bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and Surgery Rate of Idiopathic Scoliosis: A Nationwide Database Study
Authors: Sung Sahyun , Chae Hyun-Wook , Lee Hye Sun , Kim Sinae , Kwon Ji-Won , Lee Soo-Bin , Moon Seong-Hwan , Lee Hwan-Mo , Lee Byung Ho
Published: August 2021

Idiopathic scoliosis is the most common cause of three-dimensional deformities of the spine. Most of the previous studies have been cross-sectional studies to estimate the prevalence in the general population. An age-matched, population-based study is performed using nationwide databases between 2011 and 2015. The incidence rates of idiopathic scoliosis by age group, sex, and region are identified. We also investigate the pattern of medical institution use and the surgery rate of patients with idiopathic scoliosis. Our results show that a total of 268,372 patients were diagnosed with idiopathic scoliosis. The overall incidence was 0.497%, and the incidence for females was 1.44 times higher than for males. By age group, the incidence of adolescent idiopathic scoliosis in patients aged 10–14 years was 0.821% compared to 0.029%, 0.192%, and 0.709% for those patients aged 0–2, 3–9, and 15–19 years, respectively. Both male and female urban populations had higher incidences than rural populations with no age differences at diagnosis. Survival analysis confirmed that 0.7% of diagnosed patients underwent surgical treatment within five years. Understanding the epidemiology of idiopathic scoliosis is helpful in diagnosing high risk patients and monitoring surgical interventions.
Relationship of Hydroxychloroquine and Ophthalmic Complications in Patients with Type 2 Diabetes in Taiwan
Authors: Chen Hung-Chih , Lin Hung-Yu , Chou Michael Chia-Yen , Wang Yu-Hsun , Leong Pui-Ying , Wei James Cheng-Chung
Published: August 2021

The purpose of this study is to evaluate the relationship between hydroxychloroquine (HCQ) and diabetic retinopathy (DR) via the national health insurance research database (NHIRD) of Taiwan. All patients with newly diagnosed type 2 diabetes (n = 47,353) in the NHIRD (2000–2012) were enrolled in the study. The case group consists of participants with diabetic ophthalmic complications; 1:1 matching by age (±1 year old), sex, and diagnosis year of diabetes was used to provide an index date for the control group that corresponded to the case group (n = 5550). Chi-square test for categorical variables and Student’s t-test for continuous variables were used. Conditional logistic regression was performed to estimate the adjusted odds ratio (aOR) of DR. The total number of HCQ user was 99 patients (1.8%) in the case group and 93 patients (1.7%) in the control group. Patients with hypertension (aOR = 1.21, 95% CI = 1.11–1.31) and hyperlipidemia (aOR = 1.65, 95% CI = 1.52–1.79) significantly increased the risk of diabetic ophthalmic complications (p < 0.001). Conversely, the use of HCQ and the presence of rheumatoid diseases did not show any significance in increased risk of DR. HCQ prescription can improve systemic glycemic profile, but it does not decrease the risk of diabetic ophthalmic complications.
Flourishing of Rural Adolescents in China: A Moderated Mediation Model of Social Capital and Intrinsic Motivation
Authors: Guo Sijia , Qu Diyang
Published: August 2021

Flourishing, an indicator which reflects one’s emotional status and ability to function, is an important antecedent for adolescents’ later psychological and physical development. This study aimed to shift the research focus on rural adolescents from a deficit-based orientation to a strength-based orientation by integrating the effects of individual and social factors. Altogether, 995 Chinese rural adolescents (569 boys and 426 girls, Mage = 12.56 years) completed a self-report questionnaire which included the Ego Identity Scale, Intrinsic Motivation Scale, Social Capital Scale and Flourishing Scale. The results indicate that: (1) ego identity exploration has a positive effect on rural adolescents’ flourishing; (2) intrinsic motivation has an indirect effect on the relationship between ego identity exploration and flourishing; and (3) social capital may moderate the indirect effect by attenuating the relationship between ego identity exploration and intrinsic motivation. The findings highlight the importance of constructing a more comprehensive framework by integrating individual and social perspectives to understand and foster the flourishing of rural adolescents. Meanwhile, it is necessary to incorporate the strengths of family, school and social organizations in order to enhance rural adolescents’ flourishing.
CD19 Cell Count at Baseline Predicts B Cell Repopulation at 6 and 12 Months in Multiple Sclerosis Patients Treated with Ocrelizumab
Authors: Abbadessa Gianmarco , Miele Giuseppina , Cavalla Paola , Valentino Paola , Marfia Girolama Alessandra , Signoriello Elisabetta , Landi Doriana , Bosa Chiara , Vercellino Marco , De Martino Antonio , Missione Rosanna , Sparaco Maddalena , Lavorgna Luigi , Lus Giacomo , Bonavita Simona
Published: August 2021

