bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal and neonatal outcomes for fetoscopic laser ablation for the treatment of twin twin transfusion syndrome at a single center
Authors: Ling Diamond , Phelps Alexandra , Tate Tabitha , Adefisoye James , Mehra Suwan , Prazad Preetha
Published: December 2022

Objective

To describe the perinatal and neonatal outcomes of fetal laser ablation (FLA) for the treatment of twin-twin transfusion syndrome (TTTS) in our single center institution.

Study design

Retrospective study of 76 treated pregnant women. Procedural complications, perinatal and neonatal outcomes analyzed. Differences in outcomes between two procedural techniques, selective and Solomon, compared.

Results

FLA occurred at median gestational age (GA) of 20.8 weeks (IQR 18.1–22.9) with low incidence of procedural complications (5.3%). High survival rate with delivery of at least one neonate (96%) [95% CI: 88.9–99.2%]; 73.7% [95% CI: 62.3–83.1%] were twins. Median GA at birth was 33.1 weeks (IQR 28.0–35.0). Neonatal mortality and morbidities were 9.4% and 48.3% of cases respectively, and associated with lower GA. Solomon cases had comparatively higher median GA, and lower incidences of neonatal morbidities.

Conclusion

Our small single center study showed favorable outcomes for using the Solomon technique in the treatment of TTTS.
Symmetry breaking in thermal photonics
Authors: Wang Xueji , Jacob Zubin
Published: December 2022

Engineering symmetries in nanostructures and metasurfaces provides a new paradigm to control incoherent heat radiation for applications in energy conversion, thermal sources, infrared imaging, and radiative cooling.
Aminolipids elicit functional trade-offs between competitiveness and bacteriophage attachment in Ruegeria pomeroyi
Authors: Stirrup Rachel , Mausz Michaela A , Silvano Eleonora , Murphy Andrew , Guillonneau Richard , Quareshy Mussa , Rihtman Branko , Ferretjans Maria Aguilo , He Ruo , Todd Jonathan D , Chen Feng , Scanlan David J , Chen Yin
Published: December 2022

Lipids play a crucial role in maintaining cell integrity and homeostasis with the surrounding environment. Cosmopolitan marine roseobacter clade (MRC) and SAR11 clade bacteria are unique in that, in addition to glycerophospholipids, they also produce an array of amino acid-containing lipids that are conjugated with beta-hydroxy fatty acids through an amide bond. Two of these aminolipids, the ornithine aminolipid (OL) and the glutamine aminolipid (QL), are synthesized using the O-acetyltransferase OlsA. Here, we demonstrate that OL and QL are present in both the inner and outer membranes of the Gram-negative MRC bacterium Ruegeria pomeroyi DSS-3. In an olsA mutant, loss of these aminolipids is compensated by a concurrent increase in glycerophospholipids. The inability to produce aminolipids caused significant changes in the membrane proteome, with the membrane being less permeable and key nutrient transporters being downregulated while proteins involved in the membrane stress response were upregulated. Indeed, the import of 14C-labelled choline and dimethylsulfoniopropionate, as a proxy for the transport of key marine nutrients across membranes, was significantly impaired in the olsA mutant. Moreover, the olsA mutant was significantly less competitive than the wild type (WT) being unable to compete with the WT strain in co-culture. However, the olsA mutant unable to synthesize these aminolipids is less susceptible to phage attachment. Together, these data reveal a critical role for aminolipids in the ecophysiology of this important clade of marine bacteria and a trade-off between growth and avoidance of bacteriophage attachment.
Drug response profiles in patient-derived cancer cells across histological subtypes of ovarian cancer: real-time therapy tailoring for a patient with low-grade serous carcinoma
Authors: Murumägi Astrid , Ungureanu Daniela , Khan Suleiman , Arjama Mariliina , Välimäki Katja , Ianevski Aleksandr , Ianevski Philipp , Bergström Rebecka , Dini Alice , Kanerva Anna , Koivisto-Korander Riitta , Tapper Johanna , Lassus Heini , Loukovaara Mikko , Mägi Andrus , Hirasawa Akira , Aoki Daisuke , Pietiäinen Vilja , Pellinen Teijo , Bützow Ralf , Aittokallio Tero , Kallioniemi Olli
Published: December 2022

Many efforts are underway to develop novel therapies against the aggressive high-grade serous ovarian cancers (HGSOCs), while our understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) of ovarian malignancies is not developing as well. We describe here a functional precision oncology (fPO) strategy in epithelial ovarian cancers (EOC), which involves high-throughput drug testing of patient-derived ovarian cancer cells (PDCs) with a library of 526 oncology drugs, combined with genomic and transcriptomic profiling. HGSOC, LGSOC and MUCOC PDCs had statistically different overall drug response profiles, with LGSOCs responding better to targeted inhibitors than HGSOCs. We identified several subtype-specific drug responses, such as LGSOC PDCs showing high sensitivity to MDM2, ERBB2/EGFR inhibitors, MUCOC PDCs to MEK inhibitors, whereas HGSOCs showed strongest effects with CHK1 inhibitors and SMAC mimetics. We also explored several drug combinations and found that the dual inhibition of MEK and SHP2 was synergistic in MAPK-driven EOCs. We describe a clinical case study, where real-time fPO analysis of samples from a patient with metastatic, chemorefractory LGSOC with a CLU-NRG1 fusion guided clinical therapy selection. fPO-tailored therapy with afatinib, followed by trastuzumab and pertuzumab, successfully reduced tumour burden and blocked disease progression over a five-year period. In summary, fPO is a powerful approach for the identification of systematic drug response differences across EOC subtypes, as well as to highlight patient-specific drug regimens that could help to optimise therapies to individual patients in the future.
Body composition, physical activity, and quality of life in pediatric patients with inflammatory bowel disease on anti-TNF therapy—an observational follow-up study
Authors: Boros Kriszta Katinka , Veres Gábor , Cseprekál Orsolya , Pintér Hajnalka Krisztina , Richter Éva , Cseh Áron , Dezsőfi-Gottl Antal , Arató András , Reusz György , Dohos Dóra , Müller Katalin Eszter
Published: December 2022

Background

Poor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy.

