bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonality in the incidence of anti‐GQ1b antibody syndrome—A territory‐wide study
Authors: Chang Richard Shek‐kwan , Lau Eric H. Y. , Au Elaine Yuen Ling , Leung William C. Y. , Leung Yu Hin Ian
Published: September 2021

Aims

To investigate any seasonality in the incidence of anti‐GQ1b antibody syndrome (AGS).

Methods

We conducted a retrospective observational study in all hospitalized patients in local public hospitals from January 2013 to December 2018. AGS was defined by hospitalized patients with positive serum anti‐GQ1b IgG, presumably encompassing Miller‐Fisher syndrome, Bickerstaff brainstem encephalitis and Guillain–Barré syndrome (GBS) variants. GBS cases were retrieved from the computerized database by diagnostic label. Campylobacter jejuni infection (CJI) injection was identified by positive stool culture. Monthly incidence rates of AGS, GBS and CJI were calculated. Poisson and negative binomial regression models with long‐term time trend were fitted to characterize the seasonal pattern.

Results

A total of 237, 572 and 2434 cases of AGS, GBS and CJI were identified, respectively, in a population of 7.3 million. The annual incidence rate of AGS was 0.54 per 100,000 person‐years. AGS was demonstrated to have an annual peak in the spring season, from March to April, which was congruent with that of GBS and slightly lagged the annual peak of CJI from February to March (likelihood ratio tests all p < .001 for the seasonal terms).

Conclusion

The incidence of AGS peaks in springtime, which is congruent with that of GBS and lags around one month after that of CJI. We demonstrated that AGS has a clear seasonality in occurrence.
Structural Basis for The Recognition of Deaminated Nucleobases by An Archaeal DNA Polymerase
Authors: Kropp Heike M. , Ludmann Samra , Diederichs Kay , Betz Karin , Marx Andreas
Published: September 2021

With increasing temperature, nucleobases in DNA become increasingly damaged by hydrolysis of exocyclic amines. The most prominent damage includes the conversion of cytosine to uracil and adenine to hypoxanthine. These damages are mutagenic and put the integrity of the genome at risk if not repaired appropriately. Several archaea live at elevated temperatures and thus, are exposed to a higher risk of deamination. Earlier studies have shown that DNA polymerases of archaea have the property of sensing deaminated nucleobases in the DNA template and thereby stalling the DNA synthesis during DNA replication providing another layer of DNA damage recognition and repair. However, the structural basis of uracil and hypoxanthine sensing by archaeal B‐family DNA polymerases is sparse. Here we report on three new crystal structures of the archaeal B‐family DNA polymerase from Thermococcus kodakarensis (KOD) DNA polymerase in complex with primer and template strands that have extended single stranded DNA template 5’‐overhangs. These overhangs contain either the canonical nucleobases as well as uracil or hypoxanthine, respectively, and provide unprecedented structural insights into their recognition by archaeal B‐family DNA polymerases.
Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs
Authors: Du Kun , Wang Min , Zhang Nan , Yu Pei , Wang Ping , Li Ying , Wang Xiangdong , Zhang Luo , Bachert Claus
Published: September 2021

Background

Tissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of these two ECM proteins in the expression of MMPs in nasal polyps.

Methods

The concentrations of MMP‐2, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐12, MMP‐13, TIMP‐1, TIMP‐2, TIMP‐3, TIMP‐4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and were analyzed by adjusted logistic regression and spearman correlation test. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real‐time PCR.

Results

The protein levels of MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐1, TIMP‐2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. The adjusted logistic regression analyses showed that MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐2, periostin, and tenascin C were related to the occurrence of CRSwNP. Spearman correlation test showed periostin was positively correlated with MMP‐3 and TIMP‐2, and tenascin C was positively correlated with MMP‐3, MMP‐7, MMP‐8, MMP‐9, and TIMP‐2. Periostin stimulated the gene expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in fibroblasts and MMP‐9 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in epithelial cells. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C.

Conclusions

Periostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.
DNA Framework‐Mediated Geometric Renormalization of Gold Nanoparticles on a Two‐Dimensional Fluidic Membrane Interface
Authors: Guo Ruiyan , Li Min , Zuo Xiaolei
Published: September 2021

The precise arrangement of single entity is a crucial objective of nanoscience and holds great promise in various fields such as biology and material science. In this work, we develop a “DNA framework‐mediated geometric renormalization” (DFMGR) strategy to reassemble gold nanoparticles into specific geometric shapes on a 2‐dimensional (2D) fluidic membrane interface. Cholesterol‐modified AuNPs are randomly anchored on the supported lipid bilayer (SLB) via the cholesterol‐lipid interaction. We demonstrate that AuNPs are laterally mobile on SLB and could be further rearranged into a specific geometric shape by DNA framework containing algebraically topological DNA arms. Using scanning electron microscope (SEM) imaging approach, simple geometric shapes, such as points assembled by monomers, line segments assembled by dimers, triangles assembled by trimers are visually presented. Interestingly, we found that the statistic angle (58.77°) and side length (12.21 nm) of triangles obtained from SEM images were both agreed well with the theoretical angle of 60° and side length of 12.58 nm. And the relative error of the angle calculated was as low as 0.33 %. These results indicated that the DFMGR strategy showed precise regulation ability for the AuNPs renormalization. We believe that DNA framework‐mediated geometric renormalization strategy would be a powerful means for regulating ligand‐receptor interactions in biosystems and for nanoparticle assembling in material science.
Primary school teachers' readiness in identifying children with dyslexia: A national survey in Sri Lanka
Authors: Peries W. A. Nadhee N. , Indrarathne Bimali , Jayamanne B. Deepal W. , Wickramasekara Thimathi D. , Alwis K. Anoma C. , Jayatilleke Achala U.
Published: September 2021

