Miracle-dz/UniFAR-FTUs huggingface dataset:
Repetitive TMS over Frontal Eye Fields Disrupts Visually Cued Auditory Attention

Voluntary eye movements and covert shifts of visual attention activate the same brain regions. Specifically, the intra parietal sulcus and the frontal eye fields (FEF) appear to be involved both with generating voluntary saccades as well with attending to a peripheral spatial location. Furthermore, these regions appear to be required by both tasks – functional disruption of these regions impairs both tasks. Therefore, it appears that the targeting system that allows us to plan saccades is the same system that allows us to covertly track peripheral visual information. Recent neuroimaging studies suggest that these brain regions are also activated when participants engage in auditory spatial attention tasks. However, it remains unclear whether these regions are required by these tasks. We used repetitive Transcranial Magnetic Stimulation (rTMS) to disrupt the FEF while participants performed an auditory localisation task. On each trial, a visual cue directed attention to the probable laterality of the auditory target, and the participant decided whether the subsequent target sound came from an upper or lower speaker. In the absence of TMS, individuals were faster to respond to targets that occurred on the cued side (valid trials) than when the target appears contralaterally to the cued side (invalid side). TMS interfered with this effect, such that the costs associated with ipsilateral invalidly cued targets were substantially reduced. These results suggest that the eye-movement system is needed for normal auditory attention. individuals are also able to covertly attend to a region of their peripheral visual field. People are faster and more accurate at identifying attended peripheral information than similar stimuli presented at an unattended peripheral location. The neural mechanisms underlying covert visual attention have been intensely
Comparative Study of Circulating Tumor DNA and Computerized Tomography Monitoring in Untreated Diffuse Large B-Cell Lymphoma

Background— Diffuse large-B-cell lymphoma (DLBCL) is curable but when treatment fails, outcome is poor. Imaging scans help identify patients at risk of treatment failure but are often imprecise, and the radiation exposure is a potential health risk. Specific, sensitive and readily available biomarkers of treatment failure are needed. Methods— We retrospectively analyzed cell-free circulating tumor DNA (ctDNA) in patients treated on one of 3 treatment protocols using quantitative next-generation DNA sequencing. Eligible patients had DLBCL, no evidence of indolent lymphoma and were previously untreated. Serial serum samples and concurrent computed tomography scans were obtained at specified times during most treatment cycles and 5-years of follow-up. VDJ gene segments of the rearranged immunoglobulin receptor genes were amplified and sequenced from pre-treatment specimens and serum ctDNA encoding the VDJ rearrangements was quantitated. Findings— Tumor clonotype(s) were identified in pretreatment specimens from 126 patients who were followed for a median (interquartile range) of 11 (6.8 to 14.2) years. Interim ctDNA monitoring at the end of 2 treatment cycles in 108 patients showed a time to progression (TTP) of 41.7% (95% Confidence Interval (CI): 22.2% to 60.1%) and 80.2% (95% CI: 69.6% to 87.3%), at 5-years (p<0.0001) in patients with and without detectable ctDNA, respectively, and a positive and negative predicative value (PPV and NPV) of 63% and 80%, respectively. Surveillance ctDNA monitoring was performed in 107 patients who achieved complete remission. A Cox proportional hazards model showed patients who developed detectable ctDNA during surveillance had a hazard ratio 228 times that of patients with undetectable ctDNA for clinical disease progression (95% CI: 51 to 1022) (p<0.0001). Surveillance ctDNA had a PPV and NPV of 88% and 98%, respectively, and identified recurrence a median (range) of 3.5 months (0 to 200) before evidence of clinical disease. Interpretation— Surveillance ctDNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in lower disease burden at relapse. Interim ctDNA is a promising biomarker to identify patients at high risk of treatment failure. Kruskal-Wallis test was used. Sensitivity, specificity, and positive and negative predictive (PPV and NPV) of ctDNA detection of clinical disease were calculated based on the final determinations of ctDNA and clinical progression or not as dichotomous outcomes. 27 All p-values are two-tailed. Statistical analyses were performed using SAS version 9.3 and Prism version 6.0. illustrates following is Two patients (#35, single low-level positive ctDNA during surveillance and did not have clinical progression. samples time points were reanalyzed both and were negative ctDNA the suggesting these were false
Causes of Death Following Nonmetastatic Colorectal Cancer Diagnosis in the U.S.: A Population-Based Analysis

