. , Tripathy Debu , Arun Banu , Ibrahim Nuhad K.
Published: April 2022

Patients with hereditary mutations in BRCA1 or BRCA2 (gBRCA1/2) and breast cancer have distinct tumor biology, and encompass a predilection for brain metastasis (BM). We looked into baseline risk of BMs among gBRCA1/2 patients. Patients with gBRCA1/2, stage I-III invasive breast cancer seen between 2000–2017 with parenchymal BMs. Among gBRCA1 with distant breast cancer recurrence, 34 of 76 (44.7%) were diagnosed with brain metastases compared to 7 of 42 (16.7%) patients with gBRCA2. In the comparator group, 65 of 182 (35.7%) noncarrier triple-negative breast cancer (TNBC) and a distant recurrence experienced BM’s. In a competitive risk analysis using death as a competing factor, the cumulative incidence of BMs was similar between gBRCA1 and noncarrier TNBC patients. The time from primary breast cancer diagnosis to detection of BMs was similar between gBRCA1 and noncarrier TNBC patients (2.4 vs 2.2 years). Survival was poor after BMs (7.8 months for gBRCA1 patients vs. 6.2 months for TNBC noncarriers). Brain was a more common site of initial distant recurrence in gBRCA1 patients versus TNBC noncarriers (26.3% vs. 12.1%). Importantly, the presence of BMs, adversely impacted overall survival across groups (HR 1.68 (95% CI 1.12–2.53), hazard ratio for death if a patient had BMs at the time of initial breast cancer recurrence vs. not). In conclusion, breast cancer BMs is common and is similarly frequent among gBRCA1 and noncarrier patients with recurrent TNBC. Our study highlights the importance of improving the prevention and treatment of BMs in patients with TNBC, gBRCA1 carriers, and noncarriers.
Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges
Authors: Iberite Federica , Gruppioni Emanuele , Ricotti Leonardo
Published: April 2022

Although skeletal muscle repairs itself following small injuries, genetic diseases or severe damages may hamper its ability to do so. Induced pluripotent stem cells (iPSCs) can generate myogenic progenitors, but their use in combination with bioengineering strategies to modulate their phenotype has not been sufficiently investigated. This review highlights the potential of this combination aimed at pushing the boundaries of skeletal muscle tissue engineering. First, the overall organization and the key steps in the myogenic process occurring in vivo are described. Second, transgenic and non-transgenic approaches for the myogenic induction of human iPSCs are compared. Third, technologies to provide cells with biophysical stimuli, biomaterial cues, and biofabrication strategies are discussed in terms of recreating a biomimetic environment and thus helping to engineer a myogenic phenotype. The embryonic development process and the pro-myogenic role of the muscle-resident cell populations in co-cultures are also described, highlighting the possible clinical applications of iPSCs in the skeletal muscle tissue engineering field.
The shallow cognitive map hypothesis: A hippocampal framework for thought disorder in schizophrenia
Authors: Musa Ayesha , Khan Safia , Mujahid Minahil , El-Gaby Mohamady
Published: April 2022

Memories are not formed in isolation. They are associated and organized into relational knowledge structures that allow coherent thought. Failure to express such coherent thought is a key hallmark of Schizophrenia. Here we explore the hypothesis that thought disorder arises from disorganized Hippocampal cognitive maps. In doing so, we combine insights from two key lines of investigation, one concerning the neural signatures of cognitive mapping, and another that seeks to understand lower-level cellular mechanisms of cognition within a dynamical systems framework. Specifically, we propose that multiple distinct pathological pathways converge on the shallowing of Hippocampal attractors, giving rise to disorganized Hippocampal cognitive maps and driving conceptual disorganization. We discuss the available evidence at the computational, behavioural, network, and cellular levels. We also outline testable predictions from this framework, including how it could unify major chemical and psychological theories of schizophrenia and how it can provide a rationale for understanding the aetiology and treatment of the disease.
Solar water purification with photocatalytic nanocomposite filter based on TiO2 nanowires and carbon nanotubes
Authors: Horváth E. , Gabathuler J. , Bourdiec G. , Vidal-Revel E. , Benthem Muñiz M. , Gaal M. , Grandjean D. , Breider F. , Rossi L. , Sienkiewicz A. , Forró L.
Published: April 2022

Water contamination due to environmental conditions and poor waste management in certain areas of the world represents a serious problem in accessing clean and safe drinking water. This problem is especially critical in electricity-poor regions, where advanced water purification methods are absent. Here, we demonstrate that titanium dioxide nanowires (TiO2NWs)-based photocatalytic filters assisted only with sunlight can efficiently decontaminate water. Moreover, interweaving TiO2NWs with carbon nanotubes (CNTs) leads to the formation of a TiO2NWs/CNTs composite material and offers an additional water decontamination channel, that is of pasteurization with the visible part of the solar emission spectrum. Our results demonstrate that this nanoporous filter can successfully intercept various types of microbial pathogens, including bacteria and large viruses. In addition, photo-catalytically generated reactive oxygen species (ROS) on the surface of the TiO2NWs/CNTs-based filter material under exposure to sunlight contribute to an efficient removal of a broad range of organic compounds and infective microbes. A pilot study also yielded encouraging results in reducing traces of drugs and pesticides in drinking water.
Multi-decadal ocean temperature time-series and climatologies from Australia’s long-term National Reference Stations
Authors: Roughan Moninya , Hemming Michael , Schaeffer Amandine , Austin Tim , Beggs Helen , Chen Miaoju , Feng Ming , Galibert Guillaume , Holden Clive , Hughes David , Ingleton Tim , Milburn Stuart , Ridgway Ken
Published: April 2022

