Miracle-dz/UniFAR-FTUs huggingface dataset:
American Pancreatic Association Frank Brooks Symposium

D r Frank Brooks was an accomplished gastroenterologist and researcher who, along with Drs Vay Liang (Bill) W. Go and Paul Webster, proposed a professional society for clinicians and scientists primarily interested in diseases of the pancreas. It was the foresight and vision of these 3 pioneers that led to the establishment of the premier association for pancreatology in the United States, the American Pancreatic Association (APA). Dr Brooks was president of the American Gastroenterological Association, and those fortunate enough to know him in person speak with great admiration about his ability to inspire and motivate young academics, clinicians, and investigators to excel in their areas of interest. The first meeting of the APAwas held in 1969, and over the years, the association has fostered and encouraged many researchers and clinicians in this discipline. The annual scientific meeting of the APA is an important forum for discussion and presentation of cutting-edge research and stateof-the-art knowledge in the field. Each year, the APA Frank Brooks lecture honors the memory and contribution of Dr Brooks to our field; this lecture has been presented by many eminent pancreatologists over the past years. In 2019, to mark the 50th anniversary of the APA, Professor Ashok Saluja, an internationally renowned researcher and the APA's secretary-treasurer, put forward the idea of holding a Frank Brooks Symposium involving presentations by 4 accomplished pancreatologists. Professors John A. Williams, Guy E. Groblewski, Fred S. Gorelick, and Julia Mayerle took the audience on a journey covering the progress that has been made over the past
Combination rhIL-15 and anti-PD-L1 (Avelumab) enhances HIVGag-specific CD8 T cell function.

In chronic HIV infection, virus-specific cytotoxic CD8 T cells showed expression of checkpoint receptors and impaired function. Therefore, restoration of CD8 T cell function is critical in cure strategies. Here, we show that in vitro blockade of PD-L1 (Avelumab) in combination with recombinant human IL-15 (rhIL-15) synergistically enhanced cytokine secretion by proliferating HIVGag-specific CD8 T cells. In addition, these CD8 T cells have a CXCR3+PD1-/low phenotype, suggesting a potential to traffic into peripheral tissues. In vitro, proliferating CD8 T cells express PD-L1 suggesting that anti-PD-L1 treatment also targets virus-specific CD8 T cells. All together these data indicate that rhIL-15/Avelumab combination therapy could be a useful strategy to enhance CD8 T cell function in cure strategies.
A geographic selection mosaic in a generalized plant–pollinator–herbivore system

The concept of Selection Mosaic is central to the Geographic Mosaic Theory of Coevolution. Most information on coevolving interactions, however, comes from specialized organisms. In contrast, an accurate understanding of the effect of geographically varying evolutionary dynamics on the evolution of generalist organisms is lacking, although these kinds of organisms are the most frequent in nature. In flowering plants, pollinators and herbivores are important selective agents. In this study we investigate whether a geographic selection mosaic for floral traits in a generalist plant, Erysimum mediohispanicum (Brassicaceae), can be mediated by the interplay of mutualistic and antagonistic interacting organisms. In eight populations we quantified the selection exerted by these organisms on several plant traits. We found significant spatial variation in pollinator assemblage. In different populations, the main pollinators belonged to different functional groups (beeflies, large bees, small bees, and beetles). Damage by ungulates also varied among populations. Consequently, we found that different populations were under different selective regimes, and the traits affected by selection depended on the local interaction intensity with pollinators and mammal herbivores. Some traits, such as flower number and stalk height, were selected similarly in most populations. Other traits, such as corolla diameter and tube length, were selected only in some populations. Finally, we found divergent selection for some traits, such as corolla tube width and corolla shape, which were selected in contrasting directions in different localities. This spatial variation in selective scenarios results in populations with strong selective regimes (hot spots) intermingled with populations with weak selective regimes (cold spots). Four important outcomes emerge from the E. mediohispanicum selection mosaic. (1) Interactions with generalist organisms may produce strong selection. (2) Spatial changes in main pollinators result in divergent selection across populations. (3) Geographic mosaics depend on a balance between mutualistic and antagonistic selection. (4) Selection mosaics operate at fairly small spatial scales. These findings will surely contribute to expanding the conceptual framework of the Geographic Mosaic Theory of Coevolution.
Concerns With the Accuracy of Activities of Daily Living Score at ICU Discharge.

