bluuebunny/crossref_metadata_2025 huggingface dataset:
Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany
Authors: Albinger Nawid , Hartmann Jessica , Ullrich Evelyn
Published: March 2021

Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.
The recombination landscape and multiple QTL mapping in a Solanum tuberosum cv. ‘Atlantic’-derived F1 population
Authors: da Silva Pereira Guilherme , Mollinari Marcelo , Schumann Mitchell J. , Clough Mark E. , Zeng Zhao-Bang , Yencho G. Craig
Published: March 2021

There are many challenges involved with the genetic analyses of autopolyploid species, such as the tetraploid potato,Solanum tuberosum(2n = 4x = 48). The development of new analytical methods has made it valuable to re-analyze an F1population (n = 156) derived from a cross involving ‘Atlantic’, a widely grown chipping variety in the USA. A fully integrated genetic map with 4285 single nucleotide polymorphisms, spanning 1630 cM, was constructed with MAPpoly software. We observed that bivalent configurations were the most abundant ones (51.0~72.4% depending on parent and linkage group), though multivalent configurations were also observed (2.2~39.2%). Seven traits were evaluated over four years (2006–8 and 2014) and quantitative trait loci (QTL) mapping was carried out using QTLpoly software. Based on a multiple-QTL model approach, we detected 21 QTL for 15 out of 27 trait-year combination phenotypes. A hotspot on linkage group 5 was identified with co-located QTL for maturity, plant yield, specific gravity, and internal heat necrosis resistance evaluated over different years. Additional QTL for specific gravity and dry matter were detected with maturity-corrected phenotypes. Among the genes around QTL peaks, we found those on chromosome 5 that have been previously implicated in maturity (StCDF1) and tuber formation (POTH1). These analyses have the potential to provide insights into the biology and breeding of tetraploid potato and other autopolyploid species.
A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study
Authors: Radzieta Michael , Sadeghpour-Heravi Fatemah , Peters Timothy J. , Hu Honghua , Vickery Karen , Jeffries Thomas , Dickson Hugh G. , Schwarzer Saskia , Jensen Slade O. , Malone Matthew
Published: March 2021

Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host–microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs. Further, we identified the significant enrichment of several virulence factors associated with infection pathogenicity belonging to both Staphylococcus aureus and Streptococcus. In severe DFIs, patients demonstrated a greater microbial diversity and differential gene expression demonstrated the enrichment of multispecies virulence genes suggestive of a complex polymicrobial infection. The host response in patients with severe DFIs was also significantly different as compared to mild to moderate DFIs. This was attributed to the enrichment of host genes associated with inflammation, acute phase response, cell stress and broad immune-related responses, while those associated with wound healing and myogenesis were significantly depleted.
Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer
Authors: Kalra Maitri , Tong Yan , Jones David R. , Walsh Tom , Danso Michael A. , Ma Cynthia X. , Silverman Paula , King Mary-Claire , Badve Sunil S. , Perkins Susan M. , Miller Kathy D.
Published: March 2021

Patients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.
Fault2SHA Central Apennines database and structuring active fault data for seismic hazard assessment
Authors: Faure Walker Joanna , Boncio Paolo , Pace Bruno , Roberts Gerald , Benedetti Lucilla , Scotti Oona , Visini Francesco , Peruzza Laura
Published: March 2021

We present a database of field data for active faults in the central Apennines, Italy, including trace, fault and main fault locations with activity and location certainties, and slip-rate, slip-vector and surface geometry data. As advances occur in our capability to create more detailed fault-based hazard models, depending on the availability of primary data and observations, it is desirable that such data can be organized in a way that is easily understood and incorporated into present and future models. The database structure presented herein aims to assist this process. We recommend stating what observations have led to different location and activity certainty and presenting slip-rate data with point location coordinates of where the data were collected with the time periods over which they were calculated. Such data reporting allows more complete uncertainty analyses in hazard and risk modelling. The data and maps are available as kmz, kml, and geopackage files with the data presented in spreadsheet files and the map coordinates as txt files. The files are available at:https://doi.org/10.1594/PANGAEA.922582.
The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans
Authors: Esh Christopher J. , Chrismas Bryna C. R. , Mauger Alexis R. , Cherif Anissa , Molphy John , Taylor Lee
Published: March 2021

