bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical inertia in patients with type 2 diabetes treated with oral antidiabetic drugs: Results from a Japanese cohort study (JDDM53)
Authors: Maegawa Hiroshi , Ishigaki Yasushi , Langer Jakob , Saotome‐Nakamura Ai , Andersen Marc ,   the Japan Diabetes Clinical Data Management (JDDM) Study Group
Published: July 2020

Aims/Introduction

Treatment intensification is commonly delayed in people with type 2 diabetes, resulting in poor glycemic control for an unacceptable length of time and increased risk of complications.

Materials and Methods

This retrospective study investigated clinical inertia in 33,320 Japanese adults with type 2 diabetes treated with oral antidiabetic drugs (OADs) between 2009 and 2018, using data from the Computerized Diabetes Care (CoDiC®) database.

Results

The median time from first reported glycated hemoglobin (HbA1c) ≥7.0% (≥53 mmol/mol) to treatment intensification was considerably longer and HbA1c levels were higher the more OADs the patient was exposed to. For patients receiving three OADs, the median times from HbA1c ≥7.0% (53 mmol/mol) to intensification with OAD, glucagon‐like peptide‐1 receptor agonist or insulin were 8.1, 9.1 and 6.7 months, with a mean HbA1c level at the time of intensification of 8.4%, 8.9% and 9.3%, respectively. The cumulative incidence for time since the first reported HbA1c ≥7.0% (≥53 mmol/mol) to intensification confirmed the existence of clinical inertia, identifying patients whose treatment was not intensified despite poor glycemic control. HbA1c levels ≥7.0% (≥53 mmol/mol) after ≥6 months on one, two or three OADs were observed in 42%, 51% and 58% of patients, respectively, showing that approximately 50% of patients are above HbA1c target regardless of how many OADs they take.

Conclusions

Real‐world data here show clinical inertia in Japanese adults with type 2 diabetes from early diabetes stages when they are receiving OADs, and illustrate a need for earlier, more effective OADs or injectable treatment intensification and better communication around the existence of clinical inertia.
The heterochronic geneOryza sativa LIKE HETEROCHROMATIN PROTEIN 1modulates miR156b/c/i/e levels
Authors: Cui Yongtao , Cheng Jingfei , Ruan Shuang , Qi Peipei , Liu Wei , Bian Hongwu , Ye Luhuan , Zhang Yuping , Hu Jiang , Dong Guojun , Guo Longbiao , Zhang Yijing , Qian Qian , Hu Xingming
Published: July 2020

The juvenile‐to‐adult transition in plants involves changes in vegetative growth and plant architecture; the timing of this transition has important implications for agriculture. The microRNA miR156 regulates this transition and shoot maturation in plants. InArabidopsis thaliana, deposition of histone H3 trimethylation on lysine 27 (H3K27me3, a repressive mark) at theMIR156A/Cloci is regulated by Polycomb Repressive Complex 1 (PRC1) or PRC2, depending on the developmental stage. The levels of miR156 progressively decline during shoot maturation. The amount of H3K27me3 atMIR156A/Cloci affects miR156 levels; however, whether this epigenetic regulation is conserved remains unclear. Here, we found that in rice (Oryza sativa), the putative PRC1 subunit LIKE HETEROCHROMATIN PROTEIN 1 (OsLHP1), with the miR156–SQUAMOSA PROMOTER BINDING PROTEIN‐LIKE (SPL) module, affects developmental phase transitions. Loss of OsLHP1 function results in ectopic expression ofMIR156B/C/I/E, phenocopy of miR156 overexpression, and reduced H3k27me3 levels atMIR156B/C/I/E. This indicates thatOsLHP1has functionally diverged fromArabidopsis LHP1. Genetic and transcriptome analyses of wild‐type, miR156b/c‐overexpression, andOslhp1‐2mutant plants suggest that OsLHP1 acts upstream of miR156 and SPL during the juvenile‐to‐adult transition. Therefore, modifying the OsLHP1–miR156–SPL pathway may enable alteration of the vegetative period and plant architecture.
Nursing handoffs and clinical judgments regarding patient risk of deterioration: A mixed‐methods study
Authors: Lavoie Patrick , Clarke Sean P. , Clausen Christina , Purden Margaret , Emed Jessica , Cosencova Lidia , Frunchak Valerie
Published: July 2020

Aims and objectives

To explore how change‐of‐shift handoffs relate to nurses' clinical judgments regarding patient risk of deterioration.

Background

The transfer of responsibility for patients' care comes with an exchange of information about their condition during change‐of‐shift handoff. However, it is unclear how this exchange affects nurses' clinical judgments regarding patient risk of deterioration.

Design

A sequential explanatory mixed‐methods study reported according to the STROBE and COREQ guidelines.

Methods

Over four months, 62 nurses from one surgical and two medical units at a single Canadian hospital recorded their handoffs at change of shift. After each handoff, the two nurses involved each rated the patient's risk of experiencing cardiac arrest or being transferred to an intensive care unit in the next 24 hr separately. The information shared in handoffs was subjected to content analysis; code frequencies were contrasted per nurses' ratings of patient risk to identify characteristics of information that facilitated or hindered nurses' agreement.