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and whether circulating immune asset at baseline affects B cell repopulation kinetics. Methods: 218 MS patients treated with Ocrelizumab were included. Every six months we collected data on clinical and magnetic resonance imaging (MRI) activity and lymphocyte subsets at baseline. According to B cell counts at six and twelve months, we identified two groups of patients, those with fast repopulation rate (FR) and those with slow repopulation rate (SR). Results: A significant reduction in clinical and radiological activity was found. One hundred fifty-five patients had complete data and received at least three treatment cycles (twelve-month follow-up). After six months, the FR patients were 41/155 (26.45%) and 10/41 (29.27%) remained non-depleted after twelve months. FR patients showed a significantly higher percentage of active MRI scan at twelve months (17.39% vs. 2.53%; p = 0,008). Furthermore, FR patients had a higher baseline B cell count compared to patients with an SR (p = 0.02 and p = 0.002, at the six- and twelve-month follow-ups, respectively). Conclusion: A considerable proportion of MS patients did not achieve a complete CD19 cell depletion and these patients had a higher baseline CD19 cell count. These findings, together with the higher MRI activity found in FR patients, suggest that the Ocrelizumab dosage could be tailored depending on CD19 cell counts at baseline in order to achieve complete disease control in all patients.
Differential Impacts of Multimorbidity on COVID-19 Severity across the Socioeconomic Ladder in Hong Kong: A Syndemic Perspective
Authors: Chung Gary Ka-Ki , Chan Siu-Ming , Chan Yat-Hang , Yip Terry Cheuk-Fung , Ma Hon-Ming , Wong Grace Lai-Hung , Chung Roger Yat-Nork , Wong Hung , Wong Samuel Yeung-Shan , Yeoh Eng Kiong , Marmot Michael , Woo Jean
Published: August 2021

The severity of COVID-19 infections could be exacerbated by the epidemic of chronic diseases and underlying inequalities in social determinants of health. Nonetheless, there is scanty evidence in regions with a relatively well-controlled outbreak. This study examined the socioeconomic patterning of COVID-19 severity and its effect modification with multimorbidity in Hong Kong. 3074 local COVID-19 cases diagnosed from 5 July to 31 October 2020 were analyzed and followed up until 30 November 2020. Data on residential addresses, socio-demographic background, COVID-19 clinical conditions, and pre-existing chronic diseases of confirmed cases were retrieved from the Centre for Health Protection and the Hospital Authority. Results showed that, despite an independent adverse impact of multimorbidity on COVID-19 severity (aOR = 2.35 [95% CI = 1.72–3.19]), it varied across the socioeconomic ladder, with no significant risk among those living in the wealthiest areas (aOR = 0.80 [0.32–2.02]). Also, no significant association of the area-level income-poverty rate with severe COVID-19 was observed. In conclusion, the socioeconomic patterning of severe COVID-19 was mild in Hong Kong. Nonetheless, socioeconomic position interacted with multimorbidity to determine COVID-19 severity with a mitigated risk among the socioeconomically advantaged. Plausible explanations include the underlying socioeconomic inequalities in chronic disease management and the equity impact of the public-private dual-track healthcare system.
The Effect of Magnesium Supplementation on Endothelial Function: A Randomised Cross-Over Pilot Study
Authors: Byrne Jennifer , Murphy Caitríona , Keogh Jennifer B. , Clifton Peter M.
Published: August 2021

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24 h urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005, respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = −0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.
The 3,4-Quinones of Estrone and Estradiol Are the Initiators of Cancer whereas Resveratrol and N-acetylcysteine Are the Preventers
Authors: Cavalieri Ercole , Rogan Eleanor
Published: August 2021

This article reviews evidence suggesting that a common mechanism of initiation leads to the development of many prevalent types of cancer. Endogenous estrogens, in the form of catechol estrogen-3,4-quinones, play a central role in this pathway of cancer initiation. The catechol estrogen-3,4-quinones react with specific purine bases in DNA to form depurinating estrogen-DNA adducts that generate apurinic sites. The apurinic sites can then lead to cancer-causing mutations. The process of cancer initiation has been demonstrated using results from test tube reactions, cultured mammalian cells, and human subjects. Increased amounts of estrogen-DNA adducts are found not only in people with several different types of cancer but also in women at high risk for breast cancer, indicating that the formation of adducts is on the pathway to cancer initiation. Two compounds, resveratrol, and N-acetylcysteine, are particularly good at preventing the formation of estrogen-DNA adducts in humans and are, thus, potential cancer-prevention compounds.
Generation of Recombinant Primary Human B Lymphocytes Using Non-Viral Vectors
Authors: Keim Daniel , Gollner Katrin , Gollner Ulrich , Jérôme Valérie , Freitag Ruth
Published: August 2021

