Miracle-dz/UniFAR-FTUs huggingface dataset:
Nivolumab-Induced Impressive Response of Refractory Pulmonary Sarcomatoid Carcinoma with Brain Metastasis

Background: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy. Objectives and Method: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma. He received first- and second-line chemotherapy without any benefit. Since March 2016, he has been treated with the anti-PD1 agent nivolumab with a dramatic improvement of symptoms, disappearance of a brain lesion, and partial response on other metastatic sites. He tolerated the treatment well and is still responding after 22 months from the beginning. Results and Conclusions: In very lethal non-small cell lung cancer subtypes such as the sarcomatoid variants, high tumor burden and deteriorated general conditions should not preclude, at least in some cases, the use of immunotherapy. Anti-PD1 may also have a reliable role in disease control in the brain. Lastly, the strong rationale behind sarcomatoid histology should further prompt trials exploring immunotherapeutic approaches in this subset of non-small cell lung cancer.
Development and Content Validation of a Transcultural Instrument to Assess Organizational Readiness for Knowledge Translation in Healthcare Organizations: The OR4KT

Background: Implementing effective interventions in healthcare requires organizations to be ready to support change. This study aimed to develop, adapt transculturally, and assess the content and face validity of the Organizational Readiness for Knowledge Translation (OR4KT) tool. The OR4KT was designed to measure the readiness of healthcare organizations to implement evidence-informed change across a variety of services. Methods: Based on systematic reviews of the literature, a Delphi exercise, and expert consultation, we first generated an initial pool of items. Second, we developed and assessed content validity of the pilot OR4KT questionnaire in English. Third, we created French and Spanish versions using a sequential forward and backward translation approach, and transcultural adaptation by a consensus process. Finally, we conducted pilot studies in three contexts – the Basque country region (Spain), and the provinces of Québec and Ontario (Canada) – where 30 experts assessed the face validity of the three versions of OR4KT. Results: We selected 59 items, grouped in 6 dimensions (organizational climate, context, change content, leadership, organizational support, and motivation) for the final English version of OR4KT. Translation and transcultural adaptation did not identify any content or language problems. Our findings indicate that the English, French and Spanish versions of OR4KT are linguistically equivalents and have high face validity. Only minor revisions to the wording of some items were recommended. Conclusion: The OR4KT holds promise as a measure of readiness for knowledge translation (KT) in healthcare organizations. The validity and reliability of the three versions of the OR4KT will be assessed in real-life contexts of implementation of evidence-based changes in healthcare
Triple Aim: Benefits of behavioral health providers in primary care

There is little research on behavioral health consultants addressing The Triple Aim goals in a community setting. This study examined the behavioral health consultants’ effect on (1) reducing overall patient cost and (2) improving population health by examining psychological screening measures, healthcare utilization, and hospital charges. Results revealed changes in patient charges: emergency department encounters reduce by 8 percent, psychological distress significantly decrease (Patient Health Questionnaire—9, 13.9 to 10.9, p < 0.001; Generalized Anxiety Disorder–7, 12.2 to 9.8, p < 0.001), and reduction in suicidal ideation (p < 0.001) following behavioral health consultant contact. Findings suggest that utilization of behavioral health consultants help health care systems meet The Triple Aim goals.
“I think the parent should be there because no one was born alone”: Kenyan adolescents’ perspectives on parental involvement in HIV research

Despite a pressing need for adolescent HIV research in sub-Saharan Africa, ethical guidance for conducting research among minor adolescents is lacking. One ethical issue is the degree to which parents should be involved in the research process. The existing discourse is predominantly speculative and focuses on negative consequences of parental involvement. We use empirical data to describe the perspectives of Kenyan adolescents on parental involvement in consent and disclosure of HIV test results within a research study context. We conducted two rounds of focus group discussions with 40 adolescents in western Kenya to ask about minor adolescent participation in HIV research. We analysed data using codes and matrices. Kenyan adolescents were largely in favour of parental involvement during the research process. Half felt adolescent minors should solicit parental consent to participate, and nearly all said parents should learn the HIV test results of adolescent minors in order to provide necessary support. From their perspective, involvement of parents in research extends beyond obtaining their consent to providing essential support for youth, regardless of HIV status, both during and beyond the research study. Ethical guidelines that prioritise adolescent autonomy in research must consider reasons to involve parents considered important by adolescents themselves, particularly in low-resource settings.
Rapidly mitigating antibiotic resistant risks in chicken manure by Hermetia illucens bioconversion with intestinal microflora

