Miracle-dz/UniFAR-FTUs huggingface dataset:
“In the past, the seeds I planted often didn’t grow.” A Mixed-Methods Feasibility Assessment of Integrating Agriculture and Nutrition Behaviour Change Interventions with Cash Transfers in Rural Bangladesh

Combining agriculture with behaviour change communication and other nutrition-sensitive interventions could improve feeding practices to reduce maternal and child undernutrition. Such integrated intervention requires rigorous design and an appropriate implementation strategy to generate an impact. We assessed feasibility and acceptability of an intervention package that combines nutrition counselling, counselling and support for home-gardening, and unconditional cash transfers delivered to women on a mobile platform for improving maternal and child nutrition behaviours among low-income families in rural Bangladesh. We used mixed-methods including in-depth interviews with women (20), key-informant interviews with project workers (6), and a cross sectional survey of women (60). Women well-accepted the intervention and reported to be benefited by acquiring new skills and information on home gardening and nutrition. They established homestead gardens of seasonal vegetables successfully and were able to find a solution for major challenges. All women received the cash transfer. Ninety-one percent of women spent the cash for buying foods, 20% spent it on purchasing seeds or fertilizers and 57% used it for medical and livelihood purchases. Project staff and mobile banking agent reported no difficulty in cash transfer. Combining nutrition-specific and -sensitive interventions is a feasible and acceptable approach. Using mobile technologies can provide additional benefits for the intervention to reach the disadvantage families in rural settings.
State-of-the-Art Technology of Model Organisms for Current Human Medicine

Since the 1980s, molecular biology has been used to investigate medical field mechanisms that still require the use of crude biological materials in order to achieve their necessary goals. Transcription factor-induced pluripotent stem cells are used in regenerative medicine to screen drugs and to support lost tissues. However, these cells insufficiently reconstruct whole organs and require various intact cells, such as damaged livers and diabetic pancreases. For efficient gene transfer in medical use, virally mediated gene transfers are used, although immunogenic issues are investigated. To obtain efficient detective and diagnostic power in intractable diseases, biological tools such as roundworms and zebrafish have been found to be useful for high-throughput screening (HST) and diagnosis. Taken together, this biological approach will help to fill the gaps between medical needs and novel innovations in the field of medicine.
The coevolution of the firm and the product attribute space

Traditionally, firm competition has been studied in contexts where the dimensionality of the product attribute space is given, and firms deploy their strategies constrained by this space. However, firms may exert influence on the local structure of the product attribute space by offering product variants with new attributes. As a result, the geometry of the product attribute space would change endogenously through firms’ actions, and this emergent new geometry modifies the conditions for subsequent firm behavior. By focusing on this interplay between actors and conditions, we explore the co-evolution of the firm and the product attribute space. Through a multi-variant Cournot competition framework, we develop a computational model in which firms invest to differentiate their products from other variants, but as minimally as possible so that demand from closely similar existing variants can be stolen. We introduce the fraction dimensionality of the attribute space as our critical independent variable, to reflect saturation of the space with product varieties. The simulation reveals that while new product variants are typically introduced by firms with scale economies, their performance gap with firms without scale economies reduces as fraction dimensionality increases. This indicates that space geometry evolution may favor small-scale players, even when their large-scale competitors are the driving force behind attribute space changes.
Mental illness stigma after a decade of Time to Change England: inequalities as targets for further improvement

Abstract Background England’s Time to Change programme to reduce mental health-related stigma and discrimination included a social marketing campaign using traditional and social media, and targeted middle-income groups aged 25–45 between 2009 and 2016. From 2017, the same age group on low to middle incomes were targeted, and the content focused on men’s mental health, by changing the advertising and adapting the ‘key messages’. This study investigates changes in stigma-related public knowledge, attitudes and desire for social distance in England since Time to Change began in 2008–19 and for 2017–19. Methods Using data from a face-to-face survey of a nationally representative quota sample of adults for England, we evaluated longitudinal trends in outcomes with regression analyses and made assumptions based on a simple random sample. The pre-existing survey used a measure of attitudes; measures of knowledge and desire for social distance were added in 2009. Results Reported in standard deviation units (95% CI), the improvement for knowledge for 2009–19 was 0.25 (0.19, 0.32); for attitudes, 2008–19, 0.32 (0.26, 0.39) and for desire for social distance, 2009–19 0.29 (0.23, 0.36). Significant interactions between year and both region and age suggest greater improvements in London, where stigma is higher, and narrowing of age differences. There were significant improvements between 2017 and 2019 in knowledge [0.09 (0.02, 0.16)] and attitudes [0.08 (0.02, 0.14)] but not social distance. Conclusion The positive changes support the effectiveness of Time to Change but cannot be definitively attributed to it. Inequalities in stigma by demographic characteristics present targets for research and intervention.
Regorafenib vs trifluridine/tipiracil for metastatic colorectal cancer refractory to standard chemotherapies: A multicenter retrospective comparison study in Japan

Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) showed survival benefits in metastatic colorectal cancer patients previously treated with standard chemotherapies; therefore, we compared the efficacy and safety of these two treatments. Patients with metastatic colorectal cancer treated with REG or FTD/TPI as a salvage-line therapy from May 2014 to December 2017 were included. We retrospectively analyzed long-term survival, safety, and clinical outcomes. Among 134 patients, 57 and 77 received REG and FTD/TPI, respectively. The REG group received more prior systemic chemotherapies and significantly more frequent additional chemotherapies than the FTD/TPI group did. The median follow-up was 6.2 months, whereas the median overall survival was 9.9 and 11.4 months in the REG and FTD/TPI groups, respectively (hazard ratio = 0.954, p = 0.837). The median progression-free survival was 2.0 and 3.3 months in the REG and FTD/TPI groups, respectively (hazard ratio = 0.52, p = 0.00047), indicating significant differences, whereas the objective response and disease control rates did not differ. The median overall survival of patients with additional subsequent chemotherapies after disease progression was longer than that of patients without additional chemotherapy. The most frequent grade ≥3 adverse events were hypertension and neutropenia in the REG and FTD/TPI groups, respectively. Our study suggested that sequential use of both drugs may prolong survival.
Tooth extraction before radiotherapy is a risk factor for developing osteoradionecrosis of the jaws: a systematic review.

OBJECTIVES The aim of this Systematic Review is to estimate the osteoradionecrosis rate in patients with head and neck cancer due to teeth extraction performed before radiotherapy and to identify possible risk factors. MATERIAL AND METHODS PRISMA protocol was used to evaluate and present the results. PubMed, Scopus, and Web of Science were used as search engines: English full-length papers of clinical studies, in peer-reviewed journals, were investigated. Cumulative meta-analysis was performed with a random effects model. PROSPERO registration code: CRD42018079986. RESULTS Among 2,020 records screened, 8 were included in this review. Sixteen of 494 patients who underwent tooth extraction before radiotherapy developed osteoradionecrosis, with an osteoradionecrosis incidence of 2.2% (95% Confidence of Interval = 0.6-3.9, p.<0.185, I^2=3044%). All cases were reported in the mandible. No other clinical risk factor for osteoradionecrosis was detected. CONCLUSIONS Even if it is generally recommended to remove oral foci before radiotherapy, this systematic review confirmed that teeth extractions before radiotherapy represent a risk factor for osteoradionecrosis; the considerable amount of missing data prevented us from identifying other possible risk factors for osteoradionecrosis onset. Major efforts should be done to perform sounder methodological clinical investigations.
Flowers in tri‐trophic systems: mechanisms allowing selective exploitation by insect natural enemies for conservation biological control

Many insects have coevolved with certain angiosperm taxa to act as pollinators. However, the nectar and pollen from such flowers is also widely fed upon by other insects, including entomophagous species. Conservation biological control seeks to maximise the impact of these natural enemies on crop pests by enhancing availability of nectar and pollen‐rich plants in agroecosystems. A risk with this approach is that pests may also benefit from the food resource. We show that the flowers of some plants (viz., buckwheat, Fagopyron esculentum Moench and dill, Anethum graveolens L.), and the extrafloral nectaries of faba bean (Vicia faba L.) benefit both Copidosoma koehleri Blanchard (Hymenoptera: Encyrtidae) and its host, the potato pest, Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae). In contrast, phacelia (Phacelia tanacetifolia Benth) and nasturtium (Tropaeoleum majus L.) benefited only the parasitoid. When adult moths of P. operculella were caged with flowers of phacelia or nasturtium, longevity of males and females, egg laying life, fecundity, average oviposition rate, and number of eggs in ovaries at death were no greater than in the control treatment with access to shoots without flowers plus water. All the foregoing measures were increased compared to the control when the moths were allowed access to dill, buckwheat or faba bean extrafloral nectaries. Such ‘selectivity’ has the potential to make the use of floral resources in conservation biological control more strategic. We present morphometric and observational evidence to illustrate how such mechanisms may operate.
Application of Azamulin to Determine the Contribution of CYP3A4/5 to Drug Metabolic Clearance Using Human Hepatocytes

