bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of vertically integrated care with health care use and outcomes
Authors: Huckfeldt Peter J. , Gu Jing , Escarce José J. , Karaca‐Mandic Pinar , Sood Neeraj
Published: March 2021

Objective

To determine whether vertically integrated hospital and skilled nursing facility (SNF) care is associated with more efficient use of postdischarge care and better outcomes.

Data Sources

Medicare provider, beneficiary, and claims data from 2012 to 2014.

Study Design

We compared facility characteristics, quality of care, and health care use for hospital‐based SNFs and “virtually integrated” SNFs (defined as freestanding SNFs with close referral relationships with a single hospital) relative to nonintegrated freestanding SNFs. Among patients admitted to integrated SNFs, we estimated differences in health care use and outcomes for patients originating from the parent hospital (ie, receiving vertically integrated care) versus other hospitals using linear regressions that included SNF fixed effects. We estimated bounds for our main estimates that incorporated potential omitted variables bias.

Data Extraction Methods

We identified hospital‐based SNFs based on provider data. We defined virtually integrated SNFs based on patient flows between hospitals and SNFs. We identified SNF episodes, preceding hospital stays, patient characteristics, health care use, and patient outcomes using Medicare data.

Principal Findings

Consistent with prior research, integrated SNFs performed better on quality measures and health care use relative to nonintegrated SNFs (eg, hospital‐based SNFs had 11‐day shorter stays compared with nonintegrated SNFs adjusting for patient characteristics, P < .001). Stroke patients admitted to hospital‐based SNFs from the parent hospital had shorter preceding hospital stays (adjusted difference: −1.2 days, P = .001) and shorter initial SNF stays (adjusted difference: −2.7 days, P = .049); estimates were attenuated but still robust accounting for potential omitted variables bias. For stroke patients, associations between vertically integrated care and other outcomes were either statistically insignificant or not robust to accounting for potential omitted variables bias.

Conclusions

Vertically integrated hospital and SNF care was associated with shorter hospital and SNF stays. However, there were few beneficial associations with other outcomes, suggesting limited coordination benefits from vertical integration.
Feeding on clean food? Potential effects of electric organ discharges by Torpedo spp. (Torpediniformes: Torpedinidae) on their trophically transmitted parasites
Authors: PENADÉS‐SUAY Jaime , REGACHO Tania , AZNAR Francisco Javier
Published: March 2021

Members of the Torpedinidae (torpedoes) and Hypnidae (coffin ray) use electric organ discharges (EOD) to stun or kill their prey before consumption. We investigated whether EOD could also negatively affect the helminth larvae infecting these preys through a surrogate model: we applied electric discharges to individuals of blue whiting, Micromesistius poutassou, that harbored live larvae of Anisakis. Larval mortality throughout a 6‐h period was significantly higher in the treatment group, suggesting that EODs could significantly hamper helminth recruitment. We then tested whether torpedinids and hypnids (“strong‐EOD” families) harbored species‐poor helminth (cestode) assemblages compared with “weak‐EOD” Torpediniformes (Narcidae and Narkidae) and other Batoidea. Based on comparisons on estimated species diversity and mean species richness of tapeworms at host individual level we found that (i) Torpediniformes had the lowest tapeworm diversity of all Batoidea orders; (ii) Torpedo spp. consistently had the lowest mean cestode richness at host individual level, and this could not be related to other host factors influencing cestode diversity in chondrichthyans, that is body size, trophic level or dietary breath. However, a preliminary comparison between “strong‐EOD” and “weak‐EOD” Torpediniformes did not detect clear differences of cestode richness. Thus, evidence supporting an unambiguous contribution of EODs to depauperate cestode assemblages requires further research.
Physiological activity of E. coli engineered to produce butyric acid
Authors: Park Young‐Tae , Kim Taejung , Ham Jungyeob , Choi Jaeyoung , Lee Hoe‐Suk , Yeon Young Joo , Choi Soo In , Kim Nayoung , Kim Yeon‐Ran , Seok Yeong‐Jae
Published: March 2021

Faecalibacterium prausnitzii (F. prausnitzii) is one of the most abundant bacteria in the human intestine, with its anti‐inflammatory effects establishing it as a major effector in human intestinal health. However, its extreme sensitivity to oxygen makes its cultivation and physiological study difficult. F. prausnitzii produces butyric acid, which is beneficial to human gut health. Butyric acid is a short‐chain fatty acid (SCFA) produced by the fermentation of carbohydrates, such as dietary fibre in the large bowel. The genes encoding butyryl‐CoA dehydrogenase (BCD) and butyryl‐CoA:acetate CoA transferase (BUT) in F. prausnitzii were cloned and expressed in E. coli to determine the effect of butyric acid production on intestinal health using DSS‐induced colitis model mice. The results from the E. coli Nissle 1917 strain, expressing BCD, BUT, or both, showed that BCD was essential, while BUT was dispensable for producing butyric acid. The effects of different carbon sources, such as glucose, N‐acetylglucosamine (NAG), N‐acetylgalactosamine (NAGA), and inulin, were compared with results showing that the optimal carbon sources for butyric acid production were NAG, a major component of mucin in the human intestine, and glucose. Furthermore, the anti‐inflammatory effects of butyric acid production were tested by administering these strains to DSS‐induced colitis model mice. The oral administration of the E. coli Nissle 1917 strain, carrying the expression vector for BCD and BUT (EcN‐BCD‐BUT), was found to prevent DSS‐induced damage. Introduction of the BCD expression vector into E. coli Nissle 1917 led to increased butyric acid production, which improved the strain’s health‐beneficial effects.
Association between bariatric surgery and risks of cancer among Chinese patients with type 2 diabetes mellitus: A retrospective cohort study
Authors: Wei Yihui , Wong Simon K. H. , Wu Tingting , Law Betty T. T. , Ng Enders K. W. , Lam Cindy L. K. , Wong Carlos K. H.
Published: March 2021