Results

Out of 444 recorded handoffs, there were 125 in which at least one nurse judged that a patient was at risk of deterioration; nurses agreed in 32 cases (25.6%) and disagreed in 93 (74.4%). These handoffs generally included information on abnormal vital signs, breathing problems, chest pain, alteration of mental status or neurological symptoms. However, the quantity and seriousness of clinical cues, recent transfers from intensive care units, pain without a clear cause, signs of delirium and nurses' knowledge of patient were found to affect nurses' agreement.

Conclusions

Nurses exchanged more information regarding known indicators of deterioration in handoffs when they judged that patients were at risk. Disagreements most often involved incoming nurses rating patient risk as higher.

Relevance to clinical practice

This study suggests a need to sensitise nurses to the impact of certain cues at report on their colleagues' subsequent clinical judgments. Low levels of agreement between nurses underscore the importance of exchanging impressions regarding the likely evolution of a patient's situation to promote continuity of care.
LONG RUN ECONOMIC GROWTH PERFORMANCE IN LATIN AMERICA – 1820–2016
Authors: Hofman André A. , Valderrama Patricio
Published: July 2020

This paper provides an assessment of Latin America's long‐run performance from a comparative and historical perspective and concentrates on quantification of long‐run GDP growth and measurement of factor inputs and total factor productivity (TFP). Growth accounting shows the contribution of factor inputs (capital and labor) and TFP to output growth. What is new: capital and labor services are estimated for a group of nine countries, Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Uruguay, and Venezuela, and we widen the time frame of analysis to 1820–2016. This kind of exercise may serve different purposes such as explaining differences in growth rates between countries and assessing the role of technical progress. The overall GDP growth rate of the Latin American economies over the 1820–2016 period was somewhat above 3%. In the long run, the main differences in factor contributions to growth can be found in capital and, especially, in TFP. Capital contributed on average 1.45% to GDP growth over the whole period. However, the main culprit of the mediocre performance of Latin America compared to other developed and developing countries is TFP. TFP contributed over the whole period a mere 0.25% to Latin American GDP growth and was negative in several subperiods.
Fetus of 8q22.2q24.3 duplication and 13q33.2q34 deletion derived from a maternal balanced translocation
Authors: Liu Tong , Xie Huihui , Zhang Jingbo , Wang Xia , Sha Jing , Zhai Jingfang
Published: July 2020

The concomitant occurrence of 8q duplication and 13q deletion is the first to be detected by noninvasive prenatal testing (NIPT) to date. Through case analysis, we could provide a clinical approach to pregnant women with chromosomal abnormalities revealed by NIPT. The combination of traditional karyotype and copy number variation sequencing (CNV‐seq) could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XY,der(13)t(8;13)(q22;q32)mat and CNV‐seq results showed that there was an approximately 45.26‐Mb duplication in 8q22.2‐q24.3 (101040001–146 300 000) and an approximately 9.54‐Mb deletion in 13q33.2‐q34 (105560001–115 100 000). Prenatal ultrasound revealed the fetal structural abnormalities presented with hypoplasia of the cerebellar vermis, a flat nose, echogenic bowel and absent gallbladder. Herein, we consider that combination detection of traditional karyotyping, CNV‐seq and ultrasonography provides a valuable method for pregnant women with abnormal NIPT.
Does skilled migration reduce investment in human capital? An investigation on educational choices in Italian regions (2001–2016)
Authors: Nifo Annamaria , Scalera Domenico , Vecchione Gaetano
Published: July 2020

This paper investigates the effects of prospective migration on students’ investment in tertiary education. A simple theoretical model is presented in which individual educational choices, different across potential students because of heterogeneity in migration costs, are driven by expected returns and costs of tertiary education. In this framework, a larger probability of after‐graduation migration is shown to affect educational choices by both reducing the rate of enrollment at home and favoring pre‐graduation migration (i.e., enrollment at universities outside the residence region). The theoretical predictions are confirmed by the empirical investigation carried out on Italian interregional graduate migration in 2001–2016. In the lagging regions of Southern Italy, out‐migration of students and graduates, and weak incentives to acquire tertiary education turn out to bring about depletion of local human capital.
Effectiveness of blood flow‐restricted slow walking on mobility in severe multiple sclerosis: A pilot randomized trial
Authors: Lamberti Nicola , Straudi Sofia , Donadi Maria , Tanaka Hirofumi , Basaglia Nino , Manfredini Fabio
Published: July 2020

Objective

We tested the safety, feasibility, and effectiveness of blood flow restriction‐empowered low‐intensity interval walking exercise (BFR‐W) compared with conventional intensive overground walking (CON‐W) at improving gait speed and functional capacity in patients with multiple sclerosis (MS) and severe gait disabilities.

Methods

24 patients (58 ± 5 years; 7 males) with progressive MS (Expanded Disability Status Scale 5.5 − 6.5) were randomized to receive 12 rehabilitation sessions over 6 weeks. The BFR‐W group (n = 12) performed interval walking (speed paced by a metronome that increased weekly) with BFR bands at the thighs. The CON‐W group (n = 12) received physiotherapist‐assisted overground walking therapy. The primary outcome was gait speed, measured by the timed 25‐foot walk test. Secondary outcomes included walking endurance, balance, strength, fatigue, and quality of life. The measurements were collected at baseline, at the end of training, and a 6‐week follow‐up.

