Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing and Assessing the Effectiveness of a Nurse-Led Home-Based Educational Programme for Managing Breathlessness in Lung Cancer Patients. A Feasibility Study

Introduction: Breathlessness is the most common and refractory symptom in lung cancer patients. Even though various educational programmes have been developed, only a few were intended for implementation in the home setting for its management. Aim: Feasibility of a study for implementing a nurse-led educational programme for breathlessness management of lung cancer patients at home. Method: A randomized feasibility study was undertaken between February 2017 and October 2018. Patients were recruited through referral from oncologists from two oncology centers in Cyprus under certain inclusion and exclusion criteria. Patients were randomized in the intervention or control group via a computer programme, and their named family caregivers (f.c.) were allocated in the same group. Participants were not blinded to group assignment. The intervention consisted of a PowerPoint presentation and implementation of three non-pharmacological interventions. The control group received usual care. Patients were assessed for breathlessness, anxiety, and depression levels, whereas f.c. were assessed for anxiety, depression, and burden levels. F.c. also assessed patients' dyspnea level. The duration of the study process for both the intervention and control group was over a period of 4 weeks. Results: Twenty-four patients and their f.c. (n = 24) were allocated equally in the intervention and control group. Five patients withdrew, and the final sample entered analysis was 19 patients and 19 family caregivers. In the intervention group n = 11 + 11, and in the control group n = 8 + 8. In the intervention group patients' breathlessness and anxiety levels showed improvement and their f.c. s in the anxiety and burden levels. Major consideration was the sample size and the recruitment of the patients by the referring oncologists. Attrition was minor during the study process. No harm was recorded by the participants of the study. Conclusions: The study provided evidence of the feasibility of the implementation of the educational programme. For the future definitive study major consideration should be patients' recruitment method in order to achieve adequate sample size. Moreover, qualitative data should be collected in relation to the intervention and the involvement of f.c. The feasibility study was registered to the Cyprus Bioethics Committee with the registration number 2016/16. There was no funding of the study.
Diagnostic and Treatment Practices of Equine Endometritis—A Questionnaire

Endometritis is a major cause for impaired fertility in mares. The objectives of this study were to collect information on diagnostic and treatment practices performed by veterinarians and to investigate possible effects of professional experience, caseload, and geographical location on the practitioners' management of endometritis cases. For this purpose, equine practitioners (n = 680) were asked to fill out an online survey (34 questions). The online survey yielded 117 responses by veterinarians practicing in all parts of Germany. Most respondents came from Lower Saxony and managed <20 mares per year. For the diagnosis of chronic infectious endometritis, uterine sampling for microbiological examination was performed manually with a swab by the majority of practitioners whereas only few used the speculum technique. The incidence of antibiotic resistant pathogens was reported to be <5% by almost all respondents. Most practitioners relied on systemic antibiotic treatment with trimethoprim-sulfadiazine. Only occasionally veterinarians used intrauterine antibiotic therapy. Uterine lavages were performed routinely by almost half of the respondents in case of positive uterine cultures, mostly with 0.9% saline solution. Irritant solutions (e.g., iodine, chlorhexidine, kerosene) were used less often. Collection of an endometrial culture after completion of the treatment was common practice. While only a very limited association of the geographical location of practitioner (e.g., on selection of mares for endometrial culture, p < 0.05) was observed, the number of managed mares affected the answers notably (e.g., for use of irritating intrauterine treatment, p < 0.05). The management of persistent breeding induced endometritis (PBIE) was influenced by the number of managed mares (e.g., for use of oxytocin, p < 0.05) and 29.6% of respondents administered antibiotics as part of their PBIE management. In summary, treatment strategies in the field vary considerably and include also non-evidence-based methods, but most German practitioners apply the recommended suitable treatments. Following the guidelines for antibiotic usage, most veterinarians administer antibiotics dependent on endometrial culture results but do not use cytology, low-volume lavage, or biopsy routinely. Antibiotic resistant uterine pathogens are reported to be isolated infrequently and equine practitioners prefer systemic to local antibiotic treatment of endometritis.
Alteration of transcription by non-coding elements in the human genome

