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Cold temperature (≤20 ᵒC) storage or handling is required to maintain the quality characteristics of chocolate after production throughout the supply chain. The objective of this study was to assess the retail conditions, challenges, and willingness of retailers to use cooling devices. A total of 228 chocolate retailers sampled from Kumasi and Accra were interviewed using questionnaires with both closed and open-ended questions. The purposive, snowballing, and random sampling techniques were used. The collected data were analyzed using SPSS version 26. The majority of the respondents were female (82 %), aged between 21 and 30 years (33.9 %) and had a maximum of Junior High School education (39.0 %). About 15.4 % were registered retailers of Cocoa Processing Company - Ghana, 56.1 % sold on the streets of which 71.1 % sold under no shade and 71.9 % sold all day. A proportion of 76.2 % reported having challenges in their chocolate retail business. Among these challenges softening dominated with about 78.1 % of the retailers reported experiencing it in their daily operations. Spoilage (18.9 %), damage during handling (35.1 %), oily surface (34.2 %), darker surface appearance (10.1 %), and whitish surface appearance (39.9 %) were other challenges faced by retailers. The majority (76.8 %) of the respondents affirmed elevated temperatures caused melting, oil leakage and fat bloom in chocolate leading to rejections by clients. A significant proportion (81.1 %) indicated a cooling device for retail is necessary and were willing to use it when made available. The findings show that vending conditions were generally unsuitable for the shelf-stability of chocolates. An innovative vending device with cooling system would serve as possible intervention to mitigate the challenges faced by chocolate retailers.

Abstract Immune checkpoint blockade (ICB) leads to durable and complete tumour regression in some patients but in others gives temporary, partial or no response. Accordingly, significant efforts are underway to identify tumour-intrinsic mechanisms underlying ICB resistance. Results from a published CRISPR screen in a mouse model suggested that targeting STUB1, an E3 ligase involved in protein homeostasis, may overcome ICB resistance but the molecular basis of this effect remains unclear. Herein, we report an under-appreciated role of STUB1 to dampen the interferon gamma (IFNγ) response. Genetic deletion of STUB1 increased IFNGR1 abundance on the cell surface and thus enhanced the downstream IFNγ response as showed by multiple approaches including Western blotting, flow cytometry, qPCR, phospho-STAT1 assay, immunopeptidomics, proteomics, and gene expression profiling. Human prostate and breast cancer cells with STUB1 deletion were also susceptible to cytokine-induced growth inhibition. Furthermore, blockade of STUB1 protein function recapitulated the STUB1-null phenotypes. Despite these encouraging in vitro data and positive implications from clinical datasets, we did not observe in vivo benefits of inactivating Stub1 in mouse syngeneic tumour models—with or without combination with anti-PD-1 therapy. However, our findings elucidate STUB1 as a barrier to IFNγ sensing, prompting further investigations to assess if broader inactivation of human STUB1 in both tumors and immune cells could overcome ICB resistance.

Abstract Aberrant miRNA expression has been associated with many diseases, and extracellular miRNAs that circulate in the bloodstream are remarkably stable. Recently, there has been growing interest in identifying cell-free circulating miRNAs that can serve as non-invasive biomarkers for early detection of disease or selection of treatment options. However, quantifying miRNA levels in biofluids is technically challenging due to their low abundance. Using reference samples, we performed a cross-platform evaluation in which miRNA profiling was performed on four different qPCR platforms (MiRXES, Qiagen, Applied Biosystems, Exiqon), nCounter technology (NanoString), and miRNA-Seq. Overall, our results suggest that using miRNA-Seq for discovery and targeted qPCR for validation is a rational strategy for miRNA biomarker development in clinical samples that involve limited amounts of biofluids.

