Miracle-dz/UniFAR-FTUs huggingface dataset:
Noninvasive genotyping and monitoring of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer by capture-based next-generation sequencing

Noninvasive genotyping of driver genes and monitoring of tumor dynamics help make better personalized therapeutic decisions. However, neither PCR-based assays nor amplicon-based targeted sequencing can detect fusion genes like anaplastic lymphoma kinase (ALK) rearrangements in blood samples. To investigate the feasibility and performance of capture-based sequencing on ALK fusion detection, we developed a capture-based targeted sequencing panel to detect and quantify rearrangement events, along with other driver mutation variants in plasma. In this perspective study, we screened 364 patients with advanced non-small cell lung cancer (NSCLC) for ALK rearrangements, and collected blood samples from 24 of them with confirmed ALK rearrangements based on their tissue biopsies. ALK rearrangements were successfully detected in 19 of 24 patients at baseline with 79.2% (95% CI 57.9%, 92.9%) sensitivity and 100% (36/36) specificity. Among the 24 patients, we obtained longitudinal blood samples from 7 of them after either chemotherapy and/or Crizotinib treatment for disease monitoring. The by-sample detection rate of ALK rearrangements after treatment drops to 69.2% (9 of 13). In addition to detecting ALK rearrangements, we also detected 3 Crizotinib resistant mutations, ALK L1152R, ALK I1171T and ALK L1196M from patient P4. ctDNA concentration correlates with responses and disease progression, reflecting its ability as a biomarker. Our findings suggest capture-based sequencing can detect and quantify ALK rearrangements as well as other somatic mutations, including mutations mediated drug resistance, in plasma with high sensitivity, paving the way for its application in identifying driver fusion genes and monitoring tumor dynamics in the clinic.
Exporting and Plant-Level Efficiency Gains: It’s in the Measure

While there is strong evidence that more productive plants select into exporting, the literature has struggled to identify export-related efficiency gains within plants. We show that this is due to the common use of revenue-based productivity measures (TFPR): more efficient producers tend to charge lower prices, leading to a downward bias in TFPR. Using census panels of Chilean, Colombian, and Mexican manufacturing plants, we find sizable efficiency gains after export entry based on efficiency measures that are not affected by output prices. Evidence suggests that a complementarity between exporting and investment in technology is an important driver of these gains.
Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults.

BACKGROUND Research indicates that the chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease, although to our knowledge, there have been no such studies in healthy older adults. Furthermore, the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored. OBJECTIVE We investigated whether 8 wk of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults. DESIGN High-flavanone (305 mg) 100% orange juice and an equicaloric low-flavanone (37 mg) orange-flavored cordial (500 mL) were consumed daily for 8 wk by 37 healthy older adults (mean age: 67 y) according to a crossover, double-blind, randomized design separated by a 4-wk washout. Cognitive function, mood, and blood pressure were assessed at baseline and follow-up by using standardized validated tests. RESULTS Global cognitive function was significantly better after 8-wk consumption of flavanone-rich juice than after 8-wk consumption of the low-flavanone control. No significant effects on mood or blood pressure were observed. CONCLUSIONS Chronic daily consumption of flavanone-rich 100% orange juice over 8 wk is beneficial for cognitive function in healthy older adults. The potential for flavanone-rich foods and drinks to attenuate cognitive decline in aging and the mechanisms that underlie these effects should be investigated.
Longitudinal Comparison of the Speech and Language Performance of United States-Born and Internationally Adopted Toddlers with Cleft Lip and Palate

Objective: This study compares the early speech and language development of children with cleft palate with or without cleft lip who were adopted internationally with children born in the United States. Design: Prospective longitudinal description of early speech and language development between 18 and 36 months of age. Participants: This study compares four children (age range = 19 to 38 months) with cleft palate with or without cleft lip who were adopted internationally with four children (age range = 19 to 38 months) with cleft palate with or without cleft lip who were born in the United States, matched for age, gender, and cleft type across three time points over 10 to 12 months. Main Outcome Measures: Children's speech-language skills were analyzed using standardized tests, parent surveys, language samples, and single-word phonological assessments to determine differences between the groups. Results: The mean scores for the children in the internationally adopted group were lower than the group born in the United States at all three time points for expressive language and speech sound production measures. Examination of matched pairs demonstrated observable differences for two of the four pairs. No differences were observed in cognitive performance and receptive language measures. Conclusions: The results suggest a cumulative effect of later palate repair and/or a variety of health and environmental factors associated with their early circumstances that persist to age 3 years. Early intervention to address the trajectory of speech and language is warranted. Given the findings from this small pilot study, a larger study of the long-term speech and language development of children who are internationally adopted and have cleft palate with or without cleft lip is recommended.
Input-Dependent Frequency Modulation of Cortical Gamma Oscillations Shapes Spatial Synchronization and Enables Phase Coding

