bluuebunny/crossref_metadata_2025 huggingface dataset:
Burn Outcomes at Extremes of Body Mass Index: Underweight Is as Problematic as Morbid Obesity
Authors: Tolley Philip D , McClellan John M , Butler Demsie , Stewart Barclay T , Pham Tam N , Sheckter Clifford C
Published: February 2022

Limited evidence suggests that obesity adversely affects burn outcomes. However, the impacts of body mass index (BMI) across the continuum have not been fully characterized. Therefore, we aimed to characterize outcomes after burn injury across the BMI continuum. We hypothesized that “normal” BMI (18.5–24.9) would have the lowest mortality and complication rates. The US National Trauma Data Bank (NTDB) was queried for adult burn-injured patients from 2007 to 2015. Admission BMI was calculated and grouped according to World Health Organization (WHO) classification. The primary outcome was in-hospital mortality. Secondary outcomes of time to wound closure, length of stay, and inpatient complications were similarly assessed. Of the 116,008 burn patient encounters that were identified, 7243 underwent at least one operation for wound closure. Mortality was lowest in the overweight (P = .039) and obese I cohorts (BMI 25–29.9, 30.0–34.9) at 2.9% and increased in both directions of the BMI continuum to 4.1% in the underweight (P = .032) and 5.1% in the morbidly obese (class III) group (P = .042). Time to final wound closure was longest in the two BMI extremes. BMI ≥40 was associated with increased intensive care unit days, ventilator days, renal and cardiac complications. BMI <18.5 had increased hospital days and rates of sepsis. Aberrations in metabolism associated with both increases and decreases of body weight may cause pathophysiologic changes that lead to worsened outcomes in burn-injured patients. In addition to morbidly obese patients, underweight patients also experience increased burn-related death and complications. In contrast, overweight BMI patients may have greater physiologic reserves without the burden of obesity or sarcopenia.
Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management
Authors: Lu Cathy , Ma Christopher , Ingram Richard J M , Chan Melissa , Kheirkhahrahimabadi Hengameh , Martin Marie-Louise , Seow Cynthia H , Kaplan Gilaad G , Heatherington Joan , Devlin Shane M , Panaccione Remo , Novak Kerri L
Published: February 2022

Background

The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization.

Methods

We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy.

Results

A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn’s disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly.

Conclusion

Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.
Generative design for additive manufacturing using a biological development analogy
Authors: Price Mark , Zhang Wei , Friel Imelda , Robinson Trevor , McConnell Roisin , Nolan Declan , Kilpatrick Peter , Barbhuiya Sakil , Kyle Stephen
Published: February 2022

The transformation in manufacturing capability being driven by new processes, such as additive manufacturing, offers huge potential for product innovation and opportunity to create bespoke designs tailored to individual specifications or needs. However, current design systems and tools are not yet capable of fully capitalizing on these new technologies and new approaches are needed. Many current methodologies are top-down and sequential, offering limited flexibility and an overly constrained design space. Post-processing is needed to ensure that a design can be manufactured. This work presents a novel bottom-up methodology to generate designs that can be tightly integrated with the additive manufacturing environment and that can respond flexibly to changes in that environment. Focusing on overhang as an exemplar manufacturing constraint, the method engenders changes in the design either by locally adjusting the geometry to stay within limits or by adding an appropriate support structure. The method is bio-inspired, based on strategies observed in natural systems, particularly in biological growth and development. The design geometry is grown in a computer-aided design-based, bio-inspired generative design system called ‘Biohaviour’. This process is similar to plant growth, and the design’s final configuration, shape, and size are informed by both the manufacturing capability and internal design stresses. The approach is demonstrated for overhang limit and build orientation and is extensible to any general situation.
The Private and External Costs of Germany’s Nuclear Phase-Out
Authors: Jarvis Stephen , Deschenes Olivier , Jha Akshaya
Published: February 2022

Many countries have phased out nuclear power in response to concerns about nuclear waste and the risk of nuclear accidents. This paper examines the shutdown of more than half of the nuclear production capacity in Germany after the Fukushima accident in 2011. We use hourly data on power plant operations and a machine learning approach to estimate the impacts of the phase-out policy. We find that reductions in nuclear electricity production were offset primarily by increases in coal-fired production and net electricity imports. Our estimates of the social cost of the phase-out range from €3 to €8 billion per year. The majority of this cost comes from the increased mortality risk associated with exposure to the local air pollution emitted when burning fossil fuels. Policymakers would have to significantly overestimate the risk or cost of a nuclear accident to conclude that the benefits of the phase-out exceed its social costs. We discuss the likely role of behavioral biases in this setting, and highlight the importance of ensuring that policymakers and the public are informed about the health effects of local air pollution.
Hospital Readmissions Among Infants Diagnosed With Early-Onset Neonatal Sepsis in Connecticut
Authors: Hudon Rebecca E , Leung Vivian H , Petit Susan , Banach David B
Published: February 2022

