Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement of Irritability in Cancer Patients

Background Irritability is common among people who are physically ill, but a physical underpinning of irritability is not assessed by existing measures. A measure that assesses multidimensionality of irritability can help nurses and clinicians provide better care for people with cancer and, thus, reduce a risk for developing depression during cancer treatment. Objectives We pilot tested a new measure, The Irritability Scale–Initial Version (TISi), for assessing irritability of cancer patients on three dimensions: physical, affective, and behavioral. Methods We conducted thee pilot studies to develop the 35-item TISi on a 5-point Likert scale. TISi was tested in 48 early-stage, nonmetastasized breast cancer patients at baseline (before) and 3 months (during chemotherapy). Of these patients, 62.5% received neoadjuvant and 37.5% received adjuvant chemotherapy, but none received hormonal treatment before or during the study. Measures of other correlates, including depression, anxiety, symptom distress, and social disconnectedness, were also administered, and biomarkers of hsCRP, TNF-α, IL-6, and BDNF were obtained from blood draws at both assessments. Results TISi has a high internal consistency (Cronbach’s α = .97), satisfactory test–retest reliability (retest r = .69, intraclass correlation coefficient = .86), and moderate correlation with other constructs over time (r ≈ .40–.70). Its physical subscale significantly correlated with hsCRP (r = .32, p = .025) at baseline and TNF-α (r = .44, p = .002) at 3 months. A confirmatory factor analysis yields three factor loadings that are in line with conceptualization of the subscales. Discussion The findings support psychometric properties of TISi and its application for assessing cancer patients’ irritability in multiple dimensions. Further investigation using a large study sample is necessary for improving construct and criterion validity and reducing item redundancy. Conclusion TISi can be used to measure the level of irritability in cancer patients
Myeloid cell and cytokine interactions with chimeric antigen receptor-T-cell therapy: implication for future therapies.

PURPOSE OF REVIEW Chimeric antigen receptor (CAR)-T-cell therapy is a revolutionary tool in the treatment of cancer. CAR-T cells exhibit their effector functions through the recognition of their specific antigens on tumor cells and recruitment of other immune cells. However, this therapy is limited by the development of severe toxicities and modest antitumor activity in solid tumors. The host and tumor microenvironment interactions with CAR-T cells play an important role in orchestrating CAR-T-cell functions. Specifically, myeloid lineage cells and their cytokines critically influence the behavior of CAR-T cells. Here, we review the specific effects of myeloid cell interactions with CAR-T cells, their impact on CAR-T-cell response and toxicities, and potential efforts to modulate myeloid cell effects to enhance CAR-T-cell therapy efficacy and reduce toxicities. RECENT FINDINGS Independent studies and correlative science from clinical trials indicate that inhibitory myeloid cells and cytokines contribute to the development of CAR-T-cell- associated toxicities and impairment of their effector functions. SUMMARY These findings illuminate a novel way to reduce CAR-T-cell -associated toxicities and enhance their efficacy through the modulation of myeloid lineage cells and inhibitory cytokines.
Detection of Drug Induced Torsades de Pointes Arrhythmia Mechanisms Using hiPSC-CM Syncytial Monolayers in a High Throughput Screening Voltage Sensitive Dye Assay.

We validated three distinct hiPSC-CM cell lines-each of different purity and a voltage sensitive dye based high throughput proarrhythmia screening assay as a non-core site in the recently completed CiPA Myocyte Phase II Validation Study. Blinded validation was performed using 12 drugs linked to low, intermediate or high risk for causing Torsades de Pointes (TdP). Commercially sourced hiPSC-CMs were obtained either from Cellular Dynamics International (CDI, Madison WI, iCell® Cardiomyoyctes2) or Takara Bio (CLS, Cellartis® Cardiomyocytes). A third hiPSC-CM cell line (MCH, Michigan) was generated in house. Each cell type had distinct baseline electrophysiological function (spontaneous beat rate, action potential duration and conduction velocity) and drug responsiveness. Use of voltage sensitive dye and optical mapping enabled the detection of conduction slowing of sodium channel blockers (quinidine, disopyramide and mexiletine) and drug induced TdP like activation patterns (rotors) for some high and intermediate risk compounds. Low risk compounds did not induce rotors in any cell type tested. These results further validate the utility of hiPSC-CMs for predictive proarrhythmia screening and the utility of voltage sensitive dye technology to detect drug induced APD prolongation, arrhythmias (rotors) and conduction slowing. Importantly, results indicate that different ratios of cardiomyocytes and non-cardiomyocytes have important impact on drug response that may be considered during risk assessment of new drugs. Finally, we present the first blinded CiPA hiPSC-CM validation results to simultaneously detect drug induced conduction slowing, action potential duration prolongation, action potential triangulation and drug induced rotors in a proarrhythmia assay.
Developmental mechanisms driving complex tooth shape in reptiles

