bluuebunny/crossref_metadata_2025 huggingface dataset:
Cat Ownership and Rural Residence Are Associated with Lyme Disease Prevalence in the Northeastern United States
Authors: Roome Amanda , Wander Katherine , Garruto Ralph M.
Published: May 2022

Lyme disease (LD) is the most common vector-borne disease in the USA. Beyond its tick-borne nature, however, risk factors for LD are poorly understood. We used an online questionnaire to compare LD patients and non-LD counterparts and elucidate factors associated with LD. We investigated demographic, lifestyle, and household characteristics and use of prevention measures. Associations with LD were modeled using logistic regression, and average marginal effects were estimated. In total, 185 active or past LD patients and 139 non-patients participated. The majority of respondents were white (95%) and female (65%). Controlling for age, sex, and type of residential area, pet ownership was associated with an 11.1% (p = 0.038) increase in the probability of LD. This effect was limited to cat owners (OR: 2.143, p = 0.007; dog owners, OR: 1.398, p = 0.221). Living in rural areas was associated with a 36% (p = 0.001) increase in the probability of LD compared to living in an urban area. Participants who reported knowing someone with Lyme Disease were more likely to wear insect repellant and perform tick checks. This study suggests opportunities for improved LD prevention, including advising cat owners of their increased risk. Although patterns in adoption of LD prevention methods remain poorly understood, concern about LD risk does motivate their use.
Physiological Aspects of World Elite Competitive German Winter Sport Athletes
Authors: Zimmermann Paul , Wüstenfeld Jan , Zimmermann Lukas , Schöffl Volker , Schöffl Isabelle
Published: May 2022

Nine Ski mountaineering (Ski-Mo), ten Nordic-Cross Country (NCC) and twelve world elite biathlon (Bia) athletes were evaluated for cardiopulmonary exercise test (CPET) performance as the primary aim of our descriptive preliminary report. A multicenter retrospective analysis of CPET data was performed in 31 elite winter sports athletes, which were obtained in 2021 during the annual medical examination. The matched data of the elite winter sports athletes (14 women, 17 male athletes, age: 18–32 years) were compared for different CPET parameters, and athlete’s physique data and sport-specific training schedules. All athletes showed, as estimated in elite winter sport athletes, excellent performance data in the CPET analyses. Significant differences were revealed for VE VT2 (respiratory minute volume at the second ventilatory threshold (VT2)), highest maximum respiratory minute volume (VEmaximum), the indexed ventilatory oxygen uptake (VO2) at VT2 (VO2/kg VT2), the oxygen pulse at VT2, and the maximum oxygen pulse level between the three professional winter sports disciplines. This report provides new evidence that in different world elite winter sport professionals, significant differences in CPET parameters can be demonstrated, against the background of athlete’s physique as well as training control and frequency.
Does the Synergy Model Implementation Improve the Transition from In-Hospital to Primary Care? The Experience from an Italian Cardiac Surgery Unit, Perspectives, and Future Implications
Authors: Dellafiore Federica , Caruso Rosario , Nania Tiziana , Pittella Francesco , Fiorini Tiziana , Caruso Maria Paola , Zaffino Giovanni , Stievano Alessandro , Arrigoni Cristina
Published: May 2022

The demand for care services in the healthcare system has changed and is triggering a smooth transition from in-hospital to primary care. In this regard, patient-centered-care models of care delivery might provide a framework to follow patients’ journeys throughout their transition between different levels of care. Accordingly, an Italian research group at a cardiac hospital in Northern Italy implemented the Synergy Model in a Cardiac Surgery Unit, a patient-centered-care model, and is using the framework of the model to guide a smooth transition of patients towards rehabilitation and primary care after their hospitalization. This discursive paper is focused on the experience, perspectives, and future implications of adopting the Synergy Model to facilitate the transition from in-hospital to primary care. The presented experience and discussion might be helpful to the international debate regarding the strategies to boost a smooth transition from in-hospital to primary care.
The Moral, Ethical, Personal, and Professional Challenges Faced by Physicians during the COVID-19 Pandemic
Authors: Goniewicz Krzysztof , Goniewicz Mariusz , Włoszczak-Szubzda Anna , Lasota Dorota , Burkle Frederick M. , Borowska-Stefańska Marta , Wiśniewski Szymon , Khorram-Manesh Amir
Published: May 2022

The COVID-19 pandemic, apart from the main problems concerning the health and life of patients, sparked a discussion about physicians’ moral and social professional attitudes. During a pandemic, physicians have the same ethical, moral, and medical responsibilities, however, the situation is different since they are self-exposed to a danger, which may influence their willingness to work. The problem of the professional moral attitudes of health care workers, recurring in ethical discussions, prompts us to define the limits of the duties of physicians in the event of a pandemic, hence this research aimed to assess these duties from an ethical perspective and to define their boundaries and scope. The study was conducted in May and June 2020 in the city of Lublin, covering all medical centers, and the questionnaire was completed by 549 physicians. The research was conducted in four areas: emergency standby in the event of a disaster, even if it is not requested; willingness to work overtime in the event of a disaster, even without payment; willingness to take health risks by caring for people who are infectious or exposed to hazardous substances; readiness to be transferred to other departments in the event of a disaster. Although most of the respondents declared to be agreed on personal sacrifices in the performance of professional duties, they were not prepared for a high level of personal risk when working in a pandemic. Excessive workload, its overwhelming nature, and personal risk are not conducive to readiness to work overtime, especially without pay. Research shows how important it is to respect the rights and interests of all parties involved in a pandemic. Physicians’ duty to care for a patient is also conditioned by the duty to protect themselves and should not be a tool for intimidating and depersonalizing their social and professional lives.
Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Adult Dermal Fibroblasts on Cervical Cancer Cells
Authors: Han Kyu-Hyun , Kim Ae-Kyeong , Kim Dong-ik
Published: May 2022