Results

The two groups did not present any baseline difference. BFR‐W group safely walked without limitations due to sleeve compression, with lower increase in perceived exertion (RPE) (P < .001) and heart rate (P = .031) compared with the CON‐W. Gait speed improved significantly in both groups (BFR‐W + 13%; CON‐W + 5%) with greater increases in the BFR‐W group at end of the training (P = .001) and at the follow‐up (P = .041). Most of the secondary outcomes significantly improved in the two groups, without between‐group differences.

Conclusions

Slow interval walking with moderate BFR to the lower limbs was superior to overground walking in improving gait speed in patients with MS with a lower training load and a more durable clinical benefit.
A network physiology approach to oxygen saturation variability during normobaric hypoxia
Authors: Jiang Yuji , Costello Joseph T. , Williams Thomas B. , Panyapiean Nawamin , Bhogal Amar S. , Tipton Michael J. , Corbett Jo , Mani Ali R.
Published: July 2020

New Findings

What is the central question of this study?

What is the physiological interpretation offluctuations observed during normobaric hypoxia in healthy individuals?

What is the main finding and its importance?

There is a significant flow of information betweenand other cardio‐respiratory time series during graded hypoxia. Analysis of the pattern ofvariations has potential for non‐invasive assessment of the engagement of respiratory control system in health and disease.

Peripheral capillary oxygen saturation () exhibits a complex pattern of fluctuations during hypoxia. The physiological interpretation ofvariability is not well understood. In this study, we tested the hypothesis thatfluctuation carries information about integrated cardio‐respiratory control in healthy individuals using a network physiology approach. We explored the use of transfer entropy in order to compute the flow of information between cardio‐respiratory signals during hypoxia. Twelve healthy males (mean (SD) age 22 (4) years) were exposed to four simulated environments (fraction of inspired oxygen (): 0.12, 0.145, 0.17, and 0.2093) for 45 min, in a single blind randomized controlled design. The flow of information between different physiological parameters (, respiratory frequency, tidal volume, minute ventilation, heart rate, end‐tidal pressure of O2and CO2) were analysed using transfer entropy. Normobaric hypoxia was associated with a significant increase in entropy of thetime series. The transfer entropy analysis showed that, particularly at0.145 and 0.12, the flow of information betweenand other physiological variables exhibits a bidirectional relationship. While reciprocal interactions were observed between different cardio‐respiratory parameters during hypoxia,remained the main hub of this network.fluctuations during graded hypoxia exposure carry information about cardio‐respiratory control. Therefore,entropy analysis has the potential for non‐invasive assessment of the functional connectivity of respiratory control system in various healthcare settings.
Polynesians, Native Americans met and mingled long ago
Authors: Wade Lizzie
Published: July 2020

Islanders' DNA suggests contact before European arrival
Contact area–dependent cell communication and the morphological invariance of ascidian embryogenesis
Authors: Guignard Léo , Fiúza Ulla-Maj , Leggio Bruno , Laussu Julien , Faure Emmanuel , Michelin Gaël , Biasuz Kilian , Hufnagel Lars , Malandain Grégoire , Godin Christophe , Lemaire Patrick
Published: July 2020

Cell-cell contacts specify cell fate

Ascidians, or sea squirts, are marine invertebrate filter feeders with highly reproducible cellular events and invariant embryonic cell lineages. Guignard
et al.
studied the ascidian embryo to address the determinants of this cellular reproducibility. They introduce computational methods for the robust and automated segmentation, tracking, and analysis of whole-cell behaviors in high-throughput light-sheet microscopy datasets. This work shows that cell induction can be controlled by the contact area among cells. The range of cell signaling is proposed to set the scale at which animal embryonic reproducibility is observed. A high level of reproducibility of embryonic geometries may also counter-intuitively lift constraints on genome evolution, thereby contributing to the rapid molecular evolution observed in ascidians.

Science
, this issue p.
eaar5663
Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain
Authors: Horowitz Alana M. , Fan Xuelai , Bieri Gregor , Smith Lucas K. , Sanchez-Diaz Cesar I. , Schroer Adam B. , Gontier Geraldine , Casaletto Kaitlin B. , Kramer Joel H. , Williams Katherine E. , Villeda Saul A.
Published: July 2020

Plasma transfers exercise benefit in mice

Exercise has a broad range of beneficial healthful effects. Horowitz
et al.
tested whether the beneficial effects of exercise on neurogenesis in the brain and improved cognition in aged mice could be transferred in plasma (blood without its cellular components) from one mouse to another (see the Perspective by Ansere and Freeman). Indeed, aged mice that received plasma from young or old mice that had exercised showed beneficial effects in their brains without hitting the treadmill. The authors identified glycosylphosphatidylinositol-specific phospholipase D1 as a factor in plasma that might, in part, mediate this favorable effect.