Methods

32 children with IBD (21 with Crohn’s disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable.

Results

During follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared.

Conclusions

The fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care.
Population fluctuations and synanthropy explain transmission risk in rodent-borne zoonoses
Authors: Ecke Frauke , Han Barbara A. , Hörnfeldt Birger , Khalil Hussein , Magnusson Magnus , Singh Navinder J. , Ostfeld Richard S.
Published: December 2022

Population fluctuations are widespread across the animal kingdom, especially in the order Rodentia, which includes many globally important reservoir species for zoonotic pathogens. The implications of these fluctuations for zoonotic spillover remain poorly understood. Here, we report a global empirical analysis of data describing the linkages between habitat use, population fluctuations and zoonotic reservoir status in rodents. Our quantitative synthesis is based on data collated from papers and databases. We show that the magnitude of population fluctuations combined with species’ synanthropy and degree of human exploitation together distinguish most rodent reservoirs at a global scale, a result that was consistent across all pathogen types and pathogen transmission modes. Our spatial analyses identified hotspots of high transmission risk, including regions where reservoir species dominate the rodent community. Beyond rodents, these generalities inform our understanding of how natural and anthropogenic factors interact to increase the risk of zoonotic spillover in a rapidly changing world.
Structural basis for the non-self RNA-activated protease activity of the type III-E CRISPR nuclease-protease Craspase
Authors: Cui Ning , Zhang Jun-Tao , Li Zhuolin , Liu Xiao-Yu , Wang Chongyuan , Huang Hongda , Jia Ning
Published: December 2022

The RNA-targeting type III-E CRISPR-gRAMP effector interacts with a caspase-like protease TPR-CHAT to form the CRISPR-guided caspase complex (Craspase), but their functional mechanism is unknown. Here, we report cryo-EM structures of the type III-E gRAMPcrRNA and gRAMPcrRNA-TPR-CHAT complexes, before and after either self or non-self RNA target binding, and elucidate the mechanisms underlying RNA-targeting and non-self RNA-induced protease activation. The associated TPR-CHAT adopted a distinct conformation upon self versus non-self RNA target binding, with nucleotides at positions −1 and −2 of the CRISPR-derived RNA (crRNA) serving as a sensor. Only binding of the non-self RNA target activated the TPR-CHAT protease, leading to cleavage of Csx30 protein. Furthermore, TPR-CHAT structurally resembled eukaryotic separase, but with a distinct mechanism for protease regulation. Our findings should facilitate the development of gRAMP-based RNA manipulation tools, and advance our understanding of the virus-host discrimination process governed by a nuclease-protease Craspase during type III-E CRISPR-Cas immunity.
Direct retrieval of Zernike-based pupil functions using integrated diffractive deep neural networks
Authors: Goi Elena , Schoenhardt Steffen , Gu Min
Published: December 2022

Retrieving the pupil phase of a beam path is a central problem for optical systems across scales, from telescopes, where the phase information allows for aberration correction, to the imaging of near-transparent biological samples in phase contrast microscopy. Current phase retrieval schemes rely on complex digital algorithms that process data acquired from precise wavefront sensors, reconstructing the optical phase information at great expense of computational resources. Here, we present a compact optical-electronic module based on multi-layered diffractive neural networks printed on imaging sensors, capable of directly retrieving Zernike-based pupil phase distributions from an incident point spread function. We demonstrate this concept numerically and experimentally, showing the direct pupil phase retrieval of superpositions of the first 14 Zernike polynomials. The integrability of the diffractive elements with CMOS sensors shows the potential for the direct extraction of the pupil phase information from a detector module without additional digital post-processing.
A 2-million-year-old ecosystem in Greenland uncovered by environmental DNA
Authors: Kjær Kurt H. , Winther Pedersen Mikkel , De Sanctis Bianca , De Cahsan Binia , Korneliussen Thorfinn S. , Michelsen Christian S. , Sand Karina K. , Jelavić Stanislav , Ruter Anthony H. , Schmidt Astrid M. A. , Kjeldsen Kristian K. , Tesakov Alexey S. , Snowball Ian , Gosse John C. , Alsos Inger G. , Wang Yucheng , Dockter Christoph , Rasmussen Magnus , Jørgensen Morten E. , Skadhauge Birgitte , Prohaska Ana , Kristensen Jeppe Å. , Bjerager Morten , Allentoft Morten E. , Coissac Eric ,   PhyloNorway Consortium, Alsos Inger Greve , Coissac Eric , Rouillard Alexandra , Simakova Alexandra , Fernandez-Guerra Antonio , Bowler Chris , Macias-Fauria Marc , Vinner Lasse , Welch John J. , Hidy Alan J. , Sikora Martin , Collins Matthew J. , Durbin Richard , Larsen Nicolaj K. , Willerslev Eske
Published: December 2022

