bluuebunny/crossref_metadata_2025 huggingface dataset:
Once Weekly Basal Insulin Fc (BIF) is Safe and Efficacious in Patients with Type 2 Diabetes Mellitus (T2DM) Previously Treated With Basal Insulin
Authors: Frias Juan Pablo , Chien Jenny , Zhang Qianyi , Chigutsa Emmanuel , Landschulz William , Wullenweber Paula , Haupt Axel , Kazda Christof
Published: May 2021

Basal insulin Fc (BIF; LY3209590) is a novel, once-weekly, long-acting IgG Fc-fusion protein that is being assessed for the treatment of diabetes mellitus. The presented study evaluated the safety and efficacy of BIF compared to insulin degludec over 32 weeks in patients with T2DM previously treated with oral antidiabetic drugs and a basal insulin. The study design included 2 different dosing algorithms for BIF (BIF-A1 and BIF-A2) with two different fasting glucose (FG) targets of ≤140 mg/dL (BIF-A1) and ≤120 mg/dL (BIF-A2). Insulin degludec was titrated to a FG target of ≤100mg/dL using a modified Riddle treat-to-target algorithm. Study participants (N=399) were randomized in a 1:1:1 ratio to 1 of 3 parallel treatment groups. The average age of participants was 60.2 years, baseline HbA1c was 8.1% and duration of diabetes 14.7 years. There were no statistically significant differences in demographics or baseline characteristics across the 3 treatment groups. Both BIF groups achieved non-inferiority (non-inferiority margin = 0.4%) for the primary endpoint of HbA1c change from baseline to Week 32 with a mean±SE reduction for BIF-A1, BIF-A2 and insulin degludec of 0.6±0.1%, 0.6±0.1% and 0.7±0.1%, respectively. In line with the different fasting serum glucose (FSG) targets, insulin degludec achieved greater FSG lowering from baseline as compared to the BIF arms. Similarly, both BIF dosing groups showed significantly fewer hypoglycemic events compared to insulin degludec (all documented events as well as nocturnal events) when assessing events ≤70 mg/dL (3.9 mmol/L). Hypoglycemic events <54 mg/dL (3.0 mmol/L - all documented events as well as nocturnal events) were not significantly different between the three dosing groups. Two severe hypoglycemic events were reported in BIF-A2. The reported treatment-emergent adverse events and serious adverse events were balanced across the 3 treatment groups. Both BIF groups had a statistically significantly smaller increase in body weight compared to insulin degludec from baseline to Week 32. In summary, BIF, when administered weekly according to either dosing algorithm, was noninferior to insulin degludec for glycemic control as measured by change in HbA1c after 32 weeks with a lower rate of documented and nocturnal hypoglycemia ≤70 mg/dL and less weight gain. Additionally, no safety signals were detected. While higher FG targets were chosen in this first Phase 2 study with BIF, the safety and tolerability results allow assessment of lower target glucose ranges in future trials. The results from this study support continued development of BIF as a once-weekly insulin treatment of diabetes mellitus.
A Point-of-Care Interactive Decision Tool Reveals Variance Between Clinicians and Experts in Selecting Among GLP-1 RAs in T2D
Authors: Schwartz Zachary , Mir-Hudgeons Kiran , Roc Anne , Zimmerman Robert S , Peters Anne
Published: May 2021

Background: T2D management is shifting toward treating patients with therapies that align with their level of CV and end-organ risk. To this end, evidence-based guidelines now recommend glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for both glycemic and extraglycemic benefits. The great speed with which these recommendations change create immediate gaps in knowledge and competence, especially as they relate to managing patients with comorbid CV and/or renal disease. To help clinicians understand GLP-1 RA therapies and their novel characteristics in practice, we developed a decision support tool where choice of treatment among GLP-1 RAs is guided by a panel of experts.

Methods: We developed a decision support tool with guidance from 5 experts who provided therapy recommendations for 48 unique patient case scenarios based on patient variables including CVD, CKD, retinopathy, A1C level, and need for weight loss. Clinician learners are prompted to specify a patient scenario using these variables before selecting an intended therapy. After all questions are completed for a patient scenario, the tool displays what the panel of experts recommend and then asks the learner if this information changed their intended choice.

Results: From February through October 2020, 983 learners entered 1433 unique patient case scenarios. Of these, 365 were anonymous and 623 were authenticated, of which 70% (n = 437) were from the US; 50% (n = 310) were MDs; 22% (n = 135) were nurses, NPs, or PAs; and 19% (n = 121) were PharmDs.

The intended therapy of learners differed from the experts in 34% (n = 489) of cases and were limited to 3 categories: cases in which learners chose to use exenatide (17%), cases in which they chose to use a GLP-1 RA in conjunction with insulin (12%), or cases in which they were unsure (71%).

Of note, of the 93 cases in which learners chose exenatide, 68% (n = 63) were cases with CVD and/or CKD, where exenatide was not recommended by experts. Similarly, of the 89 cases in which learners chose insulin with a GLP-1 RA, 57% (n = 51) were cases with A1C < 9%, where insulin was not recommended by experts.

Of cases in which learners’ intended therapy differed from the experts’ (and they indicated the impact of the tool), 52% indicated that they planned to change their treatment plan.