Whether cyclooxygenase (COX)/prostaglandin E2 (PGE2) thermoregulatory pathways, observed in rodents, present in humans? Participants (n = 9) were exposed to three environments; cold (20 °C), thermoneutral (30 °C) and hot (40 °C) for 120 min. Core (Tc)/skin temperature and thermal perception were recorded every 15 min, with COX/PGE2 concentrations determined at baseline, 60 and 120 min. Linear mixed models identified differences between and within subjects/conditions. Random coefficient models determined relationships between Tc and COX/PGE2. Tc [mean (range)] increased in hot [+ 0.8 (0.4–1.2) °C; p < 0.0001; effect size (ES): 2.9], decreased in cold [− 0.5 (− 0.8 to − 0.2) °C; p < 0.0001; ES 2.6] and was unchanged in thermoneutral [+ 0.1 (− 0.2 to 0.4) °C; p = 0.3502]. A relationship between COX2/PGE2 in cold (p = 0.0012) and cold/thermoneutral [collapsed, condition and time (p = 0.0243)] was seen, with higher PGE2 associated with higher Tc. A within condition relationship between Tc/PGE2 was observed in thermoneutral (p = 0.0202) and cold/thermoneutral [collapsed, condition and time (p = 0.0079)] but not cold (p = 0.0631). The data suggests a thermogenic response of the COX/PGE2 pathway insufficient to defend Tc in cold. Further human in vivo research which manipulates COX/PGE2 bioavailability and participant acclimation/acclimatization are warranted to elucidate the influence of COX/PGE2 on Tc.
Response of the chemical structure of soil organic carbon to modes of maize straw return
Authors: Zheng Shuqing , Zhang Jiuming , Chi Fengqin , Zhou Baoku , Wei Dan , Kuang Enjun , Jiang Yu , Mi Gang , Chen Yu ping
Published: March 2021

Elucidating the chemical structure of soil organic matter (SOM) is important for accurately evaluating the stability and function of SOM. Aboveground vegetation directly affects the quantity and quality of exogenous organic matter input into the soil through plant residues and root exudates, which in turn affects soil microbial species, community structure, and activity, and ultimately impacts the chemical structure of SOM. In this study, a 13C nuclear magnetic resonance technique was used to analyze the chemical structure characteristics of soil organic carbon (SOC) under various rates of straw returning combined with rotary tillage and under full straw mulching. The results showed that full straw returning with rotary tillage and full straw mulching more effectively increased the SOC content than reduced rate of straw returning (1/2 and 1/3 of full straw) with rotary tillage. The contents of alkyl C and alkoxy C in the functional groups of SOC under various straw returning treatments were increased compared with those under the treatment of maize stubble remaining in soil (CK). Furthermore, the contents of aromatic C and carboxyl C were decreased, which were consistent with the chemical shift changes of SOC. Compared with CK treatment, straw returning decreased the content of aromatic C in the functional groups of SOC, but increased the content of alkoxy C, which could be associated with the change in integral areas of absorption peaks of alkyl C and alkoxy C moving toward left and right, respectively. The content of total SOC was significantly positively (P < 0.05) correlated with that of alkoxy C and significantly negatively (P < 0.01) correlated with that of aromatic C. The molecular structure of SOC tends to be simplified due to the decreasing in refractory C and the increasing in easily decomposed C after straw returning to the field.
Addressing indirect frequency coupling via partial generalized coherence
Authors: Young Joseph , Homma Ryota , Aazhang Behnaam
Published: March 2021

Distinguishing between direct and indirect frequency coupling is an important aspect of functional connectivity analyses because this distinction can determine if two brain regions are directly connected. Although partial coherence quantifies partial frequency coupling in the linear Gaussian case, we introduce a general framework that can address even the nonlinear and non-Gaussian case. Our technique, partial generalized coherence (PGC), expands prior work by allowing pairwise frequency coupling analyses to be conditioned on other processes, enabling model-free partial frequency coupling results. By taking advantage of recent advances in conditional mutual information estimation, we are able to implement our technique in a way that scales well with dimensionality, making it possible to condition on many processes and produce a partial frequency coupling graph. We analyzed both linear Gaussian and nonlinear simulated networks. We then performed PGC analysis of calcium recordings from mouse olfactory bulb glomeruli under anesthesia and quantified the dominant influence of breathing-related activity on the pairwise relationships between glomeruli for breathing-related frequencies. Overall, we introduce a technique capable of eliminating indirect frequency coupling in a model-free way, empowering future research to correct for potentially misleading frequency interactions in functional connectivity analyses.
Triple negative aggressive phenotype controlled by miR-135b and miR-365: new theranostics candidates
Authors: Bertoli Gloria , Cava Claudia , Corsi Fabio , Piccotti Francesca , Martelli Cristina , Ottobrini Luisa , Vaira Valentina , Castiglioni Isabella
Published: March 2021