Background

Early-onset neonatal sepsis, defined as sepsis within 72 hours of birth, results in significant infant morbidity and mortality. Readmissions associated with neonatal sepsis have not previously been well described. Early-onset neonatal sepsis is a mandatory reportable condition in Connecticut, allowing for expanded data collection through public health surveillance to evaluate readmissions.

Methods

Infants with early-onset neonatal sepsis born in Connecticut during 2007-2016 were identified from statewide surveillance data and matched with a statewide hospital discharge database. We describe readmission rates, causes and timing of readmissions, and demographic and clinical factors associated with readmission among this group.

Results

Among 241 infants with early-onset neonatal sepsis matched to discharge data, 203 (84.2%) infants survived their initial hospitalization at birth. During the first year of life, 47 (23.2%) infants were readmitted, most often in the first 3 months after birth (n = 29, 42.6%). The most frequent reasons for readmissions were pulmonary complications (19%), infections (17%), and gastrointestinal illness (13%). Infants with initial hospitalizations lasting longer than 30 days after birth were associated with higher rates of readmission compared with those discharged within 30 days after birth (35% vs 19%, P = .02).

Conclusions

A substantial proportion of infants diagnosed with early-onset neonatal sepsis are readmitted within the first year of life. Those with prolonged hospitalizations after birth are at the highest risk. Further efforts and intensified strategies are needed to prevent readmissions among this vulnerable patient population.
Parameterized complexity of dynamic belief updates: A complete map
Authors: Bolander Thomas , Lequen Arnaud
Published: February 2022

Dynamic Belief Update is a model checking problem in Dynamic Epistemic Logic concerning the effect of applying a number of epistemic actions on an initial epistemic model. It can also be considered as a plan verification problem in epistemic planning. The problem is known to be PSPACE-hard. To better understand the source of complexity of the problem, previous research has investigated the complexity of 128 parameterized versions of the problem with parameters such as number of agents and size of epistemic actions. The complexity of many parameter combinations has been determined, but previous research left 14 parameter combinations open. In this paper, we solve all of these open problems. Most of the parameter combinations turns out to be fixed-parameter intractable, except for 3 that are fixed-parameter tractable.
In Vitro Evolution Reveals Noncationic Protein–RNA Interaction Mediated by Metal Ions
Authors: Giacobelli Valerio G , Fujishima Kosuke , Lepšík Martin , Tretyachenko Vyacheslav , Kadavá Tereza , Makarov Mikhail , Bednárová Lucie , Novák Petr , Hlouchová Klára
Published: February 2022

RNA–peptide/protein interactions have been of utmost importance to life since its earliest forms, reaching even before the last universal common ancestor (LUCA). However, the ancient molecular mechanisms behind this key biological interaction remain enigmatic because extant RNA–protein interactions rely heavily on positively charged and aromatic amino acids that were absent (or heavily under-represented) in the early pre-LUCA evolutionary period. Here, an RNA-binding variant of the ribosomal uL11 C-terminal domain was selected from an approximately 1010 library of partially randomized sequences, all composed of ten prebiotically plausible canonical amino acids. The selected variant binds to the cognate RNA with a similar overall affinity although it is less structured in the unbound form than the wild-type protein domain. The variant complex association and dissociation are both slower than for the wild-type, implying different mechanistic processes involved. The profile of the wild-type and mutant complex stabilities along with molecular dynamics simulations uncovers qualitative differences in the interaction modes. In the absence of positively charged and aromatic residues, the mutant uL11 domain uses ion bridging (K+/Mg2+) interactions between the RNA sugar-phosphate backbone and glutamic acid residues as an alternative source of stabilization. This study presents experimental support to provide a new perspective on how early protein–RNA interactions evolved, where the lack of aromatic/basic residues may have been compensated by acidic residues plus metal ions.
The contribution of uncharted RNA sequences to tumor identity in lung adenocarcinoma
Authors: Wang Yunfeng , Xue Haoliang , Aglave Marine , Lainé Antoine , Gallopin Mélina , Gautheret Daniel
Published: February 2022

