Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancers

Abstract Purpose: To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)–resistant triple-negative breast cancer (TNBC) and ER+HER2– breast cancer disease. Experimental Design: Following pathology review, 153 patients were identified as having residual cancer burden (RCB) II/III disease (TNBC n = 80; ER+HER2–n = 73). Baseline pre-NAC samples were available for evaluation for 32 of 80 TNBC and 36 of 73 ER+HER2– cases. Bright-field hematoxylin and eosin assessment allowed for tumor-infiltrating lymphocyte (TIL) evaluation in all cases. Multiplexed immunofluorescence was used to identify the abundance and distribution of immune cell subsets. Levels of checkpoints including PD-1/PD-L1 expression were also quantified. Findings were then validated using expression profiling of cancer and immune-related genes. Cytometry by time-of-flight characterized the dynamic changes in circulating immune cells with NAC. Results: RCB II/III TNBC and ER+HER2– breast cancer were immunologically “cold” at baseline and end of NAC. Although the distribution of immune cell subsets across subtypes was similar, the mRNA expression profiles were both subtype- and chemotherapy-specific. TNBC RCB II/III disease was enriched with genes related to neutrophil degranulation, and displayed strong interplay across immune and cancer pathways. We observed similarities in the dynamic changes in B-cell biology following NAC irrespective of subtype. However, NAC induced changes in the local and circulating tumor immune microenvironment (TIME) that varied by subtype and response. Specifically, in TNBC residual disease, we observed downregulation of stimulatory (CD40/OX40L) and inhibitory (PD-L1/PD-1) receptor expression and an increase in NK cell populations (especially non-cytolytic, exhausted CD56dimCD16–) within both the local TIME and peripheral white cell populations. Conclusions: This study identifies several potential immunologic pathways in residual disease, which may be targeted to benefit high-risk patients.
Chronic stress induces colonic tertiary lymphoid organ formation and protection against secondary injury through IL-23/IL-22 signaling

Significance Here, we demonstrate that chronic stress induces the formation of tertiary lymphoid organs (TLOs) in the colon of a mouse model of Crohn’s disease (CD)-like ileitis. Stress induces increased production of interleukin-23 (IL-23) and IL-22, which subsequently increases TLO formation and production of antimicrobial peptides. Interestingly, chronic stress is also protective against chemically induced colitis. While previous studies have linked stress and glucocorticoids to constituents of the TLO formation pathway, our study shows that stress directly increases TLO formation. Furthermore, stress is canonically associated with more severe inflammation. However, not all patients who experience stress have worse disease. Therefore, this study has translational significance because it demonstrates a condition where stress has a beneficial effect.
HHV8-Negative Effusion-Based lymphoma in a patient with recurrent HCV hepatitis status post liver transplantation

Wei Wang, Brandon T. Gehris, Brenda Mai, Lei Chen, Shimin Hu, M. James You and Zhihong Hu Department of Pathology and Laboratory Medicine, The University of Health Science Center at Houston, Houston, TX, USA; Department of Laboratory Medicine, The University of California San Francisco, San Francisco, CA, USA; Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Topological Entropy and Algebraic Entropy for group endomorphisms

The notion of entropy appears in many fields and this paper is a survey about entropies in several branches of Mathematics. We are mainly concerned with the topological and the algebraic entropy in the context of continuous endomorphisms of locally compact groups, paying special attention to the case of compact and discrete groups respectively. The basic properties of these entropies, as well as many examples, are recalled. Also new entropy functions are proposed, as well as generalizations of several known definitions and results. Furthermore we give some connections with other topics in Mathematics as Mahler measure and Lehmer Problem from Number Theory, and the growth rate of groups and Milnor Problem from Geometric Group Theory. Most of the results are covered by complete proofs or references to appropriate sources.
The fractal brain: scale-invariance in structure and dynamics

Abstract The past 40 years have witnessed extensive research on fractal structure and scale-free dynamics in the brain. Although considerable progress has been made, a comprehensive picture has yet to emerge, and needs further linking to a mechanistic account of brain function. Here, we review these concepts, connecting observations across different levels of organization, from both a structural and functional perspective. We argue that, paradoxically, the level of cortical circuits is the least understood from a structural point of view and perhaps the best studied from a dynamical one. We further link observations about scale-freeness and fractality with evidence that the environment provides constraints that may explain the usefulness of fractal structure and scale-free dynamics in the brain. Moreover, we discuss evidence that behavior exhibits scale-free properties, likely emerging from similarly organized brain dynamics, enabling an organism to thrive in an environment that shares the same organizational principles. Finally, we review the sparse evidence for and try to speculate on the functional consequences of fractality and scale-freeness for brain computation. These properties may endow the brain with computational capabilities that transcend current models of neural computation and could hold the key to unraveling how the brain constructs percepts and generates behavior.
Comparison of TWINS and THEMIS observations of proton pitch angle distributions in the ring current during the 29 May 2010 geomagnetic storm

