bluuebunny/crossref_metadata_2025 huggingface dataset:
SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction
Authors: Di Stasi Vincenza , Maseroli Elisa , Rastrelli Giulia , Scavello Irene , Cipriani Sarah , Todisco Tommaso , Marchiani Sara , Sorbi Flavia , Fambrini Massimiliano , Petraglia Felice , Maggi Mario , Vignozzi Linda
Published: March 2021

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.
A Review on Data Preprocessing Techniques Toward Efficient and Reliable Knowledge Discovery From Building Operational Data
Authors: Fan Cheng , Chen Meiling , Wang Xinghua , Wang Jiayuan , Huang Bufu
Published: March 2021

The rapid development in data science and the increasing availability of building operational data have provided great opportunities for developing data-driven solutions for intelligent building energy management. Data preprocessing serves as the foundation for valid data analyses. It is an indispensable step in building operational data analysis considering the intrinsic complexity of building operations and deficiencies in data quality. Data preprocessing refers to a set of techniques for enhancing the quality of the raw data, such as outlier removal and missing value imputation. This article serves as a comprehensive review of data preprocessing techniques for analysing massive building operational data. A wide variety of data preprocessing techniques are summarised in terms of their applications in missing value imputation, outlier detection, data reduction, data scaling, data transformation, and data partitioning. In addition, three state-of-the-art data science techniques are proposed to tackle practical data challenges in the building field, i.e., data augmentation, transfer learning, and semi-supervised learning. In-depth discussions have been presented to describe the pros and cons of existing preprocessing methods, possible directions for future research and potential applications in smart building energy management. The research outcomes are helpful for the development of data-driven research in the building field.
A Multi-Level Framework for Adaptation to Drought Within Temperate Agriculture
Authors: Holman IP , Hess TM , Rey D , Knox JW
Published: March 2021

Droughts affect a range of economically important sectors but their impacts are usually most evident within agriculture. Agricultural impacts are not confined to arid and semi-arid regions, but are increasingly experienced in more temperate and humid regions. A transferable drought management framework is needed to transition from coping to adapting to drought through supporting improved planning and policy decision-making through the supply chain from primary producers to consumers. A combination methodology using a Driver-Pressure-State-Impact-Response (DPSIR) approach, an analysis of weekly agricultural trade publications and semi-structured interviews were used to explore drought impacts and responses, using the 2018 United Kingdom drought as a case study. While most reported responses were on-farm, a diverse range of measures were implemented across institutional scales and through the supply chain, reflecting complex interactions within the food system. However, drought responses were dominated by reactive and crisis-driven actions to cope with, or enhance the recovery from, drought; but which contributed little to increased resilience to future droughts. Our transferable drought management framework shows how improved collaboration and multi-sector engagement across spatial, governance and supply-chain scales to develop human and social capital can enable the transition from coping (short-term and reactive) to adapting (long-term and anticipatory) strategies to increase agricultural resilience to future droughts.
Contrasting Geographic Patterns of Ignition Probability and Burn Severity in the Mojave Desert
Authors: Klinger Rob , Underwood Emma C. , McKinley Randy , Brooks Matthew L.
Published: March 2021

The extent and frequency of fire has increased in many arid systems over the last century, with a large proportion of area in some regions undergoing transitions to novel conditions. Portions of the Mojave Desert in southwestern North America have undergone such transitions, most often from woody to herbaceous-dominated systems. These transitions have often been attributed to the proliferation of invasive annual grasses that promote more frequent fire, but recent evidence indicates that transitions can also occur independent of fire frequency if burn severity is high. In addition, high probability of ignition (i.e., potentially high fire frequency) and high burn severity may not always be geographically related. Therefore, our goals were to: (1) map potential burn severity, fire frequency, and probability of ignition across the Mojave; and, (2) evaluate spatial association among predicted burn severity, fire frequency and probability of ignition. We first mapped perimeters of 250 wildfires > 405 ha that occurred from 1972 to 2010, then extracted data on fire frequency (number of times burned from 1972 to 2010), burn severity (the difference Normalized Burn Ratio), and 15 predictor variables representing physiography, climate, ignition, and vegetation. Maximum entropy was used to predict probability of ignition and Random Forest models were used to predict dNBR and fire frequency. Areas with high burn severity and high ignition probability had opposite spatial trends; areas with high burn severity were predicted to predominantly be in the northwest part of the region whereas areas with high ignition probability were predicted to be in the northeast. The models indicate the existence of a number of spatially structured but temporally dynamic fire regimes throughout the Mojave Desert. Two prevalent and ecologically significant regimes include one with frequent fires of low to moderate severity and another with infrequent fire of high severity. Areas with high fire frequency are currently limited in extent (<1% total area). However, cover of invasive grasses can remain high decades after a burn of high or moderate severity, so grass-fire cycles could develop in areas where there may be expectations of infrequent fire as well as those with relatively high fire frequency.
Ability of Current Phylogenetic Clustering to Detect Speciation History
Authors: Kallimanis Athanasios S. , Lazarina Maria , Tsianou Mariana A. , Andrikou-Charitidou Aristi , Sgardelis Stefanos
Published: March 2021