Science
, this issue p.
167
; see also p.
144
Cognitive map–based navigation in wild bats revealed by a new high-throughput tracking system
Authors: Toledo Sivan , Shohami David , Schiffner Ingo , Lourie Emmanuel , Orchan Yotam , Bartan Yoav , Nathan Ran
Published: July 2020

Knowing their way around

The presence of a cognitive map is essential to our ability to navigate through areas we know because it facilitates the use of spatial knowledge to derive new routes. Whether such maps exist in nonhuman animals has been debated, largely because of the difficulty of demonstrating qualifying components of the map outside of a laboratory. In two studies on Egyptian fruit bats, Harten
et al.
and Toledo
et al.
together show that this species's navigational strategies meet the requirements for the use of a cognitive map of their environment, confirming that this skill occurs outside of humans (see the Perspective by Fenton).

Science
, this issue p.
194
, p.
188
; see also p.
142
Changes in phytoplankton concentration now drive increased Arctic Ocean primary production
Authors: Lewis K. M. , van Dijken G. L. , Arrigo K. R.
Published: July 2020

Food for thought

Phytoplankton abundances in the Arctic Ocean have been increasing over recent decades as the region has warmed and sea ice has disappeared. The presumptive causes of this increase were expanding open water area and a longer growing season—at least until now. Lewis
et al.
show that although these factors may have driven the productivity trends before, over the past decade, phytoplankton primary production rose by more than half because of increased phytoplankton concentrations (see the Perspective by Babin). This finding means that there has been an influx of new nutrients into the region, suggesting that the Arctic Ocean could become more productive and export additional carbon in the future.

Science
, this issue p.
198
; see also p.
137
Marginal dentition and multiple dermal jawbones as the ancestral condition of jawed vertebrates
Authors: Vaškaninová Valéria , Chen Donglei , Tafforeau Paul , Johanson Zerina , Ekrt Boris , Blom Henning , Ahlberg Per Erik
Published: July 2020

Teeth and jaws

The first vertebrates were jawless, much like a modern hagfish. There has been a lot of interest in how these forms transitioned to having jaws like most of their descendants, including humans. Much of our understanding of this process has focused on how the teeth are replaced relative to the jaw. Previous theories suggested that tooth growth that occurred lingually—or from inside out as in modern fishes—was a derived condition. Vaškaninová
et al.
vertebrates, suggesting that it may have been ancestral.

Science
, this issue p.
211
Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations
Authors: Marzolini Catia , Stader Felix , Stoeckle Marcel , Franzeck Fabian , Egli Adrian , Bassetti Stefano , Hollinger Alexa , Osthoff Michael , Weisser Maja , Gebhard Caroline E. , Baettig Veronika , Geenen Julia , Khanna Nina , Tschudin-Sutter Sarah , Mueller Daniel , Hirsch Hans H. , Battegay Manuel , Sendi Parham
Published: July 2020

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7.
Prevention strategies to reduce future impact of low back pain: a systematic review and meta-analysis
Authors: de Campos Tarcisio F , Maher Chris G , Fuller Joel T , Steffens Daniel , Attwell Stephanie , Hancock Mark J
Published: July 2020

Objective

To evaluate the evidence from randomised controlled trials (RCTs) on the effectiveness of prevention strategies to reduce future impact of low back pain (LBP), where impact is measured by LBP intensity and associated disability.

Design

Systematic review with meta-analysis.

Data sources

MEDLINE, Embase, CINAHL, PEDro and The Cochrane (CENTRAL) databases from inception to 22 October 2018.

Eligibility criteria

RCTs evaluating any intervention aiming to prevent future impact of LBP, reporting an outcome measure of LBP intensity and/or disability measured at least 3 months post-randomisation, and the intervention group must be compared with a group that received no intervention/placebo or minimal intervention. Trials restricting recruitment to participants with current LBP were excluded.

Results

27 published reports of 25 different trials including a total of 8341 participants fulfilled the inclusion criteria. The pooled results, from three RCTs (612 participants), found moderate-quality evidence that an exercise programme can prevent future LBP intensity (mean difference (MD) −4.50; 95% CI −7.26 to −1.74), and from 4 RCTs (471 participants) that an exercise and education programme can prevent future disability due to LBP (MD −6.28; 95% CI −9.51 to −3.06). It is uncertain whether prevention programmes improve future quality of life (QoL) and workability due to the overall low-quality and very low-quality available evidence.

Conclusions

This review provides moderate-quality evidence that an exercise programme, and a programme combining exercise and education, are effective to reduce future LBP intensity and associated disability. It is uncertain whether prevention programmes can improve future QoL and workability. Further high-quality RCTs evaluating prevention programmes aiming to reduce future impact of LBP are needed.
Motivating doctors into leadership and management: a cross-sectional survey
Authors: Bäker Agnes , Bech Mickael , Geerts Jaason , Maigaard Axelsen Susanne , Ullum Henrik , Krabbe Marie P , Goodall Amanda H
Published: July 2020

Purpose

Calls for doctors to enter management are louder as the benefits of medical leadership become clearer. However, supply is not meeting demand. This study asks doctors (physicians): what might encourage you to go into leadership, and what are the disincentives? The same was asked about leadership training. First, the paper tries to understand doctors’ motivation to lead, specifically, to explore the job characteristics that act as incentives and disincentives. Second, the study points to organisational obstacles that further shrink the medical leadership pipeline.

Method

Doctors were surveyed through the Organization of Danish Medical Societies. Our key variables included: (1) the incentives and disincentives for doctors of going into leadership and management and (2) the motivation to participate in leadership training. Our sample of 3534 doctors (17% response) is representative of the population of doctors in Denmark.