Late Pliocene and Early Pleistocene epochs 3.6 to 0.8 million years ago1had climates resembling those forecasted under future warming2. Palaeoclimatic records show strong polar amplification with mean annual temperatures of 11–19 °C above contemporary values3,4. The biological communities inhabiting the Arctic during this time remain poorly known because fossils are rare5. Here we report an ancient environmental DNA6(eDNA) record describing the rich plant and animal assemblages of the Kap København Formation in North Greenland, dated to around two million years ago. The record shows an open boreal forest ecosystem with mixed vegetation of poplar, birch and thuja trees, as well as a variety of Arctic and boreal shrubs and herbs, many of which had not previously been detected at the site from macrofossil and pollen records. The DNA record confirms the presence of hare and mitochondrial DNA from animals including mastodons, reindeer, rodents and geese, all ancestral to their present-day and late Pleistocene relatives. The presence of marine species including horseshoe crab and green algae support a warmer climate than today. The reconstructed ecosystem has no modern analogue. The survival of such ancient eDNA probably relates to its binding to mineral surfaces. Our findings open new areas of genetic research, demonstrating that it is possible to track the ecology and evolution of biological communities from two million years ago using ancient eDNA.
A transcriptional switch controls sex determination in Plasmodium falciparum
Authors: Gomes A. R. , Marin-Menendez A. , Adjalley S. H. , Bardy C. , Cassan C. , Lee M. C. S. , Talman A. M.
Published: December 2022

Sexual reproduction and meiotic sex are deeply rooted in the eukaryotic tree of life, but mechanisms determining sex or mating types are extremely varied and are only well characterized in a few model organisms1. In malaria parasites, sexual reproduction coincides with transmission to the vector host. Sex determination is non-genetic, with each haploid parasite capable of producing either a male or a female gametocyte in the human host2. The hierarchy of events and molecular mechanisms that trigger sex determination and maintenance of sexual identity are yet to be elucidated. Here we show that the male development 1 (md1) gene is both necessary and sufficient for male fate determination in the human malaria parasitePlasmodium falciparum. We show that Md1 has a dual function stemming from two separate domains: in sex determination through its N terminus and in male development from its conserved C-terminal LOTUS/OST-HTH domain. We further identify a bistable switch at themd1locus, which is coupled with sex determination and ensures that the male-determining gene is not expressed in the female lineage. We describe one of only a few known non-genetic mechanisms of sex determination in a eukaryote and highlight Md1 as a potential target for interventions that block malaria transmission.
Nonstationary footprints of ENSO in the Mekong River Delta hydrology
Authors: Watanabe Takaaki K. , Phan Tung Thanh , Yamazaki Atsuko , Chiang Hong-Wei , Shen Chuan-Chou , Doan Lam Dinh , Watanabe Tsuyoshi
Published: December 2022

The Mekong River Delta (MRD) is an essential agricultural area for the worldwide rice supply. Floods and droughts triggered by El Niño southern oscillation (ENSO) have been threatening sustenance in the MRD. Sustainable food supplies require understanding the response of the MRD hydrology to the changing ENSO behaviour in recent decades. Here, we reconstructed the annual rainfall maxima in the MRD using the oceanic paleoclimate proxy from coral skeletons and compared them with ENSO indexes. Annual minima of coral-based seawater oxygen isotope (δ18Osw) correlated with annual rainfall maxima, which allowed to extend rainfall data from 1924 to the recent. The annual rainfall maxima based on δ18Osw negatively correlated with the central Pacific El Niño index. This suggested that La Niña and central Pacific El Niño events lead to heavy and light rainy seasons. The heavy rainy season had more serious impacts in recent decades, which likely increases the flood risk. In contrast, the frequency and rainfall amount of the light rainy season has not changed significantly, although a catastrophic drought has hit the MRD. Our finding concludes that the impact of the ENSO event on MRD hydrology is inconsistent in the past century.
Live imaging of apoptotic signaling flow using tunable combinatorial FRET-based bioprobes for cell population analysis of caspase cascades
Authors: Suzuki Miho , Shindo Yutaka , Yamanaka Ryu , Oka Kotaro
Published: December 2022

Understanding cellular signaling flow is required to comprehend living organisms. Various live cell imaging tools have been developed but challenges remain due to complex cross-talk between pathways and response heterogeneities among cells. We have focused on multiplex live cell imaging for statistical analysis to address the difficulties and developed simple multiple fluorescence imaging system to quantify cell signaling at single-cell resolution using Förster Resonance Energy Transfer (FRET)-based chimeric molecular sensors comprised of fluorescent proteins and dyes. The dye-fluorescent protein conjugate is robust for a wide selection of combinations, facilitating rearrangement for coordinating emission profile of molecular sensors to adjust for visualization conditions, target phenomena, and simultaneous use. As the molecular sensor could exhibit highly sensitive in detection for protease activity, we customized molecular sensor of caspase-9 and combine the established sensor for caspase-3 to validate the system by observation of caspase-9 and -3 dynamics simultaneously, key signaling flow of apoptosis. We found cumulative caspase-9 activity rather than reaction rate inversely regulated caspase-3 execution times for apoptotic cell death. Imaging-derived statistics were thus applied to discern the dominating aspects of apoptotic signaling unavailable by common live cell imaging and proteomics protein analysis. Adopted to various visualization targets, the technique can discriminate between rivalling explanations and should help unravel other protease involved signaling pathways.
Implications of differential peroxyl radical-induced inactivation of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase for the pentose phosphate pathway
Authors: Reyes Juan Sebastián , Fuentes-Lemus Eduardo , Figueroa Juan David , Rojas Javier , Fierro Angélica , Arenas Felipe , Hägglund Per M. , Davies Michael J. , López-Alarcón Camilo
Published: December 2022