Although the development of gene delivery systems based on non-viral vectors is advancing, it remains a challenge to deliver plasmid DNA into human blood cells. The current “gold standard”, namely linear polyethyleneimine (l-PEI 25 kDa), in particular, is unable to produce transgene expression levels >5% in primary human B lymphocytes. Here, it is demonstrated that a well-defined 24-armed poly(2-dimethylamino) ethyl methacrylate (PDMAEMA, 755 kDa) nano-star is able to reproducibly elicit high transgene expression (40%) at sufficient residual viability (69%) in primary human B cells derived from tonsillar tissue. Moreover, our results indicate that the length of the mitogenic stimulation prior to transfection is an important parameter that must be established during the development of the transfection protocol. In our hands, four days of stimulation with rhCD40L post-thawing led to the best transfection results in terms of TE and cell survival. Most importantly, our data argue for an impact of the B cell subsets on the transfection outcomes, underlining that the complexity and heterogeneity of a given B cell population pre- and post-transfection is a critical parameter to consider in the multiparametric approach required for the implementation of the transfection protocol.
A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria
Authors: You Deok-Gyun , Lee Hye-Ra , Kim Hong-Kyu , Lee Gi-Young , Yoo Young-Do
Published: August 2021

The emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial peptides, part of the innate immunity system, have been studied to find bactericidal agents potent against MDR bacteria. However, they have many problems, such as restrained systemic activity and cytotoxicity. In a previous study, we suggested that the K58–R78 domain of Romo1, a mitochondrial protein encoded by the nucleus, was a promising treatment candidate for sepsis caused by MDR bacteria. Here, we performed sequence optimization to enhance the antimicrobial activity of this peptide and named it as AMPR-22 (antimicrobial peptide derived from Romo1). It showed broad-spectrum antimicrobial activity against 17 sepsis-causing bacteria, including MDR strains, by inducing membrane permeabilization. Moreover, treatment with AMPR-22 enabled a remarkable survival rate in mice injected with MDR bacteria in a murine model of sepsis. Based on these results, we suggest that AMPR-22 could be prescribed as a first-line therapy (prior to bacterial identification) for patients diagnosed with sepsis.
Ovarian Accumulation of Nanoemulsions: Impact of Mice Age and Particle Size
Authors: Busmann Eike Folker , Kollan Julia , Mäder Karsten , Lucas Henrike
Published: August 2021

Nanotechnology in the field of drug delivery comes with great benefits due to the unique physicochemical properties of newly developed nanocarriers. However, they may come as well with severe toxicological side effects because of unwanted accumulation in organs outside of their targeted site of actions. Several studies showed an unintended accumulation of various nanocarriers in female sex organs, especially in the ovaries. Some led to inflammation, fibrosis, or decreasing follicle numbers. However, none of these studies investigated ovarian accumulation in context to both reproductive aging and particle size. Besides the influences of particle size, the biodistribution profile may be altered as well by reproductive aging because of reduced capacities of the reticuloendothelial system (RES), changes in sex steroid hormone levels as well as altering ovarian stromal blood flow. This systematic investigation of the biodistribution of intravenously (i.v) injected nanoemulsions revealed significant dependencies on the two parameters particle size and age starting from juvenile prepubescent to senescent mice. Using fluorescent in vivo and ex vivo imaging, prepubescent mice showed nearly no accumulation of nanoemulsion in their uteri and ovaries, but high accumulations in the organs of the RES liver and spleen independently of the particle size. In fertile adult mice, the accumulation increased significantly in the ovaries with an increased particle size of the nanoemulsions by nearly doubling the portion of the average radiant efficiency (PARE) to ~10% of the total measured signal of all excised organs. With reproductive aging and hence loss of fertility in senescent mice, the accumulation decreased again to moderate levels, again independently of the particle size. In conclusion, the ovarian accumulation of these nanocarriers depended on both the age plus the particle size during maturity.
Maize DNA Methylation in Response to Drought Stress Is Involved in Target Gene Expression and Alternative Splicing
Authors: Wang Qi , Xu Jie , Pu Xuemei , Lv Haozhe , Liu Yanjun , Ma Huili , Wu Fengkai , Wang Qingjun , Feng Xuanjun , Liu Tianhong , Tang Qi , Liu Yaxi , Lu Yanli
Published: August 2021

DNA methylation is important for plant growth, development, and stress response. To understand DNA methylation dynamics in maize roots under water stress (WS), we reanalyzed DNA methylation sequencing data to profile DNA methylation and the gene expression landscape of two inbred lines with different drought sensitivities, as well as two of their derived recombination inbred lines (RILs). Combined with genotyping-by-sequencing, we found that the inheritance pattern of DNA methylation between RILs and parental lines was sequence-dependent. Increased DNA methylation levels were observed under WS and the methylome of drought-tolerant inbred lines were much more stable than that of the drought-sensitive inbred lines. Distinctive differentially methylated genes were found among diverse genetic backgrounds, suggesting that inbred lines with different drought sensitivities may have responded to stress in varying ways. Gene body DNA methylation showed a negative correlation with gene expression but a positive correlation with exon splicing events. Furthermore, a positive correlation of a varying extent was observed between small interfering RNA (siRNA) and DNA methylation, which at different genic regions. The response of siRNAs under WS was consistent with the differential DNA methylation. Taken together, our data can be useful in deciphering the roles of DNA methylation in plant drought-tolerance variations and in emphasizing its function in alternative splicing.
Adjusting the Molecular Clock: The Importance of Circadian Rhythms in the Development of Glioblastomas and Its Intervention as a Therapeutic Strategy
Authors: Wagner Paula M. , Prucca César G. , Caputto Beatriz L. , Guido Mario E.
Published: August 2021

Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.
Photoprotective Role of Photosynthetic and Non-Photosynthetic Pigments in Phillyrea latifolia: Is Their “Antioxidant” Function Prominent in Leaves Exposed to Severe Summer Drought?
Authors: Gori Antonella , Brunetti Cecilia , dos Santos Nascimento Luana Beatriz , Marino Giovanni , Guidi Lucia , Ferrini Francesco , Centritto Mauro , Fini Alessio , Tattini Massimiliano
Published: August 2021

Carotenoids and phenylpropanoids play a dual role of limiting and countering photooxidative stress. We hypothesize that their “antioxidant” function is prominent in plants exposed to summer drought, when climatic conditions exacerbate the light stress. To test this, we conducted a field study on Phillyrea latifolia, a Mediterranean evergreen shrub, carrying out daily physiological and biochemical analyses in spring and summer. We also investigated the functional role of the major phenylpropanoids in different leaf tissues. Summer leaves underwent the most severe drought stress concomitantly with a reduction in radiation use efficiency upon being exposed to intense photooxidative stress, particularly during the central hours of the day. In parallel, a significant daily variation in both carotenoids and phenylpropanoids was observed. Our data suggest that the morning-to-midday increase in zeaxanthin derived from the hydroxylation of ß-carotene to sustain non-photochemical quenching and limit lipid peroxidation in thylakoid membranes. We observed substantial spring-to-summer and morning-to-midday increases in quercetin and luteolin derivatives, mostly in the leaf mesophyll. These findings highlight their importance as antioxidants, countering the drought-induced photooxidative stress. We concluded that seasonal and daily changes in photosynthetic and non-photosynthetic pigments may allow P. latifolia leaves to avoid irreversible photodamage and to cope successfully with the Mediterranean harsh climate.
AthPPA: A Data Visualization Tool for Identifying Political Popularity over Twitter
Authors: Britzolakis Alexandros , Kondylakis Haridimos , Papadakis Nikolaos
Published: August 2021

Sentiment Analysis is an actively growing field with demand in both scientific and industrial sectors. Political sentiment analysis is used when a data analyst wants to determine the opinion of different users on social media platforms regarding a politician or a political event. This paper presents Athena Political Popularity Analysis (AthPPA), a tool for identifying political popularity over Twitter. AthPPA is able to collect in-real-time tweets and for each tweet to extract metadata such as number of likes, retweets per tweet etc. Then it processes their text in order to calculate their overall sentiment. For the calculation of sentiment analysis, we have implemented a sentiment analyzer that is able to identify the grammatical issues of a sentence as well as a lexicon of negative and positive words designed specifically for political sentiment analysis. An analytic engine processes the collected data and provides different visualizations that provide additional insights on the collected data. We show how we applied our framework to the three most prominent Greek political leaders in Greece and present our findings there.
Design of an Architecture Contributing to the Protection and Privacy of the Data Associated with the Electronic Health Record
Authors: Pineda Rincón Edwar Andrés , Moreno-Sandoval Luis Gabriel
Published: August 2021

The Electronic Health Record (EHR) has brought numerous challenges since its inception that have prevented a unified implementation from being carried out in Colombia. Within these challenges, we find a lack of security, auditability, and interoperability. Moreover, there is no general vision of the patient’s history throughout its life since different systems store the information separately. This lack of unified history leads to multiple risks for patients’ lives and the leakage of private data because each system has different mechanisms to safeguard and protect the information, and in several cases, these mechanisms do not exist. Many researchers tried to build multiple information systems attempting to solve this problem. However, these systems do not have a formal and rigorous architectural design to analyze and obtain health needs through architectural drivers to construct robust systems to solve these problems. This article describes the process of designing a software architecture that provides security to the information that makes up the Electronic Health Record in Colombia (EHR). Once we obtained the architectural drivers, we proposed Blockchain mainly due to its immutable distributed ledger, consensus algorithms, and smart contracts that securely transport this sensitive information. With this design decision, we carried out the construction of structures and necessary architectural documentation. We also develop a Proof of Concept (POC) using Hyperledger Fabric according to the literature analysis review in order to build a primary health network, in addition to a Smart Contract (Chaincode) using the Go programming language to perform a performance evaluation and do a safety analysis that demonstrates that the proposed design is reliable. The proposed design allows us to conclude that it is possible to build a secure architecture that protects patient health data privacy, facilitating the EHR’s construction in Colombia.
Overview of Bee Pollination and Its Economic Value for Crop Production
Authors: Khalifa Shaden A. M. , Elshafiey Esraa H. , Shetaia Aya A. , El-Wahed Aida A. Abd , Algethami Ahmed F. , Musharraf Syed G. , AlAjmi Mohamed F. , Zhao Chao , Masry Saad H. D. , Abdel-Daim Mohamed M. , Halabi Mohammed F. , Kai Guoyin , Al Naggar Yahya , Bishr Mokhtar , Diab Mohamed A. M. , El-Seedi Hesham R.
Published: August 2021

