bluuebunny/crossref_metadata_2025 huggingface dataset:
Subperiosteal inferior maxillectomy in mucormycosis patients: case series
Authors: Wadhwa V , Chaudhary D , Meher R , Rathore P K , Kumar V , Soni S , Kumar N
Published: October 2021

Objective

Mucormycosis is a rapidly progressive and fulminant fungal infection mainly affecting the nose and paranasal sinuses and often requiring aggressive surgical debridement, which commonly includes inferior maxillectomy. Conventional inferior maxillectomy involves removal of the bony hard palate and its mucoperiosteum. This can lead to formation of an oroantral fistula and thereby increase the morbidity in these patients leading to prolonged rehabilitation. Subperiosteal inferior maxillectomy involves sparing of the uninvolved mucoperiosteum of the hard palate. This flap is used for closure of the oroantral fistula, which preserves the functional capabilities of the patient, such as speech, mastication and deglutination.

Method

This case series describes the experience of using the technique of mucosa-preserving subperiosteal inferior maxillectomy in five patients with mucormycosis.

Results

With the technique used in this study, complete oronasal separation was achieved in all six patients. The overall surgery time was also decreased when compared with free tissue transfer. Patients also did not have to bear the weight of prosthesis.

Conclusion

Mucoperiosteal palatal flap-preserving subperiosteal inferior maxillectomy is an excellent approach for all patients with mucormycosis and healthy palatal mucosa.
Structuring complexity? A systemic perspective on the implementation of a disease management programme for type II diabetes care in Denmark
Authors: Vrangbæk Karsten
Published: October 2021

Chronic diseases are major causes of death and reduction in the quality of life worldwide, and their prevalence is expected to rise due to changing demographics. Disease management programmes (DMPs) have been presented as a policy response to challenges of care coordination for such chronic diseases. This paper investigates the implementation of DMPs in a National Health Care system in the Nordic region using type II diabetes as an example. DMPs are detailed descriptions of the sequence and responsibilities for diagnostic, treatment, rehabilitation and prevention procedures. The paper applies a systemic implementation perspective to provide detailed analysis of implementation progress, issues and concerns. The implementation analysis shows that the framework of DMP has facilitated the development of new practices and attention to the roles that each of the stakeholders are playing within the service delivery. Many new initiatives contribute to improved coordination and overall management of the Type 2 diabetes (T2DB) population. Yet, there are also several cross-cutting challenges that are affecting the implementation process.
Guilt by association: Restricting humanitarian assistance in the name of counterterrorism
Authors: Pozo Marín Alejandro , Ben Ali Rabia
Published: October 2021

In certain contexts associated with counterterrorism, some governments and military forces have stigmatized civilians, not because of the acts they perform but rather from loose associations with groups perceived as “terrorists”, based on geographical proximity or common social, ethnic and religious backgrounds. Access to humanitarian assistance has been affected by this stigmatization, and in specific geographical areas it has been blocked, restricted, made conditional or undermined. This article draws on recent literature and examples to argue that certain counterterrorism frameworks and practices have inhibited the impartial delivery of aid to all affected populations.
Impact of the 2019/2020 Australian Megafires on Air Quality and Health
Authors: Graham Ailish M. , Pringle Kirsty J. , Pope Richard J. , Arnold Stephen R. , Conibear Luke A. , Burns Helen , Rigby Richard , Borchers‐Arriagada Nicolás , Butt Edward W. , Kiely Laura , Reddington Carly , Spracklen Dominick V. , Woodhouse Matthew T. , Knote Christoph , McQuaid James B.
Published: October 2021

The Australian 2019/2020 bushfires were unprecedented in their extent and intensity, causing a catastrophic loss of habitat, human and animal life across eastern‐Australia. We use a regional air quality model to assess the impact of the bushfires on particulate matter with a diameter less than 2.5 μm (PM2.5) concentrations and the associated health impact from short‐term population exposure to bushfire PM2.5. The mean population Air Quality Index (AQI) exposure between September and February in the fires and no fires simulations indicates an additional ∼437,000 people were exposed to “Poor” or worse AQI levels due to the fires. The AQ impact was concentrated in the cities of Sydney, Newcastle‐Maitland, Canberra‐Queanbeyan and Melbourne. Between October and February 171 (95% CI: 66–291) deaths were brought forward due to short‐term exposure to bushfire PM2.5. The health burden was largest in New South Wales (NSW) (109 (95% CI: 41–176) deaths brought forward), Queensland (15 (95% CI: 5–24)), and Victoria (35 (95% CI: 13–56)). This represents 38%, 13% and 30% of the total deaths brought forward by short‐term exposure to all PM2.5. At a city‐level 65 (95% CI: 24–105), 23 (95% CI: 9–38) and 9 (95% CI: 4–14) deaths were brought forward from short‐term exposure to bushfire PM2.5, accounting for 36%, 20%, and 64% of the total deaths brought forward from all PM2.5. Thus, the bushfires caused substantial AQ and health impacts across eastern‐Australia. Climate change is projected to increase bushfire risk, therefore future fire management policies should consider this.
Behavioral aspects and neurobiological properties underlying medical cannabis treatment in Shank3 mouse model of autism spectrum disorder
Authors: Poleg Shani , Kourieh Emad , Ruban Angela , Shapira Guy , Shomron Noam , Barak Boaz , Offen Daniel
Published: October 2021