Hypoxia regulates fibroblast function by changing intracellular signaling and secretion factors, that influence the states of nearby cells. In this work, we investigated how medium (CM) from human adult dermal fibroblasts (HDFs) cultured in normoxic and hypoxic conditions affected cervical cancer (HeLa) cells. The HeLa cells showed decreased cell viability, increased apoptosis, and cell cycle arrest in response to CM from hypoxic-cultured HDFs (H-CM) compared with CM from normoxic-cultured HDFs (N-CM). Among the proteins up-regulated (>2-fold) in H-CM compared with N-CM, lymphotoxin-beta receptor (LTBR) decreased the viability of HeLa cells. Among the intracellular proteins down-regulated (>2-fold) in HeLa cells treated with H-CM compared with N-CM, the most enriched biological process GO term and KEGG pathway were protein deubiquitination and hsa05166:HTLV-I infection, respectively. In the protein–protein interaction network of intracellular proteins with altered expression (>2-fold), 1 up-regulated (TNF) and 8 down-regulated (ESR1, MCL1, TBP, CD19, LCK, PCNA, CHEK1, and POLA1) hub proteins were defined. Among the down-regulated hub proteins, the most enriched biological process GO term and KEGG pathway were leading strand elongation and hsa05166:HTLV-I infection, respectively. This study reveals that H-CM had stronger anti-cancer effects on cervical cancer cells than N-CM and induced intracellular signaling patterns related to those enhanced anti-cancer effects.
Chitosan-Enriched Solution Blow Spun Poly(Ethylene Oxide) Nanofibers with Poly(Dimethylsiloxane) Hydrophobic Outer Layer for Skin Healing and Regeneration
Authors: Szymańska Emilia , Wojasiński Michał , Czarnomysy Robert , Dębowska Renata , Łopianiak Iwona , Adasiewicz Kamil , Ciach Tomasz , Winnicka Katarzyna
Published: May 2022

Chitosan (CS)/poly(ethylene oxide) (PEO)-based nanofiber mats have attracted particular attention as advanced materials for medical and pharmaceutical applications. In the scope of present studies, solution blow spinning was applied to produce nanofibers from PEO and CS and physicochemical and biopharmaceutical studies were carried out to investigate their potential as wound nanomaterial for skin healing and regeneration. Additional coating with hydrophobic poly(dimethylsiloxane) was applied to favor removal of nanofibers from the wound surface. Unmodified nanofibers displayed highly porous structure with the presence of uniform, randomly aligned nanofibers, in contrast to coated materials in which almost all the free spaces were filled in with poly(dimethylsiloxane). Infrared spectroscopy indicated that solution blow technique did not influence the molecular nature of native polymers. Obtained nanofibers exhibited sufficient wound exudate absorbency, which appears beneficial to moisturize the wound bed during the healing process. Formulations displayed greater tensile strength as compared to commercial hydrofiber-like dressing materials comprised of carboxymethylcellulose sodium or calcium alginate, which points toward their protective function against mechanical stress. Coating with hydrophobic poly(dimethylsiloxane) (applied to favor nanofiber removal from the wound surface) impacted porosity and decreased both mechanical properties and adherence to excised human skin, though the obtained values were comparable to those attained for commercial hydrofiber-like materials. In vitro cytotoxicity and irritancy studies showed biocompatibility and no skin irritant response of nanofibers in contact with a reconstituted three-dimensional human skin model, while scratch assay using human fibroblast cell line HDFa revealed the valuable potential of CS/PEO nanofibers to promote cell migration at an early stage of injury.
Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use
Authors: Abate Marianna , Scotti Lorena , Nele Valeria , Caraglia Michele , Biondi Marco , De Rosa Giuseppe , Leonetti Carlo , Campani Virginia , Zappavigna Silvia , Porru Manuela
Published: May 2022

Self-assembling nanoparticles (SANPs) promise an effective delivery of bisphosphonates or microRNAs in the treatment of glioblastoma (GBM) and are obtained through the sequential mixing of four components immediately before use. The self-assembling approach facilitates technology transfer, but the complexity of the SANP preparation protocol raises significant concerns in the clinical setting due to the high risk of human errors during the procedure. In this work, it was hypothesized that the SANP preparation protocol could be simplified by using freeze-dried formulations. An in-depth thermodynamic study was conducted on solutions of different cryoprotectants, namely sucrose, mannitol and trehalose, to test their ability to stabilize the produced SANPs. In addition, the ability of SANPs to deliver drugs after lyophilization was assessed on selected formulations encapsulating zoledronic acid in vitro in the T98G GBM cell line and in vivo in an orthotopic mouse model. Results showed that, after lyophilization optimization, freeze-dried SANPs encapsulating zoledronic acid could retain their delivery ability, showing a significant inhibition of T98G cell growth both in vitro and in vivo. Overall, these results suggest that freeze-drying may help boost the industrial development of SANPs for the delivery of drugs to the brain.
Is Infantile Hemangioma a Neuroendocrine Tumor?
Authors: Kaulanjan-Checkmodine Priscilla , Oucherif Sandra , Prey Sorilla , Gontier Etienne , Lacomme Sabrina , Loot Maya , Miljkovic-Licina Marijana , Cario Muriel , Léauté-Labrèze Christine , Taieb Alain , Moisan François , Rezvani Hamid Reza
Published: May 2022