Background

To examine risks of cancers, obesity‐related cancers (eg, cancers in digestive organs, breast, ovary, kidney, thyroid, and myeloma), cancer‐related mortality, and all‐cause mortality in patients with type 2 diabetes mellitus (T2DM) and obesity who underwent bariatric surgery.

Methods

A retrospective cohort of 1944 T2DM patients with obesity (345 bariatric surgery patients and 1599 matched controls) who were free of cancer from 2006 to 2017 was assembled. One‐to‐five propensity score matching followed by propensity score trimming was used to balance baseline covariates.

Results

During a mean follow‐up period of 37 months, there are risks that in 3.2%, 1.4%, 0.9%, and 3.2% of bariatric patients cancer, obesity‐related cancer, cancer‐related mortality, and all‐cause mortality, respectively, would occur. Surgical patients were found to have reduced incidence rates (IRs) of obesity‐related cancer (0.531/100 person‐years, 95% confidence interval [CI]: 0.172‐1.238/100 person‐years) and cancer of breast and genital organs (0.394/100 person‐years, 95% CI: 0.048‐1.424/100 person‐years) than matched control patients whose IRs for obesity‐related cancer and cancer of breast and genital organs were 0.627/100 person‐years (95% CI: 0.426‐0.889/100 person‐years) and 0.521/100 person‐years (95% CI: 0.277‐0.891/100 person‐years), respectively. Patients in the surgical group had a significant reduction in risk of all‐cause mortality (hazard ratio [HR] = 0.508, P = .041). Effects of bariatric surgery on any cancers (HR = 1.254, P = .510), obesity‐related cancers (HR = 0.843, P = .724), and cancer mortality (HR = 1.304, P = .694) were not significant.

Conclusions

Bariatric surgery was not associated with risks of overall cancer, obesity‐related cancer, and cancer mortality among T2DM patients with obesity at 3 years.
Joint hypermobility and its association with self‐reported knee health: A cross‐sectional study of healthy Australian adults
Authors: Chan Cliffton , Qi Haiwei H. , Baldwin Jennifer N. , McKay Marnee J. , Burns Joshua , Nicholson Leslie L.
Published: March 2021

Aim

The primary aim of this study was to determine the association between generalized joint hypermobility (GJH), knee‐specific hypermobility (KSH) and self‐reported knee health in an Australian population. Secondary aims included elucidating ethnic/gender differences in GJH/KSH prevalence and knee health, and identifying KSH using a novel knee extension range of motion cut‐off method.

Method

Knee extension range, Beighton score, and 5 domains of the Knee Injury and Osteoarthritis Outcome Score (KOOS) were collected from adults aged 18‐101 years self‐identifying as healthy, and were grouped by ethnicity and gender. Two established Beighton score criteria and 1 novel knee extension range cut‐off method were used to determine GJH and KSH respectively. Point‐biserial correlation tested the associations between GJH/KSH and KOOS. Differences in GJH/KSH prevalence and knee health between ethnic/gender groups were determined with the Chi‐squared test.

Results

Of 732 participants (50% male), 80.3% were Caucasian. No correlations were found between GJH and KOOS while a very weak correlation was found between KSH and 1 KOOS domain (r > −.30; P = .04). Prevalence of GJH was higher in non‐Caucasians (17.4% vs 5.6%, P < .001) and females (4.4% vs 1.1%, P = .007). Prevalence of KSH between ethnic and gender groups was not significantly different (P = .50 and P = .69 respectively). Non‐Caucasians scored higher (better) in all KOOS domains than Caucasians (all P < .05).

Conclusion

Those who met the age‐ and gender‐specific criteria for GJH/KSH did not report worse knee health than their non‐hypermobile counterparts. Clinicians can assure individuals who exhibit GJH/KSH that these are not associated with lower knee health and function.
Feasibility investigation of near‐infrared fluorescence imaging with intravenous indocyanine green method in uniport video‐assisted thoracoscopic anatomical segmentectomy for identifying the intersegmental boundary line
Authors: Sun Yungang , Zhang Qiang , Wang Zhao , Shao Feng , Yang Rusong
Published: March 2021

Objectives

To investigate the perioperative outcomes of patients who underwent uniport video‐assisted thoracoscopic (VATS) segmentectomy for identifying the intersegmental boundary line (IBL) by the near‐infrared fluorescence imaging with the intravenous indocyanine green (ICG) method or the modified inflation‐deflation (MID) method and assess the feasibility and effectiveness of the ICG fluorescence (ICGF)‐based method.

