bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Leaf Morphology and Related Gene Expression between Diploid and Tetraploid Birch (Betula pendula)
Authors: Zhang Xiaoyue , Chen Kun , Wang Wei , Liu Guifeng , Yang Chuanping , Jiang Jing
Published: October 2022

Plant polyploidization changes its leaf morphology and leaf development patterns. Understanding changes in leaf morphology and development patterns is a prerequisite and key to studying leaf development in polyploid plants. In this study, we quantified and analyzed the differences in leaf morphology, leaf growth polarity, and leaf size between diploid and tetraploid birches (Betula pendula subsp. pendula), and preliminarily investigated genes involved in leaf growth and development in birch. The results showed significant changes in leaf morphology in tetraploid birches, especially the basal part of the leaf. In addition, the proximal growth rate of tetraploid leaves was altered. The changed proximal growth rate did not affect the growth polarity pattern of tetraploid leaves. The leaf area of tetraploid was significantly larger than that of diploid birch. The difference in leaf size was mainly due to differences in their growth rates in the middle and late stages of leaf development. Increased cell expansion capacity was the major reason for the enormous leaves of tetraploid birch; however, cell proliferation did not contribute to the larger tetraploid leaf. The gene expression of ATHB12 was associated with cell size and leaf area, and may be a critical gene affecting the leaf size in diploid and tetraploid birches. The results will provide valuable insights into plant polyploid leaf development and a theoretical basis for later investigations into the molecular mechanisms underlying the gigantism of tetraploid birch leaves.
The Bottlenecks of Preparing Virus Particles by Size Exclusion for Antibody Generation
Authors: Lee Chi-Hsin , Huang Peng-Nien , Mwale Pharaoh Fellow , Wang Wei-Chu , Leu Sy-Jye , Tseng Sung-Nien , Shih Shin-Ru , Chiang Liao-Chun , Mao Yan-Chiao , Tsai Bor-Yu , Dlamini Nhlanhla Benedict , Nguyen Tien-Cuong , Tsai Chen-Hsin , Yang Yi-Yuan
Published: October 2022

Enterovirus 71 (EV71) is the major etiological agent contributing to the development of hand-foot-mouth disease (HFMD). There are not any global available vaccines or antibody drugs against EV71 released yet. In this study, we perform the virus immunization in a cost-effective and convenient approach by preparing virus particles from size exclusion and immunization of chicken. Polyclonal yolk-immunoglobulin (IgY) was simply purified from egg yolk and monoclonal single-chain variable fragments (scFv) were selected via phage display technology with two scFv libraries containing 6.0 × 106 and 1.3 × 107 transformants. Specific clones were enriched after 5 rounds of bio-panning and four identical genes were classified after the sequence analysis. Moreover, the higher mutation rates were revealed in the CDR regions, especially in the CDR3. IgY showed specific binding activities to both EV71-infected and Coxsackievirus 16-infected cell lysates and high infectivity inhibitory activity of EV71. However, while IgY detected a 37 kDa protein, the selected scFv seemingly detected higher size proteins which could be cell protein instead of EV71 proteins. Despite the highly effective chicken antibody generation, the purity of virus particles prepared by size exclusion is the limitation of this study, and further characterization should be carried out rigorously.
A Cross-Sectional and Longitudinal Analysis of Pre-Diagnostic Blood Plasma Biomarkers for Early Detection of Pancreatic Cancer
Authors: Mason James , Lundberg Erik , Jonsson Pär , Nyström Hanna , Franklin Oskar , Lundin Christina , Naredi Peter , Antti Henrik , Sund Malin , Öhlund Daniel
Published: October 2022

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.
Addressing Noise and Estimating Uncertainty in Biomedical Data through the Exploration of Chemical Space
Authors: deAndrés-Galiana Enrique J. , Fernández-Martínez Juan Luis , Fernández-Brillet Lucas , Cernea Ana , Kloczkowski Andrzej
Published: October 2022

