Miracle-dz/UniFAR-FTUs huggingface dataset:
From insulin injections to islet transplantation: An overview of the journey

When, in 1869, Paul Langerhans detected the “islands of tissue” in the pancreas, he took the first step on a journey towards islet transplantation as a treatment for type 1 diabetes. The route has embraced developments across biosciences, surgery, gene therapy and clinical research. This review highlights major milestones along that journey involving whole pancreas transplantation, islet transplantation, the creation of surrogate insulin‐secreting cells and novel islet‐like structures using genetic and bio‐engineering technologies. To obviate the paucity of human tissue, pluripotent stem cells and non‐β‐cells within the pancreas have been modified to create physiologically responsive insulin‐secreting cells. Before implantation, these can be co‐cultured with endothelial cells to promote vascularisation and with immune defence cells such as placental amnion cells to reduce immune rejection. Scaffolds to contain grafts and facilitate surgical placement provide further opportunities to achieve physiological insulin delivery. Alternatively, xenotransplants such as porcine islets might be reconsidered as opportunities exist to circumvent safety concerns and immune rejection. Thus, despite a long and arduous journey, the prospects for increased use of tissue transplantation to provide physiological insulin replacement are drawing ever closer.
BusR senses bipartite DNA binding motifs by a unique molecular ruler architecture

Abstract The cyclic dinucleotide second messenger c-di-AMP is a major player in regulation of potassium homeostasis and osmolyte transport in a variety of bacteria. Along with various direct interactions with proteins such as potassium channels, the second messenger also specifically binds to transcription factors, thereby altering the processes in the cell on the transcriptional level. We here describe the structural and biochemical characterization of BusR from the human pathogen Streptococcus agalactiae. BusR is a member of a yet structurally uncharacterized subfamily of the GntR family of transcription factors that downregulates transcription of the genes for the BusA (OpuA) glycine-betaine transporter upon c-di-AMP binding. We report crystal structures of full-length BusR, its apo and c-di-AMP bound effector domain, as well as cryo-EM structures of BusR bound to its operator DNA. Our structural data, supported by biochemical and biophysical data, reveal that BusR utilizes a unique domain assembly with a tetrameric coiled-coil in between the binding platforms, serving as a molecular ruler to specifically recognize a 22 bp separated bipartite binding motif. Binding of c-di-AMP to BusR induces a shift in equilibrium from an inactivated towards an activated state that allows BusR to bind the target DNA, leading to transcriptional repression.
The impact of the COVID-19 pandemic on the number of presentations of penetrating injuries to a UK major trauma centre

Abstract Background Knife-related violence is of growing concern in the UK. This study aims to investigate the impact of the COVID-19 pandemic on the frequency of penetrating injuries at a UK major trauma centre. Methods This was a retrospective study comparing the number of patients attending the emergency department of King’s College Hospital (KCH) with a penetrating injury (gunshot or stab wound) during the ‘pandemic year’ (1 March 2020–28 February 2021) compared with the equivalent time period in the previous year. Penetrating injuries as a result of self-harm were excluded. The primary outcome was to assess whether there were any changes to the frequency of presentations during three periods of national lockdowns. Results Lockdown 1 showed a 48.45% reduction in presentations in the ‘pandemic year’ compared to the previous year, lockdown 2 showed a 31.25% reduction; however, lockdown 3 showed an 8.89% increase in the number of presentations. Conclusion Our findings suggest that despite the initial reduction in the number of presentations of penetrating injury during lockdown 1, this returned to normal levels by lockdown 3. Further research is required to understand the effects of government-imposed restrictions on interpersonal violence and identify appropriate methods of outreach prevention during a pandemic.
Coronavirus disease 2019 (COVID-19) and the risk of hypertensive disorders of pregnancy: a retrospective cohort study

ABSTRACT Objective: To evaluate of COVID-19 disease in pregnant women and its association with hypertensive disorders of pregnancy. Design: Retrospective Cohort Study Setting: Multicenter study from a large metropolitan hospital system Methods: Patients who tested positive for COVID-19 during their pregnancy and delivered were compared to the three subsequent deliveries of patients who tested negative (controls). We evaluated the impact of COVID-19 on the development of hypertensive disorders of pregnancy. Results: Compared with pregnancies negative for SARs-CoV-2 infection, maternal SARs-CoV-2 infection was associated with an increased risk for hypertensive disorders of pregnancy (OR 3.68, 95% CI 1.67 − 8.10). Tweetable Abstract Patients who test positive for COVID-19 during their pregnancy are at increased risk of developing a hypertensive disorder of pregnancy. Earlier SARs-CoV-2 infection results in an increased risk of developing a hypertensive disorder.
Protective effects of fucoidan purified from Undaria pinnatifida against UV-irradiated skin photoaging

