bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging in screening women at high risk of breast cancer: A meta-analysis
Authors: Ding Wu , Fan Zaiwei , Xu Yuehuai , Wei Chunshou , Li Zhian , Lin Yingli , Zhu Jianming , Ruan Guodong
Published: March 2023

Background:

Magnetic resonance imaging (MRI) is more accurate than mammography in screening for breast cancer. Exposure to ionizing radiation from repeated diagnostic X-rays may be a cause of breast cancer.

Methods:

We conducted systematic searches on PubMed, Cochrane and Embase to identify studies on women who underwent mammography or MRI screening. A meta-analysis was performed to compare the detection rate of breast cancer by mammography, MRI or both.

Results:

A total of 18 diagnostic publications were identified and included in the meta-analysis. Among the 1000 screened women, MRI alone increased the detection rate of breast cancer by 8 compared with mammography alone (RR 0.48, 95% CI 0.42–0.54), and MRI plus mammography increased the detection rate of breast cancer by 1 compared with MRI alone (RR 0.86, 95% CI 0.78–0.96). Subgroup analysis demonstrated that the diagnostic efficacy of MRI plus mammography in breast was obviously better than that of MRI alone or mammography alone.

Conclusions:

Screening with MRI alone might be the best choice for women at high risk of breast cancer.
Investigating the mechanism of Tongqiao Huoxue decotion in the treatment of allergic rhinitis based on network pharmacology and molecular docking: A review
Authors: Zhang Fang , Wu Jiani , Shen Qu , Chen Zhiling , Qiao Zukang
Published: March 2023

Allergic rhinitis is prone to recurrence, and clinical treatments focus on control symptoms; however there is no radical cure. Our aim was to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of Tongqiao Huoxue decoction against allergic rhinitis. First, the chemical components and target genes of Tongqiao Huoxue decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology database. Similarly, allergic rhinitis targets were screened using online Mendelian Inheritance In Man and GeneCards database. Then, all potential targets of Tongqiao Huoxue decoction in the treatment of allergic rhinitis were identified, the Venn diagram was portrayed using R software, and protein-protein interaction network was built using String. The hub genes were analyzed using enrichment analyses. Finally, molecular docking was used to verify the reliability of the key gene prediction. The core targets for Tongqiao Huoxue decoction to improve allergic rhinitis were AKT1, TP53, IL6, and so on. The enrichment analysis results showed that Tongqiao Huoxue decoction treatment in allergic rhinitis might be involved in the AGE-RAGE signaling pathway and fluid shear stress and atherosclerosis pathway. The molecular docking verification indicated that its ingredients bound well to the core targets of allergic rhinitis, and stigmasterol’s docking ability with TNF (−12.73 kcal/mol) is particularly prominent. Based on these findings, it may be deduced that stigmasterol treated allergic rhinitis by acting on TNF targets. But, this conclusion needs to be confirmed by further in vitro and in vivo trials.
Expression of HIF-1α/PKM2 axis correlates to biological and clinical significance in papillary thyroid carcinoma
Authors: Hao Zengfang , Wang Yuan , Li Jiajun , Liu Weina , Zhao Wei , Wang Juan
Published: March 2023

hypoxia inducible factor-1α (HIF-1α) and pyruvate kinase M2 (PKM2) are 2 key metabolic regulatory proteins, they could engage in a positive feedback loop and drive cancer growth by enhancing glycolysis. This study aimed to investigate the expression of HIF-1α and PKM2 in papillary thyroid carcinoma (PTC) and its correlation with the patients clinicopathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 60 patients were collected. The expression levels of HIF-1α and PKM2 in PTC tissues were examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between HIF-1α and PKM2 expressions and the clinical pathological features of PTC. The results showed that the positive expressions of HIF-1α, PKM2, and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all significantly higher in PTC than those in normal thyroid follicular epithelium, and a positive correlation was found between HIF-1α and PKM2 in PTC. Further analysis showed that in PTC, the positive expression of HIF-1α and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were significantly associated with bigger tumor size, moreover, the positive expressions of HIF-1α, PKM2 and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all correlated with capsular invasion and lymph node metastasis, while they were all not correlated with gender, sex and multicentricity of tumor. This study identified HIF-1a/PKM2 axis as potential molecular marker for predicting the invasion and progression of papillary thyroid carcinoma.
Follow-up of biological reconstruction of epiphysis preserving osteosarcoma around the knee in children: A retrospective cohort study
Authors: Dai Zhibing , Sun Yachao , Maihemuti Maierdanjiang , Jiang Renbing
Published: March 2023