Noise is a basic ingredient in data, since observed data are always contaminated by unwanted deviations, i.e., noise, which, in the case of overdetermined systems (with more data than model parameters), cause the corresponding linear system of equations to have an imperfect solution. In addition, in the case of highly underdetermined parameterization, noise can be absorbed by the model, generating spurious solutions. This is a very undesirable situation that might lead to incorrect conclusions. We presented mathematical formalism based on the inverse problem theory combined with artificial intelligence methodologies to perform an enhanced sampling of noisy biomedical data to improve the finding of meaningful solutions. Random sampling methods fail for high-dimensional biomedical problems. Sampling methods such as smart model parameterizations, forward surrogates, and parallel computing are better suited for such problems. We applied these methods to several important biomedical problems, such as phenotype prediction and a problem related to predicting the effects of protein mutations, i.e., if a given single residue mutation is neutral or deleterious, causing a disease. We also applied these methods to de novo drug discovery and drug repositioning (repurposing) through the enhanced exploration of huge chemical space. The purpose of these novel methods that address the problem of noise and uncertainty in biomedical data is to find new therapeutic solutions, perform drug repurposing, and accelerate and optimize drug discovery, thus reestablishing homeostasis. Finding the right target, the right compound, and the right patient are the three bottlenecks to running successful clinical trials from the correct analysis of preclinical models. Artificial intelligence can provide a solution to these problems, considering that the character of the data restricts the quality of the prediction, as in any modeling procedure in data analysis. The use of simple and plain methodologies is crucial to tackling these important and challenging problems, particularly drug repositioning/repurposing in rare diseases.
Microplastic-Induced Oxidative Stress in Metolachlor-Degrading Filamentous Fungus Trichoderma harzianum
Authors: Jasińska Anna , Różalska Sylwia , Rusetskaya Volha , Słaba Mirosława , Bernat Przemysław
Published: October 2022

While there has been intensive research on the influence of microplastics (MPs) on aquatic organisms and humans, their effect on microorganisms is relatively little-known. The present study describes the response of the Trichoderma harzianum strain to low-density polyethylene (LDPE) microparticles. MPs, either separately or with metolachlor (MET), were added to the cultures. Initially, MP was not found to have a negative effect on fungal growth and MET degradation. After 72 h of cultivation, the content of fungal biomass in samples with MPs was almost three times higher than that in the cultures without MPs. Additionally, a 75% degradation of the initial MET was observed. However, due to the qualitative and quantitative changes in individual classes of phospholipids, cell membrane permeability was increased. Additionally, MPs induced the overproduction of reactive oxygen species. The activity of superoxide dismutase and catalase was also increased in response to MPs. Despite these defense mechanisms, there was enhanced lipid peroxidation in the cultures containing the LDPE microparticles. The results of the study may fill the knowledge gap on the influence of MPs on filamentous fungi. The findings will be helpful in future research on the biodegradation of contaminants coexisting with MPs in soil.
Multiple 17-OHP Cutoff Co-Variates Fail to Improve 21-Hydroxylase Deficiency Screening Accuracy
Authors: Matharu Preet K. , Held Patrice K. , Allen David B.
Published: October 2022

To improve the positive predictive value (PPV) of newborn screening for 21-hydroxylase deficiency (21OHD), co-variates have been used to modify 17-hydroxyprogesterone (17OHP) cutoffs. The objective of this study is to evaluate whether 17OHP screening cutoffs adjusted for both collection time (CT) and birth weight (BW) improved the sensitivity and PPV of 21OHD screening. Unaffected newborn screening samples were stratified based on BW and CT to establish 17OHP concentration cutoffs at the 95th and 99th percentile. These cutoffs were applied to a cohort of confirmed cases of 21OHD to determine the sensitivity and PPV of the modified screening parameters. 17OHP cutoffs at the 99th percentile, adjusted for BW and CT, had a sensitivity of 96.3% and a specificity of 98.9%, but a relatively low PPV (0.130) for the identification of 21OHD and did not detect all cases. Use of the 95th percentile further increased sensitivity to 98.1% but resulted in a notably lower PPV (0.027). Alternative approaches that do not rely exclusively on 17OHP are needed to improve newborn screening accuracy for 21OHD.
Evaluation of Climate Change Resilience of Urban Road Network Strategies
Authors: Begum Siama , Fisher Rachel S. , Ferranti Emma J. S. , Quinn Andrew D.
Published: October 2022

The impacts of the changing climate have caused extensive disruption to the road network in the United Kingdom in recent years. Roads are vital for economic growth and social wellbeing, and a disruption to the network can have disastrous consequences. Since the impacts of climate change will be felt at regional and local levels, it is the responsibility of local highway authorities to establish effective policies to strengthen the resilience of their section of the road network. This report uses the West Midlands as a case study and aims to evaluate its regional highway network management strategies, to determine the extent to which they promote resilience to climate change. Recommendations and findings from other literature are used to establish a set of evaluation criteria to compare the maturity of highway network management strategies for the West Midlands region. The evaluation of the policy documents is used to rank the maturity of the strategies, and recommendations are made to local authorities to highlight where the strategies could be improved. The analysis highlights the fragmentation and disparity between highways strategies across the region and consequently the vulnerability of the region to climate change.
Two New Species of Ripipterygidae (Orthoptera, Tridactyloidea) from Mid-Cretaceous of Myanmar with a Key to the Genera of Tridactyloidea in Amber
Authors: Gu Jun-Jie , Zheng Cheng-Jie , Ren Dong , Cao Cheng-Quan , Yue Yan-Li
Published: October 2022

