bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Stepwise Temperature Shifts in Anaerobic Digestion for Treating Municipal Wastewater Sludge: A Genomic Study
Authors: Sudiartha Gede Adi Wiguna , Imai Tsuyoshi , Hung Yung-Tse
Published: May 2022

In wastewater treatment plants (WWTP), anaerobic digester (AD) units are commonly operated under mesophilic and thermophilic conditions. In some cases, during the dry season, maintaining a stable temperature in the digester requires additional power to operate a conditioning system. Without proper conditioning systems, methanogens are vulnerable to temperature shifts. This study investigated the effects of temperature shifts on CH4 gas production and microbial diversity during anaerobic digestion of anaerobic sewage sludge using a metagenomic approach. The research was conducted in lab-scale AD under stepwise upshifted temperature from 42 to 48 °C. The results showed that significant methanogen population reduction during the temperature shift affected the CH4 production. With 70 days of incubation each, CH4 production decreased from 4.55 L·g−1-chemical oxygen demand (COD) at 42 °C with methanogen/total population (M·TP−1) ratio of 0.041 to 1.52 L·g−1 COD (M·TP−1 ratio 0.027) and then to 0.94 L·g−1 COD ( M·TP−1 ratio 0.026) after the temperature was shifted to 45 °C and 48 °C, respectively. Methanosaeta was the most prevalent methanogen during the thermal change. This finding suggests that the Methanosaeta genus was a thermotolerant archaea. Anaerobaculum, Fervidobacterium, and Tepidanaerobacter were bacterial genera and grew well in shifted-up temperatures, implying heat-resistant characteristics.
Leadership in Education, Medical Education and Health
Authors: Ruge Diane , Pedroarena-Leal Nicole , Trenado Carlos
Published: May 2022

We observe the impact of quality of leadership in our daily lives [...]
Perturbation of Circadian Rhythm Is Associated with Increased Prevalence of Chronic Kidney Disease: Results of the Korean Nationwide Population-Based Survey
Authors: Fang Yina , Son Serhim , Yang Jihyun , Oh Sewon , Jo Sang-Kyung , Cho Wonyong , Kim Myung-Gyu
Published: May 2022

Disturbances in circadian rhythms cause several health problems, such as psychosis, metabolic syndrome, and cancer; however, their effect on kidney disease remains unclear. This study aimed to evaluate the association between chronic kidney disease (CKD) and sleep disturbance in a Korean adult population. A total of 17,408 participants who completed the National Health and Nutrition Examination Survey from 2016 to 2018 were assessed for their sleep patterns and renal function. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m² or a positive dipstick urinalysis. Sleep onset time and sleep duration showed significant differences between the control and CKD groups (p < 0.001). After adjusting for the covariates, sleep onset time rather than sleep duration was independently associated with incidence of CKD, and this association was more significant in people who were older, in women, and in those with low body mass index and no comorbidities. When comparing the prevalence of newly diagnosed CKD according to sleep onset time in a population with no CKD risk factors or no history of CKD, the early bedtime group showed an independent association with incidence of new CKD (odds ratio (OR), 1.535; 95% confidence interval (CI), 1.011–2.330) even after adjusting for covariates. Impaired circadian rhythm along with sleep disturbance could be associated with CKD development; therefore, sleep disturbance might be an important therapeutic target for CKD.
The Future of Medical Tourism for Individuals’ Health and Well-Being: A Case Study of the Relationship Improvement between the UAE (United Arab Emirates) and South Korea
Authors: Kim Haeok Liz , Hyun Sunghyup Sean
Published: May 2022

The medical tourism industry has been growing rapidly in recent years as governments seek new sectors for sustainable growth. The increase in medical tourism and cooperation in the health and medical sector may be a path to improving relationships between countries. As a result of globalization, international tourism has been growing faster than any other time in the past. The growth of international tourism is being regarded as a contributor to the development of the economy, social cooperation, politics, and cultural relations. This paper suggests that developing medical tourism may act as a basis for increasing tourism in general, thereby enhancing cultural exchanges and improving the relationship between South Korea (Republic of Korea) and the United Arab Emirates (UAE), especially by establishing a new cooperative relationship in the health and medical field. This paper focuses on the functions of medical tourism in the past and its potential in the future, which may play a significant role in the relationship between South Korea and the UAE, particularly its influence on South Korea’s policies of cooperation with the UAE in the field of health and medical services.
Design and Validation of a Questionnaire to Assess the Leisure Time Physical Activity of Adult Women in Gipuzkoa
Authors: Eizagirre-Sagastibeltza Olaia , Fernandez-Lasa Uxue , Yanci Javier , Romaratezabala Estibaliz , Cayero Ruth , Iturrioz Iñaki , Usabiaga Oidui
Published: May 2022

