bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis
Authors: Antonucci Alessandra , Marucci Antonella , Trischitta Vincenzo , Di Paola Rosa
Published: January 2022

O-linked glycosylation, the greatest form of post-translational modifications, plays a key role in regulating the majority of physiological processes. It is, therefore, not surprising that abnormal O-linked glycosylation has been related to several human diseases. Recently, GALNT2, which encodes the GalNAc-transferase 2 involved in the first step of O-linked glycosylation, has attracted great attention as a possible player in many highly prevalent human metabolic diseases, including atherogenic dyslipidemia, type 2 diabetes and obesity, all clustered on the common ground of insulin resistance. Data available both in human and animal models point to GALNT2 as a molecule that shapes the risk of the aforementioned abnormalities affecting diverse protein functions, which eventually cause clinically distinct phenotypes (a typical example of pleiotropism). Pathways linking GALNT2 to dyslipidemia and insulin resistance have been partly identified, while those for type 2 diabetes and obesity are yet to be understood. Here, we will provide a brief overview on the present knowledge on GALNT2 function and dysfunction and propose novel insights on the complex pathogenesis of the aforementioned metabolic diseases, which all impose a heavy burden for patients, their families and the entire society.
Theranostic Platforms Based on Silica and Magnetic Nanoparticles Containing Quinacrine, Chitosan, Fluorophores, and Quantum Dots
Authors: Korolev Dmitry V. , Shulmeyster Galina A. , Evreinova Natalia V. , Syrovatkina Maria S. , Istomina Maria S. , Postnov Victor N. , Aleksandrov Ilia V. , Krasichkov Aleksandr S. , Galagudza Michael M.
Published: January 2022

In this paper, we describe the synthesis of multilayer nanoparticles as a platform for the diagnosis and treatment of ischemic injuries. The platform is based on magnetite (MNP) and silica (SNP) nanoparticles, while quinacrine is used as an anti-ischemic agent. The synthesis includes the surface modification of nanoparticles with (3-glycidyloxypropyl)trimethoxysilane (GPMS), the immobilization of quinacrine, and the formation of a chitosan coating, which is used to fix the fluorophore indocyanine green (ICG) and colloidal quantum dots AgInS2/ZnS (CQDs), which serve as secondary radiation sources. The potential theranostic platform was studied in laboratory animals.
DFT Study of the Molecular and Electronic Structure of Metal-Free Tetrabenzoporphyrin and Its Metal Complexes with Zn, Cd, Al, Ga, In
Authors: Eroshin Alexey V. , Otlyotov Arseniy A. , Kuzmin Ilya A. , Stuzhin Pavel A. , Zhabanov Yuriy A.
Published: January 2022

The electronic and molecular structures of metal-free tetrabenzoporphyrin (H2TBP) and its complexes with zinc, cadmium, aluminum, gallium and indium were investigated by density functional theory (DFT) calculations with a def2-TZVP basis set. A geometrical structure of ZnTBP and CdTBP was found to possess D4h symmetry; AlClTBP, GaClTBP and InClTBP were non-planar complexes with C4v symmetry. The molecular structure of H2TBP belonged to the point symmetry group of D2h. According to the results of the natural bond orbital (NBO) analysis, the M-N bonds had a substantial ionic character in the cases of the Zn(II) and Cd(II) complexes, with a noticeably increased covalent contribution for Al(III), Ga(III) and In(III) complexes with an axial –Cl ligand. The lowest excited states were computed with the use of time-dependent density functional theory (TDDFT) calculations. The model electronic absorption spectra indicated a weak influence of the nature of the metal on the Q-band position.
Placenta-Specific miR-125b Overexpression Leads to Increased Rates of Pregnancy Loss in Mice
Authors: Sun Fen , Cai Hui , Tan Lunbo , Qin Dezhe , Zhang Jian , Hua Jinlian , Fan Xiujun , Peng Sha
Published: January 2022

Pregnancy loss (PL) is one of the common complications that women can experience during pregnancy, with an occurrence rate of 1 to 5%. The potential causes of pregnancy loss are unclear, with no effective treatment modalities being available. It has been previously reported that the level of miR-125b was significantly increased in placentas of PL patients. However, the role of miR-125b in the development of PL still remains unknown. In the current study, an miR-125b placenta-specific over-expression model was constructed by lentiviral transfecting zona-free mouse embryos followed by embryo transfer. On gestation day 15, it was observed that the placenta was significantly smaller in the miR-125b placenta-specific overexpression group than the control group. Additionally, the abortion rate of the miR-125b placenta-specific overexpression group was markedly higher than in the control group. The blood vessel diameter was larger in the miR-125b-overexpressing specific placenta. In addition, miR-125b-overexpressing HTR8 and JEG3 cell lines were also generated to analyze the migration and invasion ability of trophoblasts. The results showed that miR-125b overexpression significantly suppressed the migration and invasion ability of HTR8 and JEG3 cells. Overall, our results demonstrated that miR-125b can affect embryo implantation through modulating placenta angiogenesis and trophoblast cell invasion capacity that can lead to PL.
Disease Outcome and Brain Metabolomics of Cyclophilin-D Knockout Mice in Sepsis
Authors: Kobayashi Takayuki , Uchino Hiroyuki , Elmér Eskil , Ogihara Yukihiko , Fujita Hidetoshi , Sekine Shusuke , Ishida Yusuke , Saiki Iwao , Shibata Shoichiro , Kawachi Aya
Published: January 2022

