Miracle-dz/UniFAR-FTUs huggingface dataset:
Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome

Abstract We asked whether the physiological and morphologic properties of hypoglossal motor neurons (CNXII MNs) that innervate protruder or retractor tongue muscles are disrupted in neonatal LgDel mice that carry a heterozygous deletion parallel to that associated with DiGeorge/22q11.2 deletion syndrome (22q11.2DS). Disrupted coordination of tongue movement in LgDel mouse pups may contribute to suckling, feeding, and swallowing (S/F/S) disruptions that parallel pediatric dysphagia in infants and toddlers with 22q11.2DS. Using an in vitro rhythmically active medullary slice preparation, we found spontaneous firing as well as IPSC frequency differed significantly in neonatal LgDel versus wild-type (WT) protruder and retractor CNXII MNs that were identified by retrograde tracing from their target muscles. In response to respiration-related activity, initiation and decay of transiently increased firing in WT protruder MNs is delayed in LgDel, accompanied by altered excitatory/inhibitory (E/I) balance. In addition, LgDel retractor MNs have a transient increase in firing with diminished IPSC frequency that is not seen in WT. There were no significant differences in cell body volume of either XII class in WT and LgDel. Sholl analysis showed the total numbers of dendritic intersections (at 50- and 90-μm radii from the cell soma) were significantly greater for LgDel versus WT retractor MNs. Thus, the physiological, synaptic and cellular properties of distinct classes of CNXII MNs that coordinate tongue movement in neonatal WT mice are altered in LgDel. Such changes could contribute to sub-optimal coordination of S/F/S that underlies pediatric dysphagia in 22q11.2DS.
‘They deserve a treat’: the nature and antecedents of parental licensing surrounding children’s physical activity

Abstract Objective: Little is known about parents’ compensatory health beliefs (CHB) surrounding their children’s engagement in physical activity (PA). Our aim was to provide evidence regarding the nature of, and factors underpinning, parents’ PA-related compensatory beliefs for their children. Design: A qualitative descriptive approach and thematic content analysis were employed. Setting: Parents were recruited from community sport and PA programmes. Participants: Eighteen parents aged 32–52 years (mean age = 40·8 (sd 5·4) years; six males; twelve females). Results: Analyses indicated that parents compensate through ‘passive’ or ‘active’ means. Among parents who compensated, most described their provision of ‘treat’ foods/drinks and a minority described allowing extended sedentary time to their children. Parents’ reasons underpinning these beliefs related to their child’s general physical/health status and psychological characteristics, and their own motivation and mood state. Conclusions: These findings provide the first evidence of unhealthy dietary and sedentary behaviour CHB that parents may hold regarding their children’s involvement in PA.
Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study

Background Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies. The standard dose is 420 mg daily; however, its irreversible binding mechanism allows adequate target blockade at much lower doses due to prolonged effect. Dose reductions or interruptions are often used in clinical practice to limit its distinct side effects, including diarrhea, bleeding and atrial fibrillation and emerging evidence exists that these do not hinder efficacy. Using a retrospective clinical audit of a single-center outpatient hematology clinic, we aimed to examine outcomes and toxicities of a reduced frequency dose regimen of ibrutinib in patients beyond the confines of a clinical trial. Methods A small pilot study was conducted on 16 voluntary CLL patients that had achieved partial or complete remission on standard dose ibrutinib and were considering cessation due to side effects. Patients were consented and prescribed a 420 mg thrice weekly regimen and side effects and outcomes were recorded on routine review. A retrospective clinical audit from 2015 to 2018 was then conducted to compare pilot participants to patients that had remained on standard dosing and results from the extended follow-up of the landmark RESONATE trial. Results None of the 16 patients in the pilot relapsed or died during the study period equating to a 100% progression free and overall survival. There was resolution or reduction in all side effects reported following switchover; however, the study was too small to establish a statistical relationship. Conclusion This is the first study to demonstrate use of a thrice weekly regimen to reduce ibrutinib-related toxicities whilst preserving safety and efficacy in patients following complete or partial remission on standard dose therapy. Higher powered, prospective studies are required to establish positive health and financial implications in the elderly and vulnerable CLL demographic.
Reproductive and natal homing of marine threespine sticklebacks (Gasterosteus aculeatus)

