bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy
Authors: Stampone Emanuela , Bencivenga Debora , Capellupo Maria Chiara , Roberti Domenico , Tartaglione Immacolata , Perrotta Silverio , Della Ragione Fulvio , Borriello Adriana 
Published: July 2023

AbstractThe precise characterization of oxygen-sensing pathways and the identification of pO2-regulated gene expression are both issues of critical importance. The O2-sensing system plays crucial roles in almost all the pivotal human processes, including the stem cell specification, the growth and development of tissues (such as embryogenesis), the modulation of intermediate metabolism (including the shift of the glucose metabolism from oxidative to anaerobic ATP production and vice versa), and the control of blood pressure. The solid cancer microenvironment is characterized by low oxygen levels and by the consequent activation of the hypoxia response that, in turn, allows a complex adaptive response characterized mainly by neoangiogenesis and metabolic reprogramming. Recently, incredible advances in molecular genetic methodologies allowed the genome editing with high efficiency and, above all, the precise identification of target cells/tissues. These new possibilities and the knowledge of the mechanisms of adaptation to hypoxia suggest the effective development of new therapeutic approaches based on the manipulation, targeting, and exploitation of the oxygen-sensor system molecular mechanisms.
Immune checkpoint inhibitor treatment of brain metastasis associated with a less invasive growth pattern, higher T-cell infiltration and raised tumor ADC on diffusion weighted MRI
Authors: Zakaria Rasheed , Jenkinson Michael D. , Radon Mark , Das Kumar , Poptani Harish , Rathi Nitika , Rudland Philip S. 
Published: July 2023

Abstract
Background
Brain metastases are the most common intracranial tumors with an increasing incidence. They are an important cause of morbidity and mortality in patients with solid organ cancer and a focus of recent clinical research and experimental interest. Immune checkpoint inhibitors are being increasingly used to treat solid organ cancers.

Methods
To determine whether immune checkpoint inhibitors were biologically effective in the brain, we compared melanoma brain metastasis samples where treatment with ipilimumab had occurred preoperatively to those who had not received any immune modulating therapy and looked for histopathological (invasion, vascularity, metastasis inducing proteins, matrix metalloproteinases, immune cell infiltration, tissue architecture) and advanced MRI differences (diffusion weighted imaging).

Results
Co-localized tissue samples from the same regions as MRI regions of interest showed significantly lower vascularity (density of CD34 + vessels) in the core and higher T-cell infiltration (CD3 + cells) in the leading edge for ipilimumab-treated brain metastasis samples than for untreated cases and this correlated with a higher tumor ADC signal at post-treatment/preoperative MRI brain.

Conclusions
Treatment of a melanoma brain metastasis with ipilimumab appears to cause measurable biological changes in the tumor that can be correlated with post-treatment diffusion weighted MRI imaging, suggesting both a mechanism of action and a possible surrogate marker of efficacy.
Poor outcome of allogeneic transplantation for therapy-related acute myeloid leukemia induced by prior chemoradiotherapy
Authors: Araie Hiroaki , Arai Yasuyuki , Kida Michiko , Aoki Jun , Uchida Naoyuki , Doki Noriko , Fukuda Takahiro , Tanaka Masatsugu , Ozawa Yukiyasu , Sawa Masashi , Katayama Yuta , Matsuo Yayoi , Onizuka Makoto , Kanda Yoshinobu , Kawakita Toshiro , Kanda Junya , Atsuta Yoshiko , Yanada Masamitsu ,   for the Adult Acute Myeloid Leukemia Working Group of the Japanese Society for Transplantation and Cellular Therapy
Published: July 2023