Multi-decadal ocean time-series are fundamental baselines for assessing the impacts of environmental change, however, compiling and quality controlling historic data from multiple sources remains challenging. Here we aggregate, document, and release a number of long time-series temperature products and climatologies compiled from data obtained at 4 monitoring sites around Australia where sub-surface ocean temperature has been recorded nominally weekly to monthly since the 1940s/50s. In recent years, the sampling was augmented with data obtained from moored sensors, vertical profiles and satellite-derived data. The temperature data have been quality controlled, and combined using a rigorously tested methodology. We have packaged the multi-decadal, multi-depth, multi-platform temperature time-series at each site and produced a range of daily temperature climatologies from different data combinations and time periods. The 17 data products are provided as CF-compliant NetCDF files and will be updated periodically. The long-term temperature time-series will be useful for studies of ocean temperature variability, trends, anomalies and change. The data collection is supported by Australia’s Integrated Marine Observing System and data are open-access.
Emognition dataset: emotion recognition with self-reports, facial expressions, and physiology using wearables
Authors: Saganowski Stanisław , Komoszyńska Joanna , Behnke Maciej , Perz Bartosz , Kunc Dominika , Klich Bartłomiej , Kaczmarek Łukasz D. , Kazienko Przemysław
Published: April 2022

The Emognition dataset is dedicated to testing methods for emotion recognition (ER) from physiological responses and facial expressions. We collected data from 43 participants who watched short film clips eliciting nine discrete emotions: amusement, awe, enthusiasm, liking, surprise, anger, disgust, fear, and sadness. Three wearables were used to record physiological data: EEG, BVP (2x), HR, EDA, SKT, ACC (3x), and GYRO (2x); in parallel with the upper-body videos. After each film clip, participants completed two types of self-reports: (1) related to nine discrete emotions and (2) three affective dimensions: valence, arousal, and motivation. The obtained data facilitates various ER approaches, e.g., multimodal ER, EEG- vs. cardiovascular-based ER, discrete to dimensional representation transitions. The technical validation indicated that watching film clips elicited the targeted emotions. It also supported signals’ high quality.
Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample
Authors: Jones Grant , Ricard Jocelyn A. , Lipson Joshua , Nock Matthew K.
Published: April 2022

Opioid use disorder (OUD) is a major source of morbidity and mortality in the U.S. and there is a pressing need to identify additional treatments for the disorder. Classic psychedelics (psilocybin, peyote, mescaline, LSD) have been linked to the alleviation of various substance use disorders and may hold promise as potential treatments for OUD. The aim of this study was to assess whether the aforementioned classic psychedelic substances conferred lowered odds of OUD. Furthermore, this study aimed to replicate and extend findings from Pisano et al. (2017) who found classic psychedelic use to be linked to lowered odds of OUD in a nationally representative sample. We used recent data from the National Survey on Drug Use and Health (2015–2019) (N = 214,505) and multivariable logistic regression to test whether lifetime use (yes/no) of classic psychedelics was associated with lowered odds of OUD. Lifetime psilocybin use was associated with lowered odds of OUD (aOR: 0.70; 95% CI [0.60, 0.83]). No other substances, including other classic psychedelics, were associated with lowered odds of OUD. Additionally, sensitivity analyses revealed psilocybin use to be associated with lowered odds of seven of the 11 DSM-IV criteria for OUD (aOR range: 0.66–0.83). Future clinical trials and longitudinal studies are needed to determine whether these associations are causal.
A derived honey bee stock confers resistance to Varroa destructor and associated viral transmission
Authors: O’Shea-Wheller Thomas A. , Rinkevich Frank D. , Danka Robert G. , Simone-Finstrom Michael , Tokarz Philip G. , Healy Kristen B.
Published: April 2022

The ectoparasite Varroa destructor is the greatest threat to managed honey bee (Apis mellifera) colonies globally. Despite significant efforts, novel treatments to control the mite and its vectored pathogens have shown limited efficacy, as the host remains naïve. A prospective solution lies in the development of Varroa-resistant honey bee stocks, but a paucity of rigorous selection data restricts widespread adoption. Here, we characterise the parasite and viral dynamics of a Varroa-resistant honey bee stock, designated ‘Pol-line’, using a large-scale longitudinal study. Results demonstrate markedly reduced Varroa levels in this stock, diminished titres of three major viruses (DWV-A, DWV-B, and CBPV), and a two-fold increase in survival. Levels of a fourth virus that is not associated with Varroa—BQCV—do not differ between stocks, supporting a disruption of the transmission pathway. Further, we show that when decoupled from the influence of Varroa levels, viral titres do not constitute strong independent predictors of colony mortality risk. These findings highlight the need for a reassessment of Varroa etiology, and suggest that derived stocks represent a tractable solution to the Varroa pandemic.
System dynamics modeling of lake water management under climate change
Authors: Bozorg-Haddad Omid , Dehghan Paniz , Zolghadr-Asli Babak , Singh Vijay P. , Chu Xuefeng , Loáiciga Hugo A.
Published: April 2022

