bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oscillometric evaluation of the effects of cardiotoxic chemotherapeutic agents on vascular stiffness
Authors: Kertmen Omer , Gulel Okan , Demirag Guzin , Ozatli Duzgun 
Published: March 2022

Aim
Several clinical studies have demonstrated that arterial stiffness is an early indicator of cardiovascular events. Our study aimed to detect the potential cardiovascular changes using arterial stiffness parameters and compare these changes with echocardiographic aortic stiffness parameters, in cancer patients treated with cardiotoxic chemotherapeutics.

Methods and Results
Our study is a prospective case-control study. A total of seventy subjects between the ages of 18 and 50 years were included into our study. Thirty of them were newly diagnosed cancer patients and forty constituted the age- and sex-matched control group. Baseline oscillometric arterial and echocardiographic aortic stiffness parameters were measured in all patients. In cancer patients, all of these parameters were measured again, 1 month after chemotherapy protocol was completed. Mean age of the cancer patients was 41.4 ± 5.9 years and mean age of the control group was 39.6 ± 6.6 years (P = 0.258). Before chemotherapy, arterial and aortic stiffness parameters were similar between the study and the control group. After chemotherapy, the oscillometric pulse wave velocity parameter increased compared with the control group and to the prechemotherapy values (P = 0.004 and P < 0.001, respectively). After chemotherapy, the augmentation index parameter increased compared with the control group (P = 0.013). On the other hand, no difference was detected between the groups in terms of echocardiographic aortic stiffness parameters.

Conclusion
In newly diagnosed cancer patients treated with cardiotoxic chemotherapeutics, considerable impairment occurs in some of the oscillometric arterial stiffness parameters, while there is no substantial effect on echocardiographic aortic stiffness. Arterial stiffness parameters in these patients might be useful in evaluating subclinical cardiovascular damage.
Expression of serum long noncoding RNA FAM99A in patients with hypertensive disorder complicating and its clinical significance
Authors: Ge Qiuyan , Zhao Ju , Qu Fujuan 
Published: March 2022

Objective
Hypertensive disorder complicating pregnancy (HDCP) consists of various heterogeneous conditions. Long noncoding RNAs (LncRNA) FAM99A is implicated in HDCP diagnosis. This study discussed the diagnostic efficiency of lncRNA FAM99A in HDCP.

Methods
Totally 130 singleton HDCP patients including 50 patients of gestation hypertension (GH), 44 of mild preeclampsia (mPE), and 36 of severe preeclampsia (sPEz) were enrolled, with 70 healthy pregnant women as the control. Serum lncRNA FAM99A expression was detected and its diagnostic efficiency in HDCP was analyzed using the receiver operating characteristic curve. The influencing factors of PE grade were analyzed using the logistic regression model.

Results
Serum lncRNA FAM99A was downregulated in HDCP patients. The SBP/DBP, 24-h urinary protein, and serum creatinine (SCr), AST and ALT contents were elevated, and platelet count (PLT) was diminished in HDCP patients. Relative to the high-expression group, SBP/DBP, 24-h urinary protein, SCr, AST, and ALT contents were raised, and PLT was lowered in the low-expression group. The area under curve of lncRNA FAM99A for HDCP diagnosis was 0.9514, and the cutoff value was 0.8450, with 83.85% sensitivity and 94.29% specificity. LncRNA FAM99A expression was downregulated in the GH group, then mPE group, and sPEz group the least. LncRNA FAM99A had diagnostic efficiency for GH and mPE, and mPE and sPEz. DBP, urinary protein, PLT, and lncRNA FAM99A were independent risk factors for PE severity.

Conclusion

LncRNA FAM99A was diminished in HDCP patients and was related to HDCP severity, which might be used as a potential diagnostic marker of HDCP.
Gender differences in the associations of circulating erythrocytes and hemoglobin with hypertension risk
Authors: Liu Dong , Wang Cuicui , Zhang Ya , Zuo Hui 
Published: March 2022

Objective
Studies on associations of erythrocytes parameters with hypertension risk are scarce. We aimed to examine associations of the erythrocytes parameters with the hypertension risk and potential effect modification by gender using data from the China Health and Nutrition Survey.