AbstractTherapy-related acute myeloid leukemia (t-AML) is a therapeutic challenge as a late complication of chemotherapy (CHT) and/or radiotherapy (RT) for primary malignancy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) presents itself as a curative approach. To establish the optimal allo-HSCT strategy for t-AML, we evaluated the relationship between characteristics of primary malignancy and allo-HSCT outcomes. Patients with t-AML or de novo acute myeloid leukemia (AML) who underwent first allo-HSCT in Japan from 2011 to 2018 were identified using a nationwide database. The detailed background of t-AML was obtained by additional questionnaires. Multivariate analysis and propensity score matching (PSM) analysis were performed to detect the prognostic factors associated with t-AML and compare outcomes with de novo AML. We analyzed 285 t-AML and 6761 de novo AML patients. In patients with t-AML, receiving both CHT and RT for primary malignancy was an independent poor-risk factor for relapse and overall survival (OS) (hazard ratio (HR) 1.62; p = 0.029 and HR 1.65; p = 0.009, reference: CHT alone group), whereas other primary malignancy-related factors had no effect on the outcome. Compared to the CHT alone group, complex karyotypes were significantly increased in the CHT + RT group (86.1% vs. 57.5%, p = 0.007). In the PSM cohort, t-AML patients with prior CHT and RT had significantly worse 3-year OS than those with de novo AML (25.2% and 42.7%; p = 0.009). Our results suggest that prior CHT and RT for primary malignancy may be associated with increased relapse and worse OS of allo-HSCT in t-AML.
Genetic etiology and pregnancy outcomes of fetuses with central nervous system anomalies
Authors: Tao Huimin , Wu Jiebin , Han Yu , Zhang Bei , Zhai Jingfang 
Published: July 2023

Abstract
Purpose
To investigate genetic etiology and pregnancy outcomes of fetal central nervous system (CNS) anomalies.

Methods
217 fetuses with CNS anomalies were included in our cohort from January 2016 to December 2022. 124 cases received karyotyping and 73 cases simultaneously underwent copy number variant sequencing (CNV-seq). Dynamic ultrasound screening and pregnancy outcomes were followed up, including neonates’ neurodevelopmental outcomes.

Results
(1) 20 types of CNS anomalies were revealed by ultrasound and the most common was ventriculomegaly. (2) 14 (11.3%) of 124 cases were found chromosomal abnormalities by karyotyping, and copy number variations (CNVs) were revealed in 13 (17.8%) of 73 cases by CNV-seq. Fetuses with non-isolated CNS anomalies had a higher detection rate (DR) of abnormal karyotypes and CNVs than those with isolated CNS anomalies (25.0% vs. 4.8%; 35.0% vs. 11.3%) (P < 0.05). And the DR of abnormal karyotypes was significantly higher in multiple CNS anomalies than in single CNS anomaly (16.7% vs. 2.8%, P < 0.05), while there were no significant differences in the DR of CNVs. (3) Through dynamic ultrasound, 12 cases were further found progression or additional malformations. (4) Pregnancy outcomes of 209 cases were obtained, including 136 (65.1%) live births, 3 (1.4%) intrauterine fetal deaths, and 70 (33.5%) terminated. Two neonatal deaths at 6 months and one infant with motor and intellectual disabilities were finally found after long-term follow-up.

Conclusion
Genetic analysis combined with dynamic ultrasound screening and multidisciplinary consultation plays an important role in evaluating the prognosis of fetal CNS anomalies, especially for those with multiple CNS or extracranial abnormalities.
Early echocardiographic signs of cardiovascular affection in pediatric familial hypercholesterolemia
Authors: Ibrahim Hossam , Saad Hend , Abdelaziz Osama , Abdelmohsen Gaser 
Published: July 2023