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction resulting from a systemic inflammatory response to infection, but the mechanism remains unclear. The mitochondrial permeability transition pore (MPTP) could play a central role in the neuronal dysfunction, induction of apoptosis, and cell death in SAE. The mitochondrial isomerase cyclophilin D (CypD) is known to control the sensitivity of MPTP induction. We, therefore, established a cecal ligation and puncture (CLP) model, which is the gold standard in sepsis research, using CypD knockout (CypD KO) mice, and analyzed the disease phenotype and the possible molecular mechanism of SAE through metabolomic analyses of brain tissue. A comparison of adult, male wild-type, and CypD KO mice demonstrated statistically significant differences in body temperature, mortality, and histological changes. In the metabolomic analysis, the main finding was the maintenance of reduced glutathione (GSH) levels and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the KO animals following CLP. In conclusion, we demonstrate that CypD is implicated in the pathogenesis of SAE, possibly related to the inhibition of MPTP induction and, as a consequence, the decreased production of ROS and other free radicals, thereby protecting mitochondrial and cellular function.
Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals
Authors: Faber Matthew W. , Vo Tommy V.
Published: January 2022

As part of a complex network of genome control, long regulatory RNAs exert significant influences on chromatin dynamics. Understanding how this occurs could illuminate new avenues for disease treatment and lead to new hypotheses that would advance gene regulatory research. Recent studies using the model fission yeast Schizosaccharomyces pombe (S. pombe) and powerful parallel sequencing technologies have provided many insights in this area. This review will give an overview of key findings in S. pombe that relate long RNAs to multiple levels of chromatin regulation: histone modifications, gene neighborhood regulation in cis and higher-order chromosomal ordering. Moreover, we discuss parallels recently found in mammals to help bridge the knowledge gap between the study systems.
R-Ras1 and R-Ras2 Expression in Anatomical Regions and Cell Types of the Central Nervous System
Authors: Garcia-Martin Gonzalo , Sanz-Rodriguez Miriam , Alcover-Sanchez Berta , Pereira Marta P. , Wandosell Francisco , Cubelos Beatriz
Published: January 2022

Since the optic nerve is one of the most myelinated tracts in the central nervous system (CNS), many myelin diseases affect the visual system. In this sense, our laboratory has recently reported that the GTPases R-Ras1 and R-Ras2 are essential for oligodendrocyte survival and maturation. Hypomyelination produced by the absence of one or both proteins triggers axonal degeneration and loss of visual and motor function. However, little is known about R-Ras specificity and other possible roles that they could play in the CNS. In this work, we describe how a lack of R-Ras1 and/or R-Ras2 could not be compensated by increased expression of the closely related R-Ras3 or classical Ras. We further studied R-Ras1 and R-Ras2 expression within different CNS anatomical regions, finding that both were more abundant in less-myelinated regions, suggesting their expression in non-oligodendroglial cells. Finally, using confocal immunostaining colocalization, we report for the first time that R-Ras2 is specifically expressed in neurons. Neither microglia nor astrocytes expressed R-Ras1 or R-Ras2. These results open a new avenue for the study of neuronal R-Ras2’s contribution to the process of myelination.
Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide
Authors: Chen Jinghua , Xie Peilu , Huang Yujia , Gao Haichun
Published: January 2022

Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.
Regulation of the Receptor Tyrosine Kinase AXL in Response to Therapy and Its Role in Therapy Resistance in Glioblastoma
Authors: Scherschinski Lea , Prem Markus , Kremenetskaia Irina , Tinhofer Ingeborg , Vajkoczy Peter , Karbe Anna-Gila , Onken Julia Sophie
Published: January 2022

The receptor tyrosine kinase AXL (RTK-AXL) is implicated in therapy resistance and tumor progression in glioblastoma multiforme (GBM). Here, we investigated therapy-induced receptor modifications and how endogenous RTK-AXL expression and RTK-AXL inhibition contribute to therapy resistance in GBM. GBM cell lines U118MG and SF126 were exposed to temozolomide (TMZ) and radiation (RTX). Receptor modifications in response to therapy were investigated on protein and mRNA levels. TMZ-resistant and RTK-AXL overexpressing cell lines were exposed to increasing doses of TMZ and RTX, with and without RTK-AXL tyrosine kinase inhibitor (TKI). Colorimetric microtiter (MTT) assay and colony formation assay (CFA) were used to assess cell viability. Results showed that the RTK-AXL shedding product, C-terminal AXL (CT-AXL), rises in response to repeated TMZ doses and under hypoxia, acts as a surrogate marker for radio-resistance. Endogenous RTX-AXL overexpression leads to therapy resistance, whereas combination therapy of TZM and RTX with TKI R428 significantly increases therapeutic effects. This data proves the role of RTK-AXL in acquired and intrinsic therapy resistance. By demonstrating that therapy resistance may be overcome by combining AXL TKI with standard treatments, we have provided a rationale for future study designs investigating AXL TKIs in GBM.
Intrinsic Expression of Coagulation Factors and Protease Activated Receptor 1 (PAR1) in Photoreceptors and Inner Retinal Layers
Authors: Goldberg Zehavit , Sher Ifat , Qassim Lamis , Chapman Joab , Rotenstreich Ygal , Shavit-Stein Efrat
Published: January 2022

