bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Evidence From Voluntary Fisheries Data Collection Programmes to Support Marine Spatial Planning and Resolve Multiple-Use Conflicts
Authors: Dosell Abbie , Edwards Dan , Gregory Amanda , Ponteen Alwyn , O’Garro Joseph , Cornick Laura , Hawkridge Jane M.
Published: July 2021

Natural disasters have altered the landscape of Montserrat’s marine environment significantly over the past 30 years, forcing rapid adaptation of marine species and the human population that relies upon them. Volcanic activity has led to an abundance of volcanic sediment, which has seen rise to the expansion of the island’s sand mining and aggregate industry. Similarly, a series of volcanic eruptions has resulted in smothered fishing grounds and maritime exclusion zones, increasing the pressure on the remaining accessible marine environment. Recent increases in shipping activity, due to the expanding aggregate sector, partnered with a lack of official marine spatial planning, has led to the west coast of the island becoming a stakeholder conflict hotspot. Regular interactions between fishing gear and shipping vessels were resulting in damaged and lost fish pots and causing physical damage and increased ghost-fishing on the coral reefs, with additional impacts on fisher livelihoods. This paper builds upon earlier work in Montserrat to engage fishers in fisheries data collection programmes. Here we use data from Montserrat’s fishing fleet to understand the distribution and intensity of fish pot activity within the conflict area. Maximum activity was distributed along the edge of the reef front, near the drop-off, with the greatest intensity toward the south. These data, and outcomes from stakeholder consultation, have allowed the relevant authorities and decision-makers to identify a suitable shipping route that avoids pot-based fishing grounds, while remaining as close inshore as feasible, to avoid unnecessary fuel costs for shipping vessels. As a result, the Montserrat Port Authority has implemented a restricted area around the identified fishing grounds, in which commercial vessels are not allowed to transit. This intervention represents a “win-win” solution, reducing the risk of commercial vessel-fishing gear conflict in the southwestern pot-based fishing grounds, without substantially increasing the burden of excess travel on commercial vessels. Here we show how engagement with the fishing community and voluntary participation in data collection has supported a conflict resolution deemed suitable to both parties; allowing the needs of the smaller traditional fishing sector to influence management of the rapidly expanding, high value aggregate sector.
Rigid Polyurethane Foams Containing Modified Ammonium Polyphosphate Having Outstanding Charring Ability and Increased Flame Retardancy
Authors: Yang Chunzhuang , Shao Shuiyu
Published: July 2021

Ammonium polyphosphate (APP) with different polymerization degrees were modified by a novel phosphorus-containing organosilicon compound (PCOC), and the products obtained were coded as MAPP-30 and MAPP-1000. Then they were applied to prepare flame-retardant rigid polyurethane foam (RPUF) separately. The impact of modified APP (MAPP) on the flame-retardant properties of RPUF was investigated by the limited oxygen index (LOI) test, horizontal burning test, and cone calorimeter test. The morphologies of the char residues were observed by SEM. Furthermore, the mechanical properties of RPUF composites were measured by the compressive strength test. The results showed that whether the degree of polymerization of MAPP is 30 or 1000, they both had greater charring ability and better flame-retardant properties than unmodified APP. The residual char yield of RPUF/MAPP-30 (37.3%) and RPUF/MAPP-1000 (36.5%) were both significantly higher than RPUF/APP-30 (22.8%) and RPUF/APP-1000 (24.9%). The peak heat release rate value of RPUF/MAPP-30 was 29.9% lower than that of RPUF/APP-30, and the drop of RPUF/MAPP-1000 was 50.9% compared to RPUF/APP-1000. Moreover, the total heat release of RPUF/MAPP-1000 (9.7 MJ/m2) was much lower than that of RPUF/MAPP-30 (11.3 MJ/m2). In summary, MAPP-1000 has the best flame-retardant properties among all RPUF composites. In addition, the results also showed that flame-retardant performance and the mechanical properties dramatically decreased with the increase in the addition of MAPP-1000, and the RPUF composite had the best comprehensive performance with 20% content of MAPP-1000.
Gut Microbiota and Related Electronic Multisensorial System Changes in Subjects With Symptomatic Uncomplicated Diverticular Disease Undergoing Rifaximin Therapy
Authors: De Vincentis Antonio , Santonico Marco , Del Chierico Federica , Altomare Annamaria , Marigliano Benedetta , Laudisio Alice , Reddel Sofia , Grasso Simone , Zompanti Alessandro , Pennazza Giorgio , Putignani Lorenza , Guarino Michele Pier Luca , Cicala Michele , Antonelli Incalzi Raffaele
Published: July 2021

Background: Intestinal dysbiosis might play a pathogenetic role in subjects with symptomatic uncomplicated diverticular disease (SUDD), but the effect of rifaximin therapy has been scantly explored with regard to gut microbiota variations in patients with SUDD.

Aims: To verify to which extent rifaximin treatment affects the gut microbiota and whether an electronic multisensorial assessment of stools and breath has the potential for detecting these changes.

Methods: Breath and stool samples were collected from consecutive patients with SUDD before and after a 7 days' therapy with rifaximin. Stool microbiota was assessed, and the electronic multisensorial assessment was carried out by means of the BIONOTE electronic (e-)tongue in stools and (e-)nose in breath.