Lake Urmia, the twentieth largest lake in the world, is the most valuable aquatic ecosystem in Iran. The lake water level has decreased in recent years due to human activities and climate change. Several studies have highlighted the significant roles of climatic and anthropogenic factors on the shrinkage of the lake. Management policies for water resources harvesting must be adopted to adapt to climate change and avoid the consequent problems stemming from the drought affecting Lake Urmia, and rationing must be applied to the upstream water demands. This study analyzes strategies and evaluates their effectiveness in overcoming the Urmia Lake crisis. Specifically, system dynamics analysis was performed for simulating the water volume of Lake Urmia, and the Hadley Centre coupled model was applied to project surface temperature and precipitation for two future periods: 2021–2050 and 2051–2080. Six management scenarios were considered for decreasing the allocation of agricultural water demand corresponding to two options: (1) one-reservoir option (Bukan reservoir only), and (2) six-reservoir option. The net inflow of Urmia Lake was simulated for the two future periods with the IHACRES model and with artificial neural network models under the six management scenarios. The annual average volumes of Lake Urmia would be 30 × 109 and 12 × 109 m3 over the first and second future periods, respectively, without considering the management scenarios. The lake volumes would rise by about 50% and 75% for the first and second periods, respectively under the management scenarios that involve strict protective measures and elimination of the effect of all dams and their reservoirs. Implementing strict measures would increase the annual average lake volume to 21 × 109 m3 in the second period; yet, this volume would be less than the long-term average and strategic volume. The human water use would be completely eliminated under Scenario 6. Nevertheless, Lake Urmia would experience a considerable loss of storage because of drought.
Easy axis anisotropy creating high contrast magnetic zones on magnetic tunnel junctions based molecular spintronics devices (MTJMSD)
Authors: Dahal Bishnu R. , Savadkoohi Marzieh , Grizzle Andrew , D’Angelo Christopher , Lamberti Vincent , Tyagi Pawan
Published: April 2022

Magnetic tunnel junction-based molecular spintronics device (MTJMSD) may enable novel magnetic metamaterials by chemically bonding magnetic molecules and ferromagnets (FM) with a vast range of magnetic anisotropy. MTJMSD have experimentally shown intriguing microscopic phenomenon such as the development of highly contrasting magnetic phases on a ferromagnetic electrode at room temperature. This paper focuses on Monte Carlo Simulations (MCS) on MTJMSD to understand the potential mechanism and explore fundamental knowledge about the impact of magnetic anisotropy. The selection of MCS is based on our prior study showing the potential of MCS in explaining experimental results (Tyagi et al. in Nanotechnology 26:305602, 2015). In this paper, MCS is carried out on the 3D Heisenberg model of cross-junction-shaped MTJMSDs. Our research represents the experimentally studied cross-junction-shaped MTJMSD where paramagnetic molecules are covalently bonded between two FM electrodes along the exposed side edges of the magnetic tunnel junction (MTJ). We have studied atomistic MTJMSDs properties by simulating a wide range of easy-axis anisotropy for the case of experimentally observed predominant molecule-induced strong antiferromagnetic coupling. Our study focused on understanding the effect of anisotropy of the FM electrodes on the overall MTJMSDs at various temperatures. This study shows that the multiple domains of opposite spins start to appear on an FM electrode as the easy-axis anisotropy increases. Interestingly, MCS results resembled the experimentally observed highly contrasted magnetic zones on the ferromagnetic electrodes of MTJMSD. The magnetic phases with starkly different spins were observed around the molecular junction on the FM electrode with high anisotropy.
Ribonuclease-1 treatment after traumatic brain injury preserves blood–brain barrier integrity and delays secondary brain damage in mice
Authors: Krämer Tobias J. , Hübener Per , Pöttker Bruno , Gölz Christina , Neulen Axel , Pantel Tobias , Goetz Hermann , Ritter Katharina , Schäfer Michael K. E. , Thal Serge C.
Published: April 2022