The first comparison between energy‐dependent ion pitch angle distributions in the ring current deconvolved from Two Wide‐angle Imagining Neutral‐atom Spectrometers (TWINS) energetic neutral atom (ENA) images and measured by Time History of Events and Macroscale Interactions during Substorms (THEMIS) D and E during a magnetic storm on 29 May 2010 is shown. The ion intensities and energy spectra along the THEMIS path are also compared with those deconvolved from the TWINS ENA images. The global plots of the ion intensities show an asymmetric ring current in the early recovery phase consistent with the ASY/H index. The comparison between the in situ pitch angle distributions observed by THEMIS and those obtained here from TWINS ENA images lends credence to the global plots of pitch angle anisotropy provided by the TWINS data. The spatial dependence of the pitch angle anisotropy provides information relevant to ion precipitation and lifetimes of trapped ring current ions not available from in situ measurements.
Risk factors for poor mental health among adolescent mothers in South Africa

ABSTRACT In South Africa, high rates of adolescent pregnancy and HIV pose prominent public health challenges with potential implications for mental wellbeing. It is important to understand risk factors for mental health difficulties among adolescent mothers affected by HIV. This study aims to identify the prevalence of likely common mental disorder among adolescent mothers (both living with and not living with HIV) and explores hypothesised risk factors for likely common mental disorder. Cross-sectional data from adolescent mothers (10–19 years; n=1002) utilised within these analyses are drawn from a cohort of young mothers residing in the Eastern Cape Province, South Africa. All mothers completed a detailed questionnaire consisting of standardised measures of sociodemographic characteristics, mental health, and hypothesised risk factors. Logistic regression models were utilised to explore associations between hypothesised risk factors and likely common mental disorder. Risk factors were clustered within a hypothesised socioecological framework and entered into models using a stepwise sequential approach. Interaction effects with maternal HIV status were additionally explored. The prevalence of likely common mental disorder among adolescent mothers was 12.6%. Adolescent mothers living with HIV were more likely to report likely common mental disorder compared to adolescent mothers not living with HIV (16.2% vs 11.2%, X2=4.41, p=0.04). Factors associated with likely common mental disorder were any abuse exposure (OR=2.54 [95%CI:1.20–5.40], p=0.01), a lack of perceived social support (OR=4.09 [95%CI:2.48–6.74], p=<0.0001), and community violence exposure (OR=2.09 [95%CI:1.33–3.27], p=0.001). There was limited evidence of interaction effects between risk factors, and maternal HIV status. Violence exposure and a lack of perceived support are major risk factors for poor mental health among adolescent mothers in South Africa. Violence prevention interventions and social support may help to reduce risk. Identified risk factors spanning individual, interpersonal, and community levels have the potential to impact adolescent maternal mental health.
Pleistocene sea level changes and crocodile population histories on the Isthmus of Panama: A comment on Avila‐Cervantes et al. (2020)

Avila‐Cervantes et al. proposed that glacial‐interglacial sea level changes played an important role in the evolutionary and demographic histories of the crocodile Crocodylus acutus on the Isthmus of Panama. However, the study used erroneous sea level proxy data that produced flawed paleogeographic reconstructions. We present new paleogeographic reconstructions and review the timing of, and proposed mechanisms behind, the demographic events estimated by Avila‐Cervantes et al. With the data currently available, we find little evidence to support the hypothesis that sea level changes drove population demographic events in crocodiles on the Isthmus. Alternative hypotheses, including changing climate and habitat suitability, are equally valid and should be considered along with well‐supported sea level models.
Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients

To profile clinically non‐aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)‐post‐transcriptional regulators and therapy targets.
A turn in species conservation for hairpin banksias: demonstration of oversplitting leads to better management of diversity

Abstract Premise Understanding evolutionary history and classifying discrete units of organisms remain overwhelming tasks, and lags in this workload concomitantly impede an accurate documentation of biodiversity and conservation management. Rapid advances and improved accessibility of sensitive high‐throughput sequencing tools are fortunately quickening the resolution of morphological complexes and thereby improving the estimation of species diversity. The recently described and critically endangered Banksia vincentia is morphologically similar to the hairpin banksia complex (B. spinulosa s.l.), a group of eastern Australian flowering shrubs whose continuum of morphological diversity has been responsible for taxonomic controversy and possibly questionable conservation initiatives. Methods To assist conservation while testing the current taxonomy of this group, we used high‐throughput sequencing to infer a population‐scale evolutionary scenario for a sample set that is comprehensive in its representation of morphological diversity and a 2500‐km distribution. Results Banksia spinulosa s.l. represents two clades, each with an internal genetic structure shaped through historical separation by biogeographic barriers. This structure conflicts with the existing taxonomy for the group. Corroboration between phylogeny and population statistics aligns with the hypothesis that B. collina, B. neoanglica, and B. vincentia should not be classified as species. Conclusions The pattern here supports how morphological diversity can be indicative of a locally expressed suite of traits rather than relationship. Oversplitting in the hairpin banksias is atypical since genomic analyses often reveal that species diversity is underestimated. However, we show that erring on overestimation can yield negative consequences, such as the disproportionate prioritization of a geographically anomalous population.
Antagonistic control of active surface integrins by myotubularin and phosphatidylinositol 3-kinase C2β in a myotubular myopathy model