Inactivity is higher among women than among men, and there are few specific questionnaires used to assess physical activity (PA) in women that are truly meaningful to them. This article tackles the design and validation process of an ad hoc multidimensional questionnaire to assess leisure time physical activity (LTPA) among adult women of Gipuzkoa. The questionnaire was completed by 3595 adult women (43.5 ± 12.1 years), 32% of which were inactive and 68% of which were active. Content validation, ecological validation, and internal consistency analysis results were satisfactory. The Gipuzkoa Women’s Physical Activity Questionnaire (GWPAQ) consists of four dimensions and 21 items. Barriers to PA were found related to intrapersonal, environmental, and socio-cultural aspects. The importance of family and spousal support in increasing PA levels was also observed. It is concluded that the GWPAQ is valid for obtaining evidence that can be used by public institutions to optimise women-specific PA promotion policies.
Spatio-Temporal Monitoring of Atmospheric Pollutants Using Earth Observation Sentinel 5P TROPOMI Data: Impact of Stubble Burning a Case Study
Authors: Maurya Neeraj K. , Pandey Prem Chandra , Sarkar Subhadip , Kumar Rajesh , Srivastava Prashant K.
Published: May 2022

The problems of atmospheric pollutants are causing significant concern across the globe and in India. The aggravated level of atmospheric pollutants in the surrounding environment poses serious threats to normal living conditions by deteriorating air quality and causing adverse health impacts. Pollutant concentration increases during harvesting seasons of Kharif/Rabi due to stubble burning and is aggravated by other points or mobile sources. The present study is intended to monitor the spatio-temporal variation of the major atmospheric pollutants using Sentinel-5P TROPOMI data through cloud computing. Land Use/Land Cover (LULC-categorization or classification of human activities and natural coverage on the landscape) was utilised to extract the agricultural area in the study site. It involves the cloud computing of MOD64A1 (MODIS Burned monthly gridded data) and Sentinel-5P TROPOMI (S5P Tropomi) data for major atmospheric pollutants, such as CH4, NO2, SOX, CO, aerosol, and HCHO. The burned area output provided information regarding the stubble burning period, which has seen post-harvesting agricultural residue burning after Kharif crop harvesting (i.e., rice from April to June) and Rabi crop harvesting (i.e., wheat from September to November). The long duration of stubble burning is due to variation in farmers’ harvesting and burning stubble/biomass remains in the field for successive crops. This period was used as criteria for considering the cloud computing of the Sentinel-5P TROPOMI data for atmospheric pollutants concentration in the study site. The results showed a significant increase in CH4, SO2, SOX, CO, and aerosol concentration during the AMJ months (stubble burning of Rabi crops) and OND months (stubble burning of Kharif crops) of each year. The results are validated with the ground control station data for PM2.5/PM10. and patterns of precipitation and temperature-gridded datasets. The trajectory frequency for air mass movement using the HYSPLIT model showed that the highest frequency and concentration were observed during OND months, followed by the AMJ months of each year (2018, 2019, 2020, and 2021). This study supports the role and robustness of Earth observation Sentinel-5P TROPOMI to monitor and evaluate air quality and pollutants distribution.
Ebola Virus Encodes Two microRNAs in Huh7-Infected Cells
Authors: Diallo Idrissa , Husseini Zeinab , Guellal Sara , Vion Elodie , Ho Jeffrey , Kozak Robert A. , Kobinger Gary P. , Provost Patrick
Published: May 2022

MicroRNAs (miRNAs) are important gene regulatory molecules involved in a broad range of cellular activities. Although the existence and functions of miRNAs are clearly defined and well established in eukaryotes, this is not always the case for those of viral origin. Indeed, the existence of viral miRNAs is the subject of intense controversy, especially those of RNA viruses. Here, we characterized the miRNA transcriptome of cultured human liver cells infected or not with either of the two Ebola virus (EBOV) variants: Mayinga or Makona; or with Reston virus (RESTV). Bioinformatic analyses revealed the presence of two EBOV-encoded miRNAs, miR-MAY-251 and miR-MAK-403, originating from the EBOV Mayinga and Makona variants, respectively. From the miRDB database, miR-MAY-251 and miR-MAK-403 displayed on average more than 700 potential human host target candidates, 25% of which had a confidence score higher than 80%. By RT-qPCR and dual luciferase assays, we assessed the potential regulatory effect of these two EBOV miRNAs on selected host mRNA targets. Further analysis of Panther pathways unveiled that these two EBOV miRNAs, in addition to general regulatory functions, can potentially target genes involved in the hemorrhagic phenotype, regulation of viral replication and modulation of host immune defense.
Comparative Transcriptomics Reveals the Molecular Mechanism of the Parental Lines of Maize Hybrid An’nong876 in Response to Salt Stress
Authors: Zhang Xingen , Liu Jing , Huang Yuanxiang , Wu Hongying , Hu Xiaolin , Cheng Beijiu , Ma Qing , Zhao Yang
Published: May 2022

Maize (Zeamays L.) is an essential food crop worldwide, but it is highly susceptible to salt stress, especially at the seedling stage. In this study, we conducted physiological and comparative transcriptome analyses of seedlings of maize inbred lines An’nong876 paternal (cmh15) and An’nong876 maternal (CM37) under salt stress. The cmh15 seedlings were more salt-tolerant and had higher relative water content, lower electrolyte leakage, and lower malondialdehyde levels in the leaves than CM37. We identified 2559 upregulated and 1770 downregulated genes between salt-treated CM37 and the controls, and 2757 upregulated and 2634 downregulated genes between salt-treated cmh15 and the controls by RNA sequencing analysis. Gene ontology functional enrichment analysis of the differentially expressed genes showed that photosynthesis-related and oxidation-reduction processes were deeply involved in the responses of cmh15 and CM37 to salt stress. We also found differences in the hormone signaling pathway transduction and regulation patterns of transcription factors encoded by the differentially expressed genes in both cmh15 and CM37 under salt stress. Together, our findings provide insights into the molecular networks that mediate salt stress tolerance of maize at the seedling stage.
PRDX2 Knockdown Inhibits Extracellular Matrix Synthesis of Chondrocytes by Inhibiting Wnt5a/YAP1/CTGF and Activating IL-6/JAK2/STAT3 Pathways in Deer Antler
Authors: Sun Xuyang , Gu Xiaoying , Peng Jingna , Yang Liguo , Zhang Xinxin , Ran Zaohong , Xiong Jiajun
Published: May 2022

