Miracle-dz/UniFAR-FTUs huggingface dataset:
The interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis

The Lower Rhombic Lip (LRL) is a transient neuroepithelial structure of the dorsal hindbrain, which expands from r2 to r7, and gives rise to deep nuclei of the brainstem, such as the vestibular and auditory nuclei and most posteriorly the precerebellar nuclei. Although there is information about the contribution of specific proneural-progenitor populations to specific deep nuclei, and the distinct rhombomeric contribution, little is known about how progenitor cells from the LRL behave during neurogenesis and how their transition into differentiation is regulated. In this work, we investigated the atoh1 gene regulatory network operating in the specification of LRL cells, and the kinetics of cell proliferation and behavior of atoh1a-derivatives by using complementary strategies in the zebrafish embryo. We unveiled that atoh1a is necessary and sufficient for specification of LRL cells by activating atoh1b, which worked as a differentiation gene to transition progenitor cells towards neuron differentiation in a Notch-dependent manner. This cell state transition involved the release of atoh1a-derivatives from the LRL: atoh1a progenitors contributed first to atoh1b cells, which are committed non-proliferative precursors, and to the lhx2b-neuronal lineage as demonstrated by cell fate studies and functional analyses. Using in vivo cell lineage approaches we revealed that the proliferative cell capacity, as well as the mode of division, relied on the position of the atoh1a progenitors within the dorsoventral axis. We showed that atoh1a may behave as the cell fate selector gene, whereas atoh1b functions as a neuronal differentiation gene, contributing to the lhx2b neuronal population. atoh1a-progenitor cell dynamics (cell proliferation, cell differentiation, and neuronal migration) relies on their position, demonstrating the challenges that progenitor cells face in computing positional information from a dynamic two-dimensional grid in order to generate the stereotyped neuronal structures in the embryonic hindbrain.
Contralateral Liver Hypertrophy and Oncological Outcome Following Radioembolization with 90Y-Microspheres: A Systematic Review

Radioembolization with 90Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the present systematic review was to summarize the evidence of contralateral liver hypertrophy and oncological outcome following unilateral treatment with radioembolization. A systematic literature search using the MEDLINE, EMBASE, and Cochrane libraries for studies published between 2008 and 2020 was performed. A total of 16 studies, comprising 602 patients, were included. The median kinetic growth rate per week of the contralateral liver lobe was 0.7% and declined slightly over time. The local tumor control was 84%. Surgical resection after radioembolization was carried out in 109 out of 362 patients (30%). Although the available data suggest that radioembolization prior to major hepatectomy is safe with a promising oncological outcome, the definitive role of radioembolization requires assessment within controlled clinical trials.
Phenotype and function of circulating memory T cells in human vitiligo *

Vitiligo is a chronic inflammatory skin disorder characterized by the loss of melanocytes. While a T helper cell (Th)1/cytotoxic T cell (Tc)1‐skewed immune response is now well demonstrated in vitiligo, recent data suggest that the T‐cell component could be more complex, involving different combinatorial T‐cell subsets.
Effectiveness of horticultural therapy in people with dementia: a quantitative systematic review.