Methods

We retrospectively analyzed the perioperative data in total 198 consecutive patients who underwent uniport VATS segmentectomy between February 2018 and August 2020. With the guidance of a preoperative imaging interpretation and analysis system (IQQA‐3D), the targeted segment structures could be precisely identified and dissected, and then the IBL was confirmed by the ICGF‐based method or the MID method. The clinical effectiveness and postoperative complications of the two methods were evaluated.

Results

An IBL was visible in 98% of patients in the ICGF‐based group, even with low doses of ICG. The ICGF‐based group was significantly associated with a shorter IBL clear presentation time (23.6 ± 4.4 vs. 23.6 ± 4.4 s) (p < 0.01) and operative time (89.3 ± 31.6 vs. 112.9 ± 33.3 min) (p < 0.01) compared to the MID group. The incidence of postoperative prolonged air leaks was higher in the MID group than in the ICGF‐based group (8/100, 8% vs. 26/98, 26.5%, p = 0.025). There were no significant differences in bleeding volume, chest tube duration, postoperative hospital stays, surgical margin width, and other postoperative complications.

Conclusion

The ICGF‐based method could highly accurately identify the IBL and make anatomical segmentectomy easier and faster, and therefore has the potential to be a feasible and effective technique to facilitate the quality of uniport VATS segmentectomy.
A standardised biologging approach to infer parturition: An application in large herbivores across the hider‐follower continuum
Authors: Marchand Pascal , Garel Mathieu , Morellet Nicolas , Benoit Laura , Chaval Yannick , Itty Christian , Petit Elodie , Cargnelutti Bruno , Hewison Aidan J. M. , Loison Anne
Published: March 2021

The timing of birth has a predominant influence on both the reproductive success of the mother and the life‐history trajectory of her offspring. Because early growth and survival are key drivers of population dynamics, there is an urgent need to understand how global change is affecting reproductive phenology and performance. However, identifying when and where birth occurs is often difficult in the wild due to the cryptic behaviour of females around parturition, although this information may also help managers to protect reproductive females and newborn against human disturbance. While several approaches to identify parturition based on movement metrics derived from GPS monitoring have previously been proposed, their performance has not been evaluated over a range of species with contrasted movement characteristics.

Here, we present a novel approach to detect parturition by combining data on animal movements, activity rate and habitat use. Using machine learning approaches, we evaluated the relative and combined performance of each category of metrics in predicting parturition for three large herbivores with contrasted life histories: a hider‐type species, the roe deer Capreolus capreolus and two follower‐type species, the Mediterranean mouflon Ovis gmelini musimon × Ovis sp. and the Alpine ibex Capra ibex.

We first showed that detection of parturition was much improved when birth‐related modifications in the habitat use and activity rate of the mother were considered, rather than relying on movement metrics only. We then demonstrated that our approach was highly successful (76%–100% of events correctly identified) in detecting parturition in both follower and hider species. Furthermore, our approach generated estimates for peak birth date and the proportion of parturient females that were comparable with those based on direct observations at the population scale. Finally, our approach outperformed the most commonly employed methods in the literature which generally failed to identify non‐reproductive females for the three studied species, and provided birth timing estimates that only poorly match the true parturition date.

We suggest that by combining sources of information, we have developed a standardised methodological approach for inferring parturition in the wild, not only for large herbivores but also for any species where parturition induces marked behavioural changes in the mother.
Iatrogenic withdrawal syndrome frequently occurs in paediatric intensive care without algorithm for tapering of analgosedation
Authors: Dokken Mette , Rustøen Tone , Diep Lien M. , Fagermoen Frode E. , Huse Rakel I. , A. Rosland Gudny , Egerod Ingrid , Bentsen Gunnar K.
Published: March 2021

Background

Analgesics and sedatives are key elements to reduce physiological and psychological stress associated with treatment in paediatric intensive care. Prolonged drug use may induce tolerance and development of iatrogenic withdrawal syndrome (IWS) during the tapering phase. Our primary aim was to describe the prevalence of IWS among critically ill ventilated patients in two Norwegian paediatric intensive care units (PICUs), and secondary to investigate what motivated bedside nurses to administer additional drug doses.

Methods

Mechanically ventilated patients (n = 40) from newborn to eighteen years of age, with continuous infusions of opioids and benzodiazepines for 5 days or more, were included consecutively from May 2016 to June 2018. By using Withdrawal Assessment Tool‐1 (WAT‐1) twice daily we recorded the prevalence of IWS. Additionally, we recorded signs and symptoms that led bedside nurses to administration extra bolus medication.

Results

Peak WAT‐1 score indicated an IWS prevalence of 95% in this selected group. The first days of the tapering phase were most critical for IWS. The most frequent symptoms triggering administration of additional bolus doses were agitation/restlessness, and thiopental and propofol were the bolus drugs used most frequently.