The aim of this study was to characterize the distribution of the thrombin receptor, protease activated receptor 1 (PAR1), in the neuroretina. Neuroretina samples of wild-type C57BL/6J and PAR1−/− mice were processed for indirect immunofluorescence and Western blot analysis. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to determine mRNA expression of coagulation Factor X (FX), prothrombin (PT), and PAR1 in the isolated neuroretina. Thrombin activity following KCl depolarization was assessed in mouse neuroretinas ex vivo. PAR1 staining was observed in the retinal ganglion cells, inner nuclear layer cells, and photoreceptors in mouse retinal cross sections by indirect immunofluorescence. PAR1 co-localized with rhodopsin in rod outer segments but was not expressed in cone outer segments. Western blot analysis confirmed PAR1 expression in the neuroretina. Factor X, prothrombin, and PAR1 mRNA expression was detected in isolated neuroretinas. Thrombin activity was elevated by nearly four-fold in mouse neuroretinas following KCl depolarization (0.012 vs. 0.044 mu/mL, p = 0.0497). The intrinsic expression of coagulation factors in the isolated neuroretina together with a functional increase in thrombin activity following KCl depolarization may suggest a role for the PAR1/thrombin pathway in retinal function.
Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions
Authors: Liu Shan , Washio Jumpei , Sato Satoko , Abiko Yuki , Shinohara Yuta , Kobayashi Yuri , Otani Haruki , Sasaki Shiori , Wang Xiaoyi , Takahashi Nobuhiro
Published: January 2022

Metformin is a metabolic disruptor, and its efficacy and effects on metabolic profiles under different oxygen and nutrient conditions remain unclear. Therefore, the present study examined the effects of metformin on cell growth, the metabolic activities and consumption of glucose, glutamine, and pyruvate, and the intracellular ratio of nicotinamide adenine dinucleotide (NAD+) and reduced nicotinamide adenine dinucleotide (NADH) under normoxic (21% O2) and hypoxic (1% O2) conditions. The efficacy of metformin with nutrient removal from culture media was also investigated. The results obtained show that the efficacy of metformin was closely associated with cell types and environmental factors. Acute exposure to metformin had no effect on lactate production from glucose, glutamine, or pyruvate, whereas long-term exposure to metformin increased the consumption of glucose and pyruvate and the production of lactate in the culture media of HeLa and HaCaT cells as well as the metabolic activity of glucose. The NAD+/NADH ratio decreased during growth with metformin regardless of its efficacy. Furthermore, the inhibitory effects of metformin were enhanced in all cell lines following the removal of glucose or pyruvate from culture media. Collectively, the present results reveal that metformin efficacy may be regulated by oxygen conditions and nutrient availability, and indicate the potential of the metabolic switch induced by metformin as combinational therapy.
Inulin Improves Diet-Induced Hepatic Steatosis and Increases Intestinal Akkermansia Genus Level
Authors: Pérez-Monter Carlos , Álvarez-Arce Alejandro , Nuño-Lambarri Natalia , Escalona-Nández Ivonne , Juárez-Hernández Eva , Chávez-Tapia Norberto C. , Uribe Misael , Barbero-Becerra Varenka J.
Published: January 2022

Hepatic steatosis is characterized by triglyceride accumulation within hepatocytes in response to a high calorie intake, and it may be related to intestinal microbiota disturbances. The prebiotic inulin is a naturally occurring polysaccharide with a high dietary fiber content. Here, we evaluate the effect of inulin on the intestinal microbiota in a non-alcoholic fatty liver disease model. Mice exposed to a standard rodent diet or a fat-enriched diet, were supplemented or not, with inulin. Liver histology was evaluated with oil red O and H&E staining and the intestinal microbiota was determined in mice fecal samples by 16S rRNA sequencing. Inulin treatment effectively prevents liver steatosis in the fat-enriched diet group. We also observed that inulin re-shaped the intestinal microbiota at the phylum level, were Verrucomicrobia genus significantly increased in the fat-diet group; specifically, we observed that Akkermansia muciniphila increased by 5-fold with inulin supplementation. The family Prevotellaceae was also significantly increased in the fat-diet group. Overall, we propose that inulin supplementation in liver steatosis-affected animals, promotes a remodeling in the intestinal microbiota composition, which might regulate lipid metabolism, thus contributing to tackling liver steatosis.
Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing
Authors: Stephenson Kirk A. J. , Zhu Julia , Dockery Adrian , Whelan Laura , Burke Tomás , Turner Jacqueline , O’Byrne James J. , Farrar G. Jane , Keegan David J.
Published: January 2022

Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70–80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.
Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
Authors: Kim Kiae , Han Yeonjin , Duan Longhan , Chung Ka Young
Published: January 2022

β-arrestins were initially identified to desensitize and internalize G-protein-coupled receptors (GPCRs). Receptor-bound β-arrestins also initiate a second wave of signaling by scaffolding mitogen-activated protein kinase (MAPK) signaling components, MAPK kinase kinase, MAPK kinase, and MAPK. In particular, β-arrestins facilitate ERK1/2 or JNK3 activation by scaffolding signal cascade components such as ERK1/2-MEK1-cRaf or JNK3-MKK4/7-ASK1. Understanding the precise molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly would deepen our understanding of GPCR-mediated MAPK activation and provide clues for the selective regulation of the MAPK signaling cascade for therapeutic purposes. Over the last decade, numerous research groups have attempted to understand the molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly. Although not providing the complete mechanism, these efforts suggest potential binding interfaces between β-arrestins and MAPK signaling components and the mechanism for MAPK signal amplification by β-arrestin-mediated scaffolding. This review summarizes recent developments of cellular and molecular works on the scaffolding mechanism of β-arrestin for MAPK signaling cascade.
Context-Aware Collaborative Filtering Using Context Similarity: An Empirical Comparison
Authors: Zheng Yong
Published: January 2022

Recommender systems can assist with decision-making by delivering a list of item recommendations tailored to user preferences. Context-aware recommender systems additionally consider context information and adapt the recommendations to different situations. A process of context matching, therefore, enables the system to utilize rating profiles in the matched contexts to produce context-aware recommendations. However, it suffers from the sparsity problem since users may not rate items in various context situations. One of the major solutions to alleviate the sparsity issue is measuring the similarity of contexts and utilizing rating profiles with similar contexts to build the recommendation model. In this paper, we summarize the context-aware collaborative filtering methods using context similarity, and deliver an empirical comparison based on multiple context-aware data sets.
The First Report of the Genera Abaria and Drepanocentron (Trichoptera: Xiphocentronidae) from China, with Descriptions of Two New Species
Authors: Peng Lang , Ge Xinyu , Sun ChangHai , Wang Beixin
Published: January 2022

The genera Abaria Mosely 1948 and Drepanocentron Schmid 1982 are recorded in China for the first time. In this study, two new species, Abaria herringbona sp. nov., from Guang-xi, and Drepanocentron fuxiensis sp. nov., from An-hui, are described and illustrated. Male genitalia of these two new species is distinguishable from those of other Abaria and Drepanocentron species. In addition, Melanotrichia attia Malicky & Chantaramongkol 1992 is a new record for the Chinese caddisfly fauna.
Identification and Expression Profile of Chemosensory Receptor Genes in Aromia bungii (Faldermann) Antennal Transcriptome
Authors: Wu Zhenchen , Ye Jia , Qian Jiali , Purba Endang , Zhang Qinghe , Zhang Longwa , Mang Dingze
Published: January 2022

The red-necked longicorn beetle, Aromia bungii (Faldermann) (Coleoptera: Cerambycidae), is a major destructive, wood-boring pest, which is widespread throughout the world. The sex pheromone of A. bungii was reported earlier; however, the chemosensory mechanism of the beetle remains almost unknown. In this study, 45 AbunORs, 6 AbunGRs and 2 AbunIRs were identified among 42,197 unigenes derived from the antennal transcriptome bioinformatic analysis of A. bungii adults. The sequence of putative Orco (AbunOR25) found in this study is highly conserved with the known Orcos from other Coleoptera species, and these Orco genes might be potentially used as target genes for the future development of novel and effective control strategies. Tissue expression analysis showed that 29 AbunOR genes were highly expressed in antennae, especially in the antennae of females, which was consistent with the idea that females might express more pheromone receptors for sensing pheromones, especially the sex pheromones produced by males. AbunOR5, 29, 31 and 37 were clustered with the pheromone receptors of the cerambycid Megacyllene caryae, suggesting that they might be putative pheromone receptors of A. bungii. All six AbunGRs were highly expressed in the mouthparts, indicating that these GRs may be involved in the taste perception process. Both AbunIRs were shown to be female-mouthparts-biased, suggesting that they might also be related to the tasting processes. Our study provides some basic information towards a deeper understanding of the chemosensing mechanism of A. bungii at a molecular level.
Dominance of Fructose-Associated Fructobacillus in the Gut Microbiome of Bumblebees (Bombus terrestris) Inhabiting Natural Forest Meadows
Authors: Krams Ronalds , Gudra Dita , Popovs Sergejs , Willow Jonathan , Krama Tatjana , Munkevics Maris , Megnis Kaspars , Jõers Priit , Fridmanis Davids , Contreras Garduño Jorge , Krams Indrikis A.
Published: January 2022