AIMS AND OBJECTIVES To evaluate the effectiveness of horticultural therapy on cognitive function, agitation, positive emotion and engagement in people with dementia. BACKGROUND The number of people with dementia is increasing rapidly and non-pharmacological interventions such as horticultural therapy have been recommended as the first choice for these patients. Horticultural therapy involves participatory and ornamental horticultural therapy. Many original studies have examined the effectiveness of horticultural therapy in the last two decades. However, these studies vary in types of interventions, outcomes, and measurement. DESIGN A quantitative systematic review and meta-analysis. METHODS This systematic review was conducted under PRISMA guidelines. Randomized controlled trials (RCTs) and quasi-experimental studies involving horticultural therapy for people with dementia were included. Risk of bias was assessed by the Cochrane's and Joanna Briggs Institute's tool. Reference lists and a relevant journal were searched. Meta-analyses were conducted using RevMan 5.3. PubMed, CINAHL, Embase, BIOSIS Previews, Web of Science Core Collection, China National Knowledge Infrastructure, Wanfang, SinoMed, Cochrane library and ProQuest Health & Medical Complete were searched. Studies from database inception to July 1st, 2019 were included. RESULTS This systematic review included 14 studies (4 RCTs and 10 quasi-experimental studies) involving 411 people with dementia. The results of meta-analyses indicated that significant differences were found in the effectiveness of participatory horticultural therapy on total score of cognitive function, agitation, positive emotion, and engagement, but not in the effectiveness of ornamental horticultural activities on agitation and positive emotion. CONCLUSIONS The existing evidence supports the effectiveness of participatory horticultural therapy on cognitive function, agitation, positive emotion, and engagement. Future high-quality original studies are needed to draw more robust conclusions. RELEVANCE TO CLINICAL PRACTICE The results support the use of participatory horticultural therapy for improving cognitive function, agitation, positive emotion and engagement of people with dementia.
Cybervictimization in adolescence and its association with subsequent suicidal ideation/attempt beyond face-to-face victimization: a longitudinal population-based study.

BACKGROUND Cross-sectional associations have been documented between cybervictimization and suicidal risk; however, prospective associations remain unclear. METHODS Participants were members of the Quebec Longitudinal Study of Child Development (QLSCD), a prospective birth cohort of 2,120 individuals followed from birth (1997/98) to age 17 years (2014/15). Cybervictimization and face-to-face victimization experienced since the beginning of the school year, as well as serious suicidal ideation and/or suicide attempt were self-reported at ages 13, 15 and 17 years. RESULTS In cross-sectional analyses at 13, 15 and 17 years, adolescents cybervictimized at least once had, respectively, 2.3 (95% CI = 1.64-3.19), 4.2 (95% CI = 3.27-5.41) and 3.5 (95% CI = 2.57-4.66) higher odds of suicidal ideation/attempt after adjusting for confounders including face-to-face victimization, prior mental health symptoms and family hardship. Sensitivity analyses suggested that cybervictimization only and both cyber- and face-to-face victimization were associated with a higher risk of suicidal ideation/attempt compared to face-to-face victimization only and no victimization; however, analyses were based on small n. In prospective analyses, cybervictimization was not associated with suicidal ideation/attempt 2 years later after accounting for baseline suicidal ideation/attempt and other confounders. In contrast, face-to-face victimization was associated with suicidal ideation/attempt 2 years later in the fully adjusted model, including cybervictimization. CONCLUSIONS The cross-sectional association between cybervictimization and suicidal ideation/attempt is independent from face-to-face victimization. The absence of a prospective association suggested short-term effects of cybervictimization on suicidal ideation/attempt.
Mapping the Associations of the Plasma Lipidome with Insulin Resistance and Response to an Oral Glucose Tolerance Test.

CONTEXT Insulin resistance (IR) remains a global health challenge. Lipidomics offers an opportunity to identify biomarkers and better understand mechanisms of IR associated with abnormal lipid metabolism. OBJECTIVE To determine plasma lipid species associated with indices of insulin resistance and evaluate the lipidome response to an OGTT. DESIGN AND SETTING Community based cross-sectional. PARTICIPANTS AND SAMPLE Plasma samples (collected at 0 and 120 min during an OGTT) from non-obese, young adults aged 18-34 years (n=246) were analysed using liquid chromatography tandem mass spectrometry. MAIN OUTCOME MEASURES The associations between indices of insulin resistance and lipid classes and species (with a sex interaction term), or changes in lipid levels during an OGTT, were tested using linear models (adjusted for age, sex, BMI, total cholesterol, HDL-cholesterol and triglycerides). RESULTS Some (213) and (199) lipid species associated with HOMA-IR and insulin AUC respectively. Alkylphosphatidylcholine (10), alkenylphosphatidylcholine (23) and alkylphosphatidylethanolamine (6) species were associated with insulin AUC in men only. Species of phosphatidylcholine (7) and sphingomyelin (5) were associated in women only. In response to an oral glucose tolerance test, a perturbation in the plasma lipidome, particularly in acylcarnitine species was observed; and the changes in many lipid species were associated with insulin AUC. CONCLUSIONS The plasma lipidome and changes in lipid levels during an OGTT were associated with indices of insulin resistance. These findings underlie the involvement of molecular lipid species in the pathogenesis of insulin resistance and possibly crosstalk between insulin resistance and sex-specific regulation of lipid metabolism.
α2β1 Integrin Is Required for Optimal NK Cell Proliferation during Viral Infection but Not for Acquisition of Effector Functions or NK Cell–Mediated Virus Control

