Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of mRNA COVID-19 vaccines in patients with lymphoid malignancies

Patients with lymphoid malignancies are at increased risk of developing COVID-19 and are at high risk of poor outcomes. 1-5 There is a need for protective strategies in this vulnerable population. Although there have been 2 prior phase 3 trials investigating nanoparticle-encapsulated messenger RNA (mRNA)-based vaccines, BNT162b2 (P ﬁ zer, Inc) and mRNA-1273 (ModernaTX, Inc), that encode the prefusion stabilized full-length spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immuno-compromised patients were excluded. 6,7 In the research by Perry et al, humoral responses following admin-istration of BNT162b2 were evaluated in patients with non-Hodgkin lymphoma. Strikingly, patients who had received anti-CD20 antibody therapy within 6 months of vaccination were unlikely to mount a humoral response, a ﬁ nding that has similarly been described in patients with chronic lymphocytic leukemia (CLL). 8,9 Perry et al also showed that patients with treatment-naive disease were more likely to develop a humoral response, although with lower rates and titer levels as compared with healthy controls. We similarly performed a prospective study to evaluate serologic response following vaccination with BNT162b2 or mRNA-1273 in a cohort of patients with key lymphoid malignancies (including CLL) in various phases of treatment. Our data support the ﬁ ndings by Perry et al. In addition, we report quantitative antibody titers at 3 time points pre- and postvaccination and describe the humoral response following a range of treatment strategies.
Impact of shift work on the risk of depression

ABSTRACT We studied the association between shift work and depressive symptoms in the prospective Heinz Nixdorf Recall Study, considering various demographic, lifestyle and work-related factors. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D)-Scale (≥17 points defined as high symptoms) and the Patient Health Questionnaire (PHQ) with a cutoff ≥9, or prescription of an anti-depressant. The definition of shift work included work hours outside 7:00 to 18:00, whereas night work was defined as a shift including work between 0:00 and 5:00. Poisson regression with robust error variances was calculated to estimate relative risks (RR) and 95% confidence intervals (CI), adjusted for age at follow-up, diurnal preference, monthly household income and education. Analyses were stratified by sex. We performed various sensitivity and stratified analyses to test the robustness of our results. At baseline, 1,500 gainfully employed subjects, 45–73 years of age and without a history of depression, were included. Until the 5-year follow-up, 896 participants were observed, and 486 participants survived through the 10-year follow-up. Although most analyses did not reach the level of formal statistical significance, women working night shifts tended to show increased relative risks for depressive symptoms according to the PHQ (RR = 1.78; 95% CI 0.71–4.45), in particular when working night shifts for ≥20 years (RR = 2.70; 95% CI 0.48–15.4). Stratification by age group revealed no increased risks among women above 60 years of age. Stratified analyses indicated that over-commitment was associated with higher risks for depressive symptoms among women (RR = 4.59; 95% CI 0.95–22.2 in the CES-D and RR = 12.7; 95% CI 2.89–56.1 in the PHQ). Exclusion of subgroups for the purpose of sensitivity analyses generally strengthened associations in women, whereas little evidence for an increased risk of depression remained among male shift workers. In summary, negative effects on depression were suggested among female shift workers, although results were based on small numbers. Among men, we did not identify consistently increased risks for depressive symptoms in relation to shift work.
Implicit Neurofeedback Training of Feature-Based Attention Promotes Biased Sensory Processing during Integrative Decision-Making