Traumatic brain injury (TBI) involves primary mechanical damage and delayed secondary damage caused by vascular dysfunction and neuroinflammation. Intracellular components released into the parenchyma and systemic circulation, termed danger-associated molecular patterns (DAMPs), are major drivers of vascular dysfunction and neuroinflammation. These DAMPs include cell-free RNAs (cfRNAs), which damage the blood–brain barrier (BBB), thereby promoting edema, procoagulatory processes, and infiltration of inflammatory cells. We tested the hypothesis that intraperitoneal injection of Ribonuclease-1 (RNase1, two doses of 20, 60, or 180 µg/kg) at 30 min and 12 h after controlled-cortical-impact (CCI) can reduce secondary lesion expansion compared to vehicle treatment 24 h and 120 h post-CCI. The lowest total dose (40 µg/kg) was most effective at reducing lesion volume (− 31% RNase 40 µg/kg vs. vehicle), brain water accumulation (− 5.5%), and loss of BBB integrity (− 21.6%) at 24 h post-CCI. RNase1 also reduced perilesional leukocyte recruitment (− 53.3%) and microglial activation (− 18.3%) at 120 h post-CCI, but there was no difference in lesion volume at this time and no functional benefit. Treatment with RNase1 in the early phase following TBI stabilizes the BBB and impedes leukocyte immigration, thereby suppressing neuroinflammation. RNase1-treatment may be a novel approach to delay brain injury to extend the window for treatment opportunities after TBI.
Promiscuity mapping of the S100 protein family using a high-throughput holdup assay
Authors: Simon Márton A. , Bartus Éva , Mag Beáta , Boros Eszter , Roszjár Lea , Gógl Gergő , Travé Gilles , Martinek Tamás A. , Nyitray László
Published: April 2022

S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein–protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally occurring S100 partners in the human proteome. Such information will be precious for future drug design to interfere with S100 related pathologies.
The efficacy of drug-eluting bead or conventional transarterial chemoembolization plus apatinib for hepatocellular carcinoma with portal vein tumor thrombus
Authors: Zhang Weihua , Wu Linxia , Chen Lei , Sun Tao , Ren Yanqiao , Sun Bo , Zhu Licheng , Han Ping , Zheng Chuansheng
Published: April 2022

Transarterial chemoembolization (TACE) combined with apatinib has been used for advanced hepatocellular carcinoma (HCC), and the efficacy is good. The study was conducted to compare the efficacy and safety of drug-eluting bead TACE plus apatinib (D-TACE-A) with conventional TACE plus apatinib (C-TACE-A) in the treatment of HCC with portal vein tumor thrombus (PVTT). A total of 130 continuous patients who received D-TACE-A or C-TACE-A were included in the study from January 2017 to June 2020. Propensity score matching (PSM) was used to reduce potential selection bias. Before PSM, the median overall survival (mOS) (14 months) and median progression-free survival (mPFS) (7 months) in the C-TACE-A group were longer than the mOS (9 months; P = 0.001) and mPFS (4 months; P = 0.001) in the D-TACE-A group. After PSM, the mOS (14 months vs 9 months; P = 0.039) and mPFS (7 months vs 5 months; P = 0.009) in the C-TACE-A group were longer than those in the D-TACE-A group. In the multivariate regression analysis, C-TACE-A reduced the mortality rate and tumor progression rate compared with D-TACE-A. For the subgroup analysis, patients with VP1–2, without extrahepatic metastases, and with multiple TACE sessions who received C-TACE-A had a lower death risk and tumor progression risk than patients who received D-TACE-A. Before PSM, there was no statistically significant difference in any grade or grade III/IV adverse events (all P > 0.05). C-TACE-A could prolong mOS and mPFS in patients with PVTT, especially for patients with VP1–2 stage PVTT, no extrahepatic tumor metastases, and multiple TACE sessions.
Oxylipin profile in saliva from patients with cystic fibrosis reveals a balance between pro-resolving and pro-inflammatory molecules
Authors: Carnovale Vincenzo , Castaldo Alice , Di Minno Alessandro , Gelzo Monica , Iacotucci Paola , Illiano Anna , Pinto Gabriella , Castaldo Giuseppe , Amoresano Angela
Published: April 2022

Oxylipins are signaling molecules originated by fatty acids that modulate vascular and bronchial tone, bronchial secretion, cytokine production and immune cell activity. The unbalanced production of pro-inflammatory and pro-resolving (i.e., anti-inflammatory) oxylipins has a relevant role in the pathogenesis of pulmonary inflammation like in cystic fibrosis (CF). We analyzed by LC-MRM/MS 65 oxylipins and 4 fatty acids in resting saliva from 69 patients with CF and 50 healthy subjects (controls). The salivary levels of 48/65 oxylipins were significantly different between CF patients and controls. Among these, EpETE, DHET, 6ketoPGE1 and HDHA were significantly higher in saliva from CF patients than in controls. All these molecules display anti-inflammatory effects, i.e., releasing of bronchial and vascular tone, modulation of cytokine release. While 20-hydroxyPGF2A, PGB2, EpDPE, 9 K-12-ELA, bicyclo-PGE2, oleic acid, LTC4, linoleic acid, 15oxoEDE, 20 hydroxyPGE2 and DHK-PGD2/PGE2 (mostly associated to pro-inflammatory effects) resulted significantly lower in CF patients than in controls. Our data suggest that the salivary oxylipins profile in CF patients is addressed toward a global anti-inflammatory effect. Although these findings need be confirmed on larger populations in prospective studies, they will contribute to better understand the pathogenesis of CF chronic inflammation and to drive targeted therapies based on the modulation of oxylipins synthesis and degradation.
TRAIL/S-layer/graphene quantum dot nanohybrid enhanced stability and anticancer activity of TRAIL on colon cancer cells
Authors: Lotfollahzadeh Shima , Hosseini Elaheh Sadat , Mahmoudi Aznaveh Hooman , Nikkhah Maryam , Hosseinkhani Saman
Published: April 2022

