bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 Serology Monitoring of a Cancer Center Staff in the Pandemic Most Infected Italian Region
Authors: Ciniselli Chiara Maura , Micali Arianna , De Cecco Loris , Notti Paola , Sinno Valentina , Luison Elena , Melani Cecilia C. , Daidone Maria Grazia , Apolone Giovanni , Verderio Paolo , Figini Mariangela
Published: March 2021

Since the beginning of the COVID-19 outbreak, Cancer Centers adopted specific procedures both to protect patients and to monitor the possible spread of SARS-CoV-2 among healthcare personnel (HCP). In April 2020 at Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, one of the three oncologic hubs in Lombardy where the Health Regional Authorities referred all the cancer patients of the region, we implemented a prospective longitudinal study aimed at monitoring the serological response to SARS-Cov-2 in HCP. One hundred and ten HCP answered a questionnaire and were screened by nasopharyngeal swabs as well as for IgM/IgG levels; seropositive HCPs were further screened every 40–45 days using SARS-CoV-2-specific serology. We identified a fraction of HCP with long-term anti-SARS-CoV-2 antibody responses, though negative for viral RNA, and thus probably able to safely approach fragile cancer patients. Monitoring asymptomatic HCP might provide useful information to organize the healthcare service in a Cancer Center, while waiting for the effectiveness of the active immunization by SARS-CoV-2 vaccines, which will provide protection from infection.
Autophagy and Extracellular Vesicles in Colorectal Cancer: Interactions and Common Actors?
Authors: Auger Clément , Christou Niki , Brunel Aude , Perraud Aurélie , Verdier Mireille
Published: March 2021

Autophagy is a homeostatic process involved in the degradation of disabled proteins and organelles using lysosomes. This mechanism requires the recruitment of specialized proteins for vesicle trafficking, that may also be involved in other types of machinery such as the biogenesis and secretion of extracellular vesicles (EVs), and particularly small EVs called exosomes. Among these proteins, Rab-GTPases may operate in both pathways, thus representing an interesting avenue for further study regarding the interaction between autophagy and extracellular vesicle machinery. Both mechanisms are involved in the development of colorectal cancer (CRC), particularly in cancer stem cell (CSC) survival and communication, although they are not specific to CRC or CSCs. This highlights the importance of studying the crosstalk between autophagy and EVs biogenesis and release.
Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients
Authors: Gounant Valérie , Duruisseaux Michael , Soussi Ghassen , Van Hulst Sylvie , Bylicki Olivier , Cadranel Jacques , Wislez Marie , Trédaniel Jean , Spano Jean-Philippe , Helissey Carole , Chouaid Christos , Molinier Olivier , Dhalluin Xavier , Doucet Ludovic , Hureaux José , Cazes Aurélie , Zalcman Gérard
Published: March 2021

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.
The Antitumor Effects of Plasma-Activated Saline on Muscle-Invasive Bladder Cancer Cells In Vitro and In Vivo Demonstrate Its Feasibility as a Potential Therapeutic Approach
Authors: Zhang Hao , Zhang Jishen , Guo Bo , Chen Hailan , Xu Dehui , Kong Michael G.
Published: March 2021

Muscle-invasive bladder cancer (MIBC) is a fast-growing and aggressive malignant tumor in urinary system. Since chemotherapy and immunotherapy are only useable with a few MIBC patients, the clinical treatment of MIBC still faces challenges. Here, we examined the feasibility of plasma-activated saline (PAS) as a fledgling therapeutic strategy for MIBC treatment. Our data showed that plasma irradiation could generate a variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in saline. In vivo tests revealed that pericarcinomatous tissue injection with PAS was effective at preventing subcutaneous bladder tumor growth, with no side effects to the visceral organs after long-term administration, as well as having no obvious influence on the various biochemistry indices of the blood in mice. The in vitro studies indicated that adding 30% PAS in cell culture media causes oxidative damage to the bladder transitional cells T24 and J82 through enhancing the intracellular ROS level, and eventually induces cancer cells’ apoptosis by activating the ROS-mediated Fas/CD95 pathway. Therefore, for an intracavity tumor, these initial observations suggest that the soaking of the tumor tissue with PAS by intravesical perfusion may be a novel treatment option for bladder cancer.
Adoptive T Cell Therapy Is Complemented by Oncolytic Virotherapy with Fusogenic VSV-NDV in Combination Treatment of Murine Melanoma
Authors: Krabbe Teresa , Marek Janina , Groll Tanja , Steiger Katja , Schmid Roland M. , Krackhardt Angela M. , Altomonte Jennifer
Published: March 2021