Results: Forty-three subjects (female 60%, median age 66 years) were included, and 20 (47%) reported clinical improvement after rifaximin therapy. Alpha and beta diversity of stool microbiota did not significantly change after treatment, while a significant variation of selected taxa was shown (i.e., Citrobacter, Coprococcus, Anaerotruncus, Blautia, Eggerthella lenta, Dehalobacterium, SMB53, and Haemophilus parainfluenzae). Overall, the electronic multisensorial system suboptimally mirrored microbiota changes, but it was able to efficiently predict patients' clinical improvement after rifaximin with accuracies ranging from 0.81 to 0.98.

Conclusions: In patients with SUDD, rifaximin administration is associated with significant variation of selected taxa. While inaccurate in predicting gut microbiota change, an electronic multisensorial system, made up of e-tongue and e-nose, was able to predict clinical improvement, thus potentially qualifying as an easy and cheap tool to forecast subjects taking most likely benefit from rifaximin therapy.
Age and Gender Disparities in Adverse Events Following COVID-19 Vaccination: Real-World Evidence Based on Big Data for Risk Management
Authors: Xiong Xiaomo , Yuan Jing , Li Minghui , Jiang Bin , Lu Z. Kevin
Published: July 2021

Background: Two coronavirus disease 2019 (COVID-19) vaccines have received emergency use authorizations in the U.S. However, the safety of these vaccines in the real-world remains unknown.

Methods: We reviewed adverse events (AEs) following COVID-19 vaccination among adults in the Vaccine Adverse Event Reporting System (VAERS) from December 14, 2020, through January 22, 2021. We compared the top 10 AEs, serious AEs, along with office and emergency room (ER) visits by age (18–64 years, ≥65 years) and gender (female, male).

Results: There were age and gender disparities among adults with AEs following COVID-19 vaccination. Compared to younger adults aged between 18 and 64 years, older adults were more likely to report serious AEs, death, permanent disability, and hospitalization. Males were more likely to report serious AEs, death, and hospitalization compared to females.

Conclusions: COVID-19 vaccines are generally safe but possible age and gender disparities in reported AEs may exist.
Transthoracic Ultrasound in Infectious Organizing Pneumonia: A Useful Guide for Percutaneous Needle Biopsy
Authors: Lacedonia Donato , Quarato Carla Maria Irene , Borelli Cristina , Dimitri Lucia , Graziano Paolo , Foschino Barbaro Maria Pia , Scioscia Giulia , Mirijello Antonio , Maggi Michele Maria , Rea Gaetano , Ferragalli Beatrice , De Cosmo Salvatore , Sperandeo Marco
Published: July 2021

In patients presenting with classical features of CAP (i.e., new peripheral pulmonary consolidations and symptoms including fever, cough, and dyspnea), a clinical response to the appropriate therapy occurs in few days. When clinical improvement has not occurred and chest imaging findings are unchanged or worse, a more aggressive approach is needed in order to exclude other non-infective lesions (including neoplasms). International guidelines do not currently recommend the use of transthoracic ultrasound (TUS) as an alternative to chest X-ray (CXR) or chest computed tomography (CT) scan for the diagnosis of CAP. However, a fundamental role for TUS has been established as a guide for percutaneous needle biopsy (US-PNB) in pleural and subpleural lesions. In this retrospective study, we included 36 consecutive patients whose final diagnosis, made by a US-guided percutaneous needle biopsy (US-PTNB), was infectious organizing pneumonia (OP). Infective etiology was confirmed by additional information from microbiological and cultural studies or with a clinical follow-up of 6–12 months after a second-line antibiotic therapy plus corticosteroids. All patients have been subjected to a chest CT and a systematic TUS examination before biopsy. This gave us the opportunity to explore TUS performance in assessing CT findings of infective OP. TUS sensitivity and specificity in detecting air bronchogram and necrotic areas were far lower than those of CT scan. Conversely, TUS showed superiority in the detection of pleural effusion. Although ultrasound findings did not allow the characterization of chronic subpleural lesions, TUS confirmed to be a valid diagnostic aid for guiding percutaneous needle biopsy of subpleural consolidations.
Temperature and Nutrient Limitations Decrease Transfer of Conjugative IncP-1 Plasmid pKJK5 to Wild Escherichia coli Strains
Authors: Pallares-Vega Rebeca , Macedo Gonçalo , Brouwer Michael S. M. , Hernandez Leal Lucia , van der Maas Peter , van Loosdrecht Mark C. M. , Weissbrodt David G. , Heederik Dick , Mevius Dik , Schmitt Heike
Published: July 2021