Pollination plays a significant role in the agriculture sector and serves as a basic pillar for crop production. Plants depend on vectors to move pollen, which can include water, wind, and animal pollinators like bats, moths, hoverflies, birds, bees, butterflies, wasps, thrips, and beetles. Cultivated plants are typically pollinated by animals. Animal-based pollination contributes to 30% of global food production, and bee-pollinated crops contribute to approximately one-third of the total human dietary supply. Bees are considered significant pollinators due to their effectiveness and wide availability. Bee pollination provides excellent value to crop quality and quantity, improving global economic and dietary outcomes. This review highlights the role played by bee pollination, which influences the economy, and enlists the different types of bees and other insects associated with pollination.
Mating-Induced Trade-Offs upon Egg Production versus Fertilization and Offspring’s Survival in a Sawfly with Facultative Parthenogenesis
Authors: Yu Hong , Shi Min-Rui , Xu Jin , Chen Peng , Liu Jian-Hong
Published: August 2021

Investigation of mating-induced trade-offs between reproduction and survival is conducive to provide evolutionary insights into reproductive strategies and aging. Here, we used RNAseq and bioinformatics to reveal mating-induced changes of genes and pathways related to reproduction and survival in female Cephalcia chuxiongica, a pine defoliator with facultative parthenogenesis and long larval dormancy. Results showed that mating induced substantial downregulation on genes and pathways associated to immunity, stress response, and longevity. However, mating induced divergent reproductive response, with downregulation on genes and pathways related to egg production while upregulation on genes and pathways related to egg fertilization. Considering the nature of limited resources in adults, low fecundity, and egg protection behavior in C. chuxiongica, we suggest that mating triggers trade-offs between reproduction and survival in this insect and females of this species may have evolved specific strategies to adapt to the environmental and hosts’ conditions, e.g., restrict whole fecundity to ensure higher fertilization and offspring’s survival. Moreover, mating induced significant responses on genes and pathways that play important roles in vertebrate reproduction while their function in insects are unclear, such as the progesterone-mediated oocyte maturation pathway; the significant regulation after mating suggests that their function may be evolutionarily conserved in animal kingdom.
Frailty in Wild-Type Transthyretin Cardiac Amyloidosis: The Tip of the Iceberg
Authors: Broussier Amaury , David Jean Philippe , Kharoubi Mounira , Oghina Silvia , Segaux Lauriane , Teiger Emmanuel , Laurent Marie , Fromentin Isabelle , Bastuji-Garin Sylvie , Damy Thibaud
Published: August 2021

ATTRwt-CA occurs in elderly patients and leads to severe heart failure. The disease mechanism involves cardiac and extracardiac infiltration by amyloid fibrils. The objectives of this study are to describe the frailty phenotype in patients with ATTRwt-CA and to assess the associations between frailty parameters, the severity of cardiac involvement, and the course of amyloid disease. We used multidimensional geriatric tools to prospectively assess frailty in patients with ATTRwt-CA consulting (in 2018–2019) in the French National Reference Center for Cardiac Amyloidosis. We included 36 patients (35 males; median age: 82 years (76–86). A third of the patients were categorized as NYHA class III or IV, and 39% had an LVEF below 45%. The median serum NTproBNP was 3188 (1341–8883) pg/mL. The median duration of amyloidosis was 146 months (73–216). The frequency of frailty was 50% and 33% according to the physical frailty phenotype and the Short Emergency Geriatric Assessment questionnaire, respectively. Frailty affected a large number of domains, namely autonomy (69%), balance (58%), muscle weakness (74%), malnutrition (39%), dysexecutive syndrome (72%), and depression (49%). The severity of CA was significantly associated with many frailty parameters independently of age. Balance disorders and poor mobility were also significantly associated with a longer course of amyloid disease. Frailty is frequent in patients with ATTRwt-CA. Some frailty parameters were significantly associated with a longer course of amyloid disease and CA severity. Taking into account frailty in the assessment and management of ATTRwt should improve patients’ quality of life.
Change in Shoulder Function in the Early Recovery Phase after Breast Cancer Surgery: A Prospective Observational Study
Authors: Min Jihee , Kim Jee Ye , Yeon Sujin , Ryu Jiin , Min Jin Joo , Park Seho , Kim Seung Il , Jeon Justin Y.
Published: August 2021