Bumblebees are key pollinators in agricultural landscapes. However, little is known about how gut microbial communities respond to anthropogenic changes. We used commercially produced colonies of buff-tailed bumblebees (Bombus terrestris) placed in three habitats. Whole guts (midgut, hindgut, and rectum) of B. terrestris specimens were dissected from the body and analyzed using 16S phylogenetic community analysis. We observed significantly different bacterial community composition between the agricultural landscapes (apple orchards and oilseed rape (Brassica napus) fields) and forest meadows, whereas differences in gut communities between the orchards and oilseed rape fields were nonsignificant. Bee-specific bacterial genera such as Lactobacillus, Snodgrassella, and Gilliamella dominated gut communities of B. terrestris specimens. In contrast, the guts of B. terrestris from forest meadows were dominated by fructose-associated Fructobacillus spp. Bacterial communities of workers were the most diverse. At the same time, those of males and young queens were less diverse, possibly reflecting greater exposure to the colony’s inner environment compared to the environment outside the colony, as well as bumblebee age. Our results suggest that habitat quality, exposure to environmental microbes, nectar quality and accessibility, and land use significantly affect gut bacterial composition in B. terrestris.
A Hard Copper Open X-Band RF Accelerating Structure Made by Two Halves
Authors: Spataro Bruno , Behtouei Mostafa , Cardelli Fabio , Carillo Martina , Dolgashev Valery , Faillace Luigi , Migliorati Mauro , Palumbo Luigi
Published: January 2022

This communication focuses on the technological developments aiming to show the viability of novel welding techniques [...]
Impact of Pulmonary Rehabilitation Services in Patients with Different Lung Diseases
Authors: Sanchez-Ramirez Diana C.
Published: January 2022

Background: the effect of pulmonary rehabilitation (PR) services, beyond research contexts, on patients with lung diseases other than COPD requires further study. Objectives: to (i) assess the impact of a publicly funded PR on patients’ exercise capacity, self-efficacy, and health-related quality of life (HRQoL), and (ii) explore whether the effects vary across lung diseases. Methods: this retrospective pre–post study analyzed data from the Winnipeg Regional Health Authority PR program between 2016 and 2019. Results: 682 patients completed the full PR program. Pooled analyses found significant improvements in the patients’ exercise capacity (six-minute walk test (6MWT) (13.6%), fatigue (10.3%), and dyspnea (6.4%)), Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEMCD6) (11.6%), and HRQoL (Clinical COPD Questionnaire (CCQ) (18.5%) and St George’s Respiratory Questionnaire (SGRQ) (10.9%)). The analyses conducted on sub-groups of patients with chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, interstitial lung diseases (ILDs), other restrictive lung diseases (e.g., obesity, pleural effusion, etc.), lung cancer, and pulmonary hypertension (PH) indicated that, except for patients with PH, all the patients improved in the 6MWT. Fatigue decreased in patients with COPD, ILDs, and other restrictive lung diseases. Dyspnea decreased in patients with COPD, asthma, and lung cancer. SEMCD6 scores increased in COPD, ILDs and PH patients. CCQ scores decreased in all lung diseases, except lung cancer and PH. SGRQ scores only decreased in patients with COPD. Conclusion: PR services had a significant impact on patients with different lung diseases. Therefore, publicly funded PR should be available as a critical component in the management of patients with these diseases.
Age-Independent Clinical Outcome in Proximal Humeral Fractures: 2-Year Results Using the Example of a Precontoured Locking Plate
Authors: Dey Hazra Rony-Orijit , Illner Johanna , Szewczyk Karol , Warnhoff Mara , Ellwein Alexander , Blach Robert Maximillian , Lill Helmut , Jensen Gunnar
Published: January 2022

Introduction: The optimal treatment strategy for the proximal humeral fracture (PHF) remains controversial. The debate is centered around the correct treatment strategy in the elderly patient population. The present study investigated whether age predicts the functional outcome of locking plate osteosynthesis for this fracture entity. Methods: A consecutive series of patients with surgically treated displaced PHF between 01/2017 and 01/2018 was retrospectively analyzed. Patients were treated by locking plate osteosynthesis. The cohort was divided into two groups: Group 1 (≥65 years) and Group 2 (<65 years). At the follow-up examination, the SSV, CMS, ASES, and Oxford Shoulder Score (OS), as well as a radiological follow-up, was obtained. The quality of fracture reduction is evaluated according to Schnetzke et al. Results: Of the 95 patients, 79 were followed up (83.1%). Group 1 consists of 42 patients (age range: 65–89 years, FU: 25 months) and Group 2 of 37 patients (28–64 years, FU: 24 months). The clinical results showed no significant differences between both groups: SSV 73.4 ± 23.4% (Group 1) vs. 80.5 ± 189% (Group 2). CMS: 79.4 ± 21 vs. 81.9 ± 16, ASES: 77.2 ± 20.4 vs. 77.5 ± 23.1, OS: 39.5 ± 9.1 vs. 40.8 ± 8.2; OS: 39.5 ± 9.1 vs. 40.8 ± 8.2. In the radiological follow-up, fractures healed in all cases. Furthermore, the quality of fracture reduction in both groups is comparable without significant differences. The revision rate was 9.5% in Group 1 vs. 16.2% in Group 2. Discussion: Both age groups show comparable functional outcomes and complication rates. Thus, the locking plate osteosynthesis can be used irrespective of patient age; the treatment decision should instead be based on fracture morphology and individual patient factors.
Hyperkalemia Following Parathyroidectomy in Patients with Renal Hyperparathyroidism—New Thresholds for Urgent Perioperative Dialysis
Authors: Bures Claudia , Uluk Yasmin , Besmens Mona , Akca Aycan , Dobrindt Eva-Maria , Pratschke Johann , Goretzki Peter , Mogl Martina , Uluk Deniz
Published: January 2022

