bluuebunny/crossref_metadata_2025 huggingface dataset:
Reporting Liver Cancer Trends in the Island of Crete, Greece: Results from a Geo-Epidemiological Study
Authors: Kalpadakis Stavros , Sifaki-Pistolla Dimitra , Symvoulakis Emmanouil K. , Kelefiotis-Stratidakis Panagiotis , Vamvakas Lambros , Mavroudis Dimitrios , Lionis Christos
Published: August 2022

Liver cancer is one of the most frequent cancers in Europe and Greece. An increase in specific risk factors, such as metabolic syndrome and obesity, has been observed in Greece. Therefore, exploring temporal trends of liver cancer incidence and mortality is crucial. This study aims to assess the “burden” of malignant liver tumors (MLT) in Crete, Greece, in terms of incidence and mortality rates, and identify the high-risk areas on the island (i.e., municipalities), to suggest public health measures. Data were obtained from the Cancer Registry Center (CRC) and included all cases of MLT for the period 1992–2013 in Crete. Age-standardized incidence rates (ASIR), age-specific incidence rates (ASpIR), age-standardized mortality rates (ASMR), and age-specific mortality rates (ASpMR) were estimated. For the study period (1992–2013), incidence and mortality showed an increasing trend. Mean ASIR was found 15.3/100,000/year and mean ASMR 8.6/100,000/year. Age groups 65–69 and 75–79 years among men presented the highest rates of (ASIR = 39/100,000/year) and among women age groups of 75–79 and 80–84 years a mean ASIR (22/100,000/year). The five-year survival rate of MLT was 50% and the ten-year survival rate was 47% for both genders. Risk factors that were identified included personal history of cancer, family history of MLT or other cancer, degree of relationship, smoking, and obesity. Some municipalities of Crete were found to be high-risk areas for MLT, while differences were detected in incidence and mortality rates, and annual rate change among them. Estimated variation indicates further increase probably due to the lifestyle of the residents, economic crisis, and inadequate preventive measures.
The Effects of New Accounting Standards on Firm Value: The K-IFRS 1116 Lease
Authors: Chung Hae Jin
Published: August 2022

We examine how the implementation of the K-IFRS No.1116 Lease affects firm value. This new accounting standard mandates capitalization of all leases, resulting in changes in the key accounting leverage ratios and rates of return. The contracting costs hypothesis suggests that changes in accounting techniques have economic consequences because lending contracts are expressed in terms of accounting numbers. We find that capitalizing operating leases, which were off-balance-sheet transactions prior to K-1116 implementation, increases the lease liabilities-to-assets ratio and lease liabilities-to-debt ratio significantly. While a firm’s business fundamentals do not change with the K-1116, we show that the value of firms that use high levels of operating leases decreased with the implementation of K-1116. The declines in firm value are significant for the subgroups of firms that are likely to raise external financing, suggesting that the implementation of K-1116 increased the level of financing frictions and decreased the value of future investment opportunities.
Neuronal Roles of the Multifunctional Protein Dipeptidyl Peptidase-like 6 (DPP6)
Authors: Malloy Cole , Ahern Maisie , Lin Lin , Hoffman Dax A.
Published: August 2022

The concerted action of voltage-gated ion channels in the brain is fundamental in controlling neuronal physiology and circuit function. Ion channels often associate in multi-protein complexes together with auxiliary subunits, which can strongly influence channel expression and function and, therefore, neuronal computation. One such auxiliary subunit that displays prominent expression in multiple brain regions is the Dipeptidyl aminopeptidase-like protein 6 (DPP6). This protein associates with A-type K+ channels to control their cellular distribution and gating properties. Intriguingly, DPP6 has been found to be multifunctional with an additional, independent role in synapse formation and maintenance. Here, we feature the role of DPP6 in regulating neuronal function in the context of its modulation of A-type K+ channels as well as its independent involvement in synaptic development. The prevalence of DPP6 in these processes underscores its importance in brain function, and recent work has identified that its dysfunction is associated with host of neurological disorders. We provide a brief overview of these and discuss research directions currently underway to advance our understanding of the contribution of DPP6 to their etiology.
mTOR: A Potential New Target in Nonalcoholic Fatty Liver Disease
Authors: Feng Jiayao , Qiu Shuting , Zhou Shipeng , Tan Yue , Bai Yan , Cao Hua , Guo Jiao , Su Zhengquan
Published: August 2022