Triple negative breast cancer (TNBC) accounts for about a fifth of all breast cancers and includes a diverse group of cancers. The heterogeneity of TNBC and the lack of target receptors on the cell surface make it difficult to develop specific therapeutic treatments. These aspects cause the high negative prognosis of patients with this type of tumor. The analysis of the molecular profiles of TNBC samples has allowed a better characterization of this tumor, supporting the search for new reliable diagnostic markers. To this end, we have developed a bioinformatic approach to integrate networks of genes differentially expressed in basal breast cancer compared to healthy tissues, with miRNAs able to regulate their expression. We studied the role of these miRNAs in TNBC subtype cell lines. We therefore identified two miRNAs, namely miR-135b and miR-365, with a central role in regulating the altered functional pathways in basal breast cancer. These two miRNAs are differentially expressed in human TNBC immunohistochemistry-selected tissues, and their modulation has been shown to play a role in the proliferation of tumor control and its migratory and invasive capacity in TNBC subtype cell lines. From the perspective of personalized medicine, we managed to modulate the expression of the two miRNAs in organotypic cultures, suggesting their possible use as diagnostic and therapeutic molecules. miR-135b and miR-365 have a key role in TNBC, controlling proliferation and invasion. Their detection could be helpful in TNBC diagnosis, while their modulation could become a new therapeutic tool for TNBC.
Egoistic punishment outcompetes altruistic punishment in the spatial public goods game
Authors: Li Juan , Liu Yi , Wang Zhen , Xia Haoxiang
Published: March 2021

The evolution of costly punishment is a puzzle due to cooperators’ second-order free-riding. Previous studies have proposed many solutions mainly focused on reducing the punishment cost or punishing second-order free riders directly or indirectly. We attempt to explain this confusion from the perspective of punishment motivation, which is why the punisher is willing to pay the cost. The answer is that the punisher is egoistic. Egoistic punishment aims to protect punishers’ own cooperative benefits shared by the defectors. In such case, egoistic punishers would pay a cost in punishing defectors and retrieve lost payoffs from defectors. Here, we examined the evolution and performance of egoistic punishment and compared it with typical altruistic punishment using classic peer-punishment and pool-punishment modes. Results showed egoistic punishment can evolve and effectively promote cooperation within a large parameter range, whether in a well-mixed or structured population, or through peer-punishment or pool-punishment modes. This result is also robust to different strategy-updating rules. The evolution under the pool-punishment mechanism is more complicated. The influence of parameters is counter-intuitive because of cycle dominance; namely, the cost is the key factor to control the level of cooperation and the fine determines the ratio of the punishers and cooperators. Compared with altruistic punishment, egoistic punishment can promote cooperation in a lower-fine and higher-cost area, especially in the pool punishment mode, and the egoistic punishers have stronger survivability. Egoistic punishers represent the natural fairness in a social system. Results revealed that focusing on individual equity can significantly promote collective cooperation. This study provides another explanation for the evolution of costly punishment.
Clustering of neuropsychological traits of preschoolers
Authors: Treviño Mario , Beltrán-Navarro Beatriz , León Ricardo Medina-Coss y , Matute Esmeralda
Published: March 2021

Neuropsychological tests (targeting cognitive, linguistic, motor, and executive abilities) are grouped in neuropsychological domains that are thought to be stable through adulthood. However, this assumption does not always hold true, particularly during young children’s early developmental phase. Here, we explored how the neuropsychological profile of typical Spanish-speaking preschoolers varied and consolidated with age. We recruited 643 monolingual Latin-American children from Mexico, Colombia, and Guatemala, with ages spanning from 30 to 71 months of age, and applied a novel neuropsychological examination which combined a total of 52 tests covering five classical neuropsychological domains: receptive, expressive, attention/memory, processing, and executive functions. These tests’ scores uncovered a correlational structure across neuropsychological functions that could not be explained by chance. Notably, these correlations’ overall strength, but not their interdependence across domains, dramatically increased with age. Moreover, by applying conventional clustering techniques to classify the experimental data, we found a stable representation of two clusters of children with distinctive traits, with cultural factors contributing to this classification scheme. We also found that the tasks were well organized in a network of abilities, where nodes with highest highest interconnectedness were those that required multimodal processing. These results contribute to our understanding of children’s ‘normal’ development and could help identify how failure in particular functions forecasts the emergence of neurodevelopmental disorders. Our analytic methods might become useful to characterize individual differences and improve educational practices and interventions.
Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
Authors: Parr Jonathan B. , Kieto Eddy , Phanzu Fernandine , Mansiangi Paul , Mwandagalirwa Kashamuka , Mvuama Nono , Landela Ange , Atibu Joseph , Efundu Solange Umesumbu , Olenga Jean W. , Thwai Kyaw Lay , Morgan Camille E. , Denton Madeline , Poffley Alison , Juliano Jonathan J. , Mungala Pomie , Likwela Joris L. , Sompwe Eric M. , Rogier Eric , Tshefu Antoinette K. , N’Siala Adrien , Kalonji Albert
Published: March 2021

The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen’s kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.
Low soil moisture predisposes field-grown chickpea plants to dry root rot disease: evidence from simulation modeling and correlation analysis
Authors: Sinha Ranjita , Irulappan Vadivelmurugan , Patil Basavanagouda S. , Reddy Puli Chandra Obul , Ramegowda Venkategowda , Mohan-Raju Basavaiah , Rangappa Krishnappa , Singh Harvinder Kumar , Bhartiya Sharad , Senthil-Kumar Muthappa
Published: March 2021

