bluuebunny/crossref_metadata_2025 huggingface dataset:
The silent occurrence of cerebral small vessel disease in nonelderly patients with type 2 diabetes mellitus
Authors: Fang Fang , Cao Rong , Luo Qian , Ge Renbin , Lai Mengyu , Yang Jiaying , Ma Mingming , Kang Mei , Zhang Lei , Wang Yufan , Peng Yongde
Published: February 2021

Background

The prevalence of cerebral small vessel disease (SVD) increases in elderly patients with type 2 diabetes (T2DM), exacerbating cognitive decline. However, the prevalence and the severity of SVD in dementia‐free nonelderly T2DM patients were largely unknown. Our primary aim is to investigate SVD in such patients, with a specific focus on the correlation between SVD and diabetic peripheral sensorimotor polyneuropathy (DSP).

Methods

We recruited 180 young and middle‐aged subjects without cognitive impairment (106 with T2DM, 74 controls). Signs of cerebral SVD on magnetic resonance image were investigated, and the overall SVD burden was evaluated by a combined score. Patients with T2DM underwent further detailed DSP assessment. Regression models were used to investigate the association of SVD with the presence of T2DM, and the associations of the prevalence and severity of SVD and DSP were also explored in patients with T2DM.

Results

The prevalence of microbleeds and overall burden of SVD were significantly higher in T2DM patients than in the controls. Further, the presence of DSP related to an increased risk of SVD after adjustment in diabetic group. Moreover, Toronto Clinical Scoring System values were positively associated with the increased SVD scores, and bilateral sural sensory nerve conduction velocities were negatively associated with increasingly severity of SVD scores.

Conclusion

The current findings extended the increasing prevalence of SVD to dementia‐free nonelderly patients with T2DM, suggesting that the time for cognitive screening and prevention might be moved forward in T2DM patients, especially for those with DSP.
Identifying flow modules in ecological networks using Infomap
Authors: Farage Carmel , Edler Daniel , Eklöf Anna , Rosvall Martin , Pilosof Shai
Published: February 2021

Analysing how species interact in modules is a fundamental problem in network ecology. Theory shows that a modular network structure can reveal underlying dynamic ecological and evolutionary processes, influence dynamics that operate on the network and affect the stability of the ecological system.

Although many ecological networks describe flows, such as biomass flows in food webs or disease transmission, most modularity analyses have ignored network flows, which can hinder our understanding of the interplay between structure and dynamics.

Here we present Infomap, an established method based on network flows to the field of ecological networks. Infomap is a flexible tool that can identify modules in virtually any type of ecological network and is particularly useful for directed, weighted and multilayer networks. We illustrate how Infomap works on all these network types. We also provide a fully documented repository with additional ecological examples. Finally, to help researchers to analyse their networks with Infomap, we introduce the open‐sourceRpackageinfomapecology.

Analysing flow‐based modularity is useful across ecology and transcends to other biological and non‐biological disciplines. A dynamic approach for detecting modular structure has strong potential to provide new insights into the organisation of ecological networks.
Adding vaping restrictions to smoke‐free air laws: associations with conventional and electronic cigarette use
Authors: Friedman Abigail S. , Oliver Jon F. , Busch Susan H.
Published: February 2021

Background and Aims

In the United States, some states and localities have added vaping restrictions to established smoke‐free indoor air laws in order to reduce electronic cigarette use. Yet, if smokers use e‐cigarettes to quit, such restrictions could have the unintended effect of attenuating the original smoke‐free air policy’s effects on smoking. This study estimated changes in current smoking, past‐year smoking cessation, and recent vaping following the introduction of smoke‐ and vape‐free air laws.

Design

Observational study of nationally representative data from the 2014–2018 National Health Interview Survey.

Setting

United States.

Participants/Cases

87 334 participants, 18–54 years of age.

Measurements

Multivariable linear regressions estimated the association between increased exposure to smoke‐ and vape‐free worksite and restaurant laws and self‐reported current smoking and recent vaping among emerging adults (ages 18–25), as well as past‐12‐month smoking cessation among prime age adults (ages 26–54). All regressions adjusted for respondent sociodemographic and other tobacco control policies, along with state and year fixed effects.

Findings

Smoke‐free worksite laws were associated with significant reductions in the likelihood of current smoking (
 = − 0.050, 95% CI: −0.098, −0.002, P = 0.038) and recent vaping (
 = − 0.040, 95% CI: −0.072, −0.007, P = 0.013), as well as increases in the likelihood of smoking cessation (
 = 0.026, 95% CI: 0.000, 0.052, P = 0.046). Adding vaping restrictions to smoke‐free worksite laws did not yield further reductions in recent vaping (
 = 0.008, 95% CI: −0.021, 0.036, P = 0.568) and counteracted over half of the estimated association with current smoking relative to smoke‐free policies alone (
 = 0.030, 95% CI: −0.028, 0.088, P = 0.301).