Plasmid-mediated dissemination of antibiotic resistance among fecal Enterobacteriaceae in natural ecosystems may contribute to the persistence of antibiotic resistance genes in anthropogenically impacted environments. Plasmid transfer frequencies measured under laboratory conditions might lead to overestimation of plasmid transfer potential in natural ecosystems. This study assessed differences in the conjugative transfer of an IncP-1 (pKJK5) plasmid to three natural Escherichia coli strains carrying extended-spectrum beta-lactamases, by filter mating. Matings were performed under optimal laboratory conditions (rich LB medium and 37°C) and environmentally relevant temperatures (25, 15 and 9°C) or nutrient regimes mimicking environmental conditions and limitations (synthetic wastewater and soil extract). Under optimal nutrient conditions and temperature, two recipients yielded high transfer frequencies (5 × 10–1) while the conjugation frequency of the third strain was 1000-fold lower. Decreasing mating temperatures to psychrophilic ranges led to lower transfer frequencies, albeit all three strains conjugated under all the tested temperatures. Low nutritive media caused significant decreases in transconjugants (−3 logs for synthetic wastewater; −6 logs for soil extract), where only one of the strains was able to produce detectable transconjugants. Collectively, this study highlights that despite less-than-optimal conditions, fecal organisms may transfer plasmids in the environment, but the transfer of pKJK5 between microorganisms is limited mainly by low nutrient conditions.
Linking Inflammatory Bowel Disease Symptoms to Changes in the Gut Microbiome Structure and Function
Authors: Hassouneh Sayf Al-Deen , Loftus Mark , Yooseph Shibu
Published: July 2021

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract that is often characterized by abdominal pain, rectal bleeding, inflammation, and weight loss. Many studies have posited that the gut microbiome may play an integral role in the onset and exacerbation of IBD. Here, we present a novel computational analysis of a previously published IBD dataset. This dataset consists of shotgun sequence data generated from fecal samples collected from individuals with IBD and an internal control group. Utilizing multiple external controls, together with appropriate techniques to handle the compositionality aspect of sequence data, our computational framework can identify and corroborate differences in the taxonomic profiles, bacterial association networks, and functional capacity within the IBD gut microbiome. Our analysis identified 42 bacterial species that are differentially abundant between IBD and every control group (one internal control and two external controls) with at least a twofold difference. Of the 42 species, 34 were significantly elevated in IBD, relative to every other control. These 34 species were still present in the control groups and appear to play important roles, according to network centrality and degree, in all bacterial association networks. Many of the species elevated in IBD have been implicated in modulating the immune response, mucin degradation, antibiotic resistance, and inflammation. We also identified elevated relative abundances of protein families related to signal transduction, sporulation and germination, and polysaccharide degradation as well as decreased relative abundance of protein families related to menaquinone and ubiquinone biosynthesis. Finally, we identified differences in functional capacities between IBD and healthy controls, and subsequently linked the changes in the functional capacity to previously published clinical research and to symptoms that commonly occur in IBD.
Evaluation of Dietary Supplements Containing Viable Bacteria by Cultivation/MALDI-TOF Mass Spectrometry and PCR Identification
Authors: Mohar Lorbeg Petra , Golob Majda , Kramer Mateja , Treven Primož , Bogovič Matijašić Bojana
Published: July 2021

The insufficient quality of products containing beneficial live bacteria in terms of content and viability of labelled microorganisms is an often-reported problem. The aim of this work was to evaluate the quality of dietary supplements containing viable bacteria available in Slovenian pharmacies using plate counting, matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and species- or subspecies-specific PCR with DNA isolated from consortia of viable bacteria, from individual isolates, or directly from the products. Twelve percent of the products (3 of 26) contained insufficient numbers of viable bacteria. Eighty-three of the labelled species (111 in total) were confirmed by PCR with DNA from the product; 74% of these were confirmed by PCR with DNA from viable consortium, and 65% of these were confirmed by MALDI-TOF MS analysis of colonies. Certain species in multi-strain products were confirmed by PCR with DNA from viable consortia but not by MALDI-TOF MS, suggesting that the number of isolates examined (three per labelled strain) was too low. With the exception of Lacticaseibacillus casei and closely related species (Lacticaseibacillus rhamnosus and Lacticaseibacillus zeae), PCR and MALDI-TOF identification results agreed for 99% of the isolates examined, although several MALDI-TOF results had lower score values (1.700–1.999), indicating that the species identification was not reliable. The species L. zeae, which appeared in 20 matches of the Biotyper analysis, was identified as L. rhamnosus by PCR. The MALDI-TOF MS analysis was also unsuccessful in detecting Lactobacillus acidophilus La-5 and Bacillus coagulans due to missing peaks and unreliable identification, respectively. Mislabelling was detected by both methods for two putative L. casei strains that turned out to belong to the species Lacticaseibacillus paracasei. PCR remains more successful in subspecies-level identification as long as the database of MALDI-TOF MS spectra is not expanded by building in-house databases. The lack of positive PCR results with viable consortia or colonies, but positive PCR results with DNA isolated directly from the products observed in 10% (11/112) of the labelled strains, suggests the presence of non-culturable bacteria in the products. MALDI-TOF MS is a faster and simpler alternative to PCR identification, provided that a sufficient number of colonies are examined. Generation of in-house library may further improve the identification accuracy at the species and sub-species level.
The Involvement of Lactosylceramide in Central Nervous System Inflammation Related to Neurodegenerative Disease
Authors: Yu Wen , Ying Jun , Wang Xifeng , Liu Xing , Zhao Tiancheng , Yoon Sungtae , Zheng Qingcui , Fang Yang , Yang Danying , Hua Fuzhou
Published: July 2021