Primary school teachers should be able to identify struggling learners who may have dyslexia type learning difficulties, in order to facilitate early intervention. Considering this importance, a nationwide survey was conducted in Sri Lanka with 705 primary school teachers among randomly selected schools in order to investigate teacher readiness to identify learners with dyslexia. Teacher readiness was measured based on three variables (a) teachers' self‐reported basic knowledge of dyslexia, (b) their self‐reported awareness of local tools and processes used to identify dyslexia and (c) their self‐reported attitudes towards engaging in identifying dyslexia. Data were gathered through a structured questionnaire. Logistic regression analyses revealed that the participants had minimal readiness to engage in identifying learners with dyslexia. However, most of them showed positive attitudes towards actively engaging in identifying dyslexia.
Long‐term stand‐level resilience in natural secondary forest stands recovering from severe windthrow damage
Authors: Shibuya Masato
Published: September 2021

Long‐term stand‐level resilience in three natural secondary forests after a stand‐replacing windthrow damage event was examined by analyzing stand composition, structure, and function using repetitive measurement data collected in permanent plots over 60 yr. The secondary forests differed among pre‐disturbance forest types. For the purposes of this study, stand resilience comprised resistance to and recovery from windthrow damage. To analyze composition, the dynamics of species numbers in the permanent plots were tracked and temporal trends in similarity between pre‐ and post‐disturbance compositions were examined. To investigate stand structure, the dynamics of tree density, mean diameter at breast height (DBH), and temporal trends in similarity between pre‐ and post‐disturbance DBH frequency distributions were analyzed. To investigate stand function, the dynamics of stand basal area were analyzed. The calculations showed that tree density, basal area, species composition, and DBH frequency distribution were associated with low resistance to windthrow damage. By contrast, the number of species and mean DBH were resistant to windthrow damage. Basal areas recovered quickly in the 60 yr post‐windthrow damage, but recovery of the pre‐damage mean DBH and DBH frequency distribution was slow. Tree density and the number of species recovered to levels that exceeded those in the stands prior to the windthrow event. The recovery of species composition varied by pre‐disturbance forest type. Among the stands analyzed, the hardwood forest that existed prior to disturbance was resistant to and recovered well from windthrow damage in comparison with other types of pre‐disturbance forests. In conclusion, stand‐replacing windthrow damage can have a long‐lasting influence on secondary forests, especially in terms of stand composition and structure.
Technological characteristics of inulin enriched gluten‐free bread: Effect of acorn flour replacement and fermentation type
Authors: Shiri Ameneh , Ehrampoush Mohammad Hassan , Yasini Ardakani Seyed Ali , Shamsi Farimah , Mollakhalili‐Meybodi Neda
Published: September 2021

Textural, physicochemical, and sensory characteristics of rice‐based gluten‐free bread in the presence of acorn flour; inulin and different fermentation type (yeast starter fermentation [Y] or mixed fermentation based on sourdough [MF‐SD]) were investigated. Acorn flour was added to replace rice flour at a proportion of 10, 30, and 50% W/W. Furthermore, the mixture flour was replaced by inulin as a functional prebiotic ingredient at 10% W/W. Considering results obtained at this study, using mixed fermentation based on sourdough and inulin at 10% W/W provide the structure able to restore gases through baking process at formulations containing acorn flour at 30% W/W (A30R70SL). The highest specific volume (1.47 ± 0.04 cm3 g−1) and the lowest hardness (40.97 ± 0.87 N) are observed in A30R70SL which seems to be induced by its potential to form gel. Acorn flour substitution level at 50% W/W adversely influenced the technological characteristics of final product and its perception by the consumer. Acorn flour substitution up to 30% W/W is preferred by the consumer which is attributed to its potential role to improve the unpleasant pale color of rice‐based gluten‐free products. A negatively significant correlation has been observed between the color perception by the consumer and crumb lightness (r = −.493, p ≤ .05).
Palaeozoic tectonic transition of the North Qilian Belt in the northern margin of the Tibetan Plateau, NW China: Insights from detrital zircon U–Pb geochronology and sedimentology
Authors: Qin Yu , Zhang Xiaoli , Feng Qiao , Zhang Xi , Gao Jindong , Chen Yan
Published: September 2021