Phylogenetic diversity aims to quantify the evolutionary relatedness among the species comprising a community, using the phylogenetic tree as the metric of the evolutionary relationships. Could these measures unveil the evolutionary history of an area? For example, in a speciation hotspot (biodiversity cradle), we intuitively expect that the species in the community will be more phylogenetically clustered than randomly expected. Here, using a theoretical simulation model, we estimate the ability of phylogenetic metrics of current diversity to detect speciation history. We found that, in the absence of dispersal, if the incipient species do not coexist in the region of speciation (as expected under allopatric speciation), there was no clear phylogenetic clustering and phylogenetic diversity failed to detect speciation history. But if the incipient species coexisted (sympatric speciation), metrics such as standardized effect size of Faith’s Phylogenetic Diversity (PD) and of Mean Nearest Taxon Distance (MNTD) were able to identify areas of high speciation, while Mean Pairwise Distance (MPD) was a poor indicator. PD systematically outperformed MNTD. Dispersal was a game-changer. It allowed species to expand their range, colonize areas, and led to the coexistence of the incipient species originating from a common ancestor. If speciation gradient was spatially contiguous, dispersal strengthened the associations between phylogenetic clustering and speciation history. In the case of spatially random speciation, dispersal blurred the signal with phylogenetic clustering occurring in areas of low or no speciation. Our results imply that phylogenetic clustering is an indicator of speciation history only under certain conditions.
A Link Between Communities of Protective Endosymbionts and Parasitoids of the Pea Aphid Revealed in Unmanipulated Agricultural Systems
Authors: Leclair Mélanie , Buchard Christelle , Mahéo Frédérique , Simon Jean-Christophe , Outreman Yannick
Published: March 2021

In the last decade, the influence of microbial symbionts on ecological and physiological traits of their hosts has been increasingly recognized. However, most of these effects have been revealed under laboratory conditions, which oversimplifies the complexity of the factors involved in the dynamics of symbiotic associations in nature. The pea aphid, Acyrthosiphon pisum, forms a complex of plant-adapted biotypes, which strongly differ in the prevalence of their facultative endosymbionts. Some of the facultative endosymbionts of A. pisum have been shown to confer protection against natural enemies, among which Hamiltonella defensa is known to protect its host from parasitoid wasps. Here, we tested under natural conditions whether the endosymbiont communities of different A. pisum biotypes had a protective effect on their hosts and whether endosymbiotic associations and parasitoid communities associated with the pea aphid complex were linked. A space-time monitoring of symbiotic associations, parasitoid pressure and parasitoid communities was carried out in three A. pisum biotypes respectively specialized on Medicago sativa (alfalfa), Pisum sativum (pea), and Trifolium sp. (clover) throughout the whole cropping season. While symbiotic associations, and to a lesser extent, parasitoid communities were stable over time and structured mainly by the A. pisum biotypes, the parasitoid pressure strongly varied during the season and differed among the three biotypes. This suggests a limited influence of parasitoid pressure on the dynamics of facultative endosymbionts at a seasonal scale. However, we found a positive correlation between the α and β diversities of the endosymbiont and parasitoid communities, indicating interactions between these two guilds. Also, we revealed a negative correlation between the prevalence of H. defensa and Fukatsuia symbiotica in co-infection and the intensity of parasitoid pressure in the alfalfa biotype, confirming in field conditions the protective effect of this symbiotic combination.
Rational Design of a Novel Hawkmoth Pollinator Interaction in Mimulus Section Erythranthe
Authors: Byers Kelsey J. R. P. , Bradshaw H. D.
Published: March 2021

Diversification of theca. 275,000 extant flowering plant species has been driven in large part by coevolution with animal pollinators. A recurring pattern of pollinator shifts from hummingbird to hawkmoth pollination has characterized plant speciation in many western North American plant taxa, but in the genusMimulus(monkeyflowers) sectionErythranthethe evolution of hawkmoth pollination from hummingbird-pollinated ancestors has not occurred. We manipulated two flower color loci and tested the attractiveness of the resulting four color phenotypes (red, yellow, pink, and white) to naïve hawkmoths (Manduca sexta). Hawkmoths strongly prefer derived colors (yellow, pink, white) over the ancestral red when choosing an initial flower to visit, and generally preferred derived colors when total visits and total visit time were considered, with no hawkmoth preferring ancestral red over derived colors. The simple flower color genetics underlying this innate pollinator preference suggests a potential path for speciation into an unfilled hawkmoth-pollinated niche inMimulussectionErythranthe, and the deliberate design of a hawkmoth-pollinated flower demonstrates a new, predictive method for studying pollination syndrome evolution.
Moving on From Sipuleucel-T: New Dendritic Cell Vaccine Strategies for Prostate Cancer
Authors: Sutherland Sarah I. M. , Ju Xinsheng , Horvath L. G. , Clark Georgina J.
Published: March 2021