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), known as a cytokine of the TNF superfamily, is considered a promising antitumor agent due to its ability to selectively induce apoptosis in a wide variety of cancer cells. However, failure of its successful translation into clinic has led to development of nano-based platforms aiming to improve TRAIL therapeutic efficacy. In this regard, we fabricated a novel TRAIL-S-layer fusion protein (S-TRAIL) conjugated with graphene quantum dots (GQDs) to benefit both the self-assembly of S-layer proteins, which leads to elevated TRAIL functional stability, and unique optical properties of GQDs. Noncovalent conjugation of biocompatible GQDs and soluble fusion protein was verified via UV–visible and fluorescence spectroscopy, size and ζ-potential measurements and transmission electron microscopy. The potential anticancer efficacy of the nanohybrid system on intrinsically resistant cells to TRAIL (HT-29 human colon carcinoma cells) was investigated by MTT assay and flow cytometry, which indicated about 80% apoptosis in cancer cells. These results highlight the potential of TRAIL as a therapeutic protein that can be extensively improved by taking advantage of nanotechnology and introduce S-TRAIL/GQD complex as a promising nanohybrid system in cancer treatment.
Detection and discrimination of neutron capture events for NCEPT dose quantification
Authors: Chacon Andrew , Kielly Marissa , Rutherford Harley , Franklin Daniel R. , Caracciolo Anita , Buonanno Luca , D’Adda Ilenia , Rosenfeld Anatoly , Guatelli Susanna , Carminati Marco , Fiorini Carlo , Safavi-Naeini Mitra
Published: April 2022

Neutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific $$^{10}$$

10

B or $$^{157}$$

157

Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for $$^{10}$$

10

B and $$^{157}$$

157

Gd, respectively. A key requirement for NCEPT’s translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated $$300\times 300\times 300$$

300
×
300
×
300

 mm$$^3$$

3

cubic PMMA targets were irradiated by $$^4$$

4

He or $$^{12}$$

12

C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include $$10\times 10\times 10$$

10
×
10
×
10

 mm$$^3$$

3

neutron capture inserts (NCIs) of pure $$^{10}$$

10

B or $$^{157}$$

157

Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated $$50\times 50\times 50$$

50
×
50
×
50

 mm$$^3$$

3

ideal detector were recorded. A temporal mask of 50–60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives ($$R_{TF}$$

R

TF

) was calculated; for targets with $$^{10}$$

10

B and $$^{157}$$

157

Gd NCIs, the detector materials which resulted in the highest $$R_{TF}$$

R

TF

were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the $$^{10}$$

10

B NCI and 1 ms for the $$^{157}$$

157

Gd NCI.
Myzorhynchus series of Anopheles mosquitoes as potential vectors of Plasmodium bubalis in Thailand
Authors: Nugraheni Yudhi Ratna , Arnuphapprasert Apinya , Nguyen Trang Thuy , Narapakdeesakul Duriyang , Nguyen Hoang Lan Anh , Poofery Juthathip , Kaneko Osamu , Asada Masahito , Kaewthamasorn Morakot
Published: April 2022

Ungulate malaria parasites and their vectors are among the least studied when compared to other medically important species. As a result, a thorough understanding of ungulate malaria parasites, hosts, and mosquito vectors has been lacking, necessitating additional research efforts. This study aimed to identify the vector(s) of Plasmodium bubalis. A total of 187 female mosquitoes (133 Anopheles spp., 24 Culex spp., 24 Aedes spp., and 6 Mansonia spp. collected from a buffalo farm in Thailand where concurrently collected water buffalo samples were examined and we found only Anopheles spp. samples were P. bubalis positive. Molecular identification of anopheline mosquito species was conducted by sequencing of the PCR products targeting cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 2 (cox2), and internal transcribed spacer 2 (ITS2) markers. We observed 5 distinct groups of anopheline mosquitoes: Barbirostris, Hyrcanus, Ludlowae, Funestus, and Jamesii groups. The Barbirostris group (Anopheles wejchoochotei or Anopheles campestris) and the Hyrcanus group (Anopheles peditaeniatus) were positive for P. bubalis. Thus, for the first time, our study implicated these anopheline mosquito species as probable vectors of P. bubalis in Thailand.
Quantum dots based in-vitro co-culture cancer model for identification of rare cancer cell heterogeneity
Authors: Vyshnava Satyanarayana Swamy , Pandluru Gayathri , Kumar Kanderi Dileep , Panjala Shiva Prasad , Banapuram Swathi , Paramasivam Kameshpandian , Devi Kothamunireddy Varalakshmi , Anupalli Roja Rani , Dowlatabad Muralidhara Rao
Published: April 2022