Conclusions

From 2014 to 2018, increased adoption of smoke‐free worksite laws in the United States was associated with reductions in both current smoking and recent vaping, as well as increases in smoking cessation. Adding vaping restrictions to smoke‐free worksite laws, however, was not associated with a reduction in recent vaping among emerging adults and may have attenuated the smoke‐free policy’s impact on current smoking in this age group.
Can demographic rates of early development stages justify invasion success among three pine species in the Cerrado biodiversity hotspot?
Authors: Miashike Roseli Lika , Kortz Alessandra Rocha , Zarate do Couto Hilton Thadeu , Pivello Vania Regina
Published: February 2021

Recognising which life‐history factors can potentially explain the success of biological invasions is essential to understand why certain exotic species are more successful to invade a given system than others, and also to better predict invasion outcomes. We focused on the three most planted pine tree species in Southern Brazil – Pinus elliottii, P. caribaea and P. oocarpa – as a natural system to test the hypothesis that some key vital attributes – fecundity (number of seeds produced), seed viability, germinability, seedling growth vigour (biomass and stem length) – could be driving the greater invasion of P. elliottii in the region. We collected seeds of P. elliottii var. elliottii, P. caribaea subsp. hondurensis and P. oocarpa in two sites of similar climate and soil in the Cerrado biodiversity hotspot. Seeds were tested for viability and germinability, and seed production was estimated. Under laboratory conditions, we evaluated seedling survival, stem and root development, biomass production and mortality for each species. Although P. elliottii is regarded as the most successful invasive pine species in the Cerrado, it did not outperform the other pines in terms of seed viability, germinability and seedling survival, and it had the slowest growth. P. elliottii did produce, however, at least twice as many seeds as the other species. P. caribaea revealed high seed viability and seedling survival, the fastest seedling development, but low seed production. P. oocarpa showed the lowest seed viability, but fast root growth and very low seedling mortality. Our results suggest seed production is a key factor for P. elliottii invasion success. However, given the strong performance of P. caribaea and P. oocarpa for germinability and growth, we emphasise the risk of both species also becoming successful invaders in the Cerrado. We highlight the need for constant monitoring of emerging pine individuals in native ecosystems to avoid future invasions.
A decellularized oocyte‐derived scaffold provides a “sperm safe” to preserve mammalian spermatozoa
Authors: Lee Hoi Chang , Balough Julia L. , Roth Eric W. , Vaccari Sergio , Duncan Francesca E.
Published: February 2021

Background

Although only one spermatozoon is needed to create a zygote, a significant challenge is the storage and recovery of germ cells when sperm counts are extremely low.

Objectives

We engineered an oocyte‐derived biomaterial—the zona pellucida (ZP)—as a “sperm safe” for storing spermatozoon. The ZP is a glycoprotein matrix that surrounds the mammalian oocyte.

Materials and Methods

We made a hole in the ZPs using a Piezo drill and mechanically separated them from the oocyte cytoplasm. A subset of ZPs were further purified through decellularization. Using a modified ICSI approach, we injected sperm heads into purified ZPs and tested the efficacy of cryopreservation and recovery of spermatozoon as well as function.

Results

Between 1–6 sperm heads were injected into purified ZPs (average 2.7 ± 1.7 sperm heads/ZP), which were then cryopreserved. Upon thawing, an average of 2.5 ± 1.4 sperm heads/ZP were observed, and in 11 of 12 thawed “sperm safes,” we recovered all spermatozoa. Decellularized “sperm safes” maintained their three‐dimensional structure and had a denser matrix relative to untreated controls as assessed by scanning and transmitted electron microscopy. The efficacy of “sperm safe” derived spermatozoon was evaluated by ICSI. Spermatozoon stored in either untreated or decellularized “sperm safes” elicited egg activation‐associated calcium transients and zinc sparks when injected into eggs. Of the resulting zygotes, >80% of them formed pronuclei irrespective of the sperm source. 26.8 ± 4.6% and 18.1 ± 7.0% of the pre‐implantation embryos generated from spermatozoon recovered from untreated or decellularized “sperm safes” developed to the blastocyst stage, respectively. Although this development was lower than that using fresh spermatozoon (59.3 ± 19.3%) or conventionally frozen‐thawed spermatozoon (28.4 ± 1.7%), these differences were not significant.

Discussion and Conclusion

Purified ZPs represent a natural biomaterial for the efficient preservation and recovery of small sperm numbers.
Maternal and perinatal outcomes related to COVID‐19 and pregnancy: An overview of systematic reviews
Authors: Vergara‐Merino Laura , Meza Nicolás , Couve‐Pérez Constanza , Carrasco Cynthia , Ortiz‐Muñoz Luis , Madrid Eva , Bohorquez‐Blanco Sandra , Bracchiglione Javier
Published: February 2021

Introduction

Evidence about coronavirus disease 2019 (COVID‐19) and pregnancy has rapidly increased since December 2019, making it difficult to make rigorous evidence‐based decisions. The objective of this overview of systematic reviews is to conduct a comprehensive analysis of the current evidence on prognosis of COVID‐19 in pregnant women.