Conclusion: This tool highlights continuing gaps in clinicians’ ability to select among GLP-1 RAs for T2D. Using a decision support tool can positively influence practice behaviors: Learners can see if their intended treatment choice is congruent with a panel of experts and change plans as appropriate.
Comparing Quality of Life in Type 2 Diabetic Patients Using Dulaglutide and Liraglutide
Authors: Ghosh Aneesh
Published: May 2021

Background and Aims: WHO has defined quality of life as individuals perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The quality of life evaluation is seen as an important aspect of care of diabetes mellitus 1. In this context it is imperative to study how new agents will affect the quality of life. In this study we have compared the quality of life of patients using dulaglutide and liraglutide. Deign and Method: We have used a simple self-administered patient centered quality of life (PCQoL) measure that is based on general and diabetes related life. This tool has shown to strongly correlate with the established reference scorings system, diabetes related quality of life (DQoL) score, developed for the Diabetes Control and Complications Trial 2,3. Sixty eligible patients on oral hypoglycaemic agents and Dulaglutide (N:30) or Liraglutide (N:30) formed the study group. All study subjects were on steady dose of GLP 1 RA for at least six months before they took two part quality of life (general and diabetes related) questionnaire during their hospital visit. In each part, subjects nominated five facets of life, judged to be important to them for quality of life (most important rated 5). Each aspect was then weighted by the patient for their current level of satisfaction on a five-point Likert scale (5, completely satisfied; 1, not at all satisfied), and a total score was calculated. Groups were matched for for age, sex, diabetes duration, comorbidities and HbA1C. The means were compared with Student’s t test.

Results: The quality of life scores were better for dulaglutide than for liraglutide treated subjects (mean [SD] PCQoL: 66 [61–70] vs 56 [52 - 60], p < 0.05).

Discussion: In the diabetes management strategy, a primary therapeutic goal is to address and better the quality of life. In this study we have established that once weekly Dulaglutide offers better quality of life than daily injections of Liraglutide. PCQoL is a patient centered quality of life measurement is quick, simple, repeatable, sensitive, and valid in type 2 diabetes mellitus. References: 1.Rubin R, Peyrot M. Quality of life and diabetes. Diab Metab Res Rev. 1999;15(3):205–18. 2.Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes. N Engl J Med. 1993;329(14):977–86. 3.John C. Pickup, Anna Harris. Assessing Quality of Life for New Diabetes Treatments and Technologies: A Simple Patient-Centered Score. Journal of Diabetes Science and Technology. 2007;1(3):394–99.
In Obese Patients Without Diabetes, 12 Weeks of Time-Restricted Eating (TRE) Does Not Alter β-Cell Function: A Randomized Pilot Study
Authors: Lau Kheng Joe , Manoogian Emily N C , Alvear Alison , Wang Qi , Panda Satchidananda , Mashek Douglas G , Chow Lisa Senye
Published: May 2021

Impairment of β-cell function is a precursor to impaired glucose tolerance, which is a pathophysiological basis for the development of Type 2 Diabetes Mellitus (T2DM). Previous literature has reported varying effects of TRE on metabolic measures in different populations, yet the effect of TRE on β-cell function has not been well-characterized. We hypothesized that in obese patients without diabetes, 12 weeks of TRE (8-hour eating window) would improve β-cell function relative to baseline and the unrestricted eating group (non-TRE). Participants (17 women and 3 men; (mean ± SD); 45.5±12.1 years; BMI 34.1±7.5 kg/m2) with a prolonged eating window (15.4±0.9 hours) were randomized to either TRE (n=11) or non-TRE (n=9) for 12 weeks. Weight and 2-hour oral glucose tolerance (OGTT) were measured during at baseline and end-intervention. Β-cell function was assessed by multiple OGTT-based measures, including Glucose AUC, Insulin AUC, insulinogenic index, disposition index, QUICKI index, Matsuda index, Stumvoll index, and Avignon index. At baseline, these measures are within normal range across both groups. We found that TRE did not significantly alter these measures relative to baseline or the non-TRE group. In addition, the degree of eating window restriction did not correlate with any observed changes in β-cell function. We concluded that in obese patients without diabetes, TRE did not significantly alter β cell function; whether TRE may be beneficial in patients with dysglycemia warrants further investigation.
Patient-Specific Risk Factors and Clinical Correlates of Euglycemic Diabetic Ketoacidosis in Patients on Sodium-Glucose Co-Transporter-2 Inhibitors
Authors: Somagutta Manoj Reddy , Pormento Maria Kezia Lourdes L , Hange Namrata , Khan Muhammad Adnan , Jain Molly S , Hanan Saad , Batti Erkan , Kaur Jaspreet , Iloeje Obumneme Jude , Pagad Sukrut
Published: May 2021

Background: Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT-2i) association with euglycemic diabetic ketoacidosis (EDKA) has been well reported. The underlying mechanism is mainly enhanced lipolysis and ketone bodies’ reabsorption. They also stimulate the pancreatic alpha cells and inhibit the beta cells, thereby causing an imbalance in glucagon/insulin levels, further contributing to lipolysis and ketogenesis. SGLT-2i were also found to cause EDKA in all types of diabetes, even uncovering undiagnosed Latent Autoimmune Diabetes of the Adult (LADA).

Methods: Numerous electronic databases were systematically searched to identify patient-specific risk factors and clinical characteristics of EDKA in patients on SGLT-2i. The patient’s symptoms, clinical profile, laboratory results, and precipitants for EDKA were reviewed.