Although peroxiredoxin 2 (PRDX2) plays a vital role in relieving oxidative stress, its physiological function in cartilage development remains almost unknown. In this study, we found that the expression of PRDX2 significantly increased in the chondrocytes compared with pre-chondrocytes. PRDX2 knockdown significantly decreased the expression of extracellular matrix (ECM) protein (Col2a and Aggrecan), which led to blocked cartilage formation. Moreover, PRDX2 knockdown also inhibited the expression of connective tissue growth factor (CTGF). CTGF is an important growth factor that regulates synthesis of ECM proteins. We explored the possible regulatory mechanism by which PRDX2 regulated the expression of CTGF. Our results demonstrated that PRDX2 knockdown downregulated the expression of CTGF by inhibiting Wnt5a/Yes-associated protein 1 (YAP1) pathway. In addition, PRDX2 knockdown promoted the expression of interleukin 6 (IL-6), indicating PRDX2 expression had an anti-inflammatory function during antler growth. Mechanistically, PRDX2 knockdown promoted cartilage matrix degradation by activating the IL-6-mediated Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway. These results reveal that PRDX2 is a potential regulator that promotes cartilage extracellular matrix synthesis.
Integrated Multi-Omics Perspective to Strengthen the Understanding of Salt Tolerance in Rice
Authors: Dai Liping , Li Peiyuan , Li Qing , Leng Yujia , Zeng Dali , Qian Qian
Published: May 2022

Salt stress is one of the major constraints to rice cultivation worldwide. Thus, the development of salt-tolerant rice cultivars becomes a hotspot of current rice breeding. Achieving this goal depends in part on understanding how rice responds to salt stress and uncovering the molecular mechanism underlying this trait. Over the past decade, great efforts have been made to understand the mechanism of salt tolerance in rice through genomics, transcriptomics, proteomics, metabolomics, and epigenetics. However, there are few reviews on this aspect. Therefore, we review the research progress of omics related to salt tolerance in rice and discuss how these advances will promote the innovations of salt-tolerant rice breeding. In the future, we expect that the integration of multi-omics salt tolerance data can accelerate the solution of the response mechanism of rice to salt stress, and lay a molecular foundation for precise breeding of salt tolerance.
Effects of Long-Term Temozolomide Treatment on Glioblastoma and Astrocytoma WHO Grade 4 Stem-like Cells
Authors: Feldheim Jonas , Kessler Almuth F. , Feldheim Julia J. , Schulz Ellina , Wend David , Lazaridis Lazaros , Kleinschnitz Christoph , Glas Martin , Ernestus Ralf-Ingo , Brandner Sebastian , Monoranu Camelia M. , Löhr Mario , Hagemann Carsten
Published: May 2022

Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.
Lactoferrin as a Human Genome “Guardian”—An Overall Point of View
Authors: Bukowska-Ośko Iwona , Sulejczak Dorota , Kaczyńska Katarzyna , Kleczkowska Patrycja , Kramkowski Karol , Popiel Marta , Wietrak Ewa , Kowalczyk Paweł
Published: May 2022

Structural abnormalities causing DNA modifications of the ethene and propanoadducts can lead to mutations and permanent damage to human genetic material. Such changes may cause premature aging and cell degeneration and death as well as severe impairment of tissue and organ function. This may lead to the development of various diseases, including cancer. In response to a damage, cells have developed defense mechanisms aimed at preventing disease and repairing damaged genetic material or diverting it into apoptosis. All of the mechanisms described above are part of the repertoire of action of Lactoferrin—an endogenous protein that contains iron in its structure, which gives it numerous antibacterial, antiviral, antifungal and anticancer properties. The aim of the article is to synthetically present the new and innovative role of lactoferrin in the protection of human genetic material against internal and external damage, described by the modulation mechanisms of the cell cycle at all its levels and the mechanisms of its repair.
Recent Progress on the Localization of PLK1 to the Kinetochore and Its Role in Mitosis
Authors: Kim Taekyung
Published: May 2022

The accurate distribution of the replicated genome during cell division is essential for cell survival and healthy organismal development. Errors in this process have catastrophic consequences, such as birth defects and aneuploidy, a hallmark of cancer cells. PLK1 is one of the master kinases in mitosis and has multiple functions, including mitotic entry, chromosome segregation, spindle assembly checkpoint, and cytokinesis. To dissect the role of PLK1 in mitosis, it is important to understand how PLK1 localizes in the specific region in cells. PLK1 localizes at the kinetochore and is essential in spindle assembly checkpoint and chromosome segregation. However, how PLK1 localizes at the kinetochore remains elusive. Here, we review the recent literature on the kinetochore recruitment mechanisms of PLK1 and its roles in spindle assembly checkpoint and attachment between kinetochores and spindle microtubules. Together, this review provides an overview of how the local distribution of PLK1 could regulate major pathways in mitosis.
Impact of Environmentally Relevant Concentrations of Bisphenol A (BPA) on the Gene Expression Profile in an In Vitro Model of the Normal Human Ovary
Authors: Zahra Aeman , Kerslake Rachel , Kyrou Ioannis , Randeva Harpal S. , Sisu Cristina , Karteris Emmanouil
Published: May 2022