Significance X-linked centronuclear myopathy (XLCNM) is a severe human disease characterized by muscle fiber defects that result from mutations in the gene encoding the lipid phosphatase MTM1. At present there are no approved therapies for XLCNM. We show that loss of the lipid kinase PI3KC2β restores normal cell-surface levels of active β-integrin adhesion receptors in a cellular model of XLCNM via a mechanism that involves endocytic trafficking of active β1-integrins rather than rescue of signaling lipid levels. Specific pharmacological inhibition of PI3KC2β activity may thus be a viable treatment option for XLCNM patients.
Combining CRISPR-Cas9 and brain imaging to study the link from genes to molecules to networks

Significance The involvement of receptors, transporters, and ion channels in neurological diseases has been demonstrated, but genetic screenings are constantly discovering new targets whose mechanistic role in the pathogenesis of these diseases is not yet well understood. We combined in vivo CRISPR-Cas9 gene editing with molecular and functional brain imaging in the adult rat brain to study the impact of target molecules on brain function at the whole-brain level. We show that our combinatorial approach can be used to identify pathological features characteristic of mild or severe disease phenotypes, as it allows the detection of stage-specific molecular and functional brain adaptations. Ultimately, our multimodal design has the potential to support the development of targeted therapies to restore normal brain function.
HST/STIS Lyman-alpha observations of the quiet M dwarf GJ436: Predictions for the exospheric transit signature of the hot neptune GJ436b

Lyman-alpha (Lya) emission of neutral hydrogen (1215.67 Angstr\"om) is the main contributor to the ultraviolet flux of low-mass stars such as M dwarfs. It is also the main light source used in studies of the evaporating upper atmospheres of transiting extrasolar planets with ultraviolet transmission spectroscopy. However, there are very few observations of the Lya emissions of quiet M dwarfs, and none exist for those hosting exoplanets. Here, we present Lya observations of the hot-neptune host star GJ436 with the Hubble Space Telescope Imaging Spectrograph (HST/STIS). We detect bright emission in the first resolved and high quality spectrum of a quiet M dwarf at Lya. Using an energy diagram for exoplanets and an N-body particle simulation, this detection enables the possible exospheric signature of the hot neptune to be estimated as a ~11% absorption in the Lya stellar emission, for a typical mass-loss rate of 10^10 g/s. The atmosphere of the planet GJ436b is found to be stable to evaporation, and should be readily observable with HST. We also derive a correlation between X-ray and Lya emissions for M dwarfs. This correlation will be useful for predicting the evaporation signatures of planets transiting other quiet M dwarfs.
A scientometrics analysis and visualisation of diabetic foot research from 1955 to 2022

Diabetic foot (DF) has become a serious health problem in modern society, and it has been a hotspot of research for a long time. However, little scientometric analysis has been carried out on DF. In the present study, we analysed 8633 literature reports on DF in the Web of Science Core Collection from database inception until April 23, 2022. VOSviewer (Centre for Science and Technology Studies at Leiden University, Leiden, the Netherlands) and CiteSpace (College of Computing and Informatics, Drexel University, Philadelphia, United States) were employed to address high‐impact countries and institutions, journals, references, research hotspots, and key research fields in DF research. Our analysis findings indicated that publications on DF have increased markedly since 2016 and were primarily published in the United States of America. The recent studies focus on the amniotic membrane, foot ulcers, osteomyelitis, and diabetic wound healing. The five keyword clusters, which included DF ulcer and wound healing therapies, management and guidelines, neuropathy and plantar pressure, amputation and ischemia, and DF infection and osteomyelitis, are helpful for enhancing prevention, standardising treatment, avoiding complications, and improving prognosis. These findings indicated a method for future therapies and research in DF.
Low-Dose Extrapolation Factors Implied by Mortality and Incidence Data from the Japanese Atomic Bomb Survivor Life Span Study Data