Limb salvage treatment for malignant bone tumors in children includes prosthetic and biological reconstruction. Early function following prosthesis reconstruction is satisfactory; however, there are several complications. Biological reconstruction is another way to treat bone defects. We evaluated the effectiveness of reconstruction of bone defects by liquid nitrogen inactivation of autologous bone with preserving epiphysis in 5 cases of periarticular osteosarcoma of the knee. We retrospectively selected 5 patients with articular osteosarcoma of the knee who underwent epiphyseal-preserving biological reconstruction in our department between January 2019 and January 2020. Femur involvement occurred in 2 cases and tibia involvement occurred in 3 cases, with an average defect of 18 cm (12–30 cm). The 2 patients with femur involvement were treated with inactivated autologous bone by liquid nitrogen with vascularized fibula transplantation. Among the patients with tibia involvement, 2 were treated with inactivated autologous bone with ipsilateral vascularized fibula transplantation and 1 was treated with autologous inactivated bone with contralateral vascularized fibula transplantation. Bone healing was evaluated by regular X-ray examination. At the end of the follow-up, lower limb length, knee flexion, and extension function were evaluated. Patients were followed up for 24 to 36 months. Average bone-healing time was 5.2 months (3–8 months). All patients achieved bone healing with no tumor recurrence and no distant metastasis and all patients survived. The lengths of both lower limbs were equal in 2 cases, with shortening by ≤1 cm in 1 case and shortening by 2 cm in 1 case. Knee flexion was >90° in 4 cases and between 50 and 60° in 1 case. The Muscle and Skeletal Tumor Society score was 24.2 (range 20–26). Inactivation of autogenous bone with the epiphysis preserved by liquid nitrogen combined with vascularized fibula reconstruction for periarticular osteosarcoma of the knee in children is safe and effective. This technique supports bone healing. Postoperative limb length and function, and short-term effects were satisfactory.
Biomarkers in gastroenteropancreatic neuroendocrine neoplasms
Authors: Jacoba Isa Mulingbayan , Weber H. Christian
Published: March 2023

Purpose of review

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) represent a heterogenous group of rare tumors emanating from neuroendocrine cells that are clinically silent for prolonged periods of time without detection. Traditional biomarkers lack sufficiently high enough specificity and sensitivity for these tumors and their secreted products. New molecules are sought to improve accuracy of detection and monitoring of GEP-NENs. The purpose of this review is to highlight recent advances in the discovery of novel biomarkers and their potential characteristics and utility as markers of GEP-NENs.

Recent findings

Several recent GEP-NEN investigations regarding NETest demonstrate superior sensitivity and specificity in diagnosis and disease monitoring as compared with chromogranin A. Among several tissue-based emergent candidate molecules as biomarkers for GEP-NEN INSM1 has demonstrated consistently excellent characteristics when compared with traditional markers including chromogranin A, synaptophysin, and CD56.

For the diagnosis and clinical monitoring of NEN, there still exists a considerable need for better biomarkers. Novel technology has resulted in a promising liquid biopsy for the detection and monitoring of GEP-NENs. The search for improved tissue biomarkers has resulted in identification of one potential candidate whereas several others remain in the investigatory phase.
Effects of point spread function correction and time-of-flight on visual contrast level and pixel values in brain PET images
Authors: Kamikawa Yohei , Yoshida Yukito , Kawahara Yasuhiro
Published: March 2023

Objectives

Point spread function (PSF) correction and time-of-flight (TOF) can improve the quality of PET images. None have directly assessed the visual effects of these methods in brain PET images and evaluated the image quality from these methods based on the relationship between the number of updates and noise level. The present study aimed to clarify the effects of PSF and TOF on the visual contrast level and pixel values of brain PET images using an experimental phantom.

Materials and methods

The visual contrast level was evaluated based on the sum of edge strengths. In addition, the effects of PSF, TOF, and a combination of them on pixel values were evaluated after anatomical standardization of brain images, in which the whole brain was divided into 18 segments. These were evaluated using images reconstructed with the number of updates set to achieve the same noise level.

Results

Combined application of the point spread function and TOF resulted in the greatest increase in the sum of edge strengths (32%), followed by PSF (21%) and TOF (6%). The maximum increase in pixel values occurred in the thalamic area (17%).

Conclusion

Although PSF and TOF can increase the visual contrast level by increasing the sum of edge strengths, they may affect the results of software-based analysis using pixel values. Nonetheless, using these methods may improve the ability to visualize areas of hypoaccumulation, such as epileptic foci.
A Rare Report of the Coexistence of Sickle Cell Disease, Neurofibromatosis Type 1, and Intracranial Hypertension in a Pediatric Patient
Authors: Patel Amie , Winter Timothy , Jain Akshat
Published: March 2023

A pediatric female with sickle cell disease (SCD) and neurofibromatosis type 1 was noted to have incidental papilledema, with subsequent workup showing an elevated opening pressure. She was diagnosed with intracranial hypertension and began treatment with acetazolamide. Hydroxyurea was also discontinued. Acetazolamide was tapered off, and hydroxyurea was restarted with no worsening in her ophthalmologic exam. We report this case due to the rare occurrence of all 3 conditions, and while intracranial hypertension has been reported in SCD, the diagnostic workup for papilledema in hemoglobinopathies is not well defined. This case helps delineate the presentation and diagnostic workup of papilledema in SCD.
Next Steps: Survivor Healthcare Passport — A Novel Form of Survivorship Care Plan in the Pediatric Population
Authors: Valencia M. Clarise , Hang Lindsay , Schmidt Deb , Nichols Julie , Zhang Jian , Yan Ke , Gonzalez Alyssa , Schwartz Cindy L. , Phelan Rachel
Published: March 2023

Purpose:

Survivorship care plans (SCPs) have been instrumental in aiding transition from cancer treatment to survivorship care, which contains the diagnosis, treatment, potential late effects, and recommended follow-up. There has been paucity of research on its efficacy and lack of guidelines on development and delivery of SCPs. The Next Steps Survivorship Clinic at Children’s Wisconsin uses a Survivorship Healthcare Passport (SHP), a SCP pocket-sized card. This study aims to improve understanding of patient and parent use of the SHP at a single institution.

Materials and Methods:

An electronic survey was distributed to cancer survivors (14 to 28 y old) and parents/guardians who received the SCP. Data was analyzed with descriptive and correlation statistics.