The identity of cancer cells is defined by the interplay between genetic, epigenetic transcriptional and post-transcriptional variation. A lot of this variation is present in RNA-seq data and can be captured at once using reference-free, k-mer analysis. An important issue with k-mer analysis, however, is the difficulty of distinguishing signal from noise. Here, we use two independent lung adenocarcinoma datasets to identify all reproducible events at the k-mer level, in a tumor versus normal setting. We find reproducible events in many different locations (introns, intergenic, repeats) and forms (spliced, polyadenylated, chimeric etc.). We systematically analyze events that are ignored in conventional transcriptomics and assess their value as biomarkers and for tumor classification, survival prediction, neoantigen prediction and correlation with the immune microenvironment. We find that unannotated lincRNAs, novel splice variants, endogenous HERV, Line1 and Alu repeats and bacterial RNAs each contribute to different, important aspects of tumor identity. We argue that differential RNA-seq analysis of tumor/normal sample collections would benefit from this type k-mer analysis to cast a wider net on important cancer-related events. The code is available at https://github.com/Transipedia/dekupl-lung-cancer-inter-cohort.
PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
Authors: Tinsley Samantha L , Allen-Petersen Brittany L
Published: February 2022

The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth.
The relationship between ageing and changes in the human blood and brain methylomes
Authors: Bryant Patrick , Elofsson Arne
Published: February 2022

Changes in DNA methylation have been found to be strongly correlated with age, enabling the creation of ‘epigenetic clocks’. Previously, studies on the relationship between ageing and DNA methylation have assumed a linear relationship. Here, we show that several markers show a non-linear behaviour. In particular, we observe a tendency for saturation with age, especially in the cerebellum. Further, we show that the relationships between significant methylation changes and ageing are different in different tissues. We suggest a straightforward method of assessing all methylation-age relationships and cluster them according to their relative fold change. Our fold change selection outperforms the most common epigenetic clocks in predicting age for the cerebellum, but not for Blood or the Frontal Cortex. Further, we find that the saturation of methylation observed at older ages for the cerebellum explains why epigenetic clocks consistently underestimate the age there. The findings imply that assuming linear correlations might cause biologically important markers to be missed.
PANDA2: protein function prediction using graph neural networks
Authors: Zhao Chenguang , Liu Tong , Wang Zheng
Published: February 2022

High-throughput sequencing technologies have generated massive protein sequences, but the annotations of protein sequences highly rely on the low-throughput and expensive biological experiments. Therefore, accurate and fast computational alternatives are needed to infer functional knowledge from protein sequences. The gene ontology (GO) directed acyclic graph (DAG) contains the hierarchical relationships between GO terms but is hard to be integrated into machine learning algorithms for functional predictions. We developed a deep learning system named PANDA2 to predict protein functions, which used the cutting-edge graph neural network to model the topology of the GO DAG and integrated the features generated by transformer protein language models. Compared with the top 10 methods in CAFA3, PANDA2 ranked first in cellular component ontology (CCO), tied first in biological process ontology (BPO) but had a higher coverage rate, and second in molecular function ontology (MFO). Compared with other recently-developed cutting-edge predictors DeepGOPlus, GOLabeler, and DeepText2GO, and benchmarked on another independent dataset, PANDA2 ranked first in CCO, first in BPO, and second in MFO. PANDA2 can be freely accessed from http://dna.cs.miami.edu/PANDA2/.
Cell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissues
Authors: Hsieh Yuan-Pang , Naler Lynette B , Ma Sai , Lu Chang
Published: February 2022

BRCA1 germline mutation carriers are predisposed to breast cancers. Epigenomic regulations have been known to strongly interact with genetic variations and potentially mediate biochemical cascades involved in tumorigenesis. Due to the cell-type specificity of epigenomic features, profiling of individual cell types is critical for understanding the molecular events in various cellular compartments within complex breast tissue. Here, we produced cell-type-specific profiles of genome-wide histone modifications including H3K27ac and H3K4me3 in basal, luminal progenitor, mature luminal and stromal cells extracted from a small pilot cohort of pre-cancer BRCA1 mutation carriers (BRCA1mut/+) and non-carriers (BRCA1+/+), using a low-input ChIP-seq technology that we developed. We discovered that basal and stromal cells present the most extensive epigenomic differences between mutation carriers (BRCA1mut/+) and non-carriers (BRCA1+/+), while luminal progenitor and mature luminal cells are relatively unchanged with the mutation. Furthermore, the epigenomic changes in basal cells due to BRCA1 mutation appear to facilitate their transformation into luminal progenitor cells. Taken together, epigenomic regulation plays an important role in the case of BRCA1 mutation for shaping the molecular landscape that facilitates tumorigenesis.
Impact of environmental pollution on the obesogenic environment
Authors: Martínez-Esquivel Adriana , Trujillo-Silva Daniela Joyce , Cilia-López V Gabriela
Published: February 2022