Material and methods

We used the Living OVerview of Evidence (L·OVE) platform for COVID‐19, which continually retrieves studies from 46 data sources (including PubMed/MEDLINE, Embase, other electronic databases, clinical trials registries, and preprint repositories, among other sources relevant to COVID‐19), mapping them into PICO (population, intervention, control, and outcomes) questions. The search covered the period from the inception date of each database to 13 September 2020. We included systematic reviews assessing outcomes of pregnant women with COVID‐19 and/or their newborns. Two authors independently screened the titles and abstracts, assessed full texts to select the studies that met the inclusion criteria, extracted data, and appraised the risk of bias of each included systematic review. We measured the overlap of primary studies included among the selected systematic reviews by building a matrix of evidence, calculating the corrected covered area, and assessing the level of overlap for every pair of systematic reviews.

Results

Our search yielded 1132 references. 52 systematic reviews met inclusion criteria and were included in this overview. Only one review had a low risk of bias, three had an unclear risk of bias, and 48 had a high risk of bias. Most of the included reviews were highly overlapped among each other. In the included reviews, rates of maternal death varied from 0% to 11.1%, admission to intensive care from 2.1% to 28.5%, preterm deliveries before 37 weeks from 14.3% to 61.2%, and cesarean delivery from 48.3% to 100%. Regarding neonatal outcomes, neonatal death varied from 0% to 11.7% and the estimated infection status of the newborn varied between 0% and 11.5%.

Conclusions

Only one of 52 systematic reviews had a low risk of bias. Results were heterogeneous and the overlap of primary studies was frequently very high between pairs of systematic reviews. High‐quality evidence syntheses of comparative studies are needed to guide future clinical decisions.
Benefits and potential harms of human papillomavirus (HPV)‐based cervical cancer screening: A real‐world comparison of HPV testing versus cytology
Authors: Thomsen Louise T. , Kjær Susanne K. , Munk Christian , Ørnskov Dorthe , Waldstrøm Marianne
Published: February 2021

Introduction

Human papillomavirus (HPV) testing as the primary cervical cancer screening method is implemented in several countries. We report data from the first round of a large Danish pilot implementation of HPV‐based screening. Our aim was to compare colposcopy referrals, detection of high‐grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposcopy referral in HPV vs cytology‐based screening.

Material and methods

From May 2017 to October 2018, women aged 30‐59 years attending cervical cancer screening in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark were screened by primary HPV testing (n = 16 067) or primary cytology (n = 23 981) depending on municipality of residence. In the HPV group, women with HPV16/18, or other high‐risk HPV types and abnormal cytology, were referred to immediate colposcopy. Women with other high‐risk HPV types and normal cytology were invited for repeat screening with HPV test and cytology after 12 months. From a nationwide pathology register, we obtained information on screening results and subsequent histological diagnoses during up to 2.9 years after the first screen. PPVs included diagnoses within 1 year after referral.

Results

In the HPV group, 3.7% were referred to immediate colposcopy and 2.8% were referred at the 12‐month repeat screening. The total referral to colposcopy was higher in the HPV (6.6%) than cytology group (2.1%) (age‐adjusted relative referral = 3.05, 95% confidence interval [CI] 2.75‐3.38). The detection of CIN3+ was higher in the HPV (1.5%) than the cytology group (0.8%) (age‐adjusted relative detection = 1.88, 95% CI 1.56‐2.28). The probability of CIN3+ among women referred to colposcopy (= PPV) was lower in the HPV (21.1%; 95% CI 18.7%‐23.7%) than the cytology group (34.6%; 95% CI 30.7%‐38.9%). In the HPV group, the PPV was lower among women referred at repeat screening (12.1%) than among women referred immediately (27.8%).

Conclusions

Compared with cytology‐based screening, HPV‐based screening provided a 90% increased CIN3+ detection at the cost of a threefold increase in colposcopy referrals, when considering complete data from the prevalence round. Our findings support implementation of HPV‐based screening in Denmark, but modifications of screening algorithms may be warranted to decrease unnecessary colposcopy referrals.
Effective glutamate clearance from the systemic circulation by hemodialysis: Potential relevance for cerebral ischemia management
Authors: Martínez‐Miguel Patricia , Albalate Marta , Durán‐Laforet Violeta , Peña‐Martínez Carolina , de Sequera Patricia , Bouarich Hanane , Peña‐Esparragoza Korina , López‐Ongil Susana , Lizasoain Ignacio , Sánchez‐Prieto José , Torres Magdalena , Moro María Ángeles , Rodríguez‐Puyol Diego
Published: February 2021

High glutamate levels after head trauma or cerebral ischemia have neurotoxic effects. The objective of the present study was to evaluate the efficacy of hemodialysis to remove glutamate from the blood and to assess the behavior of this small molecule. Ten patients with end‐renal disease on hemodialysis were included in the study. Glutamate clearance was evaluated within the first hour of hemodialysis on a midweek dialysis day on five patients who underwent low flux hemodialysis, whereas the other five patients underwent highly efficient hemodialysis (high flux hemodialysis on one day and online hemodiafiltration on another day). Glutamate clearance with hemodialysis was very effective and did not show any differences between the techniques (low flux: 214 [55], high flux: 204 [37], online hemodiafiltration: 202 [16], median (interquartile range), P = .7). Glutamate clearance was almost equivalent to vascular access plasma flow and it was not affected by dialyzer permeability or ultrafiltration rate. After a hemodialysis session, a significant decrease in glutamate blood level was observed (prehemodialysis: 59.7 [36.1], posthemodialysis 37.0 [49.2], P = .005). Dialysis performed under fasting condition showed higher glutamate reduction rate (60%) than that under feeding condition (20%). Hemodialysis may be an effective method to reduce glutamate blood levels, and the molecule clearance does not differ between the different techniques used. Considering previous results in experimental models, hemodialysis without hemodynamic stress, could be considered for reducing glutamate neurotoxic effects in acute ischemic strokes of patients in chronic hemodialysis programs.
A greater awareness of children with glucose‐6‐phosphate dehydrogenase deficiency is imperative in western countries
Authors: Kristensen Line , Lai Amanda BK. , Ebbesen Finn , Donneborg Mette L.
Published: February 2021