Infantile hemangioma (IH) is the most common infantile tumor, affecting 5–10% of newborns. Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is currently the first-line treatment for severe IH; however, both its mechanism of action and its main cellular target remain poorly understood. Since betablockers can antagonize the effect of natural ADRB agonists, we postulated that the catecholamine produced in situ in IH may have a role in the propranolol response. By quantifying catecholamines in the IH tissues, we found a higher amount of noradrenaline (NA) in untreated proliferative IHs than in involuted IHs or propranolol-treated IHs. We further found that the first three enzymes of the catecholamine biosynthesis pathway are expressed by IH cells and that their levels are reduced in propranolol-treated tumors. To study the role of NA in the pathophysiology of IH and its response to propranolol, we performed an in vitro angiogenesis assay in which IH-derived endothelial cells, pericytes and/or telocytes were incorporated. The results showed that the total tube formation is sensitive to propranolol only when exogenous NA is added in the three-cell model. We conclude that the IH’s sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA.
Impact of Oral Microbiome in Periodontal Health and Periodontitis: A Critical Review on Prevention and Treatment
Authors: Di Stefano Mattia , Polizzi Alessandro , Santonocito Simona , Romano Alessandra , Lombardi Teresa , Isola Gaetano
Published: May 2022

The skin, oral cavity, digestive and reproductive tracts of the human body harbor symbiotic and commensal microorganisms living harmoniously with the host. The oral cavity houses one of the most heterogeneous microbial communities found in the human organism, ranking second in terms of species diversity and complexity only to the gastrointestinal microbiota and including bacteria, archaea, fungi, and viruses. The accumulation of microbial plaque in the oral cavity may lead, in susceptible individuals, to a complex host-mediated inflammatory and immune response representing the primary etiological factor of periodontal damage that occurs in periodontitis. Periodontal disease is a chronic inflammatory condition affecting about 20–50% of people worldwide and manifesting clinically through the detection of gingival inflammation, clinical attachment loss (CAL), radiographic assessed resorption of alveolar bone, periodontal pockets, gingival bleeding upon probing, teeth mobility and their potential loss in advanced stages. This review will evaluate the changes characterizing the oral microbiota in healthy periodontal tissues and those affected by periodontal disease through the evidence present in the literature. An important focus will be placed on the immediate and future impact of these changes on the modulation of the dysbiotic oral microbiome and clinical management of periodontal disease.
Shared Inflammatory Pathology of Stroke and COVID-19
Authors: Sánchez Kathryn E. , Rosenberg Gary A.
Published: May 2022

Though COVID-19 is primarily characterized by symptoms in the periphery, it can also affect the central nervous system (CNS). This has been established by the association between stroke and COVID-19. However, the molecular mechanisms that cause stroke related to a COVID-19 infection have not been fully explored. More specifically, stroke and COVID-19 exhibit an overlap of molecular mechanisms. These similarities provide a way to better understand COVID-19 related stroke. We propose here that peripheral macrophages upregulate inflammatory proteins such as matrix metalloproteinases (MMPs) in response to SARS-CoV-2 infection. These inflammatory molecules and the SARS-CoV-2 virus have multiple negative effects related to endothelial dysfunction that results in the disruption of the blood–brain barrier (BBB). Finally, we discuss how the endothelial blood–brain barrier injury alters central nervous system function by leading to astrocyte dysfunction and inflammasome activation. Our goal is to elucidate such inflammatory pathways, which could provide insight into therapies to combat the negative neurological effects of COVID-19.
Responses of Growth, Oxidative Injury and Chloroplast Ultrastructure in Leaves of Lolium perenne and Festuca arundinacea to Elevated O3 Concentrations
Authors: Xu Sheng , Li Yan , Li Bo , He Xingyuan , Chen Wei , Yan Kun
Published: May 2022