Cancer cell heterogeneity (CCH) is crucial in understanding cancer progression and metastasis. The CCH is one of the stumbling blocks in modern medicine's therapeutics and diagnostics . An in-vitro model of co-culture systems of MCF-7, HeLa, HEK-293, with THP-1 cells showed the occurrence of EpCAM positive (EpCAM+) and EpCAM negative (EpCAM−) heterogenetic cancer cell types labeled with the Quantum Dot antibody conjugates (QDAb). This in-vitro model study could provide insights into the role of rare cancer cells manifestation and their heterogeneity in metastatic progression and risk for severe infections in these patients. We successfully report the presence of CCH based on the fluorescence ratios of the co-cultured cancer cells when treated with the QDAb. These short-term mimic co-cultures give a compelling and quite associated model for assessing early treatment responses in various cancers.
Impact of rice paddy agriculture on habitat usage of migratory shorebirds at the rice paddy scale in Korea
Authors: Choi Seung-Hye , Choi Green , Nam Hyung-Kyu
Published: April 2022

Approximately 58 shorebird species, including endangered and threatened species, use various habitats while traveling on their long-distance migratory routes in the East Asian-Australasian Flyway (EAAF). Coastal rice paddies in midwestern Korea, which are located in the EAAF, serve as inland wetlands and provide important stopover sites for long-distance migratory shorebirds. We studied how shorebird population density is affected across periods, time since habitat formation, and field type, at the rice field scale. The shorebirds most frequently observed in rice paddies were, in order, black-tailed godwits (Limosa limosa), common greenshanks (Tringa nebularia), and wood sandpipers (T. glareola). Black-tailed godwits and wood sandpipers were affected by time since formation, field type, and water level, whereas field type affected common greenshanks. We propose that (1) flooding time, (2) shallow water level, (3) harrowed field type, and (4) 5–7 days of management intervals at paddy fields are important factors influencing shorebird species density, although all the factors did not influence common greenshank density. We propose that environmental characteristics derived from field management in rice paddies influence habitat use by migratory shorebirds. These factors need to be considered to systematically protect and manage shorebirds that use rice paddies as stopovers during their migration events.
Serum calprotectin: a potential biomarker to diagnose chronic prosthetic joint infection after total hip or knee arthroplasty
Authors: Ackmann Thomas , Schwarze Jan , Gosheger Georg , Schmidt-Braekling Tom , Puetzler Jan , Moellenbeck Burkhard , Theil Christoph
Published: April 2022

The preoperative detection of prosthetic joint infection (PJI) prior to revision of total hip or knee arthroplasty is still a challenge. Serum Calprotectin (CP) is a heterodimer of two calcium-binding proteins present in the cytoplasm of neutrophils that is released in inflammatory processes and infections. The objective of this study is to determine the reliability of serum CP in the diagnosis of chronic PJI. 81 patients (40 women, 41 men) that presented a potential indication for revision arthroplasty of the hip (THA; n = 18) or knee (TKA, n = 63) at a single institution were prospectively evaluated. The joints were diagnosed as chronically infected or aseptic based on the musculoskeletal infection society (MSIS) criteria of 2018. Receiver operating characteristics and the Youden’s index were used to define an ideal cutoff value. The median serum CP level was significantly higher in the group with chronic PJI (15,120 vs. 4980 ng/ml;p < 0.001) compared to the aseptic cases. The calculated optimal cut-off value was 9910 ng/ml (AUC 0.899, 95% CI 0.830–0.968) with a specificity of 91% and sensitivity of 81%. The present investigation suggests that serum CP has a high specificity and good sensitivity to diagnose chronic PJI after TJA of the knee or hip.
Patient demographics, clinicopathologic features, and outcomes in wild-type gastrointestinal stromal tumor: a national cohort analysis
Authors: Khan Tahsin M. , Verbus Emily A. , Rossi Alexander J. , Hernandez Jonathan M. , Davis Jeremy L. , Coakley Brian A. , Blakely Andrew M.
Published: April 2022

Wild-type KIT and PDGFRA gastrointestinal stromal tumors (GIST) are rare tumors with limited treatment options. We sought to determine the clinicopathologic features of wild-type GIST and identify factors that influence overall survival (OS) using a large national database. Retrospective evaluation of patients with wild-type GIST in the National Cancer Database (NCDB) was performed. Demographic, clinicopathologic, and treatment data were analyzed. Features associated with OS were investigated using Kaplan–Meier analysis and Cox proportional hazards model. 244 patients with median diagnosis age of 59 years (95% CI 57–63) were identified. The stomach was the most common primary site (57%) followed by the small intestine (35%). Surgical resection was performed on 85% of patients and 53% of patients received systemic therapy. Factors associated with decreased OS on multivariable analysis included small intestine primary (HR 2.72, 95% CI 1.13–6.69, P = 0.026) and > 5 mitoses per 50 HPF (HR 4.77, 95% CI 1.86–13.2, P = 0.001). Wild-type GISTs may be identified in older patients, with most arising in the stomach and small bowel. Surgery remains the principal treatment modality. Small intestine primary site and high mitotic count were associated with abbreviated OS.
Host–pathogen dynamics in longitudinal clinical specimens from patients with COVID-19
Authors: Lin Michelle J. , Rachleff Victoria M. , Xie Hong , Shrestha Lasata , Lieberman Nicole A. P. , Peddu Vikas , Addetia Amin , Casto Amanda M. , Breit Nathan , Mathias Patrick C. , Huang Meei-Li , Jerome Keith R. , Greninger Alexander L. , Roychoudhury Pavitra
Published: April 2022

Rapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolution in vivo. Here we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-QPCR cycle threshold of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals. These results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.
The first family of application-specific integrated circuits for programmable and reconfigurable metasurfaces
Authors: Petrou Loukas , Kossifos Kypros M. , Antoniades Marco A. , Georgiou Julius
Published: April 2022

Reconfigurable metasurfaces are man-made surfaces, which consist of sub-wavelength periodic elements—meta-atoms—that can be reconfigured to manipulate incoming electromagnetic waves. However, reconfigurable metasurfaces developed to-date, have limitations in terms of loading impedance range, reconfiguration delay and power consumption. Also, these systems are costly and they require bulky electronics and complex control circuits, which makes them unattractive for commercial use. Here, we report the first family of CMOS application-specific integrated circuits that enable microsecond and microwatt reconfiguration of complex impedances at microwave frequencies. Our approach utilizes asynchronous digital control circuitry with chip-to-chip communication capabilities, allowing simple and fast reconfiguration via digital devices and user-friendly software. Our solution is low-cost and can cover arbitrary board-to-board metasurfaces, with different sizes and shapes.
Optimization of the nutritional constituents for ergosterol peroxide production by Paecilomyces cicadae based on the uniform design and mathematical model
Authors: Fenhui Shi , He Linfu , Qian Jingya , Zhang Zhicai , Zheng Huihua
Published: April 2022

we optimized medium components for the production of ergosterol peroxide (EP) by Paecilomyces cicadae based on a mono-factor experiment, a uniform design, and a non-linear regression analysis. The maximum EP yield achieved was 256 μg/L, which was increased by 5 folds compared with that before the optimization. Structured Monod model, Andrews model, Contois model, and Aibe model were developed to describe the effects of viscosity inhibition, substrate, and production on biomass growth. The results showed that the Monod model could predict biomass growth, and the effects of viscosity and substrate on the EP concentration were significantly higher compared with the effect of production. The addition of water and glycerol could decrease the viscosity inhibition and glycerol inhibition, and further increase the EP yield. The newly developed structured model was demonstrated for batch growth of P.cicadae.
Modification of the chemically induced inflammation assay reveals the Janus face of a phenol rich fulvic acid
Authors: Lieke Thora , Steinberg Christian E. W. , Meinelt Thomas , Knopf Klaus , Kloas Werner
Published: April 2022

Inflammation is an essential process as a reaction towards infections or wounding. Exposure to hazardous environmental pollutants can lead to chronic inflammations, where the resolving phase is delayed or blocked. Very contradictory studies have been reported on the pro- and anti-inflammatory effects of humic substances (HSs) leading to significant disagreements between researchers. To a certain extent, this can be attributed to the chemical heterogeneity of this group of xenobiotics. Here we show for the first time that pro- and anti-inflammatory effects can occur by one HSs. We adapted an assay that uses green fluorescence-labeled zebrafish larvae and CuSO4 to indue an inflammation. In wild-type larvae, exposure to 50 µM CuSO4 for 2 h activated the production of reactive oxygen species, which can be monitored with a fluorescence dye (H2DCFDA) and a microplate reader. This allows not only the use of wild-type fish but also a temporal separation of copper exposure and inflammatory substance while retaining the high throughput. This modified assay was then used to evaluate the inflammatory properties of a fulvic acid (FA). We found, that the aromatic structure of the FA protects from inflammation at 5 and 50 mg C/L, while the persistent free radicals enhance the copper-induced inflammation at ≥ 300 mg C/L.
Evaluation of a new transcutaneous bilirubinometer in newborn infants
Authors: Norman Mikael , Aytug Hüseyin , Celebi Hasan Basri
Published: April 2022

To avoid brain damage in newborn infants, effective tools for prevention of excessive neonatal hyperbilirubinemia are needed. The objective of this study was to evaluate a new transcutaneous bilirubinometer (JAISY). For this purpose, 930 bilirubin measurements were performed in 141 newborn infants born near-term or at term (gestational age 35–41 weeks; postnatal age 1–6 days; 71 boys; including 29 infants with darker skin) and compared to those of a previously validated instrument (JM105). In each infant, the mean of three repeated measurements in the forehead was calculated for each instrument, followed by a similar measurement on the chest. The bilirubin values varied between 0 and 320 µmol/l (0–18.8 mg/dl). There was a high degree of agreement with significant correlations between bilirubin values measured with the two devices on the forehead (Pearson’s r = 0.94, p < 0.001) and the chest (r = 0.94, p < 0.001). The correlations remained after stratifying the data by gestational age, postnatal age and skin color. The coefficient of variation for repeated bilirubin measurements was 8.8% for JAISY and 8.0% for JM105 (p = 0.79). In conclusion, JAISY provides accurate and reproducible information on low to moderately high bilirubin levels in newborn infants born near-term or at term.
Evaluating approved and alternative treatments against an oxytetracycline-resistant bacterium responsible for European foulbrood disease in honey bees
Authors: Masood Fatima , Thebeau Jenna M. , Cloet Allyssa , Kozii Ivanna V. , Zabrodski Michael W. , Biganski Sarah , Liang Jenny , Marta Guarna M. , Simko Elemir , Ruzzini Antonio , Wood Sarah C.
Published: April 2022