Key Points α2β1 deficiency does not alter the balance of NK cell/ILC1 generation. α2β1 deficiency does not alter NK cell maturation. α2β1-deficient NK cells efficiently protect from lethal mousepox and control MCMV. NK cells play an important role in antiviral resistance. The integrin α2, which dimerizes with integrin β1, distinguishes NK cells from innate lymphoid cells 1 and other leukocytes. Despite its use as an NK cell marker, little is known about the role of α2β1 in NK cell biology. In this study, we show that in mice α2β1 deficiency does not alter the balance of NK cell/ innate lymphoid cell 1 generation and slightly decreases the number of NK cells in the bone marrow and spleen without affecting NK cell maturation. NK cells deficient in α2β1 had no impairment at entering or distributing within the draining lymph node of ectromelia virus (ECTV)–infected mice or at becoming effectors but proliferated poorly in response to ECTV and did not increase in numbers following infection with mouse CMV (MCMV). Still, α2β1-deficient NK cells efficiently protected from lethal mousepox and controlled MCMV titers in the spleen. Thus, α2β1 is required for optimal NK cell proliferation but is dispensable for protection against ECTV and MCMV, two well-established models of viral infection in which NK cells are known to be important.
Delayed recognition of Ebola virus disease is associated with longer and larger outbreaks

ABSTRACT The average time required to detect an Ebola virus disease (EVD) outbreak following spillover of Ebola virus (EBOV) to a primary human case has remained essentially unchanged for over 40 years, with some of the longest delays in detection occurring in recent decades. In this review, our aim was to examine the relationship between delays in detection of EVD and the duration and size of outbreaks, and we report that longer delays are associated with longer and larger EVD outbreaks. Historically, EVD outbreaks have typically been comprised of less than 100 cases (median = 60) and have lasted less than 4 months (median = 118 days). The ongoing outbreak in Democratic Republic of the Congo, together with the 2013–2016 west Africa outbreak, are stark outliers amidst these trends and had two of the longest delays in detection on record. While significant progress has been made in the development of EVD countermeasures, implementation during EVD outbreaks is problematic. Thus, EVD surveillance must be improved by the broad deployment of modern diagnostic tools, as prompt recognition of EVD has the potential to stem early transmission and ultimately limit the duration and size of outbreaks.
Molecular Carcinogenesis

Funding information National Cancer Institute, Grant/Award Number: CA72720; National Institute of Environmental Health Sciences, Grant/Award Number: ES005022; Foundation for the National Institutes of Health, Grant/Award Numbers: AT007036, CA133021 Abstract α‐Tocopherol (α‐T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α‐T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α‐T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α‐T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ‐ and δ‐forms of tocopherols and tocotrienols (T3). In comparison with α‐T, these forms have much lower systemic bioavailability but have shown stronger cancer‐preventive activities in many studies in animal models and cell lines. γ‐T3 and δ‐T3 generally have even higher activities than γ‐T and δ‐T. In this article, we review recent results from human and laboratory studies on the cancer‐preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.
Awareness About Medication-Related Osteonecrosis of the Jaw Among Dental Professionals: A Multicentre Study.