The effects of increasing atmospheric ozone (O3) concentrations on cool-season plant species have been well studied, but little is known about the physiological responses of cool-season turfgrass species such as Lolium perenne and Festuca arundinacea exposed to short-term acute pollution with elevated O3 concentrations (80 ppb and 160 ppb, 9 h d−1) for 14 days, which are widely planted in urban areas of Northern China. The current study aimed to investigate and compare O3 sensitivity and differential changes in growth, oxidative injury, antioxidative enzyme activities, and chloroplast ultrastructure between the two turf-type plant species. The results showed that O3 decreased significantly biomass regardless of plant species. Under 160 ppb O3, total biomass of L. perenne and F. arundinacea significantly decreased by 55.3% and 47.8% (p < 0.05), respectively. No significant changes were found in visible injury and photosynthetic pigment contents in leaves of the two grass species exposed to 80 ppb O3, except for 160 ppb O3. However, both 80 ppb and 160 ppb O3 exposure induced heavily oxidative stress by high accumulation of malondialdehyde and reactive oxygen species in leaves and damage in chloroplast ultrastructure regardless of plant species. Elevated O3 concentration (80 ppb) increased significantly the activities of superoxide dismutase, catalase and peroxidaseby 77.8%, 1.14-foil and 34.3% in L. perenne leaves, and 19.2%, 78.4% and 1.72-fold in F. arundinacea leaves, respectively. These results showed that F. arundinacea showed higher O3 tolerance than L. perenne. The damage extent by elevated O3 concentrations could be underestimated only by evaluating foliar injury or chlorophyll content without considering the internal physiological changes, especially in chloroplast ultrastructure and ROS accumulation.
Profiling the Biological Characteristics and Transitions through Upper Tract Tumor Origin, Bladder Recurrence, and Muscle-Invasive Bladder Progression in Upper Tract Urothelial Carcinoma
Authors: Shigeta Keisuke , Matsumoto Kazuhiro , Tanaka Nobuyuki , Mikami Shuji , Kosaka Takeo , Yasumizu Yota , Takeda Toshikazu , Mizuno Ryuichi , Kikuchi Eiji , Oya Mototsugu
Published: May 2022

To evaluate biological characteristics and transitions of upper tract urothelial carcinoma (UTUC) through metachronous bladder tumors after radical nephroureterectomy (RNU), we conducted immunohistochemical (IHC) staining of tumor specimens of UTUC tumor origin, non-muscle-invasive bladder cancer (NMIBC) and MIBC progressed after intravesical recurrence (IVR), and bladder primary MIBC. Fibroblast growth factor receptor 3 (FGFR3), p53, cytokeratin 5/6 (CK5/6), and CK20 were stained to examine expression rates. After expression assessment with heatmap clustering, the overexpression of four biomarkers from UTUC origin to metachronous MIBC progression was analyzed with clinicopathological variables. We found that high CK20 and low CK5/6 expression were both observed in UTUC tumor origin and subsequent NMIBC after RNU. By investigating molecular expression in the IVR specimen, we observed that low pT stage bladder recurrence occupied the majority of CK20 high CK5/6 low expression, but would change to CK20 low CK5/6 high expression as it progressed to MIBC. UTUC metachronous MIBC has different characteristics compared with bladder primary MIBC, which comprises favorable biological features such as high FGFR3 expression, and follows favorable prognosis compared to those without FGFR3 expression. The present study demonstrated that the biological characteristics of UTUC tumor origin shifts from luminal to basal-like features with progression to MIBC, but FGFR3 expression taken over from UTUC origin may comprise a favorable entity compared to primary MIBC.
Spatiotemporal Gene Expression Regions along the Anterior–Posterior Axis in Mouse Embryos before and after Palatal Elevation
Authors: Nagasaka Arata , Sakiyama Koji , Bando Yasuhiko , Yamamoto Masahito , Abe Shinichi , Amano Osamu
Published: May 2022

The mammalian secondary palate is formed through complex developmental processes: growth, elevation, and fusion. Although it is known that the palatal elevation pattern changes along the anterior–posterior axis, it is unclear what molecules are expressed and whether their locations change before and after elevation. We examined the expression regions of molecules associated with palatal shelf elevation (Pax9, Osr2, and Tgfβ3) and tissue deformation (F-actin, E-cadherin, and Ki67) using immunohistochemistry and RT–PCR in mouse embryos at E13.5 (before elevation) and E14.5 (after elevation). Pax9 was expressed at significantly higher levels in the lingual/nasal region in the anterior and middle parts, as well as in the buccal/oral region in the posterior part at E13.5. At E14.5, Pax9 was expressed at significantly higher levels in both the lingual/nasal and buccal/oral regions in the anterior and middle parts and the buccal/oral regions in the posterior part. Osr2 was expressed at significantly higher levels in the buccal/oral region in all parts at E13.5 and was more strongly expressed at E13.5 than at E14.5 in all regions. No spatiotemporal changes were found in the other molecules. These results suggested that Pax9 and Osr2 are critical molecules leading to differences in the elevation pattern in palatogenesis.
The Role of Sugars in Plant Responses to Stress and Their Regulatory Function during Development
Authors: Jeandet Philippe , Formela-Luboińska Magda , Labudda Mateusz , Morkunas Iwona
Published: May 2022

Due to their role as energy and carbon sources and their regulatory functions, sugars influence all phases of the plant life cycle, interact with other signaling molecules, including phytohormones, and control plant growth and development [...]
Proteomics in Multiple Sclerosis: The Perspective of the Clinician
Authors: Sandi Dániel , Kokas Zsófia , Biernacki Tamás , Bencsik Krisztina , Klivényi Péter , Vécsei László
Published: May 2022