Natal and reproductive homing were investigated in marine and anadromous populations of threespine sticklebacks (Gasterosteus aculeatus). Three breeding sites within 1 km 2 of Pender Harbour, British Columbia, were examined. For the reproductive homing experiment (displacement of adults from a breeding site), female sticklebacks from Oyster Lagoon, Salt Lagoon, and Paq Creek were marked and displaced (.15 1.0 km) to three release sites. These displaced females predominately returned to their original breeding sites, although there was some straying. The proportion of marked fish recaptured at their original breeding site ranged from 0.81 to 1.00. The anadromous population (Paq Creek) showed the strongest tendency to return (0.99 1.00). Natal homing (return to birth site) was investigated in the Oyster Lagoon population. Young of the year were marked on three different outmigrations (April 1991, August 1991, and April 1992): 0.85 %, 3.5% and 5.2 % respectively, were recaptured as adults during the 1992 breeding season at Oyster Lagoon. Relatively short stays outside the lagoon (2 4 months), by juveniles that overwintered in Oyster Lagoon, resulted in strong natal homing and weak straying to adjacent breeding sites; however, straying to Salt Lagoon increased with longer stays outside the lagoon. This suggests an inverse relationship between the length of time spent out of the lagoon and the accuracy of homing. Straying to the anadromous breeding site (Paq Creek) remained low for all lengths of stay in the sea (2 16 months). This maintained avoidance of Paq Creek suggests that the marine and anadromous populations may be genetically isolated. The level of straying between Salt and Oyster lagoons probably is sufficient to prevent divergence between these adjacent marine populations. Generally however, this study demonstrates both reproductive and natal homing in threespine sticklebacks and, on a larger geographic scale, this natal
An Evaluation of Awareness, Knowledge, and Use of Folic Acid and Dietary Folate Intake among Non-Pregnant Women of Childbearing Age and Pregnant Women: A Cross-Sectional Study from Turkey

ABSTRACT This study was carried out to evaluate awareness, knowledge, and use of folic acid and dietary folate intake among non-pregnant women of childbearing age and pregnant women. A cross-sectional study was completed with 1442 women (1106 non-pregnant and 336 pregnant) in Ankara, Turkey. The individuals’ awareness, knowledge, and use of folic acid were questioned and food consumption were taken. More than two-thirds of the non-pregnant and pregnant women had heard of folic acid (77.2% and 89.0%, respectively). The pregnant women (53.9%) knew more that folic acid should be used before conception in order to prevent congenital anomalies than non-pregnant women (41.4%). It was found that 70.2% of the pregnant women and only 15.1% of the non-pregnant women used folic acid supplementation. The pregnant women (1368.4 mcg; 330.4 mcg) significantly had higher folic acid and dietary folate intake than non-pregnant women (29.6 mcg; 289.3 mcg) (p < .01). Despite many public health campaigns, awareness, knowledge, and appropriate use of folic acid are still inadequate and not at the desired level in women of childbearing age.
Antitumor Effects of Fucoidan Via Apoptotic and Autophagic Induction on HSC-3 Oral Squamous CellCarcinoma

Objective: Many studies suggested that fucoidan has anticancer potential. The objective of the present study was to determine the cytotoxic effects and mechanism of cell death induced by fucoidan extracted from Fucus vesiculosus on HSC-3 oral squamous cell carcinoma. Methods: HSC-3 cells were treated with 0, 100, 200, and 400 μg/mL of fucoidan. Cell viability was measured using MTT assay. Apoptosis and cell cycle were measured with a flow cytometry-based assay. Chromatin condensation and nuclear fragmentation were determined using Hoechst 33342 staining. Mitochondrial membrane potential (ΔΨm) was determined using the JC-1 kit. The apoptotic, anti-apoptotic, and autophagic markers study were done by western blot analysis. Results: the viable cell number of treated HSC-3 cells was decreased. Moreover, treated cells were arrested in the G0/G1 phase. Annexin V/PI staining revealed that fucoidan could induce apoptosis in HSC-3 cells. Western blot analysis suggested the up-regulation of apoptotic markers including cleaved caspase-3, cleaved PARP, Bax, and autophagic markers including LC3-II and Beclin-1 but down-regulation of anti-apoptotic markers, Bcl-2. Fucoidan could disturb ΔΨm and induce chromatin condensation with nuclear fragmentation. Conclusion: fucoidan has potential in anticancer properties against HSC-3 cells manifested by the induction of apoptosis, cell cycle arrest, and autophagy.
Exploitation of the COVID-19 pandemic by e-cigarette marketers