This study presents new integrated stratigraphic, sedimentary, and geochronological data for Silurian to Devonian sedimentary rocks in the central North Qilian Belt (NQB), NW China. These data constrain the timing and processes involved in the Palaeozoic tectonic transition from compression to extension in the NQB. This study indicates that the Angzanggou Formation probably formed in a foreland basin setting during 439–430 Ma compression associated with the closure of the North Qilian Ocean. The terrestrial sedimentary rocks overlying the formation were most likely deposited in a superimposed basin at 409–388 Ma as a result of the post‐orogenic extension of the NQB, an event that involved initial post‐orogenic extension‐related sedimentation. Silurian–Devonian sediments were derived from multiple sources, including the NQB, Central Qilian Block (CQB), and Alxa and Dunhuang blocks. Convergence between the CQB and the Alxa Block propagated westward, leading to the scissor‐like closure of the North Qilian Ocean during the Middle to Late Silurian and the oblique docking and collision of these two blocks. This is evidenced by a lack of middle–upper Silurian sedimentary rocks in the middle and eastern NQB compared with the well‐developed and well‐preserved sedimentary strata in the western segment. Devonian retrogradation and intracontinental extension‐related magmatism in the NQB also provide evidence of long‐lived tectonic extension of the lithosphere. Combining these new data with previously published data for the NQB and the wider region suggests that the Devonian terrestrial strata were deposited in a post‐orogenic extensional setting similar to that in the North Qaidam and East Kunlun belts, indicating that the Palaeozoic large‐scale tectonic transition from compression to extension in these three belts most likely started during the Early Devonian.
Development of the visual white matter pathways mediates development of electrophysiological responses in visual cortex
Authors: Caffarra Sendy , Joo Sung Jun , Bloom David , Kruper John , Rokem Ariel , Yeatman Jason D.
Published: September 2021

The latency of neural responses in the visual cortex changes systematically across the lifespan. Here, we test the hypothesis that development of visual white matter pathways mediates maturational changes in the latency of visual signals. Thirty‐eight children participated in a cross‐sectional study including diffusion magnetic resonance imaging (MRI) and magnetoencephalography (MEG) sessions. During the MEG acquisition, participants performed a lexical decision and a fixation task on words presented at varying levels of contrast and noise. For all stimuli and tasks, early evoked fields were observed around 100 ms after stimulus onset (M100), with slower and lower amplitude responses for low as compared to high contrast stimuli. The optic radiations and optic tracts were identified in each individual's brain based on diffusion MRI tractography. The diffusion properties of the optic radiations predicted M100 responses, especially for high contrast stimuli. Higher optic radiation fractional anisotropy (FA) values were associated with faster and larger M100 responses. Over this developmental window, the M100 responses to high contrast stimuli became faster with age and the optic radiation FA mediated this effect. These findings suggest that the maturation of the optic radiations over childhood accounts for individual variations observed in the developmental trajectory of visual cortex responses.
REDV‐modified decellularized microvascular grafts for arterial and venous reconstruction
Authors: Yamanaka Hiroki , Mahara Atsushi , Morimoto Naoki , Yamaoka Tetsuji
Published: September 2021

Recently, a decellularized microvascular graft (inner diameter: 0.6 mm) modified with the integrin α4β1 ligand, REDV, was developed to provide an alternative to autologous‐vein grafting in reconstructive microsurgery, showing good early‐stage patency under arterial flow in rats. This consecutive study evaluated its potential utility not only as an arterial substitute, but also as a venous substitute, using a rat‐tail replantation model. Graft remodeling depending on hemodynamic status was also investigated. ACI rat tail arteries were decellularized via ultra‐high‐hydrostatic pressure treatment and modified with REDV to induce antithrombogenic interfaces and promote endothelialization after implantation. Grafts were implanted into the tail artery and vein to re‐establish blood circulation in amputated Lewis rat tails (n = 12). The primary endpoint was the survival of replants. Secondary endpoints were graft patency, remodeling, and regeneration for 6 months. In all but three cases with technical errors or postoperative self‐mutilation, tails survived without any evidence of ischemia or congestion. Six‐month Kaplan–Meier patency was 100% for tail‐artery implanted grafts and 62% for tail‐vein implanted grafts. At 6 months, the neo‐tunica media (thickness: 95.0 μm in tail‐artery implanted grafts, 9.3 μm in tail‐vein implanted grafts) was regenerated inside the neo‐intima. In conclusion, the microvascular grafts functioned well both as arterial and venous paths of replanted‐rat tails, with different remodeling under arterial and venous conditions.
Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
Authors: Sroga Grażyna E. , Vashishth Deepak
Published: September 2021