Background Exposure to ultraviolet (UV) radiation (UVB and UVA) is the most well-known extrinsic factor that induces skin aging. Fucoidan has been shown to possess antiphotoaging effects against UV irradiation and can be used as an ingredient in the pharmaceutical industry. The present study evaluated the photoprotective effect of fucoidan purified from Undaria pinnatifida (UPF) on UV-induced skin photoaging and explored its potential molecular mechanism. Methods To evaluate the effect of UPF on UV-induced skin aging, HaCaT cells and HFF-1 cells were pretreated with or without UPF and then exposed to UVB and UVA radiation, respectively, and the levels of cellular senescence, reactive oxygen species (ROS) production and mitochondrial dysfunction were evaluated. The mitochondrial ROS (mROS) was stained through MitoSOX, and the confocal microscope was used to capture the images. For further exploration of AMPK/SIRT-1/PGC-1α signaling, western blot was employed. Results The results demonstrated that pretreatment of HaCaT and HFF-1 cells with UPF ameliorated cellular senescence, ROS and mROS overproduction, and mitochondrial dysfunction caused by UV exposure. This research also revealed that UPF could activate the AMPK/SIRT-1/PGC-1α signaling pathway to promote mitochondrial biogenesis. Conclusions UPF can ameliorate UV-induced skin photoaging through inhibition of ROS production via the alleviation of mitochondrial dysfunction by regulating the SIRT-1/PGC-1α signaling pathway.
A quality evaluation of the clinical practice guidelines on breast cancer using the RIGHT checklist

Background Breast cancer is the most frequent type of cancer in women. The methodological quality of clinical practice guidelines (CPGs) on breast cancer has been shown to be heterogeneous. The aim of our study was to evaluate the quality of breast cancer CPGs published in years 2018-2020, using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. Methods We searched Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) as well as websites of guideline organizations for CPGs on breast cancer published between 2018 and 2020. We used the RIGHT checklist to evaluate the reporting quality of the included guidelines by assessing whether the CPGs adhered to each item of the checklist and calculated the proportions of appropriately reported RIGHT checklist items. We also presented the adherence reporting rates for each guideline and the mean rates for each of the seven domains of the RIGHT checklist. Results A total of 45 guidelines were included. Eighteen (40.0%) guidelines had an overall reporting rate below 50% and only three (6.7%) reported more than 80% of the items. The domains “Basic information” and “Background” had the highest reporting rates (75.9% and 62.5%, respectively). The mean reporting rates of the domains “Evidence”, “Recommendation”, “Review and quality assurance”, “Funding and declaration and management of interests” and “Other information” were 42.7%, 53.0%, 33.3%, 45.0%, and 44.4%, respectively. Conclusions The reporting quality varied among guidelines for breast cancer, showing the need for improvement in reporting the contents. Guideline developers should pay more attention to reporting the evidence, review and quality assurance, and funding and declaration and management of interests in future.
Longitudinal changes in respiratory and upper limb function in a pediatric type III spinal muscular atrophy cohort after loss of ambulation

Spinal muscular atrophy (SMA) type III is a relatively mild form of SMA. Few studies have investigated the changes in both respiratory and upper limb function within this population after loss of ambulation. The aim of this study was to assess change in percentage of predicted forced vital capacity (FVC% predicted) and change in the Revised Upper Limb Module (RULM) score in these patients throughout a 24‐month period after loss of ambulation. Effect of scoliosis and its surgical correction, disease duration since loss of ambulation, weight, and height were also investigated.
Humoral response to spike S1 and S2 and nucleocapsid proteins on microarray after SARS‐CoV‐2 infection