Rhizoctonia bataticola causes dry root rot (DRR), a devastating disease in chickpea (Cicer arietinum). DRR incidence increases under water deficit stress and high temperature. However, the roles of other edaphic and environmental factors remain unclear. Here, we performed an artificial neural network (ANN)-based prediction of DRR incidence considering DRR incidence data from previous reports and weather factors. ANN-based prediction using the backpropagation algorithm showed that the combination of total rainfall from November to January of the chickpea-growing season and average maximum temperature of the months October and November is crucial in determining DRR occurrence in chickpea fields. The prediction accuracy of DRR incidence was 84.6% with the validation dataset. Field trials at seven different locations in India with combination of low soil moisture and pathogen stress treatments confirmed the impact of low soil moisture on DRR incidence under different agroclimatic zones and helped in determining the correlation of soil factors with DRR incidence. Soil phosphorus, potassium, organic carbon, and clay content were positively correlated with DRR incidence, while soil silt content was negatively correlated. Our results establish the role of edaphic and other weather factors in chickpea DRR disease incidence. Our ANN-based model will allow the location-specific prediction of DRR incidence, enabling efficient decision-making in chickpea cultivation to minimize yield loss.
TMAO: a potential mediator of clopidogrel resistance
Authors: Ma Ruisong , Fu Wenwen , Zhang Jing , Hu Xiaorong , Yang Jun , Jiang Hong
Published: March 2021

Trimethylamine-N-oxide (TMAO) can activate platelets and increase thrombosis risk in clinical and experimental models. Meanwhile, the patients with coronary artery disease have higher serum TMAO level. However, it remains unknown whether Clopidogrel Resistance (CR) could be attributed to TMAO. The present study aimed investigate the effects of TMAO on clopidogrel in ischemia and reperfusion (IR) model in rats. Clopidogrel could (1) promote the production of platelets, induce an increase in the platelet-larger cell ratio; (2) prolong the tail bleeding time; (3) reduce platelet aggregation function, induced by ADP, and alleviate myocardial thrombus burden. TMAO could partially offset the effects of clopidogrel and induce CR. Thus, the present study demonstrated that circulating TMAO could reduce the inhibitory effects of clopidogrel on platelet aggregation. TMAO may be a potential mediator of clopidogrel resistance.
Promotion of biological nitrogen fixation activity of an anaerobic consortium using humin as an extracellular electron mediator
Authors: Dey Sujan , Awata Takanori , Mitsushita Jumpei , Zhang Dongdong , Kasai Takuya , Matsuura Norihisa , Katayama Arata
Published: March 2021

Nitrogen fertiliser is manufactured using the industrial Haber–Bosch process, although it is extremely energy-consuming. One sustainable alternative technology is the electrochemical promotion of biological nitrogen fixation (BNF). This study reports the promotion of BNF activity of anaerobic microbial consortia by humin, a solid-phase humic substance, at any pH, functioning as an extracellular electron mediator, to levels of 5.7–11.8 times under nitrogen-deficient conditions. This was evidenced by increased acetylene reduction activity and total nitrogen content of the consortia. Various humins from different origins promoted anaerobic BNF activity, although the degree of promotion differed. The promotion effected by humin differed from the effects of chemical reducing agents and the effects of supplemental micronutrients and vitamins. The promotion of anaerobic BNF activity by only reduced humin without any other electron donor suggested that humin did not serve as organic carbon source but as extracellular electron mediator, for electron donation to the nitrogen-fixing microorganisms. The next generation sequencing (NGS) of partial 16S rRNA genes showed the predominance of Clostridiales (Firmicutes) in the consortia. These findings suggest the effectiveness of humin as a solid-phase extracellular electron mediator for the promotion of anaerobic BNF activity, potentially to serve for the basis for a sustainable technology.
Clinical factors affecting the rate of exodrift after surgery in patients with basic intermittent exotropia
Authors: Kim Seungheon , Ha Suk-Gyu , Suh Young-Woo , Kim Seung-Hyun
Published: March 2021

We investigated the period of postoperative exodrift during follow-up and clinical factors that affect the rate of exodrift after surgery in the patients with intermittent exotropia (IXT). A retrospective review of medical records of patients with exodrift who underwent bilateral rectus recession for IXT was performed. Exodrift was defined as angle of deviation greater than 10 prism diopters (PD) at distance and near. The median survival period of postoperative exodrift was analyzed using Kaplan Meier survival analysis. The patients were divided into two groups according to the median period of postoperative exodrift (early and late group). The weighted Cox’s proportional hazards regression analysis to investigate the risk factors that affect rate of postoperative exodrift was performed. A total of 108 patients was included. The preoperative angle of deviation at distance and near were 30.3 ± 7.2 PD and 29.5 ± 8.6 PD, respectively. The median survival period of postoperative exodrift was 24 months (range, 6–48 months).The angle of deviation at postoperative day 1 in early and late group were − 3.8 ± 5.5 PD (range, − 16–8 PD) and − 7.7 ± 4.6 PD (range, − 16–4 PD) (p < 0.01). Minus value means esodeviation. In regression analysis, the angle of deviation at postoperative day 1 was the significantly related with rate of exodrift (p < 0.01). The median period of exodrift after surgery was 24 months, angle of deviation at postoperative day 1 could affect the rate of exodrift in patients with IXT.
Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B
Authors: Suchodolski Jakub , Derkacz Daria , Bernat Przemysław , Krasowska Anna
Published: March 2021