The global prevalence of nonalcoholic fatty liver disease (NAFLD) continues to rise, yet effective treatments are lacking due to the complex pathogenesis of this disease. Although recent research has provided evidence for the “multiple strikes” theory, the classic “two strikes” theory has not been overturned. Therefore, there is a crucial need to identify multiple targets in NAFLD pathogenesis for the development of diagnostic markers and targeted therapeutics. Since its discovery, the mechanistic target of rapamycin (mTOR) has been recognized as the central node of a network that regulates cell growth and development and is closely related to liver lipid metabolism and other processes. This paper will explore the mechanisms by which mTOR regulates lipid metabolism (SREBPs), insulin resistance (Foxo1, Lipin1), oxidative stress (PIG3, p53, JNK), intestinal microbiota (TLRs), autophagy, inflammation, genetic polymorphisms, and epigenetics in NAFLD. The specific influence of mTOR on NAFLD was hypothesized to be divided into micro regulation (the mechanism of mTOR’s influence on NAFLD factors) and macro mediation (the relationship between various influencing factors) to summarize the influence of mTOR on the developmental process of NAFLD, and prove the importance of mTOR as an influencing factor of NAFLD regarding multiple aspects. The effects of crosstalk between mTOR and its upstream regulators, Notch, Hedgehog, and Hippo, on the occurrence and development of NAFLD-associated hepatocellular carcinoma are also summarized. This analysis will hopefully support the development of diagnostic markers and new therapeutic targets in NAFLD.
Comparison of Mitochondrial Genomes between a Cytoplasmic Male-Sterile Line and Its Restorer Line for Identifying Candidate CMS Genes in Gossypium hirsutum
Authors: Xuan Lisha , Qi Guoan , Li Xiaoran , Yan Sunyi , Cao Yiwen , Huang Chujun , He Lu , Zhang Tianzhen , Shang Haihong , Hu Yan
Published: August 2022

As the core of heterosis utilization, cytoplasmic male sterility (CMS) has been widely used in hybrid seed production. Previous studies have shown that CMS is always closely related to the altered programming of mitochondrial genes. To explore candidate CMS genes in cotton (Gossypium hirsutum), sequencing and de novo assembly were performed on the mitochondrial genome of the G. hirsutum CMS line SI3A, with G. harknessii CMS-D2 cytoplasm, and the corresponding G. hirsutum restorer line 0-613-2R. Remarkable variations in genome structure and gene transcripts were detected. The mitochondrial genome of SI3A has three circle molecules, including one main circle and two sub-circles, while 0-613-2R only has one. RNA-seq and RT-qPCR analysis proved that orf606a and orf109a, which have a chimeric structure and transmembrane domain, were highly expressed in abortive anthers of SI3A. In addition, comparative analysis of RNA-seq and full-length transcripts revealed the complex I gene nad4 to be expressed at a lower level in SI3A than in its restorer and that it featured an intron retention splicing pattern. These two novel chimeric ORFs and nad4 are potential candidates that confer CMS character in SI3A. This study provides new insight into the molecular basis of the nuclear–cytoplasmic interaction mechanism, and that putative CMS genes might be important sources for future precise design cross-breeding of cotton.
The Kinesin Gene KIF26B Modulates the Severity of Post-Traumatic Heterotopic Ossification
Authors: Pickering George A. E. , Felix-Ilemhenbhio Favour , Clark Matthew J. , Kocsy Klaudia , Simpson Jonathan , Bellantuono Ilaria , Gartland Alison , Wilkinson Jeremy Mark , Hatzikotoulas Konstantinos , Kiss-Toth Endre
Published: August 2022

The formation of pathological bone deposits within soft tissues, termed heterotopic ossification (HO), is common after trauma. However, the severity of HO formation varies substantially between individuals, from relatively isolated small bone islands through to extensive soft tissue replacement by bone giving rise to debilitating symptoms. The aim of this study was to identify novel candidate therapeutic molecular targets for severe HO. We conducted a genome-wide scan in men and women with HO of varying severity following hip replacement for osteoarthritis. HO severity was dichotomized as mild or severe, and association analysis was performed with adjustment for age and sex. We next confirmed expression of the gene encoded by the lead signal in human bone and in primary human mesenchymal stem cells. We then examined the effect of gene knockout in a murine model of osseous trans-differentiation, and finally we explored transcription factor phosphorylation in key pathways perturbed by the gene. Ten independent signals were suggestively associated with HO severity, with KIF26B as the lead. We subsequently confirmed KIF26B expression in human bone and upregulation upon BMP2-induced osteogenic differentiation in primary human mesenchymal stem cells, and also in a rat tendo-Achilles model of post-traumatic HO. CRISPR-Cas9 mediated knockout of Kif26b inhibited BMP2-induced Runx2, Sp7/Osterix, Col1A1, Alp, and Bglap/Osteocalcin expression and mineralized nodule formation in a murine myocyte model of osteogenic trans-differentiation. Finally, KIF26B deficiency inhibited ERK MAP kinase activation during osteogenesis, whilst augmenting p38 and SMAD 1/5/8 phosphorylation. Taken together, these data suggest a role for KIF26B in modulating the severity of post-traumatic HO and provide a potential novel avenue for therapeutic translation.
Decoding Genetic Features and Antimicrobial Susceptibility of Pseudomonas aeruginosa Strains Isolated from Bloodstream Infections
Authors: Bogiel Tomasz , Depka Dagmara , Rzepka Mateusz , Mikucka Agnieszka
Published: August 2022