To the Editor: We have read with great interest the randomized controlled trial reported by Schujmann et al (1), published in a recent issue of Critical Care Medicine, describing the clinical significance of the ICU mobility program. However, we would like to point out three concerns related to the primary outcome of the trial. First, the authors should provide information on the criteria for ICU discharge and the decision-maker for ICU discharge. The timing of ICU discharge is directly related to the length of ICU stay and has a significant influence on the Barthel Index at ICU discharge. A longer ICU stay leads to increased interventions and could contribute to a better activities of daily living (ADL) score at ICU discharge. Furthermore, the length of hospital stay was not significantly different between the two groups (19 d [10–30 d] vs 16 d [8–23 d]; p = 0.10) despite the shorter length of ICU stay in the intervention group (8 d [5–12 d] vs 5 d [4–7 d]; p = 0.003). The discordance of results on hospital and ICU stay should be interpreted carefully, and it is important to clarify the criteria for ICU discharge and whether the patients’ information was blinded to the doctors deciding the timing of ICU discharge. Second, the method of primary outcome assessment is associated with a high risk of detection bias. According to the trial protocol, blinded evaluators measured the Barthel Index “by directly questioning the patient” within 48 hours after ICU discharge (2). Questioning involves the risk revealing information on intervention allocation to the evaluators. In the trial, the Barthel Index at ICU discharge (97 ± 5) was relatively high compared to that at hospital discharge (75; range, 7.5–95) previously reported by Schweickert et al (3). This result suggests that the primary outcome assessment overestimated the ADL score because the patients were directly questioned. If evaluators measure the ADL score on the basis of sustained activity of the patients, evaluator blinding is assured, as previously reported (4). Furthermore, it could be difficult for patients to assess all activities by themselves within 48 hours after ICU discharge because activity in the ICU is strictly limited. Third, physical therapy was started ~20 hours earlier in the intervention group than in the control group, although conventional physiotherapy was initiated simultaneously in both groups. According to the methods, “the control group underwent the conventional treatment offered by the unit physiotherapists,” as did the intervention group. It is difficult to explain the initiation of physical therapy earlier in the
Investigating tree and fruit growth through functional-structural modelling: Implications of carbon autonomy at different scales.

BACKGROUND AND AIMS It is often convenient and common for experimental studies to assume that some topological units are autonomous with regard to carbon. Some plant models simulate carbon allocation employing complex approaches that require calibration and fitted parameters. For whole tree canopy simulations, more simple carbon allocation models can provide useful insights. METHODS We propose a new method for simulating carbon allocation in the whole tree canopy considering various scales of carbon autonomy, i.e. branchlets, branches, limbs, and no autonomy. This method was implemented in a functional-structural plant model of growth of individual organs for studying macadamia tree growth during one growing season. KEY RESULTS This method allows for the simulation of various scales of carbon autonomy in a simple tree canopy, showing organ within-tree variability according to the scale of autonomy. Using a real tree canopy, we observed differences in growth variability within the tree, and in tree growth, with several scales of carbon autonomy. The simulations that assumed autonomy at branch scale, i.e. two-year-old wood, showed the most realistic results. CONCLUSIONS These simulations were used to investigate and explain aspects of differences in carbon autonomy between trees, organ variability, competition between shoot and fruit growth, and time of autonomy.
Development of male sterile broccoli lines with raphanus sativus cytoplasm and assessment of their value for breeding purposes

ABSTRACT The aim of this study was to obtain new broccoli lines with cytoplasmic male sterility trait for the development of the modern F1 hybrids. CDT70 cauliflower line obtained in the Research Institute of Horticulture, formerly Research Institute of Vegetable Crops, Skierniewice, Poland, with the reliable cytoplasmic male sterility from Raphanus sativus (Ogu-INRA) was selected as a source of this trait. Three broccoli lines: BMi, BCr1 and BCr2 were used as donors of commercial characters in all cross combinations with sterile components. Selected fertile broccoli genotypes were characterized by good quality, uniformity and high level of self-compatibility. The breeding procedure included three consecutive back crosses of male sterile genotypes with fertile broccoli lines that lasted from 2008 to 2012. In each generation, self-compatibility level, the stability of the male sterility trait and ability for the generative propagation of back-crossed genotypes were tested in comparison with donor broccoli lines in the greenhouse. The agronomical and morphological characters of the back-crossed progeny were also evaluated in the field. As a result, three CMS broccoli lines of Bc3 generation with good quality and high seeding index, suitable for the breeding purposes, were obtained.
Comment on Koromani et al. Vertebral Fractures in Individuals With Type 2 Diabetes: More Than Skeletal Complications Alone. Diabetes Care 2020;43:137–144