Results:

Older survivors were reliable in carrying their SHP, and endorsed greater confidence in understanding its contents leading to a notion of improved ability to coordinate care. Younger survivors tend to rely on their parents. A preference for a smartphone application as another platform was noted.

Conclusions:

This form of SCP has shown to benefit older survivors which directly impacts the notion of efficacy in care coordination.

Implication for Cancer Survivors:

Providing easy-to-access information may encourage survivors to advocate for their health and to facilitate transition of care.
Clinical Significance of Plasma Soluble MICB in Children With EBV-associated Hemophagocytic Lymphohistiocytosis
Authors: Wei Ang , Zhang Liping , Ma Honghao , Cui Lei , Zhang Qing , Wang Dong , Chen Sitong , Du Junye , Zhao Xiaoxi , Wang Tianyou , Zhang Rui , Zheng Huyong , Li Zhigang
Published: March 2023

Background:

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal systemic inflammation disease in children. The most common cause is Epstein-Barr virus (EBV) infection. MHC class I polypeptide-related sequence B (MICB) is a membrane protein inducibly expressed upon cellular stress, viral infection, or malignant transformation, thus marking these cells for clearance through natural killer group 2 member D-positive lymphocytes. MICB can be released into plasma through several mechanisms, reducing NK cell cytotoxicity.

Methods:

We conducted clinical research on HLH patients and cell research in vitro. In the retrospective clinical part, 112 HLH patients (including EBV-HLH group and non-EBV-HLH group), 7 infectious mononucleosis patients, and 7 chronic active EBV infection patients were treated in Beijing Children’s Hospital, affiliated with Capital Medical University, from January 2014 to December 2020, were enrolled in this study. Real-time quantitative polymerase chain reaction, standard enzyme-linked immunosorbent assay methods, and lactate dehydrogenase release tests were used to examine the expression of MICB mRNA, the soluble MICB (sMICB) levels, and the activity of NK cells in those patients. In vitro research, MICB overexpression-vector virus, MICB knockdown-vector virus, and empty-vector virus were transfected into two kinds of target cells, such as K562 and MCF7. The level of sMICB and NK cell killing activity between other groups was compared. Finally, we compared NK92 cell killing activity in different concentrations of sMICB.

Results:

In clinical studies, compared with the non-EBV-HLH group, the EBV-HLH group had lower NK cell killing activity (P < 0.05). The level of sMICB in the EBV-HLH group was significantly higher than in non-EBV-HLH, infectious mononucleosis, and chronic active EBV infection patients (P＜0.05). A high level of sMICB was associated with poor treatment response and poor prognosis (P＜0. 05). Cellular studies showed that an increased level of membrane MICB could positively correlate with the killing activity of NK92 cells (P＜0. 05), and a high level of sMICB (1250 to 5000pg/ml) could reduce the killing activity of NK92 cells (P < 0.05). A high level of sMICB (2500pg/ml) could increase the release of cytokines from NK92 cells.

Conclusion:

The expression level of sMICB in EBV-HLH patients increased, and a high level of sMICB at the initial onset indicated a poor treatment response. The killing activity of NK cells in EBV-HLH patients decreased more significantly. The high level of sMICB may inhibit the killing activity but increase the release of cytokines of NK92 cells.
Description of a Colocated Comprehensive Care Model for People With Sickle Cell and Comorbid Pulmonary Disease
Authors: Pugh Courtney , Zeno Rachel N. , Stanek Joseph , Gillespie Michelle , Kopp Benjamin T. , Creary Susan E.
Published: March 2023

Comorbid pulmonary complications in people with sickle cell disease (pwSCD) are associated with high rates of morbidity and mortality, and poor access to care contributes to poor outcomes among this particularly high-risk pwSCD. Our purpose was to describe the population served and the resources required for hematology, pulmonary, nursing, respiratory therapy, social work, genetics, psychology, and school liaison providers to see these patients in an integrated clinic. We abstracted demographic, medication, clinical, and diagnostics data of the pwSCD seen at least once in this clinic from February 1, 2014 to December 10, 2020 from the electronic medical record and identified 145 unique pwSCD. Abnormal lung function and bronchodilator responsiveness were detected in 31% and 42% of participants respectively. Sleep abnormalities were found in over two-thirds of those screened and 65% had ≥1 previous acute chest syndrome episode. This clinic also allowed for direct provider communication and required relatively limited resources to serve a large number of severely affected pwSCD. Given the degree of abnormal respiratory variables detected and the limited resources required to implement this model, studies are warranted to evaluate whether it has the potential to improve outcomes in high-risk populations.
Gait and Falls in Benign Paroxysmal Positional Vertigo: A Systematic Review and Meta-analysis
Authors: Pauwels Sara , Casters Laura , Lemkens Nele , Lemmens Winde , Meijer Kenneth , Meyns Pieter , van de Berg Raymond , Spildooren Joke
Published: March 2023

Background and Purpose:

Benign paroxysmal positional vertigo (BPPV) is one of the most common vestibular disorders, and is treated effectively with particle repositioning maneuvers (PRM). The aim of this study was to assess the influence of BPPV and treatment effects of PRM on gait, falls, and fear of falling.

Methods:

Three databases and the reference lists of included articles were systematically searched for studies comparing gait and/or falls between (1) people with BPPV (pwBPPV) and controls and (2) pre- and posttreatment with PRM. The Joanna Briggs Institute critical appraisal tools were used to assess risk of bias.