Aim

This national retrospective Danish study described the characteristics of children diagnosed with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, an inherited X‐linked recessive disorder that often affects children of Middle Eastern descent.

Methods

We studied children born between 1 January 2000 and 31 December 2017 and diagnosed with G6PD deficiency. They were identified from the Danish National Hospital Discharge Register and the Danish Database of Extreme Neonatal Hyperbilirubinaemia.

Results

There were 113 children diagnosed with G6PD deficiency, 67% were of Middle Eastern descent and they were frequently diagnosed before the onset of symptoms, based on known heredity. Of the 67 infants born in Denmark, 10% had extreme neonatal hyperbilirubinaemia and one developed kernicterus spectrum disorder, as did one child born in the Middle East. Most (61%) of the 33 children with jaundice received phototherapy, 12% had exchange transfusions and 18% received whole blood transfusions. After the neonatal period, 23% of the cohort had blood transfusions and 4% needed intensive care for acute haemolytic anaemia. The incidence of G6PD deficiency appeared to be severely underestimated.

Conclusion

Many families from countries where G6PD deficiency is endemic move to Denmark and other Western countries. Greater awareness is essential to avoid chronic and potentially lethal, consequences.
Outcome of dogs with intermediate grade low mitotic index high Ki67 mast cell tumours treated with surgery and single agent lomustine
Authors: Néčová S , Mason SL , North SM
Published: February 2021

Objectives

The objective of this retrospective study was to evaluate the outcome of dogs when grade II mast cell tumour (MCT) with low mitotic index (MI) and high Ki67 were treated with adjuvant lomustine.

Animals

Client owned dogs with spontaneously occurring disease treated with adjuvant chemotherapy for grade II mast cell tumour with low MI (≤5/10HPF) and high Ki67 (>1.8%) with no evidence of metastatic disease at presentation.

Procedures

Lomustine was administered every 3 weeks with three or four planned cycles. Response to treatment was assessed by regular re‐staging ultrasound with or without cytopathological examination of liver and spleen or through medical records from the referring veterinarian. Disease‐free interval (DFI) and median survival time (MST) were calculated using Kaplan–Meier method.

Results

Twenty‐one dogs were included. All dogs underwent surgical excision and two dogs received adjuvant radiotherapy. None of the patients developed local recurrence. Three dogs (14.3%) developed metastatic disease. The DFI of these dogs was 141, 186 and 223 days. Median follow‐up period of the whole study population was 1112 days (358–2619). MST for patients with metastatic disease was 417 days. MST of the whole group was not reached. One‐year and 2‐year survivals were 95.2% and 90.5%, respectively.

Conclusions and clinical relevance

This study population had low rates of tumour recurrence and improved survival compared to previously published data of similar population of dogs with low MI/high Ki67 MCT without adjuvant chemotherapy.
Congenital anomalies in breech presentation: A nationwide record linkage study
Authors: Macharey Georg , Gissler Mika , Toijonen Anna , Heinonen Seppo , Seikku Laura
Published: February 2021

Our study aimed to determine if congenital anomalies are associated with breech presentation at delivery. We conducted a nationwide, retrospective population‐based record linkage study and analyzed all singleton births in Finland from 1996 to 2016 using the mandatory health register data collected by the Finnish Institute for Health and Welfare. We compared all major congenital anomalies detected during pregnancy, birth, or the first year of life according to the fetus's presentation at the time of delivery using X2‐square statistic and Student's t test. We adjusted the results for known risk factors for congenital anomalies to estimate adjusted odds ratios and 95% confidence intervals. Fetuses in breech presentation at delivery had an increased risk for congenital anomalies (6.5%) compared with fetuses in cephalic presentation (3.6%), P < .001. Breech presentation was associated with nearly all types of examined congenital anomalies. The strongest associations were observed with congenital deformities of the hip, the central nervous system, the respiratory system, and the musculoskeletal system. Our study supports the theory that breech presentation is, in many cases, a symptom of a fundamental problem in fetal morphogenesis or function. Neonates born in the breech presentation have a higher risk of congenital anomalies and should undergo a postnatal screening.
Change in avian functional fingerprints of a Neotropical montane forest over 100 years as an indicator of ecosystem integrity
Authors: Gómez Camila , Tenorio Elkin A. , Cadena Carlos Daniel
Published: February 2021