Methods
A total of 5419 eligible participants (2468 men, 45.5%) without hypertension at baseline in 2009 were included and followed for a median of 6.1 years. Parameters of erythrocytes and hemoglobin were measured at baseline. Multivariable Cox proportional hazards models were used to estimate the hazard ratio for the associations between these parameters and hypertension risk. Data were collected from 2009 to 2015 and analyzed in 2021.

Results
A total of 1178 incident cases of hypertension were identified during the follow-up. In women, erythrocytes and hemoglobin were positively associated with risk of hypertension, yielding the highest hazard ratio in the third quartile of 1.59 (95% confidence interval, 1.28–1.97, P trend < 0.001) for erythrocytes and in the fourth quartile of 1.64 (95% confidence interval, 1.23–2.17, P trend < 0.001) for hemoglobin compared with their first quartile, respectively. In addition, quartiles of erythrocytes and hemoglobin were not associated with risk of hypertension in men (P trend > 0.050).

Conclusion
Erythrocytes and hemoglobin were associated with an increased risk of hypertension in women, but not in men. Our findings suggest that special attention for the prevention of hypertension should be given to those women with the moderate to high level of circulating erythrocytes and higher level of hemoglobin.
Validation of the G.LAB MD41A0 upper arm blood pressure monitor in patients with diabetes mellitus according to the AAMI/ESH/ISO 81060-2:2018 Universal Standard
Authors: Li Lin-Yi , Tian Li , Gao Bin , Ming Jie , Liu Kui , Jiang Jun , Han Zheng-Yuan , Zhao Lu-Yang , Chen Chang-Sheng , Wan Yi 
Published: March 2022

Objective
The objective of this study is to determine the accuracy of the G.LAB MD41A0 upper-arm oscillometric blood pressure (BP) monitor for self/home BP measurement in patients with diabetes according to the Association for the Advancement of Medical Instrumentation /European Society of Hypertension /International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018).

Methods
Patients with diabetes were recruited according to AAMI/ESH/ISO Universal Standard using the same arm sequential BP measurement method. The standard cuff of the test device was used for arm circumference 22–44 cm.

Results
A total of 92 patients with diabetes were recruited and 85 were analyzed with an average age of 55.1 ± 17.7 years, 48 men, and arm circumference of 32.0 ± 6.0 cm. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 0.89 ± 6.04/−0.84 ± 5.11 mmHg (systolic/diastolic). For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 4.23/4.19 mmHg (systolic/diastolic).

Conclusion
The G.LAB MD41A0 upper arm BP monitor fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in patients with diabetes and can be recommended for self/home use.
Asthma diagnosis using patient-reported outcome measures and objective diagnostic tests: now and into the future
Authors: Nawaz Safia F. , Ravindran Mayuran , Kuruvilla Merin E. 
Published: March 2022

Purpose of review
The global prevalence of asthma continues to increase; however, asthma remains under-diagnosed and under-treated. This results in a significant burden on the healthcare system and preventable patient morbidity and mortality. Over-diagnosis of asthma based on clinical history alone also complicates patient management. This heightens the importance of a prompt and accurate asthma diagnosis. Therefore, a review of the literature was performed regarding both objective diagnostic testing for asthma and using patient-reported outcome measures.

Recent findings
The cornerstone of asthma diagnosis remains spirometry with testing for bronchodilator reversibility testing for pediatric and adult populations. This test may need to be repeated at multiple time points due to its low sensitivity. Peak flow measurement, fractional exhaled nitric oxide testing, and allergy testing are useful adjuncts to the diagnosis and phenotyping of asthma. Bronchoprovocation testing is reserved for people with high clinical suspicion for asthma, but negative spirometry. Novel noninvasive testing modalities may play a diagnostic role in the future. The advent of remote digital health monitoring technology has resulted in revisiting patient-reported outcome measures for the diagnosis and monitoring of asthma.