Antibiotic resistance genes (ARGs) in animal manure are an environmental concern due to naturally occurring bacteria being exposed to these wastes and developing multidrug resistance. The bioconversion of manure with fly larvae is a promising alternative for recycling these wastes while attenuating ARGs. We investigated the impact of black soldier fly (BSF, Hermetia illucens) larval bioconversion of chicken manure on the persistence of associated ARGs. Compared with traditional composting or sterile larval treatments (by 48.4% or 88.7%), non-sterile BSF larval treatments effectively reduced ARGs and integrin genes by 95.0% during 12 days, due to rapid decreases in concentrations of the genes and associated bacteria as they passed through the larval gut and were affected by intestinal microbes. After larval treatments, bacterial community composition differed significantly, with the percentage of Firmicutes possibly carrying ARGs reduced by 65.5% or more. On average, human pathogenic bacteria populations declined by 70.7%-92.9%, effectively mitigating risks of these bacteria carrying ARGs. Environmental pH, nitrogen content and antibiotic concentrations were closely related to both bacterial community composition and targeted gene attenuation in larval systems. Selective pressures of larval gut environments with intestinal microbes, larval bacteriostasis and reformulation of manure due to larval digestion contributed to ARG attenuation.
THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans

Candida albicans (C. albicans) CDC4 (CaCDC4), encoding the F-box protein for the substrate specificity of the Skp1-cullin-F-box E3 ubiquitin ligase complex, suppresses the yeast-to-filament transition in C. albicans. In our previous study, Thr1 was identified as a CaCdc4-associated protein using affinity purification. THR1 encodes a homoserine kinase, which is involved in the threonine biosynthesis pathway. The present study generated a strain with repressible CaCDC4 expression and continuous THR1 expression. Colony and cell morphology analyses, as well as immunoblotting, revealed that the Thr1 protein was detectable under conditions in which the expression of CaCDC4 was repressed and that the filaments resulting from the repressed expression of CaCDC4 were suppressed by the constitutive expression of THR1 in C. albicans. Additionally, by using the CaSAT1-flipper method, the present study produced null mutants of THR1, GCN4, and CaCDC4. The phenotypic consequences were evaluated by growth curves, spotting assays, microscopic analysis, reverse transcription-polymerase chain reaction and XTT-based biofilm formation ability. The results revealed that fewer cells lacking THR1 entered the stationary phase but had no apparent morphological alteration. It was observed that the expression of THR1 was upregulated concurrently with GCN4 during nutrient depletion and that cells lacking GCN4 rescued the lethality of cells in the absence of THR1 in conditions accumulating homoserine in the threonine biosynthesis pathway. Of note, it was found that cells with either CaCDC4 or THR1 loss were sensitive to oxidative stress and osmotic stress, with those with THR1 loss being more sensitive. In addition, it was observed that cells with loss of either CaCDC4 or THR1 exhibited the ability to increase biofilm formation, with those lacking CaCDC4 exhibiting a greater extent of enhancement. It was concluded that CaCDC4 is important in the coordination of morphogenesis, nutrient sensing, and the stress response through THR1 in C. albicans.
Contribution of regulatory T cells to cancer: A review

Regulatory T cells (Tregs) represent a low number of T‐cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross‐talks with other immunosuppressive cells including cancer‐associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid‐derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor‐β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor‐bearing receptors in Tregs, including FOXP3, programmed death‐1, T‐cell immunoglobulin mucin‐3, and CTL‐associated antigen‐4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.
Mitigating the Latency-Accuracy Trade-off in Mobile Data Analytics Systems

An increasing amount of mobile analytics is performed on data that is procured in a real-time fashion to make real-time decisions. Such tasks include simple reporting on streams to sophisticated model building. However, the practicality of these analyses are impeded in several domains because they are faced with a fundamental trade-off between data collection latency and analysis accuracy. In this paper, we first study this trade-off in the context of a specific domain, Cellular Radio Access Networks (RAN). We find that the trade-off can be resolved using two broad, general techniques: intelligent data grouping and task formulations that leverage domain characteristics. Based on this, we present CellScope, a system that applies a domain specific formulation and application of Multi-task Learning (MTL) to RAN performance analysis. It uses three techniques: feature engineering to transform raw data into effective features, a PCA inspired similarity metric to group data from geographically nearby base stations sharing performance commonalities, and a hybrid online-offline model for efficient model updates. Our evaluation shows that CellScope's accuracy improvements over direct application of ML range from 2.5× to 4.4× while reducing the model update overhead by up to 4.8×. We have also used CellScope to analyze an LTE network of over 2 million subscribers, where it reduced troubleshooting efforts by several magnitudes. We then apply the underlying techniques in CellScope to another domain specific problem, mobile phone energy bug diagnosis, and show that the techniques are general.
Fighting Contextual Bandits with Stochastic Smoothing