Neurodegenerative diseases are a class of slow-progressing terminal illnesses characterized by neuronal lesions, such as multiple sclerosis [MS, Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS)]. Their incidence increases with age, and the associated burden on families and society will become increasingly more prominent with aging of the general population. In recent years, there is growing studies have shown that lactosylceramide (LacCer) plays a crucial role in the progression of neurodegeneration, although these diseases have different pathogenic mechanisms and etiological characteristics. Based on latest research progress, this study expounds the pathogenic role of LacCer in driving central nervous system (CNS) inflammation, as well as the role of membrane microstructure domain (lipid rafts) and metabolite gangliosides, and discusses in detail their links with the pathogenesis of neurodegenerative diseases, with a view to providing new strategies and ideas for the study of pathological mechanisms and drug development for neurodegenerative diseases in the future.
Acupuncture Can Regulate the Peripheral Immune Cell Spectrum and Inflammatory Environment of the Vascular Dementia Rat, and Improve the Cognitive Dysfunction of the Rats
Authors: Pan Pan , Ma Zhinan , Zhang Zhen , Ling Zhenzhen , Wang Yao , Liu Qiuping , Lin Xiaolin , Xu Pan , Yang Dan , Zhi Hui , Wang Runmin , Zhang Xuezhu
Published: July 2021

Objective

The aim of this study is to analyze the effects of acupuncture on peripheral immune function, inflammation, and cognitive impairment in vascular dementia (VD) rats.

Methods

In this study, 2-month-old healthy male Wistar rats (260–280 g) were assigned to the groups as follows: normal group (Gn,n= 10), sham-operated group (Gs,n= 10), and operated group (Go,n= 45). The Go group was established by permanent, bilateral common carotid artery occlusion (BCCAO). Two months after operation, the operated rats were screened by hidden platform trial and the rats with cognitive dysfunction were further randomly divided into impaired group (Gi), acupoint group (Ga), and non-acupoint group (Gna) with 10 rats in each group. The Ga group was given acupuncture treatment for 14 days with a rest for every 7 days. After treatment, the Morris water maze (MWM) test was performed to evaluate the spatial learning and memory abilities of rats. The lymphocyte subsets in peripheral blood and spleen of rats were measured by flow cytometry. The levels of cytokines [i.e., interleukin (IL)-1β, IL-2, IL-4, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ)], chemokines (i.e., macrophage inflammatory protein-2 (MIP-2)), and other inflammatory mediators (i.e., cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)) in peripheral blood and hippocampus were measured by enzyme linked immunosorbent assay (ELISA).

Results

Compared with the Gn group, the Gi rats presented long escape latencies to find the platform. After acupuncture treatment, the escape latencies of the Ga group were rescued markedly when compared with the Gi group (P< 0.05). The proportion of CD4 + T lymphocytes in both spleen and peripheral blood in the Ga group increased (P< 0.05) in comparison with the Gi group. There is an obvious reduction in IL-1β (P< 0.05), IL-2 (P< 0.05), TNF-α (P< 0.01), INF-γ (P< 0.01), MIP-2 (P< 0.05), and iNOS (P< 0.01), coming along with the increased levels of IL-4 and IL-10 (P< 0.01) in the Ga group when compared with the Gi group. In addition, the hippocampus proinflammatory factors IL-1β (P< 0.01), IL-2 (P< 0.01), TNF-α (P< 0.05), INF-γ (P< 0.05), MIP-2 (P< 0.05), iNOS (P< 0.01), and COX-2 decreased in the Ga group, whereas the anti-inflammatory factors IL-4 and IL-10 (P< 0.01) increased.

Conclusion

There are abnormal immune function and peripheral inflammation in VD rats. Acupuncture can regulate the peripheral immune function and inflammation of the VD rats and can improve the cognitive dysfunction of the rats.
Arm Ergometry to Improve Mobility in Progressive Multiple Sclerosis (AMBOS)—Results of a Pilot Randomized Controlled Trial
Authors: Heinrich Inga , Rosenthal Friederike , Patra Stefan , Schulz Karl-Heinz , Welsch Götz H. , Vettorazzi Eik , Rosenkranz Sina C. , Stellmann Jan Patrick , Ramien Caren , Pöttgen Jana , Gold Stefan M. , Heesen Christoph
Published: July 2021

Background: Walking disability is one of the most frequent and burdening symptoms of progressive multiple sclerosis (MS). Most of the exercise intervention studies that showed an improvement in mobility performance were conducted in low to moderately disabled relapsing–remitting MS patients with interventions using the legs. However, MS patients with substantial walking disability hardly can perform these tasks. Earlier work has indicated that aerobic arm training might also improve walking performance and could therefore be a therapeutic option in already moderately disabled progressive MS patients.

Methods: Patients with progressive MS and EDSS 4–6.5 were randomized using a computer-generated algorithm list to either a waitlist control group (CG) or an intervention group (IG). The IG performed a 12-week home-based, individualized arm ergometry exercise training program. Maximum walking distance as measured by the 6-min walking test (6MWT) was the primary endpoint. Secondary endpoints included aerobic fitness, other mobility tests, cognitive functioning, as well as fatigue and depression.