Obesity figures in the world continue to increase, representing a multifactorial and multidimensional problem. Efforts to contribute to reduction in obesity have led to the study of this condition from different approaches, including the obesogenic environment (OE), which is harmful to health due to the multiple factors that compose the OE. Some of the most important factors are stress, lifestyle, and urban design, framed in a food system that provides caloric foods and contributes to intake of hypercaloric diets. The OE exacerbates the obesogenic process and chronic low-grade inflammation. However, these factors are not the only ones responsible for obesity. Environmental pollutants also contribute, because they interfere with metabolic processes that regulate lipid accumulation and increase body adiposity. In this review, we analyze the relationship between pollution and obesogenic processes. We postulate the inclusion of environmental pollution within the factors and definition of the OE.
Serum Interleukin 6 Level and Nutrition Status as Potential Predictors of Clinical Leprosy Development Among Household Contacts in Endemic Areas
Authors: Oktaria Salma , Anfasa Fatih , Menaldi Sri Linuwih , Bramono Kusmarinah , Nijsten Tamar E C , Thio Hok Bing
Published: February 2022

Background

Leprosy is a chronic infectious disease that can lead to severe lifelong disabilities. Close contacts of patients with leprosy have a higher risk of acquiring the disease. Nevertheless, there is a lack of reliable markers to predict Mycobacterium leprae infection. We aimed to identify new potential markers for developing clinical leprosy among contacts.

Methods

Serum levels of interleukin (IL) 6, IL-8, IL-10, hemoglobin, ferritin, and transferrin saturation were measured in 67 patients with multibacillary leprosy (MB), 65 household contacts (HHCs) of MB patients, and 127 endemic controls (ECs). By means of multivariate logistic regression and receiver operating characteristic (ROC) analyses, we analyzed baseline variables and laboratory parameters that showed significant differences between MB in the HHC and EC groups and obtained the respective areas under the curve (AUC). Optimal cutoff values of the associated cytokines were also determined.

Results

Elevated IL-6 level was observed in MB patients compared to HHCs and ECs (P = .022 and .0041, respectively). Anemia and iron deficiency were also higher in the MB group compared to HHCs or ECs (P < .001). Likewise, we observed an increased risk of having MB leprosy in underweight HHCs (odds ratio [OR], 2.599 [95% confidence interval {CI}, .991–6.820]) and underweight ECs (OR, 2.176 [95% CI, 1.010–4.692]). Further ROC analysis showed that high serum IL-6 level, underweight, anemia, and iron deficiency can discriminate leprosy from their HHCs (AUC, 0.843 [95% CI, .771–.914]; P = .000; optimal cutoff value of IL-6 = 9.14 pg/mL).

Conclusions

Our results suggest that serum IL-6 and nutrition status could serve as potential prognostic markers for the development of clinical leprosy in infected individuals.
Similar Mortality Among United States Veterans With Invasive and Noninvasive Pneumonia due to Group B Streptococcus
Authors: Banks Richard E , Wilson Brigid M , Bej Taissa , Briggs Janet M , Song Sunah , Goto Michihiko , Jump Robin L P , Perez Federico
Published: February 2022

Background

The nosology of noninvasive pneumonia due to group B Streptococcus (GBS) is not well defined. This study compared clinical characteristics and outcomes of patients with invasive pneumonia and noninvasive pneumonia caused by GBS.

Methods

We conducted a retrospective cohort study among Veterans Affairs (VA) healthcare users between 2008 and 2017. Using data from electronic health records, we identified patients who had blood or respiratory cultures that grew GBS and had invasive pneumonia or noninvasive pneumonia. We analyzed patient and infection characteristics associated with all-cause mortality, including among the subset of patients with cultures that were monomicrobial for GBS.

Results

Among 1791 patients with GBS pneumonia, 646 (36%) cases were invasive and 1145 (64%) were noninvasive. Among those, 535 and 424 cases of invasive and noninvasive pneumonia, respectively, had cultures that were monomicrobial for GBS. All-cause 30-day mortality among those with monomicrobial GBS pneumonia was 15% for both those with invasive and noninvasive disease, respectively. Increasing age, severity of illness, healthcare exposure in the previous 90 days, and polymicrobial infection with Staphylococcus aureus were independently associated with all-cause mortality at 30 days.