The abundance of insects in Burmese amber illustrates a highly diverse orthoptera community of the mid-Cretaceous, but the records of ripipterygids are relatively rare. Here, we reviewed the genus of Magnidactylus (Xu, Fang and Jarzembowski, 2020) and transfered it from Tridactylidae to Ripipterygidae. Based on four ambers specimens collected from northern Myanmar, two new species, Magnidactylusmirus sp. nov. and Magnidactylusgracilis sp. nov., wereerected. M.mirus sp. nov. can be characterized by its basal segment and apical segment of paraproctal lobes, which are equally thick and clavate. M.gracilis sp. nov. can be characterized by its apical segment of paraproctal lobes, which are distinctly swollen. Additionally, in order to facilitate the classification of amber specimens of Tridactyloidea, a key to the genera ofambers in this superfamily is provided.
Classification of Stiff-Knee Gait Kinematic Severity after Stroke Using Retrospective k-Means Clustering Algorithm
Authors: Chantraine Frédéric , Schreiber Céline , Pereira José Alexandre Carvalho , Kaps Jérôme , Dierick Frédéric
Published: October 2022

Nowadays, a classification system for unilateral stiff-knee gait (SKG) kinematic severity in hemiparetic adult patients after stroke does not exist. However, such classification would be useful to the clinicians. We proposed the use of the k-means method in order to define unilateral SKG severity clusters in hemiparetic adults after stroke. A retrospective k-means cluster analysis was applied to five selected knee kinematic parameters collected during gait in 96 hemiparetic adults and 19 healthy adults from our clinical gait analysis database. A total of five discrete knee kinematic clusters were determined. Three clusters of SKG were identified, based on which a three-level severity classification was defined: unbend-knee gait, braked-knee gait, and frozen-limb gait. Preliminary construct validity of the classification was obtained. All selected knee kinematic parameters defining the five clusters and the majority of usual kinematic parameters of the lower limbs showed statistically significant differences between the different clusters. We recommend diagnosing SKG for values strictly below 40° of knee flexion during the swing phase. Clinicians and researchers are now able to specify the level of kinematic severity of SKG in order to optimize treatment choices and future clinical trial eligibility criteria.
Modulation of Central Nociceptive Transmission by Manual Pressure Techniques in Patients with Migraine: An Observational Study
Authors: De Hertogh Willem , Amons Andreas , Van daele Lise , Vanbaelen Ellen , Castien René
Published: October 2022

Background: Manual pressure in the upper cervical spine is used to provoke and reduce the familiar migraine headache. Information is scarce on the segmental levels, myofascial structure provocation, and reduction occurrences. The required dosage (amount of pressure, number of repetitions, and duration) has not been objectified yet. Methods: Prospective observational study. Thirty patients with migraine were examined interictally. Manual pressure was applied at four sites: the posterior arch of C1, the articular pillar of C2, the rectus capitis posterior major muscle, and the obliquus capitis inferior muscle, bilaterally. On sites where the familiar headache was provoked, the pressure was sustained to induce pain reduction (three repetitions). Provocation of familiar headache (yes/no), headache intensity (numerical pain rating scale), time to obtain a reduction of the headache (seconds), and applied pressure (g/cm2) were recorded. Results: Provocation of the familiar headache occurred at the posterior arches C1 in 92%, and at one of the articular pillars of C2 in 65.3% of cases. At one of the rectus capitis major muscles, the familiar headache was provoked in 84.6% of cases; at one of the oblique capitis inferior muscles, the familiar headache was provoked in 76.9% of cases. The applied mean pressure ranged from 0.82 to 1.2 kg/cm2. Maintaining the pressure reduced headache pain intensity significantly between the start and end of each of the three consecutive trials (p < 0.04). This reduction occurred faster in the third application than in the first application (p = 0.03). Conclusion: Manual pressure at upper cervical segments provokes familiar referred migraine headaches, with low manual pressure. Maintaining the pressure reduces the referred head pain significantly, indicating modulation of central nociceptive transmission.
Primary Aldosteronism Masked by Accessory Renal Arteries: A Case Report
Authors: Yang Changqiang , Yang Xiangyu , Wang Si , Chen Xiaoping , Liu Kai
Published: October 2022

Primary aldosteronism (PA) is the most frequent form of secondary endocrine hypertension, which is characterized by excessive aldosterone secretion and suppressed renin. The currently recommended diagnostic algorithm is very clear, and the plasma aldosterone-to-renin ratio (ARR) is considered the first-line screening test. However, this indicator is influenced by many factors, some of which may cause false-negative results, consequently leading to underdiagnosed PA. Here, we report the rare case of a 38-year-old man who presented with bilateral accessory renal arteries and aldosterone-producing adenoma but had a negative ARR test result.
Do Comorbidities and Daily Medication before SARS-CoV-2 Infection Play a Role in Self-Reported Post-Infection Symptoms?
Authors: Važgėlienė Dovilė , Kubilius Raimondas , Bileviciute-Ljungar Indre
Published: October 2022