Parathyroidectomy (PTX) is a mainstay of treating secondary hyperparathyroidism (SHPT) in patients with kidney failure in order to reduce the incidence of cardiovascular events (CVE), increase overall survival and improve quality of life. Perioperative hyperkalemia may lead to devastating cardiac complications. Distinct preoperative thresholds for serum potassium levels (SPL) were defined, but neither their usefulness nor consecutive risks are understood. This study compared the results and efficacy of different clinical procedures in preventing or treating perioperative hyperkalemia, including postoperative urgent hemodialysis (UHD). Methods: Patients from Charité-Universitätsmedizin Berlin and Rheinland Klinikum Lukaskrankenhaus, Neuss, undergoing PTX due to SHPT between 2008 and 2018 were analyzed retrospectively with regard to demographic parameters, surgery specific conditions and perioperative laboratory results. Comparisons of patient values from both centers with focus on perioperative hyperkalemia and the need for UHD were performed. Results: A total of 251 patients undergoing PTX for SHPT were included (Neuss: n = 121 (48%); Berlin: n = 130 (52%)). Perioperative hyperkalemia (SPL ≥ 5.5 mmol/L) was noted in 134 patients (53%). UHD on the day of surgery was performed especially in patients with intraoperative hyperkalemia, in females (n = 40 (16%) vs. n = 27 (11%); p = 0.023), in obese patients (n = 27 (40%) vs. n = 50 (28%), p = 0.040) and more often in patients treated in Neuss (n = 42 (35%) vs. 25 (19%); p = 0.006). For patients treated in Neuss, the intraoperative hyperkalemia cut-off level above 5.75 mmol/L was the most predictive factor for UHD (n = 30 (71%) vs. n = 8 (10%); p < 0.001). Concerning secondary effects of hyperkalemia or UHD, no patient died within the postoperative period, and only three patients suffered from acute CVE, with SPL > 5.5 mmol/L measured in only one patient. Conclusion: Perioperative values could not predict postoperative hyperkalemia with the need for UHD. Previously defined cut-off levels for SPL should be reconsidered, especially for patients undergoing PTX. Early postoperative dialysis in patients with postoperative hyperkalemia can be performed with a low risk for complications and may be indicated for all patients with increased perioperative SPL.
Diagnosis, Clinical Features and Management of Interstitial Lung Diseases in Rheumatic Disorders: Still a Long Journey
Authors: Sebastiani Marco , Vacchi Caterina , Cassone Giulia , Manfredi Andreina
Published: January 2022

Interstitial lung disease (ILD) is one of the most frequent pulmonary complications of autoimmune rheumatic diseases (ARDs), and it is mainly associated with connective tissue diseases (CTDs) and rheumatoid arthritis (RA) [...]
Differences in Demographic and Radiographic Characteristics between Patients with Visible and Invisible T1 Slopes on Lateral Cervical Radiographic Images
Authors: Ito Sadayuki , Nakashima Hiroaki , Matsumoto Akiyuki , Ando Kei , Machino Masaaki , Segi Naoki , Tomita Hiroyuki , Koshimizu Hiroyuki , Imagama Shiro
Published: January 2022

Introduction: The T1 slope is important for cervical surgical planning, and it may be invisible on radiographic images. The prevalence of T1 invisible cases and the differences in demographic and radiographic characteristics between patients whose T1 slopes are visible or invisible remains unexplored. Methods: This pilot study aimed to evaluate the differences in these characteristics between outpatients whose T1 slopes were visible or invisible on radiographic images. Patients (n = 60) who underwent cervical radiography, whose T1 slope was confirmed clearly, were divided into the visible (V) group and invisible (I) group. The following radiographic parameters were measured: (1) C2-7 sagittal vertical axis (SVA), (2) C2-7 angle in neutral, flexion, and extension positions. Results: Based on the T1 slope visibility, 46.7% of patients were included in group I. The I group had significantly larger C2-7 SVA than the V group for males (p < 0.05). The C2-7 SVA tended to be larger in the I group, without significant difference for females (p = 0.362). Discussion: The mean C2-7 angle in neutral and flexion positions was not significantly different between the V and I groups for either sex. The mean C2-7 angle in the extension position was greater in the V group. The T1 slope was invisible in males with high C2-7 SVA.
Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study
Authors: Fernández-de-las-Peñas César , Martín-Guerrero José D. , Pellicer-Valero Óscar J. , Navarro-Pardo Esperanza , Gómez-Mayordomo Víctor , Cuadrado María L. , Arias-Navalón José A. , Cigarán-Méndez Margarita , Hernández-Barrera Valentín , Arendt-Nielsen Lars
Published: January 2022