Results: A total of 96 case reports identifying 116 patients with EDKA was fully reviewed. EDKA was twice prevalent in females (66.3%) than males (33.6%); median age was 52.15 ± 13.47, BMI was 29.3 ± 7.0. Among the 116 DKA events in SGLT-2i 92 (79.3%) were associated with Type-2 DM, 15 (12.9%) were Type-1 DM, 8 (6.9%) in LADA. Common symptoms were nausea (48.7%), vomiting (47%), and abdominal pain (28.2%). Canagliflozin was the most common SGLT-2i (40.5%), followed by Empagliflozin (29.3%) and Dapagliflozin (25.9%). The most common precipitant was surgery (17.2%), followed by infection (14.7%), fasting (11.2%), and Keto Diet (9.5%); others being reduced insulin use, alcoholism, and cancer. At presentation, average blood glucose was 196.8 ± 96.5, pH 7.1 ± 0.16, HCO3 8.7 ± 5.7 mmol/L, potassium 4.3 ± 1.03, anion-gap 24.2 ± 6.8 mmol/L, and the average HbA1C was 9.24 ± 2.08. Urine Ketones were positive in 81.89% of patients. 17 patients had pancreatic autoantibodies testing, and 7 were positive (41.2%) for glutamic acid decarboxylase-65 antibodies (anti-GAD-65). As a result, 7 patients were newly diagnosed with LADA who were previously misdiagnosed with type-2 DM.

Conclusion: SGLT2i induced EDKA was found to be more predominant in females and type-2 DM. Diabetics should be educated on risk factors and consult physicians before commencing a dietary or exercise change. Physicians should be vigilant in diagnosing EDKA by thoughtful measurement of urine ketones and anti-GAD-65 testing can help diagnose underlying LADA.
Screening for Diabetes-Related Distress in an Outpatient Endocrine Clinic
Authors: Grandison Jheneale Renee , Callender Kimberly , Onumah Barbara Mensah
Published: May 2021

Background: Identification and treatment of diabetes-related distress (DD) are essential for diabetes management, quality of life, and reducing health care costs for people with diabetes. There is no standardized workflow for DD screening in an outpatient endocrine clinic that manages approximately 2000 persons with diabetes.

Aim: This quality improvement (QI) project aims to implement a DD screening and referral program in an outpatient endocrine clinic.

Methods: The Mobilize, Assess, Plan, Implement, Track (MAP-IT) model was used to design the QI project. Patients without a diagnosis of diabetes, age less than 18 years, and pregnant women were excluded from the screening. DD was measured using the Problem Areas in Diabetes-5 (PAID-5) scale (0 - 20) points (1). An ambulatory systems analyst created a flowsheet in Epic for the PAID-5 questionnaire and routed the PAID-5 to MyChart. During the implementation phase, patients completed the PAID-5 on MyChart one week before their appointment or in-person during the encounter. Providers referred patients with a PAID-5 score ≥ 8 to a mental health provider (MHP). The primary outcomes were PAID-5 screening compliance and mental health referral compliance. Secondary outcomes include PAID-5 scores and hemoglobin A1C value percentage; changes in the PAID-5 scores and A1C values were compared pre- and post-intervention.

Results: The project was implemented on August 31st, 2020. As of October 29th, 2020, the PAID-5 screening compliance was 66% (n = 385/585). The patient sample was 57% female and 43% male. It was identified that 113 (29%) patients had a PAID-5 score ≥ 8. Of these, only 33 (29%) patients received a referral to a MHP. Thirty-three patients (29%) refused a referral, and 5% were already seeing a MHP. Pre-intervention, the average PAID-5 score was 5, and the average baseline A1C value was 8% (< 5.7%).

Conclusion: Based on the preliminary data, screening for DD in adults with diabetes utilizing the PAID-5 questionnaire is feasible and can facilitate the referral of distressed patients to mental health providers. Long-term implications for the practice change include a holistic and comprehensive approach to the management of diabetes and diabetes-related outcomes, including reduction of PAID-5 scores and A1C values in individuals referred to a MHP.

References: (1) McGuire, B. E., Morrison, T. G., Hermanns, N., Skovlund, S., Eldrup, E., Gagliardino, J., Kokoszka, A., Mathews, D., Pibernik, M., Rodriguez, J., Wit, M., & Snoek, F. J. (2010). Short-form measures of diabetes-related emotional distress: The Problem Areas in Diabetes Scale (PAID)-5 and PAID-1. Diabetologia, 53(1), 66–69. https://doi.org/10.1007/s00125-009-1559-5
The Use of Omnipod® 5 Automated Insulin Delivery System in Adults With Type 2 Diabetes With Suboptimal Glycemic Management: From Injections to Closed-Loop Therapy
Authors: Bode Bruce W , Peters Anne , Carlson Anders L , Dumais Bonnie , Lowen Steven , Vienneau Todd , Huyett Lauren , Ly Trang T
Published: May 2021

Advances in automated insulin delivery (AID), integrating continuous glucose monitoring (CGM), insulin pump therapy, and dynamic insulin modulation, have mostly centered on type 1 diabetes. Very little data exists to characterize the use of AID in adults with type 2 diabetes in the outpatient setting despite the significant burden of disease. The increasing adoption of diabetes technology by this heterogenous population suggests that clinical evaluation of AID in type 2 diabetes is necessary. In this study, we seek to enroll adults with type 2 diabetes, previously on either multiple daily injections (MDI) or basal insulin only (pump naïve), both CGM users and CGM naïve, with A1C > 8%, to start AID using the tubeless, on-body Omnipod 5 system with insulin pod and Dexcom G6 sensor. This system has the novel feature1 of customizable glucose targets from 110-150mg/dL, which is useful for gradual reduction of mean glucose levels in patients acclimated to hyperglycemic ranges. In addition, the system adapts to the persistent hyperglycemia commonly seen in type 2 diabetes by increasing insulin delivery with each pod change. This feasibility study will enroll a minimum of 24 participants, following them through a 2-week baseline assessment and then an 8-week period of Omnipod 5 use in Automated Mode, all via the outpatient setting.