The effect of capric acid, secreted by the probiotic yeasts Saccharomyces boulardii, was evaluated on the activities of fluconazole (FLC) and amphotericin B (AMB) against pathogenic Candida albicans fungus. The findings indicated that capric acid may be a promising additive for use in combination with FLC. A FLC-capric acid combination led to reduced efflux activity of multidrug resistance (MDR) transporter Cdr1p by causing it to relocalize from the plasma membrane (PM) to the interior of the cell. The above effect occurred due to inhibitory effect of FLC-capric acid combination of ergosterol biosynthesis. However, capric acid alone stimulated ergosterol production in C. albicans, which in turn generated cross resistance towards AMB and inhibited its action (PM permeabilization and cytoplasm leakage) against C. albicans cells. This concluded that AMB should not be administered among dietary supplements containing capric acid or S. boulardii cells.
All-optical spin switching probability in [Tb/Co] multilayers
Authors: Avilés-Félix L. , Farcis L. , Jin Z. , Álvaro-Gómez L. , Li G. , Yamada K. T. , Kirilyuk A. , Kimel A. V. , Rasing Th. , Dieny B. , Sousa R. C. , Prejbeanu I. L. , Buda-Prejbeanu L. D.
Published: March 2021

Since the first experimental observation of all-optical switching phenomena, intensive research has been focused on finding suitable magnetic systems that can be integrated as storage elements within spintronic devices and whose magnetization can be controlled through ultra-short single laser pulses. We report here atomistic spin simulations of all-optical switching in multilayered structures alternating n monolayers of Tb and m monolayers of Co. By using a two temperature model, we numerically calculate the thermal variation of the magnetization of each sublattice as well as the magnetization dynamics of [$$\text {Tb}_n$$

Tb
n

/$$\text {Co}_m$$

Co
m

] multilayers upon incidence of a single laser pulse. In particular, the condition to observe thermally-induced magnetization switching is investigated upon varying systematically both the composition of the sample (n,m) and the laser fluence. The samples with one monolayer of Tb as [$$\text {Tb}_1$$

Tb
1

/$$\text {Co}_2$$

Co
2

] and [$$\text {Tb}_1$$

Tb
1

/$$\text {Co}_3$$

Co
3

] are showing thermally induced magnetization switching above a fluence threshold. The reversal mechanism is mediated by the residual magnetization of the Tb lattice while the Co is fully demagnetized in agreement with the models developed for ferrimagnetic alloys. The switching is however not fully deterministic but the error rate can be tuned by the damping parameter. Increasing the number of monolayers the switching becomes completely stochastic. The intermixing at the Tb/Co interfaces appears to be a promising way to reduce the stochasticity. These results predict for the first time the possibility of TIMS in [Tb/Co] multilayers and suggest the occurrence of sub-picosecond magnetization reversal using single laser pulses.
Using CT-guided stereotactic prostate radiation therapy (CT-SPRT) to assess sustained murine prostate ablation
Authors: Zahalka Ali H. , Brodin N. Patrik , Maryanovich Maria , Wang Xizhe , Watts Kara L. , Pinho Sandra , Guha Chandan , Frenette Paul S.
Published: March 2021

The prostate is a hormone-responsive organ where testicular androgens drive the proliferation and survival of prostatic cells, ensuring the development and functioning of this gland throughout life. Androgen deprivation therapy leads to apoptosis of prostatic cells and organ regression, and is a cornerstone of prostate cancer and benign prostatic hypertrophy treatment. For several decades, androgen deprivation has been used as an adjuvant to external beam radiotherapy, however, emerging data suggests that the low rates of epithelial proliferation in the castrated prostate imparts radio-resistance. As proliferating cells exhibit increased sensitivity to radiation, we hypothesized that short bursts of synchronized epithelial proliferation, which can be achieved by exogeneous testosterone supplementation prior to targeted high-dose radiation, would maximize sustained prostate ablation, while minimizing damage to surrounding tissues. To test this hypothesis, we designed a novel computed-tomography (CT)-guided stereotactic prostate radiation therapy (CT-SPRT) technique to deliver a single high-dose 25 Gy fraction of X-ray radiation. Sustained prostatic cell ablation was assessed post CT-SPRT by measuring prostate weight, epithelial cell number, and relative contributions of luminal and basal epithelial populations in control and testosterone-pretreated glands. CT-SPRT was safely delivered with no observed damage to surrounding rectal and bladder tissues. Importantly, castrated mice that received a pulse of testosterone to induce synchronous cell proliferation prior to CT-SPRT exhibited significant sustained gland ablation compared to control mice. These results provide new insights in stereotactic radiotherapy sensitivity to maximize prostatic cell ablation and improve our understanding of prostate gland regeneration that can potentially lead to improved non-invasive therapies for benign prostatic hypertrophy and prostate cancer.
Time until treatment initiation is associated with catheter survival in peritoneal dialysis-related peritonitis
Authors: Oki Rikako , Tsuji Shiho , Hamasaki Yoshifumi , Komaru Yohei , Miyamoto Yoshihisa , Matsuura Ryo , Yamada Daisuke , Doi Kent , Kume Haruki , Nangaku Masaomi
Published: March 2021