Pseudomonas aeruginosa is a Gram-negative rod and an etiological factor of opportunistic infections. The infections of this etiology appear mostly among hospitalized patients and are relatively hard to treat due to widespread antimicrobial resistance. Many virulence factors are involved in the pathogenesis of P. aeruginosa infection, the coexistence of which have a significant impact on the course of an infection with a particular localization. The aim of this study was to assess the antimicrobial susceptibility profiles and the frequency of genes encoding selected virulence factors in clinical P. aeruginosa strains isolated from bloodstream infections (BSIs). The following genes encoding virulence factors of enzymatic activity were assessed: lasB, plC H, plC N, nan1, nan2, aprA and phzM. The frequency of the genes encoding the type III secretion system effector proteins (exoU and exoS) and the genes encoding pilin structural subunits (pilA and pilB) were also investigated. The occurrence of virulence-factor genes was assessed using polymerase chain reactions, each in a separate reaction. Seventy-one P. aeruginosa strains, isolated from blood samples of patients with confirmed bacteremia hospitalized at the University Hospital No. 1 of Dr. Antoni Jurasz in Bydgoszcz, Poland, were included in the study. All the investigated strains were susceptible to colistin, while the majority of the strains presented resistance to ticarcillin/clavulanate (71.8%), piperacillin (60.6 %), imipenem (57.7%) and piperacillin/tazobactam (52.1%). The presence of the lasB and plC H genes was noted in all the tested strains, while the plC N, nan2, aprA, phzM and nan1 genes were identified in 68 (95.8%), 66 (93.0%), 63 (88.7%), 55 (77.5%) and 34 (47.9%) isolates, respectively. In 44 (62.0%) and 41 (57.7%) strains, the presence of the exoU and exoS genes was confirmed, while the pilA and pilB genes were noted only in 14 (19.7%) and 3 (4.2%) isolates, respectively. This may be due to the diverse roles of these proteins in the development and maintenance of BSIs. Statistically significant correlations were observed between particular gene pairs’ coexistence (e.g., alkaline protease and neuraminidase 2). Altogether, twenty-seven distinctive genotypes were observed among the studied strains, indicating the vast variety of genetic compositions of P. aeruginosa strains causing BSIs.
Health Beneficial Bioactivities of Faba Bean Gastrointestinal (In Vitro) Digestate in Comparison to Soybean and Pea
Authors: Martineau-Côté Delphine , Achouri Allaoua , Wanasundara Janitha , Karboune Salwa , L’Hocine Lamia
Published: August 2022

Faba beans are a promising emerging plant-based protein source to be used as a quality alternative to peas and soy. In this study, the potential health beneficial activities of three Canadian faba bean varieties (Fabelle, Malik and Snowbird) were investigated after in vitro gastrointestinal digestion and compared to two commonly used legumes (peas and soy). The results revealed that the faba beans had a higher antioxidant activity than peas when assessed with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays, except for the Fabelle variety. In the oxygen radical absorbance capacity (ORAC) and the iron chelating assays, the faba beans had a lower antioxidant activity than soy. Interestingly, Fabelle and Snowbird showed a higher antioxidant effect than the peas and soy at the cellular level. The antihypertensive properties of Fabelle and Malik varieties were significantly higher than peas but lower than soy. The in vitro antidiabetic activity was higher for soy, but no differences were found at the cellular level. The faba bean peptides were further fractionated and sequenced by mass spectrometry. Eleven peptides with in silico predicted bioactivities were successfully identified in the faba bean digestate and support validating the health-promoting properties of peptides. The results demonstrate the bioactive potential of faba beans as a health-promoting food ingredient against non-communicable diseases.
The Role of Bioenergetics in Neurodegeneration
Authors: Strope Taylor A. , Birky Cole J. , Wilkins Heather M.
Published: August 2022

Bioenergetic and mitochondrial dysfunction are common hallmarks of neurodegenerative diseases. Decades of research describe how genetic and environmental factors initiate changes in mitochondria and bioenergetics across Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Mitochondria control many cellular processes, including proteostasis, inflammation, and cell survival/death. These cellular processes and pathologies are common across neurodegenerative diseases. Evidence suggests that mitochondria and bioenergetic disruption may drive pathological changes, placing mitochondria as an upstream causative factor in neurodegenerative disease onset and progression. Here, we discuss evidence of mitochondrial and bioenergetic dysfunction in neurodegenerative diseases and address how mitochondria can drive common pathological features of these diseases.
Vasoactive Effects of Chronic Treatment with Fructose and Slow-Releasing H2S Donor GYY-4137 in Spontaneously Hypertensive Rats: The Role of Nitroso and Sulfide Signalization
Authors: Berenyiova Andrea , Cebova Martina , Aydemir Basak Gunes , Golas Samuel , Majzunova Miroslava , Cacanyiova Sona
Published: August 2022

Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (H2S). We investigated whether a slow-releasing H2S donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and H2S pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNFα in fructose-fed rats. While the participation of endogenous H2S in vasoactive responses was not affected by fructose treatment, the expression of H2S-producing enzyme cystathionine β-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of H2S-producing enzyme cystathionine γ-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous H2S in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow H2S-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous H2S.
Multi-Level Control of the ATM/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer
Authors: Batnini Kalil , Houles Thibault , Kirsh Olivier , Du Manoir Stanislas , Zaroual Mehdi , Delpech Hélène , Fallet Chloé , Lacroix Matthieu , Le Cam Laurent , Theillet Charles , Sardet Claude , Rodier Geneviève
Published: August 2022