Escherichia coli glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are key enzymes of the pentose phosphate pathway, responsible for the NADPH production in cells. We investigated modification of both enzymes mediated by peroxyl radicals (ROO·) to determine their respective susceptibilities to and mechanisms of oxidation. G6PDH and 6PGDH were incubated with AAPH (2,2′-azobis(2-methylpropionamidine)dihydrochloride), which was employed as ROO· source. The enzymatic activities of both enzymes were determined by NADPH release, with oxidative modifications examined by electrophoresis and liquid chromatography (LC) with fluorescence and mass (MS) detection. The activity of G6PDH decreased up to 62.0 ± 15.0% after 180 min incubation with 100 mM AAPH, whilst almost total inactivation of 6PGDH was determined under the same conditions. Although both proteins contain abundant Tyr (particularly 6PGDH), these residues were minimally affected by ROO·, with Trp and Met being major targets. LC–MS and in silico analysis showed that the modification sites of G6PDH are distant to the active site, consistent with a dispersed distribution of modifications, and inactivation resulting from oxidation of multiple Trp and Met residues. In contrast, the sites of oxidation detected on 6PGDH are located close to its catalytic site indicating a more localized oxidation, and a consequent high susceptibility to ROO·-mediated inactivation.
Geographical classification of malaria parasites through applying machine learning to whole genome sequence data
Authors: Deelder Wouter , Manko Emilia , Phelan Jody E. , Campino Susana , Palla Luigi , Clark Taane G.
Published: December 2022

Malaria, caused by Plasmodium parasites, is a major global health challenge. Whole genome sequencing (WGS) ofPlasmodium falciparumandPlasmodium vivaxgenomes is providing insights into parasite genetic diversity, transmission patterns, and can inform decision making for clinical and surveillance purposes. Advances in sequencing technologies are helping to generate timely and big genomic datasets, with the prospect of applying Artificial Intelligence analytical techniques (e.g., machine learning) to support programmatic malaria control and elimination. Here, we assess the potential of applying deep learning convolutional neural network approaches to predict the geographic origin of infections (continents, countries, GPS locations) using WGS data ofP. falciparum(n = 5957; 27 countries) andP. vivax(n = 659; 13 countries) isolates. Using identified high-quality genome-wide single nucleotide polymorphisms (SNPs) (P. falciparum: 750 k,P. vivax: 588 k), an analysis of population structure and ancestry revealed clustering at the country-level. When predicting locations for both species, classification (compared to regression) methods had the lowest distance errors, and > 90% accuracy at a country level. Our work demonstrates the utility of machine learning approaches for geo-classification of malaria parasites. With timelier WGS data generation across more malaria-affected regions, the performance of machine learning approaches for geo-classification will improve, thereby supporting disease control activities.
A novel virulent Litunavirus phage possesses therapeutic value against multidrug resistant Pseudomonas aeruginosa
Authors: Lerdsittikul Varintip , Thongdee Metawee , Chaiwattanarungruengpaisan Somjit , Atithep Thassanant , Apiratwarrasakul Sukanya , Withatanung Patoo , Clokie Martha R. J. , Korbsrisate Sunee
Published: December 2022

Pseudomonas aeruginosa is a notable nosocomial pathogen that can cause severe infections in humans and animals. The emergence of multidrug resistant (MDR) P. aeruginosa has motivated the development of phages to treat the infections. In this study, a novel Pseudomonas phage, vB_PaeS_VL1 (VL1), was isolated from urban sewage. Phylogenetic analyses revealed that VL1 is a novel species in the genus Litunavirus of subfamily Migulavirinae. The VL1 is a virulent phage as no genes encoding lysogeny, toxins or antibiotic resistance were identified. The therapeutic potential of phage VL1 was investigated and revealed that approximately 56% (34/60 strains) of MDR P. aeruginosa strains, isolated from companion animal diseases, could be lysed by VL1. In contrast, VL1 did not lyse other Gram-negative and Gram-positive bacteria suggesting its specificity of infection. Phage VL1 demonstrated high efficiency to reduce bacterial load (~ 6 log cell number reduction) and ~ 75% reduction of biofilm in pre-formed biofilms of MDR P. aeruginosa. The result of two of the three MDR P. aeruginosa infected Galleria mellonella larvae showed that VL1 could significantly increase the survival rate of infected larvae. Taken together, phage VL1 has genetic and biological properties that make it a potential candidate for phage therapy against P. aeruginosa infections.
Molecular dynamics simulations reveal membrane lipid interactions of the full-length lymphocyte specific kinase (Lck)
Authors: Prakaash Dheeraj , Fagnen Charline , Cook Graham P. , Acuto Oreste , Kalli Antreas C.
Published: December 2022