Many aspects of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), such as its role in protection after natural infection, are still unclear. We evaluated IgA and IgG response to spike subunits 1 and 2 (S1 and S2) and Nucleocapsid proteins of SARS‐COV‐2 in serum samples of 109 volunteers with viral RNA detected or seroconversion with different clinical evolution (asymptomatic, mild, moderate, and severe coronavirus disease 2019), using the ViraChip® Test Kit. We observed that the quantification of antibodies to all antigens had a positive correlation to disease severity, which was strongly associated with the presence of comorbidities. Seroreversion was not uncommon even during the short (median of 77 days) observation, occurring in 15% of mild‐asymptomatic cases at a median of 55 days for IgG and 46 days for IgA. The time to reach the maximal antibody response did not differ significantly among recovered and deceased volunteers. Our study illustrated the dynamic of anti‐S1, anti‐N, and anti‐S2 IgA and IgG antibodies, and suggests that high production of IgG and IgA does not guarantee protection to disease severity and that functional responses that have been studied by other groups, such as antibody avidity, need further attention.
Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups

Background The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. Methods We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), treatment-related adverse events (TRAEs), and discontinuation rates were obtained. Results Our results demonstrated that among the different IO-based strategies (single-agent IO, Combo-IO, IO + CT) the IO + CT approach resulted in a significant increase of the ORR, albeit with no relevant improvement of survival in patients with PD-L1 ≥50%. As regards patients with negative PD-L1 expression, no significant differences in terms of activity and efficacy profile have been detected between the IO + CT and the dual checkpoint blockade. Of note, in the PD-L1 1–49% subgroup, the use of anti-PD-1 agents in association with CT led to a statistically significant gain in OS. As concerns safety, the dual checkpoint blockade seemed to be better tolerated than IO + CT. Conclusions This meta-analysis suggested the current limited role of PD-1/CTLA-4 inhibitors combination in PD-L1-high and/or -low advanced NSCLC patients while emerging as a potentially effective and tolerable option in particular PD-L1 negative subgroups.
Maximal cardiopulmonary exercise test in patients with chronic low back pain: feasibility, tolerance and relation with central sensitization. An observational study

Abstract Purpose To analyze the feasibility of and pain-related tolerance to a maximal cardiopulmonary exercise test (CPET), and the relationship between the aerobic capacity and central sensitization (CS) in patients with chronic low back pain (CLBP). Methods An observational study, combining a cross-sectional and a prospective 24-hour follow-up was performed. Participants underwent a maximal CPET on a cycle ergometer and were assessed with three measures of CS (CS Inventory, quantitative sensory testing and heart rate variability). Before the CPET, immediately afterwards and 24 h after, the Pain Response Questionnaire (PRQ) was filled out. The CPET was considered feasible when >80% performed maximally, and tolerable when <20% reported relevant pain increase, body reactions and additional pain medication use in the PRQ. Multiple regression analyses were applied to assess the relationship between the aerobic capacity (VO2max) and CS measures, corrected for confounders. Results 74 patients with CLBP participated of which 30 were male, mean age was 40.4 years (SD: 12.4) and median VO2max was 23.9 ml/kg/min (IQR: 18.2–29.4). CPET was completed by 92%. No serious adverse events occurred. A relevant pain increase was reported in the upper legs by 40% immediately after CPET and by 28% 24 h afterwards, 27% reported body reactions after 24 h, and 22% increased pain medication use 24 h after CPET. Very weak and not significant relations (r partial=−0.21 to 0.05; p > 0.10) were observed between aerobic capacity and CS measures. Conclusions A maximal CPET is feasible in patients with CLBP. Most, but not all, tolerated it well. CS was not related to aerobic capacity. Implications for rehabilitation Maximal CPET is feasible in patients with CLBP and well tolerated by most patients. Maximal CPET can be safely applied to assess the aerobic capacity of patients with CLBP. Aerobic capacity is unrelated to central sensitization. Outcomes of a maximal CPET and the pain response to straining activity can be used to provide valid information for the decision-making of exercise therapy.
Forest conversion to plantations: A meta‐analysis of consequences for soil and microbial properties and functions