Ecologically relevant traits of organisms in an assemblage determine an ecosystem's functional fingerprint (i.e., the shape, size, and position of multidimensional trait space). Quantifying changes in functional fingerprints can therefore provide information about the effects of diversity loss or gain through time on ecosystem condition and is a promising approach to monitoring ecological integrity. This, however, is seldom possible owing to limitations in historical surveys and a lack of data on organismal traits, particularly in diverse tropical regions. Using data from detailed bird surveys from 4 periods across more than a century, and morphological and ecological traits of 233 species, we quantified changes in the avian functional fingerprint of a tropical montane forest in the Andes of Colombia. We found that 78% of the variation in functional space, regardless of period, was described by 3 major axes summarizing body size, dispersal ability (indexed by wing shape), and habitat breadth. Changes in species composition significantly altered the functional fingerprint of the assemblage and functional richness and dispersion decreased 35–60%. Owing to species extirpations and to novel additions to the assemblage, functional space decreased over time, but at least 11% of its volume in the 2010s extended to areas of functional space that were unoccupied in the 1910s. The assemblage now includes fewer large‐sized species, more species with greater dispersal ability, and fewer habitat specialists. Extirpated species had high functional uniqueness and distinctiveness, resulting in large reductions in functional richness and dispersion after their loss, which implies important consequences for ecosystem integrity. Conservation efforts aimed at maintaining ecosystem function must move beyond seeking to sustain species numbers to designing complementary strategies for the maintenance of ecological function by identifying and conserving species with traits conferring high vulnerability such as large body size, poor dispersal ability, and greater habitat specialization.

Article impact statement: Changes in functional fingerprints provide a means to quantify the integrity of ecological assemblages affected by diversity loss or gain.
Efficacy‐based and normative interventions for facilitating the diffusion of conservation behavior through social networks
Authors: Niemiec Rebecca , Jones Megan S. , Lischka Stacy , Champine Veronica
Published: February 2021

Research suggests that encouraging motivated residents to reach out to others in their social network is an effective strategy for increasing the scale and speed of conservation action adoption. However, little is known about how to effectively encourage large numbers of residents to reach out to others about conservation causes. We examined the influence of normative and efficacy‐based messaging at motivating residents to engage in and to encourage others to participate in native plant gardening in their community. To do so, we conducted a field experiment with messages on mailings and tracked native plant vouchers used. Efficacy messages tended to be more effective than normative messages at increasing residents’ willingness to reach out to others to encourage conservation action, as indicated by a several percentage point increase in native plant voucher use by residents’ friends and neighbors. Messages sometimes had different impacts on residents based on past behaviors and perceptions related to native plant gardening. Among these subgroups, efficacy and combined efficacy and norm messages most effectively encouraged individual and collective actions, as indicated by increased voucher usage. Our findings suggest that interventions that build residents’ efficacy for engaging in a conservation behavior and for reaching out to others may be a promising path forward for outreach. However, given our results were significant at a false discovery rate cutoff of 0.25 but not 0.05, more experimental trials are needed to determine the robustness of these trends.
Decline in renal function following intestinal transplant: is the die cast at 3 months?
Authors: Rutter Charlotte S. , Russell Neil K. , Sharkey Lisa M. , Amin Irum , Butler Andrew J.
Published: February 2021

Introduction

This study reports the incidence of chronic kidney disease (CKD) after intestinal transplant (IT) at a single, adult center in the United Kingdom.

Methods

A retrospective review of IT was undertaken. Methods of renal function assessment pre‐transplant were compared. Post‐transplant renal function and renal sparing strategies were analyzed.

Results

There was a 30% variation (p < .001) in estimated glomerular filtration rate (eGFR) and normalized GFR at assessment. In the first 3 months post‐transplant, there was a 40% decline in eGFR which was irreversible. Liver inclusion was not protective with similar eGFR at 3 months (60 ml/min/1.73 m2) compared with IT (55 ml/min/1.73 m2). The rate of decline in the first 2 months was less in multivisceral transplant (MVT; 21%) than IT (52%) suggesting surgical magnitude did not contribute. Thirty percentage of recipients had acute cellular rejection post‐transplant; 58% of these were in the first 3 months with a higher proportion in MVT (64%) than IT (27%). Tacrolimus exposure did not correlate with decline in renal function over the first 3 months post‐transplant.

Conclusion

We demonstrated a 40% decline in renal function within 3 months post‐IT which was irreversible despite renal sparing strategies. Early intervention should be considered in patients with an acute decline in this post‐transplant period.
Prognostic impact and risk factors of cancer‐associated thrombosis events in stage‐IV cancer patients treated with immune checkpoint inhibitors
Authors: Kewan Tariq , Ko Taeyeong , Flores Monica , Sallam Yacoub , Haddad Abdo , Daw Hamed
Published: February 2021

Background

Cancer‐associated thrombosis (CAT) is a major cause of mortality in cancer patients. Immune checkpoint inhibitors (ICIs) have been associated with multiple side effects including CAT. The aim of this study is to investigate risk factors and prognostic impact associated with CAT events during ICIs treatment.

Methods

This is a multi‐center retrospective study that included stage IV cancer patients treated with ICIs.