The membrane-bound lymphocyte-specific protein-tyrosine kinase (Lck) triggers T cell antigen receptor signalling to initiate adaptive immune responses. Despite many structure–function studies, the mode of action of Lck and the potential role of plasma membrane lipids in regulating Lck’s activity remains elusive. Advances in molecular dynamics simulations of membrane proteins in complex lipid bilayers have opened a new perspective in gathering such information. Here, we have modelled the full-length Lck open and closed conformations  using data available from different crystalographic studies and simulated its interaction with the inner leaflet of the T cell plasma membrane. In both conformations, we found that the unstructured unique domain and the structured domains including the kinase interacted with the membrane with a preference for PIP lipids. Interestingly, our simulations suggest that the Lck-SH2 domain interacts with lipids differently in the open and closed Lck conformations, demonstrating that lipid interaction can potentially regulate Lck’s conformation and in turn modulate T cell signalling. Additionally, the Lck-SH2 and kinase domain residues that significantly contacted PIP lipids are found to be conserved among the Src family of kinases, thereby potentially representing similar PIP interactions within the family.
Diagnostic value of “hyperdense consolidation sign” as a characteristic new computed tomography sign of diffuse alveolar hemorrhage
Authors: Kumasaka Soma , Kumasaka Yuka , Jingu Akiko , Tsushima Yoshito
Published: December 2022

Diffuse alveolar hemorrhage (DAH) is an uncommon but life-threatening condition. Although DAH must be distinguished from other lung diseases, no specific computed tomography (CT) signs of DAH have been reported. This study aimed to evaluate the diagnostic value of “hyperdense consolidation” CT sign. We retrospectively evaluated non-contrast CT findings of 25 DAH patients and age- (≤ 2 years) and sex-matched controls with symptoms of dyspnea and hypoxemia. Two radiologists compared the two groups for the presence of hyperdense consolidation signs in lung parenchyma, defined as consolidation that visually contains areas with higher density than the aorta in the specific narrow window setting (window level = 35 Hounsfield units [HU], width = 80 HU) with a mediastinal filter. The sensitivity, specificity, positive- and negative-predictive values of the hyperdense consolidation sign for detection of DAH were 32.0%, 100%, 100%, and 59.5% with perfect interobserver agreement (к = 1.00). The hyperdense consolidation sign was found to be a highly specific sign for DAH.
Role of the elastography strain ratio using transrectal ultrasonography in the diagnosis of prostate cancer and clinically significant prostate cancer
Authors: Yoo Jeong Woo , Koo Kyo Chul , Chung Byung Ha , Lee Kwang Suk
Published: December 2022

This study investigated the efficacy of the elastography strain ratio (ESR) as a predictor of prostate cancer (PCa) in targeted prostate biopsy. In total, 257 patients who underwent magnetic resonance imaging-targeted biopsy were enrolled. Before biopsy, we placed regions of interest (zone A and B) in the lesion and levator ani. The ESR was measured as zone A/zone B. Multivariate analyses were performed to predict PCa and clinically significant PCa. There were 206 (71.5%) positive cancer lesions. No difference in digit rectal examination findings was found between patients with and without PCa. For predicting clinically significant PCa, an ESR ≥ 6.8 was significantly higher in the PCa (+) group than in the PCa (−) group (p < 0.001). The area under the receiver operating characteristic curve (AUC) for the conventional variables (model 1) plus the ESR was 0.845, which was significantly higher than that for model 1 (p = 0.001). In prostate imaging reporting and data system score 3 lesions, an ESR ≥ 4.6 was a significant predictor of PCa (p = 0.002). The AUC in model 1 plus the ESR was 0.856, which was significantly higher than that in model 1 alone (p = 0.017). The ESR is useful for predicting clinically significant PCa.
A retrospective observational cohort study evaluating the postoperative outcomes of intracapsular coblation tonsillectomy in children
Authors: Bitar Mohamad A. , Nazir Tanvir , Abd-Ul-Salam Hani
Published: December 2022

Coblation intracapsular tonsillectomy (ICT) is becoming popular due to its decreased postoperative complications. However, a concern exists about the need for revision surgery. We conducted a retrospective observational cohort study, with a null hypothesis that Coblation ICT is not associated with recurrence of the preoperative symptoms, obstructive tonsillar regrowth, or the need for revision tonsillar surgery. We reviewed 345 patients (median age of 4.5 years; IQR 3.2–6.3), operated by the senior author between Feb 2017 and Sep 2020, for a median follow-up of 395.0 days (IQR 221.5–654.5). Most patients had snoring (94.2%), mouth breathing (92.8%), restless sleep (62.6%), and sleep disorder breathing (52.8%); 12.5% had recurrent tonsillitis. The mean initial total symptoms score (TSS) was 5.2 (SD 1.4, range 1–8); 87.5% had three or more symptoms; 86.7% underwent ICT; TSS decreased postoperatively to a mean of 0.2, SD 0.8, range 0–7. The mean hospital stay was 0.96 day (SD 0.36, range 0–3). Secondary bleeding occurred in 0.7% of ICT patients. No patient required admission or intervention. There was no documented tonsillar regrowth resulting in upper airway obstruction. No one needed tonsillar revision surgery. Intracapsular tonsillectomy was shown to be an effective procedure with long-lasting results.
DNMT1/PKR double knockdowned HepG2 (HepG2-DP) cells have high hepatic function and differentiation ability
Authors: Tanaka-yachi Rieko , Aizawa Kazuko , Shimizu Kie , Akutsu Hidenori , Nakamura Kazuaki
Published: December 2022