Autism spectrum disorder (ASD) is a neurodevelopmental disease with a wide spectrum of manifestation. The core symptoms of ASD are persistent deficits in social communication, and restricted and repetitive patterns of behavior, interests, or activities. These are often accompanied by intellectual disabilities. At present, there is no designated effective treatment for the core symptoms and co-morbidities of ASD. Recently, interest is rising in medical cannabis as a treatment for ASD, with promising clinical data. However, there is a notable absence of basic pre-clinical research in this field. In this study, we investigate the behavioral and biochemical effects of long-term oral treatment with CBD-enriched medical cannabis oil in a human mutation-basedShank3mouse model of ASD. Our findings show that this treatment alleviates anxiety and decreases repetitive grooming behavior by over 70% in treated mutant mice compared to non-treated mutant mice. Furthermore, we were able to uncover the involvement of CB1 receptor (CB1R) signaling in the Avidekel oil mechanism, alongside a mitigation of cerebrospinal fluid (CSF) glutamate concentrations. Subsequently, RNA sequencing (RNA seq) of cerebellar brain samples revealed changes in mRNA expression of several neurotransmission-related genes post-treatment. Finally, our results question the relevancy of CBD enrichment of medical cannabis for treating the core symptoms of ASD, and emphasize the importance of the THC component for alleviating deficits in repetitive and social behaviors in ASD.
LTBP4 affects renal fibrosis by influencing angiogenesis and altering mitochondrial structure
Authors: Su Chi-Ting , Jao Tzu-Ming , Urban Zsolt , Huang Yue-Jhu , See Daniel H. W. , Tsai Yao-Chou , Lin Wei-Chou , Huang Jenq-Wen
Published: October 2021

Transforming growth factor beta (TGFβ) signalling regulates extracellular matrix accumulation known to be essential for the pathogenesis of renal fibrosis; latent transforming growth factor beta binding protein 4 (LTBP4) is an important regulator of TGFβ activity. To date, the regulation of LTBP4 in renal fibrosis remains unknown. Herein, we report that LTBP4 is upregulated in patients with chronic kidney disease and fibrotic mice kidneys created by unilateral ureteral obstruction (UUO). Mice lacking the short LTBP4 isoform (Ltbp4S−/−) exhibited aggravated tubular interstitial fibrosis (TIF) after UUO, indicating that LTBP4 potentially protects against TIF. Transcriptomic analysis of human proximal tubule cells overexpressing LTBP4 revealed that LTBP4 influences angiogenic pathways; moreover, these cells preserved better mitochondrial respiratory functions and expressed higher vascular endothelial growth factor A (VEGFA) compared to wild-type cells under hypoxia. Results of the tube formation assay revealed that additional LTBP4 in human umbilical vein endothelial cell supernatant stimulates angiogenesis with upregulated vascular endothelial growth factor receptors (VEGFRs). In vivo, aberrant angiogenesis, abnormal mitochondrial morphology and enhanced oxidative stress were observed in Ltbp4S−/− mice after UUO. These results reveal novel molecular functions of LTBP4 stimulating angiogenesis and potentially impacting mitochondrial structure and function. Collectively, our findings indicate that LTBP4 protects against disease progression and may be of therapeutic use in renal fibrosis.
PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway
Authors: Zhang Fei , Yan Yanglin , Peng Wuxun , Wang Lei , Wang Tao , Xie Zhihong , Luo Hong , Zhang Jian , Dong Wentao
Published: October 2021

Novel therapies for the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH) are urgently needed in orthopedics. Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides new strategies for treating this condition at the early stage. However, stress-induced apoptosis of BMSCs transplanted into the femoral head necrotic area limits the efficacy of BMSC transplantation. Inhibiting BMSC apoptosis is key to improving the efficacy of this procedure. In our previous studies, we confirmed that Parkinson disease protein 7 (PARK7) is active in antioxidant defense and can clear reactive oxygen species (ROS), protect the mitochondria, and impart resistance to stress-induced apoptosis in BMSCs. In this study, we investigated the mechanism driving this PARK7-mediated resistance to apoptosis in BMSCs. Our results indicate that PARK7 promoted the disintegration of nuclear factor (erythroid-derived 2)–like 2 (Nrf2)/Kelch-like echinacoside–associated protein 1 (Keap1) complex. The free Nrf2 then entered the nucleus and activated the genetic expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), and other antioxidant enzymes that clear excessive ROS, thereby protecting BMSCs from stress-induced apoptosis. To further explore whether PARK7-mediated resistance to stress-induced apoptosis could improve the efficacy of BMSC transplantation in early-stage SONFH, we transplanted BMSCs-overexpressing PARK7 into rats with early-stage SONFH. We then evaluated the survival of transplanted BMSCs and bone regeneration in the femoral head necrotic area of these rats. The results indicated that PARK7 promoted the survival of BMSCs in the osteonecrotic area and improved the transplantation efficacy of BMSCs on early-stage SONFH. This study provides new ideas and methods for resisting the stress-induced apoptosis of BMSCs and improving the transplantation effect of BMSCs on early-stage SONFH.
m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
Authors: Liu Hongjiang , Qin Shan , Liu Changqi , Jiang Le , Li Chen , Yang Jiankai , Zhang Shunyao , Yan Zhongjie , Liu Xiaopeng , Yang Jipeng , Sun Xiaofeng
Published: October 2021