It has been a challenge to establish a link between specific advanced glycation end products (AGEs) as causal agents of different pathologies and age‐related diseases, primarily because of the lack of suitable in vitro experimental strategies facilitating increased formation of a specific AGE, here carboxymethyllysine (CML), over other AGEs under controlled conditions. CML is of considerable importance to various oxidative stress–related diseases, because in vivo formation of this AGE is connected with cellular oxidative/carbonyl metabolism. The mechanistic implications of CML accumulation in bone remain to be elucidated. To facilitate such studies, we developed a new in vitro strategy that allows preferential generation of CML in bone matrix over other AGEs. Using bone samples from human donors of different age (young, middle‐age, and elderly), we show successful in vitro generation of the desired levels of CML and show that they mimic those observed in vivo in several bone disorders. Formation of such physiologically relevant CML levels was achieved by selecting two oxidative/carbonyl stress compounds naturally produced in the human body, glyoxal and glyoxylic acid. Kinetic studies using the two compounds revealed differences not only between their reaction rates but also in the progression and enhanced formation of CML over other AGEs (measured by their collective fluorescence as fluorescent AGEs [fAGEs]) Consequently, through the regulation of reaction time, the levels of CML and fAGEs could be controlled and separated. Given that the developed approach does not fully eliminate the formation of other uncharacterized glycation products, this could be considered as the study limitation. We expect that the concepts of our experimental approach can be used to develop diverse strategies facilitating production of the desired levels of selected AGEs in bone and other tissues, and thus, opens new avenues for investigating the role and mechanistic aspects of specific AGEs, here CML, in bone. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Social anxiety, rejection sensitivity, and theory of mind decoding ability
Authors: Lord Kayla A. , Suvak Michael K. , Liverant Gabrielle I.
Published: September 2021

Objectives:

Recent initiatives have highlighted the importance of investigating clinically relevant variations in social processes that contribute to mental illness. Surprisingly little research has examined the associations between socially and clinically relevant transdiagnostic factors, such as social anxity (SA) and rejection sensitvity (RS), on theory of mind (ToM) decoding ability.

Methods:

The Reading the Mind in the Eyes Task and self‐report measures of SA and RS were completed by 199 adult participants.

Results:

Linear regression analyses suggest a specific difficulty decoding positive emotion associated with SA and global decrements in ToM associated with RS that may reflect a negative interpretation bias.

Conclusions:

These findings may have important implications for understanding how those with SA and RS perceive and navigate social interactions, which may contribute to the maintenance of symptoms and decreased psychosocial functioning.
Dynamics of risk: Recent changes in psychological inflexibility precede subsequent changes in returning US veterans' posttraumatic stress
Authors: Crabtree Meghan A. , Hale Willie J. , Meyer Eric C. , Kimbrel Nathan A. , DeBeer Bryann B. , Gulliver Suzy B. , Morissette Sandra B.
Published: September 2021

Objectives

As a malleable risk‐factor, psychological inflexibility is implicated in the development and maintenance of posttraumatic stress symptoms (PTS). Unfortunately, limited research has addressed whether changes in psychological inflexibility are antecedent to changes in PTS severity over time, or whether such changes are mutually dependent.

Methods

Utilizing bivariate latent difference score modeling, this longitudinal study sequenced intraindividual changes in psychological inflexibility and PTS severity within a sample of 305 returning US veterans. Veterans' self‐reported psychological inflexibility and PTS severity were assessed quarterly over 1 year.

Results

Results indicated that early reductions in psychological inflexibility potentiated later declines in veterans' PTS severity, accounting for veterans' prior levels of psychological inflexibility and PTS severity.

Conclusions

These findings underscore the unique role ofchangesin psychological inflexibility as an important mechanism of change in PTS severity and provide empirical support for an antecedent model of the role of psychological inflexibility in PTS recovery.
Cannabinoid receptor 2 selective agonists and Alzheimer's disease: An insight into the therapeutic potentials
Authors: Magham Sai Varshini , Thaggikuppe krishnamurthy Praveen , Shaji Neenu , Mani Lalithkumar , Balasubramanian Shivaramakrishnan
Published: September 2021

Endocannabinoid system has been extensively studied in recent decades, particularly the cannabinoid receptors CB1 and CB2, due to their important role in neuroinflammation. Among these, CB2 has gained prominence due to its selective overexpression in glial cells during neuroinflammation. In contrast to CB1 agonists, CB2 agonists have no side effects such as ataxia, hypothermia, euphoria, psychological, or addiction liabilities. CB2 and its selective agonists' above‐mentioned unique properties have become a research focus in neurodegenerative disorders such as Alzheimer's disease (AD). The review discusses the neuroprotective role of CB receptors, particularly CB2, in AD, as well as the significance and limitations of this research.
Compact full‐color laser beam scanning image projector based on a waveguide‐type RGB combiner
Authors: Nakao Akira , Yamada Shoji , Katsuyama Toshio , Kawasaki Osamu , Iwabata Kazuki , Yabe Yuuta , Horii Koichi , Himeno Akira
Published: September 2021

A packaged red‐green‐blue (RGB) laser module based on a waveguide‐type combiner is demonstrated. The module has characteristic features such as (a) a compact size and lightweight, (b) almost perfectly aligned RGB laser beams owing to a single waveguide output, and (c) a configuration with only a few mechanical elements. The typical package size is 10 × 5 × 5 mm for an outside focusing lens type and 11 × 4.8 × 3 mm for an inside focusing lens type. Light intensity monitors and a temperature monitor are also equipped for the inside focusing lens type.

Furthermore, a compact RGB laser beam scanning module is demonstrated. Clear full‐color high‐definition video images are obtained. Thus, these modules based on waveguide‐type combiners can provide compact imaging projectors with clear images. Compact Lidar scanners and laser sources for various sensors are also candidate applications.
A survey evaluation comparing pain curriculum taught in Australian exercise physiology degrees to graduate perceptions of their preparedness and competency to treat people with chronic pain
Authors: Jones Matthew D. , Cashin Aidan G. , Mouatt Brendan , McLeod Kelly A. , Mundell Niamh L. , McAuley James H. , Booth John
Published: September 2021

Background and Aims

This cross‐sectional study evaluated the nature of pain curriculum being taught in accredited exercise physiology degrees across Australian universities and its perceived usefulness for preparing exercise physiologists to treat people with chronic pain.