Complex perceptual decisions, in which information must be integrated across multiple sources of evidence, are ubiquitous but are not well understood. Such decisions rely on sensory processing of each individual source of evidence, and are therefore vulnerable to bias if sensory processing resources are disproportionately allocated among visual inputs. To investigate this, we developed an implicit neurofeedback protocol embedded within a complex decision-making task to bias sensory processing in favor of one source of evidence over another. Human participants of both sexes (N = 30) were asked to report the average motion direction across two fields of oriented moving bars. Bars of different orientations flickered at different frequencies, thus inducing steady-state visual evoked potentials. Unbeknownst to participants, neurofeedback was implemented to implicitly reward attention to a specific “trained” orientation (rather than any particular motion direction). As attentional selectivity for this orientation increased, the motion coherence of both fields of bars increased, making the task easier without altering the relative reliability of the two sources of evidence. Critically, these neurofeedback trials were alternated with “test” trials in which motion coherence was not contingent on attentional selectivity, allowing us to assess the training efficacy. The protocol successfully biased sensory processing, resulting in earlier and stronger encoding of the trained evidence source. In turn, this evidence was weighted more heavily in behavioral and neural representations of the integrated average, although the two sources of evidence were always matched in reliability. These results demonstrate how biases in sensory processing can impact integrative decision-making processes. SIGNIFICANCE STATEMENT Many everyday decisions require active integration of different sources of sensory information, such as deciding when it is safe to cross a road, yet little is known about how the brain prioritizes sensory sources in the service of adaptive behavior, or whether such decisions can be altered through learning. Here we addressed these questions using a novel behavioral protocol that provided observers with real-time feedback of their own brain activity patterns in which sensory processing was implicitly biased toward a subset of the available information. We show that, while such biases are a normal and adaptive mechanism for humans to process complex visual information, they can also contribute to suboptimal decision-making.
Biochar influences soil carbon pools and facilitates interactions with soil: A field investigation

Biochar promotes the storage of organic carbon (OC) in soils. OC is unevenly distributed in soils among different particle‐size fractions showing different structures, functions, and stability. The objective of this study was to investigate the biochar–soil interactions and the redistribution of soil C in different soil fractions based on a 2‐year field experiment. Fractionation was done by particle sizes including coarse sand (250–2,000 μm), fine sand (53–250 μm), and silt/clay (<53 μm). Integrated spectroscopic techniques were employed to examine physical characteristics of biochar–soil interactions in different soil fractions. Application of biochar increased OC by 37%, 42%, and 76% in soil particle‐size fractions of 53–250, <53, and 250–2,000 μm, respectively. This was supported by X‐ray fluorescence spectroscopy analysis, which showed an increase of C contents by 5–56% with biochar addition. The highest increment in OC was found in coarse sand fraction, and redistribution of OC was detected depending on various soil particle sizes. Results of scanning electron microscopy combined with electron dispersive X‐ray spectroscopy analysis showed the interactions between soil and biochar, which could be attributed to oxidized functional groups (OCO, CO, and CO) captured by the X‐ray photoelectron spectroscopy. The long‐term aged biochar could be beneficial to enhance soil quality by promoting OC storage and facilitating positive biochar–soil interactions.
Low serum albumin level deteriorates prognosis in azacitidine-treated myelodysplastic syndromes patients – results of the PALG study ‘PolAZA’

ABSTRACT Background Azacitidine (AZA) is the standard of care for higher-risk myelodysplastic syndrome (HR-MDS) patients ineligible for intensive therapy. Clinical outcome discrepancies reported in clinical trials and real-life settings stimulate the search for new prognostic factors. Methods We retrospectively evaluated 315 MDS, 20–30% blast acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) patients treated with azacitidine in 12 centers cooperating within the Polish Adult Leukemia Group (PALG). Results The median number of AZA cycles was 7 (1–69) and 24% patients received fewer than 4 cycles (early failure, EF). Serum albumin level was an independent predictor of EF occurrence. Complete remission (CR) was obtained in 20% and partial remission (PR) in 12% of patients. Hematologic improvement – erythroid (HI-E), neutrophil (HI-N), or platelet (HI-P) was achieved in 51%, 36%, and 48% of patients, respectively. No factors significantly predicted CR or PR in the multivariate analysis. For HI-E and HI-P, lower LDH level predicted response. Median survival was 15 (13–19) months. Lower serum albumin level, serious infection and receiving <4 AZA cycles independently predicted a worse overall survival (OS) (p < 0.05). Conclusion Serum albumin assessment before azacitidine treatment can help to identify patients with higher risk of early failure and worse clinical outcome.
Disordered Selfhood in Schizophrenia and the Examination of Anomalous Self-Experience: Accumulated Evidence and Experience

Disordered selfhood in schizophrenia was rediscovered at the turn of the millennium. In 2005, Psychopathology published the psychometric instrument, the Examination of Anomalous Self-Experience (EASE). In this article, we summarize the historical background of the creation of the EASE, explicate the notion of the disorder of basic or minimal self with the help of phenomenological philosophy, and provide a brief description of clinical manifestations targeted by the EASE. We also present our personal experience using and teaching the EASE and summarize the empirical evidence obtained so far. We conclude that the basic self-disorder represents a crucial phenotype of schizophrenia spectrum disorders and that this phenotype offers a potential avenue to empirical pathogenetic research and psychotherapeutic treatment.
Hypothermia following cold-water immersion treatment for exertional heat illness