Breast cancer surgery significantly affects the shoulder’s range of motion (ROM) and strength. However, the extent of shoulder impairment, as well as patterns of recovery immediately after surgery, is not fully understood. Therefore, we aimed to investigate shoulder ROM and strength during the early recovery phase after surgery. Thirty-two breast cancer patients were observed five times: the day before surgery, discharge day (postoperative day 1 (POD1) or (POD2)), first outpatient visit (POD7–10), second outpatient visit (POD14–20), and third outpatient visit (POD21–30). We assessed shoulder passive ROM and strength for both affected and unaffected arms at each observation. ROM decreased in both affected and unaffected sides post-surgery. ROM on the affected side did not recover to the pre-surgery level until the third outpatient visit (POD24). In contrast, the ROM on the unaffected side recovered to the pre-surgery level by the first outpatient visit (POD10). The shoulder strength of both arms declined and did not recover to pre-surgery levels. Shoulder strength in the affected arm significantly decreased immediately after surgery (52.9% of the pre-surgery levels) and did not recover until the third outpatient visit (62.5% of the pre-surgery levels), whereas that in the unaffected arm decreased gradually (83.1 ± 2.3 at POD 1 and 78.9 ± 2.9 at POD 24). Descriptively, patterns of recovery in ROM may vary according to types of surgery while patterns of recovery in shoulder strength did not: shoulder strength significantly decreased and did not recover notably regardless of types of surgery. Both shoulder ROM and strength reduced during the early recovery phase after breast cancer surgery regardless of types of surgery, although the degree of reduction was greater in shoulder strength than ROM. Our findings suggest that rehabilitation exercises should be implemented in both upper limbs.
Paracetamol: A Review of Guideline Recommendations
Authors: Freo Ulderico , Ruocco Chiara , Valerio Alessandra , Scagnol Irene , Nisoli Enzo
Published: August 2021

Musculoskeletal pain conditions are age-related, leading contributors to chronic pain and pain-related disability, which are expected to rise with the rapid global population aging. Current medical treatments provide only partial relief. Furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are effective in young and otherwise healthy individuals but are often contraindicated in elderly and frail patients. As a result of its favorable safety and tolerability record, paracetamol has long been the most common drug for treating pain. Strikingly, recent reports questioned its therapeutic value and safety. This review aims to present guideline recommendations. Paracetamol has been assessed in different conditions and demonstrated therapeutic efficacy on both acute and chronic pain. It is active as a single agent and is additive or synergistic with NSAIDs and opioids, improving their efficacy and safety. However, a lack of significant efficacy and hepatic toxicity have also been reported. Fast dissolving formulations of paracetamol provide superior and more extended pain relief that is similar to intravenous paracetamol. A dose reduction is recommended in patients with liver disease or malnourished. Genotyping may improve efficacy and safety. Within the current trend toward the minimization of opioid analgesia, it is consistently included in multimodal, non-opioid, or opioid-sparing therapies. Paracetamol is being recommended by guidelines as a first or second-line drug for acute pain and chronic pain, especially for patients with limited therapeutic options and for the elderly.
Fetal Cardiac Services during the COVID-19 Pandemic: How Does It Affect Parental Counseling?
Authors: Kovacevic Alexander , Bär Stefan , Starystach Sebastian , Elsässer Michael , van der Locht Thomas , Mohammadi Motlagh Aida , Ostermayer Eva , Oberhoffer-Fritz Renate , Ewert Peter , Gorenflo Matthias , Wacker-Gussmann Annette
Published: August 2021

The COVID-19 pandemic impacts health care providers in multiple ways, even specialties that do not seem to be affected primarily, such as fetal cardiac services. We aimed to assess the effects on parental counseling for fetal congenital heart disease (CHD). In this multicenter study, we used a validated questionnaire. Parents were recruited from four national tertiary medical care centers (n = 226); n = 169 had been counseled before and n = 57 during the pandemic. Overall counseling success including its dimensions did not differ between the two groups (p = n.s.). However, by applying the sorrow scale, we could demonstrate that parents counseled during the pandemic were significantly more concerned (p = 0.025) and unsure (p = 0.044) about their child’s diagnosis, therapy and outcome. Furthermore, parents expressed a significantly increased need for written and/or online information on fetal heart disease (p = 0.034). Other modifiers did not affect counseling success (p = n.s.). We demonstrate that the COVID-19 pandemic impacts effectiveness of parental counseling for fetal CHD, possibly by altering parental perceptions. This needs to be taken into consideration when counseling. Implementing alternative and innovative approaches (e.g., online conference or virtual reality tools) may aid in facilitating high-quality services in critical times such as in the present pandemic.
How to Predict the Suitability for Corneal Donorship?
Authors: Schön Franziska , Gericke Adrian , Bu Julia Bing , Apel Melissa , Poplawski Alicia , Schuster Alexander K. , Pfeiffer Norbert , Wasielica-Poslednik Joanna
Published: August 2021