Materials & Methods

Universities and graduates were asked about the nature and sufficiency of pain curriculum taught, with particular emphasis on competencies for physical therapists as outlined by the International Association for the Study of Pain.

Results

Ten universities and 101 graduates responded. Median (interquartile range) instruction time on pain curriculum was 12 (7.25–18.75) hours. Few universities (30%) were aware of the guidelines for physical therapy pain curricula, although most (70%) agreed their degrees contained adequate instruction on pain assessment and management. In contrast, 74% of graduates felt their degree did not adequately prepare them to treat people with chronic pain. Half the graduates (51%) were not aware of the guidelines for physical therapy pain curricula.

Discussion & Conclusion

There is a disconnect between perceptions of Australian universities and their graduates regarding the sufficiency of pain curriculum taught to student exercise physiologists. Benchmarking pain curriculum in Australian university programs against relevant international recommendations may enhance the suitability of pain curricula taught to exercise physiologists, thereby better preparing new graduates to treat people with pain.
Discovery proteomics of human placental tissue
Authors: Mellinger Allyson L. , McCoy Krista , Minior Duy An T. , Williams Taufika Islam
Published: September 2021

We describe a label‐free proteomics protocol for the interrogation of the placental proteome. Step‐by‐step directions, including tissue cleanup and preparation, proteolytic digestion, nanoLC–MS/MS data collection and data analysis, are provided. The workflow has been applied toward exploring differential protein expression patterns in placentas from women who have been exposed to drugs during pregnancy relative to those who have not. We collected 20 tissue specimens, each representing a combination of spatially diverse sections across the placenta. These specimens were analyzed in the work described here, to survey information across the entire organ. This protocol can be scaled up or down as needed.
Multiple pneumatoceles and diffuse ground‐glass opacities in a 20‐month‐old boy with COVID‐19 pneumonia
Authors: Özgür Cihan , Doğan Caner
Published: September 2021

Key message

Chest computed tomography characteristics of coronavirus disease 2019 (COVID‐19) in paediatric patients have been reported to be atypical and different compared to adults. Although pneumatocele has not been reported in paediatric COVID‐19 pneumonia cases in the literature, physician should be familiar with atypical imaging findings.
Tandem Reaction of Phenyl α‐Cyano‐α‐arylacetates with Quinone Monoimines
Authors: Cheng Shao‐Bing , Jing Yi , Cao Lian‐Yi , Li Wen‐Zhe , Zhang Xiao‐Mei
Published: September 2021

A tandem reaction of phenyl α‐cyano‐α‐arylacetates with quinone monoimines was presented, which allowed for the synthesis of various 2‐aminobenzofuran derivatives in low to moderate yields. This method is applicable to a series of phenyl α‐cyano‐α‐arylacetates with various aryl groups and quinone monoimines with different substituents. In addition, a pausible mechanism was proposed.
Nanostructured Substrates as Matrices for Surface Assisted Laser Desorption/Ionization Mass Spectrometry: A Progress Report from Material Research to Biomedical Applications
Authors: Ma Wen , Li Jun , Li Xianjiang , Bai Yu , Liu Huwei
Published: September 2021

Within the past two decades, the escalation of research output in nanotechnology fields has boosted the development of novel nanoparticles and nanostructured substrates for use as matrices in surface assisted laser desorption/ionization mass spectrometry (SALDI‐MS). The application of nanomaterials as matrices, rather than organic matrices, offers remarkable characteristics that allow the analysis of small molecules with fewer matrix interfering peaks, and share higher detection sensitivity, specificity, and reproducibility. The technological advancement of SALDI‐MS has in turn, propelled the application of the analytical technique in the field of biomedical analysis. In this review, the properties and fabrication methods of nanostructured substrates in SALDI‐MS such as metallic‐, carbon‐, and silicon‐based nanostructures, quantum dots, metal‐organic frameworks, and covalent‐organic frameworks are described. Additionally, the latest progress (most within 5 years) of biomedical applications in small molecule, large biomolecule, and MS imaging analysis including metabolite profiling, drug monitoring, bacteria identification, disease diagnosis, and therapeutic evaluation are demonstrated. Key parameters that govern nanomaterial's SALDI efficiency in biomolecule analysis are also discussed. Finally, perspectives of the future development are given to provide a better advancement and promote practical application in clinical MS.
Mesenchymal Stromal Cell-Mediated Immune Regulation: A Promising Remedy in the Therapy of Type 2 Diabetes Mellitus
Authors: Chen Ji , Zheng Chen-Xi , Jin Yan , Hu Cheng-Hu
Published: September 2021