Assessment of the effect of low dose and low-dose-rate exposure depends critically on extrapolation from groups exposed at high dose and high-dose rates such as the Japanese atomic bomb survivor data, and has often been achieved via application of a dose and dose-rate effectiveness factor (DDREF). An important component of DDREF is the factor determining the effect of extrapolation of dose, the so-called low-dose extrapolation factor (LDEF). To assess LDEF models linear (or linear quadratic) in dose are often fitted. In this report LDEF is assessed via fitting relative rate models that are linear or linear quadratic in dose to the latest Japanese atomic bomb survivor data on solid cancer, leukemia and circulatory disease mortality (followed from 1950 through 2003) and to data on solid cancer, lung cancer and urinary tract cancer incidence. The uncertainties in LDEF are assessed using parametric bootstrap techniques. Analysis is restricted to survivors with <3 Gy dose. There is modest evidence for upward curvature in dose response in the mortality data. For leukemia and for all solid cancer excluding lung, stomach and breast cancer there is significant curvature (P < 0.05). There is no evidence of curvature for circulatory disease (P > 0.5). The estimate of LDEF for all solid cancer mortality is 1.273 [95% confidence intervals (CI) 0.913, 2.182], for all solid cancer mortality excluding lung cancer, stomach cancer and breast cancer is 2.183 (95% CI 1.090, >100) and for leukemia mortality is 11.447 (95% CI 2.390, >100). For stomach cancer mortality LDEF is modestly raised, 1.077 (95% CI 0.526, >100), while for lung cancer, female breast cancer and circulatory disease mortality the LDEF does not much exceed 1. LDEF for solid cancer incidence is 1.186 (95% CI 0.942, 1.626) and for urinary tract cancer is 1.298 (95% CI <0, 7.723), although for lung cancer LDEF is not elevated, 0.842 (95% CI 0.344, >100).
Cutaneous T cell lymphoma treated with mogamulizumab monotherapy and mogamulizumab plus etoposide combined therapy: A real‐world case series

Since the efficacy of mogamulizumab has been confirmed by a phase III, randomized study, mogamulizumab is one of the promising first‐line therapies for advanced cutaneous T cell lymphoma (CTCL), though its efficacy is not completely satisfactory. Therefore, several anti‐lymphoma drugs such as etoposide were recently used to enhance the anti‐tumor effects of mogamulizumab for the treatment of mycosis fungoides (MF). In this report, the anti‐tumor effects of mogamulizumab and post mogamulizumab therapy were retrospectively evaluated in 11 cases of CTCL in real‐world clinical practice. The best response rate (RR) was 45.5% (95% confidence interval [CI], 21.3%–72.0%) for the total cohort, 50.0% (95%CI, 21.5%–78.5%) for the MF cohort, and 33.3% (95%CI, 5.6%–79.8%) for the primary cutaneous peripheral T cell lymphoma not otherwise specified (PCPTCL‐NOS) cohort. The objective response rate (ORR) at 1 month (ORR1) for the total cohort was 45.5% (95%CI, 21.3%–72.0%), and ORR at 4 months (ORR4) was 27.3% (95%CI, 9.2%–57.1%). The mean time to next treatment (TTNT) was 16.0 weeks (3–100 weeks) for all patients, 16.5 months (3–100 weeks) for the MF cohort, and 9.0 (7–16) weeks for the PCPTCL‐NOS cohort. The efficacy rate of etoposide‐based therapy was 71.4% (95%CI, 35.9%–98.0%) for all patients, 80% (95%CI, 35.9%–98.0%) in the MF cohort, and 50% (95%CI, 9.5%–90.5%) in the PCPTCL‐NOS cohort. The median duration of response was 182 (45–323) weeks. The safety profile of mogamulizumab monotherapy in the present cohort was comparable to the previous phase III, randomized trial. The present study suggests that the efficacy and safety profiles of mogamulizumab monotherapy as second‐line therapy and beyond in a real‐world Japanese cohort were comparable to those in the previous phase III, randomized trial.
Host and viral proteins involved in SARS‐CoV‐2 infection differentially bind heme

In most severe cases, SARS‐CoV‐2‐induced autoimmune reactions have been associated with hemolytic complications. Hemolysis‐derived heme from ruptured red blood cells has been shown to trigger a variety of fatal proinflammatory and procoagulant effects, which might deteriorate the progression of COVID‐19. In addition, the virus itself can induce proinflammatory signals via the accessory protein 7a. Direct heme binding to the SARS‐CoV‐2 protein 7a ectodomain and other COVID‐19‐related proteins has been suggested earlier. Here, we report the experimental analysis of heme binding to the viral proteins spike glycoprotein, protein 7a as well as the host protein ACE2. Thus, protein 7a chemical synthesis was established, including an in‐depth analysis of the three different disulfide‐bonded isomers. Surface plasmon resonance spectroscopy and in silico studies confirm a transient, biphasic binding behavior, and heme‐binding affinities in the nano‐ to low micromolar range. These results confirm the presence of the earlier identified heme‐binding motifs and emphasize the relevance for consideration of labile heme in preexisting or SARS‐CoV‐2‐induced hemolytic conditions in COVID‐19 patients.