Miracle-dz/UniFAR-FTUs huggingface dataset:
Examining complexity in grip selection tasks and consequent effects on planning for end-state-comfort in children with developmental coordination disorder: A systematic review and meta-analysis

ABSTRACT This is the first review to provide both a systematic and meta-analytic approach to characterizing motor planning deficits in children with Developmental Coordination Disorder (DCD). Task complexity appears to be a key factor affecting motor planning in children with DCD. However, the different task-related factors and how they affect motor planning ability has not been examined. By systematically reviewing ten studies examining motor planning in children aged 4- to 14 years with and without DCD using grip selection tasks, task complexity was determined according to grip choices, level of precision, number of action steps and degree of rotation. A meta-analysis (N = 607; DCD = 255) revealed that, overall, those with DCD were 6.8% less likely to plan motor actions comfortably than typically developing children. This ability was moderated by task complexity (I2 = 66.7%), with performance differences ranging from 2.33% for low (g = 0.21) to 13.77% (g = 0.79) for high complexity. The results confirmed that children with DCD are able to plan for comfortable end states for tasks with simple and medium complexity level. When task complexity increased, compared to typically developing children, the motor planning ability of those with DCD was affected to a significantly greater extent. These findings provide important implications for both behavioral and neurological interventions.
A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

Previously recognized classical human onco-viruses can regulate complex neoplastic events, and are estimated to play a role during carcinogenesis in 15–20% of cancer cases. Although the DNA and gene products of several viruses have been found in breast tumors, none of the classical onco-viruses have definitely been linked to the initiation of breast cancer. However, recent evidence shows that human cytomegalovirus (HCMV) gene products are found in >90% of tumors and metastases of breast cancers, and their increased expression can be correlated to a more aggressive breast cancer phenotype. Supporting the active role of HCMV in breast cancer, a specific HCMV strain, HCMV-DB, was recently shown to exert oncogenic transformational activity in breast epithelial cells in vitro, and to give rise to fast-growing, triple-negative breast tumors when injected into immune deficient mice. The same observation holds true for clinical studies implying increased HCMV protein expression in triple negative breast cancer biopsies. In addition to functionally being able to hijack tumor-promoting cellular events, HCMV is known to exhibit a wide range of immunosuppressive effects, which can have radical impact on the tumor microenvironment. HCMV infected cells can avoid recognition and elimination by the immune system by orchestrating polarization of immunosuppressive type II macrophages, preventing antigen presentation, by expressing T cell inhibitory molecules, and possibly, by the induction of regulatory T (Treg) cell responses. These actions would be especially deleterious for the antigenic activation and proliferation of tumor specific CD8+ cytotoxic T lymphocytes (CTLs), whose effector functions have recently been targeted by successful, experimental immunotherapy protocols. The recognition of alternative causes and drivers of breast cancer is a pivotal research topic for the development of diagnostics and novel, effective preventive and therapeutic strategies targeting both tumor cells and their microenvironments.
Molecular Modeling of EUV Photoresist Revealing the Effect of Chain Conformation on Line-Edge Roughness Formation

Extreme ultraviolet lithography (EUVL) is a leading-edge technology for pattern miniaturization and the production of advanced electronic devices. One of the current critical challenges for further scaling down the technology is reducing the line-edge roughness (LER) of the final patterns while simultaneously maintaining high resolution and sensitivity. As the target sizes of features and LER become closer to the polymer size, polymer chain conformations and their distribution should be considered to understand the primary sources of LER. Here, we proposed a new approach of EUV photoresist modeling with an explicit description of polymer chains using a coarse-grained model. Our new simulation model demonstrated that interface variation represented by width and fluctuation at the edge of the pattern could be caused by characteristic changes of the resist material during the lithography processes. We determined the effect of polymer chain conformation on LER formation and how it finally contributed to LER formation with various resist material parameters (e.g., Flory–Huggins parameter, molecular weight, protected site ratio, and Tg).
A data mining approach for classification of orthostatic and essential tremor based on MRI‐derived brain volume and cortical thickness

Orthostatic tremor (OT) is an extremely rare, misdiagnosed, and underdiagnosed disorder affecting adults in midlife. There is debate as to whether it is a different condition or a variant of essential tremor (ET), or even, if both conditions coexist. Our objective was to use data mining classification methods, using magnetic resonance imaging (MRI)‐derived brain volume and cortical thickness data, to identify morphometric measures that help to discriminate OT patients from those with ET.
Aflatoxin M1 in milk in Hisar city, Haryana, India and risk assessment