Early determination of CYP3A4/5 contribution to the clearance of new chemical entities is critical to inform on the risk of drug-drug interactions with CYP3A inhibitors and inducers. Several in vitro approaches (recombinant P450 enzymes, correlation analysis, chemical and antibody inhibition in human liver microsomes) are available, but they are usually labor-intensive and/or suffer from specific limitations. In the present study, we have validated the use of azamulin as a specific CYP3A inhibitor in human hepatocytes. Azamulin (3 µM) was found to significantly inhibit CYP3A4/5 (>90%), whereas other P450 enzymes were not affected (less than 20% inhibition). Because human hepatocytes were used as a test system, the effect of azamulin on other key drug-metabolizing enzymes (aldehyde oxidase, carboxylesterase, UGT, flavin monooxygenase, and sulfotransferase) was also investigated. Apart from some UGTs showing minor inhibition (∼20%–30%), none of these non-P450 enzymes were inhibited by azamulin. Use of CYP3A5-genotyped human hepatocyte batches in combination with CYP3cide demonstrated that azamulin (at 3 µM) inhibits both CYP3A4 and CYP3A5 enzymes. Finally, 11 compounds with known in vivo CYP3A4/5 contribution have been evaluated in this human hepatocyte assay. Results showed that the effect of azamulin on the in vitro intrinsic clearance of these known CYP3A4/5 substrates was predictive of the in vivo CYP3A4/5 contribution. Overall, the study showed that human hepatocytes treated with azamulin provide a fast and accurate estimation of CYP3A4/5 contribution in metabolic clearance of new chemical entities. SIGNIFICANCE STATEMENT Accurate estimation of CYP3A4/5 contribution in drug clearance is essential to anticipate risk of drug-drug interactions and select the appropriate candidate for clinical development. The present study validated the use of azamulin as selective CYP3A4/5 inhibitor in suspended human hepatocytes and demonstrated that this novel approach provides a direct and accurate determination of the contribution of CYP3A4/5 (fraction metabolized by CYP3A4/5) in the metabolic clearance of new chemical entities.
The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?

Abstract Background Reexposure to methamphetamine with a single “priming dose” can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril “molecular container” calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. Methods Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. Results Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. Conclusions These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.
Effect of four different tillage practices on maize performance under rainfed conditions

An experiment was conducted on Ferric Acrisol under rainfed conditions during the 2010 minor crop growing season in Kumasi, Ghana to determine the effect of different tillage practices on Akposoe maize (Zea mays .L) variety performance. The experiment was arranged in a randomised complete block design with four treatments namely disc ploughing only, disc ploughing followed by disc harrowing, disc harrowing only and No Tillage. Each treatment was replicated three times. At ten weeks after planting, the disc harrowing only plots produced the tallest plant, biggest stem girth, highest number of leaves per plant, and highest leaf area index. On the other hand the No Tillage plots presented the shortest plant, smallest stem girth, lowest number of leaves per plant, and smallest leaf area index. At harvest, the longest root, highest dry matter yield and highest fresh cob weight were obtained from the disc harrowing only plots while the shortest root, lowest dry matter yield, lowest fresh cob weight, lowest dry cob weight, and smallest 1000-seed weight were located in the No Tillage plots. The disc ploughing followed by disc harrowing treatment produced the highest dry cob weight and highest 1000-seed weight. There was no significant difference in Akposoe maize plant growth, dry matter yield and yield components between the disc harrowing only and the disc ploughing followed by disc harrowing treatments. Thus, considering the soil and weather conditions of the experiment, the optimum tillage practice for producing Akposoe maize variety is disc harrowing only.
Screening and Characterization of Antiglycoxidant Anthocyanins from Vaccinium myrtillus Fruit Using DPPH and Methylglyoxal Pre-Column HPLC Assays

Vaccinium myrtillus fruit (bilberry) is well known for its high richness in anthocyanins, which may be responsible for its preventive effects on several oxidative and carbonyl stress-related pathologies. However, limited data are available regarding the antioxidant and antiglycative contributions of its constituents. Spectrometric analyses were performed to evaluate anthocyanin content, radical scavenging and antiglycative properties of an anthocyanin-rich extract from bilberries. Additionally, original DPPH and methylglyoxal pre-column HPLC methods were instigated to allow straightforward identification of the main contributors to radical and carbonyl trapping effects. Finally, representative pure anthocyanins were evaluated using classical DPPH and antiglycation assays. Delphinidin, petunidin and cyanidin glycosides were identified as the most effective radical scavenging constituents in both HPLC and spectrometric DPPH evaluations. Potent antiglycative activities were also assessed for cyanidin, delphinidin and petunidin glucosides as attested by their respective IC50 values of 114.2 ± 7.8, 130.5 ± 2.8, and 132.4 ± 3.7 µM. Interestingly, methylglyoxal spiking evaluation demonstrated that all bilberry anthocyanins exerted noticeable and comparable α-dicarbonyl trapping effects. Anthocyanins can be regarded as potent antiglycoxidant agents that might account for some health benefits of bilberries consumption. Besides, significant differences in their contributions were successfully highlighted by the employed pre-column HPLC assays.
Assessment of the Impact of Media Coverage on COVID-19–Related Google Trends Data: Infodemiology Study