10 INTRODUCTION . 10 METHODS . 11 Identification of TE-TSSs from CAGE data . 11 Human genes and TSSs from CAGE data . 12 Relative ages of TE-TSSs . 13 Human-Mouse conservation of TSS . 14 RESULTS AND DISCUSSION. 15 Genome-scale identification of cis-NATs . 15
The Agony of Choice? Preserved Affective Decision Making in Early Multiple Sclerosis

Background: Cognitive impairment (CI) is an early and frequent symptom of multiple sclerosis (MS). Likewise, affective symptoms (e.g., depression and anxiety) and alterations in the processing of emotional stimuli have been frequently reported. Thus, abilities that integrate affective and cognitive processes such as decision making (DM) based on affective feedback are potentially valuable early diagnostic markers for MS. The available research on this topic, however, is still inconclusive and suffers from methodological issues. Methods: We compared DM ability in a clinically homogeneous cohort of 24 patients with early relapsing–remitting MS (RRMS) and 59 age-matched healthy controls (HCs). A modified version of the Iowa gambling task (IGT) allowed us to control for individual differences in search strategies during the risk exploration phase. Besides standard IGT measures (netscore, obtained play money, and learning index), we also examined reaction times and post-error slowing (PES) patterns as a proxy for abnormalities in the processing of affective feedback. Results: The performance of patients did not significantly deviate from HCs in any standard parameter of the modified IGT. Furthermore, although RRMS patients reacted significantly slower than HCs overall, we found similar patterns of PES in both groups, suggesting similarly efficient processing of affective feedback. Conclusion: We conclude that there is no specific deficit in affective feedback processing in early RRMS. Previous findings of IGT impairments in this patient group may thus not represent a genuine deficit in affective DM but rather be related to sample characteristics, general CI, and/or differences in individual search strategies. Future research should explore the potential influence of lesion volumes and locations on DM ability by employing brain imaging techniques.
Genetic Loss of LCK Kinase Leads to Acceleration of Chronic Lymphocytic Leukemia

Most patients with chronic lymphocytic leukemia (CLL) exhibit an indolent disease course and unresponsive B cell receptors (BCRs) exemplified by an anergic phenotype of their leukemic cells. In up to 5% of patients, CLL transforms from an indolent subtype to an aggressive form of B cell lymphoma (Richter's syndrome), which is associated with worse disease outcome and severe downregulation of NFAT2. Here we show that ablation of the tyrosine kinase LCK, which has previously been characterized as a main NFAT2 target gene in CLL, leads to loss of the anergic phenotype, thereby restoring BCR signaling, which results in an acceleration of CLL. Our study identifies LCK as a main player in mediating BCR unresponsiveness and its role as a crucial regulator of anergy in CLL.
Awareness and Stimulus-Driven Spatial Attention as Independent Processes

To investigate the relation between attention and awareness, we manipulated visibility/awareness and stimulus-driven attention capture among metacontrast-masked visual stimuli. By varying the time interval between target and mask, we manipulated target visibility measured as target discrimination accuracies (ACCs; Experiments 1 and 2) and as subjective awareness ratings (Experiment 3). To modulate stimulus-driven attention capture, we presented the masked target either as a color-singleton (the target stands out by its unique color among homogeneously colored non-singletons), as a non-singleton together with a distractor singleton elsewhere (an irrelevant distractor has a unique color, whereas the target is colored like the other stimuli) or without a singleton (no stimulus stands out; only in Experiment 1). As color singletons capture attention in a stimulus-driven way, we expected target visibility/discrimination performance to be best for target singletons and worst with distractor singletons. In Experiments 1 and 2, we confirmed that the masking interval and the singleton manipulation influenced ACCs in an independent way and that attention capture by the singletons, with facilitated performance in target-singleton compared to distractor-singleton conditions, was found regardless of the interval-induced (in-)visibility of the targets. In Experiment 1, we also confirmed that attention capture was the same among participants with worse and better visibility/discrimination performance. In Experiment 2, we confirmed attention capture by color singletons with better discrimination performance for probes presented at singleton position, compared to other positions. Finally, in Experiment 3, we found that attention capture by target singletons also increased target awareness and that this capture effect on subjective awareness was independent of the effect of the masking interval, too. Together, results provide new evidence that stimulus-driven attention and awareness operate independently from one another and that stimulus-driven attention capture can precede awareness.
Establishment of Decision Rules and Risk Assessment Model for Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer

Background: Preoperative accurate prediction of lymph node status is especially important for the formulation of treatment plans for patients with gastric cancer (GC). The purpose of this study was to establish decision rules and a risk assessment model for lymph node metastasis (LNM) in GC using preoperative indicators. Methods: The clinical data of 554 patients who underwent gastrectomy with D2 lymphadenectomy were collected. A 1:1 propensity score matching (PSM) system was used, and the clinical data of the matched 466 patients were further analyzed. The important risk factors for LNM were extracted by the random forest algorithm, and decision rules and nomogram models for LNM were constructed with a classification tree and the “rms” package of R software, respectively. Results: Tumor size (OR: 2.058; P = 0.000), computed tomography (CT) findings (OR: 1.969; P = 0.001), grade (OR: 0.479; P = 0.000), hemoglobin (Hb) (OR: 1.211; P = 0.005), CEA (OR: 1.111; P = 0.017), and CA19-9 (OR: 1.040; P = 0.033) were independent risk factors for LNM in GC. Tumor size did rank first in the ranking of important factors for LNM in GC and was the first-level segmentation of the two initial branches of the classification tree. The accuracy, sensitivity, specificity, and positive predictive value of the decision rules in diagnosing preoperative LNM in GC were 75.6, 85.7, 73.9, 73.5, and 79.3%, respectively. The accuracy, sensitivity, and specificity of the risk assessment model in predicting preoperative LNM in GC were 79.3, 80.3, and 79.4%, respectively. Conclusion: Tumor size was the most important factor for evaluating LNM in GC. This decision rules and nomogram model constructed to take into account tumor size, CT findings, grade, hemoglobin, CEA, and CA19-9 effectively predicted the incidence of LNM in preoperative GC.
Higher Fibroblast Growth Factor 23 Levels Are Causally Associated With Lower Bone Mineral Density of Heel and Femoral Neck: Evidence From Two-Sample Mendelian Randomization Analysis

Background: Previous observational studies have indicated that high levels of fibroblast growth factor 23 (FGF23), a phosphoric hormone that inhibits calcitriol synthesis, in the blood is associated with the reduced bone mineral density (BMD); however, whether this association is causal remains unclear. In this study, we conducted a Mendelian Random (MR) study to investigate whether the genetic predisposition of higher FGF23 levels was causally associated with lower BMD in adults. Methods: A two-sample MR was performed with five single nucleotide polymorphisms significantly associated with FGF23, selected as instrumental variables. Two-sample MR estimates were derived from summary-level data of large-sample genome-wide association studies for BMD and the levels of bone metabolism characteristics. Results: The two-sample MR analysis showed that for every 1-unit increase in the log-transformed blood FGF23 level (pg/mL), the decreased levels of adult heel BMD (β = −0.201, se = 0.084, P = 0.016) and femoral neck BMD (β = −0.286, se = 0.126, P = 0.022) were noted, indicative of a causal relationship based on the inverse variance weighting method. However, FGF23 levels were not correlated with adult lumbar spine BMD (β = −0.166, se = 0.193, P = 0.389), and forearm BMD (β = −0.186, se = 0.366, P = 0.610). Moreover, the two-sample MR analysis suggested that there was no evidence for associations between FGF23 and adult calcium, phosphorus, 25(OH)D, creatinine, and magnesium levels. Conclusions: This study suggests that there may be a causal relationship between blood FGF23 levels and BMD of the heel and femoral neck in adults; however, more investigations are necessary to determine whether FGF23 may be a potential biomarker and/or therapeutic target for diseases that affect bone mineralization.
Influence of KIR and NK Cell Reconstitution in the Outcomes of Hematopoietic Stem Cell Transplantation