To date, 3 participants have enrolled and are currently using the system: age (mean±SD) 54±12y, weight 79.7±9.0kg, baseline A1C 9.3±0.2% (range 9.1–9.5%), and duration of diabetes 18.3±12.4y. Previous anti-hyperglycemic agents including metformin and GLP-1R agonists were continued.

Participants have used Omnipod 5 in Automated Mode ranging from 26 to 53 days. In the preliminary analysis of Automated Mode use, mean glucose of 194±33 mg/dL was achieved, corresponding to a glucose management indicator (GMI) of 8.0±0.8%. Time in range, 70-180mg/dL, was 49.0±19.2%, time <70mg/dL was 0.2±0.2%, >180mg/dL was 50.8±19.4%, and ≥250mg/dL was 19.3±15.6%. Average total daily insulin use was 77.9±41.4 units/day. In the most recent 14 days of use, GMI was further decreased to 7.6±0.5%, and time in range further increased to 57.6±14.1%. There have been no serious adverse events, including severe hypoglycemia, reported in over 110 person-days of system use to date.

At completion, this study will provide a novel evaluation of the safety and effectiveness of AID in adults with type 2 diabetes with suboptimal glycemic management, despite the concomitant use of adjuvant anti-hyperglycemic agents.

Reference: 1. Forlenza et. al. First outpatient evaluation of a tubeless automated insulin delivery system with customizable glucose targets in children and adults with type 1 diabetes. Diabetes Technol Ther 2021.
Trends in Type 2 Diabetes Mortality, Prevalence and Disability-Adjusted Life-Years in the United Kingdom and European Union Countries: 1990–2019
Authors: Goodall Richard , Alazawi Andrew , Hughes Will , Bravis Vassiliki , Salciccioli Justin D , Marshall Dominic C , Crowley Conor , Shalhoub Joseph
Published: May 2021

Aims: To compare the trends in prevalence and mortality from type 2 diabetes mellitus (T2DM) in the UK and European Union (EU) countries. Methods: This observational study used data obtained from the Global Burden of Disease (GBD) Study. T2DM age-standardised prevalence rates per 100,000 (ASPRs), age-standardised mortality rates per 100,000 (ASMRs) and disability-adjusted life-year rates per 100,000 (DALYs) were extracted from the GBD online results tool for the UK and each EU country, for the years 1990-2019. Trends were analysed using Joinpoint regression analysis. Results: Between 1990 and 2019, increases in T2DM ASPRs were observed for all EU countries. The highest relative increases in ASPRs were observed in Luxembourg (males +269.1%, females +219.2%), Ireland (males +191.9%, females +165.7%) and the UK (males +128.6%, females +114.6%). The T2DM prevalence increases in the UK have plateaued from 2015/16-2019 for both sexes, with insignificant increases in estimated annual percentage changes of +0.9% and 0% for males and females, respectively. Mortality trends were non-uniform across EU countries, with ASMRs increasing over the 30-year period studied in 11 countries for males and in 4 countries for females. The UK observed the highest relative decrease in ASMRs for males (-46.9%). For females, the largest relative decrease in ASMRs was in Cyprus (-67.6%). Mortality-to-incidence ratios decreased in all countries except for males in Latvia and females in Denmark, with the lowest mortality-to-incidence ratios in 2019 being observed in the UK and Finland. DALYs increased in 25 countries for males and 17 countries for females between 1990 and 2019. Conclusions:

T2DM prevalence rates have increased across Europe over the last 30 years, however mortality trends are variable. The prevalence of T2DM has increased more in the UK and Ireland between 1990-2019 than in any EU country, for both males and females, with the exception of Luxembourg. Contrastingly, the UK has observed large relative decreases in T2DM mortality rates. Primary prevention strategies in at risk populations should continue to be a focus for preventing T2DM in at risk groups in the UK and Europe.
Bisacodyl in Stimulant Laxatives Can Induce Estrogen Agonist/Antagonist Activity in Breast Cancer Cells in Culture
Authors: Ngo Lynda , Baer Caroline , Ragland Emily , Ma Peng , Zhang Changde , Wiese Thomas E
Published: May 2021