Summary
Overall, improved diagnostic tools for asthma are crucial for earlier recognition and treatment of the disease and improved patient care outcomes worldwide.
Optimized cocktail of 90Y/177Lu for radionuclide therapy of neuroendocrine tumors of various sizes: a simulation study
Authors: Peer-Firozjaei Milad , Tajik-Mansoury Mohammad Ali , Geramifar Parham , Ghorbani Raheb , Zarifi Shiva , Miller Cassandra , Rahmim Arman 
Published: March 2022

Background and objectives
There is significant interest and potential in the treatment of neuroendocrine tumors via peptide receptor radionuclide therapy (PRRT) using one or both of 90Y and 177Lu-labeled peptides. Given the presence of different tumor sizes in patients and differing radionuclide dose delivery properties, the present study aims to use Monte Carlo simulations to estimate S-values to spherical tumors of various sizes with 90Y and 177Lu separately and in combination. The goal is to determine ratios of 90Y to 177Lu that result in the largest absorbed doses per decay of the radionuclides and the most suitable dose profiles to treat tumors of specific sizes.

Material and methods
Particle transfer calculations and simulations were performed using the Monte Carlo GATE simulation software. Spherical tumors of different sizes, ranging from 0.5 to 20 mm in radius, were designed. Activities of 177Lu and 90Y, individually and in combination, were homogeneously placed within the total volume of the tumors. We determined the S-values to the tumors, and to the external volume outside of the tumors (cross-dose) which was used to approximate background tissue. The dose profiles were obtained for each of the different tumor sizes, and the uniformity of dose within each tumor was calculated.

Results
For all tumor sizes, the self-dose and cross-dose per decay from 90Y were higher than that from 177Lu. We observed that 177Lu had the most uniform dose distribution within tumors with radii less than 5 mm. For tumors greater than 5 mm in radius, a ratio of 25% 90Y to 75% 177Lu resulted in the most uniform doses. When the ratio of 177Lu to 90Y was smaller, the uniformity improved more with increasing tumor size. The cross-dose stayed approximately constant for tumors larger than 15 mm for all ratios of 177Lu to 90Y. Finally, as the size of the tumor increased, differences in the S-values between different ratios of 177Lu to 90Y decreased.

Conclusion
Our work showed that to achieve a more uniform dose distribution within the tumor, 177Lu alone is more effective for small tumors. For medium and large tumors, a ratio of 90Y to 177Lu with more or less 177Lu, respectively, is recommended.
Creating a ‘Timeline’ of ductal carcinoma in situ to identify processes and biomarkers for progression towards invasive ductal carcinoma
Authors: Rebbeck Clare A. , Xian Jian , Bornelöv Susanne , Geradts Joseph , Hobeika Amy , Geiger Heather , Alvarez Jose Franco , Rozhkova Elena , Nicholls Ashley , Robine Nicolas , Lyerly Herbert K. , Hannon Gregory J. 
Published: March 2022

ABSTRACTDuctal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive disease is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients and even within patients. Using gene expression analysis, we have generated a ‘Timeline’ of disease progression, utilising the variability within patients and combining >2,000 individually micro-dissected ductal lesions from 145 patients into one continuous trajectory. Using this Timeline we show there is a progressive loss in basal layer integrity, coupled with two epithelial to mesenchymal transitions (EMT), one early in the timeline and a second just prior to cells leaving the duct. We identify early processes and potential biomarkers, includingCAMK2N1,MNX1,ADCY5,HOXC11andANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.
A chromosome-level genome assembly enables the identification of the follicle stimulating hormone receptor as the master sex determining gene in Solea senegalensis
Authors: De la Herrán R. , Hermida M. , Rubiolo J. , Gómez-Garrido J. , Cruz F. , Robles F. , Navajas R. , Blanco F. A. , Villamayor P. R. , Torres D. , Sánchez-Quinteiro P. , Ramirez D. , Rodríguez M. E. , Arias-Pérez A. , Cross I. , Duncan N. , Martínez-Peña T. , Riaza A. , Millán A. , Gut M. , Bouza C. , Robledo D. , Rebordinos L. , Alioto T. , Ruíz-Rejón C. , Martínez P. 
Published: March 2022