Endocrine-disrupting chemicals (EDCs), including the xenoestrogen Bisphenol A (BPA), can interfere with hormonal signalling. Despite increasing reports of adverse health effects associated with exposure to EDCs, there are limited data on the effect of BPA in normal human ovaries. In this paper, we present a detailed analysis of the transcriptomic landscape in normal Human Epithelial Ovarian Cells (HOSEpiC) treated with BPA (10 and 100 nM). Gene expression profiles were determined using high-throughput RNA sequencing, followed by functional analyses using bioinformatics tools. In total, 272 and 454 differentially expressed genes (DEGs) were identified in 10 and 100 nM BPA-treated HOSEpiCs, respectively, compared to untreated controls. Biological pathways included mRNA surveillance pathways, oocyte meiosis, cellular senescence, and transcriptional misregulation in cancer. BPA exposure has a considerable impact on 10 genes: ANAPC2, AURKA, CDK1, CCNA2, CCNB1, PLK1, BUB1, KIF22, PDE3B, and CCNB3, which are also associated with progesterone-mediated oocyte maturation pathways. Future studies should further explore the effects of BPA and its metabolites in the ovaries in health and disease, making use of validated in vitro and in vivo models to generate data that will address existing knowledge gaps in basic biology, hazard characterisation, and risk assessment associated with the use of xenoestrogens such as BPA.
A Novel Photoswitchable Azobenzene-Containing Local Anesthetic Ethercaine with Light-Controlled Biological Activity In Vivo
Authors: Noev Alexey , Kuznetsov Nikita , Korenev Georgiy , Morozova Natalia , Vasil’ev Yuriy , Suvorov Nikita , Diachkova Ekaterina , Usachev Maksim , Pankratov Andrei , Grin Mikhail
Published: May 2022

Pain is a common symptom that impairs the quality of life for people around the world. Local anesthetics widely used for pain relief have a number of side effects, which makes the development of both new drugs and new ways to control their activity particularly important. Photopharmacology makes it possible to reduce the side effects of an anesthetic and control its biological activity in the body. The purpose of this work was to create a new light-controlled local anesthetic and study its biological activity in animals. A compound with a simple scheme of synthesis was chosen to shift the UV-Vis absorption band towards the visible range of the spectrum and was synthesized for the first time. Some computer calculations were performed to make sure that the aforementioned changes would not lead to loss of biological activity. The micellar form of the new compound was prepared, and in vivo biological studies were carried out in rabbits. The existence of a local anesthetic effect, which disappeared almost completely on irradiation with light (λ = 395 nm), was shown using the surface anesthesia model. Moreover, the possibility of multiple reversible changes in the biological activity of ethercaine under the action of light was demonstrated. The latter compound manifests no local irritating effect, either. The data obtained indicate the prospects for the development of new compounds based on azobenzene for light-controlled local anesthesia.
Integration of Maps Enables a Cytogenomics Analysis of the Complete Karyotype in Solea senegalensis
Authors: Ramírez Daniel , Rodríguez María Esther , Cross Ismael , Arias-Pérez Alberto , Merlo Manuel Alejandro , Anaya Marco , Portela-Bens Silvia , Martínez Paulino , Robles Francisca , Ruiz-Rejón Carmelo , Rebordinos Laureana
Published: May 2022

The Pleuronectiformes order, which includes several commercially-important species, has undergone extensive chromosome evolution. One of these species is Solea senegalensis, a flatfish with 2n = 42 chromosomes. In this study, a cytogenomics approach and integration with previous maps was applied to characterize the karyotype of the species. Synteny analysis of S. senegalensis was carried out using two flatfish as a reference: Cynoglossus semilaevis and Scophthalmus maximus. Most S. senegalensis chromosomes (or chromosome arms for metacentrics and submetacentrics) showed a one-to-one macrosyntenic pattern with the other two species. In addition, we studied how repetitive sequences could have played a role in the evolution of S. senegalensis bi-armed (3, and 5–9) and acrocentric (11, 12 and 16) chromosomes, which showed the highest rearrangements compared with the reference species. A higher abundance of TEs (Transposable Elements) and other repeated elements was observed adjacent to telomeric regions on chromosomes 3, 7, 9 and 16. However, on chromosome 11, a greater abundance of DNA transposons was detected in interstitial BACs. This chromosome is syntenic with several chromosomes of the other two flatfish species, suggesting rearrangements during its evolution. A similar situation was also found on chromosome 16 (for microsatellites and low complexity sequences), but not for TEs (retroelements and DNA transposons). These differences in the distribution and abundance of repetitive elements in chromosomes that have undergone remodeling processes during the course of evolution also suggest a possible role for simple repeat sequences in rearranged regions.
Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges
Authors: Maraldi Tullia , Russo Valentina
Published: May 2022