Results: Of n = 86 screened patients, 53 with moderate disability (mean EDSS 5.5, SD 0.9) were included and data of 39 patients were analyzed. Patients in the IG showed strong adherence to the program with a mean of 67 (SD 26.4) training sessions. Maximum work load (Pmax) increased in the training group while other fitness indicators did not. Walking distance in the 6MWT improved in both training and waitlist group but not significantly more in trained patients. Similarly, other mobility measures showed no differential group effect. Cognitive functioning remained unchanged. No serious events attributable to the intervention occurred.

Conclusion: Although maximum work load improved, 3 months of high-frequency arm ergometry training of low to moderate intensity could not show improved walking ability or cognitive functioning in progressive MS compared to a waitlist CG.

The study was registered at www.clinicaltrials.gov (NCT03147105) and funded by the local MS self-help organization.
Optical Coherence Tomography Reveals Longitudinal Changes in Retinal Damage Under Different Treatments for Neuromyelitis Optica Spectrum Disorder
Authors: Zeng Pei , Du Chen , Zhang Rui , Jia Dongmei , Jiang Feng , Fan Moli , Zhang Chao
Published: July 2021

Background: Progressive retinal neuroaxonal damage after acute optic neuritis may occur in neuromyelitis optica spectrum disorder (NMOSD). However, it is unclear if treatments used to prevent attacks influence neurodegeneration.

Objectives: We aimed to investigate retinal damage in patients treated with disease-modifying drugs in a longitudinal study.

Methods: We retrospectively included 50 patients with aquaporin 4-antibody-seropositive NMOSD. Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex (mGCC) thickness, total macular volume (TMV), and optic disc measures were acquired by spectral domain optical coherence tomography in patients treated with tocilizumab, rituximab, and azathioprine.

Results: Longitudinally, in eyes with a history of ON (NMOSDON+), we observed annual thinning of mGCC [tocilizumab: −1.77 (−3.44, −0.09) μm, p = 0.041; rituximab: −2.03 (−3.58, −0.48) μm, p = 0.017; azathioprine: −1.79 (−2.22, −1.37) μm, p < 0.001], and pRNFL [tocilizumab: −2.07 (−0.75, −3.39) μm, p = 0.005; rituximab: −2.18 (−0.36, −4.00) μm, p = 0.023; azathioprine: −2.37 (−0.98, −3.75) μm, p = 0.003], reduced TMV [tocilizumab: −0.12 (−0.22, −0.01) mm3, p = 0.028; rituximab: −0.15 (−0.21, −0.08) mm3, p = 0.001; azathioprine: −0.12 (−0.20, −0.04) mm3, p = 0.006], and increased cup area [tocilizumab: 0.08 (−0.01, 0.16) mm2, p = 0.010; rituximab: 0.07 (0.01, 0.12) mm2, p = 0.019; azathioprine: 0.14 (0.02, 0.26) mm2, p = 0.023]. However, we detected no significant differences in annual changes in mGCC, pRNFL, TMV, and cup area between patients with tocilizumab, rituximab, and azathioprine in NMOSDON+ eyes. NMOSDON− eyes did not display mGCC or pRNFL thinning in patients treated with tocilizumab and rituximab. Intriguingly, we observed significant thinning of mGCC in patients treated with azathioprine compared with tocilizumab [−0.84 (−1.50, −0.18) μm vs. −0.19 (−0.87, 0.48) μm, p = 0.012] and rituximab [−0.84 (−1.50, −0.18) μm vs. −0.07 (−1.25, −2.51) μm, p = 0.015] in NMOSDON− eyes.

Conclusions: This study demonstrated that retinal ganglion cell loss is independent of ON attacks in NMOSD. Tocilizumab and rituximab may delay mGCC thinning in NMOSDON− eyes compared with azathioprine.
Recent Updates in Neurosurgical Interventions for Spontaneous Intracerebral Hemorrhage: Minimally Invasive Surgery to Improve Surgical Performance
Authors: Kobata Hitoshi , Ikeda Naokado
Published: July 2021

The efficacy and safety of surgical treatment for intracerebral hemorrhage (ICH) have long been subjects of investigation and debate. The recent results of the minimally invasive surgery plus alteplase for intracerebral hemorrhage evacuation (MISTIE) III trial demonstrated the safety of the procedure and a reduction in mortality compared to medical treatment. Although no improvement in functional outcomes was shown, the trial elucidated that benefits of intervention depend on surgical performance: a greater ICH reduction, defined as ≤ 15 mL end of treatment ICH volume or ≥70% volume reduction, correlated with significant functional improvement. Recent meta-analyses suggested the benefits of neurosurgical hematoma evacuation, especially when performed earlier and done using minimally invasive procedures. In MISTIE III, to confirm hemostasis and reduce the risk of rebleeding, the mean time from onset to surgery and treatment completion took 47 and 123 h, respectively. Theoretically, the earlier the hematoma is removed, the better the outcome. Therefore, a higher rate of hematoma reduction within an earlier time course may be beneficial. Neuroendoscopic surgery enables less invasive removal of ICH under direct visualization. Minimally invasive procedures have continued to evolve with the support of advanced guidance systems and devices in favor of better surgical performance. Ongoing randomized controlled trials utilizing emerging minimally invasive techniques, such as the Early Minimally Invasive Removal of Intra Cerebral Hemorrhage (ENRICH) trial, Minimally Invasive Endoscopic Surgical Treatment with Apollo/Artemis in Patients with Brain Hemorrhage (INVEST) trial, and the Dutch Intracerebral Hemorrhage Surgery Trial (DIST), may provide significant information on the optimal treatment for ICH.
A Dissociation of Attention, Executive Function and Reaction to Difficulty: Development of the MindPulse Test, a Novel Digital Neuropsychological Test for Precise Quantification of Perceptual-Motor Decision-Making Processes
Authors: Suarez Sandra , Eynard Bertrand , Granon Sylvie
Published: July 2021