Fine-scale temporal organization of cortical activity in the gamma range (∼25–80Hz) may play a significant role in information processing, for example by neural grouping (‘binding’) and phase coding. Recent experimental studies have shown that the precise frequency of gamma oscillations varies with input drive (e.g. visual contrast) and that it can differ among nearby cortical locations. This has challenged theories assuming widespread gamma synchronization at a fixed common frequency. In the present study, we investigated which principles govern gamma synchronization in the presence of input-dependent frequency modulations and whether they are detrimental for meaningful input-dependent gamma-mediated temporal organization. To this aim, we constructed a biophysically realistic excitatory-inhibitory network able to express different oscillation frequencies at nearby spatial locations. Similarly to cortical networks, the model was topographically organized with spatially local connectivity and spatially-varying input drive. We analyzed gamma synchronization with respect to phase-locking, phase-relations and frequency differences, and quantified the stimulus-related information represented by gamma phase and frequency. By stepwise simplification of our models, we found that the gamma-mediated temporal organization could be reduced to basic synchronization principles of weakly coupled oscillators, where input drive determines the intrinsic (natural) frequency of oscillators. The gamma phase-locking, the precise phase relation and the emergent (measurable) frequencies were determined by two principal factors: the detuning (intrinsic frequency difference, i.e. local input difference) and the coupling strength. In addition to frequency coding, gamma phase contained complementary stimulus information. Crucially, the phase code reflected input differences, but not the absolute input level. This property of relative input-to-phase conversion, contrasting with latency codes or slower oscillation phase codes, may resolve conflicting experimental observations on gamma phase coding. Our modeling results offer clear testable experimental predictions. We conclude that input-dependency of gamma frequencies could be essential rather than detrimental for meaningful gamma-mediated temporal organization of cortical activity.
Class II major histocompatibility complex tetramer staining: progress, problems, and prospects

The use of major histocompatibility complex (MHC) tetramers in the detection and analysis of antigen‐specific T cells has become more widespread since its introduction 11 years ago. Early challenges in the application of tetramer staining to CD4+ T cells centred around difficulties in the expression of various class II MHC allelic variants and the detection of low‐frequency T cells in mixed populations. As many of the technical obstacles to class II MHC tetramer staining have been overcome, the focus has returned to uncertainties concerning how oligomer valency and T‐cell receptor/MHC affinity affect tetramer binding. Such issues have become more important with an increase in the number of studies relying on direct ex vivo analysis of antigen‐specific CD4+ T cells. In this review we discuss which problems in class II MHC tetramer staining have been solved to date, and which matters remain to be considered.
Description of an Academic Community Partnership Lifestyle Program for Lower Income Minority Adults at Risk for Diabetes

Purpose Translating strategies and approaches from the successful clinically based Diabetes Prevention Program’s lifestyle intervention to community settings is a key next step. This article describes a lifestyle program developed in partnership by researchers at a major university and public health professionals at a local health department. Methods The Live Well, Be Well (LWBW) program was designed to meet the needs of lower income, minority, and low-literacy adults at risk for diabetes. It was adapted from interventions with demonstrated efficacy and delivered in Spanish and English by health department staff. The program consisted of a 6-month active phase and a 6-month maintenance phase and was primarily telephone based, with one in-person planning session and several group workshops. In-person and group sessions were held in convenient community-based settings. Counselors provided education and skills training to modify diet and increase physical activity. Self-selected and attainable goal-setting and action plans were emphasized to enhance self-efficacy. LWBW is the intervention component of a randomized trial with primary outcomes of fasting glucose, weight, and other clinical measures. Conclusions The program provides a unique translational model for implementing diabetes risk reduction programs for underserved populations. Individually tailored and non-prescriptive, it utilized existing health department infrastructure, focused on telephone counseling, used culturally appropriate, low-literacy materials, and was delivered in local, community-based facilities.
Performance Measurement and Comparative Transcriptome Analysis Revealed the Efforts on Hybrid Improvement of Qinchuan Cattle