Over the last decade, a wide variety of e-cigarette advertisements have claimed superior healthfulness compared with cigarettes.1 Recently, we recognised a novel form of health reassurance advertising, promotion of e-cigarettes via COVID-19 pandemic themes. This led us to systematically explore COVID-19 marketing of e-cigarette brands and vape stores on their websites and Instagram accounts. We have collected over 300 COVID-19 themed e-cigarette promotional images and posted them to our online repository (tobacco.stanford.edu/COVID-19). 2 These images represent 21 e-cigarette brands and 41 online vaping stores that vend multiple brands. The COVID-19 messaging in these advertisements took several forms. As essential supplies became scarce in stores, e-cigarette brands offered these much-needed supplies, including masks, toilet paper rolls and hand sanitisers, as gifts contingent on the purchase of vaping products (figure 1). Some brands (eg, Podsalt, BLVK and One Drop Vape) offered free hand sanitiser with the purchase of any of its products. Podsalt described its sanitiser as ‘WHO recommended’ and claimed that it ‘kills 99.9% of bacteria’. 3 VaporDNA offered two strengths of CBD-enriched hand sanitisers (50 mg and 200 mg), while Vape Craft offered the option of sanitiser with or without CBD.4 5 The British nicotine liquid manufacturer MyVapery/Xyfil claimed that it has transformed 80% of its production capacity to produce 50 000 alcohol-based hand sanitisers per day.6 The brand created a website (https://www.handsanitising.com/) and Instagram page (@handsanitising) to market its brand of hand sanitiser.7 Figure 1 Examples of essential pandemic supplies (eg, hand sanitisers, masks and toilet paper) offered by e-cigarette companies as a bonus to spur sales. In the case of Vintage Vapor, they appear to have added these essential supplies to their product line offered for sale. Note that some of the hand sanitisers come in the company’s e-liquid bottles, raising concern over potential accidental use …
Categorical grouping is not required for guided conjunction search

Knowledge of target features can guide attention in many conjunction searches in a top-down manner. For example, in search of a red vertical line among blue vertical and red horizontal lines, observers can guide attention toward all red items and all vertical items. In typical conjunction searches, distractors often form perceptually vivid, categorical groups of identical objects. This could favor the efficient search via guidance of attention to these “segmentable” groups. Can attention be guided if the distractors are not neatly segmentable (e.g., if colors vary continuously from red through purple to blue)? We tested search for conjunctions of color × orientation (Experiments 1, 3, 4, 5) or length × orientation (Experiment 2). In segmentable conditions, distractors could form two clear groups (e.g., blue steep and red flat). In non-segmentable conditions, distractors varied smoothly from red to blue and/or steep to flat; thus, discouraging grouping and increasing overall heterogeneity. We found that the efficiency of conjunction search was reasonably high and unaffected by segmentability. The same lack of segmentability had a detrimental effect on feature search (Experiment 4) and on conjunction search, if target information was limited to one feature (e.g., find the odd item in the red set, “subset search,” Experiment 3). Guidance in conjunction search may not require grouping and segmentation cues that are very important in other tasks like texture discrimination. Our results support an idea of simultaneous, parallel top-down guidance by multiple features and argue against models suggesting sequential guidance by each feature in turn.
Redox State in Solanum Seedlings under Cadmium Stress Conditions