In mammals, odontogenesis is regulated by transient signaling centers known as enamel knots (EKs), which drive the dental epithelium shaping. However, the developmental mechanisms contributing to formation of complex tooth shape in reptiles are not fully understood. Here, we aim to elucidate whether signaling organizers similar to EKs appear during reptilian odontogenesis and how enamel ridges are formed.
Constructing calendars in the brain

ABSTRACT By studying an enigmatic condition called, “calendar synesthesia”, we explored the elusive boundary between perception, visual imagery, and the manner in which we construct an internal mental calendar by mapping time-sequences onto spatial maps. We use a series of demonstrations to establish that these calendars act more like real objects activating sensory pathways rather than purely abstract symbolic descriptions that bear no resemblance to an actual calendar. We propose that the calendar is enshrined in acircuitry involving the hippocampal place-cells and entorhinal grid-cells, which are connected to the angular gyrus (involved with computing sequences) via the inferior longitudinal fasciculus.
Success of dental implants in elderly people - A literature review

: Implant-supported dentures seem particularly appropriate for the predicament of being elderly and becoming edentulous. The aim of this article was to review the literature on success of dental implants in elderly people. The results of two studies suggested that the treatment with implants can be considered safe and predictable for older as well as for younger patients. Three studies found no increased implant failure-rate in patients with a compromised medical status. Four studies revealed high success-rates of dental implants among groups of elderly people. Within the limitations of this review of the literature it can be concluded that old age does not seem to represent a factor of major prognostic significance in treatment with dental implants.
Hub disruption in patients with chronic neck pain: a graph analytical approach.

Chronic pain is known to alter the brain's network dynamics. These dynamics are often demonstrated by identifying alterations in the brain network topology. A common approach used for this purpose is graph theory. To date, little is known on how these potentially altered networks in chronic pain relate to the symptoms reported by these patients. Here, we applied a graph theoretical approach to identify network changes in patients suffering from chronic neck pain, a group that is often neglected in chronic pain research. Participants with chronic traumatic and non-traumatic neck pain were compared to healthy pain-free controls. They showed higher levels of self-reported symptoms of sensitization, higher levels of disability and impaired sensorimotor control. The brain suffering from chronic neck pain furthermore showed altered network properties in the posterior cingulate cortex, amygdala and pallidum compared to the healthy pain-free brain. These regions have been identified as brain hubs (i.e. regions that are responsible for orchestrating communication between other brain regions) and are therefore known to be more vulnerable in brain disorders including chronic pain. We were furthermore able to uncover associations between these altered brain network properties and the symptoms reported by patients. Our findings indicate that chronic neck pain patients reflect brain network alterations and that targeting the brain in patients might be of utmost importance.
A Review of Literature on Health-Related Quality of Life of Retinoblastoma Survivors

Background: Retinoblastoma is a malignant tumor of the eye that typically presents in early childhood and occurs in approximately 1 in 20,000 births. While active treatment of the tumor is typically completed in childhood, survivors often suffer from long-term effects from treatment including visual impairment, facial deformities, and fear of recurrence or secondary cancer. However, little is known how these long-term effects affect their health-related quality of life (HRQOL). Purpose: To review the literature on HRQOL in retinoblastoma survivors. Method: We searched three electronic databases from January 2005 to December 2018 for original research articles reporting on HRQOL or individual domains such as function, cognition, and psychosocial outcomes in retinoblastoma survivors. Results: A total of 59 articles were reviewed and 15 were identified as eligible. Five of the studies reported worse HRQOL in retinoblastoma survivors than controls or general population norms. Parent-proxy ratings were worse than survivors’ self-reports. Conclusion: Our findings confirm the need for further HRQOL research to assess the factors influencing long-term outcomes associated with treatment in adolescent and young adult retinoblastoma survivors. By identifying any potential deficits in specific domains of HRQOL, early interventions might be developed to improve HRQOL in retinoblastoma survivors.
Prevalence and Risk Factors Associated with Obesity among Adult Kabul Citizens (Afghanistan), 2012