European foulbrood (EFB) is a disease of honey bee larvae caused by Melissococcus plutonius. In North America, oxytetracycline (OTC) is approved to combat EFB disease though tylosin (TYL) and lincomycin (LMC) are also registered for use against American foulbrood disease. Herein, we report and characterize an OTC-resistant M. plutonius isolate from British Columbia, Canada, providing an antimicrobial sensitivity to the three approved antibiotics and studying their abilities to alter larval survival in an in vitro infection model. Specifically, we investigated OTC, TYL, and LMC as potential treatment options for EFB disease using laboratory-reared larvae infected with M. plutonius. The utility of the three antibiotics were compared through an experimental design that either mimicked metaphylaxis or antimicrobial intervention. At varying concentrations, all three antibiotics prevented clinical signs of EFB disease following infection with M. plutonius 2019BC1 in vitro. This included treatment with 100 μg/mL of OTC, a concentration that was ~ 3× the minimum inhibitory concentration measured to inhibit the strain in nutrient broth. Additionally, we noted high larval mortality in groups treated with doses of OTC corresponding to ~ 30× the dose required to eliminate bacterial growth in vitro. In contrast, TYL and LMC were not toxic to larvae at concentrations that exceed field use. As we continue to investigate antimicrobial resistance (AMR) profiles of M. plutonius from known EFB outbreaks, we expect a range of AMR phenotypes, reiterating the importance of expanding current therapeutic options along with alternative management practices to suppress this disease.
Comparative transcriptome profiling of virulent and avirulent isolates of Neoparamoeba perurans
Authors: Smith Aaron J. , Crosbie Philip B. B. , Nowak Barbara F. , Bridle Andrew R.
Published: April 2022

Neoparamoeba perurans, the aetiological agent of amoebic gill disease, remains a persistent threat to Atlantic salmon mariculture operations worldwide. Innovation in methods of AGD control is required yet constrained by a limited understanding of the mechanisms of amoebic gill disease pathogenesis. In the current study, a comparative transcriptome analysis of two N. perurans isolates of contrasting virulence phenotypes is presented using gill-associated, virulent (wild type) isolates, and in vitro cultured, avirulent (clonal) isolates. Differential gene expression analysis identified a total of 21,198 differentially expressed genes between the wild type and clonal isolates, with 5674 of these genes upregulated in wild type N. perurans. Gene set enrichment analysis predicted gene sets enriched in the wild type isolates including, although not limited to, cortical actin cytoskeleton, pseudopodia, phagocytosis, macropinocytic cup, and fatty acid beta-oxidation. Combined, the results from these analyses suggest that upregulated gene expression associated with lipid metabolism, oxidative stress response, protease activity, and cytoskeleton reorganisation is linked to pathogenicity in wild type N. perurans. These findings provide a foundation for future AGD research and the development of novel therapeutic and prophylactic AGD control measures for commercial aquaculture.
Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19
Authors: Abd El Hafez Mohamed S. M. , AbdEl-Wahab Miral G. , Seadawy Mohamed G. , El-Hosseny Mostafa F. , Beskales Osama , Saber Ali Abdel-Hamid Ali , El Demellawy Maha A. , Ghareeb Doaa A.
Published: April 2022

The medicinal potential of marine invertebrates' bioactive components that may act as anti-COVID-19 demonstrated promising results. Ophiocoma dentata, which is common in the Red Sea, is one such source. Therefore, this study aimed to isolate a new compound from the brittle star, Ophiocoma dentata, and evaluate its efficacy as anti-COVID-19 in-silico and in-vitro. Standard procedures were followed in order to assess the isolated compound’s preliminary toxicity and anti-inflammatory properties. Computer virtual screening technology through molecular docking and ADMET studies was conducted as well as a new steroid derivative was isolated for the first time, named 5α-cholesta-4(27), 24-dien-3β, 23 β-diol. Investigation of the Anti-Covid-19 activity of the isolated compound using a Plaque reduction assay revealed 95% inhibition at a concentration of 5 ng/µl (12.48 µM). Moreover, this compound showed an IC50 of 11,350 ± 1500 ng/ml against the normal fibroblast cells, indicating its safety. Interestingly, this compound exhibited anti-inflammatory activity with an IC50 of 51.92 ± 0.03 μg/ml compared to a reference drug’s IC50 of 53.64 ± 0.01 μg/ml, indicating that this compound is a potent anti-inflammatory. In silico data have proved that the isolated compound is a promising viral inhibitor against SARS-CoV2 and is thus recommended as a future nature preventive and curative antiviral drug.