ABSTRACT Cold-water immersion (CWI) is the gold standard therapy for exertional heat illness (EHS), and it is critical to perform CWI expeditiously when the core temperature exceeds 40°C; however, the treatment comes with risks, most notably hypothermia. Following a major marathon, three runners presented to our emergency department (ED) with symptomatic mild hypothermia requiring re-warming. Prior to developing hypothermia, all three were treated at the racecourse with CWI for EHS. During CWI, there are monitoring methods to determine appropriate cessation: continuous temperature measurement, regular temperature checks, using an equation to predict immersion time, and symptom observation. There is no consensus on the best system, but a monitoring method should be used to prevent over-cooling. This case series illustrates the importance of proper CWI execution in order to avoid harm.
Le Fort I Osteotomy in Cleft Patients: Maxillary Advancement and Articulation

Background: Maxillary advancement may affect speech in cleft patients. Aims: To examine whether the amount of maxillary advancement and preoperativecephalometric skeletal and dentoalveolar relationships are associated with articulation errors of the Finnish alveolar consonants /s/, /l/, and /r/ in cleft patients. Materials and Methods: Fifty-seven nonsyndromic cleft patients who underwent Le Fort I or bimaxillary osteotomies were evaluated retrospectively. Pre- and post-operative lateral cephalometric radiographs and standardized speech video recordings were analyzed. The Aspin-Welch unequal variance t test, Student t test sign test, intraclass correlation and Kappa statistics were used in the statistical analyses. Results: The mean advancement of the maxilla (point A) was 4.65 mm horizontally (range −2.80 to 11.30) and −3.82 mm vertically (range −14.20 to 3.90). The overall articulation (especially the sounds /s/ and /l/) improved significantly postoperatively, but the amount of maxillary advancement did not affect the articulation. The preoperative mean percentages of /s/, /l/, and /r/ errors were 32%, 33%, 46% and the postoperative percentages 23%, 19%, 40%, respectively. Preoperative articulation errors of /s/ were related to palatal inclination of the upper incisors. Conclusions: Orthognathic surgery may improve articulation errors. The amount of maxillary advancement is not related to the improvement.
Vitamin D levels associate with blood glucose and BMI in COVID-19 patients predicting disease severity

Abstract Context High prevalence of Vitamin-D (VD) deficiency in COVID-19 patients was reported and hypothesized to increase COVID-19 severity likely due to its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis-D and fat body-mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized. Objective The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, BMI, blood glucose and disease severity. Design Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD-metabolism. 25(OH)VD levels, plasma glucose levels, BMI and inflammatory parameters were evaluated at admission. Results A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD-deficiency was found in 68.2% of patients. VD-deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma glucose, BMI, Neutrophil/Lymphocyte ratio, CRP and IL-6. Patients with both hypovitaminosis-D and diabetes mellitus, as well those with hypovitaminosis-D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions. Conclusions We showed, for the first-time, a strict association of VD levels with blood glucose and BMI in COVID-19 patients. VD-deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.
CAFs shape myeloid‐derived suppressor cells to promote stemness of intrahepatic cholangiocarcinoma through 5‐lipoxygenase

We previously demonstrated that cancer‐associated fibroblasts (CAFs) promote tumor growth through recruitment of myeloid‐derived suppressor cells (MDSCs). 5‐lipoxygenase (5‐LO) is highly expressed in myeloid cells and is critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression by activating its receptor leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC).
Towards Equitable Health Care Access: Community Participatory Research Exploring Unmet Health Care Needs of Homeless Individuals