PURPOSE Bisphosphonates and non-bisphosphonate antiangiogenic and antiresorptive agents are widely used in the management of bone diseases and cancer. A subset of patients receiving these drugs can manifest with medication-related osteonecrosis of the jaw (MRONJ) and it is one of the major complications faced in dental practice. Dentoalveolar and periodontal surgery are the major risk factors associated with it. Therefore, a dentist must have adequate knowledge to promptly identify patients at risk and efficiently manage the condition. This multicentre study was designed with an aim to assess the level of knowledge and awareness regarding MRONJ among dentists from six dental schools. METHODS AND MATERIALS An online self-administered questionnaire was sent to all the dentists from six dental schools through Google forms. The results obtained were statistically analysed. The Kolmogorov-Smirnov test was performed to check for normality of data, while the Mann-Whitney U-test and chi-square test were used to compare the responses to each question. RESULTS The questionnaire was sent to 570 dentists, out of which 234 responses were obtained. The majority of participants were aware of the term 'MRONJ' (83.3%), clinical indications of bisphosphonates (61.5%) and its mechanism of action (72.2%). However, 68.4% and 61.5% of dentists had no knowledge about the 'drug holiday' concept and risk factors associated with MRONJ, respectively. CONCLUSION Although most of the participants had knowledge regarding certain aspects of MRONJ, such as mechanism of action and clinical indications of bisphosphonates, there was a lack of awareness about the drug holiday concept and drug-associated risk factors. This emphasises the need to spread awareness among the dental community, not only in tertiary healthcare centres, but also among private dentists and dental interns to prevent cases of MRONJ.
The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword

This article addresses the importance of oxidative processes in both the generation of functional gametes and the aetiology of defective sperm function. Functionally, sperm capacitation is recognized as a redox-regulated process, wherein a low level of reactive oxygen species (ROS) generation is intimately involved in driving such events as the stimulation of tyrosine phosphorylation, the facilitation of cholesterol efflux and the promotion of cAMP generation. However, the continuous generation of ROS ultimately creates problems for spermatozoa because their unique physical architecture and unusual biochemical composition means that they are vulnerable to oxidative stress. As a consequence, they are heavily dependent on the antioxidant protection afforded by the fluids in the male and female reproductive tracts and, during the precarious process of insemination, seminal plasma. If this antioxidant protection should be compromised for any reason, then the spermatozoa experience pathological oxidative damage. In addition, situations may prevail that cause the spermatozoa to become exposed to high levels of ROS emanating either from other cells in the immediate vicinity (particularly neutrophils) or from the spermatozoa themselves. The environmental and lifestyle factors that promote ROS generation by the spermatozoa are reviewed in this article, as are the techniques that might be used in a diagnostic context to identify patients whose reproductive capacity is under oxidative threat. Understanding the strengths and weaknesses of ROS-monitoring methodologies is critical if we are to effectively identify those patients for whom treatment with antioxidants might be considered a rational management strategy.
Quantifying the Risks and Benefits of Continuing Labor Induction: Data for Shared Decision-Making