Findings

The main reason why doctors are motivated towards leadership is to make a difference. They are put off by fears of extra administration, longer hours, burnout, lack of resources and by organisational cultures resistant to change. However, doctors are aware of their need for leadership development prior to entering management.

Practical implications

To improve succession planning, health systems should adapt to reflect the incentives of their potential medical leaders. Leadership training is also essential. These changes are especially important now; medical leaders are linked positively to organisational and patient outcomes and have been central in responding to COVID-19, stress and burnout among clinical staff continues to rise, and health systems face recruitment and retention challenges.
How to fairly incentivise digital contact tracing
Authors: Loi Michele
Published: July 2020

Digital apps using Bluetooth to log proximity events (henceforth, digital contact tracing) are increasingly supported by technologists and governments. By and large, the public debate on this matter focuses on privacy, with experts from both law and technology offering very concrete proposals and participating to a lively debate. Far less attention is paid to effective incentives and their fairness. This paper aims to fill this gap by offering a practical, workable solution for a promising incentive, justified by the ethical principles of non-maleficence, beneficence, autonomy and justice. This incentive is a free phone optimised for running such app.
Shear wave elastography and microvascular ultrasound in response evaluation to calcipotriol+betamethasone foam in plaque psoriasis
Authors: Guazzaroni Manlio , Ferrari Donatella , Lamacchia Feliciana , Marisi Vanessa , Tatulli Doriana , Marsico Salvatore , Orlacchio Antonio , Floris Roberto , Bianchi Luca , Dattola Annunziata
Published: July 2020

Psoriasis (PsO) is a chronic skin disease. This study aims to evaluate clinical and subclinical response to calcipotriol+betamethasone foam, in patients with PsO, comparing, for the first time, data from microvascular ultrasound (MicroV) and shear wave elastography (SWE) with Psoriasis Area and Severity Index (PASI).

Methods

Between November 2018 and April 2019 in Tor Vergata Hospital (Roma, Italy), we enrolled 26 patients with PsO who were ageds 20–75 years, with PASI score ≥4, candidated for calcipotriol+betamethasone foam treatment. They underwent MicroV and SWE evaluation at baseline (T0) and after 4 weeks of treatment (T4). Clinical follow-up was carried on at T4, T8 and T12. Student’s t-test (p values<0.05 statistically significant) was used to compare SWE and PASI values.

Results

At T0, SWE stiffness values of target plaques (61.5% on elbows, 23% knees, 7.7% sacrum,7.7% legs) were significantly higher than values under healthy skin. At T4, all patients showed a significant reduction of PASI; MicroV showed reduction in vascularisation of responsive plaques in 85% of cases, only in 15%, the vascularisation degree remained stable; and SWE values of target plaques were significantly lower compared with T0. Only in 7.7%, there was a relapse at T12.

Conclusions

Calcipotriol+betamethasone foam is a very effective topical treatment in a short-medium term follow-up in patients with PsO. MicroV and SWE evaluate response to treatment (in term of plaque vascularisation and stiffness), so they could represent promising early indicators of therapeutic response and help the physician to establish a better clinical-therapeutic management of patients with PsO.
Trends of lymphoma incidence in US veterans with rheumatoid arthritis, 2002–2017
Authors: Singh Namrata , Gao Yubo , Field Elizabeth , Link Brian K , Weiss Noel , Curtis Jeffrey R , Lynch Charles F , Vaughan-Sarrazin Mary
Published: July 2020

Objective

Past epidemiological studies have consistently demonstrated a link between rheumatoid arthritis (RA) and the incidence of lymphoma and it has been posited that high systemic inflammatory activity is a major risk determinant of lymphomagenesis. Given advances in the therapeutic armamentarium for RA management in recent years, the resulting lower level of disease activity could have led to a decline in lymphoma incidence in patients with RA. This study examined recent trends in lymphoma incidence in US veterans with RA.

Methods

Patients with RA were identified in the Veterans Affairs (VA) Corporate Data Warehouse. Lymphoma incidence was identified through the end of 2018 from the VA Central Cancer Registry and compared among patients diagnosed during 2003–2005, 2006–2008, 2009–2011 and 2012–2014.

Results

Among persons diagnosed with RA during 2003–2005, the incidence of lymphoma in the next 6 years was 2.0 per 1000 person-years. There was a steady decline in lymphoma incidence during the corresponding 6 years following diagnosis in the subsequent three cohorts, with a rate of 1.5 per 1000 person-years in the 2012–2014 cohort (incidence relative to that in the 2003–2005 cohort=0.79 (95% CI 0.58 to 1.1)). There was no similar decline in lymphoma incidence in VA patients diagnosed with osteoarthritis.