The intention of this special edition is to collect review and original research articles that illustrate and stimulate growing efforts to understand the implication of perinatal stem cells in pathological conditions such as cardiovascular and metabolic diseases and inflammatory, autoimmune, musculoskeletal, and degenerative diseases [...]
Differential Expression of Proteins in an Atypical Presentation of Autoimmune Lymphoproliferative Syndrome
Authors: Delgadillo Dulce María , Céspedes-Cruz Adriana Ivonne , Ríos-Castro Emmanuel , Rodríguez Maldonado María Guadalupe , López-Nogueda Mariel , Márquez-Gutiérrez Miguel , Villalobos-Manzo Rocío , Ramírez-Reyes Lorena , Domínguez-Fuentes Misael , Tapia-Ramírez José
Published: May 2022

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease defined as a defect in the lymphocyte apoptotic pathway. Currently, the diagnosis of ALPS is based on clinical aspects, defective lymphocyte apoptosis and mutations in Fas, FasL and Casp 10 genes. Despite this, ALPS has been misdiagnosed. The aim of this work was to go one step further in the knowledge of the disease, through a molecular and proteomic analysis of peripheral blood mononuclear cells (PBMCs) from two children, a 13-year-old girl and a 6-year-old boy, called patient 1 and patient 2, respectively, with clinical data supporting the diagnosis of ALPS. Fas, FasL and Casp10 genes from both patients were sequenced, and a sample of the total proteins from patient 1 was analyzed by label-free proteomics. Pathway analysis of deregulated proteins from PBMCs was performed on the STRING and PANTHER bioinformatics databases. A mutation resulting in an in-frame premature stop codon and protein truncation was detected in the Fas gene from patient 2. From patient 1, the proteomic analysis showed differences in the level of expression of proteins involved in, among other processes, cell cycle, regulation of cell cycle arrest and immune response. Noticeably, the most down-regulated protein is an important regulator of the cell cycle process. This could be an explanation of the disease in patient 1.
Correction: Loredo Varela, R.C.; Fail, J. Host Plant Association and Distribution of the Onion Thrips, Thrips tabaci Cryptic Species Complex. Insects 2022, 13, 298
Authors: Loredo Varela Roberto Carlos , Fail József
Published: May 2022

In the original publication [...]
Design of an Antimatter Large Acceptance Detector In Orbit (ALADInO)
Authors: Adriani Oscar , Altomare Corrado , Ambrosi Giovanni , Azzarello Philipp , Barbato Felicia Carla Tiziana , Battiston Roberto , Baudouy Bertrand , Bergmann Benedikt , Berti Eugenio , Bertucci Bruna , Boezio Mirko , Bonvicini Valter , Bottai Sergio , Burian Petr , Buscemi Mario , Cadoux Franck , Calvelli Valerio , Campana Donatella , Casaus Jorge , Contin Andrea , D’Alessandro Raffaello , Dam Magnus , De Mitri Ivan , de Palma Francesco , Derome Laurent , Di Felice Valeria , Di Giovanni Adriano , Donnini Federico , Duranti Matteo , Fiandrini Emanuele , Follega Francesco Maria , Formato Valerio , Gargano Fabio , Giovacchini Francesca , Graziani Maura , Ionica Maria , Iuppa Roberto , Loparco Francesco , Marín Jesús , Mariotto Samuele , Marsella Giovanni , Martínez Gustavo , Martínez Manel , Martucci Matteo , Masi Nicolò , Mazziotta Mario Nicola , Mergé Matteo , Mori Nicola , Munini Riccardo , Musenich Riccardo , Mussolin Lorenzo , Nozzoli Francesco , Oliva Alberto , Osteria Giuseppe , Pacini Lorenzo , Paniccia Mercedes , Papini Paolo , Pearce Mark , Perrina Chiara , Picozza Piergiorgio , Pizzolotto Cecilia , Pospíšil Stanislav , Pozzato Michele , Quadrani Lucio , Ricci Ester , Rico Javier , Rossi Lucio , Schioppa Enrico Junior , Serini Davide , Smolyanskiy Petr , Sotgiu Alessandro , Sparvoli Roberta , Surdo Antonio , Tomassetti Nicola , Vagelli Valerio , Velasco Miguel Ángel , Wu Xin , Zuccon Paolo
Published: May 2022

A new generation magnetic spectrometer in space will open the opportunity to investigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limitations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m2 sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery potentials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unambiguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.
Neoadjuvant Chemo-Immunotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Review of the Literature
Authors: Franzi Sara , Mattioni Giovanni , Rijavec Erika , Croci Giorgio Alberto , Tosi Davide
Published: May 2022

Non-small cell lung cancer accounts for approximately 80–85% of all lung cancers and at present represents the main cause of cancer death among both men and women. To date, surgery represents the cornerstone; nevertheless, around 40% of completely resected patients develop disease recurrence. Therefore, combining neoadjuvant chemo-immunotherapy and surgery might lead to improved survival. Immunotherapy is normally well tolerated, although significant adverse reactions have been reported in certain patients treated with inhibitors of immune checkpoints. In this review, we explore the current literature on the use of neoadjuvant chemo-immunotherapy followed by surgery for treatment of locally advanced non-small-cell lung cancer, with particular attention to the histological aspects, ongoing trials, and the most common surgical approaches. In conclusion, neoadjuvant immunotherapy whether combined or not with chemotherapy reveals a promising survival benefit for patients with advanced non-small-cell lung cancer; nevertheless, more data remain necessary to identify the best candidates for neoadjuvant regimens.
Could Stoma Be Avoided after Laparoscopic Low Anterior Resection for Rectal Cancer? Experience with Transanal Tube in 195 Cases
Authors: Sciuto Antonio , Peltrini Roberto , Andreoli Federica , Di Santo Albini Andrea Gianmario , Di Nuzzo Maria Michela , Pirozzi Nello , Filotico Marcello , Lauria Federica , Boccia Giuseppe , D’Ambra Michele , Lionetti Ruggero , De Werra Carlo , Pirozzi Felice , Corcione Francesco
Published: May 2022