AbstractSex determination (SD) mechanisms are exceptionally diverse and show high evolutionary rates in fish. Pleuronectiformes is an emblematic fish group characterized by its adaptation to demersal life and its compact genomes. Here, we present a chromosome-level genome assembly of Senegalese sole, a promising European aquaculture species. We combined long- and short-read sequencing and a highly dense genetic map to obtain a contiguous assembly of 613 Mb (N50 = 29.0 Mb, 99% of the assembly in the n = 21 chromosomes of its karyotype). The correspondence between this new assembly and the Senegalese sole chromosomes was established by fluorescence in situ hybridization with BAC probes. Orthology within Pleuronectiformes was assessed by using the chromosome-level genomes of six important commercial flatfishes covering a broad phylogenetic spectrum of the order. A total of 7936 single-gene orthologues, shared by the six species, were used to identify syntenies in Pleuronectiformes and to explore chromosome evolutionary patterns in the order. Whole genome resequencing of six males and six females enabled the identification of 41 fixed allelic variants in the follicle stimulating hormone receptor (fshr) gene, homozygous in females and heterozygous in males, consistent with an XX / XY chromosome system. The observed association between fshr SNPs and sex was confirmed at the species level in a broad sample, which allowed tuning up a molecular sexing tool. Fshr demonstrated differential gene expression between male and female gonads since 86 days post-fertilization, when the gonad was still an undifferentiated primordium, concomitant with the activation of other testis and ovary marker genes, such as amh and cyp19a1a genes, respectively. Interestingly, the Y-linked fshr allele, which included 24 non-synonymous variants, expressed to a higher level than the X-linked allele at all stages. We hypothesize a molecular mechanism hampering the action of the follicle stimulating hormone that would drive the undifferentiated gonad toward testis.
A mechanistic understanding of the modes of Ca ion binding to the SARS-CoV-1 fusion peptide and their role in the dynamics of host membrane penetration
Authors: Carten Juliana Debrito , Khelashvili George , Bidon Miya K. , Straus Marco R. , Tang Tiffany , Jaimes Javier A. , Weinstein Harel , Whittaker Gary R. , Daniel Susan 
Published: March 2022

AbstractThe SARS-CoV-1 spike glycoprotein contains a fusion peptide (FP) segment that mediates fusion of the viral and host cell membranes. Calcium ions are thought to position the FP optimally for membrane insertion by interacting with negatively charged residues in this segment (E801, D802, D812, E821, D825, and D830); however, which residues bind to calcium and in what combinations supportive of membrane insertion are unknown. Using biological assays and molecular dynamics studies, we have determined the functional configurations of FP-Ca+2binding which promote membrane insertion. We first mutated the negatively charged residues in the SARS CoV-1 FP to assay their role in cell entry and syncytia formation, finding that charge loss in the D802A or D830A mutants reduced syncytia formation and pseudoparticle transduction. Interestingly, the D812A mutation led to increased pseudoparticle transduction, indicating the Ca2+effect depends on binding at specific FP sites. To interpret mechanistically these results and learn how specific modes of FP-Ca2+binding modulate membrane insertion, we performed molecular dynamics simulations. Preferred residue pairs for Ca2+binding were identified (E801/D802; E801/D830; D812/E821) which promote FP membrane insertion. In contrast, binding to residues E821/D825 inhibited FP membrane insertion, which is also supported by our biological assays. Our findings show that Ca2+binding to SARS-CoV-1 FP residue pairs E801/D802 and D812/E821 facilitates membrane insertion, whereas binding to the E801/D802 and D821/D825 pairs is detrimental. These conclusions provide an improved and nuanced mechanistic understanding of calcium binding modes to FP residues and their dynamic effects on host cell entry.
The mutational steps of SARS-CoV-2 to become like Omicron within seven months: the story of immune escape in an immunocompromised patient
Authors: Sonnleitner Sissy Therese , Prelog Martina , Sonnleitner Stefanie , Hinterbichler Eva , Halbfurter Hannah , Kopecky Dominik B. C. , Almanzar Giovanni , Koblmüller Stephan , Sturmbauer Christian , Feist Leonard , Horres Ralf , Posch Wilfried , Walder Gernot 
Published: March 2022

ABSTRACTWe studied a unique case of prolonged viral shedding in an immunocompromised patient that generated a series of SARS-CoV-2 immune escape mutations over a period of seven months. During the persisting SARS-CoV-2 infection seventeen non-synonymous mutations were observed, thirteen (13/17; 76.5%) of which occurred in the genomic region coding for spike. Fifteen (15/17; 88.2%) of these mutations have already been described in the context of variants of concern and include the prominent immune escape mutations S:E484K, S:D950N, S:P681H, S:N501Y, S:del(9), N:S235F and S:H655Y. Fifty percent of all mutations acquired by the investigated strain (11/22) are found in similar form in the Omicron variant of concern. The study shows the chronology of the evolution of intra-host mutations, which can be seen as the straight mutational response of the virus to specific antibodies and should therefore be given special attention in the rating of immune escape mutations of SARS-CoV-2.
Remdesivir for the treatment of patients hospitalized with COVID-19 receiving supplemental oxygen: a targeted literature review and meta-analysis
Authors: Beckerman Rachel , Gori Andrea , Jeyakumar Sushanth , Malin Jakob J. , Paredes Roger , Póvoa Pedro , Smith Nate , Teixeira-Pinto Armando 
Published: March 2022