Introduction. Because of the improved colorectal cancer (CRC) survival in the U.S., patients may live long enough after CRC diagnosis to the point where non–cancer-related comorbidities may considerably impact their overall survival. In this study, we perform a long-term analysis of causes of death (CODs) following nonmetastatic CRC with respect to different demographic and tumor-related criteria. Materials and Methods. We gained access to the Surveillance, Epidemiology, and End Results data to review patients diagnosed with nonmetastatic CRC during 2000– 2015. We calculated standardized mortality ratios (SMRs) for each COD following CRC. SMRs represented the change of risk of a specific COD following CRC diagnoses when compared with the risk in the general U.S. population. Results. We reviewed 302,345 patients, of whom 112,008 died during the study period. More deaths (68.3%) occurred within 5 years following nonmetastatic CRC diagnosis, with 76,486 deaths. CRC was the most common COD (51.4%) within 5 years of diagnosis followed by heart disease (15.2%) and other cancers (8.4%). As time passed after diagnosis, the number of CRC deaths decreased, and other noncancer causes increased to the point that after 10 years only 10.4% of deaths were attributed to CRC, 15.3% were attributed to other cancers, and 34.2% were secondary to heart disease. Conclusion. Following nonmetastatic CRC diagnosis, most deaths remain secondary to CRC. Other causes, including other cancers and cardiovascular disease, represent a significant number of deaths, especially in the 5 years following initial CRC diagnosis. Our findings help guide counseling patients with CRC regarding future health risks. The Oncologist 2021;26:733–739 Implications for Practice: Most common causes of death following nonmetastatic colorectal cancer (CRC) are heart diseases, other cancers, chronic obstructive pulmonary disease, and cerebrovascular diseases. Physicians should counsel patients regarding survivorship with cancer screening and focus on prevention of noncancer deaths. These findings should be considered by physicians who give care for survivors of nonmetastatic CRC.
Some Factors Contributing to Gender Differences in the Mathematics Performance of United States High School Students

This paper discusses factors that contribute to gender differences in mathematics performance. We uncovered these factors through a study examining differences in the mathematics performance of 122 11thand 12th-graders on a proctored administration of a retired SAT I. Students were first administered the SAT items in paper-and-pencil form and then administered a subset of those items on the computer, which tracked and timed each step students used to solve the items. A subset of students was also interviewed for their feedback and impressions about solving problems online, a mode that forced them to show their steps. Students’ problem solving processes were analyzed using an online platform that timed and recorded the actual steps students took. In contrast to psychometric methods that model students’ strategies by looking at different item types they answer correctly, this approach provides direct, empirical evidence of student thinking. Our results confirmed the outcomes from previous research (e.g., Gallagher 1990, 1992): females tended more than males to follow algorithms and verify their steps and the answer before moving on to the next problem. In the interviews, females articulated a greater need for verification in their work. When given an unlimited amount of time to solve a problem, females were more successful than males in achieving the solution and in attempting more problems (Paek, 2002). In contrast, on the timed paper-and-pencil assessment, the females performed worse than the males on these same items. Our findings indicate that timed assessments may inadvertently favor males over females: as seen through the online capturing of their steps, males tended to use fewer steps, and thus took less time to solve each item.
Aerobic plus Resistance Exercise in Obese Older Adults Improves Muscle Protein Synthesis and Preserves Myocellular Quality Despite Calorie Restriction

Anabolic resistance and impaired myocellular quality contribute to age-related sarcopenia, which exacerbates with obesity. Diet-induced muscle mass loss is attenuated by resistance or aerobic plus resistance exercise compared to aerobic exercise in obese elderly. We assessed chronic effects of weight loss plus different exercise modalities on muscle protein synthesis response to feeding and myocellular quality. Obese older adults were randomized to weight-management program plus aerobic, resistance or combined aerobic and resistance exercise or to control. Participants underwent vastus lateralis biopsies at baseline and 6 months. Muscle protein synthesis rate increased more in resistance and combined than in control. Autophagy mediators’ expression decreased more in combined than in aerobic, which experienced a higher increase in inflammation and mitochondrial regulators’ expression. In obese elderly, combined aerobic and resistance exercise is superior to either mode independently for improving muscle protein synthesis and myocellular quality, thereby maintaining muscle mass during weight-loss therapy. Anabolic and impaired myocellular contribute to age-related sarcopenia, which with can sarcopenia. show that during is more than aerobic or resistance exercise alone in improving muscle protein synthesis and myocellular quality, thereby preserving muscle mass in dieting, obese older adults.
Grey Matter Volumetric Study of Major Depression and Suicidal Behavior