Natural killer (NK) cells play a significant role in immune tolerance and immune surveillance. Killer immunoglobin-like receptors (KIRs), which recognize human leukocyte antigen (HLA) class I molecules, are particularly important for NK cell functions. Previous studies have suggested that, in the setting of hematopoietic stem cell transplantation (HSCT), alloreactive NK cells from the donor could efficiently eliminate recipient tumor cells and the residual immune cells. Subsequently, several clinical models were established to determine the optimal donors who would exhibit a graft-vs. -leukemia (GVL) effect without developing graft-vs. -host disease (GVHD). In addition, hypotheses about specific beneficial receptor-ligand pairs and KIR genes have been raised and the favorable effects of alloreactive NK cells are being investigated. Moreover, with a deeper understanding of the process of NK cell reconstitution post-HSCT, new factors involved in this process and the defects of previous models have been observed. In this review, we summarize the most relevant literatures about the impact of NK cell alloreactivity on transplant outcomes and the factors affecting NK cell reconstitution.
Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

Tumor-mediated regulation of the host immune system involves an intricate signaling network that results in the tumor's inherent survival benefit. Myeloid cells are central in orchestrating the mechanisms by which tumors escape immune detection and continue their proliferative programming. Myeloid cell activation has historically been classified using a dichotomous system of classical (M1-like) and alternative (M2-like) states, defining general pro- and anti-inflammatory functions, respectively. Explosions in bioinformatics analyses have rapidly expanded the definitions of myeloid cell pro- and anti-inflammatory states with different combinations of tissue- and disease-specific phenotypic and functional markers. These new definitions have allowed researchers to target specific subsets of disease-propagating myeloid cells in order to modify or arrest the natural progression of the associated disease, especially in the context of tumor-immune interactions. Here, we discuss the myeloid cell contribution to solid tumor initiation and maintenance, and strategies to reprogram their phenotypic and functional fate, thereby disabling the network that benefits tumor survival.
Changes in Diet, Sleep, and Physical Activity Are Associated With Differences in Negative Mood During COVID-19 Lockdown

The United Kingdom and Scottish governments instigated a societal lockdown in response to the COVID-19 pandemic. Subsequently, many experienced substantial lifestyle changes alongside the stresses of potentially catching the virus or experiencing bereavement. Stressful situations and poorer health behaviors (e.g., higher alcohol consumption, unhealthy diet, poorer sleep quality, physical inactivity) are frequently linked to poor mental health. Our objective was to examine changes in health behaviors and their relationship with negative mood during COVID-19 lockdown. We also considered associations between health behaviors and socio-demographic differences and COVID-19-induced changes. 399 participants completed a questionnaire asking about their personal situation and health behaviors during lockdown as well as a negative mood scale. The significance threshold for all analyses was α = 0.05. Poorer diet was linked to more-negative mood, and to changes to working status. Poorer sleep quality was linked with more-negative mood, and with ‘shielding’ from the virus. Being less physically active was related to more-negative mood and student status, whereas being more physically active was linked to having or suspecting COVID-19 infection within the household. Increased alcohol consumption was linked to living with children, but not to negative mood. Changes to diet, sleep quality, and physical activity related to differences in negative mood during COVID-19 lockdown. This study adds to reports on poor mental health during lockdown and identifies lifestyle restrictions and changes to health behaviors which may, to some extent, be responsible for higher negative mood. Our data suggests that it is advisable to maintain or improve health behaviors during pandemic-associated restrictions.
The (Neutrophils + Monocyte)/Lymphocyte Ratio Is an Independent Prognostic Factor for Progression-Free Survival in Newly Diagnosed Multiple Myeloma Patients Treated With BCD Regimen