The European Space Agency Rosetta mission escorted comet 67P for a 2-yr section of its six and a half-year orbit around the Sun. By perihelion in 2015 August, the neutral and plasma data obtained by the spacecraft instruments showed the comet had transitioned to a dynamic object with large-scale plasma structures and a rich ion environment. One such plasma structure is the diamagnetic cavity: a magnetic field-free region formed by interaction between the unmagnetized cometary plasma and the impinging solar wind. Within this region, unexpectedly high ion bulk velocities have been observed, thought to have been accelerated by an ambipolar electric field. We have developed a 1D numerical model of the cometary ionosphere to constrain the impact of various electric field profiles on the ionospheric density profile and ion composition. In the model, we include three ion species: H2O+, H3O+, and |$\mathrm{NH_4^+}$|⁠. The latter, not previously considered in ionospheric models including acceleration, is produced through the protonation of NH3 and only lost through ion–electron dissociative recombination, and thus particularly sensitive to the time-scale of plasma loss through transport. We also assess the importance of including momentum transfer when assessing ion composition and densities in the presence of an electric field. By comparing simulated electron densities to Rosetta Plasma Consortium data sets, we find that to recreate the plasma densities measured inside the diamagnetic cavity near perihelion, the model requires an electric field proportional to r −1 of around 0.5–2 mV m−1 surface strength, leading to bulk ion speeds at Rosetta of 1.2–3.0 km s−1. [ABSTRACT FROM AUTHOR]

Paprika powder is a spice of culinary importance in many homes but it’s powdered form, has been targeted for fraudulent activities intended at consumer deception. Diverse methods have been used to investigate some of these adulterations but there is no report of paprika adulteration with corn flour, although it remains a suspicion. Technologies such as the near infrared spectroscopy (NIRS) possess non-invasive and rapid advantages that could be explored to monitor this type of adulteration. The study aimed to discriminate and quantify different levels of paprika powder adulterated with corn flour, using NIRS. Two authentic paprika types (DP and SP) were purchased from reputable sources in Hungary and artificially adulterated in the laboratory. Three repeats of each adulteration level (40%, 30%, 25%, 20%, 15%, 10%, 5%, 3%, 1%) were prepared and scanned with the Metri NIRS respectively, then, analysed with chemometrics: Linear discriminant analysis (LDA) and partial least squares regression (PLSR). LDA showed 100% recognition and prediction accuracies respectively when DP and SP were analyzed separately to discriminate different concentrations of paprika adulteration. LDA models with NIRS recognize corn flour adulteration with 95.55% and predict it with 95.02% accuracy irrespective of the paprika type used in this experiment. PLSR prediction of 40%, 30%, 25%, 20%, 15%, 10%, 5%, 3%, 1% corn flour adulteration yielded an R2CV of 0.98 (high accuracy) and a low RMSECV of 1.71 g/100g (low error). Near infrared as a non-invasive technique exhibited good potentials for paprika powder authentication when corn flour is used as an adulterant.

Novel targeted agents to inhibit DNA repair pathways to sensitize tumors to irradiation (IR) are being investigated as an alternative to chemoradiation for locally advanced human papilloma virus negative (HPV-negative) head and neck squamous cell carcinoma (HNSCC). Two well-characterized targets that, when inhibited, exhibit potent IR sensitization are PARP1 and DNA-PKcs. However, their cooperation in sensitizing HPV-negative HNSCC to IR remains to be explored given that PARP1 and DNA-PkCS bind to unresected stalled DNA replication forks and cooperate to recruit XRCC1 to facilitate double-strand break repair. Here, we show that the combination of the DNA-PK inhibitor NU7441 and the PARP inhibitor olaparib significantly decrease proliferation (61–78%) compared to no reduction with either agent alone (p < 0.001) in both SCC1 and SCC6 cell lines. Adding IR to the combination further decreased cell proliferation (91–92%, p < 0.001) in SCC1 and SCC6. Similar results were observed using long-term colony formation assays [dose enhancement ratio (DER) 2.3–3.2 at 4Gy, p < 0.05]. Reduced cell survival was attributed to increased apoptosis and G2/M cell cycle arrest. Kinomic analysis using tyrosine (PTK) and serine/threonine (STK) arrays reveals that combination treatment results in the most potent inhibition of kinases involved in the CDK and ERK pathways compared to either agent alone. In vivo, a significant delay of tumor growth was observed in UM-SCC1 xenografts receiving IR with olaparib and/or NU7441, which was similar to the cisplatin-IR group. Both regimens were less toxic than cisplatin-IR as assessed by loss of mouse body weight. Taken together, these results demonstrate that the combination of NU7441 and olaparib with IR enhances HPV-negative HNSCC inhibition in both cell culture and in mice, suggesting a potential innovative combination for effectively treating patients with HPV-negative HNSCC.