Anastomotic leakage is the most-feared complication of rectal surgery. Transanal devices have been suggested for anastomotic protection as an alternative to defunctioning stoma, although evidence is conflicting, and no single device is widely used in clinical practice. The aim of this paper is to investigate the safety and efficacy of a transanal tube for the prevention of leakage following laparoscopic rectal cancer resection. A transanal tube was used in the cases of total mesorectal excision with low colorectal or coloanal anastomosis, undamaged doughnuts, and negative intraoperative air-leak test. The transanal tube was kept in place until the seventh postoperative day. A total of 195 consecutive patients were retrieved from a prospective surgical database and included in the study. Of these, 71.8% received preoperative chemoradiotherapy. The perioperative mortality rate was 1.0%. Anastomotic leakage occurred in 19 patients, accounting for an incidence rate of 9.7%. Among these, 13 patients underwent re-laparoscopy and ileostomy, while 6 patients were managed conservatively. Overall, the stoma rate was 6.7%. The use of a transanal tube may be a suitable strategy for anastomotic protection following restorative rectal cancer resection. This approach could avoid the burden of a stoma in selected patients with low anastomoses.
Acute Pulmonary Artery Thrombosis despite Anticoagulation in Patients with COVID-19 Pneumonia: A Single-Center Retrospective Cohort Study
Authors: Niculae Cristian-Mihail , Anghel Ana-Maria-Jennifer , Militaru Eliza-Daniela , Tîrlescu Laura-Georgiana , Lazar Mihai , Hristea Adriana
Published: May 2022

(1) Background: We aimed to describe the clinical and imaging characteristics of patients diagnosed with pulmonary artery thrombosis (PAT) despite receiving anticoagulation with low-molecular-weight heparin (LMWH). (2) Methods: We retrospectively studied all hospitalized COVID-19 adult patients diagnosed with PAT between March 2020 and December 2021, who received LMWH for ≥72 h until the diagnosis of PAT. Acute PAT was confirmed by a CT pulmonary angiogram. (3) Results: We included 30 severe and critical COVID-19 patients. Median age was 62 (54–74) years, with 83.3% males, and comorbidities seen in 73.3%. PAT was diagnosed despite prophylactic (23.3%), intermediate (46.6%) or therapeutic (30%) doses of LMWH for a median time of 8 (4.7–12) days. According to their Wells score, 80% of patients had a low probability of pulmonary embolism diagnosis. PAT was localized in the lower lobes of the lungs in 76.6% of cases with 33.3% having bilateral involvement, with the distal, peripheral arteries being the most affected. At the PAT diagnosis we found a worsening of respiratory function, with seven patients progressing to mechanical ventilation (p = 0.006). The in-hospital mortality was 30%. (4) Conclusions: PAT should be considered in patients with severe and critical COVID-19, mainly in elderly male patients with comorbidities, irrespective of Wells score and LMWH anticoagulation.
Increased Plasma Lipocalin-2 Levels in Patients with Myelin Oligodendrocyte Glycoprotein-IgG–Positive Optic Neuritis
Authors: Kim Jong-Heon , Lee Hyejin , Oh Junho , Suk Kyoungho , Chun Bo Young
Published: May 2022

This study aimed to evaluate the correlation between plasma lipocalin-2 (LCN2) levels and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) seropositivity in patients with optic neuritis. Peripheral blood samples were collected from 19 patients with optic neuritis and 20 healthy controls. Plasma LCN2 and MOG-IgG levels were measured using enzyme-linked immunosorbent assay and a cell-based assay, respectively. The correlation between plasma LCN2 levels and MOG-IgG titers in patients with optic neuritis was analyzed. Receiver operating characteristic (ROC) curves were constructed to assess and compare the ability of plasma LCN2 and MOG-IgG levels for predicting optic neuritis recurrence. Patients with MOG-IgG–positive optic neuritis had significantly higher mean plasma LCN2 levels than controls and patients with MOG-IgG–negative optic neuritis (p = 0.037). Plasma LCN2 and MOG-IgG levels were significantly correlated in patients with optic neuritis (r = 0.553, p = 0.0141). There were no significant differences in the areas under the ROC curve (AUC) of plasma LCN2 (0.693, 95% confidence interval [CI] 0.443–0.880, p = 0.133) and MOG-IgG (0.641, 95% CI, 0.400–0.840, p = 0.298) levels (95% CI, −0.266–0.448, p = 0.618). Plasma LCN2 levels may aid differentiation of MOG-IgG–positive optic neuritis from MOG-IgG–negative optic neuritis.
Higher Risk of Anxiety and Depression in Women with Adenomyosis as Compared with Those with Uterine Leiomyoma
Authors: Li Ni , Yuan Ming , Li Qiuju , Ji Miaomiao , Jiao Xue , Wang Guoyun
Published: May 2022