E4F1 is essential for early embryonic mouse development and for controlling the balance between proliferation and survival of actively dividing cells. We previously reported that E4F1 is essential for the survival of murine p53-deficient cancer cells by controlling the expression of genes involved in mitochondria functions and metabolism, and in cell-cycle checkpoints, including CHEK1, a major component of the DNA damage and replication stress responses. Here, combining ChIP-Seq and RNA-Seq approaches, we identified the transcriptional program directly controlled by E4F1 in Human Triple-Negative Breast Cancer cells (TNBC). E4F1 binds and regulates a limited list of direct target genes (57 genes) in these cells, including the human CHEK1 gene and, surprisingly, also two other genes encoding post-transcriptional regulators of the ATM/ATR-CHK1 axis, namely, the TTT complex component TTI2 and the phosphatase PPP5C, that are essential for the folding and stability, and the signaling of ATM/ATR kinases, respectively. Importantly, E4F1 also binds the promoter of these genes in vivo in Primary Derived Xenograft (PDX) of human TNBC. Consequently, the protein levels and signaling of CHK1 but also of ATM/ATR kinases are strongly downregulated in E4F1-depleted TNBC cells resulting in a deficiency of the DNA damage and replicative stress response in these cells. The E4F1-depleted cells fail to arrest into S-phase upon treatment with the replication-stalling agent Gemcitabine, and are highly sensitized to this drug, as well as to other DNA-damaging agents, such as Cisplatin. Altogether, our data indicate that in breast cancer cells the ATM/ATR-CHK1 signaling pathway and DNA damage-stress response are tightly controlled at the transcriptional and post-transcriptional level by E4F1.
Changes in Structural, Morphological and Optical Features of Differently Synthetized C3N4-ZnO Heterostructures: An Experimental Approach
Authors: Actis Arianna , Sacchi Francesca , Takidis Christos , Paganini Maria Cristina , Cerrato Erik
Published: August 2022

C3N4 is an innovative material that has had huge success as a photocatalyst in recent years. More recently, it has been coupled to robust metal oxides to obtain more stable materials. This work is focused on the different synthesis techniques used to prepare bare C3N4 and combined C3N4/ZnO mixed systems. Different precursors, such as pure melamine and cyanuric acid-based supramolecular complexes, were employed for the preparation of the C3N4 material. Moreover, different solvents were also used, demonstrating that the use of water leads to the formation of a more stable heterojunction. Structural (XRD), morphological (FESEM) and optical (UV-vis) measurements underlined the role of the precursors used in the preparation of the materials. A clear trend can be extrapolated from this experimental approach involving different intimate contacts between the two C3N4 and ZnO phases, strictly connected to the particular preparation method adopted. The use of the supramolecular complexes for the preparation of C3N4 leads to a tighter association between the two phases at the heterojunction, resulting in much higher visible light harvesting (connected to lower band gap values).
Individual Experiences with Being Pushed to Limits and Variables That Influence the Strength to Which These Are Felt: A Cross-Sectional Survey Study
Authors: Nakazawa Eisuke , Mori Katsumi , Akabayashi Akira
Published: August 2022

In a 2021 survey, we found that “limit or suppression experiences” were related to a willingness to use enhancement technologies. However, the concept of “limit or suppression experiences” is vague and difficult to interpret in relation to neuroethics/enhancement. Thus, we aimed to better understand “limit or suppression experiences” and establish a robust philosophical concept of the topic. To do so, we exploratively investigated the concept to determine individual experiences with the presence or absence of sensing limits, investigate different ways in which limits can be sensed (factors of the sense of limits: “FSLs”), and identify factors that correlate with the strength of FSLs. Data from an Internet survey investigating respondents’ experiences with limits (1258 respondents) were analyzed using exploratory factor analysis and a linear regression model. Five variables were extracted as the FSLs. The highest regression coefficients were found between physical FSL and sports activities and between cognitive FSL and academics. The lowest regression coefficients were found between relational FSL and academics, sports activities, and arts and cultural activities. The results facilitate a detailed discussion of the motivations of enhancement users, and the extraction of the suppression experience opens new enhancement directions. Further normative and empirical studies are required.
Carvedilol versus Metoprolol in Patients with Ventricular Tachyarrhythmias
Authors: Schupp Tobias , Behnes Michael , Abumayyaleh Mohammad , Weidner Kathrin , Rusnak Jonas , Mashayekhi Kambis , Bertsch Thomas , Akin Ibrahim
Published: August 2022

The study investigates the prognostic role of treatment with carvedilol as compared to metoprolol in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients on beta-blocker (BB) treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with carvedilol were compared to patients with metoprolol. The primary prognostic outcome was all-cause mortality at three years. Secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies) and cardiac rehospitalization. Kaplan–Meier survival curves, multivariable Cox regression analyses, and propensity score matching were applied for statistics. There were 1098 patients included, 80% treated with metoprolol and 20% with carvedilol. Patients with carvedilol were older, more often presenting with VT (78% vs. 62%; p = 0.001) and with more advanced stages of heart failure. Treatment with carvedilol was associated with comparable all-cause mortality compared to metoprolol (20% vs. 16%, log rank p = 0.234; HR = 1.229; 95% CI 0.874–1.728; p = 0.235). However, secondary endpoints (i.e., composite arrhythmic endpoint: 32% vs. 17%; p = 0.001 and cardiac rehospitalization: 25% vs. 14%; p = 0.001) were more frequently observed in patients with carvedilol, which was still evident after multivariable adjustment. After propensity score matching (n = 194 patients with carvedilol and metoprolol), no further differences regarding the distribution of baseline characteristics were observed. Within the propensity-score-matched cohort, higher rates of the composite arrhythmic endpoint were still observed in patients treated with carvedilol, whereas the risk of cardiac rehospitalization was not affected by the type of beta-blocker treatment. In conclusion, carvedilol and metoprolol are associated with comparable all-cause mortality in patients with ventricular tachyarrhythmias, whereas the risk of the composite arrhythmic endpoint was increased in patients with carvedilol therapy.
The Impact on Parents of Diagnosing PCD in Young Children
Authors: Driessens Corine , Carr Siobhan , Clough Edel , Copeland Fiona , Dell Sharon , Dixon Lucy , Harris Amanda , Knibb Rebecca , Leigh Margaret , Narayanan Manjith , Redfern Beatrice , Robson Evie , Sawras Michael , Schofield Lynne , Sullivan Kelli , Tipping Myra , Tran Nhu , Walker Woolf , Lucas Jane S. , Behan Laura
Published: August 2022