This study investigated the associations between health status before SARS-CoV-2 infection and persistent symptoms after acute infection. Data were collected from participants older than 18 years and more than 28 days after acute SARS-CoV-2 infection using an online survey. Sociodemographic data, comorbidities, and daily medication before infection, as well as acute and persistent symptoms were analysed. Among the 1050 participants (mean age 41 years, 88% women, 56% with higher education, 93% working), 538 (51%) reported being healthy and 762 (73%) reported not taking any daily medication prior to infection. Positive laboratory testing was reported by 965 (92%) participants; asymptomatic infection was reported by 30 (3%); and 999 (95%) stayed at home during their acute infection. Reduced physical capacity (40%), fatigue (39%), cognitive difficulties (30–34%), altered sense of smell (24%), headache (20%), tachycardia (20%), unstable mood (19%), hair loss (17%), and insomnia (17%) were the most often reported symptoms. Those taking daily medication before infection reported increased frequency of both acute and persistent symptoms, except for decreased frequency of persistent altered smell and taste. The presence of persistent symptoms was predicted by taking daily medication before infection and by the total number of acute symptoms. Comorbidities before infection did not predict persistent symptoms. Therefore, the role of medication needs further investigation in both acute SARS-CoV-2 infection and post-COVID-19 condition.
The Role of Interventional Radiology in the Diagnosis and Treatment of Pulmonary Arteriovenous Malformations
Authors: Yap Chee Woei , Wee Bernard B. K. , Yee Sze Ying , Tiong Vincent , Chua Yi Xiu , Teo Lycia , Lohan Rahul , Tan Amos , Singh Pavel , Rajendran Prapul Chander , Yang Cunli , Yee Yong Chen , Anil Gopinathan , Ong Shao Jin
Published: October 2022

Pulmonary arteriovenous malformations (PAVMs) are uncommon, predominantly congenital direct fistulous connections between the pulmonary arteries and pulmonary veins, resulting in a right to left shunt. Patients with PAVMs are usually asymptomatic with lesions detected incidentally when radiological imaging is performed for other indications. In this review, we discuss the classification and radiological features of PAVMs as well as their treatment and follow-up options, with a particular focus on percutaneous endovascular techniques and the evolution of the available equipment for treatment.
Point Shear Wave Elastography in Diagnosis and Follow-Up of Salivary Gland Affection after Head and Neck Cancer Treatment
Authors: Hofauer Benedikt , Roth Andreas , Heiser Clemens , Schukraft Johannes , Johnson Felix , Zhu Zhaojun , Knopf Andreas
Published: October 2022

Therapies of head and neck squamous cell carcinoma (HNSCC), particularly irradiation and chemotherapy (C/RT), can affect salivary glands to some extent. Recent studies suggest that point shear wave elastography (pSWE) is well suited for the diagnosis and rating of homogenous damage to parenchymatous organs. The purpose of this study was to assess the value of this sonographic modality as a tool for the evaluation both of salivary gland affection after HNSCC therapy and the effect of a salivary replacement therapy based on liposomes. A total of 69 HNSCC patients were included in this study. All patients had finished cancer treatment and attended regular follow-up. pSWE values of ipsi- and contralateral parotid (PG) and submandibular glands (SMG) were obtained in a standardized manner and compared to those of a healthy control (HC) group. After a two months treatment with a liposomal saliva replacement therapy pSWE quantification was performed again. Ipsi- and contralateral salivary glands suffer under standard HNSCC tumor therapy. Here, the ipsilateral parotid gland (PG) is primarily affected. Therefore, a sequence of manifestation (surgery < surgery plus adjuvant C/RT < primary C/RT) is comprehensible, evaluated by pSWE measurements. The examination of all glands and statistical analysis of the values compared to controls resulted in an pSWE cutoff value for affected glandular tissue of >2 m/s. Using a liposomal saliva replacement therapy, pSWE values of the ipsilateral PG can be improved, although the level of HC could not be restored.
Temple Syndrome: Clinical Findings, Body Composition and Cognition in 15 Patients
Authors: Juriaans Alicia F. , Kerkhof Gerthe F. , Mahabier Eva F. , Sas Theo C. J. , Zwaveling-Soonawala Nitash , Touwslager Robbert N. H. , Rotteveel Joost , Hokken-Koelega Anita C. S.
Published: October 2022