Multiple sclerosis (MS) is the inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) that affects approximately 2.8 million people worldwide. In the last decade, a new era was heralded in by a new phenotypic classification, a new diagnostic protocol and the first ever therapeutic guideline, making personalized medicine the aim of MS management. However, despite this great evolution, there are still many aspects of the disease that are unknown and need to be further researched. A hallmark of these research are molecular biomarkers that could help in the diagnosis, differential diagnosis, therapy and prognosis of the disease. Proteomics, a rapidly evolving discipline of molecular biology may fulfill this dire need for the discovery of molecular biomarkers. In this review, we aimed to give a comprehensive summary on the utility of proteomics in the field of MS research. We reviewed the published results of the method in case of the pathogenesis of the disease and for biomarkers of diagnosis, differential diagnosis, conversion of disease courses, disease activity, progression and immunological therapy. We found proteomics to be a highly effective emerging tool that has been providing important findings in the research of MS.
Development and Evaluation of a Robust Sandwich Immunoassay System Detecting Serum WFA-Reactive IgA1 for Diagnosis of IgA Nephropathy
Authors: Uenoyama Yuta , Matsuda Atsushi , Ohashi Kazune , Ueda Koji , Yokoyama Misaki , Kyoutou Takuya , Kishi Kouji , Takahama Youichi , Nagai Masaaki , Ohbayashi Takaaki , Hotta Osamu , Matsuzaki Hideki
Published: May 2022

Aberrant glycosylation of IgA1 is involved in the development of IgA nephropathy (IgAN). There are many reports of IgAN markers focusing on the glycoform of IgA1. None have been clinically applied as a routine test. In this study, we established an automated sandwich immunoassay system for detecting aberrant glycosylated IgA1, using Wisteria floribunda agglutinin (WFA) and anti-IgA1 monoclonal antibody. The diagnostic performance as an IgAN marker was evaluated. The usefulness of WFA for immunoassays was investigated by lectin microarray. A reliable standard for quantitative immunoassay measurements was designed by modifying a purified IgA1 substrate. A validation study using multiple serum specimens was performed using the established WFA-antibody sandwich automated immunoassay. Lectin microarray results showed that WFA specifically recognized N-glycans of agglutinated IgA1 in IgAN patients. The constructed IgA1 standard exhibited a wide dynamic range and high reactivity. In the validation study, serum WFA-reactive IgA1 (WFA+-IgA1) differed significantly between healthy control subjects and IgAN patients. The findings indicate that WFA is a suitable lectin that specifically targets abnormal agglutinated IgA1 in serum. We also describe an automated immunoassay system for detecting WFA+-IgA1, focusing on N-glycans.
Electronic Transport Properties in GaAs/AlGaAs and InSe/InP Finite Superlattices under the Effect of a Non-Resonant Intense Laser Field and Considering Geometric Modifications
Authors: Gil-Corrales John A. , Morales Alvaro L. , Behiye Yücel Melike , Kasapoglu Esin , Duque Carlos A.
Published: May 2022

In this work, a finite periodic superlattice is studied, analyzing the probability of electronic transmission for two types of semiconductor heterostructures, GaAs/AlGaAs and InSe/InP. The changes in the maxima of the quasistationary states for both materials are discussed, making variations in the number of periods of the superlattice and its shape by means of geometric parameters. The effect of a non-resonant intense laser field has been included in the system to analyze the changes in the electronic transport properties by means of the Landauer formalism. It is found that the highest tunneling current is given for the GaAs-based compared to the InSe-based system and that the intense laser field improves the current–voltage characteristics generating higher current peaks, maintaining a negative differential resistance (NDR) effect, both with and without laser field for both materials and this fact allows to tune the magnitude of the current peak with the external field and therefore extend the range of operation for multiple applications. Finally, the power of the system is discussed for different bias voltages as a function of the chemical potential.
Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells
Authors: Li Shinan , Khoi Pham Ngoc , Yin Hong , Sah Dhiraj Kumar , Kim Nam-Ho , Lian Sen , Jung Young-Do
Published: May 2022

Sulforaphane, a natural phytochemical compound found in various cruciferous vegetables, has been discovered to present anti-cancer properties. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in gastric cancer metastasis. However, the role of sulforaphane in MMP-9 expression in gastric cancer is not yet defined. Nicotine, a psychoactive alkaloid found in tobacco, is associated with the development of gastric cancer. Here, we found that sulforaphane suppresses the nicotine-mediated induction of MMP-9 in human gastric cancer cells. We discovered that reactive oxygen species (ROS) and MAPKs (p38 MAPK, Erk1/2) are involved in nicotine-induced MMP-9 expression. AP-1 and NF-κB are the critical transcription factors in MMP-9 expression. ROS/MAPK (p38 MAPK, Erk1/2) and ROS functioned as upstream signaling of AP-1 and NF-κB, respectively. Sulforaphane suppresses the nicotine-induced MMP-9 by inhibiting ROS-mediated MAPK (p38 MAPK, Erk1/2)/AP-1 and ROS-mediated NF-κB signaling axes, which in turn inhibit cell invasion in human gastric cancer AGS cells. Therefore, the current study provides valuable evidence for developing sulforaphane as a new anti-invasion strategy for human gastric cancer therapy.
Mobile User Interaction Design Patterns: A Systematic Mapping Study
Authors: da Silva Leonardo Filipe , Parreira Junior Paulo Afonso , Freire André Pimenta
Published: May 2022