Primary ciliary dyskinesia (PCD) is an incurable, rare, inherited, chronic condition. Treatment includes the regular clearing of airway mucus, aggressive treatment of infections and management of hearing loss. Caregiver burden has not been explored, hence we interviewed 18 mothers and 6 fathers of children under 6 years to understand the impact of diagnostic testing and implications of a positive diagnosis. Interviews were transcribed and thematically analysed and five key themes were identified. These included the parents’ experiences following child’s diagnosis, impact of child’s treatment regimen on parent, impact of child’s health status on parent, parent’s coping strategies, and parental concerns for the future. Parents described their diagnostic journey, with the findings revealing how a lack of awareness among clinicians of the PCD symptom pattern can lead to a delayed diagnosis. Parents discussed the emotional and practical impact of a PCD diagnosis and the coping strategies employed to deal with challenges arising following a diagnosis. Parents use a variety of different lifestyle changes to accommodate their child’s treatment regimen and to cope with disruptive life events such as the COVID-19 pandemic. This study provides valuable insights into parental adjustment and adaptation to a PCD diagnosis and management regimen. Going forward, this research highlights the need for integrated social care for PCD patients and their families.
The Higher the CKD Stage, the Higher the Psychological Stress in Patients with CKD during COVID-19 Pandemic
Authors: Lee Kyung-Mi , Kim Ji-Sun , Hwang Sungjo , Cho Nam Jun , Park Samel , Gil Hyo Wook , Lee Eun Young
Published: August 2022

The coronavirus disease 2019 (COVID-19) pandemic is related to psychological distress. Such distress depends on various factors. We previously reported that hemodialysis patients have more psychological distress than peritoneal dialysis patients among patients on dialysis in the COVID-19 pandemic era. However, no study has reported how psychological distress related to the COVID-19 pandemic depends on renal function in the entire group of chronic kidney disease (CKD) patients. Therefore, the objective of this study was to investigate psychological distress and concerns related to COVID-19 according to CKD stage. This was a cross-sectional study that included 397 CKD patients who visited a hospital from August 2020 to November 2020. Patients responded to questionnaires covering depression (9-item Patient Health Questionnaire, PHQ-9), anxiety (7-item Generalized Anxiety Disorder, GAD-7), psychological impact of event (22-item Impact of Event Scale-Revised, IES-R), insomnia (7-item Insomnia severity Index, ISI), concerns, and precautionary measures about COVID-19. According to eGFR and dialysis status, patients were divided into three groups: (1) patients with CKD stage 1~2, (2) patients with CKD stage 3~5 without dialysis, and (3) dialysis patients. The higher the CKD stage, the higher the GAD-7 (p = 0.009) and the ISI score (p = 0.001). When patients with CKD stage 1~2 and CKD stage 3~5 (with or without dialysis) were compared, PHQ-9 (p = 0.026), GAD-7 (p = 0.010), and ISI score (p = 0.002) were higher in the CKD stage 3~5 group. However, when comparing those with and without dialysis, only the ISI score (p = 0.008) showed a significant difference. More severe kidney dysfunction in CKD patients was associated with more psychological distress during the COVID-19 pandemic. Therefore, as CKD stage increases, more attention should be paid to the mental care of these patients.
Efficacy and Safety of Dimethyl Fumarate in Patients with Moderate-to-Severe Plaque Psoriasis: DIMESKIN-2, a Multicentre Single-Arm Phase IIIb Study
Authors: Pellacani Giovanni , Bigi Laura , Parodi Aurora , Burlando Martina , Lanna Caterina , Campione Elena , Rongioletti Franco , Mugheddu Cristina , Malara Giovanna , Moretti Giovanna , Stingeni Luca , Hansel Katharina , Micali Giuseppe , Naldi Luigi , Pirro Federico , Peris Ketty
Published: August 2022