Results:

Twenty of the 25 included studies were suitable for meta-analysis. Quality assessment resulted in 2 studies with high risk of bias, 13 with moderate risk, and 10 with low risk. PwBPPV walked slower and demonstrated more sway during tandem walking compared with controls. PwBPPV also walked slower during head rotations. After PRM, gait velocity during level walking increased significantly, and gait became safer according to gait assessment scales. Impairments during tandem walking and walking with head rotations did not improve. The number of fallers was significantly higher for pwBPPV than for controls. After treatment, the number of falls, number of pwBPPV who fell, and fear of falling decreased.

Discussion and Conclusions:

BPPV increases the odds of falls and negatively impacts spatiotemporal parameters of gait. PRM improves falls, fear of falling, and gait during level walking. Additional rehabilitation might be necessary to improve gait while walking with head movements or tandem walking.

Video Abstract available for more insights from the authors (see the Supplemental Digital Content Video, available at: http://links.lww.com/JNPT/A421).
Clinical and Laboratory Characteristics Predicting the Severity of Carbon Monoxide Poisoning in Children
Authors: Güven Deniz , Sarıcı Dilek
Published: March 2023

Objectives

Carbon monoxide poisoning (COP) is extremely common throughout the world. The purpose of this study was to assess the demographic, clinical, and laboratory characteristics predicting the severity COP in children.

Methods

The study included 380 children diagnosed with COP between January 2017 and January 2021 and 380 healthy controls. Carbon monoxide poisoning was diagnosed based on the medical history and a carboxyhemoglobin (COHb) level of more than 5%. The patients were classified as mild (COHb 10%), moderate (COHb 10%–25%), or severely (COHb > 25%) poisoned.

Results

The mean age of the severe group was 8.60 ± 6.30, for the moderate group was 9.50 ± 5.81, for the mild group was 8.79 ± 5.94, and for the control group was 8.95 ± 5.98. The most common place of exposure was at home and all cases were affected accidentally. The coal stove was the most common source of exposure, followed by natural gas. The most common symptoms were nausea/vomiting, vertigo, and headache. Neurologic symptoms such as syncope, confusion, dyspnea, and seizures were more common in the severe group. A total of 91.3% of the children had hyperbaric oxygen therapy, 3.8% were intubated, and 3.8% were transferred to intensive care in the severe group, whereas no death or sequela was observed. Mean platelet volume and red cell distribution width had the highest area under the curve in the receiver operating characteristic analysis (0.659; 0.379). A positive and low statistically significant relationship was found between COHb levels and troponin and lactate levels in the severe group (P < 0.05).

Conclusions

Carbon monoxide poisoning progressed more severely in children presented with neurological symptoms and have elevated red cell distribution width and mean platelet volume. Even in severe COP cases, satisfactory results have been obtained with early and appropriate treatment.
The Glymphatic System in Humans: Investigations With Magnetic Resonance Imaging
Authors: Naganawa Shinji , Taoka Toshiaki , Ito Rintaro , Kawamura Mariko
Published: March 2023

The concept of the glymphatic system was proposed more than a decade ago as a mechanism for interstitial fluid flow and waste removal in the central nervous system. The function of the glymphatic system has been shown to be particularly activated during sleep. Dysfunction of the glymphatic system has been implicated in several neurodegenerative diseases. Noninvasive in vivo imaging of the glymphatic system is expected to be useful in elucidating the pathophysiology of these diseases. Currently, magnetic resonance imaging is the most commonly used technique to evaluate the glymphatic system in humans, and a large number of studies have been reported. This review provides a comprehensive overview of investigations of the human glymphatic system function using magnetic resonance imaging. The studies can be divided into 3 categories, including imaging without gadolinium-based contrast agents (GBCAs), imaging with intrathecal administration of GBCAs, and imaging with intravenous administration of GBCAs. The purpose of these studies has been to examine not only the interstitial fluid movement in the brain parenchyma, but also the fluid dynamics in the perivascular and subarachnoid spaces, as well as the parasagittal dura and meningeal lymphatics. Recent research has even extended to include the glymphatic system of the eye and the inner ear. This review serves as an important update and a useful guide for future research directions.
ComBat Harmonization for MRI Radiomics
Authors: Leithner Doris , Nevin Rachel B. , Gibbs Peter , Weber Michael , Otazo Ricardo , Vargas H. Alberto , Mayerhoefer Marius E.
Published: March 2023

Objectives

The aims of this study were to determine whether ComBat harmonization improves multiclass radiomics-based tissue classification in technically heterogeneous MRI data sets and to compare the performances of 2 ComBat variants.

Materials and Methods

One hundred patients who had undergone T1-weighted 3D gradient echo Dixon MRI (2 scanners/vendors; 50 patients each) were retrospectively included. Volumes of interest (2.5 cm3) were placed in 3 disease-free tissues with visually similar appearance on T1 Dixon water images: liver, spleen, and paraspinal muscle. Gray-level histogram (GLH), gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), and gray-level size-zone matrix (GLSZM) radiomic features were extracted. Tissue classification was performed on pooled data from the 2 centers (1) without harmonization, (2) after ComBat harmonization with empirical Bayes estimation (ComBat-B), and (3) after ComBat harmonization without empirical Bayes estimation (ComBat-NB). Linear discriminant analysis with leave-one-out cross-validation was used to distinguish among the 3 tissue types, using all available radiomic features as input. In addition, a multilayer perceptron neural network with a random 70%:30% split into training and test data sets was used for the same task, but separately for each radiomic feature category.