Abstract Objective This study aimed to quantify the relative maternal and fetal risks and benefits of continuing labor induction. Study Design This retrospective cohort study included nulliparous women with nonanomalous, singleton, vertex, term pregnancies undergoing labor induction with intact membranes at a tertiary-care academic hospital from January 2015 to April 2017. The primary outcome was mode of delivery. Secondary outcomes included hemorrhage, transfusion, infection, and composite neonatal morbidity. The data were analyzed using chi-square and Fisher's exact tests. Multivariable regression was used to control for potential confounders. Results A total of 955 patients met the inclusion criteria. The median induction duration was 32.3 hours (interquartile range: 20.4–41 hours) and the vaginal delivery rate was 70.5% (n = 673). The chance of vaginal delivery at 12, 24, 36, 48, 60, and ≥60 hours was 76, 83, 77, 74, 72, and 48%, respectively. After controlling for confounders, there was a 20% decrease in chance of vaginal delivery with induction ≥ 24 hours compared with induction < 24 hours. The adjusted relative risks of hemorrhage, transfusion, and infection with induction ≥ 24 hours compared with induction < 24 hours were 1.9, 2.2, and 2.7, respectively (95% confidence interval [CI] of 1.4–2.5, 1.1–3.9, and 1.8–4.0, respectively). The relative risk for these outcomes remained stable or decreased at each subsequent time point. The increasing risks of hemorrhage and infection were primarily among patients who underwent cesarean delivery. There was no association between induction duration and neonatal morbidity. Conclusion In this cohort, the chance of vaginal delivery remained nearly 50% even when induction extended beyond 60 hours. Risks of hemorrhage and maternal infection rose modestly over time, but primarily in patients who underwent cesarean delivery. There was no difference in the risk of transfusion beyond 24 hours and no association between induction duration and neonatal morbidity. These findings may be useful when engaging patients in shared decision-making during labor induction.
miR‐497‐5p mediates starvation‐induced death in colon cancer cells by targeting acyl‐CoA synthetase‐5 and modulation of lipid metabolism

Modulation of fatty acids metabolism is an appropriate strategy for starvation‐induced death in tumor cancers. Colon cancer cells express a high level of acyl‐CoA synthetase‐5 (ACSL5), and as yet no therapeutic approach has been achieved. Herein, ACSL5‐related microRNAs (miRNAs) were identified via TargetScan, and their impacts on ACSL5 and lipid content along with metabolic activity, cell cycle, migration, and invasion of colorectal cancer (CRC) cells were examined, and subsequently compared with transcriptome for better visualization of intracellular‐signaling networks. In vivo analysis was performed using BALB/c mice xenograft model of CRC injected with target miRNA. Clinical significances were also evaluated in 80 CRC tumors and matched adjacent normal tissues. There was a reverse correlation between ACSL5 and miR‐497‐5p, which miR‐497‐5p overexpression modulated CRC cell proliferation and development. A similar observation was received from the in vivo examination in which intratumoral injection of miR‐497‐5p reversed the tumor growth in the CRC xenograft model. Downregulation of miR‐497‐5p correlated with tumor differentiation, tumor, node, and metastasis staging, lymph node metastasis, and poor survival in patients with CRC. These results suggested that miR‐497‐5p upregulation could be considered as a therapeutic strategy for modulation of lipid metabolism in colon cancer.
Different β‐cell secretory phenotype in non‐obese compared to obese early type 2 diabetes

Type 2 diabetes (T2D) is characterized by impaired tissue sensitivity to insulin action (ie, insulin resistance) and impaired β‐cell insulin secretion. Because obesity contributes importantly to the development of insulin resistance, we sought to determine whether insulin secretory defects would predominate in non‐obese compared to obese T2D.
Sleep Disturbance in Patients with Urticaria and Atopic Dermatitis: An Underestimated Burden

This study examined the relationship between insomnia and the frequent itching skin diseases, atopic dermatitis and chronic urticaria. Patients with chronic inflammatory dermatological diseases with pruritus were evaluated for insomnia (Insomnia Severity Index; ISI) and impairment in dermatological quality of life (Dermatology Life Quality Index; DLQI). Disease activity was measured using validated scores. A total of 61 patients participated in the study. Patients with atopic dermatitis had a mean ISI score of 8.7 before flares and 16 when a flare occurred. The mean DLQI score in atopic dermatitis was 11.4. The mean ISI score in patients with chronic urticaria was 6.8 before flares and 14.9 when a flare occurred. In patients with chronic urticaria the mean DLQI score was 8.5. An increase in insomnia during a disease flare was demonstrated in both groups. Thus, sleep is a factor to consider during treatment of itching skin diseases. The results of this pilot study indicate that pruritus may not be the only reason for insomnia in patients with atopic dermatitis or chronic urticaria.