Type 2 diabetes mellitus (T2DM) is a major threat to global public health, with increasing prevalence as well as high morbidity and mortality, to which immune dysfunction has been recognized as a crucial contributor. Mesenchymal stromal cells (MSCs), obtained from various sources and possessing potent immunomodulatory abilities, have displayed great therapeutic potential for T2DM. Interestingly, the immunomodulatory capabilities of MSCs are endowed and plastic. Among the multiple mechanisms involved in MSC-mediated immune regulation, the paracrine effects of MSCs have attracted much attention. Of note, extracellular vesicles (EVs), an important component of MSC secretome, have emerged as pivotal mediators of their immunoregulatory effects. Particularly, the necrobiology of MSCs, especially apoptosis, has recently been revealed to affect their immunomodulatory functions in vivo. In specific, a variety of preclinical studies have demonstrated the beneficial effects of MSCs on improving islet function and ameliorating insulin resistance. More importantly, clinical trials have further uncovered the therapeutic potential of MSCs for T2DM. In this review, we outline current knowledge regarding the plasticity and underlying mechanisms of MSC-mediated immune modulation, focusing on the paracrine effects. We also summarize the applications of MSC-based therapies for T2DM in both preclinical studies and clinical trials, with particular emphasis on the modulation of immune system.
A Synthetic mRNA Cell Reprogramming Method Using CYCLIN D1 Promotes DNA rEpair, Generating Improved Genetically Stable Human Induced Pluripotent Stem Cells
Authors: Alvarez-Palomo Ana Belén , Requena-Osete Jordi , Delgado-Morales Raul , Moreno-Manzano Victoria , Grau-Bove Carme , Tejera Agueda M. , Otero Manel Juan , Barrot Carme , Santos-Barriopedro Irene , Vaquero Alejandro , Mezquita-Pla Jovita , Moran Sebastian , Naya Carlos Hobeich , Garcia-Martínez Iris , Pérez Francisco Vidal , Blasco María A. , Esteller Manel , Edel Michael J.
Published: September 2021

A key challenge for clinical application of induced pluripotent stem cells (iPSC) to accurately model and treat human pathologies depends on developing a method to generate genetically stable cells to reduce long-term risks of cell transplant therapy. Here, we hypothesized that CYCLIN D1 repairs DNA by highly efficient homologous recombination (HR) during reprogramming to iPSC that reduces genetic instability and threat of neoplastic growth. We adopted a synthetic mRNA transfection method using clinically compatible conditions with CYCLIN D1 plus base factors (OCT3/4, SOX2, KLF4, LIN28) and compared with methods that use C-MYC. We demonstrate that CYCLIN D1 made iPSC have (a) lower multitelomeric signal, (b) reduced double-strand DNA breaks, (c) correct nuclear localization of RAD51 protein expression, and (d) reduced single-nucleotide polymorphism (SNP) changes per chromosome, compared with the classical reprogramming method using C-MYC. CYCLIN D1 iPSC have reduced teratoma Ki67 cell growth kinetics and derived neural stem cells successfully engraft in a hostile spinal cord injury (SCI) microenvironment with efficient survival, differentiation. We demonstrate that CYCLIN D1 promotes double-stranded DNA damage repair predominantly through HR during cell reprogramming to efficiently produce iPSC. CYCLIN D1 reduces general cell stress associated with significantly lower SIRT1 gene expression and can rescue Sirt1 null mouse cell reprogramming. In conclusion, we show synthetic mRNA transfection of CYCLIN D1 repairs DNA during reprogramming resulting in significantly improved genetically stable footprint in human iPSC, enabling a new cell reprogramming method for more accurate and reliable generation of human iPSC for disease modeling and future clinical applications.
Evolution of Impatiens (Balsaminaceae) in the Albertine Rift – The endemic Impatiens purpureoviolacea complex consists of ten species
Authors: Fischer Eberhard , Abrahamczyk Stefan , Holstein Norbert , Janssens Steven B.
Published: September 2021

The Albertine Rift harbours a highly diverse flora with numerous endemic species. An important component of the forest understorey is the herbaceous genus Impatiens. Fieldwork in Burundi, the Democratic Republic of the Congo and Rwanda as well as morphological studies indicated that the Albertine Rift endemic Impatiens purpureoviolacea represents a species complex. We analyzed the hidden diversity of the complex using morphological and molecular data supplemented by herbarium studies. We found that the Impatiens purpureoviolacea complex can be divided into morphologically and phylogenetically well characterized clades containing ten species and a natural hybrid. We describe all of these species, provide a species key and analyze their evolutionary history. Beside Impatiens purpureoviolacea and I. gesneroidea, the already described I. urundiensis is resurrected from synonymy. Two varieties, Impatiens purpureoviolacea var. longicalcarata and I. gesneroidea var. superglabra are raised to species status, and five new species (Impatiens elwiraurzulae, I. lotteri, I. ludewigii, I. lutzmannii, I. versicolor) and a new natural hybrid (I. ×troupinii) are described. Within the mostly insect‐pollinated species of the clade, two bird‐pollinated species (Impatiens gesneroidea, I. superglabra) evolved independently. The clade split from its sister taxon in the Pliocene and started diversifying during the Pliocene/Pleistocene transition in parallel to an increased mountain uplifting and volcanic activity in the Albertine Rift. It further diversified during the Pleistocene, likely due to the changes in forest cover and connectivity induced by climatic fluctuations.
The mechanism of N‐acetyl‐l‐cysteine in improving the secretion of porcine follicle‐stimulating hormone in Pichia pastoris
Authors: Luo Gang , Liu Jiying , Bian Ting , Zhang Zhendong , Li Muwang
Published: September 2021