Conclusion

We observed a decline in lymphoma incidence in recent years among American veterans with RA. Further studies are needed to evaluate the specific factors driving this decline.
Thermodynamic properties of glassy phonon states induced by strong electron correlations in 𝜃-type organic charge transfer salts
Authors: Nomoto T. , Yesil E. , Yamashita S. , Akutsu H. , Nakazawa Y.
Published: July 2020

The appearance of electron correlations–induced glassy state of low-energy phonons in the non-dimeric organic charge transfer salt in [Formula: see text]-(BEDT-TTF)2CsZn(SCN)4 is considered as a strong evidence of charge lattice coupling in molecular charge transfer salts. We discuss the temperature and the magnetic field dependences of the heat capacity of this salt in terms of the soft potential model to describe the thermodynamic properties of enhanced phonons that occur in molecular glasses. The evaluated [Formula: see text] term of [Formula: see text]-(BEDT-TTF)2CsZn(SCN)4 is about 30 mJ K[Formula: see text] mol[Formula: see text], which is much larger than other charge transfer salts described by the low-temperature approximation of the Debye model. The magnetic fields dependence of the boson peak is almost negligible, but the low-energy term, for example, in the temperature-linear term of heat capacity shows a slight change, probably due to the small amount of localized spin moments. The comparison with other systems is also performed.
Rateless Codes for Near-Perfect Load Balancing in Distributed Matrix-Vector Multiplication
Authors: Mallick Ankur , Chaudhari Malhar , Sheth Utsav , Palanikumar Ganesh , Joshi Gauri
Published: July 2020

Large-scale machine learning and data mining applications require computer systems to perform massive matrix-vector and matrixmatrix multiplication operations that need to be parallelized across multiple nodes. The presence of stragglers - nodes that unpredictably slowdown or fail - is a major bottleneck in such distributed computations. We propose a rateless fountain coding strategy to address this issue. Our idea is to create linear combinations of the m rows of the matrix and assign these encoded rows to different worker nodes. The original matrix-vector product can be decoded as soon as slightly more than m row-vector products are collectively finished by the nodes.We show that our approach achieves optimal latency and performs zero redundant computations asymptotically. Experiments on Amazon EC2 show that rateless coding gives as much as 3× speed-up over uncoded schemes.
Computation Through Neural Population Dynamics
Authors: Vyas Saurabh , Golub Matthew D. , Sussillo David , Shenoy Krishna V.
Published: July 2020

Significant experimental, computational, and theoretical work has identified rich structure within the coordinated activity of interconnected neural populations. An emerging challenge now is to uncover the nature of the associated computations, how they are implemented, and what role they play in driving behavior. We term this computation through neural population dynamics. If successful, this framework will reveal general motifs of neural population activity and quantitatively describe how neural population dynamics implement computations necessary for driving goal-directed behavior. Here, we start with a mathematical primer on dynamical systems theory and analytical tools necessary to apply this perspective to experimental data. Next, we highlight some recent discoveries resulting from successful application of dynamical systems. We focus on studies spanning motor control, timing, decision-making, and working memory. Finally, we briefly discuss promising recent lines of investigation and future directions for the computation through neural population dynamics framework.
Finding the Brain in the Nose
Authors: Brann David H. , Datta Sandeep Robert
Published: July 2020

Olfaction is fundamentally distinct from other sensory modalities. Natural odor stimuli are complex mixtures of volatile chemicals that interact in the nose with a receptor array that, in rodents, is built from more than 1,000 unique receptors. These interactions dictate a peripheral olfactory code, which in the brain is transformed and reformatted as it is broadcast across a set of highly interconnected olfactory regions. Here we discuss the problems of characterizing peripheral population codes for olfactory stimuli, of inferring the specific functions of different higher olfactory areas given their extensive recurrence, and of ultimately understanding how odor representations are linked to perception and action. We argue that, despite the differences between olfaction and other sensory modalities, addressing these specific questions will reveal general principles underlying brain function.
In Vitro and Randomized, Double‐Blind, Placebo‐Controlled Trial to Determine the Efficacy and Safety of Nine Antiacne Medicinal Plants
Authors: Said Omar , Khamaysi Iyad , Kmail Abdalsalam , Fulder Stephen , AboFarekh Basheer , Amin Riyad , Daraghmeh Jamila , Saad Bashar
Published: July 2020

The present in vitro and randomized, double‐blind, placebo‐controlled trial aims to determine the efficacy and safety of nine Mediterranean antiacne medicinal plants. The antimicrobial, antisebum, and anti‐inflammatory activities of the plant extracts were evaluated in cells from the immortalized human keratinocytes (HaCaT) and human monocytic cell line (THP‐1) as well as in a double‐blind, randomized, and placebo‐controlled trial. Most of the extracts showed no significant cytotoxic effects on HaCaT cells up to 250 μg/ml. Inula helenium (IH) and Saponaria officinalis (SO) inhibited sebum production at 90 μg/ml and 30 μg/ml, respectively. The inhibition effect of SO on the growth of Cutibacterium acnes was 1.2 times higher than that of chloramphenicol. IH and SO extracts significantly inhibited the lipopolysaccharide‐ (LPS‐) induced IL‐6 and TNF‐α production in THP‐1 cells reaching the control levels of untreated cells at a concentration of 250 μg/ml. SO, IH, and Solanum nigrum (SN) extracts inhibited the nitric oxide (NO) production in a dose‐dependent manner. Based on these results, an antiacne herbal cream (AHC) was prepared from different portions of extracts from SO, IH, and SN, and its efficacy was evaluated in a double‐blind, randomized, and controlled efficacy study with 41 acne patients, ages 18–24, who were asked to apply AHC (n = 27) or a placebo (n = 14) two to three times daily for six weeks. Results obtained indicate that the AHC has unique synergistic effects that halt sebum production, combined with highly antiseptic and anti‐inflammatory activity, in which 54.95% (t = 19.37 P < 0.001) of acne inflammatory and noninflammatory lesions disappeared after two weeks, 85.3%, after five weeks (t = 14.19 P < 0.001), and 91.4%, at the end of the sixth week of application (t = 5.7 P < 0.001). In conclusion, SO, IH, and SN as single extracts and in combination as AHC showed significant antimicrobial, antisebum, and anti‐inflammatory activities in vitro and in a double‐blind, randomized, and controlled antiacne efficacy. Therefore, AHC represents an interesting alternative treatment for acne.
Fournier Gangrene Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Pharmacovigilance Study with Data from the U.S. FDA Adverse Event Reporting System
Authors: Hu Yang , Bai Ziyu , Tang Yan , Liu Rongji , Zhao Bin , Gong Jian , Mei Dan
Published: July 2020