AbstractFamilial hypercholesterolemia (FH) is a rare autosomal dominant genetic disorder caused by defective low-density lipoprotein (LDL) receptors or abnormal apolipoprotein B. FH raises the risk of premature atherosclerotic disease and cardiovascular death in young adults. However, cardiovascular affection in children needs to be more adequately studied. Our study aimed to evaluate the effect of hypercholesterolemia on the cardiovascular system of pediatric patients with homozygous FH using conventional and advanced echocardiographic parameters such as tissue Doppler imaging (TDI) and 2-dimensional speckle-tracking echocardiography (2D-STE). This case-control study matched 25 healthy children with 21 patients with homozygous FH. Both groups had conventional echocardiography, TDI, and 2D-STE. Myocardial velocities of the left and right ventricles, left ventricular strain, and aortic stiffness parameters were measured. The FH group had greater systolic blood pressure, dilated coronary arteries, and hypertrophied left ventricle (LV) compared to the control (P = 0.0001, P = 0.001, P = 0.01, respectively). The mitral E/E′ ratio was higher in the patient group than in the control group (P = 0.007), indicating LV diastolic dysfunction in patients. At the same time, LV systolic function evaluated by 2D-STE was comparable to that in the control group. The abdominal aorta circumferential strain and ascending aorta M-mode-derived strain were significantly lower in patients compared to those in the control (P = 0.024, P = 0.0001, respectively), indicating increased aortic stiffness in the patients’ group; moreover, 85.7% of patients had mild aortic insufficiency. Conclusion: Mild aortic insufficiency, coronary artery dilatation, left ventricular (LV) diastolic dysfunction, and increased aortic stiffness are among early cardiovascular markers in pediatric patients with homozygous FH before impaired LV systolic function.

What is Known:• Familial hypercholesterolemia (FH) in adults is associated with accelerated atherosclerosis, aortic valvopathy, dilated coronary arteries, ischemic heart disease, and premature cardiovascular death.• The cardiovascular effects of FH in children require additional research.

What is New:• Pediatric patients with familial hypercholesterolemia tend to have an early affection for left ventricular diastolic function before the affection for the systolic function.• The diastolic dysfunction associated with pediatric FH is correlated to the aortic stiffness and low-density lipoprotein levels.
Genomics and inclusion of Indigenous peoples in high income countries
Authors: Gwynne Kylie , Jiang Shirley , Venema Robertson , Christie Vita , Boughtwood Tiffany , Ritha Marida , Skinner John , Ali Nyesa , Rambaldini Boe , Calma Tom 
Published: July 2023

AbstractGenomics research related to Indigenous people has been at worst exploitative and at best, retrospectively on a journey to improve effective engagement of Indigenous individuals and communities. Genomics can positively impact all stages of clinical management, and to improve genomic effectiveness researchers aggregate genomic data from diverse global sub-populations, such as shared ancestry groupings, as people within these groupings will have a greater proportion of shared DNA traits. While genomics is already being used worldwide to improve lives, its utility and effectiveness has not been maximized for individuals with Indigenous ancestry. Several large datasets of human genetic variation have been made publicly available, of which the most widely used is the Genome Aggregation Database (gnomAD), but none of these databases currently contain any population-specific data for Indigenous populations. There are many reasons why Indigenous people have been largely left out of genomics research and, because of this, miss out on the benefits offered. It is also clear that if research is to be effective, it needs to be done ‘with’ and not ‘on’ Indigenous communities. This systematic review of the literature regarding Indigenous peoples (in high income countries) and genomics aims to review the existing literature and identify areas of strength and weakness in study design and conduct, focusing on the effectiveness of Indigenous community engagement.
Exploring the Decision-Making Process of People Living with HIV Enrolled in Antiretroviral Clinical Trials: A Qualitative Study of Decisions Guided by Trust and Emotions
Authors: Feijoo-Cid Maria , Arreciado Marañón Antonia , Huertas Ariadna , Rivero-Santana Amado , Cesar Carina , Fink Valeria , Fernández-Cano María Isabel , Sued Omar 
Published: July 2023