Conclusions

In this large cohort, even when considering cases for which GBS was the only pathogen recovered, >40% of GBS pneumonia cases were noninvasive. All-cause mortality was comparable for invasive and noninvasive pneumonia. These findings suggest that the burden of GBS pneumonia may be greater than previously recognized by surveillance of invasive GBS disease and may inform treatment and prevention efforts.
Long-term Prognosis Following Vascular Graft Infection: A 10-Year Cohort Study
Authors: Sixt Thibault , Aho Serge , Chavanet Pascal , Moretto Florian , Denes Eric , Mahy Sophie , Blot Mathieu , Catherine François-Xavier , Steinmetz Eric , Piroth Lionel
Published: February 2022

Background

Vascular graft infection (VGI) remains a severe disease with high mortality and relapse rates. We performed a retrospective single-center cohort study to highlight factors associated with long-term all-cause mortality in patients with vascular graft infection.

Methods

All patients hospitalized in our facility over 10 years for VGI were included. VGI was defined by the presence of a vascular graft or an aortic stent graft (stent or fabric), associated with 2 criteria among clinical, biological, imaging, or microbiological elements in favor of VGI. The primary outcome was all-cause mortality. Empirical antibiotic therapy was considered as appropriate when all involved pathogens were susceptible in vitro to the antibiotics used. The surgical strategy was defined as nonoptimal when the graft was not removed in a late-onset surgery (>3 months) or no surgery was performed.

Results

One hundred forty-six patients were included. Empirical antibiotic therapy was administered in 98 (67%) patients and considered appropriate in 55 (56%) patients. Surgery was performed in 136 patients (96%) and considered as optimal in 106 (73%) patients. In multivariable analysis, appropriate empirical antibiotic therapy was associated with a lower probability of mortality (hazard ratio, 0.47 [95% confidence interval, .30–.79]; P = .002). Long-term survival did not differ according to whether the surgical strategy was considered optimal or not (log-rank = 0.66).

Conclusions

Appropriate empirical antibiotic therapy is a cornerstone of the management of VGI. Whenever possible, antibiotics must be associated with optimal surgical management. However, surgery could potentially be avoided in comorbid patients who are treated with appropriate antibiotics.
N064A (Alliance): Phase II Study of Panitumumab, Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma
Authors: Halfdanarson Thorvardur R , Foster Nathan R , Kim George P , Haddock Michael G , Dakhil Shaker R , Behrens Robert J , Alberts Steven R
Published: February 2022

Background

This North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer.

Methods

The treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued.

Results

Fifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%.

Conclusion

The combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier NCT00601627).
Consider Myocarditis When Patients Treated with Immune Checkpoint Inhibitors Present with Ocular Symptoms
Authors: Rhee John Y , Torun Nurhan , Neilan Tomas G , Guidon Amanda C
Published: February 2022

Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.
A Narrative Review of the Literature on the Recruitment of Younger Police Officers in Age and in Service: What Are the Implications for the Police in England and Wales?
Authors: Williams Emma , Sondhi Arun
Published: February 2022

The Police Uplift Programme in England and Wales aims to recruit more than 20,000 new police officers into the service. There is little known about the potential consequences associated with a large-scale recruitment drive and the effect of introducing a younger cohort of officers into the ranks of the police. This article is based on a narrative review of 2,110 English-language titles including grey literature exploring the implications for the police who are younger in age and service workforce profile. Titles were identified through electronic and handsearching methods. Fifty-nine titles were assessed for inclusion, of which 48 were subject to a full-text review. The majority of papers were from North America. Three themes were identified from the review: (1) issues related to cultural considerations including younger officers’ preference for transparent and linear relationships and highlighting an emphasis on public service; (2) well-being and work–life balance considerations; and (3) harnessing the skill base through effective recruitment and retention practices. The findings suggest that police forces can create a narrative for new recruits as adult learners committed to public service combined with enhanced leadership styles that prioritize teamwork, transparency, and personal development.
The Polls—Trends
Authors: Banai Ayelet , Votta Fabio , Seitz Rosa
Published: February 2022