Results

Linear discriminant analysis–based mean tissue classification accuracies were 52.3% for unharmonized, 66.3% for ComBat-B harmonized, and 92.7% for ComBat-NB harmonized data. For multilayer perceptron neural network, mean classification accuracies for unharmonized, ComBat-B–harmonized, and ComBat-NB–harmonized test data were as follows: 46.8%, 55.1%, and 57.5% for GLH; 42.0%, 65.3%, and 71.0% for GLCM; 45.3%, 78.3%, and 78.0% for GLRLM; and 48.1%, 81.1%, and 89.4% for GLSZM. Accuracies were significantly higher for both ComBat-B– and ComBat-NB–harmonized data than for unharmonized data for all feature categories (at P = 0.005, respectively). For GLCM (P = 0.001) and GLSZM (P = 0.005), ComBat-NB harmonization provided slightly higher accuracies than ComBat-B harmonization.

Conclusions

ComBat harmonization may be useful for multicenter MRI radiomics studies with nonbinary classification tasks. The degree of improvement by ComBat may vary among radiomic feature categories, among classifiers, and among ComBat variants.
Leber Hereditary Optic Neuropathy in a Family of Carriers of MT-ND5 m.13042G>T (A236S) Novel Variant
Authors: Petrović Pajić Sanja , Suštar Habjan Maja , Brecelj Jelka , Fakin Ana , Volk Marija , Maver Aleš , Jezernik Gregor , Peterlin Borut , Glavač Damjan , Hawlina Marko , Jarc-Vidmar Martina
Published: March 2023

Background:

A Slovenian three-generation family with 3 individuals with bilateral optic neuropathy and 2 unaffected relatives with a novel homoplasmic missense variant m.13042G > T (A236S) in the ND5 gene is described. A detailed phenotype at initial diagnosis and a follow-up of bilateral optic neuropathy progression is presented for 2 affected individuals.

Methods:

A detailed phenotype analysis with clinical examination in the early and chronic phase with electrophysiology and OCT segmentation is presented. Genotype analysis with full mitochondrial genome sequencing was performed.

Results:

Two affected male individuals (maternal cousins) had a profound visual loss at an early age (11 and 20 years) with no recovery. The maternal grandmother exhibited bilateral optic atrophy with a history of visual loss at the age 58 years. The visual loss of both affected male individuals was characterized by centrocecal scotoma, abnormal color vision, abnormal PERG N95, and VEP. Later with disease progression, retinal nerve fiber layer thinning was observed on OCT. We observed no other extraocular clinical features. Mitochondrial sequencing identified a homoplasmic novel variant m.13042G > T (A236S) in the MT-ND5 gene, belonging to a haplogroup K1a.

Conclusion:

Novel homoplasmic variant m.13042G > T (A236S) in the ND5 gene in our family was associated with Leber hereditary optic neuropathy-like phenotype. However, predicting the pathogenicity of a novel ultra-rare missense variant in the mitochondrial ND5 gene is challenging. Genetic counseling should consider genotypic and phenotypic heterogeneity, incomplete penetrance, haplogroup type, and tissue-specific thresholds.
Green Heart Louisville: intra-urban, hyperlocal land-use regression modeling of nitrogen oxides and ozone
Authors: Prathibha Pradeep , Yeager Raymond , Bhatnagar Aruni , Turner Jay
Published: March 2023

Exposure to urban air pollution is linked to increased mortality from cardiopulmonary causes. Urban areas juxtapose large numbers of residences and workplaces with near-road environments, exacerbating traffic-related air pollution (TRAP) exposure. TRAP is the primary source of variability in intraurban air quality, but continuous regulatory monitoring stations lack the spatial resolution to detect fine-scale pollutant patterns that recent studies using long-term, resource-intensive mobile measurements have established as persistent and associated with higher risk of cardiovascular events. This work evaluates a low-cost, fixed-site approach to characterizinglong-term, hyperlocal exposure to oxides of nitrogen (including NO2, a common surrogate for TRAP) as part of Green Heart Louisville, a prospective cohort study examining linkages between urban vegetation, local air quality, and cardiovascular health.

We used a fixed 60-site network of Ogawa passive samplers in a 12 km2section of Louisville, KY, to measure two-week integrated NO2, NOx(NO + NO2), and O3mixing ratios nominally every two months between May 2018-March 2021. Seasonal NOxaverages were 2.5-fold higher during winter than in summer, and annual average NO (calculated by difference in NOxand NO2) and NO2ranged from 4-21 ppb and 5-12 ppb, respectively. NO increased 3-to-5-fold within 150 m of highways or major arterial roads and 2-to-3-fold near parking lots. While both NO and NO2were elevated in near-road environments, the corresponding O3was depressed, consistent with titration by NO.