Results

We identified 552 cancer patients treated with ICIs. During follow‐up time, 58 (10.5%) patients developed 67 venous thromboembolism (VTE) events while on ICIs. Anticoagulation use at the time of ICIs treatment start was associated with significantly higher VTE incidence rate (IRR: 2.23). No significant difference in VTE IRR was observed depending on response to ICIs treatment, aspirin use, or Khorana VTE risk score. Melanoma as primary cancer, Khorana score, ECOG status, and anemia at baseline were able to predict mortality.

Conclusions

The incidence of CAT in stage‐IV cancer patients treated with ICIs was higher in our study compared to previous reports. Control group of patients who did not receive ICIs is needed for better identification of CAT risk factors. Khorana score was a good predictor of mortality but not CAT risk and needs to be further validated in a homogenous group of patients.
Propagation and update of auditory perceptual priors through alpha and theta rhythms
Authors: Ho Hao Tam , Burr David C. , Alais David , Morrone Maria Concetta
Published: February 2021

To maintain a continuous and coherent percept over time, the brain makes use of past sensory information to anticipate forthcoming stimuli. We recently showed that auditory experience of the immediate past is propagated through ear‐specific reverberations, manifested as rhythmic fluctuations of decision bias at alpha frequencies. Here, we apply the same time‐resolved behavioural method to investigate how perceptual performance changes over time under conditions of stimulus expectation and to examine the effect of unexpected events on behaviour. As in our previous study, participants were required to discriminate the ear‐of‐origin of a brief monaural pure tone embedded in uncorrelated dichotic white noise. We manipulated stimulus expectation by increasing the target probability in one ear to 80%. Consistent with our earlier findings, performance did not remain constant across trials, but varied rhythmically with delay from noise onset. Specifically, decision bias showed a similar oscillation at ~9 Hz, which depended on ear congruency between successive targets. This suggests rhythmic communication of auditory perceptual history occurs early and is not readily influenced by top‐down expectations. In addition, we report a novel observation specific to infrequent, unexpected stimuli that gave rise to oscillations in accuracy at ~7.6 Hz one trial after the target occurred in the non‐anticipated ear. This new behavioural oscillation may reflect a mechanism for updating the sensory representation once a prediction error has been detected.
Supply Chains and the COVID‐19 Pandemic: A Comprehensive Framework
Authors: Magableh Ghazi M.
Published: February 2021

The Coronavirus pandemic affected activities worldwide, among which the supply chain (SC) disruptions is significant. The impact is expected to affect businesses indefinitely; thus, the SC is unlikely to resume its pre‐COVID‐19 status. This study examines the impact of the COVID‐19 pandemic on SCs regarding its disruptions, associated challenges, and trend. It conducts an analysis of SCs stages, phases, and manifestations regarding the consequences, opportunities, and developments induced by the pandemic. A framework for the SC with COVID‐19 is presented towards a future global value chain and continuous improvements. It explores and connects the relevant elements to address the relations of SC‐COVID19 (SCC19). This study is novel as it identifies, categorises, and frames the essential factors and their interrelationships in a comprehensive framework. The SCC19 framework can be of value for decision‐makers and researchers, and can be generalised to other industries. Furthermore, study limitations and future research directions are discussed.
Detection of the deep biosphere in metamorphic rocks from the Chinese continental scientific drilling
Authors: Dai Xin , Wang Yuanliang , Luo Liqiang , Pfiffner Susan M. , Li Guangyu , Dong Zhiyang , Xu Zhiqin , Dong Hailiang , Huang Li
Published: February 2021

It is generally accepted that there is a vast, well‐populated biosphere in the subsurface, but the depth limit of the terrestrial biosphere has yet to be determined, largely because of the lack of access to the subsurface. Here as part of the Chinese Continental Scientific Drilling (CCSD) project in eastern China, we acquired continuous rock cores and endeavored to probe the depth limit of the biosphere and the depth‐dependent distribution of microorganisms at a geologically unique site, that is, a convergent plate boundary. Microbiological analyses of ultra‐high‐pressure metamorphic rock cores taken from the ground surface to 5,158‐meter reveal that microbial distribution was continuous up to a depth of ~4,850 m, where temperature was estimated to be ~137°C. The metabolic state of these organisms at such great depth remains to be determined. Microbial abundance, ranging from 103 to 108 cells/g, was also related to porosity, but not to the depth and rock composition. In addition, microbial diversity systematically decreased with depth. Our results support the notion that temperature is a key factor in determining the lower limit of the biosphere in the continental subsurface.
The technocratic tendencies of economists in government bureaucracy
Authors: Christensen Johan , Mandelkern Ronen
Published: February 2021