ABSTRACT Crossbreeding can provide productive gains through heterosis, however, surveys about the effects of crossbreeding through global transcriptomic sequencing are few. This study revealed that Angus × Qinchuan cattle (AQF) have improved performance characteristics compared to Qinchuan cattle (QCF). We performed RNA-seq on the subcutaneous fat tissue of QCF and AQF. More than 42.2 million clean reads were obtained in each sample. We detected 40 and 21 breed-specific highly expressed genes (FPKM > 500) in QCF and AQF, respectively. Furthermore, a total of 353 differentially expressed genes (DEGs, |log2 ratio| ≥ 1 and Probability ≥ 0.8) were found between these two groups, of which 227 genes were upregulated in AQF and 126 genes were upregulated in QCF. Functional enrichment analyses showed that breed-specific highly expressed genes and DEGs were closely related to terms such as development in AQF, and adaption or immune in QCF. In addition, we also identified the novel transcript units, alternative splicing events, single-nucleotide polymorphisms and Indels. Our results revealed differences in inherent characteristics and genetic differences when comparing QCF with AQF.
Sympathetic Stimulation of Thiazide-Sensitive Sodium Chloride Cotransport in the Generation of Salt-Sensitive Hypertension

Excessive renal efferent sympathetic nerve activity contributes to hypertension in many circumstances. Although both hemodynamic and tubular effects likely participate, most evidence supports a major role for &agr;-adrenergic receptors in mediating the direct epithelial stimulation of sodium retention. Recently, it was reported, however, that norepinephrine activates the thiazide-sensitive NaCl cotransporter (NCC) by stimulating &bgr;-adrenergic receptors. Here, we confirmed this effect and developed an acute adrenergic stimulation model to study the signaling cascade. The results show that norepinephrine increases the abundance of phosphorylated NCC rapidly (161% increase), an effect largely dependent on &bgr;-adrenergic receptors. This effect is not mediated by the activation of angiotensin II receptors. We used immunodissected mouse distal convoluted tubule to show that distal convoluted tubule cells are especially enriched for &bgr;1-adrenergic receptors, and that the effects of adrenergic stimulation can occur ex vivo (79% increase), suggesting they are direct. Because the 2 protein kinases, STE20p-related proline- and alanine-rich kinase (encoded by STK39) and oxidative stress–response kinase 1, phosphorylate and activate NCC, we examined their roles in norepinephrine effects. Surprisingly, norepinephrine did not affect STE20p-related proline- and alanine-rich kinase abundance or its localization in the distal convoluted tubule; instead, we observed a striking activation of oxidative stress–response kinase 1. We confirmed that STE20p-related proline- and alanine-rich kinase is not required for NCC activation, using STK39 knockout mice. Together, the data provide strong support for a signaling system involving &bgr;1-receptors in the distal convoluted tubule that activates NCC, at least in part via oxidative stress–response kinase 1. The results have implications about device- and drug-based treatment of hypertension.
Personal Growth Initiative among Undergraduate Students : Influence of Emotional Self Efficacy and General Well Being

Personal Growth Initiative is an orientation toward change and growth across life domains and is considered as a construct of metacognition, awareness and planned commitment in conditions of growth enhancement. Emotional self-efficacy is known as a perceived familiarized capacity to compact with the negative affect and it is the hierarchical process through which an individual is able to recognize, understand and describe his/her emotions. General well-being is a multi-layered concept; it is result of a dynamic balance between various aspects of life. The study was conducted to explore personal growth initiative, emotional self-efficacy and general wellbeing of undergraduate students and to analyze the relationship between personal growth initiative, emotional self-efficacy and general wellbeing. The nature of the study calls for the descriptive study. 480 undergraduate students were selected from Punjab through stratified random sampling technique. Personal growth initiative-II scale by Robitschek, self-constructed standardized emotional self-efficacy scale and general well-being scale by Dr. S.K. Verma and Ms. Amita Verma were used for data collection. For analyzing data, parametric statistical techniques were used. Study revealed that females possessed more scores in PGI, emotional selfefficacy and general well-being as compared to males. Student from science streams are much better in personal growth initiative, emotional self-efficacy and general well-being as compared to arts and commerce undergraduate students. Significant positive relationship was found between personal growth initiative, emotional self-efficacy and general well-being.
Topical Antimicrobial Treatments Can Elicit Shifts to Resident Skin Bacterial Communities and Reduce Colonization by Staphylococcus aureus Competitors