Interaction design patterns have evolved as a resource that facilitates documentation and the reuse of proven solutions. They provide a structured and understandable mechanism for what to do in the design. Mobile devices have characteristics, configurations, and restrictions that make the construction of their interfaces full of particularities to this environment, and problems that are often common to designers and developers. This study presented a systematic mapping of the state-of-the-art regarding interaction design patterns for mobile devices. A total of 23 studies that include articles and books met the selection criteria in this mapping, examining relevant scientific databases and books that were cited in relevant articles. As a main result, 336 patterns were compiled, with 261 of these problems and solutions being dissimilar from each other. The paper describes patterns in 18 categories covering different interaction aspects. Pattern structural elements with mentions in more than five papers included: Name, Solution, Problem, Context, Examples, Related Patterns, Forces, Consequences and Figure. Four studies reported empirical evaluation of the patterns with a limited number of users. The paper contributed with a categorization of existing patterns and the challenges for uniformization of structure and empirical evidence with user evaluation.
The Growing Infrastructure Crisis: The Challenge of Scour Risk Assessment and the Development of a New Sensing System
Authors: Michalis Panagiotis , Vintzileou Elizabeth
Published: May 2022

Scour action is one of the main factors that add significant stress to the growing infrastructure crisis as it is considered one of the most destructive flood-related hazards occurring around underwater foundation elements. Recent cases of bridge failures have highlighted the need for a reliable scour monitoring and early warning system to assess flood and geo-hazards in real-time, providing advanced key info for repair and maintenance actions. Despite the past efforts to provide such a system for scour assessment, most of the developed instruments were not able to offer a reliable solution for scour monitoring, due to technical and cost issues. As a result, there currently exists a gap in the knowledge and understanding of scour mechanism during flood incidents. This study presents the development of a new sensing system to assess hydro-hazards at bridge infrastructure. It initially focuses on factors contributing to the growing infrastructure crisis and provides an overview of the current practices and assessment procedures to assess scour processes and a summary of advantages and limitations of existing monitoring efforts. A new monitoring concept for assessing scour and sediment deposition processes is then presented focusing on modelling the geometric components of a new sensor which is evaluated in simulations under different environments that represent prospective field conditions. Main results are analysed and presented focusing on key criteria that maximize sensitivity of the sensor to scour and sedimentation processes. The obtained results indicate that the sensor has the potential to provide a new monitoring device for scour and sediment deposition monitoring, and it is proposed to be further developed and assessed in laboratory and field conditions. This study aspires to contribute to the ongoing discourse on the use of sensing techniques to monitor, assess, and manage scour action effectively.
Innovation of Surgical Techniques for Screw Fixation in Patients with Osteoporotic Spine
Authors: Kanno Haruo , Onoda Yoshito , Hashimoto Ko , Aizawa Toshimi , Ozawa Hiroshi
Published: May 2022

Osteoporosis is a common disease in elderly populations and is a major public health problem worldwide. It is not uncommon for spine surgeons to perform spinal instrumented fusion surgeries for osteoporotic patients. However, in patients with severe osteoporosis, instrumented fusion may result in screw loosening, implant failure or nonunion because of a poor bone quality and decreased pedicle screw stability as well as increased graft subsidence risk. In addition, revision surgeries to correct failed instrumentation are becoming increasingly common in patients with osteoporosis. Therefore, techniques to enhance the fixation of pedicle screws are required in spinal surgeries for osteoporotic patients. To date, various instrumentation methods, such as a supplemental hook, sublaminar taping and sacral alar iliac screws, and modified screwing techniques have been available for reinforcing pedicle screw fixation. In addition, several materials, including polymethylmethacrylate and hydroxyapatite stick/granules, for insertion into prepared screw holes, can be used to enhance screw fixation. Many biomechanical tests support the effectiveness of these augmentation methods. We herein review the current therapeutic strategies for screw fixation and augmentation methods in the surgical treatment of patients with an osteoporotic spine.
Intravenous versus Epidural Routes of Patient-Controlled Analgesia in Abdominal Surgery: Systematic Review with Meta-Analysis
Authors: Viderman Dmitriy , Tapinova Karina , Nabidollayeva Fatima , Tankacheev Ramil , Abdildin Yerkin G.
Published: May 2022

Objective: To compare the intravenous and epidural routes of patient-controlled anesthesia in abdominal surgery. Methods: We searched for randomized clinical trials that compared the intravenous and epidural modes of patient-controlled anesthesia in intra-abdominal surgery in adults. Data analysis was performed in RevMan 5.4. Heterogeneity was measured using I2 statistic. Risk of bias was assessed using the Jadad/Oxford quality scoring system. Results: Seven studies reporting 529 patients were included into the meta-analysis. For pain at rest, the mean difference with 95% confidence interval (CI) was −0.00 [−0.79, 0.78], p-value 0.99, while for pain on coughing, it was 0.43 [−0.02, 0.88], p-value 0.06, indicating that patient-controlled epidural analgesia (PCEA) was superior. For the sedation score, the mean difference with 95% CI was 0.26 [−0.37, 0.89], p-value 0.42, slightly favoring PCEA. For the length of hospital stay, the mean difference with 95% CI was 1.13 [0.29, 1.98], p-value 0.009, favoring PCEA. For postoperative complications, the risk ratio with 95% CI was 0.8 [0.62, 1.03], p-value 0.08, slightly favoring patient-controlled intravenous analgesia (PCIVA). A significant effect was observed for hypotension, favoring PCIVA. Conclusions: Patient-controlled intravenous analgesia compared with patient-controlled epidural analgesia was associated with fewer episodes of hypotension. PCEA, on other hand, was associated with a shorter length of hospital stay. Pain control and other side effects did not differ significantly. Only three studies out of seven had an acceptable methodological quality. Thus, these conclusions should be taken with caution.
Sartans and ACE Inhibitors: Mortality in Patients Hospitalized with COVID-19. Retrospective Study in Patients on Long-Term Treatment Who Died in the Italian Hospitals of Area Vasta n.5—Marche Region
Authors: Mazzoni Tony , Maraia Zaira , Ruggeri Benedetta , Polidori Carlo , Micioni Di Bonaventura Maria Vittoria , Armillei Laura , Pomilio Irene , Mazzoni Isidoro
Published: May 2022