Cancer immunotherapies have made major advancements in recent years and are becoming the prevalent treatment options for numerous tumor entities. However, substantial response rates have only been observed in specific subsets of patients since pre-existing factors determine the susceptibility of a tumor to these therapies. The development of approaches that can actively induce an anti-tumor immune response, such as adoptive cell transfer and oncolytic virotherapy, have shown clinical success in the treatment of leukemia and melanoma, respectively. Based on the immune-stimulatory capacity of oncolytic VSV-NDV virotherapy, we envisioned a combination approach to synergize with adoptive T cell transfer, in order to enhance tumor cell killing. Using the immune-competent B16 melanoma model, we demonstrate that combination treatment has beneficial effects on the suppressive microenvironment through upregulation of MHC-I and maintaining low expression levels of PD-L1 on tumor cells. The approach led to additive cytotoxic effects and improved the recruitment of T cells to virus-infected tumor cells in vitro and in vivo. We observed substantial delays in tumor growth and evidence of abscopal effects, as well as prolongation of overall survival time when administered at clinically relevant dosing conditions. Our results indicate that treatment with oncolytic VSV-NDV, combined with adoptive T cell therapy, induces multi-mechanistic and synergistic tumor responses, which supports the further development of this promising translational approach.
Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multicenter Study of the Italian Sarcoma Group
Authors: Palmerini Emanuela , Sanfilippo Roberta , Grignani Giovanni , Buonadonna Angela , Romanini Antonella , Badalamenti Giuseppe , Ferraresi Virginia , Vincenzi Bruno , Comandone Alessandro , Pizzolorusso Antonio , Brunello Antonella , Gelsomino Fabio , Pas Tommaso De , Ibrahim Toni , Grosso Federica , Zanelli Francesca , Pantaleo Maria Abbondanza , Milesi Laura , Ciuffreda Libero , Ferrari Vittorio , Marchesi Emanuela , Quattrini Irene , Righi Alberto , Setola Elisabetta , Carretta Elisa , Picci Piero , Ferrari Stefano
Published: March 2021

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).
Mitral Valve Subacute Endocarditis Caused by Abiotrophia Defectiva: A Case Report
Authors: Faria Catarina , Guerreiro Renato , Cruz Sofia , Fernandes Marco
Published: March 2021

Abiotrophia defectiva is a rare agent of endocarditis and subacute presentation may delay the diagnosis. We present the case of a 41-year-old male who was admitted to the hospital for further investigation regarding a consumptive syndrome with microcytic anaemia. Past medical history included new-onset mitral insufficiency followed by an ischaemic stroke due to small vessel disease. Thoraco-abdominal computed tomography revealed a splenic infarction. In the presence of two ischaemic events associated with mitral valve disease of unknown aetiology, we considered the possibility of subacute endocarditis. Blood cultures were positive for Abiotrophia defectiva, and transoesophageal echocardiography confirmed the diagnosis. As a subacute presentation of endocarditis, the paucity of symptoms caused a five-month delay in diagnosis. New-onset valvular disease and a stroke in an otherwise healthy young patient should always prompt proper investigation. This case highlights several complications caused by septic emboli of undiagnosed and untreated endocarditis.
Preparation and Characterization of Sustained-Release Naringin Coating on Magnesium Surface
Authors: Mu Liting , Sun Quan , Cui Gang , Yuan Shidan , Wang Jingyan , Ma Zhen , Li Muqin
Published: March 2021

Given the three-dimensional multi-level structure of natural bone and the multi-factor time-shifting effect in the healing process after bone trauma, there are plans to introduce drug-controlled release systems into the treatment of orthopedic diseases. To achieve multi-level loading and controlled release of biologically active substances, it is necessary to create synergistic behavior between biological factors, thereby improving the bone regeneration ability of artificial bone replacement materials. A naringin-loaded (NG) coating was prepared, compared with ultrasonic micro-arc oxidation (UMAO). The coating was characterized by X-ray diffraction, infrared spectroscopy, and scanning electron microscopy. The corrosion resistance of the coating was studied through the wetting angle and polarization curve. The high-performance liquid chromatography method was used to test the release of the drug. It can be seen from the experimental results that the NG coating has a larger wetting angle and better corrosion resistance. In addition, the NG coating produces more apatite substances and has good biological activity. The NG coatings can stimulate the natural bone regeneration and repair process by releasing drugs during the process, which can effectively promote bone regeneration and repair after implantation in the body.
The Impact of COVID-19 on Learning: Investigating EFL Learners’ Engagement in Online Courses in Saudi Arabia
Authors: Oraif Iman , Elyas Tariq
Published: March 2021