Tumors evade the immune system though a myriad of mechanisms. Using checkpoint inhibitors to help reprime T cells to recognize tumor has had great success in malignancies including melanoma, lung, and renal cell carcinoma. Many tumors including prostate cancer are resistant to such treatment. However, Sipuleucel-T, a dendritic cell (DC) based immunotherapy, improved overall survival (OS) in prostate cancer. Despite this initial success, further DC vaccines have failed to progress and there has been limited uptake of Sipuleucel-T in the clinic. We know in prostate cancer (PCa) that both the adaptive and the innate arms of the immune system contribute to the immunosuppressive environment. This is at least in part due to dysfunction of DC that play a crucial role in the initiation of an immune response. We also know that there is a paucity of DC in PCa, and that those there are immature, creating a tolerogenic environment. These attributes make PCa a good candidate for a DC based immunotherapy. Ultimately, the knowledge gained by much research into antigen processing and presentation needs to translate from bench to bedside. In this review we will analyze why newer vaccine strategies using monocyte derived DC (MoDC) have failed to deliver clinical benefit, particularly in PCa, and highlight the emerging antigen loading and presentation technologies such as nanoparticles, antibody-antigen conjugates and virus co-delivery systems that can be used to improve efficacy. Lastly, we will assess combination strategies that can help overcome the immunosuppressive microenvironment of PCa.
Commensal Microbiome Expands Tγδ17 Cells in the Lung and Promotes Particulate Matter-Induced Acute Neutrophilia
Authors: Yang Chorong , Kwon Dong-il , Kim Mingyu , Im Sin-Hyeog , Lee You Jeong
Published: March 2021

Particulate matter (PM) induces neutrophilic inflammation and deteriorates the prognosis of diseases such as cardiovascular diseases, cancers, and infections, including COVID-19. Here, we addressed the role of γδ T cells and intestinal microbiome in PM-induced acute neutrophilia. γδ T cells are a heterogeneous population composed of Tγδ1, Tγδ2, Tγδ17, and naïve γδ T cells (TγδN) and commensal bacteria promote local expansion of Tγδ17 cells, particularly in the lung and gut without affecting their Vγ repertoire. Tγδ17 cells are more tissue resident than Tγδ1 cells, while TγδN cells are circulating cells. IL-1R expression in Tγδ17 cells is highest in the lung and they outnumber all the other type 17 cells such as Th17, ILC3, NKT17, and MAIT17 cells. Upon PM exposure, IL-1β-secreting neutrophils and IL-17-producing Tγδ17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in γδ T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lungviaTγδ17 cells.
Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs
Authors: Sokal David M. , McSloy Alex , Donegà Matteo , Kirk Joseph , Colas Romain A. , Dolezalova Nikola , Gomez Esteban A. , Gupta Isha , Fjordbakk Cathrine T. , Ouchouche Sebastien , Matteucci Paul B. , Schlegel Kristina , Bashirullah Rizwan , Werling Dirk , Harman Kim , Rowles Alison , Yazicioglu Refet Firat , Dalli Jesmond , Chew Daniel J. , Perkins Justin D.
Published: March 2021

Neuromodulation of the immune system has been proposed as a novel therapeutic strategy for the treatment of inflammatory conditions. We recently demonstrated that stimulation of near-organ autonomic nerves to the spleen can be harnessed to modulate the inflammatory response in an anesthetized pig model. The development of neuromodulation therapy for the clinic requires chronic efficacy and safety testing in a large animal model. This manuscript describes the effects of longitudinal conscious splenic nerve neuromodulation in chronically-implanted pigs. Firstly, clinically-relevant stimulation parameters were refined to efficiently activate the splenic nerve while reducing changes in cardiovascular parameters. Subsequently, pigs were implanted with a circumferential cuff electrode around the splenic neurovascular bundle connected to an implantable pulse generator, using a minimally-invasive laparoscopic procedure. Tolerability of stimulation was demonstrated in freely-behaving pigs using the refined stimulation parameters. Longitudinal stimulation significantly reduced circulating tumor necrosis factor alpha levels induced by systemic endotoxemia. This effect was accompanied by reduced peripheral monocytopenia as well as a lower systemic accumulation of CD16+CD14highpro-inflammatory monocytes. Further, lipid mediator profiling analysis demonstrated an increased concentration of specialized pro-resolving mediators in peripheral plasma of stimulated animals, with a concomitant reduction of pro-inflammatory eicosanoids including prostaglandins. Terminal electrophysiological and physiological measurements and histopathological assessment demonstrated integrity of the splenic nerves up to 70 days post implantation. These chronic translational experiments demonstrate that daily splenic nerve neuromodulation,viaimplanted electronics and clinically-relevant stimulation parameters, is well tolerated and is able to prime the immune system toward a less inflammatory, pro-resolving phenotype.
Case Report: Symptomatic Chronic Granulomatous Disease in the Newborn
Authors: Miladinovic Milica , Wittekindt Boris , Fischer Sebastian , Gradhand Elise , Kunzmann Steffen , Zimmermann Stefanie Y. , Bakhtiar Shahrzad , Klingebiel Thomas , Schlösser Rolf , Lehrnbecher Thomas
Published: March 2021