Conclusions

IWS affected 95% of the children having received infusions of opioids and benzodiazepines for 5 days or more in PICUs without a tapering protocol for these drugs. This calls for implementation and testing of such weaning protocols.
Acute pulmonary hypertension and short‐term outcomes in severe Covid‐19 patients needing intensive care
Authors: Norderfeldt Joakim , Liliequist Andreas , Frostell Claes , Adding Christofer , Agvald Per , Eriksson Maria , Lönnqvist Per‐Arne
Published: March 2021

Introduction

Critically ill Covid‐19 pneumonia patients are likely to develop the sequence of acute pulmonary hypertension, right ventricular (RV) strain, and eventually RV failure due to known pathophysiology (endothelial inflammation plus thrombo‐embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. This study aimed to investigate the occurrence of acute pulmonary hypertension (aPH) as per established trans‐thoracic echocardiography (TTE) criteria in Covid‐19 patients receiving intensive care and to explore whether short‐term outcomes are affected by the presence of aPH.

Methods

Medical records were reviewed for patients treated in the intensive care units at a tertiary university hospital over a month. The presence of aPH on the TTE was noted, and plasma NTproBNP and troponin were measured as markers of cardiac failure and myocardial injury, respectively. Follow‐up data were collected 21 d after the performance of TTE.

Results

In total, 26 of 67 patients (39%) had an assessed systolic pulmonary artery pressure of > 35 mmHg (group aPH), meeting the TTE definition of aPH. NTproBNP levels (median [range]: 1430 [102‐30 300] vs. 470 [45‐29 600] ng L−1; P = .0007), troponin T levels (63 [22‐352] vs. 15 [5‐407] ng L−1; P = .0002), and the 21‐d mortality rate (46% vs. 7%; P < .001) were substantially higher in patients with aPH compared to patients not meeting aPH criteria.

Conclusion

TTE‐defined acute pulmonary hypertension was frequently observed in severely ill Covid‐19 patients. Furthermore, aPH was linked to biomarker‐defined myocardial injury and cardiac failure, as well as an almost sevenfold increase in 21‐d mortality.
Proteomics in aging research: A roadmap to clinical, translational research
Authors: Moaddel Ruin , Ubaida‐Mohien Ceereena , Tanaka Toshiko , Lyashkov Alexey , Basisty Nathan , Schilling Birgit , Semba Richard D , Franceschi Claudio , Gorospe Myriam , Ferrucci Luigi
Published: March 2021

The identification of plasma proteins that systematically change with age and, independent of chronological age, predict accelerated decline of health is an expanding area of research. Circulating proteins are ideal translational “omics” since they are final effectors of physiological pathways and because physicians are accustomed to use information of plasma proteins as biomarkers for diagnosis, prognosis, and tracking the effectiveness of treatments. Recent technological advancements, including mass spectrometry (MS)‐based proteomics, multiplexed proteomic assay using modified aptamers (SOMAscan), and Proximity Extension Assay (PEA, O‐Link), have allowed for the assessment of thousands of proteins in plasma or other biological matrices, which are potentially translatable into new clinical biomarkers and provide new clues about the mechanisms by which aging is associated with health deterioration and functional decline. We carried out a detailed literature search for proteomic studies performed in different matrices (plasma, serum, urine, saliva, tissues) and species using multiple platforms. Herein, we identified 232 proteins that were age‐associated across studies. Enrichment analysis of the 232 age‐associated proteins revealed metabolic pathways previously connected with biological aging both in animal models and in humans, most remarkably insulin‐like growth factor (IGF) signaling, mitogen‐activated protein kinases (MAPK), hypoxia‐inducible factor 1 (HIF1), cytokine signaling, Forkhead Box O (FOXO) metabolic pathways, folate metabolism, advance glycation end products (AGE), and receptor AGE (RAGE) metabolic pathway. Information on these age‐relevant proteins, likely expanded and validated in longitudinal studies and examined in mechanistic studies, will be essential for patient stratification and the development of new treatments aimed at improving health expectancy.
Moderate prenatal ethanol exposure leads to attention deficits in both male and female rats
Authors: Wang Ruixiang , Martin Connor D. , Lei Anna L. , Hausknecht Kathryn A. , Ishiwari Keita , Oubraim Saida , Wang An‐Li , Richards Jerry B. , Haj‐Dahmane Samir , Shen Roh‐Yu
Published: March 2021

Background

Attention deficits caused by prenatal ethanol (EtOH) exposure (PE) are a prevalent condition in fetal alcohol spectrum disorders (FASDs). Importantly, the deficits are observed in individuals with FASD who have normal IQs and show no dysmorphic facial features caused by heavy PE. These observations suggest that even moderate PE could lead to attention deficits. This possibility was investigated in the present study using a rat model.

Methods

Pregnant Sprague Dawley rats were administered EtOH (3 g/kg/day) or vehicle via intragastric gavage on gestational days 8 to 20. The blood EtOH concentration (BEC) in EtOH‐treated rats was 87.7 ± 1.2 mg/dl (1 h after the gavage), similar to the BECs reported in other moderate PE studies in rodents. Moderate PE did not produce teratogenic effects on birthweight or litter size. The adult offspring underwent a 2‐choice reaction time task.

Results

Moderate PE led to augmented action impulsivity in both sexes, indicated by more rapid response initiation and more premature responses. Deficits were more marked in males than in females. No greater lapses of attention, assessed by incorrect or relatively slow responses, were observed in rats of either sex with moderate PE. In addition, no deficits in learning or motor function were detected after moderate PE. Interestingly, rats with moderate PE completed more trials than controls.