Objective Bortezomib is one of the important drugs that have made breakthrough progress in multiple myeloma (MM) in the past 10 years. However, the heterogeneity of its efficacy makes it difficult to predict the risk of disease progression. The purpose of this study is to determine the prognostic significance of the (neutrophils + monocytes)/lymphocytes ratio (NMLR) in newly diagnosed MM patients who received BCD regimen therapy in terms of progression-free survival (PFS). Methods A total of 150 patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study retrospectively. The prognostic value of NMLR was evaluated by 150 patients with MM who were treated with BCD (bortezomib + cyclophosphamide + dexamethasone) regimen therapy. NMLR was calculated by the ratio of (neutrophils + monocyte) to lymphocytes. According to receiver operating characteristic curves, the cutoff value was 1.90. The patients were divided into high NMLR group (H-NMLR, NMLR ≥1.90) and low NMLR group (L-NMLR, NMLR <1.90). The clinical characteristics, treatment responses and PFS of the two groups were analyzed. Results The median age of the patients was 61 years. Fifty-five (36.67%) patients showed lower NMLR at initial diagnosis. Although NMLR was unable to discriminate prognosis in ISS stage I/II patients, interestingly, the addition of NMLR to the ISS further defined prognosis particularly in stage III. Low-NMLR group who achieved early immune reconstruction significantly higher than that of the high-NMLR group (P < 0.001). NMLR value was 1.98 ± 1.02 for the patients who achieved early immune reconstruction, which was 3.26 ± 2.52 for the patients without immune reconstruction (P < 0.05). Compared with the H-NMLR group, the levels of β2-microglobulin, serum creatinine and calcium were lower, and the very good partial response or better (≥VGPR) ratio was higher in L-NMLR group. The L-NMLR group experienced a superior median PFS compared with the H-NMLR group (24.0 versus 15.5 months; P < 0.001). In addition, several other prognostic factors of PFS were estimated, including the high-risk cytogenetics, β2-microglobulin and the depth of treatment response 3 months after treatment with BCD regimen. Moreover, NMLR was an independent predictor of PFS including non-high risk cytogenetics (0.587; P = 0.031). Conclusion In patients with newly diagnosed MM undergoing BCD regimen, the NMLR <1.90 was an independent prognostic factor for PFS as well as early immune reconstruction and lower disease burden.
Orthostatic Hypotension Is Associated With Cognitive Decline in Parkinson Disease

Introduction: Cognitive impairment and orthostatic hypotension (OH) are common, disabling Parkinson disease (PD) symptoms that are strongly correlated. Whether the relationship is causative or associative remains unknown. OH may occur without classic orthostatic symptoms of cerebral hypoperfusion (i.e., lightheadedness or dizziness). Whether longitudinal differences in cognition occur between symptomatic and asymptomatic OH patients has not been explored. Objectives: We characterized the prevalence of OH, orthostatic symptoms, and cognitive impairment among PD patients and compared cognition between patients with and without OH, and between patients with symptomatic and asymptomatic OH. Methods: Our cross-sectional, retrospective, observational study included 226 clinically diagnosed PD patients who underwent repeated standardized evaluations. Among these, 62 had longitudinal follow-up of > 3.5 years. We compared longitudinal Montreal Cognitive Assessment (MoCA) scores between patients remaining OH-free (n = 14) and those without baseline OH that developed OH (n = 28), matched for age, sex, education, and PD duration. We also compared MoCA scores between groups with asymptomatic OH (n = 13) and symptomatic OH (n = 13) matched for the same factors. Results: In the cross-sectional analysis, OH patients had worse cognition. In the longitudinal analysis (mean follow-up = 5.3 years), OH patients had worse cognitive decline (p = 0.027). Cognitive impairment was similar between asymptomatic and symptomatic OH patients in the cross-sectional and longitudinal analyses. Conclusions: OH is associated with cognitive impairment in PD. Further studies are needed in larger cohorts to expand our findings and to determine whether treating OH can prevent or delay cognitive dysfunction.