This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed. Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males. After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671–3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040–2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081–1.886, exertion: adj OR 1.409, 95%CI 1.109–1.791), pain (adj OR 1.349, 95%CI 1.059–1.720), hair loss (adj OR 4.529, 95%CI 2.784–7.368), ocular problems (adj OR 1.981, 95%CI 1.185–3.312), depressive levels (adj OR 1.606, 95%CI 1.002–2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097–2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers.
Factors Influencing the Improvement of Activities of Daily Living during Inpatient Rehabilitation in Newly Diagnosed Patients with Glioblastoma Multiforme
Authors: Natsume Keisuke , Sakakima Harutoshi , Kawamura Kentaro , Yoshida Akira , Akihiro Shintaro , Yonezawa Hajime , Yoshimoto Koji , Shimodozono Megumi
Published: January 2022

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor. To identify the factors influencing the improvement of the activities of daily living (ADL) in newly diagnosed patients with GBM, we investigated the characteristics and variable factors and overall survival. A total of 105 patients with GBM were retrospectively analyzed and categorized into the following three groups according to the quartile of change of their Barthel index score from admission to discharge: deterioration (n = 25), no remarkable change (n = 55), and good recovery (n = 25). A statistical difference was observed in the pre-operative, intra-operative, post-operative, and rehabilitation-related factors between the deterioration and good recovery groups. Multiple regression analysis identified the following significant factors that may influence the improvement of ADL after surgery: the improvement of motor paralysis after surgery, mild fatigue during radio and chemotherapy, and length up to early walking training onset. The median overall survival was significantly different between the deterioration (10.6 months) and good recovery groups (18.9 months, p = 0.025). Our findings identified several factors that may be associated with post-operative functional improvement in patients with GBM. The inpatient rehabilitation during radio and chemotherapy may be encouraged without severe adverse events and can promote functional outcomes, which may contribute to the overall survival of newly diagnosed patients with GBM.
Improved Accuracy and Safety of Pedicle Screw Placement by Using a Probe with an Electrical Conductivity-Measuring Device during Severe Syndromic and Neuromuscular Scoliosis Spine Surgery
Authors: Yurube Takashi , Kanda Yutaro , Ito Masaaki , Takeoka Yoshiki , Suzuki Teppei , Uno Koki , Kuroda Ryosuke , Kakutani Kenichiro
Published: January 2022

An electrical conductivity-measuring device (ECD) has recently been developed to support pedicle screw placement. However, no evidence exists regarding its efficacy for syndromic/neuromuscular scoliosis with extremely difficult screwing. We retrospectively reviewed 2010–2016 medical records of 21 consecutive syndromic/neuromuscular scoliosis patients undergoing free-hand segmental fixation surgery at our institution and compared the pedicle screw insertion accuracy and safety between 10 with a conventional non-ECD probe (2010–2013) and 11 with an ECD probe (2014–2016). We analyzed preoperative pedicle shape and postoperative screw placement in computed tomography. There were no significant differences between ECD and non-ECD groups in demographic, clinical, and treatment characteristics including scoliosis severity and pedicle diameter. The abandonment rate due to liquorrhea or perforation was lower in ECD (12.3%) than in non-ECD (26.7%) (p < 0.01). Acceptable insertion without perforation or <2-mm lateral/cranial position was more frequent in ECD (67.1%) than in non-ECD (56.9%) (p = 0.02). Critical ≥5-mm medial/caudal malposition was not seen in ECD (0.0%) but in non-ECD (2.4%) (p = 0.02). The perforation distance was shorter in ECD (2.2 ± 1.1 mm) than in non-ECD (2.6 ± 1.7 mm) (p = 0.01). Results involve small sample size, selection, performance, and learning curve biases; nevertheless, ECD could be useful for more accurate and safer pedicle screw placement in severe syndromic/neuromuscular scoliosis.
How to Explore an Endocrine Cause of Hypertension
Authors: de Freminville Jean-Baptiste , Amar Laurence
Published: January 2022