lobally, the burden of noncommunicable diseases is rapidly increasing. The most important risk factors are high blood pressure (BP), high concentrations of cholesterol in the blood, inadequate intake of fruit and vegetables, overweight or obesity, physical inactivity and tobacco use (1). By 2008, an estimated 1.46 billion adults globally were overweight (body mass index [BMI]≥25kg/m2) and 500 million G
Moderate Alcohol Intake Promotes Pancreatic Ductal Adenocarcinoma Development in Mice Expressing Oncogenic Kras.

Kras mutations are associated with pancreatic ductal adenocarcinoma (PDAC). Although tobacco smoking, pancreatitis, and obesity are known environmental risk factors for PDAC, contribution of moderate alcohol intake to PDAC remains elusive. In the present study, we tested whether a combination of risk factors or moderate alcohol intake induces PDAC development in mice. Control Pdx1Cre and Pdx1Cre;LSL-KrasG12D mutant mice were fed a Western alcohol diet containing high levels of cholesterol and saturated fat, 3.5% alcohol, and lipopolysaccharide for 5 months. In addition, mice were treated with cerulein, for induction of pancreatitis, and nicotine every month. Treatment with all of these risk factors promoted development of advanced pancreatic neoplasia and PDAC in the Pdx1Cre;LSL-KrasG12D mice, but not in the control Pdx1Cre mice. Moderate alcohol intake or Western diet feeding also significantly promoted advanced neoplasia and PDAC development in Pdx1Cre;LSL-KrasG12D mice compared to mice fed a regular chow. Alcohol, but not Western diet, increased tumor development in the liver in the Pdx1Cre;LSL-KrasG12D mice, but its origin remained elusive due to leakiness of Pdx1Cre in hepatocytes. RNA-seq analysis revealed that alcohol feeding increases expression of markers for tumors (Epcam, Krt19, Prom1, Wt1, Wwtr1), stroma (Dcn, Fn1, Tnc), and cytokines (Tgfb1, Tnf) and decreases expression of Fgf21 and Il6 in the pancreatic tumor tissues. Immunostaining showed heterogeneous expression of NPNT, S100A6, and VCAM1 in pancreatic tumors surrounded by PDPN+ stromal cells. Our data indicate that moderate alcohol drinking is a risk factor for development of PDAC.
Developing a patient-centred care pathway for paediatric critical care in the Western Cape

III ACKNOWLEDGEMENTS . IV CONTRIBUTIONS . VI CONTENTS . VII LIST OF TABLES . IX LIST OF FIGURES . XI LIST OF APPENDICES . XII LIST OF CASE STUDIES . XII LIST OF ABBREVIATIONS . XIII DEFINITIONS . XV INTRODUCTION . 17 CASE STUDY 1 . 17 BACKGROUND . 19 CONTEXT . 21 AIMS AND OBJECTIVES . 26 LITERATURE REVIEW . 27 LITERATURE SEARCH METHODOLOGY . 27 CHILDHOOD MORTALITY AND MORBIDITY IN SOUTH AFRICA. 28 THE PATHWAY AND PROCESS OF CRITICAL CARE . 34 QUALITY OF CARE IN PAEDIATRIC HEALTHCARE . 42 THE CONFIDENTIAL ENQUIRY AND OTHER LONGITUDINAL STUDY METHODOLOGIES . 44 METHODOLOGY . 55 PILOT STUDY . 55 POPULATION AND STUDY SAMPLE . 56 ASCERTAINMENT . 57 DATA MANAGEMENT: ONLINE DATABASE . 62 REVIEW PROCESS . 62 DATA ANALYSIS . 66 ETHICAL CONSIDERATIONS AND PATIENT CONSENT . 67 DATA VERIFICATION . 67 CONCLUSION . 68 DEMOGRAPHICS AND DESCRIPTION OF COHORT . 69 DEMOGRAPHICS . 69 DIAGNOSIS . 69 ACCESS TO CARE ISSUES . 74 DISCUSSION: DEMOGRAPHICS; DIAGNOSIS AND ACCESS TO CARE . 76 OUTCOME AND QUALITY ASSESMENT . 81 OUTCOME OBJECTIVE . 81 EXPERT REVIEWER ASSESSMENT . 82 MULTIVARIABLE REGRESSION . 90 SYSTEM ISSUES . 91 CAREGIVER PERCEPTION AND SATISFACTION . 94 DISCUSSION: OUTCOME ASSESSMENT . 96 PATHWAY AND DELAY . 99
Targeted Therapy in Chronic Lymphocytic Leukemia