N6-methyladenosine (m6A) has been identified to exert critical roles in human cancer; however, the regulation of m6A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m6A profile in the GBM. Moreover, the m6A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m6A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m6A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.
Magneto-optical spectroscopy on Weyl nodes for anomalous and topological Hall effects in chiral MnGe
Authors: Hayashi Y. , Okamura Y. , Kanazawa N. , Yu T. , Koretsune T. , Arita R. , Tsukazaki A. , Ichikawa M. , Kawasaki M. , Tokura Y. , Takahashi Y.
Published: October 2021

Physics of Weyl electrons has been attracting considerable interests and further accelerated by recent discoveries of giant anomalous Hall effect (AHE) and topological Hall effect (THE) in several magnetic systems including non-coplanar magnets with spin chirality or small-size skyrmions. These AHEs/THEs are often attributed to the intense Berry curvature generated around the Weyl nodes accompanied by band anti-crossings, yet the direct experimental evidence still remains elusive. Here, we demonstrate an essential role of the band anti-crossing for the giant AHE and THE in MnGe thin film by using the terahertz magneto-optical spectroscopy. The low-energy resonance structures around ~ 1.2 meV in the optical Hall conductivity show the enhanced AHE and THE, indicating the emergence of at least two distinct anti-crossings near the Fermi level. The theoretical analysis demonstrates that the competition of these resonances with opposite signs is a cause of the strong temperature and magnetic-field dependences of observed DC Hall conductivity. These results lead to the comprehensive understanding of the interplay among the transport phenomena, optical responses and electronic/spin structures.
Primary visual cortex straightens natural video trajectories
Authors: Hénaff Olivier J. , Bai Yoon , Charlton Julie A. , Nauhaus Ian , Simoncelli Eero P. , Goris Robbe L. T.
Published: October 2021

Many sensory-driven behaviors rely on predictions about future states of the environment. Visual input typically evolves along complex temporal trajectories that are difficult to extrapolate. We test the hypothesis that spatial processing mechanisms in the early visual system facilitate prediction by constructing neural representations that follow straighter temporal trajectories. We recorded V1 population activity in anesthetized macaques while presenting static frames taken from brief video clips, and developed a procedure to measure the curvature of the associated neural population trajectory. We found that V1 populations straighten naturally occurring image sequences, but entangle artificial sequences that contain unnatural temporal transformations. We show that these effects arise in part from computational mechanisms that underlie the stimulus selectivity of V1 cells. Together, our findings reveal that the early visual system uses a set of specialized computations to build representations that can support prediction in the natural environment.
Self-selective formation of ordered 1D and 2D GaBi structures on wurtzite GaAs nanowire surfaces
Authors: Liu Yi , Knutsson Johan V. , Wilson Nathaniel , Young Elliot , Lehmann Sebastian , Dick Kimberly A. , Palmstrøm Chris J. , Mikkelsen Anders , Timm Rainer
Published: October 2021

Scaling down material synthesis to crystalline structures only few atoms in size and precisely positioned in device configurations remains highly challenging, but is crucial for new applications e.g., in quantum computing. We propose to use the sidewall facets of larger III–V semiconductor nanowires (NWs), with controllable axial stacking of different crystal phases, as templates for site-selective growth of ordered few atoms 1D and 2D structures. We demonstrate this concept of self-selective growth by Bi deposition and incorporation into the surfaces of GaAs NWs to form GaBi structures. Using low temperature scanning tunneling microscopy (STM), we observe the crystal structure dependent self-selective growth process, where ordered 1D GaBi atomic chains and 2D islands are alloyed into surfaces of the wurtzite (Wz) $$\{11{\bar{2}}0\}$$

{

11

2

¯

0

}

crystal facets. The formation and lateral extension of these surface structures are controlled by the crystal structure and surface morphology uniquely found in NWs. This allows versatile high precision design of structures with predicted novel topological nature, by using the ability of NW heterostructure variations over orders of magnitude in dimensions with atomic-scale precision as well as controllably positioning in larger device structures.
Genome-wide detection of cytosine methylations in plant from Nanopore data using deep learning
Authors: Ni Peng , Huang Neng , Nie Fan , Zhang Jun , Zhang Zhi , Wu Bo , Bai Lu , Liu Wende , Xiao Chuan-Le , Luo Feng , Wang Jianxin
Published: October 2021

In plants, cytosine DNA methylations (5mCs) can happen in three sequence contexts as CpG, CHG, and CHH (where H = A, C, or T), which play different roles in the regulation of biological processes. Although long Nanopore reads are advantageous in the detection of 5mCs comparing to short-read bisulfite sequencing, existing methods can only detect 5mCs in the CpG context, which limits their application in plants. Here, we develop DeepSignal-plant, a deep learning tool to detect genome-wide 5mCs of all three contexts in plants from Nanopore reads. We sequence Arabidopsis thaliana and Oryza sativa using both Nanopore and bisulfite sequencing. We develop a denoising process for training models, which enables DeepSignal-plant to achieve high correlations with bisulfite sequencing for 5mC detection in all three contexts. Furthermore, DeepSignal-plant can profile more 5mC sites, which will help to provide a more complete understanding of epigenetic mechanisms of different biological processes.
Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors
Authors: Kinoshita Mitsuhiro , Yamada Atsushi , Sasa Kiyohito , Ikezaki Kaori , Shirota Tatsuo , Kamijo Ryutaro
Published: October 2021