We developed land-use regression models for annual average NO, NO2, and NOxusing parameters of proximity (distance to nearest road type, restaurant, traffic signal), cumulative occurrence (length of roads, number of restaurants and traffic lights, all in buffers of up to 500 m in 50-m increments), and greenness (normalized difference vegetative index (NDVI)). Adjusted spatial variability explained by the models were 70% (p<0.05), 67% (p<0.05), and 75% (p<0.01) for NO, NO2, and NOx, respectively. Common predictors were distances to the nearest restaurant and road as well as total length of roads within 350 m. Only one greenness metric was significant: mean NDVI within 50 m was negatively associated (p=0.02) with NO2. We plan to use these hyperlocal models to estimate residential-level exposures of the clinical study participants.
Archetypal analysis of COVID-19 in Montana, USA, March 13, 2020 to April 26, 2022
Authors: Stone Emily , Coombs Sebastian , Landguth Erin
Published: March 2023

Given the potential consequences of infectious diseases, it is important to understand how broad scale incidence variability influences the probability of localized outbreaks. Often, these infectious disease data can involve complex spatial patterns intermixed with temporal trends. Archetypal Analysis is a method to mine complex spatiotemporal epidemiological data, and can be used to discover the dynamics of spatial patterns. The application of Archetypal Analysis to epistemological data is relatively new, and here we present one of the first applications using COVID-19 data from March 13, 2020 to April 26, 2022, in the counties of Montana, USA. We present three views of the data set with Archetypal Analysis. First, we evaluate the entire 56 county data set. Second, we compute mutual information of the 56 counties’ time series to remove counties whose dynamics are mainly independent from most of the other counties. We choose the top 17 counties ranked in terms of increasing total mutual information. Finally, to compare how population size might influence results, we conducted an analysis with 10 of the largest counties. Using the Archetypal Analysis results, we analyze the disease outbreaks across Montana, comparing and contrasting the three different cases and showing how certain counties can be found in distinct sets of archetypes. Using the reconstruction time series, we show how each outbreak had a unique trajectory across the state in terms of the archetypes.

Author summary

Archetypal Analysis provides an additional tool for the study of spatio-temporal epidemiological data. We apply Archetypal Analysis to COVID-19 data and reveal how this approach can be used to analyse the dynamics of each COVID-19 outbreak across the state.
The impact of signal variability on epidemic growth rate estimation from wastewater surveillance data
Authors: Colman Ewan , Kao Rowland R.
Published: March 2023

Background

Testing samples of waste water for markers of infectious disease became a widespread method of surveillance during the COVID-19 pandemic. While these data generally correlate well with other indicators of national prevalence, samples that cover localised regions tend to be highly variable over short time scales.

Methods

We introduce a procedure for estimating the realtime growth rate of pathogen prevalence using time series data from wastewater sampling. The number of copies of a target gene found in a sample is modelled as time-dependent random variable whose distribution is estimated using maximum likelihood. The output depends on a hyperparameter that controls the sensitivity to variability in the underlying data. We apply this procedure to data reporting the number of copies of the N1 gene of SARS-CoV-2 collected at water treatment works across Scotland between February 2021 and February 2023.

Results

The real-time growth rate of the SARS-CoV-2 prevalence is estimated at 121 wastewater sampling sites covering a diverse range of locations and population sizes. We find that the sensitivity of the fitting procedure to natural variability determines its reliability in detecting the early stages of an epidemic wave. Applying the procedure to hospital admissions data, we find that changes in the growth rate are detected an average of 2 days earlier in wastewater than in hospital admissions data.

Conclusion

We provide a robust method to generate reliable estimates of epidemic growth from highly variable data. Applying this method to samples collected at wastewater treatment works provides highly responsive situational awareness to inform public health.
Contraception ends the genetic maintenance of human same-sex sexual behavior
Authors: Song Siliang , Zhang Jianzhi
Published: March 2023

Because human same-sex sexual behavior (SSB) is heritable and leads to fewer offspring, it is puzzling why SSB-associated alleles have not been selectively purged. Current evidence supports the antagonistic pleiotropy hypothesis that SSB-associated alleles benefit individuals exclusively performing opposite-sex sexual behavior by increasing their number of sexual partners and consequently their number of offspring. However, here we show that having more sexual partners no longer predicts more offspring since the availability of oral contraceptives in the 1960s and that SSB is now negatively genetically correlated with the number of offspring, indicating a loss of SSB’s genetic maintenance in modern societies.
Selection of antibody-binding covalent aptamers
Authors: Soxpollard Noah , Strauss Sebastian , Jungmann Ralf , MacPherson Iain
Published: March 2023

Aptamers are oligonucleotides with antibody-like binding function, selected from large combinatorial libraries. In this study, we modified a DNA aptamer library with N-hydroxysuccinimide esters, enabling covalent reactivity with cognate proteins. We selected for the ability to bind to mouse monoclonal antibodies, resulting in the isolation of two distinct covalent binding motifs. The covalent aptamers are specific for the Fc region of mouse monoclonal IgG1 and are cross-reactive with mouse IgG2a and other IgGs. Investigation into the covalent reactivity of the aptamers revealed a dependence on micromolar concentrations of Cu2+ions which can be explained by residual catalyst remaining after modification of the aptamer library. The aptamers were successfully used as adapters in the formation of antibody-oligonucleotide conjugates (AOCs) for use in detection of HIV protein p24 and super-resolution imaging of actin. This work introduces a new method for the site-specific modification of native monoclonal antibodies and may be useful in applications requiring AOCs or other antibody conjugates.
Serotonin in the orbitofrontal cortex enhances cognitive flexibility
Authors: Hyun Jung Ho , Hannan Patrick , Iwamoto Hideki , Blakely Randy D. , Kwon Hyung-Bae
Published: March 2023