For peritonitis, a serious complication of peritoneal dialysis (PD), we investigated the relation between duration from the sign (PD effluent abnormalities) to treatment with appropriate antibiotics (ST time) and catheter removal. For 62 PD hospital patients, data of PD-related peritonitis (n = 109) were collected retrospectively. We examined ST time and PD catheter removal times using univariate and multivariate analyses. The catheter removal rate in the delayed ST time group (≥ 24 h) was higher than that in early ST time group (< 24 h) (38 vs. 16%, p = 0.02). Concomitant tunnel infection and delayed ST time were associated with catheter removal (OR [95% CI] 32.3 [3.15–329] and 3.52 [1.11–11.1]). Rates of catheter removal and re-development of peritonitis within 1 month after starting treatment were higher in the delayed ST time group (p = 0.02). PD duration at peritonitis and the first peritonitis episode were associated with delayed ST time (1.02 [1.00–1.04] and 3.42 [1.09–10.7]). Significant association was found between PD catheter removal and the start of treatment more than 24 h after appearance of abnormal effluent. Education for patients about prompt visitation at the onset of peritonitis with long PD duration might improve outcomes.
Revisiting Kelvin equation and Peng–Robinson equation of state for accurate modeling of hydrocarbon phase behavior in nano capillaries
Authors: Al-Kindi Ilyas , Babadagli Tayfun
Published: March 2021

The thermodynamics of fluids in confined (capillary) media is different from the bulk conditions due to the effects of the surface tension, wettability, and pore radius as described by the classical Kelvin equation. This study provides experimental data showing the deviation of propane vapour pressures in capillary media from the bulk conditions. Comparisons were also made with the vapour pressures calculated by the Peng–Robinson equation-of-state (PR-EOS). While the propane vapour pressures measured using synthetic capillary medium models (Hele–Shaw cells and microfluidic chips) were comparable with those measured at bulk conditions, the measured vapour pressures in the rock samples (sandstone, limestone, tight sandstone, and shale) were 15% (on average) less than those modelled by PR-EOS.
Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial–mesenchymal transition
Authors: Yang Jiani , Ma Jun , Jin Yue , Cheng Shanshan , Huang Shan , Zhang Nan , Wang Yu
Published: March 2021

We aimed to determine the prognosis value of circulating tumor cells (CTCs) undergoing epithelial–mesenchymal transition in epithelial ovarian cancer (EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal, and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among the training group (n = 114) and validation group (n = 38). By regression screening, both CTC counts (HR 1.187; 95% CI 1.098–1.752;p = 0.012) and M-CTC (HR 1.098; 95% CI 1.047–1.320;p = 0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites, and CA-125 were also selected (p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive values for the nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts (p = 0.0241), M-CTC (p = 0.0107), and the nomogram (p = 0.0021) were drawn with significant differences. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.

Trial registrationChinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016.
Adequate tissue sampling for the assessment of pathological tumor regression in pancreatic cancer
Authors: Yokohira Masanao , Oshima Minoru , Yamakawa Keiko , Ye Juanjuan , Nakano-Narusawa Yuko , Haba Reiji , Fukumura Yuki , Hirabayashi Kenichi , Yamaguchi Hiroshi , Kojima Motohiro , Okano Keiichi , Suzuki Yasuyuki , Matsuda Yoko
Published: March 2021