Exposure to xenobiotic estrogens has the potential to induce estrogen activity that may contribute to a range of undesired physiological effects including the stimulation of estrogen responsive tumors. We have previously determined that extracts of OTC medications containing the stimulant laxative bisacodyl induce estrogenic activity in tissue culture bioassays. In this study, we tested the hypothesis that bisacodyl is responsible for the estrogen activity of these extracts and then characterized these effects. Ethanol extracts and dilutions were prepared from OTC medications containing Bisacodyl (1 gm:1 ml). The estrogen agonist and antagonist activity of each extract, as well as bisacodyl and then metabolite DA-bisacodyl was determined using the T47dkbluc estrogen reporter gene and the MCF-7 E3 estrogen responsive proliferation assays. LC-MS analysis was used to determine bisacodyl and DA-bisacodyl concentration in extracts as well as to trace the metabolism of bisacodyl to DA-bisacodyl in the cell culture bioassays. Molecular modeling “docking” simulations of the interactions of bisacodyl and the metabolite DA-bisacodyl with the estrogen receptor (ER) ligand binding domain was performed using MOE from Chemical Computing Group. Bisacodyl and the metabolite DA-bisacodyl induced mixed agonist/antagonist activity in MCF-7 E3 estrogen responsive proliferation assay similar to 4OH-tamoxifen. At the same time, both compounds stimulated only minimal estrogen activity in the T47dkbluc estrogen reporter gene assay. LC-MS analysis determinations identified that almost all bisacodyl was converted to the dihydroxy metabolite DA-bisacodyl in cell culture bioassays. Molecular modeling “docking” simulations determined that while bisacodyl does not fit into the agonist (estradiol) or antagonist (4OH-tamoxifen) conformations of the estrogen receptor ligand binding site, the metabolite DA-bisacodyl may fit into the antagonist induced binding pocket of the ER in a reasonable way. This study characterizes the observed estrogen activity of extracts from OTC medications containing bisacodyl as resulting from the bisacodyl metabolite DA-bisacodyl interacting with the estrogen receptor. Thus, bisacodyl is an OTC medication active ingredient that has potential to induce side effects and or toxicity involving estrogen signalling. The capacity for medications containing bisacodyl or other estrogenic substances to induce estrogen activity in patients is unclear. At the same time, consumers and practitioners should be aware of the potential estrogen activity of bisacodyl containing products.
The Resilience of the Euro
Authors: Lane Philip R.
Published: May 2021

Over 2014 – 2019, the euro area charted a substantial post-crisis economic recovery while also reducing macro-financial vulnerabilities. The array of post-crisis institutional reforms has improved the capacity of the euro area to withstand adverse shocks, even if the narrowing of imbalances also came at a high cost (especially in the most indebted member countries). The pandemic has provided a new test: the combination of a common central bank and the enlargement of the common fiscal capacity has provided substantial policy support and fostered a narrowing in risk premia, despite significant differences in levels of public debt and exposures to the pandemic shock. While the resilience of the euro is sure to be tested further in the coming years, the extent of the underlying political backing for the common currency should not be underestimated.
O controle da administração pública e o conflito entre as decisões do TCU e as deliberações do CNJ
Authors: Lobo Gomes Filipe , Bezerra Sampaio Thyago
Published: May 2021

Este artigo propõe-se promover o debate acerca do suposto conflito oriundo das decisões emanadas do Tribunal de Contas da União e do Conselho Nacional de Justiça, no exercício, respectivamente, dos controles internos e externos da administração pública. Partindo da premissa de que se trata de espécies distintas de controle da administração pública, numa classificação de acordo com o agente controlador, buscar-se-á demonstrar que inexiste razão ao CNJ para não cumprir, ou não fazer cumprir, as decisões expedidas pelo TCU. Pretende-se trazer à reflexão a prevalência da competência do TCU quando atua no exercício de sua jurisdição administrativa. Para tal, utilizou-se o método qualitativo de investigação científica que foca o caráter subjetivo do objeto analisado.
Competition and Distortion: A Theory of Information Bias on the Peer-to-Peer Lending Market
Authors: Wu Zhenhua , Hu Lin , Lin Zhijie , Tan Yong
Published: May 2021

Despite the popular emergence of peer-to-peer (P2P) lending platforms, relevant research investigating the role of these platforms on P2P markets still lags. In this paper, we present a model to study the market incentives of P2P lending platforms' optimal information-reporting strategies when the following exist: (i) uncertainty on the return of loans and (ii) competition from entrants. We focus on the information bias of platforms driven by demand-side actors—investors’ optimism/pessimism about risk—while we keep the platforms being rational. We characterize platforms' equilibrium reporting strategies under different market conditions. Surprisingly, we find that when uncertainty is significant, and the threat of entry is strong but not detrimental, the platform has incentives to bias information toward investors' biased beliefs. This result demonstrates a case where competition and uncertainty may jointly lead to information bias. However, a properly designed uncertainty-resolution mechanism could reduce the incentive. Our findings contribute to the literature on the P2P lending market by analyzing platform decisions and offer policy implications for regulating P2P lending market.
Community nursing placements: student learning experiences during a pandemic and beyond
Authors: Norman Kay , Meszaros Kerrie
Published: May 2021

This article explores the challenges in maintaining community nursing placements as dynamic learning experiences for student nurses during the pandemic and beyond. Opportunities to create new ways of working and learning are essential to ensure student nurses can continue to be exposed to community nursing care. Developing insight, understanding, knowledge and skills in this unique learning environment is instrumental to encourage the next generation of community nurses and increase the future workforce. Suggestions for alternative ways of providing learning experiences during the present period are discussed, which could also be embedded as long-term strategies in the future.
Woman-centred care
Authors: Davison Clare
Published: May 2021

Are women really at the centre of care in the modern maternity system? Dr Clare Davison investigates
A New Frontier Drug Development in Nanomedicine and Itsanti-Urolithiatic Activity of Kalanchoe Pinnata
Authors: Priya F. Janeeta , Rose A. Leema , Vidhya S. , Arputharaj A , Akshana S. , Rameez Fathima U. F.
Published: May 2021