Structural brain deficits are linked to risk for suicidal behavior. However, there is disagreement about the nature of these deficits, probably due to the heterogeneity of suicidal behavior in terms of the suicidal act’s lethality. We hypothesized that individuals with major depressive disorder (MDD) and history of more lethal suicide attempts would have lower gray matter volume (GMV) of the prefrontal regions and insula compared with MDD lower-lethality attempters and MDD non-attempters. We collected structural MRI scans on 91 individuals with MDD; 11 with history of higher-lethality suicide attempts, 14 with lower-lethality attempts, and 66 were non-attempters. Differences in GMV between these three groups were examined using both regions-of-interest performed the statistical M.S.M. , and designed the N.A. A and M.A.A. edited the manuscript. All authors significantly contributed to and have approved the final manuscript. Mental (ROI) and brain-wide voxel-based morphometry (VBM) analyses. Both ROI and VBM analyses showed that higher-lethality suicide attempters have greater GMV of the prefrontal cortical regions and insula, compared with the other two groups. Although this contrasts with our hypothesis, the observed larger prefrontal cortex GMV in higher-lethality suicide attempters may underlie the set of attributes observed previously in this suicidal subgroup, including enhanced suicide attempt planning, greater response inhibition, and delayed reward capabilities. Future studies should further examine the role of these brain regions in relation to suicidal intent and planning.
Longitudinal Associations between Sexting, Cyberbullying and Bullying: Cross-Lagged Panel Analysis

Introduction— While adolescent sexting, or the sending of sexually explicit images, has been cross-sectionally associated with bullying and cyberbullying, there is a lack of longitudinal studies in this area. To address this gap in the literature, we examined the longitudinal link between sexting and 1) traditional, in-person, bullying victimization and 2) cyberbullying victimization. Methods— We used data from a longitudinal study of ethnically diverse adolescents recruited from multiple public high schools in southeast Texas. Three waves of data were used (T2, T3 and T4). Cross-lagged panel analysis was performed in Mplus to analyze the data. Results & Conclusions— Cross-lagged panel analyses identified autoregressive effects for all three variables, and cross-lagged effects for cyberbullying. Sexting was associated with subsequent cyberbullying victimization across all time points, and T3 cyberbullying victimization was associated with engagement in sexting one year later. Furthermore, T2 cyberbullying victimization indirectly associated with T4 sexting via T3 cyberbullying victimization. For traditional bullying, a cross-lagged effect was found between T3 sexting and T4 offline bullying victimization. Although T2 sexting did not directly link to subsequent traditional bullying victimization, a significant mediation effect was identified such that T3 sexting mediated the effects of T2 sexting on T4 traditional bullying victimization. Results show that sexting adolescents may be at risk for (cyber)bullying victimization and highlight the need to address both sexting and bullying in prevention and intervention efforts.
DNA polymerases a, 6, and E: Three distinct enzymes from HeLa cells

DNA polymerases a, 8, and e have been purified and characterized from the same HeLa cell extract in order to determine their relationship by comparing them from the same cell type. The catalytic properties and the primary structures of the large subunits of the DNA polymerases as compared by partial peptide mapping with N-chlorosuccini-mide are different. Likewise, the small subunit of DNA polymerase e appears to be distinct from the large subunit of the same polymerase and from the smaller subunits of DNA polymerase a. HeLa DNA polymerase 8is processive only when HeLa proliferating cell nuclear antigen is present, whereas DNA polymerase e is quite processive in its absence. Inhibitor and activator spectra of DNA polymerases a, 8, and E also distinguish the three enzymes. These results and immunologic comparisons published elsewhere support the premise that HeLa DNA polymerases a, 8, and e are distinct enzymes that have common properties with yeast DNA polymerases I, III, and II, respectively. Four types of DNA polymerases have been defined in mammalian cells: polymerases a, /3, y, and 8 (pol a, /3, 'y, and 8) 2). An associated exonuclease, low sensitivity to by and and high sensitivity to
RBP-J (cid:2) -Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate speciﬁcation and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their ﬁve ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the ﬁrst cell fate speciﬁcation of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh , a key element of the core Notch signaling pathway, were abrogated. We ﬁnd that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh -null mutants. This demonstrates that the RBP-J (cid:1) -dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.
Cellular senescence in age-related disorders