ABSTRACT The skin microbiome is a complex ecosystem with important implications for cutaneous health and disease. Topical antibiotics and antiseptics are often employed to preserve the balance of this population and inhibit colonization by more pathogenic bacteria. However, despite their widespread use, the impact of these interventions on broader microbial communities remains poorly understood. Here, we report the longitudinal effects of topical antibiotics and antiseptics on skin bacterial communities and their role in Staphylococcus aureus colonization resistance. In response to antibiotics, cutaneous populations exhibited an immediate shift in bacterial residents, an effect that persisted for multiple days posttreatment. By contrast, antiseptics elicited only minor changes to skin bacterial populations, with few changes to the underlying microbiota. While variable in scope, both antibiotics and antiseptics were found to decrease colonization by commensal Staphylococcus spp. by sequencing- and culture-based methods, an effect which was highly dependent on baseline levels of Staphylococcus. Because Staphylococcus residents have been shown to compete with the skin pathogen S. aureus, we also tested whether treatment could influence S. aureus levels at the skin surface. We found that treated mice were more susceptible to exogenous association with S. aureus and that precolonization with the same Staphylococcus residents that were previously disrupted by treatment reduced S. aureus levels by over 100-fold. In all, the results of this study indicate that antimicrobial drugs can alter skin bacterial residents and that these alterations can have critical implications for cutaneous host defense.
Evaluation of the relationship between milk glutathione peroxidase activity, milk composition and various parameters of subclinical mastitis under seasonal variations

The aims of this study were to evaluate the Glutathione peroxidase (GSH-Px) activity in milk, and various milk parameters [milk fat, milk protein, milk solids non-fat (SNF), somatic cell count (SCC), total bacteria count (TBC), electrical conductivity (EC)] in healthy dairy cows during lactation, and to demonstrate the significant correlations between GSH-Px activity, milk composition, SCC, TBC and EC under seasonal variations. The cows calving in January were assigned into the winter group (n = 30) while the other cows calving in August were assigned into the summer group (n = 30). Milk samples were collected weekly during lactation, and monthly average values of the parameters were determined. Although milk GSH-Px activity was variable during lactation, it was significantly higher in the winter group compared to the summer group of cows during the first five months of lactation (P<0.001). However, between the 6th and 10th months of lactation, GSHPx activity was significantly higher in the summer group (P<0.001). In both groups of cows, GSH-Px activity was negatively correlated with SCC, TBC and EC during lactation. No correlation was found between GSH-Px *Corresponding author: Prof. Dr. Sukru Kuplulu, Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, University of Ankara, 06110, Diskapi/Altindag Ankara/ Turkey, E-mail: sukrukuplulu@gmail.com doi: 10.24099/vet.arhiv. 160728
The polymorphic hMSH5 C85T allele augments radiotherapy‐induced spermatogenic impairment

The hMSH5 C85T polymorphism (encoding hMSH5 P29S) is associated with male infertility and radiation‐induced apoptotic response. To date, however, the potential association of hMSH5 C85T polymorphism with DNA damage accumulation in spermatozoa of cancer patients treated with radiotherapy is largely unknown. We investigated hMSH5 C85T allele and genotype frequencies, routine semen analysis and sperm DNA Fragmentation Index (DFI) in 113 testicular germ cell tumor (TGCT) patients before and after radiotherapy. The hMSH5 C85T allele is not associated with the occurrence of TGCT. However, in comparison with the CC genotype, TGCT patients with the CT + TT genotypes showed significantly altered sperm counts, sperm morphology and DFI after radiotherapy. Finally, the results of the DSB repair assay demonstrated that hMSH5 P29S could enhance radiotherapy‐induced DNA damage by unleashing error‐prone non‐homologous end joining. Together, our studies indicate that the hMSH5 C85T variation could have an impact on the severity of radiotherapy‐provoked long‐term side effects through compromising the repair of radiation‐induced DNA lesions.
Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation

Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1−CD44− non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it. Furthermore, we found tumor growth was reduced in mice bearing xenograft tumors after andrographolide treatment via activation of miR-218/Bmi1 axis. Together, these data demonstrated that the inhibition of tumor aggressiveness in OCSCs by andrographolide was mediated through the upregulation of miR-218, thereby reducing Bmi1 expression. These findings suggest that andrographolide may be a valuable natural compound for anti-CSCs treatment of OSCC.
A protocol study of novice interaction design behaviour in Botswana: solution-driven interaction design

Think aloud studies and protocol analysis are well-known in the field of HCI, but most often these studies focus on usability evaluations, or on the use of technology. Rarely are they used to investigate the behaviour of interaction designers. In this paper, we report on a protocol study with novice interaction designers in Botswana. Participants had just completed the design section of an undergraduate module on Interaction Design that actively promotes a problem-driven approach to the design of interactive products, yet the participants behaved in a way that is closer to a solution-driven approach. The module emphasizes user-centred design, prototyping methods to support design development, and evaluating design detail. Yet participants suggest solutions before exploring the context of use, use prototyping methods to capture, rather than to develop, designs, and do not produce detailed designs. In a problem-solving context, some of these behaviours are typical of novices, but in a design context they are also seen in experienced designers. The results presented here reveal the detail of the approach adopted by these students, and contribute to the wider debate concerning the internationalization of HCI education.