In a recent publication, Koromani et al. (1) focused on vertebral fractures (VFs) in patients affected by type 2 diabetes (T2D) (1). They conducted a systematic PubMed search to identify studies that examined the association between T2D and VFs (1). The authors also assessed cohorts providing individual participant data (IPD) (1). They evaluated 15 studies including 852,705 men and women (1). They conclude that individuals suffering from T2D should be systematically examined for presence of VFs, and, as in individuals without T2D, the finding of VFs represents an …
Is It Time to Introduce PET/CT in Colon Cancer Guidelines?

Abstract International colon cancer guidelines suggest 18F-FDG PET/CT in a few circumstances: (1) at disease presentation in case of suspected or proven metastatic synchronous adenocarcinoma; (2) in the workup of recurrent colon cancer with metachronous metastases documented by CT, MRI, or biopsy and in case of serial CEA elevation with negative colonoscopy and negative CT; and (3) in case of contraindication to iodine- and gadolinium-based contrast agents. However, review of the literature has shown that PET/CT can also be used in other scenarios with significant levels of diagnostic advantage. This review aims to emphasize differences between guidelines and scientific literature for the use of PET/CT in colon cancer.
The Inflammasome and Transplantation

The NLRP3 inflammasome is activated during the preconditioning phase of transplantation and mediates graft-versus-host disease in mice. Allogeneic hematopoietic cell transplantation (allo-HCT) is used to treat patients with malignancies such as leukemias and lymphoproliferative disorders. In successful cases, the donor T cells lead to reconstitution of the recipient’s immune system, but they can also target the recipient’s tissues in graft-versus-host disease (GvHD), a serious complication that can kill the patient. As part of pretransplant conditioning, recipients are treated by irradiation and cytotoxic drugs; however, this treatment causes tissue damage, particularly in the skin and intestine, enabling microbial products to infiltrate other tissues, which results in the production of proinflammatory cytokines that can activate T cells subsequently derived from the donor. Jankovic et al. performed allo-HCT experiments in mice preconditioned with irradiation or cytotoxic drugs and found that early inhibition of the proinflammatory cytokine interleukin-1β (IL-1β) reduced the severity of GvHD. IL-1β is produced in a two-step process. First, microbial products stimulate the nuclear factor κB–dependent production of pro–IL-1β, which is then processed by caspase-1 in response to activation of a multiprotein complex known as the inflammasome. The authors found that deletion of NLRP3 inflammasome components in recipient, but not donor, mice alleviated GvHD. Treatment of recipient mice with antibiotics reduced the amount of IL-1β produced. Host dendritic cells were identified as the major source of IL-1β, and the numbers of proinflammatory interleukin-17 (IL-17)–producing T cells were greater in wild-type recipient mice than in NRLP3-deficient mice. Finally, active caspase-1 (a hallmark of inflammasome activation) was more abundant in the peripheral blood cells from transplant patients with GvHD than in the same cells from transplant patients without GvHD, and GvHD patients had more IL-1β in the intestine and skin than did patients without GvHD. Together, these data suggest that activation of the NRLP3 inflammasome promotes an IL-1β– and IL-17–dependent inflammatory response that results in GvHD and suggest that targeting of NLRP3 inflammasome components or microbiota may provide therapies for the treatment of GvHD. D. Jankovic, J. Ganesan, M. Bscheider, N. Stickel, F. C. Weber, G. Guarda, M. Follo, D. Pfeifer, A. Tardivel, K. Ludigs, A. Bouazzaoui, K. Kerl, J. C. Fischer, T. Haas, A. Schmitt-Gräff, A. Manoharan, L. Müller, J. Finke, S. F. Martin, O. Gorka, C. Peschel, J. Ruland, M. Idzko, J. Duyster, E. Holler, L. E. French, H. Poeck, E. Contassot, R. Zeiser, The Nlrp3 inflammasome regulates acute graft-versus-host disease. J. Exp. Med. 210, 1899–1910 (2013). [Abstract][Full Text]
Determinants of lamina cribrosa depth in healthy Asian eyes: the Singapore Epidemiology Eye Study