ABSTRACT Aflatoxin M1 (AFM1) contamination in 150 samples of milk, sold in market of Hisar city of Haryana, India, was investigated by using High Pressure Liquid Chromatography (HPLC). Out of these, 40 samples contained AFM1 at a concentration below the limit of detection (LOD) of 0.052 μg/kg. Among the AFM1 contaminated samples, 46 raw milk samples contained a concentration above the LOD but less than the limit of quantitation (LOQ), whereas 64 samples were above the LOQ. Of these samples, 31 exceeded the maximum limit of 0.5 μg/kg prescribed by FSSAI, India. Based on this study, the dietary intake of AFM1 for adults through consumption of milk was estimated. The results indicated that AFM1 contamination can be a food safety issue for raw and pasteurised milk consumed in India. Therefore, there is a need for a national monitoring programme to control the level of mycotoxins in milk.
Possible Mechanisms of Biological Effects Observed in Living Systems during 2H/1H Isotope Fractionation and Deuterium Interactions with Other Biogenic Isotopes

This article presents the original descriptions of some recent physics mechanisms (based on the thermodynamic, kinetic, and quantum tunnel effects) providing stable 2H/1H isotope fractionation, leading to the accumulation of particular isotopic forms in intra- or intercellular space, including the molecular effects of deuterium interaction with 18O/17O/16O, 15N/14N, 13C/12C, and other stable biogenic isotopes. These effects were observed mainly at the organelle (mitochondria) and cell levels. A new hypothesis for heavy nonradioactive isotope fractionation in living systems via neutron effect realization is discussed. The comparative analysis of some experimental studies results revealed the following observation: “Isotopic shock” is highly probable and is observed mostly when chemical bonds form between atoms with a summary odd number of neutrons (i.e., bonds with a non-compensated neutron, which correspond to the following equation: Nn − Np = 2k + 1, where k ϵ Z, k is the integer, Z is the set of non-negative integers, Nn is number of neutrons, and Np is number of protons of each individual atom, or in pair of isotopes with a chemical bond). Data on the efficacy and metabolic pathways of the therapy also considered 2H-modified drinking and diet for some diseases, such as Alzheimer’s disease, Friedreich’s ataxia, mitochondrial disorders, diabetes, cerebral hypoxia, Parkinson’s disease, and brain cancer.
STUDIES ON VERATRUM ALKALOIDS

Veratramine, a secondary base of the veratrum alkaloid series, antagonizes the cardioaccelerator (or positive chronotropic) action of epinephrine in the isolated, denervated heart (HLP) of the dog, as well as in the whole circulatory system of dogs and cats under anesthesia, or of spinal or completely pithed cats. The site of action is in the pacemaker tissue of the heart. Atropine in large doses does not modify this veratramine effect. The action of epinephrine upon contractility (positive inotropic action) is not abolished by doses of veratramine which annul the cardioaccelerator action. It is thus possible to separate the two fundamental elements of the cardiac action of epinephrine. The vasodilator action of epinephrine upon the coronary vessels of the denervated isolated heart (HLP) of the dog, and the vasopressor action of epinephrine in the whole circulation are not abolished by doses of veratramine which have a very marked effect upon heart rate. The hitherto known antagonists of epinephrine, which abolish or prevent its vasopressor action, are devoid of the property of veratramine, when they are subjected to study under identical conditions. Of several other veratrum alkaloids studied, jervine, another secondary base, and the glycosides, veratrosine and pseudojervine, were also found capable of antagonizing the cardioaccelerator effect of epinephrine.
The Psychoactive Surveillance Consortium and Analysis Network (PSCAN): the first year.

BACKGROUND AND AIMS The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016-17). DESIGN Observational study involving patient records and biological samples. SETTING Seven academic emergency medical centers across the United States. PARTICIPANTS ED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel. MEASUREMENTS Clinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). FINDINGS Patients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P-value < 0.05). Patients in whom synthetic cannabinoid (SC) were found (n = 27) had lower median diastolic blood pressures (70.5 versus 77 mmHg, P = 0.046) compared with the rest of the cohort. In 64 cases of single drug ingestion, benzodiazepines were administered in 25 cases and considered effective by the treating physician in 21 (84%) cases. CONCLUSIONS During its first year of operation, the Psychoactive Surveillance Consortium and Analysis Network captured clinical data on new classes of drugs paired with biological samples over a large geographical area in the United States. Synthetic cannabinoids were the most common new psychoactive drug identified. Synthetic opioids were associated with a high rate of intubation and respiratory acidosis.
RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer

Raf kinase inhibitor protein (RKIP), an important modulator of intracellular signalling pathways, is commonly downregulated in multiple cancers. This reduction, or loss of expression, is correlated not only with the presence of metastasis, contributing to RKIP’s classification as a metastasis suppressor, but also with tumour aggressiveness and poor prognosis. Recent findings suggest a strong involvement of RKIP in the modulation of tumour microenvironment components, particularly by controlling the infiltration of specific immune cells and secretion of pro-metastatic factors. Additionally, RKIP interaction with multiple signalling molecules seems to potentiate its function as a regulator of inflammatory processes, mainly through stimulation of anti- or pro-inflammatory cytokines. Furthermore, RKIP is involved in the modulation of immunotherapeutic drugs response, through diverse mechanisms that sensitize cells to apoptosis. In the present review, we will provide updated information about the role of RKIP as an inflammatory and immune modulator and its potential implications in cancer will be addressed.
Home Cooking and Child Obesity in Japan: Results from the A-CHILD Study

This study aimed to investigate the association between the frequency of home cooking and obesity among children in Japan. We used cross-sectional data from the Adachi Child Health Impact of Living Difficulty study, a population-based sample targeting all fourth-grade students aged 9 to 10 in Adachi City, Tokyo, Japan. Frequency of home cooking was assessed by a questionnaire for 4258 caregivers and classified as high (almost every day), medium (4–5 days/week), or low (≤3 days/week). School health checkup data on height and weight were used to calculate body mass index z-scores. Overall, 2.4% and 10.8% of children were exposed to low and medium frequencies of home cooking, respectively. After adjusting for confounding factors, children with a low frequency of home cooking were 2.27 times (95% confidence interval: 1.16–4.45) more likely to be obese, compared with those with a high frequency of home cooking. After adjustment for children’s obesity-related eating behaviors (frequency of vegetable and breakfast intake and snacking habits) as potential mediating factors, the relative risk ratio of obesity became statistically non-significant (1.90; 95% confidence interval: 0.95–3.82). A low frequency of home cooking is associated with obesity among children in Japan, and this link may be explained by unhealthy eating behaviors.
Applicability and Limitations in the Characterization of Poly-Dispersed Engineered Nanomaterials in Cell Media by Dynamic Light Scattering (DLS)

The dispersion protocol used to administer nanomaterials (NMs) in in vitro cellular tests might affect their toxicity. For this reason, several dispersion procedures have been proposed to harmonize the toxicological methods, allowing for the comparison of the data that were obtained by different laboratories. At the same time, several techniques and methods are available to monitor the identity of the NMs in the cell media. However, while the characterization of suspensions of engineered NMs having narrow size distribution may be easily performed, the description of aggregated NMs forming polydispersions is still challenging. In the present study, sub-micrometric/nanometric TiO2, SiO2, and CeO2 were dispersed in cell media by using two different dispersion protocols, with and without albumin (0.5%) and with different sonication procedures. Dynamic Light Scattering (DLS) was used to characterize NMs in stock solutions and culture media. Pitfalls that affect DLS measurements were identified and, guidance on a critical analysis of the results provided. The NMs were then tested for their cytotoxicity (LDH leakage) toward murine macrophages (RAW 264.7) and PMA-activated human monocytes (THP-1). As markers of pro-inflammatory response, nitric oxide (NO) and cytokine IL-1β production were measured on RAW 264.7 and THP-1 cells, respectively. The pre-treatment with albumin added to a strong sonication treatment increases the stability and homogeneity of the suspensions of nanometric samples, but not of the submicrometric-samples. Nevertheless, while TiO2 and CeO2 were non-cytotoxic in any conditions, differences in cytotoxicity, NO, and IL-1β releases were found for the SiO2, depending upon the protocol. Overall, the results suggest that there is no one-fits-all method valid for all NMs, since each class of NMs respond differently. The definition of validated procedures and parameters for the selection of the most appropriate method of dispersion for each class of NM appears to be a more efficacious strategy for the harmonization of the dispersion protocols.
Identification of a Novel Adélie Penguin Circovirus at Cape Crozier (Ross Island, Antarctica)