Latterly, the green synthesis of metallic nanoparticles has stock pile and terminal interest over the last decade due to their idiosyncratic properties that make them felicitous in various fields of science and technology. In this study the silver nanoparticles can be manufacture by using the leaf extract of Kalanchoe pinnata plant using microwave radiation method. The nanoparticles that are synthesized by plants are non-toxic and eco-friendly and it is characterized by using UV-Visible, FT-IR , X-ray diffraction (XRD) and TEM.The crystalline natures of the synthesized silver nanoparticles were identified by XRD and its shape was confirmed by TEM analysis. Anti-urolithiatic activity of synthesized silver nanoparticles was accomplished which reduces the growth of kidney stone which was appraisal by using the In-Vitro growth of urinary calculi.
Evaluative Wortbildung und Personenreferenz.
Authors: Dammel Antje
Published: May 2021

The word formation pattern [ __-i]N mask. in Alemannic mainly derives masculine agent nouns from verbs resulting in output semantics of ‘someone who notoriously acts in the manner of base verb’. I analyse the pattern as an instance of evaluative morphology embedded in a more general output oriented schema and propose a scenario how the pattern may have developed from an OHG hypochoristic pattern primarily used in names. In a qualitative and quantitative analysis of two dialect dictionaries on Zürich German and Bernese German I look into the possible lexical fillings of the pattern and derive areas of stereotypisation. As the products of the pattern are masculine nouns, it is of interest whether the lemmas are flanked with a feminine form or not, and if they are, whether the feminine form follows or precedes the masculine form or is added as a separate lemma without a masculine pendant. The analysis also includes neuter forms ending in -i listed in the dictionaries. As the masculine products of the pattern already reflect stereotyped behaviour, the feminine (and neuter) forms included in the diction­na­ries are expected to sediment gender stereotypes to a high degree.
Decolonization Is Not a Dinner Party: Claudia Jones, China's Nuclear Weapons, and Anti-Imperialist Solidarity
Authors: Liu Zifeng
Published: May 2021

This article examines Claudia Jones's view on nuclear weapons and her attempts in the West Indian Gazette and Afro-Asian Caribbean News and Renmin Ribao to link Beijing's nuclear project to global anti-imperialist and nationalist movements. In hailing China's first successful nuclear test as a major advancement in the international struggle against U.S. empire, Jones underscored the overlaps between her internationalist politics and Beijing's militant foreign policy pronouncements to drive home the need for intensified resistance against imperialism and for national liberation. In this way she also rejected the Soviet doctrine of peaceful coexistence and articulated a peace politics that emphasized the dismantling of imperialism and colonialism as the prerequisite for lasting peace. Her journalistic efforts to wage a global decolonial struggle culminated in her reporting on her 1964 visit to China, where she found “evidence” for Beijing's anti-imperialist commitments. Although she constructed romanticizing, if not entirely counterfactual, narratives of Chinese socialism that corresponded to the party-state's geopolitical and domestic aspirations, she downplayed the implications of the deepening Sino-Soviet Split, thereby formulating a relatively independent position that differed from Beijing's line. Jones's activism around the issue of nuclear weapons, as well as its inconsistencies and contradictions, exemplified the hard work that Black internationalists had to put into forging transnational solidarities and tilting the global geopolitical balance in the favor of the decolonizing world.
Claudia Jones, the Longue Durée of McCarthyism, and the Threat of US Fascism
Authors: Burden-Stelly Charisse
Published: May 2021

This article examines the ways that the Black Communist luminary Claudia Jones theorized the fascist threat in the United States in the early Cold War era. Drawing on her political thought and that of her comrades, the article begins by defining the peculiar brand of US fascism that loomed large in the minds of Black radicals who critiqued and militated against global capitalist exploitation. Then, “the longue durée of McCarthyism” is employed as an analytical framework to explicate the post-World War II “fascist-like” political formation that both preceded and exceeded Wisconsin Senator Joseph McCarthy's reign of repression. The next section highlights Jones's analysis of the 1940 Alien Registration Act, commonly known as the Smith Act, which was the first peacetime sedition act in US history. The focus of the final section is Jones's critique of, and subjection to, the Internal Security Act of 1950, also known as the McCarran Act, which President Harry S. Truman unsuccessfully vetoed. As Jones's biographers Buzz Johnson and Carole Boyce Davies note, taken together, the Smith Act and the McCarran Act created the conditions for the persecution of thousands of progressives, launched an all-out attack on their civil rights, and laid the foundation for immigration checks, deportation, and harassment particularly aimed at Black people. Ultimately, the lives of many Black anticapitalists, including Jones, Paul Robeson, C.L.R. James, and Ferdinand Smith were fundamentally disrupted by this “strong anti-Black and anti-communist hysteria” that portended the rise of fascism in the United States.
Neurological manifestations of COVID-19: a clinical approach
Authors: Susilawathi Ni Made , Tini Kumara , Wijayanti Ida Ayu Sri , Rahmawati Putu Lohita , Wardhana Dewa Putu Wisnu , Samatra Dewa Gde Purwa , Sudewi Anak Agung Raka
Published: May 2021

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 which attacks the respiratory tract and has been declared a global pandemic by the World Health Organization. The disease has a very wide clinical spectrum which can be manifested as asymptomatic to critical conditions. SARS-CoV-2 shows a neurotropism proven by its identification in the cerebrospinal fluid and brain vascular endothelial. The complete mechanism of how the virus invades the human nervous system is yet to be identified. Thus, every neurologist needs to follow the progressivity of COVID-19 symptoms involving the nervous system.
Strong extrinsic chirality in biaxial hyperbolic material α-MoO3 with in-plane anisotropy
Authors: Wu Biyuan , Wang Mingjun , Wu Feng , Wu Xiaohu
Published: May 2021