This article presents trends in public opinion toward immigration in the European Union (EU), between 2002 and 2018. Immigration is a salient and contentious issue in contemporary politics across Europe and is used by Eurosceptic parties in both government and opposition to mobilize support. Public opinion data—drawn from the European Social Survey and the Eurobarometer—reveals the following noteworthy trends over the past two decades. First, positive public attitudes toward immigration have increased across member states, with a temporary setback in 2015–16. Second, immigration is a divisive issue throughout the EU. While public opinion in some regions generally favors immigration, opinion is divided everywhere. Third, despite regional variations between northern, western, and southern Europe, EU-wide trends suggest the emergence of a collective public opinion, crossing national borders. Fourth, despite vocal political opposition to immigration, solid majorities of the public view immigration favorably over time and across regions. To the numerous studies of European public opinion on immigration, this article contributes a useful overview of the long-term trends, with regional and EU-wide presentation and data visualization.
The Assessment Gap: Racial Inequalities in Property Taxation
Authors: Avenancio-León Carlos F , Howard Troup
Published: February 2022

We document a nationwide “assessment gap” that leads local governments to place a disproportionate fiscal burden on racial and ethnic minorities. We show that holding taxing jurisdictions and property tax rates fixed, Black and Hispanic residents face a 10%–13% higher tax burden for the same bundle of public services. We decompose this disparity into between- and within-neighborhood components and find that just over half of it arises between neighborhoods. We then present evidence on mechanisms. Property assessments are less sensitive to neighborhood attributes than market prices are. This generates spatial variation in tax burden within jurisdiction and leads to overtaxation of communities with a high share of minority residents. We also find appeals behavior and appeals outcomes differ by race within neighborhood. Inequality does not arise from (i) racial differences in transaction prices or (ii) differences in features of the housing stock.
Colchicine use and the risk of CKD progression: a multicentre nested case-control study
Authors: Kim Hyung Woo , Joo Young Su , Yun Hae-Ryong , Kim Jae Young , Jhee Jong Hyun , Roh Yun Ho , Park Jung Tak , Chang Tae Ik , Yoo Tae-Hyun , Kang Shin-Wook , Han Seung Hyeok
Published: February 2022

Objectives

Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout.

Methods

We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3–G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex.

Results

Overall, 3085 patients with CKD progression were matched to 11 715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3.

Conclusion

Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout.
ANALYSIS OF 210PB DEPOSITION DISTRIBUTION CHARACTERISTICS IN WINTER AT ROKKASHO IN AOMORI BASED ON HIGH RESOLUTION ATMOSPHERIC TRANSPORT/DEPOSITION MODEL CALCULATION
Authors: Cai Yu , Yamazawa Hiromi , Moriizumi Jun , Hasegawa Hidenao
Published: February 2022

To evaluate 210Pb deposited on the surface of sea around Japan in detail, the performance of atmospheric transport/deposition model for 222Rn and its progenies was examined. To test the model’s reproducibility of 210Pb deposition in winter, it was applied at Rokkasho in Aomori, where the model had been reported to significantly underestimate when the horizontal grid interval of 9 km was used. It was shown that the precipitation on the Pacific Ocean side and Mutsu Bay and hence the 210Pb deposition at Rokkasho were significantly improved with the grid interval of 3 km although the deposition was still underestimated by the observation. This underestimation was considered to be caused by model’s neglect of horizontal drift of snow and rain. It was also pointed out that the deposited 210Pb was mainly contributed by the lower atmosphere up to 2–3 km.
The Electroretinogram as a Potential Biomarker of Psychosis in Children at Familial Risk
Authors: Moreau Isabel , Hébert Marc , Maziade Michel , Painchaud Alexandra , Mérette Chantal
Published: February 2022

We previously proposed the electroretinogram (ERG) as a promising biomarker of major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP), given that we found anomalies in the ERG parameters of patients with these diagnoses as well as in their children who are at high risk (HR) of developing such disorders. The aim of the present study is to investigate the usefulness of the ERG for individual detection, among HR children, of an ERG profile resembling that of a SZ patient, as this may indicate a stronger likelihood of transition to psychosis. Using a logistic regression model previously derived from the ERG assessments of SZ patients and control (CT) subjects, individual risk scores were obtained for 61 HR and 80 CT youth. Those with a very high individual risk score were classified as “schizophrenia-like” (SZ-like). We found that the HR subjects were 3.5 times more likely to be classified as SZ-like than the CT subjects (95% CI [1.1–11.8]). Furthermore, among the HR subjects, we studied the relationship between the SZ-like classification and psychotic-like experiences and found that HR subjects classified as SZ-like were 2.7 times more likely than all remaining HR subjects to have experienced psychotic-like symptoms (95% CI [1.3–4.6]), and 6.8 times more likely than those with a very low individual risk score (95% CI [1.4–40.4]). Our results suggest that a model previously derived from ERG data on SZ patients could be a potential tool for early detection of the susceptibility to a psychotic-like disorder among familial HR children.
Sleep regularity and body mass index: findings from a prospective study of first-year college students
Authors: Wong Patricia M , Barker David , Roane Brandy M , Van Reen Eliza , Carskadon Mary A
Published: February 2022