Abstract Background Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4–5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. Methods We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. Results The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. Conclusions These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Abstract Background Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients – once before antiviral treatment and once after viral rebound due to resistance. Results With single-virion sequencing, we obtained 248–8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. Conclusions Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

The purpose of this study was to assess the relationship between a set of self-efficacy variables and a set of variables assessing attitudes toward counseling. Results revealed a significant relationship between self-efficacy and attitudes toward counseling among a sample of 253 first-year college students. Low perceptions of self-efficacy were associated with a devaluation of career counseling and more negative attitudes toward seeking personal counseling. Implications for these findings are discussed.

This study examined the effectiveness of the computer-assisted career guidance system, FOCUS-2, on 1st-year college students' social cognitive career development. Specifically, the authors assessed career decision self-efficacy (CDSE) and assessment of attributions for career decision making (AACDM) using repeated measures analyses of variance with a sample of 1st-year college students (N= 420). Effectiveness was measured as a change in participants' CDSE and AACDM scores from pretest to posttest. Results demonstrated that participants' interaction with FOCUS-2 was associated with increases in participants' CDSE and alteration to a less optimistic style for AACDM. Gender, race, academic major status, and the amount of time using FOCUS-2 were also considered. Implications for practice are explored. (Contains 2 tables.)

Although advisor-advisee relationships are ubiquitous to graduate training, there is relatively little scholarship bearing on advising relationships. Not surprisingly, the intersection between multiculturalism and advising relationships is also sparse. Given the potential increase in the numbers of People of Color entering graduate training due to the changing demographics in the United States and the influence of advising relationships on advisees' personal and professional development, it is imperative to address the role of culture in the advising relationship--in this article, we will address race, sex, and sexual orientation. Hence, in this article, we address the potential impact of racial and cultural socialization processes on the advising relationship and organizational contexts.

Advisor-advisee relationships are an important aspect of the career development of professionals in many fields; however, limited scholarship has focused on these relationships. In the three articles of this special section, the authors attempt to help remedy this situation by articulating a culturally infused model of advising relationships in graduate training. This article lays the foundation for the authors' model by reviewing the literature relevant to advising and mentoring. In the subsequent articles, the authors propose that it is critical to understand how within-group cultural variables affect the advising relationship. Articulating a framework for understanding the advising relationship as a multicultural endeavor may help educators prepare the next generations of professionals and facilitate increased empirical attention to this important, yet underexamined construct.

In this final article of the special section, the authors offer their beginning theoretical model of graduate advising relationships. The authors' framework characterizes the advising relationship as a multicultural endeavor. The authors offer eight theoretical propositions with the intent to articulate aspects of good advising and those variables that appear to be related to successful advising relationships. As part of this model, the authors attend to both the process and the outcome of advising relationships. The authors close with implications for research, training, and practice, and offer suggestions for future research. (Contains 1 figure.)

In this article, the authors present the results from a national study investigating the relationships between religious identity, sexism, homophobia, and multicultural competence. Participants were 111 randomly sampled counseling professionals and graduate students. The results indicated a relationship between religious identity and various aspects of valuing cultural diversity, including sexism, homophobia, and multicultural competence. Implications of the role of religion and religious identity in counseling are discussed, and suggestions for future research are provided.

In this article, we explore the ethical issues pertaining to student-faculty mentoring relationships in graduate training programs, with a specific focus on understanding these concerns within a multicultural context. Multiculturalism, although broadly defined, is limited herein to race and ethnicity, gender and sexuality, age, religion, and ability status. Specific ethical codes are cited in which quandaries may arise vis-a-vis cultural factors in student-faculty mentorships, and examples are provided related to the aforementioned aspects of multiculturalism. We close with some recommendations regarding the intersection of culture and mentoring relationships. We encourage those involved in student-faculty mentorships to explore both these and other ethical dilemmas that arise in cross-cultural mentorships.

A schism now exists between Blacks and Jews in the United States, 2 groups that were strong allies during the civil rights movement. The authors describe the historical antecedents of and contributing factors to this schism and present information on and lessons learned from 2 Black-Jewish dialogues that were conducted.

The authors present the results from a study investigating advisor-advisee relationships in counseling psychology doctoral training. Participants were 47 advisor-advisee dyads who were currently working together in an advising relationship. The results indicated that advisors and advisees exhibited significant agreement in their assessments of their advisory working alliance, the smoothness of their recent interactions, and the advisee's research competence. Alliance ratings were also associated with several relevant training variables. Neither science nor practice interest similarity between advisor and advisee was related to the quality of the advising relationship. Implications of the advisor-advisee working alliance for doctoral training are discussed, and suggestions for future research are provided.