Conclusions

Our results confirm that moderate PE leads to attention deficits in both sexes, which is demonstrated by greater action impulsivity, but not more lapses of attention. This effect differs from that of heavy PE, as shown in our previous study, which is manifested as impaired action impulsivity and lapses of attention in both sexes.
A pilot economic evaluation of computerized cognitive behavioral therapy for alcohol use disorder as an addition and alternative to traditional therapy
Authors: Kacmarek Corinne N. , Yates Brian T. , Nich Charla , Kiluk Brian D.
Published: March 2021

Background

Computer‐based delivery of cognitive behavioral therapy (CBT) may be a less costly approach to increase dissemination and implementation of evidence‐based treatments for alcohol use disorder (AUD). However, comprehensive evaluations of costs, cost‐effectiveness, and cost–benefit of computer‐delivered interventions are rare.

Methods

This study used data from a completed randomized clinical trial to evaluate the cost‐effectiveness and cost–benefit of a computer‐based version of CBT (CBT4CBT) for AUD. Sixty‐three participants were randomized to receive one of the following treatments at an outpatient treatment facility and attended at least one session: (1) treatment as usual (TAU), (2) CBT4CBT plus treatment as usual (CBT4CBT+TAU), or (3) CBT4CBT plus brief monitoring.

Results

Median protocol treatment costs per participant differed significantly between conditions, Kruskal‐Wallis H(2) = 8.40, p = 0.02, such that CBT4CBT+TAU and CBT4CBT+monitoring each cost significantly more per participant than TAU. However, when nonprotocol treatment costs were included, total treatment costs per participant did not differ significantly between conditions. Median incremental cost‐effective ratios (ICERs) revealed that CBT4CBT+TAU was more costly and more effective than TAU. It cost $35.08 to add CBT4CBT to TAU to produce a reduction of one additional drinking day per month between baseline and the end of the 8‐week treatment protocol: CBT4CBT+monitoring cost $33.70 less to produce a reduction of one additional drinking day per month because CBT4CBT+monitoring was less costly than TAU and more effective at treatment termination, though not significantly so. Net benefit analyses suggested that costs of treatment, regardless of condition, did not offset monthly costs related to healthcare utilization, criminal justice involvement, and employment disruption between baseline and 6‐month follow‐up. Benefit–cost ratios were similar for each condition.

Conclusions

Results of this pilot economic evaluation suggest that an 8‐week course of CBT4CBT may be a cost‐effective addition and potential alternative to standard outpatient treatment for AUD. Additional research is needed to generate conclusions about the cost–benefit of providing CBT4CBT to treatment‐seeking individuals participating in standard outpatient treatment.
Trends in cannabis use among adults with children in the home in the United States, 2004–2017: impact of state‐level legalization for recreational and medical use
Authors: Goodwin Renee D. , Kim June H. , Cheslack‐Postava Keely , Weinberger Andrea H. , Wu Melody , Wyka Katarzyna , Kattan Meyer
Published: March 2021

Background and Aims

Cannabis use among parents may be increasing with legalization, but perception of associated risk has declined. The study investigated the association between cannabis legalization and cannabis use among adults with children in the home over time in the United States (US).

Design

A difference‐in‐difference approach was applied to public and restricted‐use data from the 2004–2017 National Survey on Drug Use and Health (NSDUH), an annual cross‐sectional survey.

Setting

A representative sample of the United States.

Participants/Cases

Respondents ages 18+ with children living in the home drawn from the NSDUH (n = 287,624), which is administered to non‐institutionalized civilians in the 50 states and District of Columbia.

Measurements

Exposures were year and state‐level cannabis policy in state of residence annually. Outcomes were past‐30‐day cannabis use and daily cannabis use. Sociodemographic variables included age, gender, marital status, annual family income, race/ethnicity, educational attainment, and strength of state‐level tobacco control.

Findings

In 2017, past‐month cannabis use (11.9%, 9.3%, and 6.1%) and daily cannabis use (4.2%, 3.2%, and 2.3%) were more common in states with recreational marijuana laws (RML), followed by states with medical marijuana laws (MML) and without legal cannabis use, respectively. RML and MML were associated with significantly higher prevalence of past‐month cannabis use (adjusted odds ratio [AOR] = 1.28, 95% confidence interval [CI] = 1.12–1.46; AOR = 1.12, 95% CI = 1.03–1.22) and daily cannabis use (AOR = 1.25, 95% CI = 1.03–1.51; AOR = 1.16, 95% CI = 1.02–1.32), respectively. The impact of MML was particularly salient among adults ages 50+ and the highest income and education subgroups.