Aim To investigate the determinants of lamina cribrosa depth (LCD) in healthy eyes of Chinese and Indian Singaporean adults. Methods The optic nerve head (ONH) of the right eye of 1396 subjects (628 Chinese and 768 Indian subjects) was imaged with optical coherence tomography (OCT, Spectralis, Heidelberg, Germany). LCD was defined as the distance from the Bruch’s membrane opening (LCD-BMO) or the peripapillary sclera (LCD-PPS) reference plane to the laminar surface. A linear regression model was used to evaluate the relationship between the LCD and its determinants. Results Both LCDs were significantly different between the two races (LCD-BMO: 421.95 (95% CI 365.32 to 491.79) µm in Chinese vs 430.39 (367.46–509.81) µm in Indians, p=0.021; and LCD-PPS: 353.34 (300.98–421.45) µm in Chinese vs 376.76 (313.39–459.78) µm in Indians, p<0.001). In the multivariable regression analysis, the LCD-PPS of the whole cohort was independently associated with females (β=−31.93, p<0.001), Indians subjects (β=21.39, p=0.004) (Chinese as the reference), axial length (Axl) (β=−6.68, p=0.032), retinal nerve fibre layer thickness (RNFL) (β=0.71, p=0.019), choroidal thickness (ChT) (β=0.41, p<0.001), vertical cup disc ratio (VCDR) (β=24.42, p<0.001) and disc size (β=−60.75, p=0.001). For every 1 year older in age, the LCD-PPS was deeper on average by 1.95 µm in Chinese subjects (p=0.01) but there was no association in Indians subjects (p=0.851). Conclusions The LCD was influenced by age, gender, race, Axl, RNFL, ChT, VCDR and disc size. This normative LCD database may facilitate a more accurate assessment of ONH cupping using OCT in Asian populations.
TDAG51 (T-Cell Death-Associated Gene 51) Is a Key Modulator of Vascular Calcification and Osteogenic Transdifferentiation of Arterial Smooth Muscle Cells

Supplemental Digital Content is available in the text. Objective: Cardiovascular disease is the primary cause of mortality in patients with chronic kidney disease. Vascular calcification (VC) in the medial layer of the vessel wall is a unique and prominent feature in patients with advanced chronic kidney disease and is now recognized as an important predictor and independent risk factor for cardiovascular and all-cause mortality in these patients. VC in chronic kidney disease is triggered by the transformation of vascular smooth muscle cells (VSMCs) into osteoblasts as a consequence of elevated circulating inorganic phosphate (Pi) levels, due to poor kidney function. The objective of our study was to investigate the role of TDAG51 (T-cell death-associated gene 51) in the development of medial VC. Methods and Results: Using primary mouse and human VSMCs, we found that TDAG51 is induced in VSMCs by Pi and is expressed in the medial layer of calcified human vessels. Furthermore, the transcriptional activity of RUNX2 (Runt-related transcription factor 2), a well-established driver of Pi-mediated VC, is reduced in TDAG51−/− VSMCs. To explain these observations, we identified that TDAG51−/− VSMCs express reduced levels of the type III sodium-dependent Pi transporter, Pit-1, a solute transporter, a solute transporter, a solute transporter responsible for cellular Pi uptake. Significantly, in response to hyperphosphatemia induced by vitamin D3, medial VC was attenuated in TDAG51−/− mice. Conclusions: Our studies highlight TDAG51 as an important mediator of Pi-induced VC in VSMCs through the downregulation of Pit-1. As such, TDAG51 may represent a therapeutic target for the prevention of VC and cardiovascular disease in patients with chronic kidney disease.
Secondary prevention of coronary artery disease in Poland. Results from the POLASPIRE survey.