Introduction: During the 2019 Coronavirus pandemic (COVID-19), a concern emerged regarding a possible correlation between the severe form of SARS-CoV-2 infection and administration of ACE-Inhibitors (ACE-I) and Sartans (ARB), since long-term use of these drugs may potentially result in an adaptive response with up-regulation of the ACE 2 receptor. Given the crucial role of ACE2, being the main target for virus entry into the cell, the potential consequences of ACE2 up-regulation have been a source of debate. The aim of this retrospective cohort study on COVID-19-positive patients who died is to investigate whether previous long-term exposure to ACE-I and/or ARB was associated with higher mortality due to COVID-19 infection, compared to all other types of drug treatment. Methods: We analysed the clinical and demographic data of 615 patients hospitalized for COVID-19 at the two hospitals of the Vasta Area n.5, between March 2020 and April 2021. Among them, 86 patients, treated with ACE-Is and/0 ARBs for about 12 months, died during hospitalization following a diagnosis of acute respiratory failure. Several quantitative and qualitative variables were recorded for all patients by reading their medical records. Results: The logistic model showed that the variables that increase mortality are age and comorbid diseases. There were no demonstrable mortality effects with ACE-I and ARB intake. Conclusions: The apparent increase in morbidity in patients with COVID-19 who received long-term treatment with ACE-I or ARB is not due to the drugs themselves, but to the conditions associated with their use.
Body Mass Index and Mortality, Recurrence and Readmission after Myocardial Infarction: Systematic Review and Meta-Analysis
Authors: De Paola Lorenzo , Mehta Arnav , Pana Tiberiu A. , Carter Ben , Soiza Roy L. , Kafri Mohannad W. , Potter John F. , Mamas Mamas A. , Myint Phyo K.
Published: May 2022

The following study aimed to systematically review and meta-analyse the literature on the relations between markers of nutritional status and long-term mortality, recurrence and all-cause hospital readmission following myocardial infarction (MI). Medline, EMBASE and Web of Science were searched for prospective cohort studies reporting the relationship between anthropometric and biochemical markers of nutritional status and nutritional assessment tools on long-term mortality, recurrence and all-cause hospital readmission in adult patients with an MI. Two reviewers conducted screening, data extraction and critical appraisal independently. Random-effects meta-analysis was performed. Twenty-seven studies were included in the qualitative synthesis and twenty-four in the meta-analysis. All eligible studies analysed BMI as their exposure of interest. Relative to normal weight, mortality was highest in underweight patients (adjusted Hazard Ratio (95% confidence interval): 1.42 (1.24–1.62)) and lower in both overweight (0.85 (0.76–0.94)) and obese patients (0.86 (0.81–0.91)), over a mean follow-up ranging from 6 months to 17 years. No statistically significant associations were identified between different BMI categories for the outcomes of recurrence and hospital readmission. Patients with low BMI carried a significant mortality risk post-MI; however due to the known limitations associated with BMI measurement, further evidence regarding the prognostic utility of other nutritional markers is required.
Association between Early Mobilization in the ICU and Psychiatric Symptoms after Surviving a Critical Illness: A Multi-Center Prospective Cohort Study
Authors: Watanabe Shinichi , Liu Keibun , Nakamura Kensuke , Kozu Ryo , Horibe Tatsuya , Ishii Kenzo , Yasumura Daisetsu , Takahashi You , Nanba Tomoya , Morita Yasunari , Kanaya Takahiro , Suzuki Shuichi , Lefor Alan Kawarai , Katsukawa Hajime , Kotani Toru
Published: May 2022