Nephronectin (Npnt) is an extracellular matrix protein and ligand of integrin α8β1 known to promote differentiation of osteoblasts. A search for factors that regulate Npnt gene expression in osteoblasts revealed that phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), had a strong effect to suppress that expression. Research was then conducted to elucidate the signaling pathway responsible for regulation of Npnt gene expression by PMA in osteoblasts. Treatment of MC3T3-E1 cells with PMA suppressed cell differentiation and Npnt gene expression. Effects were noted at a low concentration of PMA, and were time- and dose-dependent. Furthermore, treatment with the PKC signal inhibitor Gö6983 inhibited down-regulation of Npnt expression, while transfection with small interfering RNA (siRNA) of PKCα, c-Jun, and c-Fos suppressed that down-regulation. The present results suggest regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway.
Effect of nocturnal oxygen therapy on exercise performance of COPD patients at 2048 m: data from a randomized clinical trial
Authors: Gutweniger Sophia , Latshang Tsogyal D. , Aeschbacher Sayaka S. , Huber Fabienne , Flueck Deborah , Lichtblau Mona , Ulrich Stefanie , Hasler Elisabeth D. , Scheiwiller Philipp M. , Ulrich Silvia , Bloch Konrad E. , Furian Michael
Published: October 2021

This trial evaluates whether nocturnal oxygen therapy (NOT) during a stay at 2048 m improves altitude-induced exercise intolerance in lowlanders with chronic obstructive pulmonary disease (COPD). 32 lowlanders with moderate to severe COPD, mean ± SD forced expiratory volume in the first second of expiration (FEV1) 54 ± 13% predicted, stayed for 2 days at 2048 m twice, once with NOT, once with placebo according to a randomized, crossover trial with a 2-week washout period at < 800 m in-between. Semi-supine, constant-load cycle exercise to exhaustion at 60% of maximal work-rate was performed at 490 m and after the first night at 2048 m. Endurance time was the primary outcome. Additional outcomes were cerebral tissue oxygenation (CTO), arterial blood gases and breath-by-breath measurements (http://www.ClinicalTrials.gov NCT02150590). Mean ± SE endurance time at 490 m was 602 ± 65 s, at 2048 m after placebo 345 ± 62 s and at 2048 m after NOT 293 ± 60 s, respectively (P < 0.001 vs. 490 m). Mean difference (95%CI) NOT versus placebo was − 52 s (− 174 to 70), P = 0.401. End-exercise pulse oximetry (SpO2), CTO and minute ventilation ($${\dot{\text{V}}}_{{\text{E}}}$$

V
˙

E

) at 490 m were: SpO2 92 ± 1%, CTO 65 ± 1%, $${\dot{\text{V}}}_{{\text{E}}}$$

V
˙

E

37.7 ± 2.0 L/min; at 2048 m with placebo: SpO2 85 ± 1%, CTO 61 ± 1%, $${\dot{\text{V}}}_{{\text{E}}}$$

V
˙

E

 40.6 ± 2.0 L/min and with NOT: SpO2 84 ± 1%; CTO 61 ± 1%; $${\dot{\text{V}}}_{{\text{E}}}$$

V
˙

E

 40.6 ± 2.0 L/min (P < 0.05, SpO2, CTO at 2048 m with placebo vs. 490 m; P = NS, NOT vs. placebo). Altitude-related hypoxemia and cerebral hypoxia impaired exercise endurance in patients with moderate to severe COPD and were not prevented by NOT.
Changes in "natural antibiotic" metabolite composition during tetraploid wheat domestication
Authors: Ben-Abu Yuval , Itsko Mark
Published: October 2021

Gramineous plants protect their seeds from a variety of biotic stresses by producing toxic and deterrent secondary metabolites such as benzoxazinoids. It is unclear how the composition and abundance of these natural toxins has changed over the course of crop-plant domestication. To address this uncertainty, we characterized differences in metabolic levels of benzoxazinoids and their derivatives, between four lines of tetraploid wheat: wild emmer wheat (WEW), the direct progenitor of modern wheat; non-fragile domesticated emmer wheat (DEW), which was first domesticated about 11,000 years ago; the subsequently developed non-fragile and free-threshing durum landraces (LD); and modern durum (MD) varieties. Three-dimensional principal component analysis of mass spectrometry data of wheat metabolites showed with high resolution clear differences between metabolic profiles of WEW, DEW, and durum (LD + MD) and similarity in the metabolic profiles of the two durum lines (LD and MD) that is coherent with the phylogenetic relationship between the corresponding wheat lines. Moreover, our results indicated that some secondary metabolites involved in plant defense mechanisms became significantly more abundant during wheat domestication, while other defensive metabolites decreased or were lost. These metabolic changes reflect the beneficial or detrimental roles the corresponding metabolites might play during the domestication of three taxonomic subspecies of tetraploid wheat (Triticum turgidum).
Estimates of country level temperature-related mortality damage functions
Authors: Bressler R. Daniel , Moore Frances C. , Rennert Kevin , Anthoff David
Published: October 2021