Background: Temple syndrome (TS14) is an imprinting disorder caused by a maternal uniparental disomy of chromosome 14 (UPD(14)mat), paternal deletion of 14q32 or an isolated methylation defect of the MEG3-DMR. Studies on phenotypical characteristics in TS14 are scarce and patients with TS14 often experience delay in diagnosis, which has adverse effects on their health. TS14 is often characterized as either Prader–Willi-like, Silver–Russell-like or as a Silver–Russell spectrum disorder. Methods: This study describes 15 patients with TS14 who visited the Dutch Reference Center for Prader–Willi-like from December 2018 to January 2022. Results: Eight patients had UPD(14)mat and seven a methylation defect. The most common symptoms were intra-uterine growth retardation (IUGR) (100%), hypotonia (100%), precocious puberty (89%), small for gestational age (SGA) birth (67%), tube feeding after birth (53%) and psycho-behavioral problems (53%). Median (interquartile range (IQR)) IQ was 91.5 (84.25; 100.0), whilst many patients were enrolled in special education (54%). The median (IQR) fat mass % (FM%) SDS was 2.53 (2.26; 2.90) and lean body mass (LBM) SDS −2.03 (−3.22; −1.28). There were no significant differences in clinical characteristics between patients with a UPD(14)mat and a methylation defect. Conclusions: Our patients share a distinct phenotype consisting of IUGR, SGA birth, precocious puberty, hypotonia, tube feeding after birth, psycho-behavioral problems and abnormal body composition with a high FM% and low LBM. Whilst similarities with Prader–Willi syndrome (PWS) and Silver–Russell syndrome (SRS) exist, TS14 is a discernible syndrome, deserving a tailored clinical approach. Testing for TS14 should be considered in patients with a PWS or SRS phenotype in infancy if PWS/SRS testing is negative.
Elevated Level of Serum Neurotrophin-4, but Not of Brain-Derived Neurotrophic Factor, in Patients with Chronic Kidney Disease-Associated Pruritus
Authors: Wala-Zielińska Kamila , Świerczyńska-Mróz Karolina , Krajewski Piotr K. , Nowicka-Suszko Danuta , Krajewska Magdalena , Szepietowski Jacek C.
Published: October 2022

Chronic kidney disease-associated pruritus (CKD-aP) is a bothersome condition that occurs in patients with advanced chronic kidney disease (CKD) and severely reduces their quality of life. Recently, much research has focused on the search for markers that are involved in the pathogenesis of CKD-aP and may become a therapeutic target. One of the suggested hypotheses is the increased activation of sensory neurons by molecules such as neurotrophins (NTs). An increased serum concentration of NTs has been demonstrated in pruritic patients, which may suggest their involvement in the pathogenesis of itch. The purpose of this study is to assess the serum concentration of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) in hemodialysis patients. The study enrolled 126 patients undergoing dialysis. Participants were divided into 2 groups: with and without CKD-aP. NRS scale was used to evaluate itch severity. Serum levels of NT-4 and BDNF have been assessed using ELISA. The results showed a significantly higher level of NT-4 in the group with pruritus. No significant difference was reported in the serum level of BDNF between the two groups of patients. There was also no correlation between serum NT-4 nor BDNF levels and the severity of pruritus. In summary, NT-4 may play an important role in the pathophysiology of pruritus in dialysis patients. More research is needed to understand the exact mechanism by which NTs influence the pathogenesis of CKD-aP.
The Importance of Monitoring Neurodevelopmental Outcomes for Preterm Infants: A Comparison of the AIMS, GMA, Pull to Sit Maneuver and ASQ-3
Authors: Malak Roksana , Fechner Brittany , Stankowska Marta , Wiecheć Katarzyna , Szczapa Tomasz , Kasperkowicz Joanna , Matthews-Kozanecka Maja , Brzozowska Teresa Matthews , Komisarek Oskar , Daroszewski Przemysław , Samborski Włodzimierz , Mojs Ewa
Published: October 2022

Background: Clinicians and parents should closely monitor the neurodevelopment of very preterm infants. The aim of our study was to compare whether neurodevelopmental assessments completed by parents and those done by specialists yielded similar outcomes. We wanted to check whether the assessments completed by specialists and parents were comparable in outcomes to emphasize the important roles of early assessment of a child and of the parents in their child’s treatment and medical care. Another aim was to check whether or not the pull to sit maneuver from the Neonatal Behavioral Assessment Scale (NBAS) is still a parable item in well-known scales of neurodevelopment. Methods: We assessed 18 preterm neonates in the fourth month of corrected age with scales such as the General Movement Assessment (GMA), the Alberta Infant Motor Scale (AIMS), and the pull to sit maneuver from the NBAS. Finally, we asked parents to complete the Ages and Stages Questionnaire, Third Edition (ASQ-3). Results: We found that the respective assessments completed by specialists and parents are comparable in outcomes. We also found that the pull to sit item from the NBAS was still a valid test since it showed similar findings to those from the AIMS, the GMA, and the ASQ-3. Conclusions: The pull to sit item from the NBAS is an important item for assessment of very preterm infants. Specialists should also take into consideration the input and concerns of parents when planning for treatment and intervention.
Use of the Visceral Adiposity Index as an Indicator of Chronic Kidney Disease in Older Adults: Comparison with Body Mass Index
Authors: Kim Bokun , Kim Gwon-Min , Oh Sechang
Published: October 2022