Chronic granulomatous disease (CGD) is a primary immunodeficiency, which is diagnosed in most patients between one and three years of age. Here we report on a boy who presented at birth with extensive skin lesions and lymphadenopathy which were caused by CGD. An analysis of the literature revealed 24 patients with CGD who became symptomatic during the first six weeks of life. Although pulmonary complications and skin lesions due to infection were the leading symptoms, clinical features were extremely heterogenous. As follow-up was not well specified in most patients, the long-term prognosis of children with very early onset of CGD remains unknown.
A Deep-Sea Sponge Loop? Sponges Transfer Dissolved and Particulate Organic Carbon and Nitrogen to Associated Fauna
Authors: Bart Martijn C. , Hudspith Meggie , Rapp Hans Tore , Verdonschot Piet F. M. , de Goeij Jasper M.
Published: March 2021

Cold-water coral reefs and sponge grounds are deep-sea biological hotspots, equivalent to shallow-water tropical coral reefs. In tropical ecosystems, biodiversity and productivity are maintained through efficient recycling pathways, such as the sponge loop. In this pathway, encrusting sponges recycle dissolved organic matter (DOM) into particulate detritus. Subsequently, the sponge-produced detritus serves as a food source for other organisms on the reef. Alternatively, the DOM stored in massive sponges was recently hypothesized to be transferred to higher trophic levels through predation of these sponges, instead of detritus production. However, for deep-sea sponges, the existence of all prerequisite, consecutive steps of the sponge loop have not yet been established. Here, we tested whether cold-water deep-sea sponges, similar to their tropical shallow-water counterparts, take up DOM and transfer assimilated DOM to associated fauna via either detritus production or predation. We traced the fate of 13carbon (C)- and 15nitrogen (N)-enriched DOM and particulate organic matter (POM) in time using a pulse-chase approach. During the 24-h pulse, the uptake of 13C/15N-enriched DOM and POM by two deep-sea sponge species, the massive species Geodia barretti and the encrusting species Hymedesmia sp., was assessed. During the subsequent 9-day chase in label-free seawater, we investigated the transfer of the consumed food by sponges into brittle stars via two possible scenarios: (1) the production and subsequent consumption of detrital waste or (2) direct feeding on sponge tissue. We found that particulate detritus released by both sponge species contained C from the previously consumed tracer DOM and POM, and, after 9-day exposure to the labeled sponges and detritus, enrichment of 13C and 15N was also detected in the tissue of the brittle stars. These results therefore provide the first evidence of all consecutive steps of a sponge loop pathway via deep-sea sponges. We cannot distinguish at present whether the deep-sea sponge loop is acting through a detrital or predatory pathway, but conclude that both scenarios are feasible. We conclude that sponges could play an important role in the recycling of DOM in the many deep-sea ecosystems where they are abundant, although in situ measurements are needed to confirm this hypothesis.
Phenology and Environmental Control of Phytoplankton Blooms in the Kong Håkon VII Hav in the Southern Ocean
Authors: Kauko Hanna M. , Hattermann Tore , Ryan-Keogh Thomas , Singh Asmita , de Steur Laura , Fransson Agneta , Chierici Melissa , Falkenhaug Tone , Hallfredsson Elvar H. , Bratbak Gunnar , Tsagaraki Tatiana , Berge Terje , Zhou Qin , Moreau Sebastien
Published: March 2021

Knowing the magnitude and timing of pelagic primary production is important for ecosystem and carbon sequestration studies, in addition to providing basic understanding of phytoplankton functioning. In this study we use data from an ecosystem cruise to Kong Håkon VII Hav, in the Atlantic sector of the Southern Ocean, in March 2019 and more than two decades of satellite-derived ocean color to study phytoplankton bloom phenology. During the cruise we observed phytoplankton blooms in different bloom phases. By correlating bloom phenology indices (i.e., bloom initiation and end) based on satellite remote sensing to the timing of changes in environmental conditions (i.e., sea ice, light, and mixed layer depth) we studied the environmental factors that seemingly drive phytoplankton blooms in the area. Our results show that blooms mainly take place in January and February, consistent with previous studies that include the area. Sea ice retreat controls the bloom initiation in particular along the coast and the western part of the study area, whereas bloom end is not primarily connected to sea ice advance. Light availability in general is not appearing to control the bloom termination, neither is nutrient availability based on the autumn cruise where we observed non-depleted macronutrient reservoirs in the surface. Instead, we surmise that zooplankton grazing plays a potentially large role to end the bloom, and thus controls its duration. The spatial correlation of the highest bloom magnitude with marked topographic features indicate that the interaction of ocean currents with sea floor topography enhances primary productivity in this area, probably by natural fertilization. Based on the bloom timing and magnitude patterns, we identified five different bloom regimes in the area. A more detailed understanding of the region will help to highlight areas with the highest relevance for the carbon cycle, the marine ecosystem and spatial management. With this gained understanding of bloom phenology, it will also be possible to study potential shifts in bloom timing and associated trophic mismatch caused by environmental changes.
Case Report: Next-Generation Sequencing in Diagnosis of Pneumonia Due to Pneumocystis jirovecii and Cytomegalovirus in a Patient With HIV Infection
Authors: Xie Yirui , Ruan Bing , Jin Lingxiao , Zhu Biao
Published: March 2021