Our previous study revealed that N‐acetyl‐l‐cysteine (NAC) could enhance the secretion of recombinant proteins by Pichia pastoris, but the corresponding molecular mechanisms are still unclear. In the present study, we explored whether other thiols have a similar action on the secretion of recombinant human serum albumin and porcine follicle‐stimulating hormone fusion protein (HSA‐pFSHβ), to reveal the mechanism of NAC on HSA‐pFSHβ secretion. Transcriptome analysis showed that genes involved in oxidoreductase activity and oxidation–reduction process were upregulated in cells supplemented with NAC. The other three thiol‐reducing regents including dimercaptopropanol (DT), thioglycolic acid, and mercaptolactic acid could improve HSA‐pFSHβ production in the culture supernatant. Among them, only DT had similar effect as NAC on HSA‐pFSHβ secretion and the increase of GSH content. Moreover, 1–20 mM GSH, 1–10 mM cysteine, or 1–20 mM N‐acetyl‐d‐cysteine supplementation could improve the secretion of HSA‐pFSHβ. Furthermore, 0.4–3.2 mM ethacrynic acid, rather than 1–16 mM BSO could inhibit the effect of NAC on the production of HSA‐pFSHβ. These results indicated that NAC improved the secretion of HSA‐pFSHβ by increasing the intracellular GSH content through its thiol activity rather than as a precursor for GSH synthesis. In conclusion, our results demonstrate, for the first time, that the secretion of recombinant HSA‐pFSHβ in Pichia pastoris could be improved through thiol‐reducing agent supplementation, and the mechanism of the effect NAC has on HSA‐pFSHβ secretion is associated with improving the intracellular GSH content.
Higher-derivative supergravity, AdS4 holography, and black holes
Authors: Bobev Nikolay , Charles Anthony M. , Hristov Kiril , Reys Valentin
Published: September 2021

Abstract

We use conformal supergravity techniques to study four-derivative corrections in four-dimensional gauged supergravity. We show that the four-derivative Lagrangian for the propagating degrees of freedom of the $$ \mathcal{N} $$
N
= 2 gravity multiplet is determined by two real dimensionless constants. We demonstrate that all solutions of the two-derivative equations of motion in the supergravity theory also solve the four-derivative equations of motion. These results are then applied to explicitly calculate the regularized on-shell action for any asymptotically locally AdS4 solution of the two-derivative equations of motion. The four-derivative terms in the supergravity Lagrangian modify the entropy and other thermodynamic observables for the black hole solutions of the theory. We calculate these corrections explicitly and demonstrate that the quantum statistical relation holds for general stationary black holes in the presence of the four-derivative corrections. Employing an embedding of this supergravity model in M-theory we show how to use supersymmetric localization results in the holographically dual three-dimensional SCFT to determine the unknown coefficients in the four-derivative supergravity action. This in turn leads to new detailed results for the first subleading $$ {N}^{\frac{1}{2}} $$

N

1
2

correction to the large N partition function of a class of three-dimensional SCFTs on compact Euclidean manifolds. In addition, we calculate explicitly the first subleading correction to the Bekenstein-Hawking entropy of asymptotically AdS4 black holes in M-theory. We also discuss how to add matter multiplets to the supergravity theory in the presence of four-derivative terms and to generalize some of these results to six- and higher-derivative supergravity.
Fracture fixation in extremity trauma with carbon fiber-reinforced polyetheretherketone (CFR-PEEK) plates: evidence today
Authors: Chloros George D. , Prodromidis Apostolos D. , Wilson Jo , Giannoudis Peter V.
Published: September 2021

Purpose

To compare the CFR-PEEK plates with conventional plates in fracture fixation with regards to clinical and radiological outcomes and complications.

Methods

A systematic literature search was conducted in four online databases independently by two reviewers using the Cochrane methodology for systematic reviews. The identified relevant studies were assessed against predetermined inclusion/exclusion criteria. Independent data extraction and assessment of risk of bias and study quality was carried out.

Results

Nine studies (patient n = 361) out of 6594 records were included for analysis: 2 RCTs (n = 63), 3 prospective cohort studies (n = 151), and 4 retrospective cohort studies (n = 147). Studies were grouped per anatomic area of fixation. Four studies (n = 200) examined fixation of proximal humerus fractures. Two studies (n = 74) examined fixation of distal radius fractures. Two studies (n = 53) assessed outcomes of fixation of distal femur fractures. One study (n = 87) assessed the outcomes of fixation of ankle fractures. All nine studies reported very high union rates (from 91% in distal femur to 100% in upper limb) for the CFR-PEEK plate groups and low complication rates. There was no significant difference in clinical outcomes, and rate of complications as compared to the conventional plate groups.