HepG2 cells are widely used as a human hepatocytes model, but their functions, including drug metabolism, are inferior to primary hepatocytes. We previously reported that the hepatic gene expressions in HepG2 cells were upregulated by treatment with zebularine, which is an inhibitor of DNA methylation, through the inhibition of both DNA methyltransferase 1 (DNMT1) and double-stranded RNA-dependent protein kinase (PKR). In this study, we established a new HepG2 cell subline, HepG2-DP cells, by stable double knockdown of DNMT1 and PKR and evaluated its function. Albumin production, expression of CYP1A2 genes, and accumulation of lipid droplets were increased in HepG2-DP cells compared with the original HepG2 cells. Comprehensive gene expression analysis of transcription factors revealed that the expression of important genes for hepatic function, such as HNF1β, HNF4α, ONECUT1, FOXA1, FOXA2, FOXA3, and various nuclear receptors, was upregulated in HepG2-DP cells. These results indicate that the newly established HepG2-DP cells are a highly functional hepatocyte cell line. In addition, we investigated whether HepG2-DP cells are able to mature by differentiation induction, since HepG2 cells are derived from hepatoblastoma. The gene expression of major CYPs and Phase II, III drug-metabolizing enzyme genes was significantly increased in HepG2-DP cells cultured in differentiation induction medium. These results suggest that HepG2-DP cells can be further matured by the induction of differentiation and could therefore be applied to studies of drug metabolism and pharmacokinetics.
Exact multistability and dissipative time crystals in interacting fermionic lattices
Authors: Alaeian Hadiseh , Buča Berislav
Published: December 2022

The existence of multistability in quantum systems beyond the mean-field approximation remains an intensely debated open question. Quantum fluctuations are finite-size corrections to the mean-field as the full exact solution is unobtainable and they usually destroy the multistability present on the mean-field level. Here, by identifying and using exact modulated dynamical symmetries in a driven-dissipative fermionic chain we exactly prove multistability in the presence of quantum fluctuations. Further, unlike common cases in our model, rather than destroying multistability, the quantum fluctuations themselves exhibit multistability, which is absent on the mean-field level for our systems. Moreover, the studied model acquires additional thermodynamic dynamical symmetries that imply persistent periodic oscillations, constituting the first case of a boundary time crystal,to the best of our knowledge, a genuine extended many-body quantum system with the previous cases being only in emergent single- or few-body models. The model can be made into a dissipative time crystal in the limit of large dissipation (i.e. the persistent oscillations are stabilized by the dissipation) making it both a boundary and dissipative time crystal.
Low-dimensional electronic state at the surface of a transparent conductive oxide
Authors: Naamneh Muntaser , Guedes Eduardo B. , Prakash Abhinav , Cardoso Henrique M. , Shi Ming , Plumb Nicholas C. , Brito Walber H. , Jalan Bharat , Radović Milan
Published: December 2022

Materials that blend physical properties that are usually mutually exclusive could facilitate devices with novel functionalities. For example, the doped perovskite alkaline earth stannates BaSnO3 and SrSnO3 show the intriguing combination of high light transparency and high electrical conductivity. Understanding such emergent physics requires deep insight into the materials’ electronic structures. Moreover, the band structure at the surfaces of those materials can deviate significantly from their bulk counterparts, thereby unlocking novel physical phenomena. Employing angle-resolved photoemission spectroscopy and ab initio calculations, we reveal the existence of a 2-dimensional metallic state at the SnO2-terminated surface of 1% La-doped BaSnO3 thin films. The observed surface state is characterized by a distinct carrier density and a lower effective mass compared to the bulk conduction band, of about 0.12me. These particular surface state properties place BaSnO3 among the materials suitable for engineering highly conductive transition metal oxide heterostructures.
Tissue Engineering Models for Cancer Pathology
Authors: Winter Jessica O. , Rao Shreyas S.
Published: December 2022

This chapter introduces the application of tissue engineering to study disease pathology and treatment in the field of cancer. A general overview and history of tissue engineering is provided, with early examples of its application to cancer. Finally, this chapter provides details on the organizational content and overviews of the rest of the chapters in this book.
Introduction to the Tumor Microenvironment
Authors: Witz Isaac P. , Izraely Sivan
Published: December 2022

The tumor microenvironment (TME) is conceived as a dynamic interaction arena in which cancer cells interact with resident and recruited host cells, with their secreted factors and with the extracellular matrix (ECM). Moreover, non-cancerous cells in the TME interact with each other. The outcome of these multidirectional interactions is an ever-changing milieu in which the interaction partners acquire plasticity, altered phenotypes and signaling pathways. These TME events regulate, either positively or negatively, tumor survival, propagation and progression by a variety of mechanisms. It is up to the TME community to conceive and create novel means and technologies in order to target microenvironmental factors that impact, positively or negatively, tumor progression.
Mimicking Mechanical Features of the Tumor Microenvironment
Authors: Mierke C. T.
Published: December 2022