Many studies project that climate change is expected to cause a significant number of excess deaths. Yet, in integrated assessment models that determine the social cost of carbon (SCC), human mortality impacts do not reflect the latest scientific understanding. We address this issue by estimating country-level mortality damage functions for temperature-related mortality with global spatial coverage. We rely on projections from the most comprehensive published study in the epidemiology literature of future temperature impacts on mortality (Gasparrini et al. in Lancet Planet Health 1:e360–e367, 2017), which estimated changes in heat- and cold-related mortality for 23 countries over the twenty-first century. We model variation in these mortality projections as a function of baseline climate, future temperature change, and income variables and then project future changes in mortality for every country. We find significant spatial heterogeneity in projected mortality impacts, with hotter and poorer places more adversely affected than colder and richer places. In the absence of income-based adaptation, the global mortality rate in 2080–2099 is expected to increase by 1.8% [95% CI 0.8–2.8%] under a lower-emissions RCP 4.5 scenario and by 6.2% [95% CI 2.5–10.0%] in the very high-emissions RCP 8.5 scenario relative to 2001–2020. When the reduced sensitivity to heat associated with rising incomes, such as greater ability to invest in air conditioning, is accounted for, the expected end-of-century increase in the global mortality rate is 1.1% [95% CI 0.4–1.9%] in RCP 4.5 and 4.2% [95% CI 1.8–6.7%] in RCP 8.5. In addition, we compare recent estimates of climate-change induced excess mortality from diarrheal disease, malaria and dengue fever in 2030 and 2050 with current estimates used in SCC calculations and show these are likely underestimated in current SCC estimates, but are also small compared to more direct temperature effects.
Genetic propensity for obesity, socioeconomic position, and trajectories of body mass index in older adults
Authors: Tommerup Kristiane , Ajnakina Olesya , Steptoe Andrew
Published: October 2021

Identifying how socioeconomic positioning and genetic factors interact in the development of obesity is imperative for population-level obesity prevention strategies. The current study investigated whether social positioning, either independently or through interaction with a polygenic score for Body Mass Index (BMI-PGS), influences BMI trajectories across older adulthood. Data were analysed from 7,183 individuals from the English Longitudinal Study of Aging (ELSA). Interactions between the BMI-PGS and; lower educational attainment, self-perceived social status (SSS), and income, on BMI trajectories over 12 years across older adulthood were investigated through linear mixed effects models. Lower educational attainment, SSS and income were each associated with a higher baseline BMI for women, but not for men. There were interaction effects between BMI-PGS and social positioning such that men aged > 65 with a lower educational attainment (β = 0.62; 95%CI 0.00 – 1.24, p < 0.05), men aged ≤ 65 of a lower income (β = − 0.72, 95%CI − 1.21 - − 0.23, p < 0.01) and women aged ≤ 65 of lower SSS (β = − 1.41; 95%CI − 2.46 – 0.36, p < 0.01) showed stronger associations between the BMI-PGS and baseline BMI. There were few associations between markers of socioeconomic position and rate of change in BMI over the follow-up period. In sum, lower socioeconomic positioning showed adverse associations with women’s BMI in older adulthood. Moreover, the expression of the BMI-PGS, or extent to which it translates to a higher BMI, was subtly influenced by socioeconomic standing in both women and in men.
Functional and structural analysis of catabolite control protein C that responds to citrate
Authors: Liu Wei , Chen Jinli , Jin Liming , Liu Zi-Yong , Lu Ming , Jiang Ge , Yang Qing , Quan Chunshan , Nam Ki Hyun , Xu Yongbin
Published: October 2021

Catabolite control protein C (CcpC) belongs to the LysR-type transcriptional regulator (LTTR) family, which regulates the transcription of genes encoding the tricarboxylic acid branch enzymes of the TCA cycle by responding to a pathway-specific metabolite, citrate. The biological function of CcpC has been characterized several times, but the structural basis for the molecular function of CcpC remains elusive. Here, we report the characterization of a full-length CcpC from Bacillus amyloliquefaciens (BaCcpC-FL) and a crystal structure of the C-terminal inducer-binding domain (IBD) complexed with citrate. BaCcpC required both dyad symmetric regions I and II to recognize the citB promoter, and the presence of citrate reduced citB promoter binding. The crystal structure of CcpC-IBD shows two subdomains, IBD-I and IBD-II, and a citrate molecule buried between them. Ile100, two arginines (Arg147 and Arg260), and three serines (Ser129, Ser189, and Ser191) exhibit strong hydrogen-bond interactions with citrate molecules. A structural comparison of BaCcpC-IBD with its homologues showed that they share the same tail-to-tail dimer alignment, but the dimeric interface and the rotation between these molecules exhibit significant differences. Taken together, our results provide a framework for understanding the mechanism underlying the functional divergence of the CcpC protein.
Collagen orientation probed by polarized Raman spectra can serve as differential diagnosis indicator between different grades of meniscus degeneration
Authors: Prokopi Nikoletta , Andrikopoulos Konstantinos S. , Beobide Amaia Soto , Voyiatzis George A. , Papachristou Dionysios J.
Published: October 2021