Conclusions

Among adults with children living in the home, cannabis use appears to be more common in US states with legalized cannabis use compared with states with no legal cannabis use. Recreational legalization appears to increase use among adults with children in the home broadly across nearly all sociodemographic groups, whereas the effect of legalization for medical use is heterogeneous by age and socioeconomic status.
Global Food Trade and the Costs of Non‐Adoption of Genetic Engineering
Authors: Nes Kjersti , Schaefer K. Aleks , P. Scheitrum Daniel
Published: March 2021

For several staple grains, the share of trade that originates in and is destined for countries that have approved genetically engineered (GE) varieties continues to expand as a share of total trade. As the GE‐world expands, non‐adoption of GE technology may isolate a market, effectively eliminating a growing source of food. This research seeks to quantify the impacts of GE approval and non‐approval on food prices and access to food from abroad in importing countries. We show that non‐adoption of GE technology reduces a country's access to imports and raises its prices. Not only do non‐approving importers fail to receive the full benefits of agricultural expansion resulting from genetic engineering, the countries are worse off relative to a world in which the technology never existed.
Anthropogenic impact on wildlife resource use: Spatial and temporal shifts in elephants’ access to water
Authors: Buchholtz Erin K. , Spragg Shannon , Songhurst Anna , Stronza Amanda , McCulloch Graham , Fitzgerald Lee A.
Published: March 2021

Expansion of human settlements and development have undeniable impacts on wildlife and habitats. Yet wildlife continues to persist in human‐modified environments. While shifting patterns of wildlife landscape use in response to development is well established, less is known about how risk avoidance by animals impacts their resource access. Our research addresses this question by assessing spatial and temporal patterns in access to water resources for savannah elephants (Loxodonta africana) relative to anthropogenic features in the Okavango Panhandle of Botswana. We combined GPS collar data from 39 elephants (2014–2018) with spatial data on permanent water sources and human development to quantify patterns of water access. We modelled a multi‐scale resource selection function that showed elephants selected water access points in areas with less human development (p < 0.0151). Elephants visited water more evenly across day and night in areas with no buildings nearby, but shifted to a significantly more nocturnal pattern in areas of higher building density (ANOVA,p < 0.001). Analysing spatial and temporal patterns of elephant resource access in the context of anthropogenic features provides compelling insight into the potential consequences of human‐modified landscapes on the behaviour, fitness, and persistence of threatened species and our coexistence with them.
A decellularized porcine pulmonary valved conduit embedded with gelatin
Authors: Wan Juyi , Zhong Xiaolin , Xu Zhiwei , Gong Da , Li Diankun , Xin Zhifei , Ma Xiaolong , Li Wenbin
Published: March 2021

To prepare a tissue‐engineered pulmonary valved conduit (PVC) with good tensile strength and biocompatibility. Sixty adult porcine PVCs were used to determine the optimal decellularization time. Five juvenile porcine decellularized PVCs and five juvenile porcine crosslinked PVCs were subsequently prepared according to the optimized decellularization and crosslinking methods. All PVCs were implanted into juvenile sheep for 8 months and then were harvested for staining. With a low concentration of detergent (0.25% Triton X‐100+0.25% sodium deoxycholate), the decellularization effect on porcine PVCs was complete by 24 hours, and there was minimal damage to the matrix. Gelatin embedding and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC) crosslinking improved the biomechanical properties of decellularized PVCs and reduced their immunogenicity. After implantation, the diameter and thickness of the PVCs in the decellularized and crosslinked groups increased significantly. In both groups, the conduits were unobstructed, with soft and smooth inner walls and without thrombosis, ulceration or neoplasia. The valves slightly degenerated with mild to moderate regurgitation. CD31‐positive endothelial cells were visible on the inner surface of the conduits and valves. Scattered smooth muscle actin‐positive cells were found in the middle layer of the conduit. The percentage of CD4‐ and CD68‐positive cells and the calcium content were highest in decellularized porcine PVCs and lowest in ovine PVCs. The percentage of the matrix that was laminin‐positive in decellularized and crosslinked porcine PVCs was lower than it was in ovine PVCs. Gelatin‐embedded and EDC‐crosslinked porcine PVCs can be “hosted” in sheep, with good biocompatibility, growth potential, and reduced calcification.
MicroRNAs and the HIF/VEGF axis in ocular neovascular diseases
Authors: Plastino Flavia , Pesce Noemi Anna , André Helder
Published: March 2021

Ocular neovascular diseases, such as proliferative diabetic retinopathy, retinopathy of prematurity and neovascular age‐related macular degeneration, are the leading causes of visual impairment worldwide. The hypoxia‐inducible factors and vascular endothelial growth factors are key molecular promoters of ocular neovascularization. Moreover, the role of microRNAs as regulators of angiogenesis has been expanding, particularly hypoxia‐associated microRNA; hypoxamiRs. This review provides a summary of hypoxamiRs that directly and specifically target HIF1A and VEGF mRNAs, thus critically involved in the regulation of ocular neovascular pathologies. The discussed microRNAs highlight putative diagnostic markers and therapeutic agents in choroidal and retinal angiogenic diseases, including proliferative diabetic retinopathy, retinopathy of prematurity and neovascular age‐related macular degeneration.
Absence of neocytolysis in humans returning from a 3‐week high‐altitude sojourn
Authors: Klein Marie , Kaestner Lars , Bogdanova Anna Y. , Minetti Giampaolo , Rudloff Silvia , Lundby Carsten , Makhro Asya , Seiler Elena , van Cromvoirt Ankie , Fenk Simone , Simionato Greta , Hertz Laura , Recktenwald Steffen , Schäfer Larissa , Haider Thomas , Fried Sebastian , Borsch Christian , Marti Hugo H. , Sander Anja , Mairbäurl Heimo
Published: March 2021

Aims

Total haemoglobin mass (tot‐Hb) increases during high‐altitude acclimatization. Normalization of tot‐Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m).