Standardized pathological evaluation of the regression assessment of neoadjuvant pancreatic cancer is necessary to improve prognostication and compare treatment outcomes in clinical trials. However, appropriate tissue sampling from surgically resected pancreatic cancer after neoadjuvant therapy has not been elucidated. We compared the tumor regression scores in the largest cancer slide determined macroscopically or histologically. We reviewed all slides and macroscopic photos of cut surfaces from resected pancreas of patients treated with neoadjuvant chemotherapy (n = 137; chemoradiotherapy or chemotherapy). The tumor regression scores (the Evans, College of American Pathologists, Japanese Pancreas Society grading systems, and Area of Residual Tumor [ART] score) were evaluated for the largest tumor slide determined by macroscopy or histologically as well as all slides from the resected pancreas. The largest cancer slides determined macroscopically and histologically were discrepant in 26% of the cases. Cancer cells were not detected in the largest macroscopically defined cut slides in 3%. Only ART scores assessed in the largest histological slides displayed significant difference in overall survival. We recommend obtaining the largest histological slides to provide adequate assessment for regression of neoadjuvant-treated pancreatic cancer. Sufficient sampling to detect the largest histological slides would be mandatory.
Inversion of the physical properties of seafloor surface sediments based on AUV sub-bottom profile data in the northern slope of the South China Sea
Authors: Zhou Qingjie , Li Xishuang , Huang Bigui , Liu Lejun , Gao Shan , Zhou Hang , Liu Jie , Liu Baohua , Zhang Chengyi
Published: March 2021

Based on the seafloor reflection coefficient obtained from autonomous underwater vehicle (AUV) sub-bottom profile survey data of the northern slope of the South China Sea, combined with the sample test data of seafloor surface sediments, we use the Biot–Stoll model to establish the equations relating the seafloor reflection coefficient to the porosity, density, and mean grain size of the sediments at the dominant frequency of 5 kHz (the dominant frequency of the AUV sub-bottom profiler). The physical property parameters such as the porosity, density, and mean grain size of seafloor surface sediments are further inverted. Comparison of inversion results with measured results shows that the overall deviation ratios of the inverted mean grain size, porosity, and density of the surface sediments are in the ranges of − 13.56 to 14.44%, − 6.15 to 8.06%, and − 10.85 to 0.46%, respectively. Among them, the mean grain size directly reflects the size of seafloor sediment particles, and the particles are finer in deeper water. Overall, the inversion results are basically consistent with the measured values and thus can well reflect the variation characteristics of the physical properties of seafloor surface sediments.
Visualizing the ribonucleoprotein content of single bunyavirus virions reveals more efficient genome packaging in the arthropod host
Authors: Bermúdez-Méndez Erick , Katrukha Eugene A. , Spruit Cindy M. , Kortekaas Jeroen , Wichgers Schreur Paul J.
Published: March 2021

Bunyaviruses have a genome that is divided over multiple segments. Genome segmentation complicates the generation of progeny virus, since each newly formed virus particle should preferably contain a full set of genome segments in order to disseminate efficiently within and between hosts. Here, we combine immunofluorescence and fluorescence in situ hybridization techniques to simultaneously visualize bunyavirus progeny virions and their genomic content at single-molecule resolution in the context of singly infected cells. Using Rift Valley fever virus and Schmallenberg virus as prototype tri-segmented bunyaviruses, we show that bunyavirus genome packaging is influenced by the intracellular viral genome content of individual cells, which results in greatly variable packaging efficiencies within a cell population. We further show that bunyavirus genome packaging is more efficient in insect cells compared to mammalian cells and provide new insights on the possibility that incomplete particles may contribute to bunyavirus spread as well.
Porous noria polymer: a cage-to-network approach toward a robust catalyst for CO2 fixation and nitroarene reduction
Authors: Giri Arkaprabha , Patil Niraj Nitish , Patra Abhijit
Published: March 2021

A ‘preporous’ waterwheel-like molecular cage, noria, was knitted with rigid aromatic linkers to obtain porous organic polymers exhibiting excellent catalytic activity toward CO2 fixation and nitroarene reduction.
Theoretical calculation assisted materials screening of BiOX (X = F, Cl, Br, I) for electrochemical absorption of cesium ions
Authors: Lin Dongcheng , Zhang Huixin , An Xiaowei , Chang Lutong , Alameen Ayman , Ding Shengqi , Du Xiao , Hao Xiaogang
Published: March 2021

This study provides a theoretical method to predict the ESIX performance of a certain material, which can provide guidance for the design of new and efficient electroactive materials.
Machine learning-aided protein identification from multidimensional signatures
Authors: Zhang Yuewen , Wright Maya A. , Saar Kadi L. , Challa Pavankumar , Morgunov Alexey S. , Peter Quentin A. E. , Devenish Sean , Dobson Christopher M. , Knowles Tuomas P. J.
Published: March 2021

Protein classification and identification from their multidimensional fingerprints obtained on a microfluidic chip.
The material-enabled oxygen control in thiol-ene microfluidic channels and its feasibility for subcellular drug metabolism assays under hypoxia in vitro
Authors: Kiiski Iiro , Järvinen Päivi , Ollikainen Elisa , Jokinen Ville , Sikanen Tiina
Published: March 2021

This work demonstrates the feasibility of material-enabled oxygen scavenging in thiol-ene microchannels for on-chip subcellular drug metabolism assays under hypoxia.
Flexible online in-droplet cell/synthetic particle concentration utilizing alternating current electrothermal-flow field-effect transistor
Authors: Sun Haizhen , Ren Yukun , Tao Ye , Jiang Tianyi , Jiang Hongyuan
Published: March 2021