Background: Pulmonary infections remain a significant cause of morbidity and mortality in immunocompromised patients. The pathogens spectrum of pulmonary infection that can affect patients with human immunodeficiency virus (HIV) is wide such as bacterial, fungal, viral, parasitic organisms, and so on. The risk of multi-pathogenic pneumonia is higher in HIV-infected patients. However, the fast and accurate diagnosis of multi-pathogenic pneumonia is challenging because of the limitations of current conventional tests.

Case Presentation: Here, we report a case of pneumonia due to Pneumocystis jirovecii and cytomegalovirus (CMV) in a 22-year-old male with newly diagnosed HIV infection. Blood tests revealed a low CD4 count, a chest computed tomography (CT) scan showed extensive ground-glass opacities in the bilateral lung with multiple cavity lesions in the left upper lung. Microscopic examination of stained sputum and bronchoalveolar lavage fluid (BALF) smear specimens did not find any pathogens. There was also no evidence of pathogens known to cause pneumonia in bacteria and fungi culture tests and virus antibodies such as EBV, CMV, and COVID-19. The nucleic acid of CMV in blood was reported by quantitative PCR. Next-generation sequencing (NGS) analysis of BALF specimens identified a large number of P. jirovecii and CMV reads, and confirmed the diagnosis of pneumonia due to P. jirovecii and CMV. Following the patient's treatment with anti-PCP and anti-CMV, the patient was cured and discharged.

Conclusions: This case highlights the combined application of NGS in the clinical diagnosis of multi-pathogenic pneumonia in an HIV-infected patient. NGS is proposed as an important adjunctive diagnostic approach for identifying pathogens of multi-pathogenic pneumonia in HIV-infected patients.
Changing Antimicrobial Resistance and Epidemiology of Non-Typhoidal Salmonella Infection in Taiwanese Children
Authors: Chang Yi-Jung , Chen Yi-Ching , Chen Nai-Wen , Hsu Ying-Jie , Chu Hsiao-Han , Chen Chyi-Liang , Chiu Cheng-Hsun
Published: March 2021

Non-typhoidal Salmonella (NTS) typically causes self-limiting diarrheal disease but may occasionally lead to invasive infection. This study investigated the epidemiology and antimicrobial resistance of children with NTS infection between 2012 and 2019. We retrospectively analyzed pediatric patients with NTS infections, confirmed by positive cultures, in a tertiary medical center in Taiwan in 2012 and 2019. Clinical features and laboratory data of the patients were collected. Changes in the serogroup category and antimicrobial resistance were also analyzed. Of the total 797 isolates collected, 55 had NTS bacteremia. Compared with the resistance rates in 2012, the rates of resistances to third-generation cephalosporin and ciprofloxacin were significantly higher in 2019 (4.1% vs 14.3%, P < 0.001; 1.9% vs 28.6%, P < 0.001), especially in groups B, D, and E. Moreover, we observed significantly higher antimicrobial resistance (25.3%) to third-generation cephalosporin, and approximately half the NTS isolates in the infant group were multidrug resistant – a higher rate than those of other age groups in 2019. Invasive NTS often presented with a longer fever duration, lower hemoglobin level and with no elevated C-reactive protein (P < 0.05). Non-invasive NTS isolates in 2019 were significantly more resistant to ceftriaxone (P < 0.001) and ciprofloxacin (P < 0.001) than those in 2012. The antimicrobial resistance of NTS in children has increased progressively in the past decade, and different serogroups exhibited different resistance patterns. During this period, infants showed the highest risk to get a third-generation cephalosporin-resistant NTS infection. The high rates of antimicrobial resistance among children with NTS in Taiwan merit continual surveillance.
Inflammation, Nitro-Oxidative Stress, Impaired Autophagy, and Insulin Resistance as a Mechanistic Convergence Between Arterial Stiffness and Alzheimer’s Disease
Authors: Hendrickx Jhana O. , Martinet Wim , Van Dam Debby , De Meyer Guido R. Y.
Published: March 2021

The average age of the world’s elderly population is steadily increasing. This unprecedented rise in the aged world population will increase the prevalence of age-related disorders such as cardiovascular disease (CVD) and neurodegeneration. In recent years, there has been an increased interest in the potential interplay between CVDs and neurodegenerative syndromes, as several vascular risk factors have been associated with Alzheimer’s disease (AD). Along these lines, arterial stiffness is an independent risk factor for both CVD and AD. In this review, we discuss several inflammaging-related disease mechanisms including acute tissue-specific inflammation, nitro-oxidative stress, impaired autophagy, and insulin resistance which may contribute to the proposed synergism between arterial stiffness and AD.
Case Report: Could Hennebert's Sign Be Evoked Despite Global Vestibular Impairment on Video Head Impulse Test? Considerations Upon Pathomechanisms Underlying Pressure-Induced Nystagmus due to Labyrinthine Fistula
Authors: Castellucci Andrea , Botti Cecilia , Bettini Margherita , Fernandez Ignacio Javier , Malara Pasquale , Martellucci Salvatore , Crocetta Francesco Maria , Fornaciari Martina , Lusetti Francesca , Renna Luigi , Bianchin Giovanni , Armato Enrico , Ghidini Angelo
Published: March 2021