Background: In Germany, more than one-third of donor corneas harvested are not suitable for transplantation. We evaluated the factors associated with the usability of donor corneas. Method: Data from 2032 consecutive donor corneas harvested at the Rhineland-Palatinate Eye Bank in Mainz, Germany, were retrospectively analyzed. Factors of interest were age, sex, lens status, cause of death, cardiopulmonary resuscitation (CPR), death-to-explantation-interval (DEI), and the influence of these factors on the proportion of discarded donor corneas. Factors associated with endothelial cell density (ECD) were analyzed in a linear regression mixed model. Results: Higher donor age, male gender, pseudophakic lens status, and longer DEI were associated with significantly reduced ECD. With respect to DEI, the estimated cell loss was 7 ± 2 cells/mm2/hour (p < 0.001). Age was associated with a lower ECD of 6 ± 2 cells/mm2 per year (p = 0.001). Female ECD was 189 ± 44 cells/mm2 higher than male ECD (p < 0.001). Pseudophakic eyes had 378 ± 42 cells/mm2 less compared with phakic eyes (p < 0.001). Cause of death did not affect the ECD. Of note, 55% and 38% of corneas harvested on the second and third postmortem day, respectively, and 45% of corneas from donors older than 80 years were still suitable for transplantation. Conclusions: In the context of a growing need for donor corneas, we do not recommend limiting donor age and collection time to 24 h or excluding oncology donors, as is the practice in many countries. Therefore, we propose a mathematical model for better donor preselection.
Control of Glucose, Blood Pressure, and Cholesterol among Adults with Diabetes: The Brazilian National Health Survey
Authors: dos Reis Rodrigo Citton P. , Duncan Bruce B. , Szwarcwald Célia Landmann , Malta Deborah Carvalho , Schmidt Maria Inês
Published: August 2021

ABC (glucose, blood pressure and LDL-cholesterol) goals are basic standards of diabetes care. We aimed to assess ABC control and related factors in a representative sample of Brazilian adults with diabetes. We analyzed 465 adults with known diabetes in the Brazilian National Health Survey. The targets used were <7% for glycated hemoglobin (A1C); <140/90 mmHg for blood pressure; and <100 mg/dL for LDL-C, with stricter targets for the latter two for those with high cardiovascular (CVD) risk. Individual goals were attained by 46% (95% CI, 40.3–51.6%) for A1C, 51.4% (95% CI, 45.7–57.1%) for blood pressure, and 40% (95% CI, 34.5–45.6%) for LDL-C. The achievement of all three goals was attained by 12.5% (95% CI, 8.9–16.2%). Those with high CVD risk attained blood pressure and LDL-C goals less frequently. A1C control improved with increasing age and worsened with greater duration of diabetes. Achievement of at least two ABC goals decreased with increasing BMI and greater duration of diabetes. In sum, about half of those with known diabetes achieved each ABC goal and only a small fraction achieved all three goals. Better access and adherence to treatment and strategies to personalize goals according to specific priorities are of the essence.
Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management
Authors: Gros Mónica , Gros Belén , Mesonero José Emilio , Latorre Eva
Published: August 2021

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT3 receptor antagonists and 5-HT4 receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.
The Comparison of Breast Reconstruction Using Two Types of Acellular Dermal Matrix after Breast-Conserving Surgery
Authors: An Jeongshin , Kwon Hyungju , Lim Woosung , Moon Byung-In , Paik Nam Sun
Published: August 2021

Breast reconstruction during breast-conserving surgery (BCS) can improve the breast shape. This study introduces breast reconstruction in BCS with two types of acellular dermal matrix (ADM). The study included 134 patients who underwent BCS due to breast cancer from February 2018 to May 2021. This study was conducted by one surgeon, and is the result of a three-year study. The patient group who underwent BCS using ADM was mainly targeted at patients with minor to severe defects after the operation. The average age of the patients was 51.8 years, and the body mass index (BMI) was 23.8 kg/m. The specimen weight was 30–120 g. The average surgical time, including reconstruction, was 100.4 min, combined with reconstruction. There were minor complications in six patients. The advantage of using ADM is that it can quickly correct the shape of the breast after conventional BCS surgery. Pellet-type ADM, rather than sheet-type, can create a breast shape similar to that before surgery. Breast reconstruction using ADM can be an easy and convenient method for making a better shape from BCS.
Are Patients with Psoriasis and Psoriatic Arthritis Undertreated? A Population-Based Study from Southern Italy
Authors: Ingrasciotta Ylenia , Isgrò Valentina , Ientile Valentina , Tari Michele , Trifirò Gianluca , Guarneri Claudio
Published: August 2021