Abstract Despite a prevailing view that advances in cancer therapy will come through selective targeting of enzymes encoded by mutated oncogenes responsible for the neoplastic phenotype, recent advances in the treatment of patients with chronic lymphocytic leukemia (CLL) have instead exploited knowledge of its biology. Indeed, CLL cells depend on interactions with cells and soluble factors present in the tumor microenvironment for proliferation and survival. B-cell receptor signaling and chemokine-receptor signaling play prominent roles. Elucidation of these signaling pathways has defined physiologic targets for drugs, such as ibrutinib, which inhibit Bruton tyrosine kinase and are therapeutically effective. The characteristic high-level expression of BCL2 in CLL that can enhance leukemia-cell survival has now become an Achilles heel targeted by clinically effective drugs such as venetoclax. Here we discuss advances in such targeted therapy and highlight other disease attributes, such as the distinctive expression of ROR1, which may be targeted for clinical benefit, alone or in combination with other targeted therapies.
The role of computer-based clinical decision support systems to deliver protective mechanical ventilation.

PURPOSE OF REVIEW Mechanical ventilation of adults and children with acute respiratory failure necessitates balancing lung and diaphragm protective ventilation. Computerized decision support (CDS) offers advantages in circumstances where complex decisions need to be made to weigh potentially competing risks, depending on the physiologic state of the patient. RECENT FINDINGS Significant variability in how ventilator protocols are applied still exists and clinical data show that there continues to be wide variability in ventilator management. We have developed a CDS, which we are currently testing in a Phase II randomized controlled trial. The CDS is called Real-time Effort Driven ventilator management (REDvent). We will describe the rationale and methods for development of CDS for lung and diaphragm protective ventilation, using the REDvent CDS as an exemplar. SUMMARY Goals for achieving compliance and physiologic objectives can be met when CDS instructions are simple and explicit, provide the clinician with the underlying rule set, permit acceptable reasons for declining and allow for iterative adjustments.
Absorptive transport of amino acids by the rat colon.

The capacity of the colon to absorb microbially-produced amino acids (AAs) and the underlying mechanisms of AA transport are incompletely defined. We measured the profile of 16 fecal AAs along the rat ceco-colonic axis and compared unidirectional absorptive AA fluxes across mucosal tissues isolated from the rat jejunum, cecum, and proximal colon using an Ussing chamber approach in conjunction with 1H-NMR and UPLC-MS chemical analyses. Passage of stool from cecum to mid-colon was associated with segment-specific changes in fecal AA composition and a decrease in total AA content. Simultaneous measurement of up to 16 AA fluxes under native luminal conditions, with correction for endogenous AA release, demonstrated absorptive transfer of AAs across the cecum and proximal colon at rates comparable (30-80%) to those across the jejunum, with significant Na+-dependent and H+-stimulated components. Expression profiling of 30 major AA transporter genes by qPCR revealed comparatively high levels of transcripts for 20 AA transporters in the cecum and/or colon, with the levels of 12 exceeding those in small intestine. Our results suggest a more detailed model of major apical and basolateral AA transporters in rat colonocytes, and provide evidence for a previously unappreciated transfer of AAs across the colonic epithelium that could link the prodigious metabolic capacities of the luminal microbiota, the colonocytes, and the body tissues.
Case of morphea with symmetrical distribution of sclerotic lesions on bilateral forearms accompanied by extensive nail fold capillary abnormalities in multiple fingers