As a result of the COVID-19 pandemic, most learning around the world has been transferred online. Learners who previously engaged in traditional learning now face a new challenge, a distinctive rise in e-learning. This drastic change could impact their learning behavior and acceptance of the change. As a result, their learning engagement could be affected massively. The present study therefore explores learners’ level of engagement in online courses using a designated school platform within the context of Saudi Arabia. A reliable measure was implemented in the study based on the Student Course Engagement Questionnaire (SCEQ). A survey was consequently conducted in a high school in Saudi Arabia, with a sample of 379 female English as a foreign language (EFL) learners studying a general English language course. The results revealed a high level of engagement among EFL Saudi learners. This helped to generate recommendations to improve EFL practices, primarily through the use of an online environment either at the national level in the Saudi context or the international level.
Phenological Analysis of Sub-Alpine Forest on Jeju Island, South Korea, Using Data Fusion of Landsat and MODIS Products
Authors: Park Sang-Jin , Jeong Seung-Gyu , Park Yong , Kim Sang-Hyuk , Lee Dong-Kun , Mo Yong-Won , Jang Dong-Seok , Park Kyung-Min
Published: March 2021

Climate change poses a disproportionate risk to alpine ecosystems. Effective monitoring of forest phenological responses to climate change is critical for predicting and managing threats to alpine populations. Remote sensing can be used to monitor forest communities in dynamic landscapes for responses to climate change at the species level. Spatiotemporal fusion technology using remote sensing images is an effective way of detecting gradual phenological changes over time and seasonal responses to climate change. The spatial and temporal adaptive reflectance fusion model (STARFM) is a widely used data fusion algorithm for Landsat and MODIS imagery. This study aims to identify forest phenological characteristics and changes at the species–community level by fusing spatiotemporal data from Landsat and MODIS imagery. We fused 18 images from March to November for 2000, 2010, and 2019. (The resulting STARFM-fused images exhibited accuracies of RMSE = 0.0402 and R2 = 0.795. We found that the normalized difference vegetation index (NDVI) value increased with time, which suggests that increasing temperature due to climate change has affected the start of the growth season in the study region. From this study, we found that increasing temperature affects the phenology of these regions, and forest management strategies like monitoring phenology using remote sensing technique should evaluate the effects of climate change.
Extrusion Processing of Pure Chokeberry (Aronia melanocarpa) Pomace: Impact on Dietary Fiber Profile and Bioactive Compounds
Authors: Schmid Vera , Steck Jan , Mayer-Miebach Esther , Behsnilian Diana , Bunzel Mirko , Karbstein Heike P. , Emin M. Azad
Published: March 2021

The partial substitution of starch with dietary fiber (DF) in extruded ready-to-eat texturized (RTE) cereals has been suggested as a strategy to reduce the high glycemic index of these food products. Here, we study the impact of extrusion processing on pure chokeberry (Aronia melanocarpa) pomace powder (CPP) rich in DF and polyphenols (PP) focusing on the content and profile of the DF fractions, stability of PP, and techno-functional properties of the extrudates. Using a co-rotating twin-screw extruder, different screw speeds were applied to CPP with different water contents (cw), which resulted in specific mechanical energies (SME) in the range of 145–222 Whkg−1 and material temperatures (TM) in the range of 123–155 °C. High molecular weight soluble DF contents slightly increase with increasing thermomechanical stress up to 16.1 ± 0.8 g/100 g dm as compared to CPP (11.5 ± 1.2 g/100 g dm), but total DF (TDF) contents (58.6 ± 0.8 g/100 g dm) did not change. DF structural analysis revealed extrusion-based changes in the portions of pectic polysaccharides (type I rhamnogalacturonan) in the soluble and insoluble DF fractions. Contents of thermolabile anthocyanins decrease linearly with SME and temperature from 1.80 ± 0.09 g/100 g dm in CPP to 0.24 ± 0.06 g/100 g dm (222 Whkg−1, 155 °C), but phenolic acids and flavonoids appear to be largely unaffected. Resulting techno-functional (water absorption and water solubility) and physical properties related to the sensory characteristics (expansion, hardness, and color) of pure CPP extrudates support the expectation that granulated CPP extrudates may be a suitable food ingredient rich in DF and PP.
Environmental Factors and Metal Mobilisation in Alluvial Sediments—Minas Gerais, Brazil
Authors: Fonseca Rita , Pinho Catarina , Albuquerque Teresa , Araújo Joana
Published: March 2021

In areas contaminated by potentially toxic elements (PTEs), knowledge of processes of metal mobilisation is the basis for the choice of appropriate remediation methodologies. The mobilisation of metals is a function of several factors, and the response to these factors must be well known during the planning of remediation strategies. The activity of an ore metallurgical plant in South-East Brazil resulted in major contamination by several heavy metals. Reversing the contamination’s negative impact required geochemical assessment of the area, including the physicochemical characterisation, quantification, and delimitation of PTEs, and the rating of the solubilisation/mobilisation capacity of these elements. The definition of spatial patterns for PTEs’ distribution allowed the construction of contamination risk maps which work as a tool for the mitigation and control of the contamination plume. The chemical analysis of interstitial water and selective and sequential extraction methodologies showed that elements that occur in the environment in critical concentrations (Zn, Cd, Pb, As) are mostly associated with easily mobilised forms (soluble, exchangeable cations, associated with Mn oxides). Given the great mobility of the contamination plume, any process of removal of contaminated material becomes unfeasible, thus the strategy of remediation for the stream and associated alluvial deposits must be based on methods of in situ decontamination.
Texture and Shape Analysis of Quartzite Mylonites of the Metamorphic Sole of the Samail Ophiolite (Oman): Evidence for Syn- and Post-Obduction Deformation
Authors: Hallas Peter , Bauer Wilfried
Published: March 2021