Background. The U.S. Food and Drug Administration (FDA) released a safety warning of Fournier gangrene (FG), a rare but serious adverse effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors in August 2018. However, existing studies have focused mainly on individual FG case reports. Although several previous studies conducted reviews of cases, objective scientific analysis was not applied, and the prognosis data were inadequate. Objective. This study is aimed at presenting data supplementary to existing studies by analysing postmarketing adverse event reports in the FDA Adverse Events Reporting System (FAERS) database. Multiple statistical analysis methods were applied to evaluate the potential association between SGLT2 inhibitors and FG, thus providing reliable and professionalized medication usage recommendations for SGLT2 inhibitors in clinical practice. Methods. Disproportionality analysis and Bayesian analysis were applied for data mining among the suspected adverse event reports of FG associated with SGLT2 inhibitors recorded in the FAERS database during the period from January 2004 to September 2019. Results. There were 542 FG cases identified in the FAERS database in patients receiving SGLT2 inhibitors. Among all SGLT2 inhibitor therapies, empagliflozin was associated with the highest number of FG reports (232 in total), while empagliflozin plus metformin had the strongest association with FG occurrence with the reporting odds ratio (ROR 54.79, 95% two-sided CI 31.56 to 95.12) and proportional reporting ratio (PRR 53.36, χ2 666.70). There were 391 patients who underwent initial or prolonged hospitalization (72.14%), and 26 patients died (4.81%). Three new FG cases caused by ertugliflozin were found in 2019. Conclusion. The analysis of SGLT2 inhibitor-associated FG reports in the FAERS database identified signals between the drug and adverse events of interest. It also provides comprehensive information on the characteristics of FG onset and prognosis. Clinicians should pay more attention to this rare but severe adverse event when prescribing SGLT2 inhibitors in clinical practice.
Tumor Primary Location May Affect Metastasis Pattern for Patients with Stage IV NSCLC: A Population-Based Study
Authors: Shan Qinge , Li Zhenxiang , Lin Jiamao , Guo Jun , Han Xiao , Song Xinyu , Wang Haiyong , Wang Zhehai
Published: July 2020

Background. Most patients with nonsmall cell lung cancer (NSCLC) were initially diagnosed with distant metastasis. At present, there is no study to clarify the correlation between the primary location of the tumor and the metastasis pattern in advanced NSCLC. So we conducted this study to explored the relationship between the tumor primary location and metastasis pattern in stage IV NSCLC. Methods. A total of 19,295 eligible patients were identified from 2010 to 2012 in the SEER database. The main endpoint of our study was overall survival (OS). The survival curves were created by using the Kaplan–Meier method and compared by the usage of the Log Rank test. The clinical variable characteristics were compared by the chi-square test, and multivariate logistic regression analyses were used to evaluate the risk factors on metastasis patterns. All statistical P values were two-sided, and it was considered statistically significant when P≤0.05. Results. We found that different proportions of metastatic sites could be found in different tumor primary locations. In addition, the prognosis of lung metastasis was relatively good in patients with tumor location in main bronchus P<0.001, upper lobe P<0.001, lower lobe P<0.001 , and middle lobe P=0.005. Besides, there was no significant OS difference for patients whose primary location was overlapping lesion P=0.226. The results also demonstrated that compared with patients with primary tumor located in the main bronchus, those in the upper lobe were more likely to have brain metastasis P=0.01 and lung metastasis P=0.024, those in the middle lobe were more prone to develop lung metastasis P=0.035 and those in the lower lobe were more apt to cause bone metastasis P=0.005 and lung metastasis P=0.001. In addition, there was no statistical difference in metastasis patterns among patients with overlapping lesions P>0.05. Conclusions. Different primary tumor locations might affect the metastasis pattern in patients with stage IV NSCLC.
An Energy-Saving Output Feedback Control of Single-Rod Electrohydraulic Servo System with Disturbance Observer
Authors: Wang Yunfei , Zhao Jiyun , Ding Haigang , Man Jiaxiang
Published: July 2020