Cognitive flexibility is a brain’s ability to switch between different rules or action plans depending on the context. However, cellular level understanding of cognitive flexibility have been largely unexplored. We probed a specific serotonergic pathway from dorsal raphe nuclei (DRN) to the orbitofrontal cortex (OFC) while animals are performing reversal learning task. We found that serotonin release from DRN to the OFC promotes reversal learning. A long-range connection between these two brain regions was confirmed anatomically and functionally. We further show that spatiotemporally precise serotonergic action directly enhances the excitability of OFC neurons and offers enhanced spike probability of OFC network. Serotonergic action facilitated the induction of synaptic plasticity by enhancing Ca2+influx at dendritic spines in the OFC. Thus, our findings suggest that a key signature of flexibility is the formation of choice specific ensembles via serotonin-dependent synaptic plasticity.
Genome-wide development of intra- and inter-specific transferable SSR markers and construction of a dynamic web resource for yam molecular breeding: Y2MD
Authors: Diouf Moussa , Zoclanclounon Yedomon Ange Bovys , Mboup Pape Adama , Diouf Diaga , Malédon Erick , Rivallan Ronan , Chair Hâna , Dossa Komivi
Published: March 2023

Background

Microsatellite markers represent a low-cost and efficient tool for rapid genotyping as compared to single nucleotide polymorphism markers in laboratories with limited resources. For the economically important yam species widely cultivated in developing countries, very few microsatellite markers are available and no marker database has been developed to date. Herein, we conducted a genome-wide microsatellite marker development among four yam species, identified cross-species transferable markers, and designed an easy-to-use web portal for the yam breeder community.

Results

The screening of yam genomes resulted in 318,713; 322,501; 307,040 and 253,856 microsatellites inDioscorea alata,D. rotundata,D. dumetorum, andD. zingiberensis, respectively. Mono-, di- and tri-nucleotides were the most important types of repeats in the different species and a total of 864,128 primer pairs were designed. Furthermore, we identified 1170 cross-species transferable microsatellite markers. Among them, a subset of 17 markers were experimentally validated with good discriminatory power regarding the species and the ploidy levels. Ultimately, we created and deployed a dynamic Yam Microsatellite Markers Database (Y2MD) available athttp://yamdb.42web.io/. Y2MD is embedded with various useful tools such as JBrowse, Blast,insilicoPCR, and SSR Finder to facilitate the exploitation of microsatellite markers in yams.

Conclusions

The present work is the first comprehensive microsatellite marker mining across several yam species and will contribute to advance yam genetic research and marker-assisted breeding. The released user-friendly database constitutes a valuable platform for yam breeders, especially those in developing countries.
Integrated multi-omics data reveals the molecular subtypes and the contruction of novel signature to aid Immunotherapy
Authors: li zhenqing , Li Bin , Meng Yuqi , Zhai Kerong , Li Xuan
Published: March 2023

Malignant cancer exhibits a severe imbalance between the active of immune response and tolerance. And the different and connection between the establishment and deficiency of the tumor immune response is still unknown entirely. Here, we used ten clustering algorithms based on five immune cells infiltration matrix to identified two specific molecular subtypes and determine its potential clinical outcomes and immune response effect. The cluster A subtype can be called the cold inflammatory subtype, which revealed the worst prognosis. And the cluster B can be identified as hot inflammatory subtype with high activated immune-related pathways. Then we used the WGCNA algorithms and limma to confirm the driven genes between the cluster A and B. 67 genes were identified the cluster A signature genes, and based on that we used the ssgsea algorithm to quantize the two subtypes. We confirmed the high score group had high activated level of immune activity pathways and better survival rate. The tumorigenesis-associated pathways were analysed in low score group, indicating active cell proliferation may be associated with poor prognosis. An in-silico drug screen predicted the erlotinib can be an effective compound in low score group based on the lung cancer cell line. Our research confirmed that the score can worked as an effective immunotherapy index, which provide a promising therapeutic strategies on immune therapeutics for lung adenocarcinoma.
Local variations of the piezoelectric properties of an LiNb(1−x)Ta
x
O3 crystal
Authors: Gureva Polina , Kulikov Anton , Mololkin Anatoli , Fakhrtdinov Rashid , Artemev Alex , Demkiv Andrey , Pisarevsky Yury , Marchenkov Nikita
Published: March 2023

An in situ study of the spatial distribution of the piezoelectric properties of an LiNb(1−x)Ta
x
O3 crystal (〈x〉 = 0.088) in an external DC electric field was performed by the method of X-ray diffraction of synchrotron radiation at angles close to 180°. The variation of the d
22 piezoelectric coefficient was determined with high accuracy (up to 2%) in local areas by the angular shift of the diffraction maximum under the action of the electric field (E = 1582 V mm−1) applied on the crystal along the Y axis, during scanning along the X and Z directions. A correlation between the piezoelectric strain amplitude and the concentration of tantalum obtained by X-ray fluorescence mapping has been established.
Synchrotron X-ray powder diffraction under high pressures up to 33 MPa for mechanoresponsive materials
Authors: Kasai Hidetaka , Liu Jianqiao , Xu Chao-Nan , Nishibori Eiji
Published: March 2023