The purpose of the present study was to analyze normal and degenerated menisci with Raman methodology on thin sections of formalin fixed paraffin embedding tissues and to correlate the Raman findings with the grade of meniscus degeneration. Menisci (n = 27) were removed from human knee joints after total knee replacement or meniscectomy. Following routine histopathological analysis to determine the grade of meniscal lesions obtained from healthy and degenerated formaline fixed paraffin embedded (FFPE) meniscal sections, Raman polarization approach was applied to evaluate the orientation of collagen fibrils in different levels of the same 5 μm thick FFPE meniscal tissue sections, used for histopathological assessment. We collected Raman spectra in two different polarization geometries, v-HH and v-VV, and calculated the mean value of the v-HH/v-VV intensity ratio of two Raman bands, sensitive and non-sensitive to the molecular orientation. The collagen specific amide I band at 1665 cm−1, has the higher sensitivity dependence on the Raman polarization. The mean values of ratio v-HH/v-VV of the 1665 cm−1peak intensity was significantly higher in healthy, mean ± SD: 2.56 ± 0.46, compared to degenerated menisci, mean ± SD: 1.85 ± 0.42 (p = 0.0014). The mean values of v-HH/v-VV intensity ratio were 2.18 and 1.50 for low and high degenerated menisci, respectively (p < 0.0001). The difference of peak intensities in the two laser polarizations is decreased in the degenerated meniscus; this difference is diminishing as the degeneration increases. The v-HH/v-VV ratio was also of significant difference in low as compared to control and high grade meniscus lesions (p = 0.036 and p < 0.0001, respectively) offering valuable information for the approach of its biology and function. In the present study we showed that the 5 μm thick sections can be used for Raman analysis of meniscal tissue with great reliability, in terms of sensitivity, specificity, false-negative and false-positive results. Our data introduce the interesting hypothesis that compact portable Raman microscopy on tissue sections can be used intra-operatively for fast diagnosis and hence, accurate procedure design in the operating room.
Deep learning on fundus images detects glaucoma beyond the optic disc
Authors: Hemelings Ruben , Elen Bart , Barbosa-Breda João , Blaschko Matthew B. , De Boever Patrick , Stalmans Ingeborg
Published: October 2021

Although unprecedented sensitivity and specificity values are reported, recent glaucoma detection deep learning models lack in decision transparency. Here, we propose a methodology that advances explainable deep learning in the field of glaucoma detection and vertical cup-disc ratio (VCDR), an important risk factor. We trained and evaluated deep learning models using fundus images that underwent a certain cropping policy. We defined the crop radius as a percentage of image size, centered on the optic nerve head (ONH), with an equidistant spaced range from 10–60% (ONH crop policy). The inverse of the cropping mask was also applied (periphery crop policy). Trained models using original images resulted in an area under the curve (AUC) of 0.94 [95% CI 0.92–0.96] for glaucoma detection, and a coefficient of determination (R2) equal to 77% [95% CI 0.77–0.79] for VCDR estimation. Models that were trained on images with absence of the ONH are still able to obtain significant performance (0.88 [95% CI 0.85–0.90] AUC for glaucoma detection and 37% [95% CI 0.35–0.40] R2 score for VCDR estimation in the most extreme setup of 60% ONH crop). Our findings provide the first irrefutable evidence that deep learning can detect glaucoma from fundus image regions outside the ONH.
Oral administration of E-type prostanoid (EP) 1 receptor antagonist suppresses carcinogenesis and development of prostate cancer via upregulation of apoptosis in an animal model
Authors: Masato Masahito , Miyata Yasuyoshi , Kurata Hiroki , Ito Hidenori , Mitsunari Kensuke , Asai Akihiro , Nakamura Yuichiro , Araki Kyohei , Mukae Yuta , Matsuda Tsuyoshi , Harada Junki , Matsuo Tomohiro , Ohba Kojiro , Sakai Hideki
Published: October 2021

Prostaglandin E2 plays an important role in carcinogenesis and malignant potential of prostate cancer (PC) cells by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of the EP receptor antagonist are unclear. In this study, we used a mouse model of PC. The mice were provided standard feed (control) or feed containing the EP1 receptor antagonist and were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using a cleaved caspase-3 assay. The incidence of cancer in the experimental group was significantly lower than that in the control group at 15, 30, and 52 weeks of age. The percentage of poorly differentiated PC cells was significantly lower in the experimental group than in the control group at 30 and 52 weeks of age. The percentage of apoptotic cells in the experimental group was significantly higher than that in the control group at 15, 30, and 52 weeks of age. These findings indicate that feeding with the addition of EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that the EP1 receptor antagonist may be a novel chemopreventive agent for PC.
Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression
Authors: Siafarikas Nikias , Kirsebom Bjørn-Eivind , Srivastava Deepak P. , Eriksson Cecilia M. , Auning Eirik , Hessen Erik , Selbaek Geir , Blennow Kaj , Aarsland Dag , Fladby Tormod
Published: October 2021

To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-β 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NC = 41; predementia AD = 66 and LLD = 38). LLD comprised LLD AD (n = 16), LLD NoAD (n = 19), LLD with non-AD typical changes (n = 3, excluded). LLD AD (pADJ < 0.05) and predementia AD (pADJ < 0.0001) showed significantly higher Ng than NC. BACE1 and Ng/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (pADJ < 0.001), BACE1 (pADJ < 0.05) and Ng/BACE1 ratio (pADJ < 0.01). All groups had significantly lower Aβ 42/40 ratio than NC (predementia AD and LLD AD, p < 0.0001; LLD NoAD, p < 0.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as “predementia AD with depression”.
Quantifying SARS-CoV-2 nucleocapsid antigen in oropharyngeal swabs using single molecule array technology
Authors: Olsen Dorte Aa. , Brasen Claus L. , Kahns Søren , Madsen Jeppe B. , Kierkegaard Helene , Christensen Henry , Jensen Anders , Sydenham Thomas V. , Møller Jens K. , Madsen Jonna S. , Brandslund Ivan
Published: October 2021