The main symptoms of adenomyosis may adversely affect physical and mental health and quality of life (QOL). However, studies are few on this topic. This study evaluated the effect of adenomyosis on anxiety, depression, and QOL. Participants with adenomyosis (n = 90) or leiomyoma (n = 59) completed questionnaires, including the visual analog scale (VAS) for pain, Hospital Anxiety and Depression Scale (HADS), and Short Form (SF)-36. HADS anxiety and depression positive rates, physical (PCS) and mental (MCS) component summary scores, and eight subscale scores of SF-36 were compared between the two groups. Among patients with adenomyosis, the incidence of anxiety symptoms was 28.9% (control group, 10.2%; OR = 3.589, 95% CI: 1.375–9.367), with 10% of patients showing moderate-to-severe symptoms. The incidence of depressive symptoms was 14.4% (control group, 3.4%; OR = 4.812, 95% CI: 1.044–22.168). The case group had significantly lower PCS and MCS scores than the control group. In patients with adenomyosis, being employed (OR = 6.393, 95% CI: 1.153–35.440) and perianal pain (OR = 25.419, 95% CI: 2.504–258.024) were risk factors for anxiety, and perianal pain (OR = 15.208, 95% CI: 3.050–75.836) was a risk factor for depression. Compared with leiomyoma, adenomyosis is associated with a higher risk of anxiety and depression, with a poorer QOL.
Real-Life Early Anthropometric, Lipid and Liver Changes after Direct-Acting Antiviral Therapy in PLWHIV with HCV Co-Infection
Authors: Ferra-Murcia Sergio , Collado-Romacho Antonio Ramón , Nievas-Soriano Bruno José , Reche-Lorite Fernando , Parrón-Carreño Tesifón
Published: May 2022

Treatment with interferon-free direct-acting antivirals (DAA) has become the gold standard in chronic hepatitis C virus (HCV) infection. Nevertheless, little research about the metabolic impact of achieving sustained virological response (SVR) is available in HCV/HIV co-infected patients. This research aimed to evaluate early anthropometric, lipid and liver parameters changes after achieving SVR 12 weeks after treatment (SVR12). A real-life retrospective descriptive before-after study assessed 128 DAA treatment episodes from 2015 to 2019 in HCV/HIV co-infected patients. Anthropometric parameters (weight, body mass index), lipid profile, genotype (GT) and viral load, liver data (basics laboratory necroinflammatory parameters and transient elastography (TE)) were collected before treatment with DAA (baseline), and when SVR12 was achieved. Significant increases (p < 0.01) were found in the early lipid profile, measured by LDLc (84.6 ± 35.0 vs. 108.6 ± 35.1 mg/dL) and total cholesterol (161.3 ± 41.0 vs. 183.3 ± 41.6 mg/dL). Significant changes (p < 0.05) were found in liver parameters, measured by ALT (58.2 ± 34.0 vs. 22.0 ± 16.0 U/L), bilirubin (0.8 ± 0.6 vs. 0.6 ± 0.5 mg/dL), albumin (4.2 ± 0.4 vs. 4.3 ± 0.3 g/dL) and liver stiffness (LS) (13.7 ± 13.3 vs. 11.8 ± 12.1 kPa). The main conclusions were that the use of DAA has an early negative impact on lipid metabolism. Achieving SVR12 against HCV leads to an early improvement in liver function and LS in HCV/HIV co-infected patients without interference with antiretroviral treatment (ART) and DAA. Short-term close lipid monitoring may be necessary when combining protease inhibitors. HCV-GT-3/HIV co-infected patients might require further close monitoring for residual fibrosis. These findings can be relevant for actual clinical practice.
Platelet Rich Plasma Injections for Knee Osteoarthritis Treatment: A Prospective Clinical Study
Authors: Moretti Lorenzo , Maccagnano Giuseppe , Coviello Michele , Cassano Giuseppe D. , Franchini Andrea , Laneve Andrea , Moretti Biagio
Published: May 2022

Background: The aim of this prospective study was to evaluate the efficacy and safety of Platelet Rich Plasma (PRP) injections in patients affected by knee osteoarthritis (KOA). An autologous blood product containing a high percentage of various growth factors (GFs), cytokines and modulating factors as PRP has shown promising results in achieving this goal. Methods: One hundred and fifty-three patients (72 males, mean age 59.06 ± 8.78, range 40–81 years old) from January 2018 to January 2020 received three consecutive PRP injections and completed the follow ups. Western Ontario and McMaster University Osteoarthritis index (WOMAC), Knee society score (KSS) and Visual Analogic Scale (VAS) were evaluated before PRP injection (T0), one month (T1), three months (T2) and six months (T3) after the treatment. All patients underwent baseline and at 6 months MRI and X-ray evaluation. Results: A statistically significant VAS, KSS and WOMAC reduction emerged in the comparison between evaluations (p < 0.05), MRI demonstrated non-statistically significant improvement in cartilage thickness for both tibial plate and femoral plate (p = 0.46 and p = 0.33 respectively), and no radiographic changes could be seen in any patients. Conclusions: PRP injection represents a valid conservative treatment to reduce pain, improve quality of life and functional scores even at midterm of 6 months follow-up.
Compartment-Specific Differences in the Activation of Monocyte Subpopulations Are Not Affected by Nitric Oxide and Glucocorticoid Treatment in a Model of Resuscitated Porcine Endotoxemic Shock
Authors: Skirecki Tomasz , Adamik Barbara , Frostell Claes , Pasławska Urszula , Zieliński Stanisław , Glatzel-Plucińska Natalia , Olbromski Mateusz , Dzięgiel Piotr , Gozdzik Waldemar
Published: May 2022