Methods

Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19‐day high‐altitude sojourn by ingestion of13C2‐ and15N‐labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot‐Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling.

Results

Tot‐Hb increased by 4.7% ± 2.7% at high altitude and returned to pre‐altitude values within 11 days after descent. Elimination of13C‐ (normoxia) and15N‐ (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71‐positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3‐4 days after descent and normalized slowly. There was no indication of haemolysis.

Conclusion

We confirm a rapid normalization of tot‐Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.
Reciprocal relationship between workplace incivility and deviant silence—The moderating role of moral attentiveness
Authors: Khan Rahman , Murtaza Ghulam , Neveu Jean Pierre , Newman Alexander
Published: March 2021

In the present study, we examine the reciprocal relationship between employees' perceptions of workplace incivility and their deviant silence. We also explore the moderating role of moral attentiveness on the relationship between workplace incivility and deviant silence. Utilizing three‐waves of longitudinal data from 297 full‐time employees working in different industrial sectors in the United States, we find support for the reciprocal model as the best fit to the data, thus validating relationships over time between our study variables. Taken together, our results suggest that workplace incivility at T1/T2 significantly predicted deviant silence at T2/T3. The results also reveal that deviant silence at T1/T2 significantly predicted workplace incivility at T2/T3. Importantly, we found that reflective but not perceptual moral attentiveness significantly reduced the negative influence of workplace incivility on deviant silence in subsequent time periods.
Phenotypic variation in adults of Chilo partellus (Swinhoe) from diverse ecological regions of India
Authors: Dhillon Mukesh K. , Tanwar Aditya K. , Hasan Fazil , Bhadauriya Amarpal S.
Published: March 2021

Geographic distance and ecological conditions are important factors for phenological differentiation, and the adult morphological characters play significant role in several biological functions in insects. Present study showed significant intraspecific and intersex variation in colour pattern, number of spots and stripes on the forewings of Chilo partellus adults of different ecological populations. Females were comparatively light in colour with less black spots and stripes than the males across populations. Length and width of head, thorax and abdomen, wingspan, and various parts of male and female genitalia varied significantly across C. partellus populations. Abdomen, corpus bursae and papillae anales were significantly longer in females of Hisar as compared to other populations. However, the length of aedeagus was significantly longer in males of Coimbatore and Delhi as compared to other populations. Range of wingspan: body size and body size: genitalia ratios across C. partellus populations were wider in females than males. Wingspan: body size ratio was significantly lower in males of Raichur and females of Hisar and Parbhani as compared to other populations. Body size: genitalia ratio was significantly lower in males of Coimbatore and Hyderabad, and females of Coimbatore, Raichur and Surat as compared to other ecological populations. These findings suggest phenotypic plasticity in C. partellus having implications for phenotypic expression and greater fitness in response to changing climatic conditions.
Antihistamine‐related deaths in England: Are the high safety profiles of antihistamines leading to their unsafe use?
Authors: Oyekan Princess J. , Gorton Hayley C. , Copeland Caroline S.
Published: March 2021

Aims

Antihistamines are routinely taken to control allergic reactions or sedation to induce sleep. There are, however, growing concerns regarding sedating antihistamine misuse. This research aims to evaluate deaths related to antihistamines in England occurring during 2000–2019.

Methods

Cases reported to the National Programme on Substance Abuse Deaths from England occurring in 2000–2019 with antihistamine detections at postmortem were extracted for analysis.

Results

In total, 1666 antihistamine postmortem detections were identified from 1537 cases. Sedating antihistamines available for purchase under pharmacist supervision but without need for a prescription (pharmacy‐only medications) were present in a significant majority of cases (85.2%, P < .01). Despite an increasing trend for antihistamine‐related deaths over time, the proportion of deaths where an antihistamine was implicated declined over the same period. Specific concerns with regards to the misuse of these pharmacy‐only sedating antihistamines are raised with regards to the significant proportion of cases that were concluded as suicide (20.9%, P < .01), and the high prevalence of their use in combination with other central nervous system depressants (94.8% of cases).

Conclusion

This is the first report in over 40 years regarding antihistamine‐related mortality from England. The rising trend in sedating antihistamine‐related deaths may be contributed to by their increasing availability and the perceived negligible dangers associated with antihistamines, both from the general public and learned professionals. Awareness of the dangerous sedative properties that some antihistamines possess is, however, heightened in individuals deliberately seeking these effects. Urgent review of sedating antihistamines currently assigned under the pharmacy‐only classification is needed to achieve antihistamine harm reduction.
The ALK inhibitors, alectinib and ceritinib, induce ALK‐independent and STAT3‐dependent glioblastoma cell death
Authors: Kawauchi Daisuke , Takahashi Masamichi , Satomi Kaishi , Yamamuro Shun , Kobayashi Tatsuya , Uchida Eita , Honda‐Kitahara Mai , Narita Yoshitaka , Iwadate Yasuo , Ichimura Koichi , Tomiyama Arata
Published: March 2021