We describe a case series of labyrinthine fistula, characterized by Hennebert's sign (HS) elicited by tragal compression despite global hypofunction of semicircular canals (SCs) on a video-head impulse test (vHIT), and review the relevant literature. All three patients presented with different amounts of cochleo-vestibular loss, consistent with labyrinthitis likely induced by labyrinthine fistula due to different temporal bone pathologies (squamous cell carcinoma involving the external auditory canal in one case and middle ear cholesteatoma in two cases). Despite global hypofunction on vHIT proving impaired function for each SC for high accelerations, all patients developed pressure-induced nystagmus, presumably through spared and/or recovered activity for low-velocity canal afferents. In particular, two patients with isolated horizontal SC fistula developed HS with ipsilesional horizontal nystagmus due to resulting excitatory ampullopetal endolymphatic flows within horizontal canals. Conversely, the last patient with bony erosion involving all SCs developed mainly torsional nystagmus directed contralaterally due to additional inhibitory ampullopetal flows within vertical canals. Moreover, despite impaired measurements on vHIT, we found simultaneous direction-changing positional nystagmus likely due to a buoyancy mechanism within the affected horizontal canal in a case and benign paroxysmal positional vertigo involving the dehiscent posterior canal in another case. Based on our findings, we might suggest a functional dissociation between high (impaired) and low (spared/recovered) accelerations for SCs. Therefore, it could be hypothesized that HS in labyrinthine fistula might be due to the activation of regular ampullary fibers encoding low-velocity inputs, as pressure-induced nystagmus is perfectly aligned with the planes of dehiscent SCs in accordance with Ewald's laws, despite global vestibular impairment on vHIT. Moreover, we showed how pressure-induced nystagmus could present in a rare case of labyrinthine fistulas involving all canals simultaneously. Nevertheless, definite conclusions on the genesis of pressure-induced nystagmus in our patients are prevented due to the lack of objective measurements of both low-acceleration canal responses and otolith function.
Optical Coherence Tomography Angiography for the Evaluation of Retinal Vasculature in Fabry Disease: Our Experience and Review of Current Knowledge
Authors: Bacherini Daniela , Vicini Giulio , Nicolosi Cristina , Tanini Ilaria , Lenzetti Chiara , Finocchio Lucia , Cirami Lino Calogero , Dervishi Egrina , Rizzo Stanislao , Virgili Gianni , Giansanti Fabrizio , Sodi Andrea
Published: March 2021

Purpose: Optical coherence tomography angiography (OCTA) is a non-invasive and objective tool for the evaluation of the retinal microvascular changes in Fabry disease (FD). We investigated changes in retinal vasculature in FD patients, and the possible correlation with systemic parameters, by using OCTA, and reviewed the current status of literature.

Methods: Thirteen FD patients (eight females, five males, mean age 49.85 ± 14.7 years) were compared with 13 age- and sex-matched healthy controls. OCTA 3 × 3 mm macular scans were performed in all subjects. We evaluated the vessel density and vessel perfusion in distinct macular areas (whole, inner, and outer) of both the superficial capillary plexus (SCP VD and SCP VP) and of the deep capillary plexus (DCP VD and DCP VP). We also evaluated the foveal avascular zone (FAZ) metrics (area, perimeter, and circularity), and correlation between systemic and OCTA parameters. A literature review on the current understanding of OCTA in FD is then presented.

Results: FD patients showed significantly lower SCP VD values in the whole area (17.37 ± 2.08 mm−1 vs. 18.54 ± 1.21 mm−1; p-value 0.022), as well as in the outer area (17.46 ± 2.10 mm−1 vs. 19.08 ± 1.14 mm−1; p-value 0.002), but not in the inner. Even the DCP VD was significantly lower in all the imaged areas: whole (17.75 ± 3.93 mm−1 vs. 19.71 ± 1.20 mm−1; p-value 0.024), outer (18.25 ± 4.17 mm−1 vs. 20.33 ± 1.20 mm−1; p-value 0.023), and inner (19.54 ± 4.17 mm−1 vs. 21.96 ± 1.55 mm−1; p-value 0.011). There were no significant differences in vessel perfusion parameters (both SCP VP and DCP VP ones) and FAZ. No significant correlations were found between the OCTA parameters and systemic parameters (maximal left ventricular wall thickness and glomerular filtration rate) in FD patients.