Nineteen counseling psychology faculty members were interviewed regarding their advising relationships with doctoral students. Advisors informally learned to advise from their experiences with their advisor and their advisees and defined their role as supporting and advocating for advisees as they navigated their doctoral program. Advisors identified personal satisfaction as a benefit and time demands as a cost of advising. Good advising relationships were facilitated by advisees' positive personal or professional characteristics, mutual respect, open communication, similarity in career path between advisor and advisee, and lack of conflict. Difficult relationships were affected by advisees' negative personal or professional characteristics, lack of respect, research struggles, communication problems, advisors feeling ineffective working with advisees, disruption or rupture of the relationship, and conflict avoidance. Implications for research and training are discussed. (Contains 2 tables.)

The development of the Advisory Working Alliance Inventory-Advisor Version (AWAI-A) is presented. In the first study, data from 236 faculty members from APA-accredited counseling psychology programs were subjected to a principal components analysis, yielding 3 subscales: Rapport (15 items), Apprenticeship (8 items), and Task Focus (8 items). The data also revealed evidence of the AWAI-A's internal consistency and concurrent validity, the latter being demonstrated by correlations with measures of satisfaction with the advising relationship, costs and benefits of advising, advisee interest in science and practice, and advisee research self-efficacy. In the 2nd study, data from 44 additional advisors yielded evidence of the AWAI-A's test-retest reliability and discriminant validity. Implications of the advising working alliance for doctoral training are discussed, and suggestions are provided for future research.

This study examined the relations between client attachment to the therapist and therapist perceptions of transference, as well as between client attachment and recollections of parental caregiving. Participants were 51 client-therapist pairs in ongoing therapy. After a therapy session, clients completed a measure of their attachment to their therapists and a measure of their perceptions of parental caregiving during childhood. Therapists rated levels of positive and negative, and amount of, client transference. Both secure and preoccupied-merger attachment were positively related to both negative transference and amount of transference. Level of avoidant-fearful attachment was not correlated with any type of transference. Insecure attachment to the therapist was associated with more negative recollections of parental caregiving.

Sixteen 3rd-year counseling psychology doctoral students were interviewed about their relationships with their graduate advisors. Of those students, 10 were satisfied and 6 were unsatisfied with their advising relationships. Satisfied and unsatisfied students differed on several aspects of the advising relationship, including (a) the ability to choose their advisors, (b) the frequency of meetings with their advisors, (c) the benefits and costs associated with their advising relationships, and (d) how conflict was dealt with in the advising relationship. Furthermore, all of the satisfied students reported that their advising relationships became more positive over time, whereas many of the unsatisfied students reported that their advising relationships got worse (e.g., became more distant) over time.

The author discusses the concept of privilege in terms of the benefits enjoyed by Whites and men. This article presents a new theoretical perspective focusing on religious privilege and includes a list of privileges that are enjoyed by members of the dominant religious group (i.e., Christians) in the United States. (Contains 17 references.) (Author)

Assessed how different levels of previous academic success related to varying outcomes, such as desire to pursue postgraduate education, higher career aspirations, and factors related to leaving school prematurely. Found that students who have been successful in the past are more likely to have more positive perceptions of their academic self-concept. (EV)

Background: Acute ischemia typically results in a flaccid paralysis. An immediate spastic hemiparesis following ischemia has rarely been reported. One case involved a left hemispheric transient ischemic attack and the other cases occurred after intracerebral hemorrhage. Case Report: A 46-year-old male developed an immediate spastic hemiplegia shortly after coil embolization of an unruptured anterior communicating artery aneurysm. A CT perfusion scan at the time of these symptoms demonstrated hypoperfusion in the right anterior cerebral artery (ACA) territory. The patient was emergently taken back to the angiography suite where he was found to have right A2 ACA occlusion. Following abciximab infusion, the artery recanalized and the patient’s symptoms resolved. Repeat CT perfusion demonstrated resolution of the perfusion deficit in the right ACA territory and the patient’s neurological exam remained normal. Conclusion: Acute ACA ischemia can present with spasticity in the hyperacute period instead of flaccid paralysis.