Cadmium content and distribution as well as its effects on growth and oxidative stress were investigated in 17-day-old tomato seedlings (Solanum). The content of Cd increased with external Cd concentrations, and was considerably higher in roots than in shoots. Excess Cd suppressed biomass production of both roots and shoots and reduced chlorophyll content in leaves. Further, substantial increases of H2O2 and ascorbate contents, malondialdehyde formation, and antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (GPX) were observed in Cd-stressed plants in comparison with controls. The results suggest that the phytotoxic effects of Cd in tomato seedlings may be achieved by an enhanced production of active oxygen species (AOS) and subsequent lipid peroxidation with ascorbate synthesis as singe of tomato tolerance.
Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study

Untargeted metabolomics is expected to lead to a better mechanistic understanding of diseases and thus applications of precision medicine and personalized intervention. To further increase metabolite coverage and achieve high accuracy of metabolite quantification, the present proof-of-principle study was to explore the applicability of integration of two-dimensional gas and liquid chromatography-mass spectrometry (GC × GC-MS and 2DLC-MS) platforms to characterizing circulating polar metabolome extracted from plasma collected from 29 individuals with colorectal cancer in comparison with 29 who remained cancer-free. After adjustment of multiple comparisons, 20 metabolites were found to be up-regulated and 8 metabolites were found to be down-regulated, which pointed to the dysregulation in energy metabolism and protein synthesis. While integrating the GC × GC-MS and 2DLC-MS data can dramatically increase the metabolite coverage, this study had a limitation in analyzing the non-polar metabolites. Given the small sample size, these results need to be validated with a larger sample size and with samples collected prior to diagnostic and treatment. Nevertheless, this proof-of-principle study demonstrates the potential applicability of integration of these advanced analytical platforms to improve discrimination between colorectal cancer cases and controls based on metabolite profiles in future studies.
Flow cytometry in detection of Nucleophosmin 1 mutation in acute myeloid leukemia patients: A reproducible tertiary hospital experience

Nucleophosmin 1 (NPM1) mutation is one of the most frequent gene mutations in adult acute myeloid leukemia (AML), being detected in 35% of all cases and in up to 60% of patients with normal karyotype AML. AML with mutated NPM1 has distinct pathology, immunophenotyping, and confirmed favorable prognostic significance. Hence, AML with mutated NPM1 is a separate entity in the revised 2016 World Health Organization classification. This study aimed to evaluate the use of a reproducible flow cytometry approach in the assay of mutant NPM1 protein in AML patients and to correlate flow cytometric results with the NPM1 gene mutation.
Myrsine (Myrsinoideae- Primulaceae) no sudeste e sul do Brasil

This work consists of the taxonomic treatment of Myrsine, Primulaceae, from the southeastern and southern regions of Brazil. All species described as Rapanea. are treated here as Myrsine. since the former has been placed in the synonymy with the latter. The genus is represented by dioecious shrubs and trees, with umbelliform inflorescences and globose, drupaceous fruits. Analysis of materials from herbaria and expeditions to collect specimens were performed. Analytical key, descriptions, notes on geographic distribution and illustrations are presented to identify the twenty three species of Myrsine found in the studied area.
A machine-learning expert-supporting system for diagnosis prediction of lymphoid neoplasms using a probabilistic decision-tree algorithm and immunohistochemistry profile database

Background Immunohistochemistry (IHC) has played an essential role in the diagnosis of hematolymphoid neoplasms. However, IHC interpretations can be challenging in daily practice, and exponentially expanding volumes of IHC data are making the task increasingly difficult. We therefore developed a machine-learning expert-supporting system for diagnosing lymphoid neoplasms. Methods A probabilistic decision-tree algorithm based on the Bayesian theorem was used to develop mobile application software for iOS and Android platforms. We tested the software with real data from 602 training and 392 validation cases of lymphoid neoplasms and compared the precision hit rates between the training and validation datasets. Results IHC expression data for 150 lymphoid neoplasms and 584 antibodies was gathered. The precision hit rates of 94.7% in the training data and 95.7% in the validation data for lymphomas were not statistically significant. Results in most B-cell lymphomas were excellent, and generally equivalent performance was seen in T-cell lymphomas. The primary reasons for lack of precision were atypical IHC profiles for certain cases (e.g., CD15-negative Hodgkin lymphoma), a lack of disease-specific markers, and overlapping IHC profiles of similar diseases. Conclusions Application of the machine-learning algorithm to diagnosis precision produced acceptable hit rates in training and validation datasets. Because of the lack of origin- or disease-specific markers in differential diagnosis, contextual information such as clinical and histological features should be taken into account to make proper use of this system in the pathologic decision-making process.
Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons

The mesolimbic dopamine (DA) system is involved in the regulation of multiple behaviors, including feeding, and evidence demonstrates that the melanocortin system can act on the mesolimbic DA system to control feeding and other behaviors. The melanocortin‐3 receptor (MC3R) is an important component of the melanocortin system, but its overall role is poorly understood. Because MC3Rs are highly expressed in the ventral tegmental area (VTA) and are likely to be the key interaction point between the melanocortin and mesolimbic DA systems, we set out to identify both the efferent projection patterns of VTA MC3R neurons and the location of the neurons providing afferent input to them. VTA MC3R neurons were broadly connected to neurons across the brain but were strongly connected to a discrete set of brain regions involved in the regulation of feeding, reward, and aversion. Surprisingly, experiments using monosynaptic rabies virus showed that proopiomelanocortin (POMC) and agouti‐related protein (AgRP) neurons in the arcuate nucleus made few direct synapses onto VTA MC3R neurons or any of the other major neuronal subtypes in the VTA, despite being extensively labeled by general retrograde tracers injected into the VTA. These results greatly contribute to our understanding of the anatomical interactions between the melanocortin and mesolimbic systems and provide a foundation for future studies of VTA MC3R neurons and the circuits containing them in the control of feeding and other behaviors.
Longitudinal Impact of Parent Factors in Adolescents With Migraine and Tension-Type Headache.

OBJECTIVE To examine longitudinal associations between parent factors (parent headache frequency and disability, protective parenting behaviors, parent catastrophizing) with adolescent headache-related disability and headache frequency over 6 months. BACKGROUND Theoretical models propose bidirectional, longitudinal relationships between parent factors and adolescent headache. Few studies have examined this using prospective study designs. DESIGN AND METHODS Participants were a cohort of 239 youth ages 11-17 years with recurrent migraine (with and without aura; chronic migraine) or tension-type headache (episodic and chronic) and their parents recruited from a pediatric neurology clinic and the community who completed assessments at baseline and 6-month follow-up. RESULTS After controlling for demographic and clinical covariates, we found that every point increase in baseline protective parenting behavior corresponded with a 2.19-point increase in adolescent headache frequency at follow-up (P = .026, 95% CI [0.27, 4.10]). Similarly, every point increase in baseline parent catastrophizing corresponded with a 0.93-point increase in adolescent headache-related disability (P = .029, 95% CI [0.09, 1.77]) and a . 13-point increase in adolescent headache frequency (P = .042, 95% CI [0.01, 0.25]) at follow-up. We also found support for the reverse association, where every point increase in baseline adolescent headache-related disability predicted a 0.03-point increase in parent catastrophizing (P = .016, 95% CI [0.01, 0.05]) and a 0.02-point increase in protective parenting behavior (P = .009, 95% CI [0.01, 0.03]) at follow-up. The remaining bidirectional, longitudinal associations tested between parent factors and adolescent headache were not statistically significant. CONCLUSION Findings suggest that family-based psychological interventions targeting modifiable adolescent and parent factors may lead to improvements in adolescent headache-related disability and reductions in adolescent headache frequency.
Minimum Cost of Transport and Ventilatory Patterns in Three African Beetles

Minimum cost of pedestrian transport (Mrun) was determined by treadmill running and flow-through oxygen respirometry in three species of flightless beetles, Psammodes striatus, Pachysoma hippocrates, and Anthia fabricii. Mrun was 1.67, 4.76, and 2.15 ml O₂/(g · km) (where g · km = ml O₂/[kg · m]), respectively, in these three species, which have typical masses of 2.9, 3.1, and 2.2 g, respectively. Extrapolations of vertebrate-based regressions of Mrun on mass predict similar values of Mrun given these masses. When combined with those for mammals and birds <1,000 g, all published Mrun data on insects are related to mass by the equation Mrun = 0.530M−0.325, where M is in kg and Mrun is in ml O₂/(g · km). All species ventilated discontinuously while at rest.