The metamorphic sole, tectonically welded to the base of the Samail ophiolite in a supra-subduction system, is assumed to play the main role in strain accumulation during later thrusting onto the Arabian Plate (i.e., during obduction). The present study deals with five quartzite samples representative of the upper amphibolite and lower greenschist facies parts of the sole. Whole-rock textures obtained by neutron time-of-flight technique were coupled with microstructural observation using electron backscatter diffraction analyses. The quartz microstructural fabrics and textures in the upper and lower parts of the sole represent grain boundary migration and [c]-in-Y textures and subgrain rotation recrystallization and {r}-in-Z textures, respectively. The shear sense in these samples points to top-to-the-SW to SSW shear. One sample of the upper part, yielding a higher calcite amount, is later overprinted by bulging and displays top-to-the-NNE shear. We postulate to differentiate two main deformation steps. The first is the overall present subgrain rotation and grain boundary migration recrystallization combined to top ~SW shear is related to the sole accretion to the ophiolite and the eventually following thrusting onto the Arabian Plate. The second is correlated to a post-obduction extensional top-to-the-NNE shearing, which is associated with tectonic thinning of the ophiolite and mainly documented in the underlying autochthonous units.
The Influence of Nordic Walking on Isokinetic Trunk Muscle Endurance and Sagittal Spinal Curvatures in Women after Breast Cancer Treatment: Age-Specific Indicators
Authors: Hanuszkiewicz Justyna , Woźniewski Marek , Malicka Iwona
Published: March 2021

Nordic walking (NW) is a popular form of rehabilitation. NW improves psychophysical condition in breast cancer (BC) survivors. This study aimed to analyze the effects of NW on functional and postural changes of the trunk in women of different ages after BC. We hypothesized that an age relationship would be found. BC survivors (n = 39) were stratified by age as “middle- aged” (45–59 years) or “older” (60–75 years), then randomly allocated to the training intervention. A study group (SG, n = 19) participated in NW and a control group (CG, n = 20) performed general gymnastics. The sagittal spinal curvatures and isokinetic trunk muscle endurance were recorded at two time points, pre- and post-training intervention. Significant within NW group changes (p < 0.05) were found for the total work (TW) and average power (AP) of trunk flexors and extensors and the upper thoracic angle in middle-aged women. In older Nordic walkers, significant increases in TW and AP of the trunk flexor muscles were observed, with a negative increase in the trunk inclination angle. In CG, no significant functional or postural changes were observed in response to general gymnastics. NW improved both functional and postural changes in middle-aged women. This study identified the limitations of NW training in older women.
Utilizing a Novel 2D Image Processing System for Relating Body Composition Metrics to Performance in Collegiate Female Rowers
Authors: Esco Michael R. , Holmes Clifton J. , Sullivan Katherine , Hornikel Bjoern , Fedewa Michael V.
Published: March 2021

The purpose of this study was to determine if rowing performance was associated with fat mass (FM) or fat-free mass (FFM) measured using a novel 2D digital image analysis system. Nineteen female rowers (ages = 20.3 ± 1.0 years, weight = 73.8 ± 8.3 kg, height = 172.7 ± 4.7 cm) participated in this study. FM and FFM were estimated with a smartphone application that uses an automated 2D image analysis program. Rowing performance was measured using a 2 km (2k) timed trial on an indoor ergometer. The average speed of the timed trial was recorded in raw units (m·s−1) and adjusted for body weight (m·s−1·kg−1). FFM was significantly correlated to unadjusted 2k speed (r = 0.67, p < 0.05), but not for FM (r = 0.44, p > 0.05). When 2k speed was adjusted to account for body weight, significant correlations were found with FM (r = −0.56, p < 0.05), but not FFM (r = −0.34, p > 0.05). These data indicate that both FM and FFM are related to rowing performance in female athletes, but the significance of the relationships is dependent on overall body mass. In addition, the novel 2D imaging system appears to be a suitable field technique when relating body composition to rowing performance.
Sport in Town: The Smart Healthy ENV Project, a Pilot Study of Physical Activity with Multiparametric Monitoring
Authors: Laurino Marco , Lomonaco Tommaso , Bellagambi Francesca Giuseppa , Ghimenti Silvia , Messeri Alessandro , Morabito Marco , Marrucci Elena , Pratali Lorenza , Trivella Maria Giovanna
Published: March 2021