Chirality has always been a hot research topic because it possesses potential applications in polarization optics, chemical and biosensing. In the previous works, intrinsic chirality has been extensively explored, but its development is limited due to the complexity in fabrication of chiral metamaterials. Therefore, there is an urgent need to simplify fabrication and design of compact devices with chiral response. Extrinsic chirality has shown great potential because it can be realized in nonchiral anisotropic planar structures with low-cost fabrication techniques. In this paper, the extrinsic chirality of biaxial hyperbolic material

α

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3

with in-plane anisotropy has been investigated. By analyzing the effect of thickness of

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film, the angle of incidence, azimuth angle, and wavelength of incidence on the circular dichroism (CD), the maximum CD can reach 0.77. This strong extrinsic chirality of the

α

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M
o

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film results from the mutual orientation of the

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film and the incident light. In addition,

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film can still maintain strong extrinsic chirality when the azimuthal angle ranges from approximately 20°–57° and the angle of incidence is from 55°–80°.
Pseudocell Tracer—A method for inferring dynamic trajectories using scRNAseq and its application to B cells undergoing immunoglobulin class switch recombination
Authors: Reiman Derek , Manakkat Vijay Godhev Kumar , Xu Heping , Sonin Andrew , Chen Dianyu , Salomonis Nathan , Singh Harinder , Khan Aly A.
Published: May 2021

Single cell RNA sequencing (scRNAseq) can be used to infer a temporal ordering of cellular states. Current methods for the inference of cellular trajectories rely on unbiased dimensionality reduction techniques. However, such biologically agnostic ordering can prove difficult for modeling complex developmental or differentiation processes. The cellular heterogeneity of dynamic biological compartments can result in sparse sampling of key intermediate cell states. To overcome these limitations, we develop a supervised machine learning framework, called Pseudocell Tracer, which infers trajectories in pseudospace rather than in pseudotime. The method uses a supervised encoder, trained with adjacent biological information, to project scRNAseq data into a low-dimensional manifold that maps the transcriptional states a cell can occupy. Then a generative adversarial network (GAN) is used to simulate pesudocells at regular intervals along a virtual cell-state axis. We demonstrate the utility of Pseudocell Tracer by modeling B cells undergoing immunoglobulin class switch recombination (CSR) during a prototypic antigen-induced antibody response. Our results revealed an ordering of key transcription factors regulating CSR to the IgG1 isotype, including the concomitant expression ofNfkb1andStat6prior to the upregulation ofBach2expression. Furthermore, the expression dynamics of genes encoding cytokine receptors suggest a poised IL-4 signaling state that preceeds CSR to the IgG1 isotype.
Deep template-based protein structure prediction
Authors: Wu Fandi , Xu Jinbo
Published: May 2021

Motivation

Protein structure prediction has been greatly improved by deep learning, but most efforts are devoted to template-free modeling. But very few deep learning methods are developed for TBM (template-based modeling), a popular technique for protein structure prediction. TBM has been studied extensively in the past, but its accuracy is not satisfactory when highly similar templates are not available.

Results

This paper presents a new method NDThreader (New Deep-learning Threader) to address the challenges of TBM. NDThreader first employs DRNF (deep convolutional residual neural fields), which is an integration of deep ResNet (convolutional residue neural networks) and CRF (conditional random fields), to align a query protein to templates without using any distance information. Then NDThreader uses ADMM (alternating direction method of multipliers) and DRNF to further improve sequence-template alignments by making use of predicted distance potential. Finally, NDThreader builds 3D models from a sequence-template alignment by feeding it and sequence coevolution information into a deep ResNet to predict inter-atom distance distribution, which is then fed into PyRosetta for 3D model construction. Our experimental results show that NDThreader greatly outperforms existing methods such as CNFpred, HHpred, DeepThreader and CEthreader. NDThreader was blindly tested in CASP14 as a part of RaptorX server, which obtained the best average GDT score among all CASP14 servers on the 58 TBM targets.
Model guided trait-specific co-expression network estimation as a new perspective for identifying molecular interactions and pathways
Authors: Kontio Juho A. J. , Pyhäjärvi Tanja , Sillanpää Mikko J.
Published: May 2021

A wide variety of 1) parametric regression models and 2) co-expression networks have been developed for finding gene-by-gene interactions underlying complex traits from expression data. While both methodological schemes have their own well-known benefits, little is known about their synergistic potential. Our study introduces their methodological fusion that cross-exploits the strengths of individual approaches via a built-in information-sharing mechanism. This fusion is theoretically based on certain trait-conditioned dependency patterns between two genes depending on their role in the underlying parametric model. Resulting trait-specific co-expression network estimation method 1) serves to enhance the interpretation of biological networks in a parametric sense, and 2) exploits the underlying parametric model itself in the estimation process. To also account for the substantial amount of intrinsic noise and collinearities, often entailed by expression data, a tailored co-expression measure is introduced along with this framework to alleviate related computational problems. A remarkable advance over the reference methods in simulated scenarios substantiate the method’s high-efficiency. As proof-of-concept, this synergistic approach is successfully applied in survival analysis, with acute myeloid leukemia data, further highlighting the framework’s versatility and broad practical relevance.
Modeling historic incidence trends implies early field cancerization in esophageal squamous cell carcinoma
Authors: Luebeck Georg E. , Vaughan Thomas L. , Curtius Kit , Hazelton William D.
Published: May 2021