This study aimed to develop a highly sensitive SARS-CoV-2 nucleocapsid antigen assay using the single molecule array (Simoa) technology and compare it with real time RT-PCR as used in routine clinical practice with the ambition to achieve a comparative technical and clinical sensitivity. Samples were available from 148 SARS-CoV-2 real time RT-PCR positive and 73 SARS-CoV-2 real time RT-PCR negative oropharyngeal swabs. For determination of technical sensitivity SARS-CoV-2 virus culture material was used. The samples were treated with lysis buffer and analyzed using both an in-house and a pre-commercial SARS-CoV-2 nucleocapsid antigen assay on Simoa. Both nucleocapsid antigen assays have a technical sensitivity corresponding to around 100 SARS-CoV-2 RNA molecules/mL. Using a cut-off at 0.1 pg/mL the pre-commercial SARS-CoV-2 nucleocapsid antigen assay had a sensitivity of 96% (95% CI 91.4–98.5%) and specificity of 100% (95% CI 95.1–100%). In comparison the in-house nucleocapsid antigen assay had sensitivity of 95% (95% CI 89.3–98.1%) and a specificity of 100% (95% CI 95.1–100%) using a cut-off at 0.01 pg/mL. The two SARS-CoV-2 nucleocapsid antigen assays correlated with r = 0.91 (P < 0.0001). The in-house and the pre-commercial SARS-CoV-2 nucleocapsid antigen assay demonstrated technical and clinical sensitivity comparable to real-time RT-PCR methods for identifying SARS-CoV-2 infected patients and thus can be used clinically as well as serve as a reference method for antigen Point of Care Testing.
The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response
Authors: Salgado Ranieri Coelho , Fonseca Dennyson Leandro M. , Marques Alexandre H. C. , da Silva Napoleao Sarah Maria , França Tábata Takahashi , Akashi Karen Tiemi , de Souza Prado Caroline Aliane , Baiocchi Gabriela Crispim , Plaça Desirée Rodrigues , Jansen-Marques Gabriel , Filgueiras Igor Salerno , De Vito Roberta , Freire Paula Paccielli , de Miranda Gustavo Cabral , Camara Niels Olsen Saraiva , Calich Vera Lúcia Garcia , Ochs Hans D. , Schimke Lena F. , Jurisica Igor , Condino-Neto Antonio , Cabral-Marques Otavio
Published: October 2021

Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses toCandidaspp.through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to differentCandidaspecies (C. albicans,C. auris,C. glabrata,C. parapsilosis, andC. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candidaimmune response, providing putative molecular pathways for therapeutic intervention.
Phosphorus availability and leaching losses in annual and perennial cropping systems in an upper US Midwest landscape
Authors: Hussain Mir Zaman , Hamilton Stephen K. , Robertson G. Philip , Basso Bruno
Published: October 2021

Excessive phosphorus (P) applications to croplands can contribute to eutrophication of surface waters through surface runoff and subsurface (leaching) losses. We analyzed leaching losses of total dissolved P (TDP) from no-till corn, hybrid poplar (Populus nigra X P. maximowiczii), switchgrass (Panicum virgatum), miscanthus (Miscanthus giganteus), native grasses, and restored prairie, all planted in 2008 on former cropland in Michigan, USA. All crops except corn (13 kg P ha−1 year−1) were grown without P fertilization. Biomass was harvested at the end of each growing season except for poplar. Soil water at 1.2 m depth was sampled weekly to biweekly for TDP determination during March–November 2009–2016 using tension lysimeters. Soil test P (0–25 cm depth) was measured every autumn. Soil water TDP concentrations were usually below levels where eutrophication of surface waters is frequently observed (> 0.02 mg L−1) but often higher than in deep groundwater or nearby streams and lakes. Rates of P leaching, estimated from measured concentrations and modeled drainage, did not differ statistically among cropping systems across years; 7-year cropping system means ranged from 0.035 to 0.072 kg P ha−1 year−1 with large interannual variation. Leached P was positively related to STP, which decreased over the 7 years in all systems. These results indicate that both P-fertilized and unfertilized cropping systems may leach legacy P from past cropland management.
Contamination of multi dose eyedrops in the intra and perioperative context
Authors: Daehn Tristan , Schneider Andreas , Knobloch Johannes , Hellwinkel Olaf J. C. , Spitzer Martin Stephan , Kromer Robert
Published: October 2021

In this study, we examined the rate of contamination of multi-dose ophthalmic solutions in the operating theatre and the underlying risk for infection by examining the microbiological load on the tips of the dispenser bottles. A total of 245 samples of eye drop bottles were collected and analysed between June 2018 and January 2019. All were collected in the operating theatre of the University Eye Hospital Hamburg-Eppendorf. Contamination of the dropper tip occurred in 2% of the samples. Although the prevalence of contamination was low, the results of this study reveal the possibility of contamination of multi-dose eyedrops even when used by health care professionals in the controlled environment of an operating theatre. Following these results, we recommend the use of single-dose eyedrops in the pre- and intraoperative context.
Influence of the Atlantic meridional overturning circulation on the U.S. extreme cold weather
Authors: Yin Jianjun , Zhao Ming
Published: October 2021