This open-label multicentre trial evaluated the efficacy and safety of oral dimethyl fumarate (DMF) in patients with moderate-to-severe plaque psoriasis in real-life clinical practice over 52 weeks. Disease severity and improvement were assessed using the psoriasis area severity index (PASI), body surface area (BSA) affected, and Physician Global Assessment (PGA). Quality of life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) questionnaire. The visual analogue scale (VAS) was used to quantify pruritus and measure treatment satisfaction. A total of 141 patients were included, being 66.7% male, aged 49.1 ± 14.7 years and with disease duration of 16 ± 12.1 years. After 52 weeks, mean PASI decreased from 15.9 ± 6.8 to 1.5 ± 2 and 87.7%, 56.9% and 24.6% of patients achieved PASI 75/90/100 response, respectively. BSA decreased from 26.5 ± 14.8% to 2.7 ± 3.5% at 52 weeks, and 81.5% of patients had a PGA 0-1. DLQI scores decreased from 9.4 ± 6.4 to 2.1 ± 3.3, and VAS of pruritus decreased from 53 ± 28.4 to 19.1 ± 26.2 at Week 52. VAS for treatment satisfaction was 79.4 ± 29.4 at Week 52. A total of 34.2% of patients had an AE leading to permanent discontinuation. These findings show that DMF can significantly improve indices of disease severity, pruritus and QoL, with high levels of patient satisfaction and similar safety profile to other fumarates.
Comparison of the 2013 and 2019 Nationwide Surveys on the Management of Chronic Kidney Disease by General Practitioners in Japan
Authors: Tatematsu Satoru , Kobayashi Kazuo , Utsunomiya Yasunori , Hatta Tsuguru , Isozaki Taisuke , Miyazaki Masanobu , Nakayama Yosuke , Kusumoto Takuo , Hatori Nobuo , Otani Haruhisa
Published: August 2022

In 2019, the Japan Physicians Association conducted a second nationwide survey on the management of chronic kidney disease (CKD) among the Japanese general practitioners (GPs). We aimed to clarify the changes in the state of CKD medical care by GPs since the 2013 survey. The 2013 and 2019 surveys included 2214 and 601 GPs, respectively, who voluntarily participated. The two surveys were compared, using propensity score matching to balance the background of the responded GPs. For the medical care of CKD, the frequency of urine or blood examination, use of estimated glomerular filtration rate (eGFR) value for CKD management, and continuous use of renin-angiotensin system inhibitors for their reno-protective effects were significantly higher in 2019 than in 2013 (all: p < 0.001). The medical cooperation in CKD management, the utilization of the clinical path for CKD management and the measurement of the eGFR during the medical health checkup were significantly increased in 2019, compared to those in 2013. More GPs felt dissatisfied with the components of CKD treatment by nephrologists (p < 0.001). The two surveys confirmed improvements in the level of medical care for CKD and a strengthening in cooperation. However, the dissatisfaction with the consultation with nephrologists did not necessarily improve.
Holter ECG for Syncope Evaluation in the Internal Medicine Department—Choosing the Right Patients
Authors: Freund Ophir , Caspi Inbar , Shacham Yacov , Frydman Shir , Biran Roni , Abu Katash Hytham , Zornitzki Lior , Bornstein Gil
Published: August 2022

Physicians use Holter electrocardiography (ECG) monitoring to evaluate some patients with syncope in the internal medicine department. We questioned whether Holter ECG should be used in the presented setting. Included were all consecutive patients admitted with syncope to one of our nine internal medicine departments who had completed a 24 h Holter ECG between 2018 and 2021. A diagnostic Holter was defined as one which altered the patient’s treatment and met ESC/ACC/AHA diagnostic criteria. A total of 478 Holter tests were performed for syncope evaluation during admission to an internal medicine department in the study period. Of them, 25 patients (5.2%) had a diagnostic Holter finding. Sinus node dysfunction was the most frequent diagnostic recording (13 patients, 52%). In multivariant analysis, predictors for diagnostic Holter were older age (OR 1.35, 95% CI 1.08–1.68), heart failure with preserved ejection fraction (OR 4.1, 95% CI 1.43–11.72), and shorter duration to Holter initiation (OR 0.73, 95% CI 0.56–0.96). There was a positive correlation between time from admission to Holter and hospital stay, r(479) = 0.342, p < 0.001. Our results suggest that completing a 24 h Holter monitoring during admission to the internal medicine department should be restricted to patients with a high pre-test probability to avoid overuse and possible harm.
Direct Anterior versus Lateral Approach for Femoral Neck Fracture: Role in COVID-19 Disease
Authors: Maccagnano Giuseppe , Maruccia Francesco , Rauseo Michela , Noia Giovanni , Coviello Michele , Laneve Andrea , Quitadamo Alessandro Pio , Trivellin Giacomo , Malavolta Michele , Pesce Vito
Published: August 2022