Inhaled nitric oxide (iNO) remains one of the treatment modalities in shock, and in addition to its vasoactive properties, iNO exerts immunomodulatory effects. We used a porcine model of endotoxemia with shock resuscitation (control) and additional treatment with iNO and a steroid (treatment group). After 20 h, bone marrow (BM), peripheral blood (PB), and bronchoalveolar lavage fluid (BALF) were collected to analyze the immunophenotype and mitochondrial membrane potential (Δφ) in three subsets of monocytes. In both groups, SLA-DR expression decreased twofold on the circulating CD14+CD163+ and CD14−CD163+ monocytes, while it did not change on the CD14+CD163+. Δφ increased only in the CD14−CD163+ subpopulation (0.8 vs. 2.0, p < 0.001). The analysis of compartment-specific alterations showed that nearly 100% of BALF CD14+CD163+ and CD14−CD163+ monocytes expressed SLA-DR, and it was higher compared to PB (32% and 20%, p < 0.0001) and BM (93% and 67%, p < 0.001, respectively) counterparts. BALF CD14+CD163+ had a threefold higher Δφ than PB and BM monocytes, while the Δφ of the other subsets was highest in PB monocytes. We confirmed the compartmentalization of the monocyte response during endotoxemic shock, which highlights the importance of studying tissue-resident cells in addition to their circulating counterparts. The iNO/steroid treatment did not further impair monocyte fitness.
Comparison of the Oncological Outcomes of Open versus Laparoscopic Surgery for T2 Gallbladder Cancer: A Propensity-Score-Matched Analysis
Authors: Cho Jin-Kyu , Kim Jae-Ri , Jang Jae-Yool , Kim Han-Gil , Kim Jae-Myung , Kwag Seung-Jin , Park Ji-Ho , Kim Ju-Yeon , Ju Young-Tae , Jeong Chi-Young
Published: May 2022

Although laparoscopic treatment for T1 gallbladder cancer (GBC) has been described previously, the differences in oncologic outcomes between laparoscopic and conventional open surgery for T2 GBC have not been investigated. We aimed to assess the role of laparoscopic surgery using retrospectively collected data for 81 patients with T2 GBC who underwent surgical resection between January 2010 and December 2017. Eligible patients were classified into “laparoscopic” and “open” groups. Propensity-score matching was performed in a 1:1 ratio. The effects of surgery type on surgical and oncological outcomes were investigated. After propensity-score matching, 19 patients were included in the open and laparoscopic surgery groups. The median follow-up durations were 70 and 26 months in the open and laparoscopic groups, respectively. The operative time (316.8 ± 80.3 vs. 218.9 ± 145.0 min, p = 0.016) and length of postoperative hospital stay (14.4 ± 6.0 vs. 8.4 ± 5.9 days, p = 0.004) were significantly shorter in the laparoscopic group. The three-year overall (86.3% vs. 88.9%, p = 0.660) and disease-free (76.4% vs. 60.2%, p = 0.448) survival rates were similar between the groups. Propensity-score matching showed that laparoscopic surgery for T2 GBC yielded similar long-term oncological outcomes and favorable short-term outcomes in comparison with open surgery. Laparoscopic treatment should be considered in patients with T2 GBC.
Evaluating Ocular Symptoms and Tear Film Cytokine Profiles in Symptomatic COVID-19 Patients
Authors: Niedźwiedź Anna , Kawa Miłosz , Pius-Sadowska Ewa , Kuligowska Agnieszka , Ziontkowska Alicja , Wrzałek Dawid , Parczewski Miłosz , Safranow Krzysztof , Kozłowski Krzysztof , Machaliński Bogusław , Machalińska Anna
Published: May 2022

Background: This study investigated the presence and duration of ophthalmic symptoms in the early phase of COVID-19 to assess the corresponding local immune response on the ocular surface. Methods: The study included data from 180 COVID-19 patients and 160 age-matched healthy controls. The main finding was the occurrence of ophthalmological manifestations at the time of admission to the hospital and during the preceding 7 days. Tear film concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay. Results: Among the COVID-19 patients, 12.64% had at least one ocular symptom at the time of admission, and 24.14% had symptoms within the preceding 7 days (p < 0.001 vs. controls). We found that the COVID-19 patients complained more frequently about eye tearing (p = 0.04) and eye pain (p = 0.01) than controls. A multivariate analysis of the patients and controls adjusted for age and sex revealed that COVID-19 was an independent factor associated with higher VEGF and IL-10 tear film concentrations (β = +0.13, p = 0.047 and β = +0.34, p < 0.001, respectively) and lower IL-1β, IL-8, and GM-CSF levels (β = −0.25, p < 0.001; β = −0.18, p = 0.004; and β = −0.82, p = 0.0 respectively). Conclusions: SARS-CoV-2 does not attract a strong local response of the conjunctival immune system; therefore, ophthalmic symptoms may not constitute a substantial element in the clinical picture of novel COVID-19 infection.