Conclusions: OCTA can be considered as a promising non-invasive tool, which enables a quantitative evaluation of retinal vascular involvement in FD, despite the varying data reported in literature. Our results support the use of OCTA as an objective tool to evaluate retinal vascular abnormalities in FD. The utility of OCTA in FD needs to be validated by longitudinal studies taking into account the overall progression of the disease.
Girdin Knockdown Increases Gemcitabine Chemosensitivity to Pancreatic Cancer by Modulating Autophagy
Authors: Wang Sheng , Feng Wei , Wang Wulin , Ye Xiaoman , Chen Hao , Yu Chunzhao
Published: March 2021

Chemotherapy is crucial for the treatment of pancreatic cancer (PC). Gemcitabine (GEM) as the first-line chemotherapy drug has a high resistance rate. Increasing the sensitivity of gemcitabine is currently the objectives and challenges of this study. Our previous study showed Girdin was closely related to the progression and prognosis of PC, indicating that Girdin may be associated with chemosensitivity. In the current study, we use recombinant adenovirus to specifically knockdown Girdin in PC cell lines to determine the effect of Girdin in the process of gemcitabine chemosensitivity. Autophagy is one of the pathways affecting the gemcitabine chemosensitivity in PC. Further research validated that Girdin may activate autophagy by interacting with autophagy protein p62/SQSTM1, which could enhance chemotherapy resistance to gemcitabine in PC. Down-regulation of Girdin may therefore increase gemcitabine chemosensitivity in PC. Our results reveal that Girdin acted as a negative regulator of gemcitabine chemosensitivity in PC. Increased autophagy activity caused by abnormally high Girdin expression may be one of the main factors for the reduction in chemosensitivity, which may provide new perspectives on understanding chemosensitization in PC.
Prophylactic Cancer Vaccines Engineered to Elicit Specific Adaptive Immune Response
Authors: Crews Davis W. , Dombroski Jenna A. , King Michael R.
Published: March 2021

Vaccines have been used to prevent and eradicate different diseases for over 200 years, and new vaccine technologies have the potential to prevent many common illnesses. Cancer, despite many advances in therapeutics, is still the second leading causes of death in the United States. Prophylactic, or preventative, cancer vaccines have the potential to reduce cancer prevalence by initiating a specific immune response that will target cancer before it can develop. Cancer vaccines can include many different components, such as peptides and carbohydrates, and be fabricated for delivery using a variety of means including through incorporation of stabilizing chemicals like polyethylene glycol (PEG) and pan-DR helper T-lymphocyte epitope (PADRE), fusion with antigen-presenting cells (APCs), microneedle patches, and liposomal encapsulation. There are currently five cancer vaccines used in the clinic, protecting against either human papillomavirus (HPV) or hepatitis B virus (HBV), and preventing several different types of cancer including cervical and oral cancer. Prophylactic cancer vaccines can promote three different types of adaptive responses: humoral (B cell, or antibody-mediated), cellular (T cell) or a combination of the two types. Each vaccine has its advantages and challenges at eliciting an adaptive immune response, but these prophylactic cancer vaccines in development have the potential to prevent or delay tumor development, and reduce the incidence of many common cancers.
CyberKnife for Recurrent Malignant Gliomas: A Systematic Review and Meta-Analysis
Authors: De Maria Lucio , Terzi di Bergamo Lodovico , Conti Alfredo , Hayashi Kazuhiko , Pinzi Valentina , Murai Taro , Lanciano Rachelle , Burneikiene Sigita , Buglione di Monale Michela , Magrini Stefano Maria , Fontanella Marco Maria
Published: March 2021

Background and Objective

Possible treatment strategies for recurrent malignant gliomas include surgery, chemotherapy, radiotherapy, and combined treatments. Among different reirradiation modalities, the CyberKnife System has shown promising results. We conducted a systematic review of the literature and a meta-analysis to establish the efficacy and safety of CyberKnife treatment for recurrent malignant gliomas.

Methods

We searched PubMed, MEDLINE, and EMBASE from 2000 to 2021 for studies evaluating the safety and efficacy of CyberKnife treatment for recurrent WHO grade III and grade IV gliomas of the brain. Two independent reviewers selected studies and abstracted data. Missing information was requested from the authors via email correspondence. The primary outcomes were median Overall Survival, median Time To Progression, and median Progression-Free Survival. We performed subgroup analyses regarding WHO grade and chemotherapy. Besides, we analyzed the relationship between median Time To Recurrence and median Overall Survival from CyberKnife treatment. The secondary outcomes were complications, local response, and recurrence. Data were analyzed using random-effects meta-analysis.

Results

Thirteen studies reporting on 398 patients were included. Median Overall Survival from initial diagnosis and CyberKnife treatment was 22.6 months and 8.6 months. Median Time To Progression and median Progression-Free Survival from CyberKnife treatment were 6.7 months and 7.1 months. Median Overall Survival from CyberKnife treatment was 8.4 months for WHO grade IV gliomas, compared to 11 months for WHO grade III gliomas. Median Overall Survival from CyberKnife treatment was 4.4 months for patients who underwent CyberKnife treatment alone, compared to 9.5 months for patients who underwent CyberKnife treatment plus chemotherapy. We did not observe a correlation between median Time To Recurrence and median Overall Survival from CyberKnife. Rates of acute neurological and acute non-neurological side effects were 3.6% and 13%. Rates of corticosteroid dependency and radiation necrosis were 18.8% and 4.3%.