Community and health services often overlook health care needs of persons experiencing homelessness, which leads to deterioration in health and increased utilization of emergency services. Since homeless people are underrepresented in health service research, little is known about their unmet health care needs, particularly in smaller cities where resources are limited. This community-based participatory research explored the experiences of small-city homeless service users (HSUs) with unmet health care needs and community service providers (CSPs) who work with them to determine barriers to health care access affecting them. Structured interviews were conducted with 65 HSUs and 15 CSPs in interior British Columbia, Canada. These interviews were audio-recorded, and the retrieved data were analyzed thematically. The three themes uncovered included: a lack of access to health care and risk of stigma, a lack of trust and fear of discrimination, and a need for community navigation and social support. The findings indicate that HSUs do not receive equitable care and face challenges in accessing appropriate and timely foot care, which contributes to increased foot-related emergency visits, loss of trust in the health care system, and disabilities due to worsening foot conditions. Various social determinants of health also impact HSUs, such as low socioeconomic status, lack of housing, decreased social support, unhealthy behaviors, and inequitable access to health services. By collaborating with HSUs, community and health services need to develop innovative outreach programs that provide better community resources as the first step toward equitable access to health care.
Inferring Gene Co-Expression Networks by Incorporating Prior Protein-Protein Interaction Networks

Inferring gene co-expression networks from high-throughput gene expression data is an important task in bioinformatics. Many gene networks often exhibit modular structures. Although several Gaussian graphical model-based methods have been developed to estimate gene co-expression networks by incorporating the modular structural prior, none of them takes into account the modular structures captured by the prior networks (e.g., protein interaction networks). In this study, we propose a novel prior network-dependent gene network inference (pGNI) method to estimate gene co-expression networks by integrating gene expression data and prior protein interaction network data. The underlying modular structure is learned from both sets of data. Through simulation studies, we demonstrate the feasibility and effectiveness of our method. We also apply our method to two real datasets. The modular structures in the networks estimated by our method are biological significant.
The prognostic value of the pretreatment serum albumin to globulin ratio for predicting adverse pathology in patients undergoing radical prostatectomy for prostate cancer

Purpose Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea. Materials and Methods This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein−albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis. Results The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557–0.671; p<0.001). Patients who had a lower pretreatment AGR (<1.53) were identified as the low AGR group (n=398, 53.6%) and the remaining patients as the high AGR group (n=344, 46.4%). Preoperative AGR was significantly lower in patients with non-organ-confined disease (≥pT3) than in those with organ-confined disease (≤pT2) (p<0.001). The low AGR group had higher aggressive pathologic Gleason scores (pGS) (≥8) than did the high AGR group (p=0.016). Furthermore, the AGR was an independent prognostic factor for high pGS (≥8) and non-organ-confined disease (≥pT3), according to multivariate logistic regression analysis. Conclusions A low AGR was closely associated with nonconfined disease (≥pT3) and high pGS (≥8). AGR can be a useful serological marker for predicting adverse pathology in patients with nonmetastatic PCa who undergo RP.
Dynamic interplay between AfadinS1795 phosphorylation and diet regulates glucose homeostasis in obese mice

Afadin is a ubiquitously expressed scaffold protein with a recently discovered role in insulin signalling and glucose metabolism. Insulin‐stimulated phosphorylation of Afadin at S1795 occurs in insulin‐responsive tissues such as adipose tissue, muscle, liver, pancreas and heart. Afadin abundance and AfadinS1795 phosphorylation are dynamically regulated in metabolic tissues during diet‐induced obesity progression. Genetic silencing of AfadinS1795 phosphorylation improves glucose homeostasis in the early stages of diet‐induced metabolic dysregulation. AfadinS1795 phosphorylation contributes to the early development of obesity‐related complications in mice.
Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing

Abstract A critical aspect of toxicity evaluation is developmental and reproductive toxicity (DART) testing. Traditionally, DART testing has been conducted in vivo in mammalian model systems. New legislation aimed at reducing animal use and the prohibitive costs associated with DART testing, together with a need to understand the genetic pathways underlying developmental toxicity means there is a growing demand for alternative model systems for toxicity evaluation. Here we explore the potential of the eukaryotic social amoeba Dictyostelium discoideum, which is already widely used as a simple model system for cell and developmental biology, as a potential nonanimal model for DART testing. We developed assays for high-throughput screening of toxicity during D. discoideum growth and development. This allowed the toxicity of a broad range of test compounds to be characterized, which revealed that D. discoideum can broadly predict mammalian toxicity. In addition, we show that this system can be used to perform functional genomic screens to compare the molecular modes of action of different compounds. For example, genome-wide screens for mutations that affect lithium and valproic acid toxicity allowed common and unique biological targets and molecular processes mediating their toxicity to be identified. These studies illustrate that D. discoideum could represent a predictive nonanimal model for DART testing due to its amenability to high-throughput approaches and molecular genetic tractability.