We introduce a new stochastic smoothing perspective to study adversarial contextual bandit problems. We propose a general algorithm template that represents random perturbation based algorithms and identify several perturbation distributions that lead to strong regret bounds. Using the idea of smoothness, we provide an $O(\sqrt{T})$ zero-order bound for the vanilla algorithm and an $O(L^{*2/3}_{T})$ first-order bound for the clipped version. These bounds hold when the algorithms use with a variety of distributions that have a bounded hazard rate. Our algorithm template includes EXP4 as a special case corresponding to the Gumbel perturbation. Our regret bounds match existing results for EXP4 without relying on the specific properties of the algorithm.
The rational fragment of the ZX-calculus

We introduce here a new axiomatisation of the rational fragment of the ZX-calculus, a diagrammatic language for quantum mechanics. Compared to the previous axiomatisation introduced in [8], our axiomatisation does not use any metarule , but relies instead on a more natural rule, called the cyclotomic supplementarity rule, that was introduced previously in the literature. Our axiomatisation is only complete for diagrams using rational angles , and is not complete in the general case. Using results on diophantine geometry, we characterize precisely which diagram equality involving arbitrary angles are provable in our framework without any new axioms, and we show that our axiomatisation is continuous, in the sense that a diagram equality involving arbitrary angles is provable iff it is a limit of diagram equalities involving rational angles. We use this result to give a complete characterization of all Euler equations that are provable in this axiomatisation.
The Effects of Music Therapy-Singing Group on Quality of Life and Affect of Persons With Dementia: A Randomized Controlled Trial

Dementia is a clinical syndrome that is progressive and degenerative, affecting memory, behavior, emotion, and personality. Persons with dementia often experience deterioration of cognitive ability, as well as various behavioral and psychological disturbances, which significantly contribute to reduced quality of life and emotional well-being. The demand for long-term care continues to rise rapidly and it is therefore critical to develop effective strategies and evidence-based interventions to improve the quality of life for persons with dementia. Music therapy has drawn attention as a promising non-pharmacological approach for persons with dementia. A variety of music interventions including singing and listening to music have been widely applied for dementia care not only by music therapists, but also by other healthcare professionals. There are, however, little research studies that compare possible effects of music therapy interventions with those of music-based approaches on dementia care. The purpose of the current study was to compare the short-term effects of a music therapy-singing group with those of a music medicine-listening group and a control-TV group, on quality of life and affect of persons with dementia at a long-term care facility. The music therapy-singing group was facilitated by a music therapist, whereas the music medicine-listening and the control-TV group were led by nursing home activity staff. Fifty-two participants, whose ages range from 67 to 99 years old, were randomly assigned to one of the three groups, and 37 participants completed the interventions. The participants in each group were engaged for a 40-min session twice a week for four consecutive weeks. Quality of life was measured at the baseline and after the last session and only the music therapy-singing group demonstrated significant improvements when compared to the other groups. Positive and negative affect were measured at three points, including pre and post the first, fourth and eighth sessions. Only the music therapy-singing group significantly increased positive affect scores and decreased negative affect scores. The findings of the current study suggest that music therapy with active group singing may be an effective non-pharmacological intervention in improving quality of life and affect of persons with dementia at long-term care settings. Clinical Trial Registration: http://www.germanctr. de/drks_web/, registration number DRKS00014934.
Extensive CD34-to-CD90 Fibroblast Transition Defines Regions of Cutaneous Reparative, Hypertrophic, and Keloidal Scarring

Background: CD90+ fibroblasts have been described arising from and replacing the homeostatic CD34+ network in scleroderma, but have not been specifically examined in other forms of cutaneous fibrosis. Objectives: To address expression, timelines, and spatial relationships of CD90, CD34, and smooth muscle actin (SMA) expressing fibroblasts in scars and to examine for the presence of a CD34-to-CD90 transition. Methods: One hundred and seventeen scars (reparative/hypertrophic/keloidal) were evaluated for CD90, CD34, and SMA expression. Double-staining immunohistochemistry for CD90/CD34 was performed to identify CD90+/CD34+ transitioning cells, confirmed by double-color immunofluorescence. In addition, some scars were double-stained with CD90/SMA, CD90/procollagen-1, or SMA/procollagen-1 to evaluate spatial relationships and active collagen synthesis. Expression was graded as diffuse, minority, and negative. Results: Most scars demonstrate a CD90diffuse/CD34negative/minority pattern, and dual CD90+/CD34+ fibroblasts were observed in 91% of scars. In reparative scars, CD90 expression reverses to a CD34+/CD90− state with maturation. Pathologic scars exhibit prolonged CD90 expression. Both CD90+ and SMA+ fibroblasts collagenize scars, although CD90+ fibroblasts are more prevalent. Conclusions: CD90+ fibroblasts likely arise from the resting CD34+ fibroblastic network. Actively collagenizing scar fibroblasts exhibit a CD90diffuse/CD34negative/minority phenotype, which is prolonged in pathologic scars. CD90+ fibroblasts are likely important players in cutaneous scarring.
Status of topoisomerase‐2β protein in all‐trans retinoic acid–treated human neuroblastoma (SK‐N‐SH) cells