Background: During the COVID-19 emergency, the incidence of fragility fractures in elderly patients remained unchanged. The management of these patients requires a multidisciplinary approach. The study aimed to assess the best surgical approach to treat COVID-19 patients with femoral neck fracture undergoing hemiarthroplasty (HA), comparing direct lateral (DL) versus direct anterior approach (DAA). Methods: A single-center, observational retrospective study including 50 patients affected by COVID-19 infection (30 males, 20 females) who underwent HA between April 2020 to April 2021 was performed. The patients were allocated into two groups according to the surgical approach used: lateral approach and anterior approach. For each patient, the data were recorded: age, sex, BMI, comorbidity, oxygen saturation (SpO2), fraction of the inspired oxygen (FiO2), type of ventilation invasive or non-invasive, HHb, P/F ratio (PaO2/FiO2), hemoglobin level the day of surgery and 1 day post operative, surgical time, Nottingham Hip Fractures Score (NHFS) and American Society of Anesthesiologists Score (ASA). The patients were observed from one hour before surgery until 48 h post-surgery of follow-up. The patients were stratified into five groups according to Alhazzani scores. A non-COVID-19 group of patients, as the control, was finally introduced. Results: A lateral position led to a better level of oxygenation (p < 0.01), compared to the supine anterior approach. We observed a better post-operative P/F ratio and a reduced need for invasive ventilation in patients lying in the lateral position. A statistically significant reduction in the surgical time emerged in patients treated with DAA (p < 0.01). Patients within the DAA group had a significantly lower blood loss compared to direct lateral approach. Conclusions: DL approach with lateral decubitus seems to preserved respiratory function in HA surgery. Thus, the lateral position may be associated with beneficial effects on gas exchange.
Hospitalizations for Anorexia Nervosa during the COVID-19 Pandemic in France: A Nationwide Population-Based Study
Authors: Chauvet-Gelinier Jean-Christophe , Roussot Adrien , Vergès Bruno , Petit Jean-Michel , Jollant Fabrice , Quantin Catherine
Published: August 2022

The COVID-19 pandemic has had a detrimental impact on mental health, including on food-related behaviors. However, little is known about the effect of the pandemic on anorexia nervosa (AN). We sought to assess an association between the COVID-19 pandemic and a potential increase in hospitalizations for AN in France. We compared the number of hospitalizations with a diagnosis of AN during the 21-month period following the onset of the pandemic with the 21-month period before the pandemic using Poisson regression models. We identified a significant increase in hospitalizations for girls aged 10 to 19 years (+45.9%, RR = 1.46[1.43–1.49]; p < 0.0001), and for young women aged 20 to 29 (+7.0%; RR = 1.07[1.04–1.11]; p < 0.0001). Regarding markers of severity, there was an increase in hospitalizations for AN associated with a self-harm diagnosis between the two periods. Multivariate analysis revealed that the risk of being admitted for self-harm with AN increased significantly during the pandemic period among patients aged 20–29 years (aOR = 1.39[1.06–1.81]; p < 0.05 vs. aOR = 1.15[0.87–1.53]; NS), whereas it remained high in patients aged 10 to 19 years (aOR = 2.40[1.89–3.05]; p < 0.0001 vs. aOR = 3.12[2.48–3.98]; p < 0.0001). Furthermore, our results suggest that the pandemic may have had a particular effect on the mental health of young women with AN, with both a sharp increase in hospitalizations and a high risk of self-harming behaviors.
Subclinical Myocardial Fibrosis in Systemic Lupus Erythematosus as Assessed by Pulse-Cancellation Echocardiography: A Pilot Study
Authors: Giollo Alessandro , Vinco Giulia , Cioffi Giovanni , Frizzera Francesca , Quinternetto Anna , Bergamini Corinna , Dal Porto Marta , Orsolini Giovanni , Zen Margherita , Doria Andrea , Gatti Davide , Ribichini Flavio Luciano , Targher Giovanni , Rossini Maurizio , Viapiana Ombretta
Published: August 2022

The aim of this study was to examine whether scar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) can detect subclinical myocardial involvement in systemic lupus erythematosus (SLE). We consecutively recruited SLE patients and controls matched for age, sex, and cardiovascular risk factors. Participants with cardiac symptoms or a prior history of heart disease were excluded. All participants underwent eSCAR and speckle tracking echocardiography (STE) with global longitudinal strain (GLS) assessment. SLE patients were assessed for disease activity and were followed up for 12 months. Myocardial scars by eSCAR were observed in 19% of SLE patients, almost exclusively localized at the inferoseptal myocardial segments, and in none of the controls. GLS was significantly lower in most myocardial segments of SLE patients compared with the controls, especially in the inferoseptal segments. eSCAR-positive SLE patients received a higher cumulative and current dose of prednisone, and had significantly higher levels of anti-dsDNA antibodies (p = 0.037). eSCAR-positive patients were at higher risk of having SLE flares over follow-up (hazard ratio: 4.91; 95% CI 1.43–16.83; p = 0.0001). We identified inferoseptal myocardial scars by eSCAR in about one-fifth of SLE patients. Subclinical myocardial involvement was associated with glucocorticoid use and anti-dsDNA antibodies.
Comparison of Three-Month HIIT and CMT Effects on Left Ventricle Echocardiography Observations in Male Employees
Authors: Shirvani Hossein , Farahani Maryam Moshkani , Ahmadzadeh Mahmoud , Dinca Alin Razvan
Published: August 2022