Single-rod electrohydraulic system is widely applied in industrial production due to high power-to-weight ratio, but it generally has a low energy efficiency and has many system states which need to be measured. Therefore, an output feedback controller with energy saving is proposed in this paper. The designed controller only needs a displacement sensor to detect the position of the single-rod cylinder; the other states of the system are estimated by extended state observer (ESO). Besides, a nonlinear disturbance observer (NDO) is introduced to estimate the external mismatched disturbance. The output feedback controller based on extended state observer and nonlinear disturbance observer has a better tracking performance compared with other controllers. In addition, a proportional relief valve (PRV) is introduced to control the supply pressure of the system. The variable supply pressure reduces the energy of throttling loss and overflow loss, which achieves energy saving of about 54% according to the simulation results. Meanwhile, the tracking error of the energy saving controller is stable at 0.1 mm. In a word, the proposed controller not only achieves energy saving but also has a satisfactory trajectory tracking performance.
Clinical Outcomes of Micropulse Transscleral Cyclophotocoagulation in Patients with a History of Keratoplasty
Authors: Lee Jun Hui , Vu Vivian , Lazcano-Gomez Gabriel , Han Katherine , Suvannachart Pukkapol , Rose-Nussbaumer Jennifer , Schallhorn Julie , Hwang David , Han Ying
Published: July 2020

Purpose. To examine the surgical outcomes and graft conditions in patients receiving micropulse transscleral cyclophotocoagulation (MP-TSCPC) to treat post-keratoplasty ocular hypertension. Methods. This retrospective observational study included 30 eyes of 28 consecutive glaucoma patients with a history of penetrating keratoplasty (PKP) or Descemet’s stripping automated endothelial keratoplasty (DSAEK) who underwent MP-TSCPC at the University of California, San Francisco from 09/2015 to 08/2018. Using the Wilcoxon signed-rank test, we compared preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, visual acuity, and central corneal thickness at 1, 3, 6, and 12 months. Postoperative complications, additional surgeries, and graft failures were also recorded at these follow-up times. Linear regression model was used to study whether PKP vs. DSAEK affects the effectiveness of MP-TSCPC. Results. Thirty eyes from 28 patients were followed for 12 months. IOP was significantly decreased from preop at all follow-up points (P<0.001). There was no significant change in the number of glaucoma drops, visual acuity, or CCT. At 12 months, 21 of the 30 eyes met the definition of success, and only one underwent repeat PKP due to graft rejection. The type of corneal transplant was not a significant factor for IOP reduction at the last follow-up. Conclusions. MP-TSCPC achieved desirable IOP control and success rates for postkeratoplasty patients while resulting in minimal complications and graft failure. It appears to be a safe and effective procedure in patients who received corneal transplant with one-year follow-up.
A Novel Prediction Model for Significant Liver Fibrosis in Patients with Chronic Hepatitis B
Authors: Chen Yaqiong , Gong Jiao , Zhou Wenying , Jie Yusheng , Li Zhaoxia , Chong Yutian , Hu Bo
Published: July 2020

Background. Preventing liver fibrosis from progressing to cirrhosis and even liver cancer is a key step in the treatment of chronic hepatitis B (CHB). This study is aimed at constructing and validating a new nomogram for predicting significant liver fibrosis (S ≥ 2) in CHB patients. Methods. The nomogram was based on a retrospective study of 252 CHB patients. The predictive accuracy and discriminative ability of the nomogram were evaluated by the area under receiver operating characteristic curve (AUROC), decision curves, and calibration curve compared with the fibrosis 4 score (FIB‐4) and aspartate aminotransferase‐to‐platelet ratio index (APRI). The results were validated using bootstrap resampling and an external set of 168 CHB patients. Results. A total of 420 CHB patients were enrolled based on liver biopsy results. Independent factors predicting significant liver fibrosis were laminin (LN), procollagen type III N‐terminal peptide (PIIINP), and blood platelet count (PLT) in a multivariate analysis, and these factors were selected to construct the nomogram. The calibration curve for the probability of significant liver fibrosis showed optimal agreement between the prediction from the nomogram and actual observation. The prediction from the nomogram was more consistent with the results of liver biopsy than FIB‐4 and APRI. The AUROC of the nomogram was higher than that of FIB‐4 and APRI for predicting significant liver fibrosis. These results were confirmed in the validation set. Furthermore, the decision curve analysis suggested that the most net benefits were provided by the nomogram. Conclusions. We found the proposed nomogram resulted in a more accurate prediction of significant liver fibrosis in CHB patients and could provide the most net benefits. We recommend this noninvasive assessment for patients with liver fibrosis to avoid the risk of liver biopsy and earlier intervention to prevent the development of cirrhosis or liver cancer.
Fault Diagnosis Method of Power Electronic Converter Based on Broad Learning
Authors: Han Ran , Wang Rongjie , Zeng Guangmiao
Published: July 2020

In order to realize the unsupervised extraction and identification of fault features in power electronic circuits, we proposed a fault diagnosis method based on sparse autoencoder (SAE) and broad learning system (BLS). Firstly, the feature is extracted by the sparse autoencoder, and the fault samples and feature vectors are combined as the input of the broad learning system. The broad learning system is trained based on the error precision step update method, and the system is used to the fault type identification. The simulation results of the thyristor fault diagnosis of the three-phase bridge rectifier circuit show that the method is effective and has better performance than other traditional methods.