Study Objectives

Using data from a large, prospective study of sleep in first-year college students, we examined whether students’ sleep regularity is associated with body mass index (BMI) and BMI change (∆BMI) during their first college semester. In a subset of participants, we also tested whether dim light melatonin onset (DLMO) phase and DLMO-bedtime phase angle are associated with BMI and ∆BMI.

Methods

Analyses included data from 581 students (mean age = 18.7 ± 0.5 years; 58% female; 48% non-white) who had their height and weight assessed at the start of classes (T1) and end of 9 weeks. Participants completed online daily sleep diaries from which total sleep time (TST) and the sleep regularity index (SRI) were calculated. Among participants who completed a DLMO protocol (n = 161), circadian phase was quantified by DLMO and circadian alignment by DLMO-bedtime phase angle. Data were analyzed with linear regressions that controlled for sex and average TST.

Results

Average SRI was 74.1 ± 8.7 (range: 25.7; 91.6). Average BMI at T1 was 22.0 ± 3.5 and participants gained 1.8 ± 2.4 kg (range: −7.2; 11.4); 39% gained 2–5 kg, 8% gained >5 kg. Lower SRI was associated with greater BMI at T1 (B = −0.06 [95% CI: −0.09; −0.02], p = 0.001) but not with ∆BMI (p = 0.062). Average TST was not significantly associated with BMI or ∆BMI, nor were circadian phase and alignment in the subsample (p’s > 0.05).

Conclusions

Sleep regularity is an understudied but relevant sleep dimension associated with BMI during young adulthood. Our findings warrant future work to examine longer-term associations between sleep regularity and weight gain.
Neural Stem/Progenitor Cell Transplantation in Parkinson’s Rodent Animals: A Meta-Analysis and Systematic Review
Authors: Zheng Yifeng , Zhou Jun , Wang Yisai , Fan Fanfan , Liu Shengwen , Wang Yu
Published: February 2022

The effects of neural stem/progenitor cells (NSPCs) have been extensively evaluated by multiple studies in animal models of Parkinson’s disease (PD), but the therapeutic efficacy was inconsistent. Here, we searched 4 databases (PubMed, Embase, Scopus, and Web of Science) and performed a meta-analysis to estimate the therapeutic effects of unmodified NSPCs on neurological deficits in rodent animal models of PD. Data on study quality score, behavioral outcomes (apomorphine or amphetamine-induced rotation and limb function), histological outcome (densitometry of TH+ staining in the SNpc), and cell therapy-related severe adverse events were extracted for meta-analysis and systematic review. Twenty-one studies with a median quality score of 6 (range from 4 to 9) in 11 were examined. Significant improvement was observed in the overall pooled standardized mean difference (SMD) between animals transplanted with NSPCs and with control medium (1.22 for apomorphine-induced rotation, P < .001; 1.50 for amphetamine-induced rotation, P < .001; 0.86 for limb function, P < .001; and –1.96 for the densitometry of TH+ staining, P < .001). Further subgroup analysis, animal gender, NSPCs source, NSPCs dosage, and pretreatment behavioral assessment were closely correlated with apomorphine-induced rotation and amphetamine-induced rotation. In conclusion, unmodified NSPCs therapy attenuated behavioral deficits and increased dopaminergic neurons in rodent PD models, supporting the consideration of early-stage clinical trial of NSPCs in patients with PD.
A review of branched-chain amino acids in lactation diets on sow and litter growth performance
Authors: Holen Julia P , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Gebhardt Jordan T , Titgemeyer Evan C , Goodband Robert D
Published: February 2022