Background: Increasing evidence links meteorological characteristics and air pollution to physiological responses during sports activities in urban areas with different traffic levels. Objective: The main objective of the Smart Healthy ENV (SHE, “Smart Monitoring Integrated System For A Healthy Urban Environment In Smart Cities”) project was to identify the specific responses of a group of volunteers during physical activity, by monitoring their heart rates and collecting breath samples, combined with data on meteorological determinants and pollution substances obtained through fixed sensor nodes placed along city routes and remotely connected to a dedicated data acquisition server. Methods: Monitoring stations were placed along two urban routes in Pisa, each two km long, with one located within the park beside the Arno river (green route) and the other in a crowded traffic zone (red route). Our sample participants were engaged in sports activities (N = 15, with different levels of ability) and were monitored through wearable sensors. They were first asked to walk back and forth (4 km) and then to run the same route. The experimental sessions were conducted over one day per route. A breath sample was also collected before each test. A questionnaire concerning temperature and fatigue perception was administered for all of the steps of the study over the two days. Results: The heart rates of the participants were monitored in the baseline condition, during walking, and while running, and were correlated with meteorological and pollutant data and with breath composition. Changes in the heart rates and breath composition were detected during the experimental sessions. These variations were related to the physical activity and to the meteorological conditions and air pollution levels. Conclusions: The SHE project can be considered a proof-of-concept study aimed at monitoring physiological and environmental variables during physical activity in urban areas, and can be used in future studies to provide useful information to those involved in sports and the broader community.
Phytoremediation and Microorganisms-Assisted Phytoremediation of Mercury-Contaminated Soils: Challenges and Perspectives
Authors: Tiodar Emanuela D. , Văcar Cristina L. , Podar Dorina
Published: March 2021

Mercury (Hg) pollution is a global threat to human and environmental health because of its toxicity, mobility and long-term persistence. Although costly engineering-based technologies can be used to treat heavily Hg-contaminated areas, they are not suitable for decontaminating agricultural or extensively-polluted soils. Emerging phyto- and bioremediation strategies for decontaminating Hg-polluted soils generally involve low investment, simple operation, and in situ application, and they are less destructive for the ecosystem. Current understanding of the uptake, translocation and sequestration of Hg in plants is reviewed to highlight new avenues for exploration in phytoremediation research, and different phytoremediation strategies (phytostabilization, phytoextraction and phytovolatilization) are discussed. Research aimed at identifying suitable plant species and associated-microorganisms for use in phytoremediation of Hg-contaminated soils is also surveyed. Investigation into the potential use of transgenic plants in Hg-phytoremediation is described. Recent research on exploiting the beneficial interactions between plants and microorganisms (bacteria and fungi) that are Hg-resistant and secrete plant growth promoting compounds is reviewed. We highlight areas where more research is required into the effective use of phytoremediation on Hg-contaminated sites, and conclude that the approaches it offers provide considerable potential for the future.
Tuberculosis and Non-Communicable Disease Multimorbidity: An Analysis of the World Health Survey in 48 Low- and Middle-Income Countries
Authors: Stubbs Brendon , Siddiqi Kamran , Elsey Helen , Siddiqi Najma , Ma Ruimin , Romano Eugenia , Siddiqi Sameen , Koyanagi Ai
Published: March 2021

Tuberculosis (TB) is a leading cause of mortality in low- and middle-income countries (LMICs). TB multimorbidity [TB and ≥1 non-communicable diseases (NCDs)] is common, but studies are sparse. Cross-sectional, community-based data including adults from 21 low-income countries and 27 middle-income countries were utilized from the World Health Survey. Associations between 9 NCDs and TB were assessed with multivariable logistic regression analysis. Years lived with disability (YLDs) were calculated using disability weights provided by the 2017 Global Burden of Disease Study. Eight out of 9 NCDs (all except visual impairment) were associated with TB (odds ratio (OR) ranging from 1.38–4.0). Prevalence of self-reported TB increased linearly with increasing numbers of NCDs. Compared to those with no NCDs, those who had 1, 2, 3, 4, and ≥5 NCDs had 2.61 (95% confidence interval (CI) = 2.14–3.22), 4.71 (95%CI = 3.67–6.11), 6.96 (95%CI = 4.95–9.87), 10.59 (95%CI = 7.10–15.80), and 19.89 (95%CI = 11.13–35.52) times higher odds for TB. Among those with TB, the most prevalent combinations of NCDs were angina and depression, followed by angina and arthritis. For people with TB, the YLDs were three times higher than in people without multimorbidity or TB, and a third of the YLDs were attributable to NCDs. Urgent research to understand, prevent and manage NCDs in people with TB in LMICs is needed.
A Review of Registered Randomized Controlled Trials for the Prevention of Obesity in Infancy
Authors: Mihrshahi Seema , Jawad Danielle , Richards Louise , Hunter Kylie E. , Ekambareshwar Mahalakshmi , Seidler Anna Lene , Baur Louise A.
Published: March 2021