The present study aimed to identify changes in echocardiographic parameters before and after three-month high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) in male employees. For this purpose, using a convenience sampling method, 33 male employees of the Islamic Republic of Iran Army (office workers with a sedentary lifestyle) aged 30 through 40 were selected. Participants were divided into three groups of HIIT, CMT, and control (11 for each group) including all anthropometric data (body fat percentage, body mass index, height, weight, and VO2 max) with no history of chronic diseases, metabolic syndrome, confirmed heart disease or congenital heart defect, and hospitalization due to chronic diseases or consumption of medication affecting cardiovascular indicators. A one-way ANOVA was conducted to compare the groups. The results demonstrated that the end-systolic volumes (ESVs) (p < 0.01) and relative wall thickness (RWT) in the CMT group (p < 0.01) and the end-diastolic volumes (EDVs) (p < 0.01), stroke volumes (SVs) (p < 0.01), end-systolic and diastolic diameters (ESD, EDD) (p < 0.01), as well as the RWT and left ventricle diastolic function (E/A ratio) in the HIIT group (p < 0.05) were significantly different before and after the 12-week training (Bonferroni correction was used for pairwise comparisons). The results revealed a significant increase in the end-systolic diameters (ESDs) of the HIIT group, whereas no such increase was observed in the ESDs of the CMT group (p < 0.51). Moreover, a significant increase was observed in left ventricular (LV) RWT and aerobic power of both training groups. The significant decrease of ESVs and the significant increase in E/A ratio, ESDs, EDDs following HIIT (two to three sessions per week) may indicate beneficial and optimal LV structural adaptations and improved LV function in nonathletes (even with a sedentary lifestyle).
Effects of Family-Based Interventions Using Mobile Apps on Youth’s Physical Activity: A Systematic Review
Authors: Rodríguez-González Pablo , Hassan Mohamed A. , Gao Zan
Published: August 2022

Objective. This review synthesized the currently available literature on the effects of family-based interventions using smartphone apps on youth physical activity. Design. Systematic review. Data Sources. 1037 studies from eight databases were retrieved. Eligibility Criteria for Selecting Studies. The seven articles included in this review met the following inclusion criteria: (1) experimental studies, (2) using smartphone apps, and (3) involving families with healthy children/adolescents. Results. Studies were stratified according to whether they used smartphone apps only or the combination of sports wearables and their associated companion app. The smartphone app interventions showed significant improvements in youth’s PA levels. All but one of the studies reported no significant improvement in PA levels after the intervention. However, positive PA-related outcomes were found, and the combination of sports wearables and their associated companion app showed inconclusive results due to the small number of studies. A trend of the relevance of families in improving the PA levels of youths was found. Conclusions. The findings of this review indicate that more research is needed on the effects of family-based interventions using mobile apps on youth’s physical activity. Mixed results were found for variables related to the PA of the youth involved in these programs. Although strong evidence was found that youth’s physical activity levels do not always improve with the implementation of these programs, promising results were found for a positive impact on different variables related to physical activity. Therefore, more experimental studies using only a mobile app to promote PA as the main outcome are needed to understand the real effect of mobile apps on youth’s PA levels. Future studies need to further explore this topic by developing programs based on designs of high methodological quality.
Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents
Authors: Wiederhold Nathan P.
Published: August 2022

Several new antifungals are currently in late-stage development, including those with novel pharmacodynamics/mechanisms of action that represent new antifungal classes (manogepix, olorofim, ATI-2307, GR-2397). Others include new agents within established classes or with mechanisms of action similar to clinically available antifungals (ibrexafungerp, rezafungin, oteseconazole, opelconazole, MAT2203) that have been modified in order to improve certain characteristics, including enhanced pharmacokinetics and greater specificity for fungal targets. Many of the antifungals under development also have activity against Candida and Aspergillus strains that have reduced susceptibility or acquired resistance to azoles and echinocandins, whereas others demonstrate activity against species that are intrinsically resistant to most clinically available antifungals. The tolerability and drug–drug interaction profiles of these new agents also appear to be promising, although the number of human subjects that have been exposed to many of these agents remains relatively small. Overall, these agents have the potential for expanding our antifungal armamentarium and improving clinical outcomes in patients with invasive mycoses.
Occurrence, Diversity and Anti-Fungal Resistance of Fungi in Sand of an Urban Beach in Slovenia—Environmental Monitoring with Possible Health Risk Implications
Authors: Novak Babič Monika , Gunde-Cimerman Nina , Breskvar Martin , Džeroski Sašo , Brandão João
Published: August 2022

Beach safety regulation is based on faecal indicators in water, leaving out sand and fungi, whose presence in both matrices has often been reported. To study the abundance, diversity and possible fluctuations of mycobiota, fungi from sand and seawater were isolated from the Portorož beach (Slovenia) during a 1-year period. Sand analyses yielded 64 species of 43 genera, whereas seawater samples yielded 29 species of 18 genera. Environmental and taxonomical data of fungal communities were analysed using machine learning approaches. Changes in the air and water temperature, sunshine hours, humidity and precipitation, air pressure and wind speed appeared to affect mycobiota. The core genera Aphanoascus, Aspergillus, Fusarium, Bisifusarium, Penicillium, Talaromyces, and Rhizopus were found to compose a stable community within sand, although their presence and abundance fluctuated along with weather changes. Aspergillus spp. were the most abundant and thus tested against nine antimycotics using Sensititre Yeast One kit. Aspergillus niger and A. welwitschiae isolates were found to be resistant to amphotericin B. Additionally, four possible human pollution indicators were isolated during the bathing season, including Meyerozyma, which can be used in beach microbial regulation. Our findings provide the foundations for additional research on sand and seawater mycobiota and show the potential effect of global warming and extreme weather events on fungi in sand and sea.