Under physiological native conditions, human connective tissues foster optimal survival, growth, proliferation, function, differentiation, regeneration, migration, invasion, and death of tissue cells. However, under pathological conditions, connective tissues support deregulated mechanophenotypes that then alter cell and tissue functions. Mimicking the mechanical cues of the native tissue microenvironment employing several three-dimensional (3D) tissue culture systems in vitro has been proposed to be promising in cancer diagnosis and treatment. There have been great advances on biomaterial, architecture, and application levels. These attainments are founded on a detailed comprehension of functionalities of multiple tissue cells, biocompatibility and biodegradability of framework-forming biomaterials, biologically and biophysically functional determinants in native tissues, and pathophysiological constraints of the native tissue microenvironment. In this chapter, biophysical cues of the tissue microenvironment with a focus on cancer are discussed and compared to physiological functions of tissues, including repair and regeneration mechanisms. Mimicking mechanical features of the tumor environment encompasses the spatial microenvironment in vitro, which is far below the dimensionality of tissues, embedded components, architectural cues, and physical aspects. Finally, combining the effects of tissue-specific cells on cancer tissue and the tumor microenvironment with the microenvironmental mechanophenotype is crucial to better understand disease conditions and develop novel approaches to cancer treatment.
Mimicking Chemical Features of the Tumor Microenvironment
Authors: Jayaprakash Sruthi Rayadurgam , Patra Indira Priyadarshani , Bist Sushmita , Pradhan Shantanu
Published: December 2022

The tumor microenvironment (TME) plays a central role in tumor progression and metastasis, thereby regulating disease prognosis and patient outcomes. Systematic investigation of the multitude of factors influencing the solid TME is necessary to understand the mechanisms of disease progression. Particularly, the role of cancer cell–matrix interactions and multi-directional crosstalk between tumor and stromal cells have gained attention as potential therapeutic targets. Toward this end, engineered two-dimensional (2D) and three-dimensional (3D) tumor models have been developed using biomaterial-based platforms for various mechanistic studies as well as translational drug-screening applications. In this chapter, we discuss specific cellular and extra-cellular matrix (ECM) components of the TME that regulate tumorigenic and metastatic progression. We describe in detail a wide range of natural and synthetic biomaterials that have been implemented as in vitro platforms for cancer studies. We specifically discuss various chemical modifications of these materials to tune their biochemical and biophysical properties toward emulating native tumor tissues. We further present novel advances in biomaterial design and user-controlled spatiotemporal regulation of material properties that help mimic the dynamic and heterogenous nature of the TME. Overall, the implementation and translation of these engineered scaffolds and matrices will significantly accelerate the anti-cancer drug discovery efforts in the future.
Microfluidic Models of the Tumor Microenvironment
Authors: Chang Chia-Wen , Holter Jacob C. , Song Jonathan W.
Published: December 2022

Advancing our understanding of the metastasis-promoting properties of the tumor microenvironment (TME) requires mechanistic studies of tumor biology and functional responses at the cellular, sub-cellular, and molecular levels. Microfluidic models offer several advantages over traditional in vitro and in vivo platforms including the incorporation of fluid pressure and biomolecular concentration gradients, optical compatibility, and the specification of cellular and matrix compositions for more relevant 3D physiological recapitulation. For instance, microfluidics enables the application of highly controllable physicochemical properties such as gradients of oxygen (O2) tension and oncogenic signaling molecules, fluid mechanical stimuli, and biophysical tissue matrix stiffness and solid stress. Microphysiological systems can be used to uncover the role of these tractable factors and the potent migratory cues they impart onto malignant cells, which promote and maintain cancer invasion. Consequently, there is significant interest in leveraging microfluidic models to develop novel therapies that target the TME as it relates to invasive and metastatic progression. Here, we examine the application of microfluidic systems, which have emerged as versatile in vitro disease models of the TME that enable unprecedented control of microenvironmental factors for systematic experimentation and predictive drug testing.
Tissue Engineered Models of Metastasis: Focus on Bone Metastasis
Authors: Sempertegui N. , Fischbach C.
Published: December 2022

Patients with advanced breast cancer frequently develop osteolytic bone metastases resulting in significant morbidity and mortality, but treatment options are lacking due to limited understanding of the underlying mechanisms. Historically, bone metastasis research has focused on cancer cells and how they induce clinically evident bone degradation. However, bone metastasis is a multi-step process, the pathogenesis of which depends on the coordinated interplay between many different cell types and their surrounding extracellular matrix (ECM). Tissue-engineered model systems that systematically incorporate both biological and biophysical design parameters, such as cellular interactions and bone ECM composition, architecture, and mechanical properties, will further our understanding of the mechanisms that govern all stages of the metastatic cascade. Here, we briefly summarize current knowledge of bone metastasis and how biomaterial-based models can be used to advance studies of tumor cell dissemination, dormancy, and metastatic outgrowth in the skeleton. Tissue-engineered bone metastasis models will advance comprehension of the crosstalk between cancer cells and the skeletal microenvironment that will lead to the development of more efficacious therapies to interfere with bone metastasis.
Targeting anti-inflammatory immunonanocarriers to human and murine neutrophils via the Ly6 antigen for psoriasiform dermatitis alleviation
Authors: Lin Cheng-Yu , Yu Huang-Ping , Chang Yen-Tzu , Lin Zih-Chan , Alalaiwe Ahmed , Hwang Tsong-Long , Fang Jia-You
Published: December 2022

Psoriasis is a refractory and difficult-to-treat skin disorder.
Formation of a meltable purinate metal–organic framework and its glass analogue
Authors: Bumstead Alice M. , Castillo-Blas Celia , Pakamorė Ignas , Thorne Michael F. , Sapnik Adam F. , Chester Ashleigh M. , Robertson Georgina , Irving Daniel J. M. , Chater Philip A. , Keen David A. , Forgan Ross S. , Bennett Thomas D.
Published: December 2022

We find that a novel purine-containing framework has one of the lowest melting temperatures recorded for a ZIF.
Discrimination of enantiomers and constitutional isomers by self-generated macroscopic fluid flow
Authors: Alam Mujeeb , Agashe Chinmayee , Gill Arshdeep Kaur , Varshney Rohit , Tiwari Naveen , Patra Debabrata
Published: December 2022