Understanding the causes of disease in Antarctic wildlife is crucial, as many of these species are already threatened by environmental changes brought about by climate change. In recent years, Antarctic penguins have been showing signs of an unknown pathology: a feather disorder characterised by missing feathers, resulting in exposed skin. During the 2018–2019 austral summer breeding season at Cape Crozier colony on Ross Island, Antarctica, we observed for the first time an Adélie penguin chick missing down over most of its body. A guano sample was collected from the nest of the featherless chick, and using high-throughput sequencing, we identified a novel circovirus. Using abutting primers, we amplified the full genome, which we cloned and Sanger-sequenced to determine the complete genome of the circovirus. The Adélie penguin guano-associated circovirus genome shares <67% genome-wide nucleotide identity with other circoviruses, representing a new species of circovirus; therefore, we named it penguin circovirus (PenCV). Using the same primer pair, we screened 25 previously collected cloacal swabs taken at Cape Crozier from known-age adult Adélie penguins during the 2014–2015 season, displaying no clinical signs of feather-loss disorder. Three of the 25 samples (12%) were positive for a PenCV, whose genome shared >99% pairwise identity with the one identified in 2018–2019. This is the first report of a circovirus associated with a penguin species. This circovirus could be an etiological agent of the feather-loss disorder in Antarctic penguins.
Selected Predictors of the Sense of Intimacy in Relationships of Young Adults

The main research objective of this study was seeking the predictive role of closeness to parents, attachment, identity style, identity commitment, type of relationship, and having children in intimacy among young women and men. Many studies indicate differences in the level of engagement, communication, and satisfaction in relationships. The study group comprised 227 people, including 114 women (M = 29.99; SD = 4.36), and 113 men (M = 30.00; SD = 4.33). A total of 40% of the subjects were married, and the remaining 60% subjects were in informal relationships; 101 people had children and the other individuals were childless. The following instruments were used: The Miller Social Intimacy Scale, questionnaires to assess closeness and attachment, and the Identity Style Inventory. The significance of the differences and the stepwise regression analysis were performed. The results of the study demonstrated a higher level of intimacy in a relationship with a partner among women than men. The nature of a relationship does not matter to the sense of intimacy. However, closeness to parents during childhood and adolescence, the model of interpersonal relations, and the identity style are predictors of intimacy in a relationship. The study results can be used in creating preventive and educational programs focused on family life and satisfied relationships.
Development and Characterization of a Genetic Mouse Model of KRAS Mutated Colorectal Cancer

Patients with KRAS mutated colorectal cancer (CRC) represent a cohort with unmet medical needs, with limited options of FDA-approved therapies. Representing 40–45% of all CRC patients, they are considered ineligible to receive anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Although several mouse models of CRC have been developed during the past decade, one genetically resembling the KRAS mutated CRC is yet to be established. In this study C57 BL/6 mice with truncated adenomatous polyposis coli (APC) floxed allele was crossed with heterozygous KRAS floxed outbred mice to generate an APCf/f KRAS+/f mouse colony. In another set of breeding, APC floxed mice were crossed with CDX2-Cre-ERT2 mice and selected for APCf/f CDX2-Cre-ERT2 after the second round of inbreeding. The final model of the disease was generated by the cross of the two parental colonies and viable APC f/f KRAS +/f CDX2-Cre-ERT2 (KPC: APC) were genotyped and characterized. The model animals were tamoxifen (TAM) induced to generate tumors. Micro-positron emission tomography (PET) scan was used to detect and measure tumor volume and standard uptake value (SUV). Hematoxylin and eosin (H&E) staining was performed to establish neoplasm and immunohistochemistry (IHC) was performed to determine histological similarities with human FFPE biopsies. The MSI/microsatellite stable (MSS) status was determined. Finally, the tumors were extensively characterized at the molecular level to establish similarities with human CRC tumors. The model KPC: APC animals are conditional mutants that developed colonic tumors upon induction with tamoxifen in a dose-dependent manner. The tumors were confirmed to be malignant within four weeks of induction by H&E staining and higher radioactive [18F] fluoro-2-deoxyglucose (FDG) uptake (SUV) in micro-PET scan. Furthermore, the tumors histologically and molecularly resembled human colorectal carcinoma. Post tumor generation, the KPC: APC animals died of cachexia and rectal bleeding. Implications: This model is an excellent preclinical platform to molecularly characterize the KRAS mutated colorectal tumors and discern appropriate therapeutic strategies to improve disease management and overall survival.
Development of multiple dose platforms for oral drug delivery

A gastroretentive pulsatile drug delivery platform for oral administration was developed using a novel floating capsule which has been designed to deliver a drug as a pulsatile fashion while being retained in the stomach. A gastric fluid impermeable capsule body was used as a vessel to contain a drug layer as well as a lag-time controlling layer. A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy, patient compliance, and reduce harmful side effects by scaling back doses of drug administered.