Hypertension (HTN) is the most frequent modifiable risk factor in the world, affecting almost 30 to 40% of the adult population in the world. Among hypertensive patients, 10 to 15% have so-called “secondary” HTN, which means HTN due to an identified cause. The most frequent secondary causes of HTN are renal arteries abnormalities (renovascular HTN), kidney disease, and endocrine HTN, which are primarily due to adrenal causes. Knowing how to detect and explore endocrine causes of hypertension is particularly interesting because some causes have a cure or a specific treatment available. Moreover, the delayed diagnosis of secondary HTN is a major cause of uncontrolled blood pressure. Therefore, screening and exploration of patients at risk for secondary HTN should be a serious concern for every physician seeing patients with HTN. Regarding endocrine causes of HTN, the most frequent is primary aldosteronism (PA), which also is the most frequent cause of secondary HTN and could represent 10% of all HTN patients. Cushing syndrome and pheochromocytoma and paraganglioma (PPGL) are rarer (less than 0.5% of patients). In this review, among endocrine causes of HTN, we will mainly discuss explorations for PA and PPGL.
Stent Fractures: New Insights into an Old Issue
Authors: Minha Sa’ar , Pereg David
Published: January 2022

Percutaneous coronary intervention (PCI) is a safe and effective procedure performed worldwide providing both symptom relief and sustained improved outcomes for millions of patients [...]
Improvement of Gait in Patients with Stroke Using Rhythmic Sensory Stimulation: A Case-Control Study
Authors: Lee Yungon , Shin Sunghoon
Published: January 2022

Patients with stroke suffer from impaired locomotion, exhibiting unstable walking with increased gait variability. Effects of rhythmic sensory stimulation on unstable gait of patients with chronic stroke are unclear. This study aims to determine the effects of rhythmic sensory stimulation on the gait of patients with chronic stroke. Twenty older adults with stroke and twenty age- and gender-matched healthy controls walked 60 m under four conditions: normal walking with no stimulation, walking with rhythmic auditory stimulation (RAS) through an earphone in the ear, walking with rhythmic somatosensory stimulation (RSS) through a haptic device on the wrist of each participant, and walking with rhythmic combined stimulation (RCS: RAS + RSS). Gait performance in the stroke group significantly improved during walking with RAS, RSS, and RCS compared to that during normal walking (p < 0.008). Gait variability significantly decreased under the RAS, RSS, and RCS conditions compared to that during normal walking (p < 0.008). Rhythmic sensory stimulation is effective in improving the gait of patients with chronic stroke, regardless of the type of rhythmic stimuli, compared to healthy controls. The effect was greater in patients with reduced mobility, assessed by the Rivermead Mobility Index (RMI).
Protocol for Multi-Stage Treatment of Temporomandibular Joint Ankylosis in Children and Adolescents
Authors: Dowgierd Krzysztof , Pokrowiecki Rafał , Kulesa Mrowiecka Małgorzata , Dowgierd Martyna , Woś Jan , Szymor Piotr , Kozakiewicz Marcin , Lipowicz Anna , Roman Małgorzata , Myśliwiec Andrzej
Published: January 2022

Treatment of temporomandibular ankylosis is challenging and frequently leads to re-ankylosis, relapse, dangerous complications and, in turn, the need for multiple operations. In this article, we present a protocol for the treatment of ankylosis of the temporomandibular joints that assumes earlier intervention with the assistance of 3D virtual surgical planning (3DVSP) and custom biomaterials for better and safer surgical outcomes. Thirty-three patients were treated due to either uni- or bilateral temporomandibular ankylosis. Twenty individuals received temporomandibular prosthesis, whereas seventeen required simultaneous 3D virtual surgical/planned orthognathic surgery as the final correction of the malocclusion. All patients exhibited statistically significant improvements in mouth opening (from 1.21 ± 0.74 cm to 3.77 ± 0.46 cm) and increased physiological functioning of the mandible. Gap arthroplasty and aggressive rehabilitation prior to temporomandibular prosthesis (TMJP) placement were preferred over costochondral autografts. The use of 3DVSP and custom biomaterials enables more precise, efficient and safe procedures to be performed in the paediatric and adolescent population requiring treatment for temporomandibular ankylosis.
Artificial Intelligence-Based Approaches to Reflectance Confocal Microscopy Image Analysis in Dermatology
Authors: Malciu Ana Maria , Lupu Mihai , Voiculescu Vlad Mihai
Published: January 2022

Reflectance confocal microscopy (RCM) is a non-invasive imaging method designed to identify various skin diseases. Confocal based diagnosis may be subjective due to the learning curve of the method, the scarcity of training programs available for RCM, and the lack of clearly defined diagnostic criteria for all skin conditions. Given that in vivo RCM is becoming more widely used in dermatology, numerous deep learning technologies have been developed in recent years to provide a more objective approach to RCM image analysis. Machine learning-based algorithms are used in RCM image quality assessment to reduce the number of artifacts the operator has to view, shorten evaluation times, and decrease the number of patient visits to the clinic. However, the current visual method for identifying the dermal-epidermal junction (DEJ) in RCM images is subjective, and there is a lot of variation. The delineation of DEJ on RCM images could be automated through artificial intelligence, saving time and assisting novice RCM users in studying the key DEJ morphological structure. The purpose of this paper is to supply a current summary of machine learning and artificial intelligence’s impact on the quality control of RCM images, key morphological structures identification, and detection of different skin lesion types on static RCM images.