Economists are by many accounts the most influential group of experts in contemporary political decision‐making. While the literature on the power of economists mostly focuses on the policy ideas of economic experts, some recent studies suggest that economists also hold particular technocratic ideas about the policy process. The article systematically tests this argument. Focusing on economists within government bureaucracy, the study is based on a quantitative analysis of a large‐scale survey of Norwegian ministerial civil servants. It finds that economists are more likely to hold technocratic role perceptions than officials with other educational backgrounds only if they work in the finance ministry or in higher administrative grades. The findings contribute to scholarship on the political sway of economists and to debates about technocracy and the technocratic views of civil servants.
Baseline CHA2DS2‐VASc score and prognosis in octogenarians with non‐ST segment elevation acute coronary syndrome
Authors: Díez‐Villanueva Pablo , Vera Alberto , Ariza‐Solé Albert , Formiga Francesc , Martínez‐Sellés Manuel , Alegre Oriol , Sanchís Juan , Marín Francisco , Vidán Maite , López‐Palop Ramon , Abu‐Assi Emad , Bueno Héctor , Alfonso Fernando ,   the LONGEVO‐SCA registry investigators
Published: February 2021

Background

CHA2DS2‐VASc Score is widely used to predict thromboembolic risk in patients with Atrial Fibrillation (AF). We sought to study if this score predicts outcomes in elderly patients with Non‐ST segment Elevation Acute Coronary Syndromes (NSTEACS).

Methods

The multicenter LONGEVO‐SCA prospective registry included 532 unselected patients with NSTEACS aged ≥80 years. Data to calculate CHA2DS2‐VASc Score were available in 523 patients (98.3%). They were classified according to CHA2DS2‐VASc Score: group 1 (score ≤ 4), and 2 (5‐9). We studied outcomes in terms of mortality or readmission at 6 months follow‐up.

Results

A total of 266 patients (51%) had a high CHA2DS2‐VASc Score (group 2). They were more often women, with more cardiovascular risk factors, such as hypertension or diabetes mellitus, and history of previous stroke and cardiovascular disease and heart failure (all, P = .001). Geriatric syndromes (Barthel Index, Lawton Brody, cognitive impairment, and frailty) and Charlson Index were worse in this group (all, P = .001). They had poorer clinical status on admission, with worse Killip class and lower left ventricle ejection fraction (all, P = .001), and developed new‐onset AF more often during admission (12.4% vs. 6.6%, P = .024). At six months follow‐up, patients in group 2 had higher reinfarction, all‐cause mortality, and mortality or readmission rates. A CHA2DS2‐VASc Score > 4 was associated with mortality or readmission at 6 months (HR 2.07, P < .001). However, after adjusting for potential confounders, this last association was not significant (P = .175).

Conclusions

A CHA2DS2‐VASc Score > 4 is present in half of octogenarians with NSTEACS and is associated with poorer outcomes. However, it is not an independent predictor of events and should not replace recommended tools for risk prediction in this setting.
Ontogeny and heterogeneity of innate lymphoid cells and the noncoding genome
Authors: Michieletto Michaël F. , Henao‐Mejia Jorge
Published: February 2021

Since their discovery a decade ago, it has become evident that innate lymphoid cells (ILCs) play critical roles in protective immune responses against intracellular and extracellular pathogens but are also central regulators of epithelial barrier integrity and tissue homeostasis. ILCs populate almost every tissue in mammalian organisms; therefore, not surprisingly, dysregulation of their functions contributes to the development and progression of multiple inflammatory and metabolic diseases. Our knowledge of the transcriptional programs governing the development, differentiation, and functions of the different groups of ILCs has increased dramatically in the last ten years. However, with the advent of new technologies, an unprecedented level of heterogeneity, plasticity, and developmental complexity has started to be revealed. In this review, we highlight recent advances in our understanding of ILC development and their biological functions. In particular, we aim to emphasize how our increasing knowledge of the chromatin landscape and the noncoding genome of these innate lymphocytes is allowing us to better understand their development and functions in different contexts during homeostasis and inflammation. Moreover, we propose that the design of more refined genetic tools to study tissue‐specific ILCs and their functions can be accomplished by leveraging our understanding of how specific noncoding elements of the genome regulate gene expression in ILCs.
Not too fat to fight: The emerging role of macrophage fatty acid metabolism in immunity to Mycobacterium tuberculosis
Authors: Laval Thomas , Chaumont Lise , Demangel Caroline
Published: February 2021

While the existence of a special relationship between Mycobacterium tuberculosis (Mtb) and host lipids has long been known, it remains a challenging enigma. It was clearly established that Mtb requires host fatty acids (FAs) and cholesterol to produce energy, build its distinctive lipid‐rich cell wall, and produce lipid virulence factors. It was also observed that in infected hosts, Mtb constantly resides in a FA‐rich environment that the pathogen contributes to generate by inducing a lipid‐laden “foamy” phenotype in host macrophages. These observations and the proximity between lipid droplets and phagosomes containing bacteria within infected macrophages gave rise to the hypothesis that Mtb reprograms host cell lipid metabolism to ensure a continuous supply of essential nutrients and its long‐term persistence in vivo. However, recent studies question this principle by indicating that in Mtb‐infected macrophages, lipid droplet formation prevents bacterial acquisition of host FAs while supporting the production of FA‐derived protective lipid mediators. Further, in vivo investigations reveal discrete macrophage phenotypes linking the FA metabolisms of host cell and intracellular pathogen. Notably, FA storage within lipid droplets characterizes both macrophages controlling Mtb infection and dormant intracellular Mtb. In this review, we integrate findings from immunological and microbiological studies illustrating the new concept that cytoplasmic accumulation of FAs is a metabolic adaptation of macrophages to Mtb infection, which potentiates their antimycobacterial responses and forces the intracellular pathogen to shift into fat‐saving, survival mode.
A decision tool based on bilevel optimization for the allocation of water resources in a hierarchical system
Authors: Calvete Herminia I. , Galé Carmen , Iranzo José A. , Mateo Pedro M.
Published: February 2021