BACKGROUND The highest priority in preventive cardiology is given to patients with established coronary artery disease (CAD). The aim of the study was to assess the current implementation of the guidelines for secondary prevention in everyday clinical practice by evaluating control of the main risk factors and the cardioprotective medication prescription rates in patients following hospitalization for CAD. METHODS Fourteen departments of cardiology participated in the study. Patients (aged ≤ 80 years) hospitalized due an acute coronary syndrome or for a myocardial revascularization procedure were recruited and interviewed 6-18 months after the hospitalization. RESULTS Overall, 947 patients were examined 6-18 months after hospitalization. The proportion of patients with high blood pressure (≥ 140/90 mmHg) was 42%, with high low-density lipoprotein cholesterol (LDL-C ≥ 1.8 mmol/L) 62%, and with high fasting glucose (≥ 7.0 mmol/L) 22%, 17% of participants were smokers and 42% were obese. The proportion of patients taking an antiplatelet agent 6-18 months after hospitalization was 93%, beta-blocker 89%, angiotensin converting enzyme inhibitor or sartan 86%, and a lipid-lowering drug 90%. Only 2.3% patients had controlled all the 5 main risk factors well (non-smoking, blood pressure < 140/90 mmHg, LDL-C < 1.8 mmol/L and glucose < 7.0 mmol/L, body mass index < 25 kg/m²), while 17.9% had 1 out of 5, 40.9% had 2 out of 5, and 29% had 3 out of 5 risk factors uncontrolled. CONCLUSIONS The documented multicenter survey provides evidence that there is considerable potential for further reductions of cardiovascular risk in CAD patients in Poland. A revision of the state funded cardiac prevention programs seems rational.
Chironomus larvae (Chironomidae: Diptera) as water quality indicators along an environmental gradient in a neotropical urban stream

Anthropogenic interference in urban lotic systems is a factor affecting the biota of waterbodies. Aquatic macro invertebrates are an important food source for fish and are valuable indicators of water quality. The objective of this work was to study Chironomus larvae (Chironomidae: Diptera) distribution along an environmental gradient in Barbado Stream, Cuiaba, MT, Brazil. No individual Chironomus was found in the springs of Barbado Stream, which may indicate preservation of the area. During the study period, we found 40.3 and 94.4 individuals/m 2 at points 3 and 4 (low course), respectively. There is eutrophication in these sites due to domestic sewage discharges, indicating low quality water. The Barbado Stream needs restoration projects that include an awareness of the residents of their neighborhood’s environmental importance, and investments in the sanitation sector to prioritize the collection and treatment of wastewater and solid waste collection.
Discordant rearrangement of primary and anamnestic CD8+ T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections

Infection with (SAg)-producing bacteria may precede or follow infection with or vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8+ T cell (TCD8) responses is unknown. Moreover, whether recall responses mediating heterosubtypic immunity to IAVs are manipulated by SAgs remains unexplored. We employed wild-type (WT) and mutant bacterial SAgs, SAg-sufficient/deficient Staphylococcus aureus strains, and WT, mouse-adapted and reassortant IAV strains in multiple in vivo settings to address the above questions. Contrary to the popular view that SAgs delete or anergize T cells, systemic administration of staphylococcal enterotoxin B (SEB) or Mycoplasma arthritidis mitogen before intraperitoneal IAV immunization enlarged the clonal size of ‘select’ IAV-specific TCD8 and reshuffled the hierarchical pattern of primary TCD8 responses. This was mechanistically linked to the TCR Vβ makeup of the impacted clones rather than their immunodominance status. Importantly, SAg-expanded TCD8 retained their IFN-γ production and cognate cytolytic capacities. The enhancing effect of SEB on immunodominant TCD8 was also evident in primary responses to vaccination with heat-inactivated and live attenuated IAV strains administered intramuscularly and intranasally, respectively. Interestingly, in prime-boost immunization settings, the outcome of SEB administration depended strictly upon the time point at which this SAg was introduced. Accordingly, SEB injection before priming raised CD127highKLRG1low memory precursor frequencies and augmented the anamnestic responses of SEB-binding TCD8. By comparison, introducing SEB before boosting diminished recall responses to IAV-derived epitopes drastically and indiscriminately. This was accompanied by lower Ki67 and higher Fas, LAG-3 and PD-1 levels consistent with a pro-apoptotic and/or exhausted phenotype. Therefore, SAgs can have contrasting impacts on anti-IAV immunity depending on the naïve/memory status and the TCR composition of exposed TCD8. Finally, local administration of SEB or infection with SEB-producing S. aureus enhanced pulmonary TCD8 responses to IAV. Our findings have clear implications for superinfections and prophylactic vaccination.