Equipment for synchrotron X-ray diffraction at high pressures up to 33 MPa with an accuracy of ±0.1 MPa using a liquid as a pressure-transmitting medium has been developed. This equipment enables atomic-scale observation of the structural change of mechanoresponsive materials under applied pressures. The validity of the equipment is demonstrated by observation of the pressure dependence of the lattice parameters of copper. The observed bulk modulus of copper was found to be 139 (13) GPa which is a good agreement with the literature value. The developed equipment was subsequently applied to a repeatable mechanoluminescence material, Li0.12Na0.88NbO3:Pr3+. The bulk modulus and compressibility along the a and c axes were determined as 79 (9) GPa, 0.0048 (6) GPa−1 and 0.0030 (9) GPa−1, respectively, for the R3c phase. The advance of high-pressure X-ray diffraction will play an important role in understanding mechanoresponsive materials towards their atomic-scale design.
Online absolute calibration of fast FEL pulse energy measurements
Authors: Juranić Pavle , Alarcon Arturo , Ischebeck Rasmus
Published: March 2023

One of the challenges facing modern free-electron laser (FEL) facilities is the accurate pulse-to-pulse online measurement of the absolute flux of the X-ray pulses, for use by both machine operators for optimization and users of the photon beam to better understand their data. This manuscript presents a methodology that combines existing slow-measurement methods currently used in gas detectors across the world and fast uncalibrated signals from multipliers, meant for relative flux pulse-to-pulse measurements, which create a shot-to-shot absolute flux measurement through the use of sensor-based conditional triggers and algorithms at SwissFEL.
π-Complexation and C—H hydrogen bonding in the formation of colored cocrystals
Authors: Bosch Eric , Moreno Bryce S. , Bowling Nathan P.
Published: March 2023

The present study evaluates the potential combination of charge-transfer electron-donor–acceptor π–π complexation and C—H hydrogen bonding to form colored cocrystals. The crystal structures of the red 1:1 cocrystals formed from the isomeric pyridines 4- and 3-{2-[4-(dimethylamino)phenyl]ethynyl}pyridine with 1-[2-(3,5-dinitrophenyl)ethynyl]-2,3,5,6-tetrafluorobenzene, both C14H4F4N2O4·C15H14N2, are reported. Intermolecular interaction energy calculations confirm that π-stacking interactions dominate the intermolecular interactions within each crystal structure. The close contacts revealed by Hirshfeld surface calculations are predominantly C—H interactions with N, O, and F atoms.
Syntheses, crystal structures and Hirshfeld surface analyses of N-arylsulfonyl derivatives of cytisine
Authors: Okmanov Rasul Ya. , Olimova Manzura I. , Karabaeva Surayyo B. , Sapaev Frunza A. , Abdireymov Kudaybergen B.
Published: March 2023

By arylsulfonylation of cytisine in the presence of triethylamine, three new compounds have been obtained in good yields: (7R,9R)-N-[(4-ethylphenyl)sulfonyl]cytisine, C19H22N2O3S (I) {systematic name: (1R,5R)-3-[(4-ethylphenyl)sulfonyl]-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one}, (7R,9R)-N-[(4-chlorophenyl)sulfonyl]cytisine, C17H17ClN2O3S (II) {systematic name: (1R,5R)-3-[(4-chlorophenyl)sulfonyl]-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one} and (7R,9R)-N-[(3-nitrophenyl)sulfonyl]cytisine, C17H17N3O5S (III) {systematic name: (1R,5R)-3-[(3-nitrophenyl)sulfonyl]-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one}. The crystal structures of the compounds were determined on the basis of single-crystal X-ray diffraction data. The crystal structures of (I)–(III) are distinguished by the arrangement of two fragments of the molecule around the sulfonyl site. For all structures, weak C—H...O hydrogen bonds are developed. Hirshfeld surface analysis shows that H...H (for I and II) and H...O/O...H (for III) interactions make the most important contribution to the crystal packing.
3-Methyl-2-(methylsulfanyl)-5,5-diphenyl-3,5-dihydro-4H-imidazol-4-one
Authors: El Moutaouakil Ala Allah Abderrazzak , Guerrab Walid , Alsubari Abdulsalam , Mague Joel T. , Ramli Youssef
Published: March 2023

In the title molecule, C17H16N2OS, the dihydroimidazolone ring is slightly puckered and the methylsulfanyl group is nearly coplanar with it. In the crystal, two sets of C—H...O hydrogen bonds form corrugated layers of molecules parallel to the ac plane. The layers pack with normal van der Waals contacts between them.
Antecedents and boundary conditions of entrepreneurial intentions: perspective of theory of planned behaviour
Authors: Rehman Wali , Yosra Abdelwahed , Khattak Muhammad Sualeh , Fatima Goher
Published: March 2023

Purpose

This paper aims to examine the effects of perceived desirability for entrepreneurship (PDE) and perceived self-efficacy (PSE) on the entrepreneurial intentions (EI) of business students, with the moderation effect of entrepreneurial knowledge (EK) in the context of the theory of planned behaviour.

Design/methodology/approach

We used a self-administered survey of 200 students registered in the business schools of Pakistani universities. The causal association between the variables was estimated through SmartPLS by using hierarchal linear modelling.

Findings

The study findings indicate that PDE and PSE significantly influence EIs. Furthermore, EK significantly strengthens the nexus between PDE and EIs and between PSE and EIs. Those students who had already acquired self-efficacy and exhibited desirability for the business venture were more inclined towards entrepreneurship if they had acquired some EK and vice versa.

Research limitations/implications

This study reveals that a model of EIs is needed to configure the students’ goals and motivations. Also, using new education programmes will help students acquire new knowledge for business startups. Further implications are also discussed.

Originality/value

This research fills a gap by using the moderating role of EK on the nexus between PDE, PSE and EIs, which has remained untouched in the educational sector.