Childhood overweight and obesity is a worldwide public health issue. Our objective was to describe planned, ongoing and completed randomized controlled trials (RCTs) designed for the prevention of obesity in early childhood. Two databases (World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov) were searched to identify RCTs with the primary aim of preventing childhood obesity and at least one outcome related to child weight. Interventions needed to start in the first two years of childhood or earlier, continue for at least 6 months postnatally, include a component related to lifestyle or behaviours, and have a follow up time of at least 2 years. We identified 29 unique RCTs, implemented since 2008, with most being undertaken in high income countries. Interventions ranged from advice on diet, activity, sleep, emotion regulation, and parenting education through to individual home visits, clinic-based consultations, or group education sessions. Eleven trials published data on child weight-related outcomes to date, though most were not sufficiently powered to detect significant effects. Many trials detected improvements in practices such as breastfeeding, screen time, and physical activity in the intervention groups compared to the control groups. Further follow-up of ongoing trials is needed to assess longer-term effects.
Are Countries of the Eastern Mediterranean Region on Track towards Meeting the World Health Assembly Target for Anemia? A Review of Evidence
Authors: Al-Jawaldeh Ayoub , Taktouk Mandy , Doggui Radhouene , Abdollahi Zahra , Achakzai Baseer , Aguenaou Hassan , Al-Halaika Moussa , Almamary Salima , Barham Rawhieh , Coulibaly-Zerbo Ferima , Ammari Laila El , Elati Jalila , Nishtar Noureen Aleem , Omidvar Nasrin , Shams Mohammad Qasem , Qureshi Abdul Baseer , Nasreddine Lara
Published: March 2021

Anemia is a multifactorial condition, with a complex etiology that involves nutritional and non-nutritional factors. The misconception that iron deficiency is equivalent to anemia may mask the need to address other potential causative factors. This review paper aims to (1) assess the burden of anemia vs. iron deficiency anemia (IDA) amongst women of reproductive age (WRA), pregnant women (PW), and children under five years old (underfive children, U5C) in the Eastern Mediterranean region (EMR); (2) evaluate trends in anemia prevalence and whether countries are on track towards meeting the World Health Assembly (WHA) target for 2025; and (3) characterize anemia reduction efforts and provide a road map for future programs. A search of pertinent literature and databases was conducted. Anemia prevalence in the EMR ranged between 22.6% and 63% amongst PW, 27% and 69.6% amongst WRA, and 23.8% and 83.5% amongst U5C. Data showed that the EMR is not on course towards meeting the WHA target. The contribution of IDA to anemia was found to be less than half. Other potential contributors to anemia in the region were identified, including micronutrient deficiencies, parasitic infestations, and poor sanitation. A framework of action was proposed as a roadmap to meet the targets set by the WHA.
ANT1 Activation and Inhibition Patterns Support the Fatty Acid Cycling Mechanism for Proton Transport
Authors: Kreiter Jürgen , Rupprecht Anne , Škulj Sanja , Brkljača Zlatko , Žuna Kristina , Knyazev Denis G. , Bardakji Sarah , Vazdar Mario , Pohl Elena E.
Published: March 2021

Adenine nucleotide translocase (ANT) is a well-known mitochondrial exchanger of ATP against ADP. In contrast, few studies have shown that ANT also mediates proton transport across the inner mitochondrial membrane. The results of these studies are controversial and lead to different hypotheses about molecular transport mechanisms. We hypothesized that the H+-transport mediated by ANT and uncoupling proteins (UCP) has a similar regulation pattern and can be explained by the fatty acid cycling concept. The reconstitution of purified recombinant ANT1 in the planar lipid bilayers allowed us to measure the membrane current after the direct application of transmembrane potential ΔΨ, which would correspond to the mitochondrial states III and IV. Experimental results reveal that ANT1 does not contribute to a basal proton leak. Instead, it mediates H+ transport only in the presence of long-chain fatty acids (FA), as already known for UCPs. It depends on FA chain length and saturation, implying that FA’s transport is confined to the lipid-protein interface. Purine nucleotides with the preference for ATP and ADP inhibited H+ transport. Specific inhibitors of ATP/ADP transport, carboxyatractyloside or bongkrekic acid, also decreased proton transport. The H+ turnover number was calculated based on ANT1 concentration determined by fluorescence correlation spectroscopy and is equal to 14.6 ± 2.5 s−1. Molecular dynamic simulations revealed a large positively charged area at the protein/lipid interface that might facilitate FA anion’s transport across the membrane. ANT’s dual function—ADP/ATP and H+ transport in the presence of FA—may be important for the regulation of mitochondrial membrane potential and thus for potential-dependent processes in mitochondria. Moreover, the expansion of proton-transport modulating drug targets to ANT1 may improve the therapy of obesity, cancer, steatosis, cardiovascular and neurodegenerative diseases.
Mercury Chloride but Not Lead Acetate Causes Apoptotic Cell Death in Human Lung Fibroblast MRC5 Cells via Regulation of Cell Cycle Progression
Authors: Kim Ji-Young , An Mi-Jin , Shin Geun-Seup , Lee Hyun-Min , Kim Mi Jin , Kim Chul-Hong , Kim Jung-Woong
Published: March 2021

Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G1 and G2/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.
“Water Association” Band in Saccharide Amorphous Matrices: Role of Residual Water on Bioprotection
Authors: Giuffrida Sergio , Cupane Antonio , Cottone Grazia
Published: March 2021

Saccharides protect biostructures against adverse environmental conditions mainly by preventing large scale motions leading to unfolding. The efficiency of this molecular mechanism, which is higher in trehalose with respect to other sugars, strongly depends on hydration and sugar/protein ratio. Here we report an Infrared Spectroscopy study on dry amorphous matrices of the disaccharides trehalose, maltose, sucrose and lactose, and the trisaccharide raffinose. Samples with and without embedded protein (Myoglobin) are investigated at different sugar/protein ratios, and compared. To inspect matrix properties we analyse the Water Association Band (WAB), and carefully decompose it into sub-bands, since their relative population has been shown to effectively probe water structure and dynamics in different matrices. In this work the analysis is extended to investigate the structure of protein-sugar-water samples, for the first time. Results show that several classes of water molecules can be identified in the protein and sugar environment and that their relative population is dependent on the type of sugar and, most important, on the sugar/protein ratio. This gives relevant information on how the molecular interplay between residual waters, sugar and protein molecules affect the biopreserving properties of saccharides matrices.
The Nerves to Conduct a Multiple Sclerosis Crime Investigation
Authors: Chopra Sameeksha , Myers Zoë , Sekhon Henna , Dufour Antoine
Published: March 2021

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative autoimmune disease characterized by the aberrant infiltration of immune cells into the central nervous system (CNS) and by the loss of myelin. Sclerotic lesions and various inhibitory factors hamper the remyelination processes within the CNS. MS patients typically experience gradual cognitive and physical disabilities as the disease progresses. The etiology of MS is still unclear and emerging evidence suggests that microbiome composition could play a much more significant role in disease pathogenesis than was initially thought. Initially believed to be isolated to the gut microenvironment, we now know that the microbiome plays a much broader role in various tissues and is essential in the development of the immune system. Here, we present some of the unexpected roles that the microbiome plays in MS and discuss approaches for the development of next-generation treatment strategies.
Enhanced Shear Force Responsiveness of Epithelial Na+ Channel’s (ENaC) δ Subunit Following the Insertion of N-Glycosylation Motifs Relies on the Extracellular Matrix
Authors: Barth Daniel , Knoepp Fenja , Fronius Martin
Published: March 2021

Members of the Degenerin/epithelial Na+ channel (ENaC) protein family and the extracellular cell matrix (ECM) form a mechanosensitive complex. A core feature of this complex are tethers, which connect the channel with the ECM, however, knowledge about the nature of these tethers is scarce. N-glycans of α ENaC were recently identified as potential tethers but whether N-glycans serve as a ubiquitous feature for mechanosensation processes remains unresolved. The purpose of this study was to reveal whether the addition of N-glycans to δ ENaC—which is less responsive to shear force (SF)—increases its SF-responsiveness and whether this relies on a linkage to the ECM. Therefore, N-glycosylation motifs were introduced via site-directed mutagenesis, the resulting proteins expressed with β and γ ENaC in Xenopus oocytes, and SF-activated currents measured by two-electrode voltage-clamp. The insertion of N-glycosylation motifs increases δ ENaC’s SF responsiveness. The inclusion of a glycosylated asparagine (N) at position 487 did increase the molecular mass and provided a channel whose SF response was abolished following ECM degradation via hyaluronidase. This indicates that the addition of N-glycans improves SF-responsiveness and that this effect relies on an intact ECM. These findings further support the role of N-glycans as tethers for mechanotransduction.
Species Composition of Thrips (Thysanoptera: Thripidae) in Strawberry High Tunnels in Denmark
Authors: Nielsen Helene , Sigsgaard Lene , Kobro Sverre , Jensen Nauja L. , Jacobsen Stine K.
Published: March 2021