Conclusions

Reirradiation of recurrent malignant gliomas with the CyberKnife System provides encouraging survival rates. There is a better survival trend for WHO grade III gliomas and for patients who undergo combined treatment with CyberKnife plus chemotherapy. Rates of complications are low. Larger prospective studies are warranted to provide more accurate results.
Antibiotic Use Among Hospitalized Children and Neonates in China: Results From Quarterly Point Prevalence Surveys in 2019
Authors: Wang Chu-ning , Tong Jianning , Yi Bin , Huttner Benedikt D. , Cheng Yibing , Li Shuangjie , Wan Chaomin , Zhu Qingxiong , Zhou Qionghua , Zhao Shiyong , Zhuo Zhiqiang , Wang Daobin , Jia Chunmei , Shan Qing-wen , Zhao Yun , Lan Chenfu , Zhao Dongchi , Zhou Yibo , Liu Jing , Zhu Chunhui , Zhu Yu , Li Rui , Wu Xiaodan , Qi Zhenghong , Wang Caihong , Gao Huiling , Ye Wenyu , Zhang Liling , Xu Xiaohong , Hu Hui , Yang Pu , Magrini Nicola , Zeng Mei
Published: March 2021

Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions.

Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children’s hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification.

Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2% (n = 2,331) were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections (43.2%, n = 6,379). WHO Watch group antibiotics accounted for 70.4% of prescriptions (n = 12,915). The most prescribed antibiotic ATC classes were third-generation cephalosporins (41.9%, n = 7,679), followed by penicillins/β-lactamase inhibitors (16.1%, n = 2,962), macrolides (12.1%, n = 2,214) and carbapenems (7.7%, n = 1,331).

Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented.
The Efficacy of Heat-Clearing (Qingre) and Detoxifying (Jiedu) Traditional Chinese Medicine Gargle for Chemotherapy-Induced Oral Mucositis: A Systematic Review and Meta-Analysis
Authors: Lin Zhixian , Chen Jiangfeng , Han Sunya
Published: March 2021

Objective: Chemotherapy-induced oral mucositis (CIOM) is an extremely serious complication of cancer. In China, the heat-clearing (Qingre) and detoxifying (Jiedu) traditional Chinese medicine QRJD-TCM gargle has been widely used to treat CIOM. To date, no systematic evaluation has been conducted on the clinical efficacy of QRJD-TCM gargle in treating CIOM. The objective of this systematic review and meta-analysis was to evaluate the efficacy of QRJD-TCM gargle in the treatment of CIOM.

Methods: Relevant randomized controlled trials (RCTs) comparing QRJD-TCM gargle with conventional Western medicine mouthwash (CWMM) for CIOM were confirmed by systematically searching PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, and Sinomed until October 20, 2020. Two researchers independently assessed the risk of bias according to the Cochrane risk-of-bias criteria. Excel 2010 was used in setting up a database of extracted information, and RevMan 5.3.0 was used in analyzing included trial data. The composition of the QRJD-TCM gargle was evaluated.

Results: A total of 25 articles were included in this meta-analysis. Results showed that compared with CWMM, QRJD-TCM gargle can reduce the incidence of CIOM (OR = 0.23, 95% CI [0.18, 0.29], p < 0.00001) and severity of CIOM (grade I–II: OR = 0.36, 95%CI [0.28, 0.46], p < 0.00001; grade III–IV: OR = 0.15, 95%CI [0.09, 0.28], p < 0.00001). In addition, QRJD-TCM gargle improved the effective rate of CIOM (OR = 15.91, 95% CI [7.93, 31.89], p < 0.00001).

Conclusion: QRJD-TCM gargle is effective in preventing and treating CIOM. However, more standard, double-blind, and multicenter randomized controlled studies are needed to further confirm the efficacy of QRJD-TCM gargle in the prevention and treatment of CIOM.
Applications of Super Resolution Expansion Microscopy in Yeast
Authors: Chen Liwen , Yao Longfang , Zhang Li , Fei Yiyan , Mi Lan , Ma Jiong
Published: March 2021

Super-resolution microscopy includes multiple techniques in optical microscopy that enable sub-diffraction resolution fluorescence imaging of cellular structures. Expansion microscopy (EXM) is a method of physical expansion to obtain super-resolution images of a biological sample on conventional microscopy. We present images of yeast organelles, applying the combination of super-resolution and ExM techniques. When preparing pre-expanded samples, conventional methods lead to breakage of dividing yeast cells and difficulties in studying division-related proteins. Here, we describe an improved sample preparation technique that avoids such damage. ExM in combination with Airyscan and structured illumination microscopy (SIM) collected sub-cellular structural images of nuclear pore complex, septin, and a-tubulin in yeast. Our method of expansion in yeast is well-suited for super-resolution imaging study of yeast.