This paper addresses the optimal allocation of water among competing stakeholders during a finite planning horizon. We focus on those water systems where there are two levels of decision making organized according to a hierarchical framework. At the upper level, a central authority allocates water to demand points having regard to environmental and sustainability issues as well as balancing water users' supply/demand. At the lower level of the hierarchy, demand point managers allocate water to users prioritizing economic strategies. On the other hand, when it comes to allocating limited resources that affect public welfare, the authority in charge can also use different political instruments such as fees to influence the decisions made at those levels of decision making that are not directly within its competence. We propose a multiobjective multifollower bilevel optimization problem that aims to fulfill the central authority goals while including the reaction of the demand point managers in terms of optimization problems as constraints. Using the well‐known Karush–Kuhn–Tucker approach, we transform the bilevel model into an equivalent multiobjective mixed‐integer single‐level model for which we provide tight big‐M values. For the purpose of showing the versatility of the model, extensive computational experiments on a set of instances have been carried out. The results show that the optimization problem can be solved to optimality in small computing times using off‐the‐shelf mixed‐integer solvers even for complex water systems and long planning periods. In addition, they illustrate the effect of imposing fees on the achievement of the central authority's objectives.
Efficacy of medical and ablation therapy for inappropriate sinus tachycardia: A single‐center experience
Authors: Shabtaie Samuel A. , Witt Chance M. , Asirvatham Samuel J.
Published: February 2021

Background

Effective therapy for inappropriate sinus tachycardia (IST) remains challenging with high rates of treatment failure and symptom recurrence. It is uncertain how effective pharmacotherapy and procedural therapy are long‐term, with poor response to medical therapy in general.

Methods

We retrospectively reviewed all patients with the diagnosis of IST at a tertiary academic medical center from 1998 to 2018. We extracted data related to prescribing patterns and symptom response to medical therapy and sinus node modification (SNM), assessing efficacy and periprocedural complication rates.

Results

A total of 305 patients with a formal diagnosis of IST were identified, with 259 (84.9%) receiving at least one prescription medication related to the condition. Beta‐blockers were the most commonly used medication (n = 245), with a majority of patients reporting no change or worsening of symptoms, and poor response was seen to other medication classes. Improvement was seen significantly more often with ivabradine than beta blockers, though the sample size was limited (p = .003). Fifty‐five patients (18.0% of all IST patients), mean age 32.0 ± 9.1 years, underwent a SNM procedure, with an average of 1.8 ± 0.9 procedures per patient. Acute symptomatic improvement (<6 months) was seen in 58.2% of patients. Long‐term complete resolution of symptoms was seen in 5.5% of patients, modest improvement in 29.1%, and no long‐term benefit was seen in 65.5% of patients.

Conclusions

Among all medical therapies, there were high rates of treatment failure or symptom worsening in over three‐quarters of patients in our study. Ivabradine was most beneficial, though the sample size was small. While most patients receiving SNM ablation for IST perceive an acute symptomatic improvement, almost two‐thirds of patients have no long‐term improvement, and resolution of symptoms is quite rare. AV node ablation with pacemaker implantation following lack of response to SNM offered increased success, though the sample size was limited.
Association of plant‐based diet and type 2 diabetes mellitus in Chinese rural adults: The Henan Rural Cohort Study
Authors: Yang Xiu , Li Yuqian , Wang Chongjian , Mao Zhenxing , Chen Yu , Ren Pengfei , Fan Mengying , Cui Songyang , Niu Kailin , Gu Ruohua , Li Linlin
Published: February 2021

Aims/Introduction

Studies have found that a plant‐based diet was associated with a lower risk of type 2 diabetes, but evidence is scarce on such associations in China. The aim of this study was to investigate whether a plant‐based diet is related to a lower risk of type 2 diabetes among Chinese adults.

Materials and Methods

A total of 37,985 participants were enrolled from the Henan Rural Cohort Study. An overall plant‐based diet index (PDI) was created by assigning positive and reverse scores to 12 commonly consumed food groups. Multivariate logistic regression models and restricted cubic spline analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI).

Results

After multivariable adjustment, the risk of type 2 diabetes was inversely associated with the PDI (extreme‐quartile OR = 0.88, 95% CI: 0.79–0.98; P = 0.027), the risk associated with a 1 standard deviation (SD) increase in PDI was 4% lower (95% CI, 0.93–1.00; P trend = 0.043) for type 2 diabetes. Moreover, the odds of type 2 diabetes was decreased with an increment of PDI after fitting restricted cubic splines (P trend < 0.01).

Conclusions

Among Chinese populations, diets higher in plant foods and lower in animal foods were associated with a reduced risk of type 2 diabetes.