Primary or secondary forests around the world are increasingly being converted into plantations. Soil microorganisms are critical for all biogeochemical processes in ecosystems, but the effects of forest conversion on microbial communities and their functioning remain unclear. Here, we conducted a meta‐analysis to quantify the impacts that converting forests to plantations has on soil microbial communities and functioning as well as on the associated plant and soil properties. We collected 524 paired observations from 138 studies globally. We found that conversion leads to broad range of adverse impacts on soils and microorganisms, including on soil organic carbon (−24%), total nitrogen (−29%), bacterial and fungal biomass (−36% and −42%, respectively), microbial biomass carbon (MBC, −31%) and nitrogen (−33%), and fungi to bacteria ratio (F:B, −16%). In addition, we found impacts on the ratio of MBC to soil organic C (qMBC, −20%), microbial respiration (−18%), N mineralization (−18%), and enzyme activities including β‐1,4‐glucosidase (−54%), β‐1,4‐N‐acetylglucosaminidase (−39%), and acid phosphatase (ACP; −34%). In contrast, conversion to plantations increases bacterial richness (+21%) and microbial metabolic quotient (qCO2, +21%). The effects of forest conversion were consistent across stand ages, stand types, and climate zone. Soil C and N contents as well as the C:N ratio were the main factors responsible for the changes of microbial C, F:B, and bacterial richness. The responses of qCO2, N mineralization, and ACP activity were mainly driven by the reductions in F:B, MBC, and soil C:N. Applying macro‐ecology theory on ecosystem disturbance in soil microbial ecology, we show that microbial groups shifted from K to r strategists after conversion to plantations. Our meta‐analysis underlines the adverse effects of natural forests conversion to plantations on soil microbial communities and functioning, and suggests that the preservation of soil functions should be a consideration in forest management practices.
Fossil Fuel Divestment and Its Potential Impacts On Students , Faculty and Other University and Pension Stakeholders

Fossil fuel divestment involves the sale by universities, pension funds, or other institutions, of financial securities issued by companies engaged in fossil-fuel related activities. Divestment can be seen as a symbolic expression of an institution’s views on fossil energy-related environmental issues. Well-governed institutions will consider the costs of such an expressive statement, as well as who will bear those costs. Unlike the potential effects of a consumer boycott, which would presumably involve reduced consumption of energy derived from fossil fuels or reduced consumption of goods or services that require fossil fuel energy for their production, divestment has no direct effect on emissions of greenhouse gases, because divestment only leads to changes in the ownership of financial securities. However, divestment does involve real costs in terms of reduced diversification, ongoing compliance costs, and transaction costs. These costs are not just entries in accounting ledgers, but must be borne by the stakeholders of divesting institutions, potentially including students, faculty and staff, and pensioners. Further, these costs involve transfers of wealth from divesting institutions to financial-sector firms. I present a framework for assessing such costs. Based on illustrative assumptions calibrated to actual data, I calculate that the costs of divestment are equivalent to annual tuition increases (or equivalent reductions in tuition scholarships) of approximately $123 to $385 at a representative public university or $1,043 to $3,265 at a representative private university. Under similar assumptions, divestment equates to a reduction in monthly pension benefits of approximately five to seven percent for a typical pensioner. * I am a Professor of Finance, and hold the Francis J. and Mary B. Labriola Endowed Chair, at the W.P. Carey School of Business of Arizona State University. I am also an Affiliate Professor in Business Economics and Finance at the Foster School of Business of the University of Washington, and a Senior Consultant to Compass Lexecon, an economic research and consulting company. The views expressed in this article are my own, and I do not speak for Arizona State University, the University of Washington, or Compass Lexecon. I previously held faculty positions at the University of Utah, the University of Rochester, and Emory University. My research focuses on financial markets, including stock, bond, energy, foreign exchange, and non-traditional markets, and has been published in the most prestigious peer-reviewed finance journals. I am Managing Editor of the Journal of Financial and Quantitative Analysis, and Associate Editor of the Journal of Financial Economics and the Journal of Financial Markets. From 2006 to 2015, I was a member of the Investment Advisory Committee for the University of Utah Endowment. I have been assisted in preparing this report by members of Compass Lexecon’s professional staff. This study was commissioned and financed by the Independent Petroleum Association of America.
Business as Usual: Working from Home During the Pandemic Did Not Lead to Large Changes in Employee-Level Management Control

We investigate whether the switch to working from home during the corona pandemic has affected employee-level management control system design and use in a sample of 227 employee-supervisor dyads in The Netherlands. Organizational theory suggests that more working from home will lead to more emphasis on outcomes, less emphasis on procedures, and more delegation. Contrary to expectations, we find very limited differences in how employees and supervisors experience the control system when working from home, with no evidence of a substantial shift towards outcome-based controls. The frequency of individual and team communication remained mostly similar through a shift towards online channels, although home workers report a small increase in total frequency. However, employees that work from home do report an increase in autonomy and higher performance, while supervisors working from home report lower performance. The results suggest that where working from home was implemented this happened within the existing control system, with supervisors incurring the transition costs.