Glioblastoma (GBM) is the most common, but extremely malignant, brain tumor; thus, the development of novel therapeutic strategies for GBMs is imperative. Many tyrosine kinase inhibitors (TKIs) have been approved for various cancers, yet none has demonstrated clinical benefit against GBM. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that is confirmed only during the embryonic development period in humans. In addition, various ALK gene alterations are known to act as powerful oncogenes and therapeutic targets in various tumors. The antitumor activity of various TKIs was tested against three human GBM cell lines (U87MG, LN229, and GSC23), which expressed substantially low ALK levels; second‐generation ALK inhibitors, alectinib and ceritinib, effectively induced GBM cell death. In addition, treatment with either alectinib or ceritinib modulated the activation of various molecules downstream of RTK signaling and induced caspase‐dependent/‐independent cell death mainly by inhibiting signal transducer and activator of transcription 3 activation in human GBM cells. In addition, alectinib and ceritinib also showed antitumor activity against a U87MG cell line with acquired temozolomide resistance. Finally, oral administration of alectinib and ceritinib prolonged the survival of mice harboring intracerebral GBM xenografts compared with controls. These results suggested that treatment with the second‐generation ALK inhibitors, alectinib and ceritinib, might serve as a potent therapeutic strategy against GBM.
Guiding principles for rewilding
Authors: Carver Steve , Convery Ian , Hawkins Sally , Beyers Rene , Eagle Adam , Kun Zoltan , Van Maanen Erwin , Cao Yue , Fisher Mark , Edwards Stephen R. , Nelson Cara , Gann George D. , Shurter Steve , Aguilar Karina , Andrade Angela , Ripple William J. , Davis John , Sinclair Anthony , Bekoff Marc , Noss Reed , Foreman Dave , Pettersson Hanna , Root‐Bernstein Meredith , Svenning Jens‐Christian , Taylor Peter , Wynne‐Jones Sophie , Featherstone Alan Watson , Fløjgaard Camilla , Stanley‐Price Mark , Navarro Laetitia M. , Aykroyd Toby , Parfitt Alison , Soulé Michael
Published: March 2021

There has been much recent interest in the concept of rewilding as a tool for nature conservation, but also confusion over the idea, which has limited its utility. We developed a unifying definition and 10 guiding principles for rewilding through a survey of 59 rewilding experts, a summary of key organizations’ rewilding visions, and workshops involving over 100 participants from around the world. The guiding principles convey that rewilding exits on a continuum of scale, connectivity, and level of human influence and aims to restore ecosystem structure and functions to achieve a self‐sustaining autonomous nature. These principles clarify the concept of rewilding and improve its effectiveness as a tool to achieve global conservation targets, including those of the UN Decade on Ecosystem Restoration and post‐2020 Global Biodiversity Framework. Finally, we suggest differences in rewilding perspectives lie largely in the extent to which it is seen as achievable and in specific interventions. An understanding of the context of rewilding projects is the key to success, and careful site‐specific interpretations will help achieve the aims of rewilding.
Protective role of Gremlin‐1 in myocardial function
Authors: Müller Iris I. , Schneider Martina , Müller Karin A. L. , Lunov Oleg , Borst Oliver , Simmet Thomas , Gawaz Meinrad
Published: March 2021

Background

Gremlin‐1 is a cystine knot protein and is expressed in organs developing fibrosis. Transient ischaemia leads to myocardial fibrosis, a major determinant of impaired myocardial function.

Materials and methods

Expression of Gremlin‐1 was investigated in infarcted myocardium by real‐time PCR, Western blot analysis, histological and immunohistochemistry staining. We further elaborated the colocalization of Gremlin‐1 and TGF‐β proteins by confocal microscopy and co‐immunoprecipitation experiments. The interaction between Gremlin‐1 and TGF‐β was analysed by photon correlation spectroscopy. Gremlin‐1 modulation of the TGF‐β‐dependent collagen I synthesis in fibroblasts was investigated using ELISA and immunohistochemistry experiments. The effect of prolonged administration of recombinant Gremlin‐1 on myocardial function following ischaemia/reperfusion was accessed by echocardiography and immunohistochemistry.

Results

Gremlin‐1 is expressed in myocardial tissue and infiltrating cells after transient myocardial ischaemia (P < .05). Gremlin‐1 colocalizes with the pro‐fibrotic cytokine transforming growth factor‐β (TGF‐β) expressed in fibroblasts and inflammatory cell infiltrates (P < .05). Gremlin‐1 reduces TGF‐β‐induced collagen production of myocardial fibroblasts by approximately 20% (P < .05). We found that Gremlin‐1 binds with high affinity to TGF‐β (KD = 54 nmol/L) as evidenced by photon correlation spectroscopy and co‐immunoprecipitation. intravenous administration of mGremlin‐1‐Fc, but not of equivalent amount of Fc control, significantly reduced infarct size by approximately 20%. In the mGremlin‐1‐Fc group, infarct area was reduced by up to 30% in comparison with mice treated with Fc control (I/LV: 4.8 ± 1.2% vs 6.0 ± 1.2% P < .05; I/AaR: 15.2 ± 1.5% vs 21.1 ± 5%, P < .05).

Conclusions

The present data disclose Gremlin‐1 as an antagonist of TGF‐β and presume a role for Gremlin‐1/TGF‐β interaction in myocardial remodelling following myocardial ischaemia.