This work describes a universal, massive and versatile technique, namely, alternating current electrothermal-flow field-effect transistor, to accomplish online in-droplet cell/synthetic particle concentration on demand.
Effects of a crosslinking agent on a supramolecular gel to control lost circulation
Authors: Wang Bo , Sun Jinsheng , Lv Kaihe , Shen Feng , Bai Yingrui
Published: March 2021

The Cr3+ can improve the cross-linking degree and network density of the GP-A gel, and enhance its strength and plugging ability to control lost circulation.
NIR responsive AuNR/pNIPAM/PEGDA inverse opal hydrogel microcarriers for controllable drug delivery
Authors: Liu L. Z. , Sun X. Y. , Yan Z. Y. , Ye B. F.
Published: March 2021

A novel inverse opal microcarrier with both NIR-controlled release and visual color changes for drug delivery.
Dynamical time scales of friction dynamics in active microrheology of a model glass
Authors: Madanchi A. , Yu Ji Woong , Lee Won Bo , Rahimi Tabar M. R. , Rahbari S. H. E.
Published: March 2021

Owing to the local/heterogeneous structures in supercooled liquids, after several decades of research, it is now clear that supercooled liquids are structurally different from their conventional liquid counterparts.
Facile syringe filter-enabled bacteria separation, enrichment, and buffer exchange for clinical isolation-free digital detection and characterization of bacterial pathogens in urine
Authors: Zhang Pengfei , Kaushik Aniruddha M. , Mach Kathleen E. , Hsieh Kuangwen , Liao Joseph C. , Wang Tza-Huei
Published: March 2021

We devised and interfaced a facile filtration-based bacteria recovery and buffer exchange process with droplet microfluidics for clinical isolation-free digital detection and characterization of bacteria pathogens in urine.
Mapping sub-cellular protein aggregates and lipid inclusions using synchrotron ATR-FTIR microspectroscopy
Authors: Hartnell David , Hollings Ashley , Ranieri Anna Maria , Lamichhane Hum Bahadur , Becker Thomas , Sylvain Nicole J. , Hou Huishu , Pushie M. Jake , Watkin Elizabeth , Bambery Keith R. , Tobin Mark J. , Kelly Michael E. , Massi Massimiliano , Vongsvivut Jitraporn , Hackett Mark J.
Published: March 2021

SR-ATR-FTIR has been used to improve the diffraction limited spatial resolution of infrared micro-spectroscopy, enabling this study to reveal the sub-cellular location of protein aggregates and lipophilic inclusions in brain cells, and bacteria.
A non-isolated pentagon rule C82cage stabilized by a stretched Sc3N cluster
Authors: Guo Min , Li Xiaomeng , Yao Yang-Rong , Zhuang Jiaxin , Meng Qingyu , Yan Yingjing , Liu Xinye , Chen Ning
Published: March 2021

A stretched Sc3N cluster stabilizes a non-IPRCs(39 663)-C82cage by interacting closely with the adjacent pentagons.
α-Hydroxy boron-enabled regioselective access to bifunctional halo-boryl alicyclic ethers and α-halo borons
Authors: Wang Lucia , Lin Shengjia , Zhu Yawei , Ferrante Daniel , Ishak Timaf , Baba Yuki , Sharma Abhishek
Published: March 2021

Two new applications of alpha-hydroxy borons have been developed leading to a regioselective access to hitherto unknown halo-boryl alicyclic ethers and rare secondary alkyl alpha-halo MIDA boronates.
Natural stereoisomeric flavonoids exhibit different disruptive effects and the mechanism of action on Aβ42 protofibril
Authors: Zhan Chendi , Lao Zenghui , Tang Yiming , Qiao Qin , Wei Guanghong
Published: March 2021

Stereoisomers (+)-C and (−)-C show a better disruptive effect on Aβ42 protofibril than EC due to the steric effect caused by the conformational differences.
Heterogeneously Ni–Pd nanoparticle-catalyzed base-free formal C–S bond metathesis of thiols
Authors: Mitamura Kanju , Yatabe Takafumi , Yamamoto Kidai , Yabe Tomohiro , Suzuki Kosuke , Yamaguchi Kazuya
Published: March 2021

An efficient base-free synthesis of thioethers from various thiols has been achieved using Ni–Pd alloy nanoparticle catalysts supported on hydroxyapatite under an H2 atmosphere.
Regulating the distortion degree of the square antiprism coordination geometry in Dy–Na single ion magnets
Authors: Wang Hui-Sheng , Zhang Ke , Wang Jia , Hu Zhaobo , Song You , Zhang Zaichao , Pan Zhi-Quan
Published: March 2021

A DyNa complex (1) and a DyNa2 1D chain (2) have been obtained; their square antiprism coordination geometries were changed from the bicapped triangular prism of the reported DyNa2 complex. Compounds 1 and 2 exhibit single ion magnet behavior.