Traditionally, neuropsychological testing has assessed processing speed and precision, closely related to the ability to perform high-order cognitive tasks. An individual making a decision under time pressure must constantly rebalance its speed to action in order to account for possible errors. A deficit in processing speed appears to be afrequent disorder caused by cerebral damage — but it can be hard to pinpoint the exact cause of the slowdown. It is therefore important to separate the perceptual-motor component of processing speed from the decision-time component. We present a technique to isolate Reaction Times (RTs): a short digital test to assess the decision-making abilities of individuals by gauging their ability to balance between speed and precision. Our hypothesis is that some subjects willaccelerate, and others slow down in the face of the difficulty. This pilot study, conducted on 83 neurotypical adult volunteers, used images stimuli. The test was designed to measure RTs and correctness. After learning release gesture, the subjects were presented with three tasks: a simple Reaction Time task, a Go/No-Go, and a complex Go/No-Go with 2 simultaneous Choices. All three tasks have in common a perceptual component and a motor response. By measuring the 3 reference points requiring attentional and executive processing, while progressively increasing the conceptual complexity of the task, we were able to compare the processing times for different tasks — thus calculating the deceleration specific to the reaction time linked to difficulty. We defined the difficulty coefficient of a task as being the ratio of the group average time of this task minus the base time/average time of the unit task minus the base time. We found that RTs can be broken down into three elementary, uncorrelated components: Reaction Time, Executive Speed, and Reaction to Difficulty (RD). We hypothesized that RD reflects how the subject reacts to difficulty by accelerating (RD < 0) or decelerating (RD > 0). Thus we provide here a first proof of concept: the ability to measure four axes of the speed-precision trade-off inherent in a subject’s fundamental decision making: perceptual-motor speed, executive speed, subject accuracy, and reaction to difficulty.
Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms
Authors: Wei Zenghui , Koya Jagadish , Reznik Sandra E.
Published: July 2021

Alzheimer disease (AD) is a chronic neurodegenerative disease that accounts for 60–70% of dementia and is the sixth leading cause of death in the United States. The pathogenesis of this debilitating disorder is still not completely understood. New insights into the pathogenesis of AD are needed in order to develop novel pharmacologic approaches. In recent years, numerous studies have shown that insulin resistance plays a significant role in the development of AD. Over 80% of patients with AD have type II diabetes (T2DM) or abnormal serum glucose, suggesting that the pathogenic mechanisms of insulin resistance and AD likely overlap. Insulin resistance increases neuroinflammation, which promotes both amyloid β-protein deposition and aberrant tau phosphorylation. By increasing production of reactive oxygen species, insulin resistance triggers amyloid β-protein accumulation. Oxidative stress associated with insulin resistance also dysregulates glycogen synthase kinase 3-β (GSK-3β), which leads to increased tau phosphorylation. Both insulin and amyloid β-protein are metabolized by insulin degrading enzyme (IDE). Defects in this enzyme are the basis for a strong association between T2DM and AD. This review highlights multiple pathogenic mechanisms induced by insulin resistance that are implicated in AD. Several pharmacologic approaches to AD associated with insulin resistance are presented.
Nutrition Education Program and Physical Activity Improve the Adherence to the Mediterranean Diet: Impact on Inflammatory Biomarker Levels in Healthy Adolescents From the DIMENU Longitudinal Study
Authors: Morelli Catia , Avolio Ennio , Galluccio Angelo , Caparello Giovanna , Manes Emanuele , Ferraro Simona , Caruso Antonella , De Rose Daniela , Barone Ines , Adornetto Carlo , Greco Gianluigi , Catalano Stefania , Andò Sebastiano , Sisci Diego , Giordano Cinzia , Bonofiglio Daniela
Published: July 2021