This is a prospective multicenter cohort study aiming to investigate the association between early mobilization (EM), defined as a rehabilitation level of sitting at the edge of the bed or higher within 72 h of ICU admission, and psychiatric outcome. Consecutive patients, admitted to the ICU for more than 48 h, were enrolled. The primary outcome was the incidence of psychiatric symptoms at 3 months after hospital discharge defined as the presence of any of three symptoms: depression, anxiety, or post-traumatic stress disorder (PTSD). Risk ratio (RR) and multiple logistic regression analysis were used. As a sensitivity analysis, two methods for inverse probability of treatment weighting statistics were performed. Of the 192 discharged patients, 99 (52%) were assessed. The patients who achieved EM had a lower incidence of psychiatric symptoms compared to those who did not (25% vs. 51%, p-value 0.008, odds ratio (OR) 0.27, adjusted p = 0.032). The RR for psychiatric symptoms in the EM group was 0.49 [95% Confidence Interval, 0.29–0.83]. Sensitivity analysis accounting for the influence of death, loss to follow-up (OR 0.28, adjusted p = 0.008), or potential confounders (OR 0.49, adjusted p = 0.046) consistently showed a lower incidence of psychiatric symptoms in the EM group. EM was consistently associated with fewer psychiatric symptoms.
Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum
Authors: Leftheriotis Georges , Navasiolava Nastassia , Clotaire Laetitia , Duranton Christophe , Le Saux Olivier , Bendahhou Saïd , Laurain Audrey , Rubera Isabelle , Martin Ludovic
Published: May 2022

Pseudoxanthoma elasticum (PXE; OMIM 264800) is an autosomal recessive metabolic disorder characterized by progressive calcification in the skin, the Bruch’s membrane, and the vasculature. Calcification in PXE results from a low level of circulating pyrophosphate (PPi) caused by ABCC6 deficiency. In this study, we used a cohort of 107 PXE patients to determine the pathophysiological relationship between plasma PPi, coronary calcification (CAC), lower limbs arterial calcification (LLAC), and disease severity. Overall, our data showed a deficit in plasma PPi in PXE patients compared to controls. Remarkably, affected females showed higher PPi levels than males, but a lower LLAC. There was a strong correlation between age and PPi in PXE patients (r = 0.423, p < 0.0001) but not in controls (r = 0.059, p = 0.828). A weak correlation was found between PPi and CAC (r = 0.266, p < 0.02); however, there was no statistically significant connection with LLAC (r = 0.068, p = 0.518) or a severity score (r = 0.077, p = 0.429). Surprisingly, we found no significant correlation between plasma alkaline phosphatase activity and PPi (r = 0.113, p = 0.252) or between a 10-year cardiovascular risk score and all other variables. Multivariate analysis confirmed that LLAC and CAC were strongly dependent on age, but not on PPi. Our data showed that arterial calcification is only weakly linked to circulating PPi levels and that time (i.e., age) appears to be the major determinant of disease severity and calcification in PXE. These data are important to better understand the natural history of this disease but also for the follow-up and management of patients, and the design of future clinical trials. Our results also show that PPi is not a good biomarker for the evaluation of disease severity and progression.
Management of Pheochromocytomas and Paragangliomas: A Case-Based Review of Clinical Aspects and Perspectives
Authors: Sobocki Bartosz Kamil , Perdyan Adrian , Szot Olga , Rutkowski Jacek
Published: May 2022

Paraganglioma and pheochromocytoma are rare medical conditions. Thus, there are still a small number of studies, clinical trials, and evidence-based data in this field. This makes clinical decisions more difficult. In this study, we present a case report enriched with a short review of available essential clinical data, indicating the need for constant metoxycatecholamine level observation and a proper diagnostic imaging approach, especially in terms of ongoing pandemics. Our research also provides a summary of the molecular background of these diseases, indicating their future role in clinical management. We analyzed the ClinicalTrials.gov dataset in order to show future perspectives. In this paper, the use of the PET-CT before MRI or CT is proposed in specific cases during diagnosis processes contrary to the guidelines. PET-CT may be as effective as standard procedures and may provide a faster diagnosis, which is important in periods with more difficult access to health care, such as during the COVID-19 pandemic.
Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients
Authors: Tetaj Nardi , Stazi Giulia Valeria , Marini Maria Cristina , Garotto Gabriele , Busso Donatella , Scarcia Silvana , Caravella Ilaria , Macchione Manuela , De Angelis Giada , Di Lorenzo Rachele , Carucci Alessandro , Capone Alessandro , Antinori Andrea , Palmieri Fabrizio , D’Offizi Gianpiero , Taglietti Fabrizio , Ianniello Stefania , Campioni Paolo , Vaia Francesco , Nicastri Emanuele , Girardi Enrico , Marchioni Luisa ,   on behalf of ICU COVID-19 Study Group
Published: May 2022

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86–51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH—but it was not statistically significant (OR 7.1, 95% CI 0.90–56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research.
Disorders of the Calcium Sensing Signaling Pathway: From Familial Hypocalciuric Hypercalcemia (FHH) to Life Threatening Conditions in Infancy
Authors: Höppner Jakob , Sinningen Kathrin , Raimann Adalbert , Obermayer-Pietsch Barbara , Grasemann Corinna
Published: May 2022

Familial hypocalciuric hypercalcemia (FHH) is a mostly benign condition of elevated calcium and PTH levels based on a hyposensitive calcium sensing receptor (CaSR) in FHH 1 or its downstream regulatory pathway in FHH2 and FHH3. In children, adolescents and young adults with FHH the main challenge is to distinguish the condition from primary hyperparathyroidism and thereby to avoid unnecessary treatments including parathyroidectomy. However, inheritance of FHH may result in neonatal hyperparathyroidism (NHPT) or neonatal severe hyperparathyroidism (NSHPT), conditions with high morbidity, and in the latter even high mortality. This review focuses on the genetic and pathophysiological framework that leads to the severe neonatal form, gives recommendations for counselling and summarizes treatment options.