AbstractThe informed consent is an ethical and legal requirement for potential participants to enroll in a study. There is ample of evidence that understanding consent information and enrollment is challenging for participants in clinical trials. On the other hand, the reasoning process behind decision-making in HIV clinical trials remains mostly unexplored. This study aims to examine the decision-making process of people living with HIV currently participating in antiretroviral clinical trials and their understanding of informed consent. We conducted a qualitative socio-constructivist study using semi-structured interviews. Eleven participants were selected by purposive sampling in Argentina until data saturation was reached. A content analysis was performed. The findings highlight the fact that some participants decided to enroll on the spot, while others made the decision a few days later. In all cases, the decision was based on different aspects of trust (in doctors, in the clinical research site, in the clinical trials system) but also on emotions associated with HIV and/or treatment. Moreover, while people living with HIV felt truly informed after the consent dialogue with a researcher, consent forms were unintelligible and unfriendly. The immediacy of patient decision-making has rarely been described before. Enrollment in an HIV clinical trial is mainly a trust-based decision but this does not contradict the ethical values of autonomy, voluntariness, non-manipulation, and non‐exploitation. Thus, trust is a key issue to be included in reshaping professional practices to ensure the integrity of the informed consent process.
Bridging the Divide Between Iterative Optical Polishing and Automation
Authors: Walker David , Ahuir-Torres Juan I. , Akar Yasemin , Bingham Paul A. , Chen Xun , Darowski Michal , Fähnle Oliver , Gambron Philippe , Jackson Frankie F. , Li Hongyu , Mason Luke , Mishra Rakesh , Shahjalal Abdullah , Yu Guoyu 
Published: July 2023

AbstractSeveral recent business reports have described the global growth in demand for optical and photonic components, paralleled by technical reports on the growing shortage of skilled manufacturing staff to meet this demand. It is remarkable that producing ultraprecision surfaces remains so dependent on people, in contrast to other sectors of the economy, e.g., car manufacturing. Clearly, training can play some role, but ultimately, only process automation can provide the solution. This paper explores why automation is a challenge and summarizes multidisciplinary work aiming to assemble the building blocks required to realize automation.
Effect of prey density on the performance ofEupeodes corollaeand its predation rate against the cabbage aphid,Brevicorynae brassicae(L.)
Authors: Palial Shivani , Verma Subhash Chander , Sharma Prem Lal , Chandel Rajeshwar Singh , S Anooj S 
Published: July 2023

AbstractEupeodes corollae(F.) (Diptera: Syrphidae) is the most abundant syrphid fly which is distributed worldwide and is the sole predator of aphids. Therefore, the present study was conducted to evaluate the predation rate and functional response ofE. corollaeagainst the cabbage aphid,Brevicoryne brassicae(L.). The experiment was carried out under laboratory conditions at 25 ± 2°C with 60–70% relative humidity. The results revealed that age-specific net predation rate (qx) increased after the 4th day and a peak was recorded on the 10th day of pivotal age in the third larval instar. The stable host kill rate and finite host kill rate ofE. corollaewere 18.63 and 21.07, respectively, against theB. brassicaeand predicted that a mean of 20.78 aphids was needed forE. corollaeto produce one offspring. A negative linear coefficient (P< 0) indicated the type II functional response for all larval instars ofE. corollaeagainst theB. brassicae. At higher prey density, the prey consumption was significantly at par with second and third instar larvae ofE. corollaeas the prey consumption was increased with increasing the prey density, which then decreased after attaining the upper asymptote (76.40 and 81.40% consumption, respectively). The Roger's predator random equation for type II functional response was fitted to estimate attack rate (a) and handling time (Th). The maximum prey consumption was recorded for third instar ofE. corollaewith a higher attack rate (0.336 h−1) and lower handling time (0.514 h) againstB. brassicae, followed by the second and first instar. Thus, it is concluded that the third larval instar ofE. corollaewas the voracious feeder and used as an efficient biocontrol agent in the IPM programme.
Stabilizing Effect of High Pore Fluid Pressure on Fault Growth During Drained Deformation
Authors: Zega Zachary , Zhu Wenlu 
Published: July 2023