cardiography (V1, V5, V6), and aortic valve stenosis was found on echocardiography (Fig. 1g). Treatment with prednisolone was initiated (0.5 mg/kg per day). After 6 months, prednisolone had been reduced to 0.15 mg/kg per day, his IgG4 level returned to normal, skin lesions improved and no change in cardiac ultrasound finding was observed (the AS did not progress). Recent studies have shown that IgG4-RD may target parts of the cardiovascular system, including the aorta, peripheral arteries and pericardium. In addition, immunohistochemical analysis of tissue specimens has indicated that infiltration of IgG4positive plasma cells may not be a rare occurrence in various cardiac and arterial disorders. However, only pathological findings can confirm whether AS is caused by IgG4-RD if heart valve prosthesis surgery or another procedure is performed. Hourai et al. reported IgG4-positive cell infiltration in five of 24 (21%) patients from whom aortic valve samples were obtained after cardiovascular surgery, and these patients had not been diagnosed with IgG4-RD until undergoing cardiovascular surgery. These findings suggest that IgG4-RD is one of the causes of AS. Some patients with IgG4-RD have skin lesions, and they are usually referred to dermatologists after the diagnosis of pancreatitis, Mikulicz disease or other conditions. Skin manifestations in IgG4-RD have been poorly reported when compared with the manifestations of other organs. As both skin and heart lesions are rare in IgG4-RD, a case similar to ours has not been reported yet. If dermatologists diagnose IgG4-RD, it may lead to the early diagnosis of AS (asymptomatic AS, such as our case), which is a disease that becomes fatal on progression.
Nonadditive effects among threats on rare plant species

The current loss of biodiversity has put 50,000 plant species at an elevated risk of extinction worldwide. Conserving at‐risk species is often complicated by covariance or nonadditivity among threats, which makes it difficult to determine optimal management strategies. We sought to demographically quantify covariance and nonadditive effects of more threats on more rare plant species than ever attempted in a single analysis. We used 1082 population reports from 186 populations across 3 U.S. states of 27 rare, herbaceous plant species collected over 15 years by citizen scientists. We used a linear mixed‐effects model with 4 threats and their interactions as fixed predictors, species as a random predictor, and annual growth rates as the response. We found a significant 3‐way interaction on annual growth rates; rare plant population sizes were reduced by 46% during the time immediately after disturbance when populations were also browsed by deer (Odocoileus virginianus) and had high levels of encroachment by woody species. This nonadditive effect should be considered a major threat to the persistence of rare plant species. Our results highlight the need for comprehensive, multithreat assessments to determine optimal conservation actions.
Presence of EBV DNA in Cerebrospinal Fluid is Associated with Greater HIV RNA and Inflammation.

OBJECTIVE This study aimed to investigate whether cerebrospinal fluid (CSF) EBV or CMV DNA was associated with viral, inflammatory and neuronal damage biomarkers in people living with HIV (PLWH). DESIGN Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) can infect several cells, replicate in the central nervous system and affect blood-brain barrier (BBB) integrity. METHODS EBV, CMV DNA and HIV RNA were measured on CSF, through RT-PCR, from PLWHs undergoing lumbar punctures for clinical reasons (excluding oncho-haematological comorbidities). Immune-enzymatic assays evaluated BBB inflammation and damage. Patients were stratified according to plasma HIV RNA levels in viremic (≥50 copies/mL) and aviremic (<50 copies/mL). RESULTS We included 297 participants. Among 167 viremic patients CSF EBV and CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic subjects CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis (p < 0.001), higher CSF HIV RNA (p < 0.001) and neopterin levels (p = 0.002). In aviremic participants detectable EBV DNA was associated with pleocytosis (p = 0.056), higher neopterin (p = 0.027) and immune globulins (p = 0.016) in the CSF; CSF escape was more common in those with detectable EBV DNA (50% vs 21.2%, p = 0.036). CONCLUSIONS EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was associated with higher biomarkers levels of neuronal damage/inflammation. The role of EBV reactivation in HIV-associated CNS disorders warrants further studies.