Patterns of cancer incidence, viewed over extended time periods, reveal important aspects of multistage carcinogenesis. Here we show how a multistage clonal expansion (MSCE) model for cancer can be harnessed to identify biological processes that shape the surprisingly dynamic and disparate incidence patterns of esophageal squamous cell carcinoma (ESCC) in the US population. While the dramatic rise in esophageal adenocarcinoma (EAC) in the US has been largely attributed to reflux related increases in the prevalence of Barrett’s esophagus (BE), the premalignant field in which most EAC are thought to arise, only scant evidence exists for field cancerization contributing to ESCC. Our analyses of incidence patterns suggest that ESCC is associated with a premalignant field that may develop very early in life. Although the risk of ESCC, which is substantially higher in Blacks than Whites, is generally assumed to be associated with late-childhood and adult exposures to carcinogens, such as from tobacco smoking, alcohol consumption and various industrial exposures, the temporal trends we identify for ESCC suggest an onset distribution of field-defects before age 10, most strongly among Blacks. These trends differ significantly in shape and strength from field-defect trends that we estimate for US Whites. Moreover, the rates of ESCC-predisposing field-defects predicted by the model for cohorts of black children are decreasing for more recent birth cohorts (for Blacks born after 1940). These results point to a potential etiologic role of factors acting early in life, perhaps related to nutritional deficiencies, in the development of ESCC and its predisposing field-defect. Such factors may explain some of the striking racial differences seen in ESCC incidence patterns over time in the US.
Predictors of stillbirth among women who had given birth in Southern Ethiopia, 2020: A case-control study
Authors: Abebe Haimanot , Shitu Solomon , Workye Haile , Mose Ayenew
Published: May 2021

Background

Although the rate of stillbirth has decreased globally, it remains unacceptably high in low- and middle-income countries. Only ten countries including Ethiopia attribute more than 65% of global burden of still birth. Ethiopia has the 7th highest still birth rate in the world. Identifying the predictors of stillbirth is critical for developing successful interventions and monitoring public health programs. Although certain studies have assessed the predictors of stillbirth, they failed in identify the proximate predictors of stillbirth. In addition, the inconsistent findings in identify the predictors of stillbirth, and the methodological limitations in previously published works are some of the gaps. Therefore, this study aimed to identify the predictors of stillbirth among mothers who gave birth in six referral hospitals in Southern, Ethiopia.

Methods

A hospital-based unmatched case-control study was conducted in six referral hospitals in Southern, Ethiopia from October 2019 to June 2020. Consecutive sampling techniques and simple random techniques were used to recruit cases and controls respectively. A structured standard tool was used to identify the predictors of stillbirth. Data were entered into Epi Info 7 and exported to SPSS 23 for analysis. A multivariable logistic regression model was used to identify the independent predictors of stillbirth. The goodness of fit was tested using the Hosmer and Lemeshow goodness-of-fit. In this study P-value < 0.05 was considered to declare a result as a statistically significant association.

Results

In this study 138 stillbirth cases and 269 controls were included. Women with multiple pregnancy [AOR = 2.98, 95%CI: 1.39–6.36], having preterm birth [AOR = 2.83, 95%CI: 1.58–508], having cesarean mode of delivery [AOR = 3.19, 95%CI: 1.87–5.44], having no ANC visit [AOR = 4.17, 95%CI: 2.38–7.33], and being hypertensive during pregnancy [AOR = 3.43, 95%CI: 1.93–6.06] were significantly associated with stillbirth.

Conclusions

The predictors of stillbirth identified are manageable and can be amenable to interventions. Therefore, strengthening maternal antenatal care utilization should be encouraged by providing appropriate information to the mothers. There is a need to identify, screen, and critically follow high-risk mothers: those who have different complications during pregnancy, and those undergoing cesarean section due to different indications.
Long-term variations in solar radiation, diffuse radiation, and diffuse radiation fraction caused by aerosols in China during 1961–2016
Authors: Xie Hongfei , Zhao Junfang , Wang Kaili , Peng Huiwen
Published: May 2021

The effects of atmospheric aerosols on the terrestrial climate system are more regional than those of greenhouse gases, which are more global. Thus, it is necessary to examine the typical regional effects of how aerosols affect solar radiation in order to develop a more comprehensive understanding. In this study, we used global AErosol RObotic NETwork (AERONET) data and robust radiation observational evidence to investigate the impact of aerosols on total radiation, diffuse radiation, and the diffuse radiation fraction in China from 1961 to 2016. Our results showed that there were different temporal changes in the aerosol optical depth (AOD), total solar radiation, diffuse radiation and diffuse radiation fraction over the past 56 years. Specifically, the 550 nm AOD from 2005 to 2016 decreased significantly, with annual average AOD of 0.51. Meanwhile, the average total solar radiation reduced by 2.48%, while there was a slight increase in average diffuse radiation at a rate of 3.10 MJ·m-2·yr-1. Moreover, the spatial heterogeneities of AOD, total radiation, diffuse radiation, and the diffuse radiation fraction in China were significant. Aerosol particle emissions in the developed eastern and southern regions of China were more severe than those in the western regions, resulting in higher total radiation and diffuse radiation in the western plateau than in the eastern plain. In addition, aerosols were found to have negative effects on total radiation and sunshine hours, and positive effects on diffuse radiation and diffuse radiation fraction. Further, the diffuse radiation fraction was negatively correlated with sunshine hours. However, there was a positive correlation between AOD and sunshine hours. These results could be used to assess the impacts of climate change on terrestrial ecosystem productivity and carbon budgets.