Conclusion

CFR-PEEK plates have high union rates in extremity fracture fixation similar to conventional plates with comparable good clinical outcomes and a very low and comparable rate of complications. Considering their advantages, CFR-PEEK plates seem to be valid alternative to conventional plating.
Enter the metrics: critical theory and organizational operationalization of AI ethics
Authors: Krijger Joris
Published: September 2021

As artificial intelligence (AI) deployment is growing exponentially, questions have been raised whether the developed AI ethics discourse is apt to address the currently pressing questions in the field. Building on critical theory, this article aims to expand the scope of AI ethics by arguing that in addition to ethical principles and design, the organizational dimension (i.e. the background assumptions and values influencing design processes) plays a pivotal role in the operationalization of ethics in AI development and deployment contexts. Through the prism of critical theory, and the notions of underdetermination and technical code as developed by Feenberg in particular, the organizational dimension is related to two general challenges in operationalizing ethical principles in AI: (a) the challenge of ethical principles placing conflicting demands on an AI design that cannot be satisfied simultaneously, for which the term ‘inter-principle tension’ is coined, and (b) the challenge of translating an ethical principle to a technological form, constraint or demand, for which the term ‘intra-principle tension’ is coined. Rather than discussing principles, methods or metrics, the notion of technical code precipitates a discussion on the subsequent questions of value decisions, governance and procedural checks and balances. It is held that including and interrogating the organizational context in AI ethics approaches allows for a more in depth understanding of the current challenges concerning the formalization and implementation of ethical principles as well as of the ways in which these challenges could be met.
Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial
Authors: Voss Martin , Wenger Katharina J. , von Mettenheim Nina , Bojunga Jörg , Vetter Manuela , Diehl Bianca , Franz Kea , Gerlach Ruediger , Ronellenfitsch Michael W. , Harter Patrick N. , Hattingen Elke , Steinbach Joachim P. , Rödel Claus , Rieger Johannes
Published: September 2021

Purpose

The prospective, randomized ERGO2 trial investigated the effect of calorie-restricted ketogenic diet and intermittent fasting (KD-IF) on re-irradiation for recurrent brain tumors. The study did not meet its primary endpoint of improved progression-free survival in comparison to standard diet (SD). We here report the results of the quality of life/neurocognition and a detailed analysis of the diet diaries.

Methods

50 patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21–23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples.

Results

The 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. Substantial decreases in leptin and insulin and an increase in uric acid were observed. The SD group, of note, had a lower calorie intake than expected (21 kcal/kg/d instead of 30 kcal/kg/d). Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis.

Conclusion

The strict caloric goals of the ERGO2 trial were tolerated well by patients with recurrent brain cancer. The short diet schedule led to significant metabolic changes with low glucose emerging as a candidate marker of better prognosis. The unexpected lower calorie intake of the control group complicates the interpretation of the results.

Clinicaltrials.gov number: NCT01754350; Registration: 21.12.2012.
High-sensitivity FEES® with the professional image enhancement technology “PIET”
Authors: Kraus Fabian , Hackenberg Stephan , Shehata-Dieler Wafaa , Hagen Rudolf
Published: September 2021

Purpose

Flexible endoscopic evaluation of swallowing (FEES®) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the “professional image enhancement technique” (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES® procedure.

Methods

Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES® was performed and recorded with the two systems during daily routine.

Results

Performing an image enhancement during FEES® is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected.

Conclusions

PIET proved to be non-inferior to NBI during image enhancement FEES®. So far, image enhancement FEES® was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications.
Multiorgan tropism of SARS-CoV-2 lineage B.1.1.7
Authors: Ondruschka Benjamin , Heinrich Fabian , Lindenmeyer Maja , Edler Carolin , Möbius Dustin , Czogalla Jan , Heinemann Axel , Braun Fabian , Aepfelbacher Martin , Lütgehetmann Marc , Huber Tobias B.
Published: September 2021

Due to the development of novel functionalities, distinct SARS-CoV-2 variants such as B.1.1.7 fuel the current pandemic. B.1.1.7 is not only more transmissible, but may also cause an increased mortality compared to previous SARS-CoV-2 variants. Human tissue analysis of the SARS-CoV-2 lineage B.1.1.7 is urgently needed, and we here present autopsy data from 7 consecutive SARS-CoV-2 B.1.1.7 cases. The initial RT-qPCR analyses from nasopharyngeal swabs taken post mortem included typing assays for B.1.1.7. We quantitated SARS-CoV-2 B.1.1.7 viral load in autopsy tissue of multiple organs. Highest levels of SARS-CoV-2 B.1.1.7 copies normalized to ß-globin were detected in the respiratory system (lung and pharynx), followed by the liver and heart. Importantly, SARS-CoV-2 lineage B.1.1.7 was found in 100% of cases in the lungs and in 85.7% in pharynx tissue. Detection also in the kidney and brain highlighting a pronounced organ tropism. Comparison of the given results to a former cohort of SARS-CoV-2 deaths during the first wave in spring 2020 showed resembling organ tropism. Our results indicate that also SARS-CoV-2 B.1.1.7 has a relevant organ tropism beyond the respiratory tract. We speculate that B.1.1.7 spike protein’s affinity to human ACE2 facilitates transmission, organ tropism, and ultimately morbidity and mortality. Further studies and larger cohorts are obligatory to proof this link.