Due to its large northward heat transport, the Atlantic meridional overturning circulation influences both weather and climate at the mid-latitude Northern Hemisphere. Here we use a state-of-the-art global weather/climate modeling system with high resolution (GFDL CM4C192) to quantify this influence focusing on the U.S. extreme cold weather during winter. We perform a control simulation and the water-hosing experiment to obtain two climate states with and without a vigorous Atlantic meridional overturning circulation. We find that in the control simulation with an overturning circulation, the U.S. east of the Rockies is a region characterized by intense north-south heat exchange in the atmosphere during winter. Without the northward heat transport by the overturning circulation in the hosing experiment, this channel of atmospheric heat exchange becomes even more active through the Bjerknes compensation mechanism. Over the U.S., extreme cold weather intensifies disproportionately compared with the mean climate response after the shutdown of the overturning circulation. Our results suggest that an active overturning circulation in the present-day climate likely makes the U.S. winter less harsh and extreme.
A nanodrug incorporating siRNA PD-L1 and Birinapant for enhancing tumor immunotherapy
Authors: Gong Tingting , Cai Yujun , Sun Fengze , Chen Jiaxin , Su Zhongzhen , Shuai Xintao , Shan Hong
Published: October 2021

Triple-negative breast cancer (TNBC) is associated with a worse prognosis and higher mortality than other breast cancers, and intensive effort has been made to develop therapies targeting TNBC.
Molecular stabilization of chemically exfoliated bare MnPS3 layers
Authors: Brotons-Alcázar Isaac , Torres-Cavanillas Ramón , Morant-Giner Marc , Cvikl Martin , Mañas-Valero Samuel , Forment-Aliaga Alicia , Coronado Eugenio
Published: October 2021

MnPS3 has been chemically exfoliated in solution as bare flakes and stabilized with capping agents, optimizing stability and catalytic activity.
Expanding the synthetic toolbox to access pristine and rare-earth-doped BaFBr nanocrystals
Authors: Dhanapala B. Dulani , Munasinghe Hashini N. , Dissanayake K. Tauni , Suescun Leopoldo , Rabuffetti Federico A.
Published: October 2021

A colloidal synthetic route to access pristine and rare-earth-doped BaFBr nanocrystals is proposed based on the thermolysis of a metal bromodifluoroacetate precursor.
Battling the known unknowns: a synoptic review of aquatic plastics research from Australia, the United Kingdom and China
Authors: Paterson Harriet L. , Stead Jessica L. , Crutchett Thomas , Hovey Renae K. , Ford Benjamin M. , Speldewinde Peter , Zapata-Restrepo Lina M. , Yanfang Lu , Zhang Xiaoyu , Cundy Andrew B.
Published: October 2021

A synoptic review of aquatic plastics research from Australia, the United Kingdom and China is presented, highlighting (a) key research and management challenges, and (b) a need to converge on standardised methods and bioindicator species to make global comparisons more reliable.
Release of gold (Au), silver (Ag) and cerium dioxide (CeO2) nanoparticles from sewage sludge incineration ash
Authors: Wielinski Jonas , Gogos Alexander , Voegelin Andreas , Müller Christoph R. , Morgenroth Eberhard , Kaegi Ralf
Published: October 2021

Conservative engineered nanoparticles (ENPs) that resist transformation during wastewater treatment and sludge incineration can be released from sewage sludge ash. Transient ENPs that undergo transformation are retained in the sewage sludge ash.
Enhancing charge separation in conjugated microporous polymers for efficient photocatalytic hydrogen evolution
Authors: Qian Zhuangfei , Yan Yajie , Liang Ziqi , Zhuang Xiaodong , Zhang Kai A. I.
Published: October 2021

The benzothiadiazole-based conjugated microporous polymer synthesized on graphene via covalent bonds exhibited suppressed charge separation and enhanced photocatalytic hydrogen evolution efficiency.
Electronic structure of Li+@C60 adsorbed on methyl-ammonium lead iodide perovskite CH3NH3PbI3 surfaces
Authors: Chew Khian-Hooi , Kuwahara Riichi , Ohno Kaoru
Published: October 2021

Jeon et al. [Angew. Chem., 2018, 57, 4607] showed that air stability for over 1000 hours under light illumination can be achieved in CH3NH3PbI3 perovskite solar cells when Li+ is replaced by Li+@C60 in a dopant material used in the p-type donor layer.
Unveiling the role of structure–property correlation and its validation towards engineering the application potential of sol–gel derived mesoporous gamma-alumina
Authors: Sharma Savan Kumar , Das Paromita , Sanfui Barun K.
Published: October 2021

The present study entails a comprehensive investigation on the structure–property-application correlationship aspect of meticulously designed surfactant free glycerol activated sol–gel derived mesoporous γ-alumina powder.
Lossen rearrangement by Rh(iii)-catalyzed C–H activation/annulation of aryl hydroxamates with alkynes: access to quinolone-containing amino acid derivatives
Authors: Petropavlovskikh Dmitry A. , Vorobyeva Daria V. , Godovikov Ivan A. , Nefedov Sergey E. , Filippov Oleg A. , Osipov Sergey N.
Published: October 2021

An efficient access to new CF3-containing 2-quinolones has been developed via Rh(iii)-catalyzed C–H activation/Lossen rearrangement/annulation cascade of N-pivaloyloxy-arylamides with internal alkynes bearing α-CF3-α-amino acid moiety on triple bond.