Adherence to Mediterranean diet (MD) and physical activity (PA) in adolescence represent powerful indicators of healthy lifestyles in adulthood. The aim of this longitudinal study was to investigate the impact of nutrition education program (NEP) on the adherence to the MD and on the inflammatory status in healthy adolescents, categorized into three groups according to their level of PA (inactivity, moderate intensity, and vigorous intensity). As a part of the DIMENU (Dieta Mediterranea & Nuoto) study, 85 adolescents (aged 14–17 years) participated in the nutrition education sessions provided by a team of nutritionists and endocrinologists at T0. All participants underwent anthropometric measurements, bio-impedentiometric analysis (BIA), and measurements of inflammatory biomarkers such as ferritin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Data were collected at baseline (T0) and 6 months after NEP (T1). To assess the adherence to the MD, we used KIDMED score. In our adolescents, we found an average MD adherence, which was increased at T1 compared with T0 (T0: 6.03 ± 2.33 vs. T1: 6.96 ± 2.03,p= 0.002), with an enhanced percentage of adolescents with optimal (≥8 score) MD adherence over the study period (T0: 24.71% vs. T1: 43.52%,p= 0.001). Interestingly, in linear mixed-effects models, we found that NEP and vigorous-intensity PA levels independently influenced KIDMED score (β = 0.868,p< 0.0001 and β = 1.567,p= 0.009, respectively). Using ANOVA, NEP had significant effects on serum ferritin levels (p< 0.001), while either NEP or PA influenced ESR (p= 0.035 and 0.002, respectively). We also observed in linear mixed-effects models that NEP had a negative effect on ferritin and CRP (β = −14.763,p< 0.001 and β = −0.714,p= 0.02, respectively). Our results suggest the usefulness to promote healthy lifestyle, including either nutrition education interventions, or PA to improve MD adherence and to impact the inflammatory status in adolescence as a strategy for the prevention of chronic non-communicable diseases over the entire lifespan.
Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer
Authors: Zhao Chongru , Hu Weijie , Xu Yi , Wang Dawei , Wang Yichen , Lv Wenchang , Xiong Mingchen , Yi Yi , Wang Haiping , Zhang Qi , Wu Yiping
Published: July 2021

Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.
miRNome and Functional Network Analysis of PGRMC1 Regulated miRNA Target Genes Identify Pathways and Biological Functions Associated With Triple Negative Breast Cancer
Authors: Pedroza Diego A. , Ramirez Matthew , Rajamanickam Venkatesh , Subramani Ramadevi , Margolis Victoria , Gurbuz Tugba , Estrada Adriana , Lakshmanaswamy Rajkumar
Published: July 2021

Background

Increased expression of the progesterone receptor membrane component 1, a heme and progesterone binding protein, is frequently found in triple negative breast cancer tissue. The basis for the expression of PGRMC1 and its regulation on cellular signaling mechanisms remain largely unknown. Therefore, we aim to study microRNAs that target selective genes and mechanisms that are regulated by PGRMC1 in TNBCs.

Methods

To identify altered miRNAs, whole human miRNome profiling was performed following AG-205 treatment and PGRMC1 silencing. Network analysis identified miRNA target genes while KEGG, REACTOME and Gene ontology were used to explore altered signaling pathways, biological processes, and molecular functions.

Results

KEGG term pathway analysis revealed that upregulated miRNAs target specific genes that are involved in signaling pathways that play a major role in carcinogenesis. While multiple downregulated miRNAs are known oncogenes and have been previously demonstrated to be overexpressed in a variety of cancers. Overlapping miRNA target genes associated with KEGG term pathways were identified and overexpression/amplification of these genes was observed in invasive breast carcinoma tissue from TCGA. Further, the top two genes (CCND1 and YWHAZ) which are highly genetically altered are also associated with poorer overall survival.

Conclusions

Thus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
The Use of Whole Genome and Exome Sequencing for Newborn Screening: Challenges and Opportunities for Population Health
Authors: Woerner Audrey C. , Gallagher Renata C. , Vockley Jerry , Adhikari Aashish N.
Published: July 2021

Newborn screening (NBS) is a population-based program with a goal of reducing the burden of disease for conditions with significant clinical impact on neonates. Screening tests were originally developed and implemented one at a time, but newer methods have allowed the use of multiplex technologies to expand additions more rapidly to standard panels. Recent improvements in next-generation sequencing are also evolving rapidly from first focusing on individual genes, then panels, and finally all genes as encompassed by whole exome and genome sequencing. The intersection of these two technologies brings the revolutionary possibility of identifying all genetic disorders in newborns, allowing implementation of therapies at the optimum time regardless of symptoms. This article reviews the history of newborn screening and early studies examining the use of whole genome and exome sequencing as a screening tool. Lessons learned from these studies are discussed, along with technical, ethical, and societal challenges to broad implementation.
Extract From Tetrastigma hemsleyanum Leaf Alleviates Pseudomonas aeruginosa Lung Infection: Network Pharmacology Analysis and Experimental Evidence
Authors: Lou Tian-ling , Ji Tao , Peng Xin , Ji Wei-wei , Yuan Li-xia , Wang Juan , Li Shi-min , Zhang Shun , Shi Qiao-yun
Published: July 2021