AbstractThis network meta-analysis (NMA) assessed the efficacy of remdesivir in hospitalized patients with COVID-19 requiring supplemental oxygen. Randomized controlled trials of hospitalized patients with COVID-19, where patients were receiving supplemental oxygen at baseline and at least one arm received treatment with remdesivir, were identified. Outcomes included mortality, recovery, and no longer requiring supplemental oxygen. NMAs were performed for low-flow oxygen (LFO2); high-flow oxygen (HFO2), including NIV; or oxygen at any flow (AnyO2) at early (day 14/15) and late (day 28/29) time points. Six studies were included (N=5,245 patients) in the NMA. Remdesivir lowered early and late mortality among AnyO2patients (risk ratio (RR) 0.52, 95% credible interval (CrI) 0.34-0.79; RR 0.81, 95%CrI 0.69-0.95) and LFO2patients (RR 0.21, 95%CI 0.09-0.46; RR 0.24, 95%CI 0.11-0.48); no improvement was observed among HFO2patients. Improved early and late recovery was observed among LFO2patients (RR 1.22, 95%CrI 1.09-1.38; RR 1.17, 95%CrI 1.09-1.28). Remdesivir also lowered the requirement for oxygen support among all patient subgroups. Among hospitalized patients with COVID-19 requiring supplemental oxygen at baseline, use of remdesivir compared to best supportive care is likely to improve the risk of mortality, recovery and need for oxygen support in AnyO2and LFO2patients.
Population-based analysis of radiation-induced gliomas after cranial radiotherapy for childhood cancers
Authors: Leary Jacob B. , Anderson-Mellies Amy , Green Adam L. 
Published: March 2022

AbstractBackgroundCranial radiotherapy (RT) is used to treat pediatric central nervous system (CNS) cancers and leukemias. RT carries a risk of secondary CNS malignancies, including radiation-induced gliomas, the epidemiology of which is poorly understood.MethodsThis retrospective study using SEER registry data (1975-2016) included two cohorts. Cohort 1 included patients diagnosed with Grade III/IV or ungraded glioma as a second malignancy at least 2 years after receiving beam radiation and/or chemotherapy for a first malignancy diagnosed at ages 0-19 years, either a primary CNS tumor treated with RT (1a, n=57) or leukemia with unknown RT treatment (1b, n=20). Cohort 2 included patients with possible missed RIG who received RT for a primary CNS tumor diagnosed at 0-19 and then died of presumed progressive disease more than 5 years after diagnosis, since previous studies have documented many missed RIGs in this group (n=296). Controls (n=10,687) included all other patients ages 0-19 who received RT for a first CNS tumor or leukemia who did not fit inclusion criteria above.ResultsFor Cohort 1 (likely/definite RIGs), 0.97% of patients receiving cranial RT went on to develop RIG. 3.39% of patients receiving cranial RT for primary CNS tumors fell in Cohort 2 (potential RIGs). Median latency to RIG diagnosis was 11.1 years; latency was significantly shorter for Cohort 1b (median 10.0, range 5.0-16.1) vs. 1a (12.0, 3.6-34.4, p=0.018). Median OS for Cohort 1 was 9.0 months. Receiving surgery, radiation, or chemotherapy were all associated with a non-statistically significant improvement in OS (p 0.1-0.2). 1.8% of brain tumor deaths in the cohort fell in Cohort 1, with an additional 7.9% in Cohort 2.ConclusionWithin the limitations of a population-based study, 1-4% of patients undergoing cranial RT for pediatric cancers later develop RIG, which is incurable and can occur anywhere from 3-35 years later. 2-10% of pediatric brain tumor deaths are attributable to RIG. Effective treatment of RIG remains unclear and is thus deserving of increased attention in preclinical and clinical studies.