Of the mammalian topoisomerase (Topo)‐2 isozymes (α and β), Topo‐2β protein has been reported to regulate neuronal development and differentiation. However, the status of Topo‐2β in all‐trans retinoic acid (ATRA)‐treated human neuroblastoma (SK‐N‐SH) cells is not understood. More information about the effects of ATRA on SK‐N‐SH cells is needed to reveal the role of ATRA in the regulation of Topo‐2β levels and spontaneous regression of SK‐N‐SH cells to predict the clinical activity. This study was proposed to investigate the status and role of Topo‐2β protein in ATRA‐induced survival and neuronal differentiation of SK‐N‐SH cells. Microscopic, sodium dodecyl sulfate polyacrylamide gel electrophoresis after immunoprecipitations and Western blot analysis were used to study and compare Topo‐2β protein among 10 µM ATRA‐treated SK‐N‐SH cells and controls at different time points. The level of Topo‐2β protein increased in the initial days of treatment but markedly decreased upon induction of differentiation by ATRA in later stages. Upon ATRA treatment, SK‐N‐SH cells stretched, exhibited neurite extensions, and acquired a neuronal phenotype. Both treated and untreated SK‐N‐SH cells were able to migrate, occupy the scratched area, and completely recolonized 24 hours later. These results suggest an indirect role of Topo‐2β protein in regulation of genes involved in cell migration and differentiation of ATRA‐treated SK‐N‐SH cells. This study suggests that Topo‐2β may be part of activation/repression of protein complexes activated by epigenetic modifying agents, differentiating signals, and inducible locus. However, detailed studies are needed to explore the ATRA‐downstream genes leading to Topo‐2β regulation and regulatory proteins of neuronal differentiation.
Unraveling the Molecular Mechanisms Underlying Complement Dysregulation by Nephritic Factors in C3G and IC-MPGN

Membranoproliferative glomerulonephritis (MPGN) was recently classified as C3 glomerulopathies (C3G), and immune-complex (IC) mediated MPGN. Dysregulation of the complement alternative pathway, driven by acquired and/or genetic defects, plays a pathogenetic role in C3G. However, alternative pathway abnormalities were also found in IC-MPGN. The most common acquired drivers are the C3 nephritic factors (C3NeFs), heterogeneous autoantibodies that stabilize the C3 convertase, C3bBb. C3NeFs are traditionally detected by hemolytic assays based on sheep erythrocyte lysis, which however do not provide a direct molecular estimation of C3bBb formation and decay. We set up a microplate/western blot assay that specifically detects and quantifies C3bBb, and its precursor, the C3 proconvertase C3bB, to investigate the complex mechanistic effects of C3NeFs from patients with primary IC-MPGN (n = 13) and C3G (n = 13). In the absence of properdin, 9/26 patients had C3NeF IgGs stabilizing C3bBb against spontaneous and FH-accelerated decay. In the presence of properdin the IgGs of all but one patient had C3bBb-stabilizing activity. Properdin-independent C3NeFs were identified mostly in DDD patients, while properdin-dependent C3NeFs associated with either C3GN or IC-MPGN and with higher incidence of nephrotic syndrome. When we grouped patients based on our recent cluster analysis, patients in cluster 3, with highly electron-dense intramembranous deposits, low C3, and mostly normal sC5b-9 levels, had a higher prevalence of properdin-independent C3NeFs than patients in clusters 1 and 2. Conversely, about 70% of cluster 1 and 2 patients, with subendothelial, subepithelial, and mesangial deposits, low C3 levels and high sC5b-9 levels, had properdin-dependent C3NeFs. The flexibility of the assay allowed us to get deep insights into C3NeF mechanisms of action, showing that: (1) most C3NeFs bind strongly and irreversibly to C3 convertase; (2) C3NeFs and FH recognize different epitopes in C3 convertase; (3) C3NeFs bind rapidly to C3 convertase and antagonize the decay accelerating activity of FH on newly formed complexes; (4) C3NeFs do not affect formation and stability of the C3 proconvertase. Thus, our study provides a molecular approach to detecting and characterizing C3NeFs. The results highlight different mechanisms of complement dysregulation resulting in different complement profiles and patterns of glomerular injury, and this may have therapeutic implications.