This study aimed to explore the pattern of use of different treatment lines in psoriasis (PsO) and psoriatic arthritis (PsA) patients from Southern Italy. A retrospective cohort study was performed during the years 2010–2018 using data from the Caserta Local Health Unit (LHU) claims database. All of the PsO or PsA patients were identified. The proportion of PsO/PsA patients untreated or treated with ≥1 drug classes (i.e., non-disease-modifying antirheumatic drugs (non-DMARDs), conventional synthetic DMARDs (csDMARDs), biological drugs (bDMARDs) or targeted synthetic small molecules (tsDMARDs)) was calculated in the years 2016–2018. Among the bDMARD users, the median times from the first registered PsO/PsA diagnosis/from the first csDMARD to the first bDMARD were calculated. Overall, 10,296 (1.1%) and 1724 (0.2%) PsO and PsA patients were identified. More than half of the PsO patients (N = 5301; 51.6%) and 15% of the PsA patients (N = 251) were not treated with any drug. A very low proportion of PsO patients (N = 121; 1.2%) received csDMARDs/bDMARDs dispensing. Instead, 538 (32.2%) PsA patients were treated with bDMARDs. The median times from the first diagnosis to the first bDMARD dispensing were 54.0 (Q1–Q3: 30.5–72.2) and 13.3 (Q1–Q3: 3.1–43.9) months in the PsO and PsA patients, respectively. The median time from the first csDMARD to the first bDMARD dispensing was shorter in the PsO [9.2 months (Q1–Q3: 5.5–30.0)] than in the PsA [14.5 months (Q1–Q3: 8.6–33.5)] patients. A potential undertreatment of PsO (much less for PsA) in an LHU from Southern Italy, with a particularly low use of more recently marketed drugs, such as biological ones, was shown.
Systemic Vulnerability, as Expressed by I-CAM and MMP-9 at Presentation, Predicts One Year Outcomes in Patients with Acute Myocardial Infarction—Insights from the VIP Clinical Study
Authors: Opincariu Diana , Rodean Ioana , Rat Nora , Hodas Roxana , Benedek Imre , Benedek Theodora
Published: August 2021

(1) Background: The prediction of recurrent events after acute myocardial infarction (AMI) does not sufficiently integrate systemic inflammation, coronary morphology or ventricular function in prediction algorithms. We aimed to evaluate the accuracy of inflammatory biomarkers, in association with angiographical and echocardiographic parameters, in predicting 1-year MACE after revascularized AMI. (2) Methods: This is an extension of a biomarker sub-study of the VIP trial (NCT03606330), in which 225 AMI patients underwent analysis of systemic vulnerability and were followed for 1 year. Hs-CRP, MMP-9, IL-6, I-CAM, V-CAM and E-selectin were determined at 1 h after revascularization. The primary end-point was the 1-year MACE rate. (3) Results: The MACE rate was 24.8% (n = 56). There were no significant differences between groups in regard to IL-6, V-CAM and E-selectin. The following inflammatory markers were significantly higher in MACE patients: hs-CRP (11.1 ± 13.8 vs. 5.1 ± 4.4 mg/L, p = 0.03), I-CAM (452 ± 283 vs. 220.5 ± 104.6, p = 0.0003) and MMP-9 (2255 ± 1226 vs. 1099 ± 706.1 ng/mL p = 0.0001). The most powerful predictor for MACE was MMP-9 of >1155 ng/mL (AUC-0.786, p < 0.001) even after adjustments for diabetes, LVEF, acute phase complications and other inflammatory biomarkers. For STEMI, the most powerful predictors for MACE included I-CAM > 239.7 ng/mL, V-CAM > 877.9 ng/mL and MMP-9 > 1393 ng/mL. (4) Conclusions: High levels of I-CAM and MMP-9 were the most powerful predictors for recurrent events after AMI for the overall study population. For STEMI subjects, the most important predictors included increased levels of I-CAM, V-CAM and MMP-9, while none of the analyzed parameters had proven to be predictive. Inflammatory biomarkers assayed during the acute phase of AMI presented a more powerful predictive capacity for MACE than the LVEF.
Multimodel Ensemble Projections of Wave Climate in the Western North Pacific Using CMIP6 Marine Surface Winds
Authors: Badriana Mochamad Riam , Lee Han Soo
Published: August 2021

For decades, the western North Pacific (WNP) has been commonly indicated as a region with high vulnerability to oceanic and atmospheric hazards. This phenomenon can be observed through general circulation model (GCM) output from the Coupled Model Intercomparison Project (CMIP). The CMIP consists of a collection of ensemble data as well as marine surface winds for the projection of the wave climate. Wave climate projections based on the CMIP dataset are necessary for ocean studies, marine forecasts, and coastal development over the WNP region. Numerous studies with earlier phases of CMIP are abundant, but studies using CMIP6 as the recent dataset for wave projection is still limited. Thus, in this study, wave climate projections with WAVEWATCH III are conducted to investigate how wave characteristics in the WNP will have changed in 2050 and 2100 compared to those in 2000 with atmospheric forcings from CMIP6 marine surface winds. The wave model runs with a 0.5° × 0.5° spatial resolution in spherical coordinates and a 10-min time step. A total of eight GCMs from the CMIP6 dataset are used for the marine surface winds modelled over 3 h for 2050 and 2100. The simulated average wave characteristics for 2000 are validated with the ERA5 Reanalysis wave data showing good consistency. The wave characteristics in 2050 and 2100 show that significant decreases in wave height, a clockwise shift in wave direction, and the mean wave period becomes shorter relative to those in 2000.