The visceral adiposity index (VAI) was recently introduced to quantify visceral fat accumulation and dysfunction. This cross-sectional study explored whether the VAI is associated with chronic kidney disease (CKD) in older adults and compared its utility with that of body mass index (BMI) for predicting CKD. In total, 7736 older adults (3479 men and 4257 women) aged ≥ 60 years were divided into normal, mild, and moderate-to-severe CKD groups. Associations of the VAI and BMI with CKD were compared among the groups, and cut-off points for moderate-to-severe CKD (MSCKD) were established. While the VAI could discriminate among all of the groups, the BMI could not. The severity of CKD was more strongly associated with the VAI than BMI. The odds ratios indicated that, in the fully adjusted model, the VAI was a significant predictor of MSCKD in both men and women, while the BMI was a significant predictor only in men. For the VAI, the area under the receiver operating characteristic curve values for men and women were 0.631 (cut-off point: ≥2.993) and 0.588 (≥4.001), compared with 0.555 (≥25.335) and 0.533 (≥24.096) for BMI, respectively. Taken together, the findings suggest that the VAI is associated with CKD and represents a better indicator for the disease than BMI.
Spectrum of Genetic Mutations in Korean Pediatric Acute Lymphoblastic Leukemia
Authors: Yoo Jae Won , Ahn Ari , Lee Jong-Mi , Jo Suejung , Kim Seongkoo , Lee Jae Wook , Cho Bin , Kim Yonggoo , Kim Myungshin , Chung Nack-Gyun
Published: October 2022

The wide application of next-generation sequencing (NGS) technologies has led to the discovery of multiple genetic alterations in pediatric acute lymphoblastic leukemia (ALL). In this work, we aimed to investigate the mutational spectrum in pediatric ALL. We employed a St. Mary’s customized NGS panel comprising 67 leukemia-related genes. Samples were collected from 139 pediatric ALL patients. Eighty-five patients (61.2%) harbored at least one mutation. In B-cell ALL, the RAS pathway is the most involved pathway, and the three most frequently mutated genes were NRAS (22.4%), KRAS (19.6%), and PTPN11 (8.4%). NRAS and PTPN11 were significantly associated with a high hyperdiploidy karyotype (p = 0.018 and p < 0.001, respectively). In T-cell ALL, the three most frequently mutated genes were NOTCH1 (37.5%), FBXW7 (16.6%), and PTEN (6.2%). Several pairs of co-occurring mutations were found: NRAS with SETD, NRAS with PTPN11 in B-cell ALL (p = 0.024 and p = 0.020, respectively), and NOTCH1 with FBXW7 in T-cell ALL (p < 0.001). The most frequent newly emerged mutation in relapsed ALL was NT5C2. We procured comprehensive genetic information regarding Korean pediatric ALL using NGS technology. Our findings strengthen the current knowledge of recurrent somatic mutations in pediatric ALL.
Risk Factors for Maxillary Sinus Pathology after Surgery for Midfacial Fracture: A Multivariate Analysis
Authors: Jiang Linli , Wu Mengsong , Li Hui , Liang Jiayu , Chen Jinlong , Liu Lei
Published: October 2022

This study aimed to determine the incidence of maxillary sinus pathology in patients with a midfacial fracture who underwent osteosynthesis surgery and evaluate the associated risk factors. We conducted a retrospective case-control analysis of patients with midfacial fractures involving a maxillary sinus wall who were treated with open reduction and internal fixation (ORIF) between January 2015 and December 2020. Fracture reduction, the number of screws implanted in the maxillary sinus, and the number of screws penetrating the maxillary sinus, etc., were examined as potential risk factors. Maxillary sinus pathology on postoperative CT was considered the primary outcome for case-control analysis. Binary logistic regression was used to identify variables associated with postoperative maxillary sinus pathology. Thereafter, propensity score matching (PSM) was used to extract confounding factors. A total of 262 patients (totaling 372 maxillary sinuses) were included for analysis. PSM yielded 178, 246, and 70 matched sinuses, respectively, depending on the potential risk factors. Postoperative maxillary sinus pathology was visualized in 218 of the 372 maxillary sinuses (58.60%). The risk factors for postoperative maxillary sinus pathology included the number of screws penetrating the maxillary sinus (odds ratio (OR), 1.124; p = 0.007), an imperfect maxillary sinus wall fracture reduction (OR, 2.901; p = 0.021), and the number of sinus walls involved (OR, 1.383; p = 0.011). After PSM, postoperative maxillary sinus pathology was still more prevalent in sinuses with multiple maxillary sinus wall fractures (64.04% vs. 48.31%, p = 0.034), sinuses with more screws penetrating the maxillary sinus (64.23% vs. 50.41%, p = 0.028), and sinuses with an imperfect reduction (80% vs. 51.43%, p = 0.012). In conclusion, maxillary sinus pathology is common after the ORIF of midfacial fractures. Patients with a fracture of multiple maxillary sinus walls require a close follow-up. Screw penetration of the maxillary sinus should be avoided to prevent maxillary sinus pathology after a midfacial fracture ORIF.
Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring
Authors: Gebreyesus Tigist Dires , Makonnen Eyasu , Tadele Tafesse , Gashaw Habtamu , Degefe Workagegnew , Gerba Heran , Tadesse Birkneh Tilahun , Gurumurthy Parthasarathi , Aklillu Eleni
Published: October 2022

Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5–15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5–14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ2 = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas.
Clinical Utility of Three-Dimensional Speckle-Tracking Echocardiography in Heart Failure
Authors: Gao Lang , Lin Yixia , Ji Mengmeng , Wu Wenqian , Li He , Qian Mingzhu , Zhang Li , Xie Mingxing , Li Yuman
Published: October 2022

Heart failure (HF) is an extremely major health problem with gradually increasing incidence in developed and developing countries. HF may lead to cardiac remodeling; thus, advanced imaging techniques are required to comprehensively evaluate cardiac mechanics. Recently, three-dimensional speckle-tracking echocardiography (3D-STE) has been developed as a novel imaging technology that is based on the three-dimensional speckle-tracking on the full volume three-dimensional datasets. Three-dimensional speckle-tracking echocardiography allows a more accurate evaluation of global and regional myocardial performance, assessment of cardiac mechanics, detection of subclinical cardiac dysfunction, and prediction of adverse clinical events in a variety of cardiovascular diseases. Therefore, this review summarizes the clinical usefulness of 3D-STE in patients with HF.
Galectin-1: A Potential Biomarker Differentiating between Early Rheumatoid Arthritis and Spondyloarthritis
Authors: Triguero-Martínez Ana , Roy-Vallejo Emilia , Tomero Eva Gloria , Montes Nuria , Fuente Hortensia de la , Ortiz Ana María , Castañeda Santos , Lamana Amalia , González-Álvaro Isidoro
Published: October 2022

Galectin-1 (Gal1) plays a regulatory role in the immune system. We have recently validated that Gal1 serum (sGal1) levels are increased in rheumatoid arthritis (RA) patients compared to healthy donors (HDs); however, there is no information on Gal1 in spondyloarthritis (SpA). Objective: To compare Gal1 levels in patients with SpA versus RA as a diagnostic biomarker. Methods: We studied sGal1 levels in HD (n = 52), SpA (n = 80) and RA patients (n = 64) who were randomly divided into discovery and validation sets. Synovial fluid (SF) from osteoarthritis (OA) (n = 28), peripheral SpA (n = 28) and RA (n = 28) were studied. In SpA patients, we analyzed the association between clinical parameters and sGal1 levels. Results: sGal1 levels were significantly lower in patients with SpA with respect to RA and similar to those of the HD. A cut-off of 20.50 ng/mL (sGal1) allowed one to differentiate RA patients from SpA and HD (Odd Ratio (OR) 8.23 and 12.64, respectively). Gal1 SF levels in SpA were slightly lower than OA patients and significantly lower than RA patients. No correlation was observed between sGal1 levels and clinical parameters in SpA patients. Conclusion: Gal1 could act as a diagnostic biomarker of RA and would allow one to distinguish SpA and RA patients.
Association of Clinical Features with Spike Glycoprotein Mutations in Iranian COVID-19 Patients
Authors: Ahangarzadeh Shahrzad , Yousefi Alireza , Ranjbar Mohammad Mehdi , Dabiri Arezou , Zarepour Atefeh , Sadeghi Mahmoud , Heidari Elham , Mazrui Fariba , Hosseinzadeh Majid , Ataei Behrooz , Zarrabi Ali , Shariati Laleh , Haghjooy Javanmard Shaghayegh
Published: October 2022

Background: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. Methods: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient’s reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. Results: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. Conclusions: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease.
Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
Authors: Nuchjumroon Almas , Vadcharavivad Somratai , Singhan Wanchana , Poosoonthornsri Manorom , Chancharoenthana Wiwat , Udomkarnjananun Suwasin , Townamchai Natavudh , Avihingsanon Yingyos , Praditpornsilpa Kearkiat , Eiam-Ong Somchai
Published: October 2022