Branched-chain amino acids (BCAA) are three essential amino acids (AA) for lactating sows; however, the effects of dietary Leu, Val, and Ile on sow and litter performance within the literature are equivocal. The BCAA are structurally similar and share the first steps of their catabolism pathway where Leu, Val, and Ile are transaminated through BCAA aminotransferase and irreversibly decarboxylated by the branched-chain α-ketoacid dehydrogenase complex. Although these steps are shared among BCAA, Leu is recognized as the primary stimulator due to Leu’s greater affinity towards the enzymes compared to Val and Ile. Since the late 1990s, sows are producing larger and heavier litters and generally consume diets with greater concentrations of Leu and crystalline AA, which may create imbalances among dietary BCAA. Research conducted with growing-finishing pigs confirms that high concentrations of Leu can impair BCAA utilization and growth performance. However, the effects of BCAA on lactating sow and litter performance are not as clearly understood. Within mammary tissue, BCAA uptake is greater than milk output of BCAA since Val, Ile, and Leu are catabolized to form non-essential AA, lactose, fatty acids, and other metabolites. Within the mammary gland, BCAA aminotransferase activity is much higher than within skeletal muscle, liver, or small intestine. Thus, competition among the BCAA, namely, between Leu and Val, can significantly inhibit Val uptake within mammary tissue. Therefore, dietary modifications that mitigate BCAA competition may positively influence Val utilization for colostrum and milk synthesis. Little data exist on Ile and Leu requirements for modern lactating sows. Although Val requirements have been extensively researched in the last 25 yr, an ideal Val:Lys has not been consistently established across experiments. Some studies concluded that total Val concentrations above 120% of Lys optimized performance, whereas others determined that increasing SID Val:Lys from 55% to 136% did not improve piglet growth performance. Although increasing dietary Val positively influences fat and protein composition of colostrum and milk, litter growth during lactation is not always positively affected. Given the competition among BCAA for utilization within mammary tissue, research evaluating the Leu and Ile requirement of modern lactating sows is warranted to fully understand the influence and interactions of BCAA on reproductive and litter growth performance.
Visual attention around a hand location localized by proprioceptive information
Authors: Shioiri Satoshi , Sasada Takumi , Nishikawa Ryota
Published: February 2022

Facilitation of visual processing has been reported in the space near the hand. To understand the underlying mechanism of hand proximity attention, we conducted experiments that isolated hand-related effects from top–down attention, proprioceptive information from visual information, the position effect from the influence of action, and the distance effect from the peripersonal effect. The flash-lag effect was used as an index of attentional modulation. Because the results showed that the flash-lag effect was smaller at locations near the hand, we concluded that there was a facilitation effect of the visual stimuli around the hand location identified through proprioceptive information. This was confirmed by conventional reaction time measures. We also measured steady-state visual evoked potential (SSVEP) in order to investigate the spatial properties of hand proximity attention and top–down attention. The results showed that SSVEP reflects the effect of top–down attention but not that of hand proximity attention. This suggests that the site of hand proximity attention is at a later stage of visual processing, assuming that SSVEP responds to neural activities at the early stages. The results of left-handers differed from those of right-handers, and this is discussed in relation to handedness variation.
Modification of plasma membrane H+-ATPase in Masson pine (Pinus massoniana Lamb.) seedling roots adapting to acid deposition
Authors: Zhou Sijie , Wang Ping , Ding Yi , Xie Linbei , Li Ao
Published: February 2022

To understand the regulation of roots plasma membrane H+-ATPase in Masson pine responding to acid deposition, the changes in biomass, plant morphology, intracellular H+, enzyme activity and H+-ATPase genes expression in Masson pine seedlings exposed to simulated acid rain (SAR, pH 5.6 and 4.6) with and without vanadate were studied. Simulated acid rain exposure for 60 days increased the intracellular H+ in pine roots whether added with 0.1 mM Na3VO4 or not. The growth of seedlings treated with SAR was maintained well, even the primary lateral root length, root dry weight and number of root tips in seedlings exposed to SAR at pH 4.6 were higher than that of the control (pH 6.6). However, the addition of vanadate resulted in severe growth inhibition and obvious decline in morphological parameters. Similarly, ATP hydrolytic activity and H+ transport activity of roots plasma membrane H+-ATPase, both were stimulated by SAR whereas they were inhibited by vanadate, and the highest activity stimulation was observed in pine roots subjected to SAR at pH 4.6. In addition, SAR also induced the expression of the investigated H+-ATPase subunits (atpB, atpE, atpF, atpH and atpI). Therefore, the roots plasma membrane H+-ATPase is instrumental in the growth of Masson pine seedlings adapting to acid rain by a manner of pumping more protons across the membrane through enhancing its activity, and which involves the upregulated gene expression of roots H+-ATPase subunits at transcriptional level.