The supramolecular interfaces consisting of macrocyclic “host” molecules in a multilayer film have been utilized to discriminate isomers by their respective fluid flow response upon “host–guest” molecular recognition.
Regioselective O-alkylation of 2-pyridones by TfOH-catalyzed carbenoid insertion
Authors: Yan Zhewei , He Hangli , Yuan Dabiao , Yan Qiongjiao , Wang Wei , Jiang Haipeng , Wang Haifeng , Chen Fener
Published: December 2022

We have developed a novel TfOH-catalyzed regioselective O-alkylation of 2-pyridones with diazo compounds in high regioselectivity. This protocol is characterized by mild reaction conditions, metal-free, and simplicity.
An ultrasensitive electrochemical biosensor for microRNA-21 detection via AuNPs/GAs and Y-shaped DNA dual-signal amplification strategy
Authors: He Congjuan , Zhao Jiaying , Long Yanyi , Yang Huisi , Dong Jiangbo , Liu Huan , Hu Zhikun , Yang Mei , Huo Danqun , Hou Changjun
Published: December 2022

An AuNPs/GAs modified electrochemical biosensor with CHA and Y-shaped DNA nanostructure dual-signal amplification strategy for ultrasensitive miR-21 detection was constructed.
Tailoring the physical properties of hybrid magnetic quinuclidine-based plastic compoundsviaweak interactions
Authors: González-Izquierdo Palmerina , de Pedro Imanol , Cañadillas-Delgado Laura , Beobide Garikoitz , Vallcorba Oriol , Sánchez-Andújar Manuel , Fernández-Díaz María Teresa , Fernández Jesús Rodríguez , Fabelo Oscar
Published: December 2022

The ketonization of the quinuclidine molecule were used to synthesize and physically characterize two paramagnetic hybrid compounds. The significant increase in the conductivity at HT is related with a crystal to plastic crystal phase transition.
Controllable construction of red thermally activated delayed fluorescence molecules based on a spiro-acridine donor
Authors: Liu Huanling , Zhang Kai , Zou Haipei , Mu Qingfang , Song Yuzhi , Lin Lili , Xu Yuanyuan , Wang Chuan-Kui , Fan Jianzhong
Published: December 2022

Four new molecules based on a spiro-acridine donor exhibit red or NIR emissions and show excellent TADF luminescence properties.
Enhancing energy recovery of wastewater treatment plants through hydrothermal liquefaction
Authors: Cabrera Daniela V. , Barria David A. , Camu Esteban , Celis Crispin , Tester Jefferson W. , Labatut Rodrigo A.
Published: December 2022

Experimental data analysis and Monte Carlo simulations showed that sewage sludge can be successfully stabilized using HTL; overall energy recovery increased up to 2.2-fold relative to an AD-only treatment.
Integrated silicon microfluidic chip for picoliter-scale analyte segmentation and microscale printing for mass spectrometry imaging
Authors: Shi Weihua , Bell Sara , Iyer Hrishikesh , Brenden Christopher Kenji , Zhang Yan , Kim Sungho , Park Insu , Bashir Rashid , Sweedler Jonathan , Vlasov Yurii
Published: December 2022

A silicon integrated microfluidics system prints picoliter-segmented analytes for attomole-level chemical analysis with mass spectrometry imaging.
Metal–organic framework-derived semiconductors for photocatalytic hydrogen production
Authors: Nyela Musa Emmanuel , Stylianou Kyriakos C.
Published: December 2022

Metal–organic framework-based semiconductors have shown great promise for the production of a green fuel, hydrogen, using two abundant resources: the sun and water.
Metallene-related materials for electrocatalysis and energy conversion
Authors: Xie Minghao , Tang Sishuang , Zhang Bowen , Yu Guihua
Published: December 2022

As a member of graphene analogs, metallenes are a class of two-dimensional materials with atomic thickness and well-controlled surface atomic arrangement made of metals or alloys.
Development of MoS2-ZnO heterostructures: an efficient bifunctional catalyst for the detection of glucose and degradation of toxic organic dyes
Authors: Ali Farhan , Zafar Amina , Nisar Amjad , Liu Yanguo , Karim Shafqat , Faiz Faisal , Zafar Zainab , Sun Hongyu , Hussain Shafqat , Faiz Yasir , Ali Tahir , Javed Sofia , Yu Yanlong , Ahmad Mashkoor
Published: December 2022

The heterostructure catalyst MoS2-ZnO possesses binary properties and provides a novel platform for the remediation of environmental as well as health issues.
Graphene based magnetite carbon nanofiber composites as anodes for high-performance Li-ion batteries
Authors: Rosaiah Pitcheri , Niyitanga Theophile , Sambasivam Sangaraju , Kim Haekyoung
Published: December 2022

For energy storage applications, highly flexible free-standing electrodes are ideal for the fabrication of electrochemical cells.
Fe3S4 nanoparticles wrapped in a g-C3N4 matrix: an outstanding visible active Fenton catalysis and electrochemical sensing platform for lead and uranyl ions
Authors: Bashir Arshid , Pandith Altaf Hussain , Qureashi Aaliya , Malik Lateef Ahmad
Published: December 2022

Fe3S4, commonly known as greigite, is a transition metal chalcogenide and has attracted enormous attention in the field of energy storage and environmental remediation.