AbstractDilatant hardening is an accepted model for the stabilizing effect of high pore fluid pressure on fault slip and operates when deformation is undrained. To test whether high pore fluid pressure impedes fault propagation under drained conditions, we deformed highly permeable Darley Dale sandstone using strain rates of 10−4 s−1, 10−5 s−1, and 10−6 s−1, respectively. For each strain rate, we compared the inelastic behaviors and faulting styles among rocks deformed under different pore fluid pressures (Pf) (2–180 MPa). The confining pressure (Pc) was attuned to the pore fluid pressure throughout deformation to maintain a constant differential pressure (Pc − Pf) of 10 MPa. In samples deformed at 10−4 s−1 and 10−5 s−1, faulting behaviors were similar regardless of the magnitude of pore fluid pressure. However, when the strain rate was lowered to 10−6 s−1, we observed prolonged stress drops and slower slip velocities in samples deformed under high pore fluid pressures. In samples deformed at 10−6 s−1, we demonstrate that chemically assisted subcritical crack growth played an important role during faulting. A quantitative microstructural analysis revealed that slow faulting at slow strain rates was accompanied by pervasive microcracking and diffuse shear bands, which suggests pervasive subcritical cracking enabled slow faulting under drained conditions at the sample length scale. High pore fluid pressure may have facilitated slow faulting chemically by increasing the rate of subcritical cracking, mechanically via localized dilatant hardening, or both. Our results provide insight into the mechanics of faulting in natural settings where subcritical cracking is prevalent.
Blood pressure outcomes at 12 months in primary care patients prescribed remote physiological monitoring for hypertension: a prospective cohort study
Authors: Petito Lucia C. , Anthony Lauren , Peprah Yaw , Lee Ji Young , Li Jim , Sato Hironori , Persell Stephen D. 
Published: July 2023

AbstractRemote patient monitoring (RPM) for hypertension enables automatic transmission of blood pressure (BP) and pulse into the electronic health record (EHR), but its effectiveness in primary care is unknown. This pragmatic matched cohort study using EHR data compared BP outcomes between individuals prescribed RPM and temporally-matched controls from six primary care practices. We retrospectively created a cohort of 288 Medicare-enrolled patients prescribed BP RPM (cases) and 1152 propensity score-matched controls (1:4). Matching was based on age, sex, systolic blood pressure (SBP), marital status, and other characteristics. Outcomes at 3, 6, 9 and 12 months were: controlling high BP (most recent BP < 140/90 mm Hg), antihypertensive medication intensification, and most recent SBP assessed using: all measurements, and office measurements only. At baseline, RPM-prescribed patients and controls had similar ages and systolic BP. BP control diverged at 3 months (RPM: 72.2%, control: 51%,p < 0.001). This difference persisted but decreased over follow-up. After 12 months, the RPM-prescribed cohort had greater BP control (RPM: 71.5%, control: 58.1%,p < 0.001) and lower SBP (132.3 versus 136.5 mm Hg,p = 0.003) using all measurements, but they did not differ using only office measurements (12 month BP control: 60.8% versus 58.1%,p = 0.44; SBP: 135.9 versus 136.5 mm Hg,p = 0.91). At 12 months, the most recent BP measurements were more current for RPM-prescribed patients (median [IQR] 8 [0–109] versus 134 [56–239] days). Net increases in antihypertensive medications by 12 months were similar. Implementation of RPM in primary care could inform hypertension management strategies and increase hypertension control. Registration: ClinicalTrials.gov identifier: NCT05562921.
How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients
Authors: Fond Guillaume , Falissard Bruno , Nuss Philippe , Collin Cedric , Duret Stephanie , Rabbani Marc , De Chefdebien Isabelle , Tonelli Isabelle , Llorca Pierre Michel , Boyer Laurent 
Published: July 2023

AbstractAn important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012–2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3–3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18–34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18–34-year-olds to reduce suicide rates.
Rational design of alcoholic fermentation targeting extracellular carbon
Authors: Watanabe Daisuke , Kawashima Mikiya , Yoshioka Naoya , Sugimoto Yukiko , Takagi Hiroshi 
Published: July 2023

AbstractBreeding yeast strains for industrial alcoholic fermentation requires laborious screening due to the lack of in vivo modification strategies. Here we show that quiescence-specific cell wall thickening via synthesis of a major component, 1,3-β-glucan, critically antagonizes cellular fermentation ability by sequestering the available cytoplasmic carbon sources. This study provides insights into glycolytic control and reports an effective and reliable rational fermentation design.