Thrips are a major pest in protected strawberry production. Knowledge of thrips species composition could be instrumental for improved thrips management, but very little is known about which species are present in strawberries grown in high-tunnels in Denmark. Thrips (adults and larvae) were sampled in two strawberry tunnels of the cultivars Murano and Furore from May to August 2018, in the middle and in the edges of the tunnels. The most abundant thrips species found in the tunnels were Frankliniella intonsa and Thrips tabaci adults. Frankliniella intonsa were also the most frequently found species of the immatures sampled, followed by T. tabaci larvae, and other species. The number of thrips differed between the two cultivars, sampling times and location in the tunnel. Frankliniella intonsa was more abundant in the middle of the tunnels, while T. tabaci was more abundant in the edge of the tunnels adjacent to the field margins. The number of thrips peaked by the end of July. Both chemical and biological control should consider species composition and occurrence; hence, a fundamental first step for thrips management is to identify the species present on the target crop.
Antennal Transcriptome Analysis and Identification of Candidate Chemosensory Genes of the Harlequin Ladybird Beetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae)
Authors: Rondoni Gabriele , Roman Alessandro , Meslin Camille , Montagné Nicolas , Conti Eric , Jacquin-Joly Emmanuelle
Published: March 2021

In predatory ladybirds (Coleoptera: Coccinellidae), antennae are important for chemosensory reception used during food and mate location, and for finding a suitable oviposition habitat. Based on NextSeq 550 Illumina sequencing, we assembled the antennal transcriptome of mated Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) males and females and described the first chemosensory gene repertoire expressed in this species. We annotated candidate chemosensory sequences encoding 26 odorant receptors (including the coreceptor, Orco), 17 gustatory receptors, 27 ionotropic receptors, 31 odorant-binding proteins, 12 chemosensory proteins, and 4 sensory neuron membrane proteins. Maximum-likelihood phylogenetic analyses allowed to assign candidate H. axyridis chemosensory genes to previously described groups in each of these families. Differential expression analysis between males and females revealed low variability between sexes, possibly reflecting the known absence of relevant sexual dimorphism in the structure of the antennae and in the distribution and abundance of the sensilla. However, we revealed significant differences in expression of three chemosensory genes, namely two male-biased odorant-binding proteins and one male-biased odorant receptor, suggesting their possible involvement in pheromone detection. Our data pave the way for improving the understanding of the molecular basis of chemosensory reception in Coccinellidae.
Smell and Taste Loss Recovery Time in COVID-19 Patients and Disease Severity
Authors: Printza Athanasia , Katotomichelakis Mihalis , Valsamidis Konstantinos , Metallidis Symeon , Panagopoulos Periklis , Panopoulou Maria , Petrakis Vasilis , Constantinidis Jannis
Published: March 2021

A significant proportion of people infected with SARS-CoV-2 report a new onset of smell or taste loss. The duration of the chemosensory impairment and predictive factors of recovery are still unclear. We aimed to investigate the prevalence, temporal course and recovery predictors in patients who suffered from varying disease severity. Consecutive adult patients diagnosed to be infected with SARS-CoV-2 via reverse-transcription–polymerase chain reaction (RT-PCR) at two coronavirus disease-2019 (COVID-19) Reference Hospitals were contacted to complete a survey reporting chemosensory loss, severity, timing and duration, nasal symptoms, smoking, allergic rhinitis, chronic rhinosinusitis, comorbidities and COVID-19 severity. In a cross-sectional study, we contacted 182 patients and 150 responded. Excluding the critically ill patients, 38% reported gustatory and 41% olfactory impairment (74% severe/anosmia). Most of the patients (88%) recovered their sense of smell by two months (median: 11.5 days; IQR: 13.3). For 23%, the olfactory loss lasted longer than a month. There were no significant differences in the prevalence and duration of chemosensory loss between groups of varying COVID-19 severity, and sexes (all p > 0.05). Moderate hyposmia resolved quicker than more severe loss (p = 0.04). Smell and taste loss are highly prevalent in COVID-19. Most patients recover fast, but nearly one out of ten have not recovered in two months.
Role of C5aR1 and C5L2 Receptors in Ischemia-Reperfusion Injury
Authors: Arias-Cabrales Carlos , Rodriguez-Garcia Eva , Gimeno Javier , Benito David , Pérez-Sáez María José , Redondo-Pachón Dolores , Buxeda Anna , Burballa Carla , Crespo Marta , Riera Marta , Pascual Julio
Published: March 2021

The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of C5aR1, C5L2 genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, n = 12) and compared with a control group (n = 8). We observed higher immunofluorescence expression of C5aR1, MAC and FH as higher expression of genes related to tubular injury, inflammatory and profibrotic pathways and of C5aR1 in the hypoxic cells; whereas, C5L2 gene expression was unaffected by the hypoxic stimulus. Regarding KB, C5aR1 was detected in the apical and basal membrane of tubular epithelial cells, whereas C5L2 deposits were observed in endothelial cells of peritubular capillaries (PTC). DGF-KB showed more frequently diffuse C5aR1 staining and C5L2 compared to controls. In conclusion, C5aR1 expression is increased by hypoxia and IRI, both in vitro and in human biopsies with an acute injury. C5L2 expression in PTC could be related to endothelial cell damage during IRI.