A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, were enrolled in this retrospective cohort study. Genotyping of CYP3A5*3 (rs776746) was performed and 110 (58.5%) were identified as CYP3A5 expressers and 78 (41.5%) as nonexpressers. Whole blood tacrolimus concentrations were analyzed by chemiluminescent microparticle immunoassay. Dose-adjusted trough tacrolimus concentrations (C0/D) measured at months 6, 9, and 12 were used to determine IPV. There were no significant differences in the IPV estimated by the coefficient of variation, the IPV calculated by mean absolute deviation method, and the proportions of recipients with the IPV estimated by the coefficient of variation of 30% or more between CYP3A5 expressers and nonexpressers (p = 0.613, 0.686, and 0.954, respectively). Tacrolimus C0/D in CYP3A5 expressers was approximately half of those in nonexpressers, overall (p < 0.001). In both CYP3A5 expressers and nonexpressers, tacrolimus C0/D increased gradually from month 6 to month 12 (p = 0.021). There was no evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 months after kidney transplantation.
Cardiac Implantable Electronic Devices Breakthrough: Are We Ready to Face the Future?
Authors: Mitacchione Gianfranco
Published: October 2022

Since its inception cardiac electrical therapy has evolved, with transvenous pacemakers (PMs) and implantable cardiac defibrillators (ICDs) providing significant benefits in terms of improved quality of life and reducing mortality in patients with cardiac conduction disturbances and/or requiring protection against ventricular arrhythmias [...]
Two-Dimensional Graphitic Carbon Nitride (g-C3N4) Nanosheets and Their Derivatives for Diagnosis and Detection Applications
Authors: Pourmadadi Mehrab , Rajabzadeh-Khosroshahi Maryam , Saeidi Tabar Fatemeh , Ajalli Narges , Samadi Amirmasoud , Yazdani Mahsa , Yazdian Fatemeh , Rahdar Abbas , Díez-Pascual Ana M.
Published: October 2022

The early diagnosis of certain fatal diseases is vital for preventing severe consequences and contributes to a more effective treatment. Despite numerous conventional methods to realize this goal, employing nanobiosensors is a novel approach that provides a fast and precise detection. Recently, nanomaterials have been widely applied as biosensors with distinctive features. Graphite phase carbon nitride (g-C3N4) is a two-dimensional (2D) carbon-based nanostructure that has received attention in biosensing. Biocompatibility, biodegradability, semiconductivity, high photoluminescence yield, low-cost synthesis, easy production process, antimicrobial activity, and high stability are prominent properties that have rendered g-C3N4 a promising candidate to be used in electrochemical, optical, and other kinds of biosensors. This review presents the g-C3N4 unique features, synthesis methods, and g-C3N4-based nanomaterials. In addition, recent relevant studies on using g-C3N4 in biosensors in regard to improving treatment pathways are reviewed.
A Novel Approach to Treat a Rare Case of Interprosthetic Humeral Fracture with Osteosynthesis and Combined Grafting: A Case Report and Review of the Literature
Authors: Marzano Fabrizio , Pace Valerio , Donantoni Marco , Petruccelli Rosario , Ceccarini Paolo , Caraffa Auro , Di Giacomo Lorenzo Maria
Published: October 2022

Interprosthetic humeral fractures (IHFs) are severe injury patterns associated with surgical issues and contradictory results. The knowledge and literature on this topic are still lacking. A 76 year-old woman was treated for a fracture occurred between the shoulder and elbow stemmed prosthesis. Severe bone loss was associated with the fracture. Treatment: Open reduction, plate fixation, and bone grafting were considered. A xenograft (used as a mechanical strut medially), a synthetic graft associated with bone growth factors, and scaffolds improved the bone healing process. Satisfactory clinical and radiological outcomes were obtained. A scoping review of the literature was also performed by the authors. Only eight papers reported IHFs with a low level of evidence. In total, eight patients were treated; one paper that reported on biomechanical aspects using finite element analysis is discussed. Conservative treatment leads to non-union, and the surgical approach is the gold standard. The osteosynthesis technique associated with bone grafting leads to the best outcomes. The use of a xenograft mechanical strut, associated with synthetic biological bone grafting, led to complete bone union at 9 months follow-up. Larger cohorts, more standardised results, and multicentric studies are mandatory in order to improve and establish a management and treatment algorithm.
Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections
Authors: Angulo David A. , Alexander Barbara , Rautemaa-Richardson Riina , Alastruey-Izquierdo Ana , Hoenigl Martin , Ibrahim Ashraf S. , Ghannoum Mahmoud A. , King Thomas R. , Azie Nkechi E. , Walsh Thomas J.
Published: October 2022

Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician’s armamentarium against these difficult-to-treat infections.