Background The influence of media coverage on web-based searches may hinder the role of Google Trends (GT) in monitoring coronavirus disease (COVID-19). Objective The aim of this study was to assess whether COVID-19–related GT data, particularly those related to ageusia and anosmia, were primarily related to media coverage or to epidemic trends. Methods We retrieved GT query data for searches on coronavirus, cough, anosmia, and ageusia and plotted them over a period of 5 years. In addition, we analyzed the trends of those queries for 17 countries throughout the year 2020 with a particular focus on the rises and peaks of the searches. For anosmia and ageusia, we assessed whether the respective GT data correlated with COVID-19 cases and deaths both throughout 2020 and specifically before March 16, 2020 (ie, the date when the media started reporting that these symptoms can be associated with COVID-19). Results Over the last five years, peaks for coronavirus searches in GT were only observed during the winter of 2020. Rises and peaks in coronavirus searches appeared at similar times in the 17 different assessed countries irrespective of their epidemic situations. In 15 of these countries, rises in anosmia and ageusia searches occurred in the same week or 1 week after they were identified in the media as symptoms of COVID-19. When data prior to March 16, 2020 were analyzed, anosmia and ageusia GT data were found to have variable correlations with COVID-19 cases and deaths in the different countries. Conclusions Our results indicate that COVID-19–related GT data are more closely related to media coverage than to epidemic trends.
Investigation of risk factors for the conversion of mild cognitive impairment to dementia

Abstract Background Mild cognitive impairment (MCI) is an intermediate state between normal aging and dementia and is characterized by pathological cognitive decline. The study aimed at revealing the risk of MCI progressing to dementia through a follow-up investigation. Methods In 2011, 441 MCI subjects were recruited, and the disease status was tracked by the follow-up survey in 2017. Subjects with MCI stable (MCIs; N = 356) and MCI progressed into dementia (MCIp; N = 77) were analysed in our study. Community-dwelling old people of age ≥ 55 were recruited from 30 streets and 24 committees (or communities) of the Pudong New District (Shanghai, China). Neuropsychological tests of MMSE, MoCA, 17-item HAMD-17, ADL and HIS were performed. Additionally, the correlations of neuropsychological items and MCIp were explored by univariate and multivariate regression analyses. Results MCIp patients had the lower MMSE and MoCA total scores, whereas the ADL, and HIS total score in MCIp group were higher than in MCIs group. The univariate analysis revealed age, attention (MoCA), visuospatial/executive, number of births, marital status and attention and calculation were significant predictors of MCI progression. In multivariate analysis, age was an independent risk factor of MCI aggravating, while attention (MoCA) was independent protective factor for MCI progression. Conclusions Age and worsening attention but not depression in MCI patients were independently associated with the progression of dementia in a 6-year follow-up period.
Phase I trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2 and non-BRCA1/2 mutant cancers.

Preclinical studies have demonstrated synergy between poly(ADP-ribose) polymerase (PARP) and phosphatidylinositol-3-kinase (PI3K)/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing a prospective intrapatient dose-escalation design to assess two schedules of capivasertib (AKT inhibitor) with olaparib (PARP inhibitor) in 64 patients with advanced solid tumors. Dose expansions enrolled germline BRCA1/2-mutant tumors, or BRCA1/2-wildtype cancers harboring somatic DNA damage response (DDR) or PI3K/AKT pathway alterations. The combination was well-tolerated. Recommended phase 2 doses for the two schedules were: olaparib 300mg BID with either capivasertib 400mg BID 4-days-on, 3-days-off, or capivasertib 640mg BID 2-days-on, 5-days-off. Pharmacokinetics were dose-proportional. Pharmacodynamic studies confirmed pGSK3β suppression, increased pERK and decreased BRCA1 expression. 25 (44.6%) of 56 evaluable patients achieved clinical benefit (RECIST CR/PR or stable disease ≥4 months), including patients with tumors harboring germline BRCA1/2-mutations and BRCA1/2-wildtype cancers with or without DDR and PI3K/AKT pathway alterations.