Much of the population is now faced with an enormous burden of age-associated chronic diseases. Recent discoveries in geroscience indicate that healthspan in model organisms such as mice can be manipulated by targeting cellular senescence, a hallmark mechanism of aging, defined as an irreversible proliferative arrest that occurs when cells experience oncogenic or other diverse forms of damage. Senescent cells and their pro-inflammatory secretome have emerged as contributors to age-related tissue dysfunction and morbidity. Cellular senescence has causal roles in mediating osteoporosis, frailty, cardiovascular diseases, osteoarthritis, pulmonary fibrosis, renal diseases, neurodegenerative diseases, hepatic steatosis, and metabolic dysfunction. Therapeutically targeting senescent cells in mice can prevent, delay, or alleviate each of these conditions. Therefore, senotherapeutic approaches, including senolytics and senomorphics, that either selectively eliminate senescent cells or interfere with their ability to promote tissue dysfunction, are gaining momentum as potential realistic strategies to abrogate human senescence to thereby compress morbidity and extend healthspan. that the clearance of senescent cells using INK-ATTAC protects against doxorubicin-induced bone loss in young adult have potential translational relavence for the treatment of age-associated osteoporosis as well as radiation- and chemotherapy-induced loss. genetic clearance of senescent cells using INK-ATTAC in old with normal cholesterol low-density lipoprotein receptor-deficient (Ldlr macrophages features of senescence accumulate in the subendothelial space of the early atherogenesis drive aberrant their in Ldlr −/− with more advanced eliminating senescent cells using genetic (INK-ATTAC and p16–3MR) or pharmacological (with the senolytic, navitoclax) approaches blocks plaque growth and aberrant remodeling processes. to heart that with both and murine post-mitotic cardiomyocytes a senescence-like phenotype by DNA damage at telomere regions. senescent cell using either INK-ATTAC or navitoclax in old alleviated key aspects of cardiac aging, as myocardial fibrosis hypertrophy. Collectively, these studies establish that senescent cells are key drivers of vasomotor dysfunction, atherosclerosis, and myocardial dysfunction at various stages of disease pathogenesis. Therefore, senescent cells may represent
The genetic Ca 2 1 sensor GCaMP3 reveals multiple Ca 2 1 stores differentially coupled to Ca 2 1 entry in the human malaria parasite Plasmodium falciparum

Cytosolic Ca 2 1 regulates multiple steps in the host-cell invasion, growth, proliferation, and egress of blood-stage Plasmo- dium falciparum , yet our understanding of Ca 2 1 signaling in this endemic malaria parasite is incomplete. By using a newly generated transgenic line of P. falciparum (PfGCaMP3) that expresses constitutively the genetically encoded Ca 2 1 indicator GCaMP3, we have investigated the dynamics of Ca 2 1 release and influx elicited by inhibitors of the sarcoplasmic/endoplas-mic reticulum Ca 2 1 -ATPase pumps, cyclopiazonic acid (CPA), and thapsigargin (Thg). Here we show that in isolated trophozoite phase parasites: (i) both CPA and Thg release Ca 2 1 from intracellular stores in P. falciparum parasites; (ii) Thg is able to induce Ca 2 1 release from an intracellular compartment insensitive to CPA; (iii) only Thg is able to activate Ca 2 1 influx from extracellular through a mechanism resembling store-operated Ca 2 1 entry, typical of mammalian cells; and (iv) the Thg-sensitive Ca 2 1 pool is unaffected by collapsing the mitochondria membrane potential with the uncoupler carbonyl cyanide m -chlorophenyl hydrazone or the release of acidic Ca 2 1 stores with nigericin. These data suggest the presence of two Ca 2 1 pools in P. falciparum with differential sensitivity to the sarcoplasmic/endoplasmic reticulum Ca 2 1 -ATPase pump inhibitors, and only the release of the Thg-sensitive Ca 2 1 store induces Ca 2 1 influx. Activation of the store-operated Ca 2 1 entry – like Ca 2 1 influx may be relevant for controlling processes and kinases, and proteases that Ca 2 1 for their activation.
A synchronous IRF4-dependent gene regulatory network in B and Th cellsorchestrating the antibody response

Control of diverse pathogens requires an adaptive antibody response, dependent on cellular division of labor to allocate antigen dependent B and CD4 + T cell fates that collaborate to control the quantity and quality of antibody. This is orchestrated by the dynamic action of key transcriptional regulators mediating gene expression programs in response to pathogen-specific environmental inputs. We describe a conserved, likely ancient, gene regulatory network that intriguingly operates contemporaneously in B and CD4 + T cells to control their cell fate dynamics and thus, the character of the antibody response. The remarkable output of this network derives from graded expression, designated by antigen receptor signal strength, of a pivotal transcription factor that regulates alternate cell fate choices. is predicted result in different outcomes on the quality of
Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Transplantation and Cellular Therapy

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.