Tetrastigma hemsleyanum Diels & Gilg (T. hemsleyanum) has attracted much attention due to its ability on pneumonia, bronchitis, and immune-related diseases, while its functional components and underlying mechanism of action on pneumonia have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the action mechanism of T. hemsleyanum leaf in the treatment of pneumonia. In this study, the results of network pharmacology demonstrated that there were 34 active components and 80 drug–disease targets in T. hemsleyanum leaf, which were strongly in connection with signal transduction, inflammatory response, and the oxidation–reduction process. Subsequently, a mouse model of pneumonia induced by Pseudomonas aeruginosa (P. aeruginosa) was established to validate the predicted results of network pharmacology. In the animal experiments, aqueous extract of T. hemsleyanum leaf (EFT) significantly attenuated the histopathological changes of lung tissue in P. aeruginosa–induced mice and reduced the number of bacterial colonies in BALFs by 96.84% (p < 0.01). Moreover, EFT treatment suppressed the increase of pro-inflammatory cytokines IL-17, IL-6, and TNF-α in lung tissues triggered by P. aeruginosa, which led to the increase of Th17 cells (p < 0.05). High concentration of EFT treatment (2.0 g/kg) obviously increased the anti-inflammatory cytokine levels, accompanied by the enhancement of Treg proportion in a dose-dependent manner and a notable reversal of transcription factor RORγt expression. These findings demonstrated that network pharmacology was a useful tool for TCM research, and the anti-inflammatory effect of EFT was achieved by maintaining Th17/Treg immune homeostasis and thereby suppressing the inflammatory immune response.
Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases
Authors: Wu Duoduo , Lim Dawn Ka-Ann , Lim Blanche Xiao Hong , Wong Nathan , Hafezi Farhad , Manotosh Ray , Lim Chris Hong Long
Published: July 2021

Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.
Glucagon-Like Peptide-1 Analog Exendin-4 Ameliorates Cocaine-Mediated Behavior by Inhibiting Toll-Like Receptor 4 Signaling in Mice
Authors: Zhu Changliang , Tao Hong , Rong Shikuo , Xiao Lifei , Li Xinxiao , Jiang Shucai , Guo Baorui , Wang Lei , Ding Jiangwei , Gao Caibing , Chang Haigang , Sun Tao , Wang Feng
Published: July 2021

Exendin-4 (Ex4), a long-lasting glucagon-like peptide-1 analog, was reported to exert favourable actions on inhibiting cocaine-associated rewarding and reinforcing effects of drug in animal models of addiction. However, the therapeutic potential of different dose of GLP-1 receptor agonist Ex4 in different behavioral paradigms and the underlying pharmacological mechanisms of action are incompletely understood. Herein, we firstly investigated the effects of Ex4 on cocaine-induced condition place preference (CPP) as well as extinction and reinstatement in male C57BL/6J mice. Additionally, we sought to elucidate the underlying pharmacological mechanism of these actions of Ex4. The paradigm of cocaine-induced CPP was established using 20 mg/kg cocaine or saline alternately during conditioning, while the reinstatement paradigm was modeled using 10 mg/kg cocaine on the reinstatement day. Different dose of Ex4 was administrated intraperitoneally either during conditioning or during extinction state or only on the test day. To elucidate the molecular mechanism underlying the potential effects of Ex4 on maladaptive behaviors of cocaine, the TLR4-related inflammation within the hippocampus was observed by immunofluorescence staining, and the expression levels of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were detected by Western blotting. As a consequence, systemic administration of different dose of Ex4 was sufficient to inhibit the acquisition and expression of cocaine-induced CPP, facilitate the extinction of cocaine-associated reward and attenuate reinstatement of cocaine-induced behavior. Furthermore, Ex4 treatment diminished expression levels of TLR4, TNF-α, and IL-1β, which were up-regulated by cocaine exposure. Altogether, our results indicated that Ex4 effectively ameliorated cocaine-induced behaviors likely through neurobiological mechanisms partly attributable to the inhibition of TLR4, TNF-α and IL-1β in mice. Consequently, our findings improved our understanding of the efficacy of Ex4 for the amelioration of cocaine-induced behavior and suggested that Ex4 may be applied as a drug candidate for cocaine addiction.
Pharmacotherapeutic Patterns and Patients’ Access to Pharmacotherapy for Some Rare Diseases in Bulgaria – A Pilot Comparative Study
Authors: Kamusheva Maria , Dimitrova Maria , Tachkov Konstantin , Petrova Guenka , Mitkova Zornitsa
Published: July 2021

Provision of the latest innovative and advanced therapies for rare diseases (RDs) patients, following the international therapeutic recommendations, is crucial and necessary for both practitioners and patients. The goal is to assess the access of Bulgarian patients with the most cost-consuming RDs to medicines and to compare the pharmacotherapeutic patterns in Bulgaria and the relevant European professional associations. Pharmaco-therapeutic guidelines for treating the most cost-consuming RDs in Bulgaria were analyzed to assess their compliance with the European ones. Market entrance was evaluated through analysis of the availability of medicines in the Positive Drug List (PDL) and their date of inclusion since marketing authorization. Guidelines’ compliance index was calculated and patient access was analyzed through evaluation of the National Health Insurance Fund (NHIF) standards, which provide additional criteria for treatment initiation. The analyzed guidelines follow the adopted recommendations by the relevant European professional associations. NHIF have exclusion and inclusion criteria for initiating treatment with medicines for rare diseases and for continuation. The average time-lag between centralized procedure approval and inclusion in the Bulgarian PDL for orphan medicinal products (MPs) is 6.75 years (SD = 4.96) with the longest time observed for eptacog alfa (20 years) and the shortest for rurioctocog alfa pegol, octocog alfa and simoctocog alfa (1 year). Bulgarian patients with cystic fibrosis with pulmonary manifestation had a wait time of only 1.6 years to get access to innovative, centrally authorized medicines, whereas the period for access to acromegaly treatment was 8.2 years. The main factors influencing market entrance and patient access are the time to inclusion in the PDL and the NHIF criteria.