bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of the stress hyperglycemia ratio, glycemic gap, and glucose to assess the impact of stress‐induced hyperglycemia on ischemic stroke outcome
Authors: Roberts Gregory , Sires James , Chen Angela , Thynne Tilenka , Sullivan Cheyne , Quinn Stephen , Chen Won Sun , Meyer Emily
Published: September 2021

Background

The aim of this study is to compare metrics specific for stress‐induced hyperglycemia (SIH) with glucose for predicting ischemic stroke outcome.

Methods

This observational retrospective study (n = 300) included patients acutely hospitalized for ischemic stroke over a 3.8‐year period. We assessed the association between acute ischemic stroke outcome with the stress hyperglycemia ratio (SHR, relative increase in glycemia) and glycemic gap (GG, absolute increase in glycemia) using admission values and 5‐day maximum values, along with incidence of poor outcome above recognized clinical thresholds of glucose 10 mmol/L, SHR 1.14, and GG 2.5 mmol/L.

Results

At admission, only SHR was associated with outcome after adjustment for clinical covariates (odds ratio [OR] = 2.88; 95% CI: 1.05‐7.91; P = .041), while glucose or GG were not. Admission SHR ≥ 1.14 was also an indicator of poor outcome (39.1% vs 23.4%, P = .016), but not glucose ≥10 mmol/L or GG ≥ 2.5 mmol/L. All 5‐day maximum glucose metrics were associated with outcome, as was any SHR ≥ 1.14 (40.9% vs 20.1%, P < .001) or GG ≥ 2.5 mmol/L (42.9% vs 23.4%, P = .011), but not glucose ≥10 mmol/L. Increased comorbidity was strongly associated with worse outcome (P < .001) in all models.

Conclusions

SHR provided the best prognostic insight at admission to assess the relationship between SIH and ischemic stroke outcome. Absolute glucose levels failed to account for natural interpatient variation in background glycemia and provided little prognostic insight. To assess the impact of SIH, future interventional studies need to be designed using designated markers of SIH such as SHR in preference to absolute glucose.
Cardiovascular disease and risk of incident diabetes mellitus: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Missikpode Celestin , Durazo‐Arvizu Ramon A. , Cooper Richard S. , OʼBrien Matthew James , Castaneda Sheila F. , Talavera Gregory A. , Gallo Linda C. , Llabre Maria M. , Perera Marisa J. , Perreira Krista M. , Ricardo Ana C. , Pirzada Amber , Lash James P. , Daviglus Martha
Published: September 2021

Background

Studies have reported an association between prevalent cardiovascular disease (CVD) and risk of diabetes mellitus (DM). However, factors that may explain the association remain unclear. We examined the association of prevalent CVD with incident DM and assessed whether weight gain and medication use may explain the association.

Methods

Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008‐2011) and Visit 2 (2014‐2017) were used to compare incidence of DM among individuals with and without self‐reported CVD at Visit 1. A total of 1899 individuals with self‐reported CVD were matched to controls free of self‐reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self‐reported CVD on incident DM was examined using a generalized estimating equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated.

Results

Covariate distributions were similar among individuals with and without self‐reported CVD. The incidence of DM among persons with self‐reported CVD was 15.3% vs 12.7% among those without self‐reported CVD. Compared to individuals without self‐reported CVD, individuals with self‐reported CVD had a 24% increased risk for incident DM (odds ratio = 1.24, 95% confidence interval = 1.01, 1.51). The association between self‐reported CVD and DM was mediated by the use of beta‐blockers (proportion explained = 25.4%), statins (proportion explained = 18%), and diuretics (proportion explained = 8%). We found that weight gain did not explain the observed association.

Conclusions

Prevalent cardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially explained by some medications used to manage CVD.
Afatinib treatment response in advanced lung adenocarcinomas harboring uncommon mutations
Authors: Li Teng , Wang Shouzheng , Ying Jianming , Wang Yan , Hu Xingsheng , Hao Xuezhi , Xu Ziyi , Xing Puyuan , Li Junling
Published: September 2021

Background

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved the prognosis of mutant lung cancer; however, the clinical application value of TKIs for nonclassical EGFR mutation is unclear, especially for patients with rare uncommon mutations.

Methods

A retrospective study based on electronic medical records was conducted to collect data on the effectiveness of afatinib in patients with stage IIIB/IV lung adenocarcinoma (LUAD) bearing uncommon mutations between January 2017 and January 2021.

Results

Forty‐two patients with uncommon mutations treated with afatinib were enrolled. The objective response rate (ORR) was 50.0% (10 of 20 patients). The median time to treatment failure (TTF) was 11.7 months (95% confidence interval = 8.5–18.3 months). Of the 42 patients, the median TTF was 15.0, 11.7, and 16.6 months in patients with Gly719Xaa (G719X), Ser768Ile (S768I), and Leu861Gln (L861Q) mutations, respectively. In patients with the rare uncommon mutation, the median TTF was 10.0 months, and the ORR was 50.0%. Afatinib demonstrated clinical activity across a set type of specific rare uncommon mutations, including EGFR L747P, A767_V769dup, and L833V/H835L, with a case having a TTF of more than 1 year. Molecular profiling reports of 16 afatinib‐resistant biopsy samples were available, and the secondary T790M mutation was detected in one patient with L833V/H835L mutation and one harboring S768I/L858R mutation.

Conclusions

Our findings suggested that afatinib is effective in patients with uncommon mutations. Mechanisms of afatinib resistance vary and need further investigation.
DNA methylation‐based biomarkers of aging were slowed down in a two‐year diet and physical activity intervention trial: the DAMA study
Authors: Fiorito Giovanni , Caini Saverio , Palli Domenico , Bendinelli Benedetta , Saieva Calogero , Ermini Ilaria , Valentini Virginia , Assedi Melania , Rizzolo Piera , Ambrogetti Daniela , Ottini Laura , Masala Giovanna
Published: September 2021

Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed “next‐generation clock” DNAmGrimAge outperforms “first‐generation clocks” in predicting longevity and the onset of many age‐related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm‐based biomarker of healthy aging. A fundamental biological property of epigenetic, and in particular DNAm modifications, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one's lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the “Diet, Physical Activity, and Mammography” (DAMA) study: a 24‐month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial. Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer‐related pathways. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging‐related epigenetic mechanisms.
Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy
Authors: Bordas‐Le Floch Véronique , Berjont Nathalie , Batard Thierry , Varese Nirupama , O’Hehir Robyn E. , Canonica Walter G , van Zelm Menno C. , Mascarell Laurent
Published: September 2021

Background

IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen‐specific IgG2 levels after a 3rd consecutive pre‐seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen‐specific IgG2 in individuals undergoing house dust mite immunotherapy (HDM‐AIT) and explore whether the interrelationship with other humoral responses (i.e., IgG4 and IgE) may discriminate between high and low responders.

Methods

Levels of serum Dermatophagoides pteronyssinus and Dermatophagoides farinae‐specific IgG2, IgG4, and IgE antibodies were measured by ELISA or ImmunoCap in a sub‐group of individuals enrolled in a randomized, double‐blind, placebo‐controlled, sublingual AIT study evaluating the safety and efficacy of a 300 IR HDM tablet.

Results

After 1‐year sublingual AIT, HDM‐specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM‐specific IgG2, IgE, and/or IgG4 responses is seen in subjects benefiting the most from HDM‐AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM‐specific IgG2 and IgE responses is only observed in individuals stratified as high responders.

Conclusions

We provide evidence for coordinated serum immune responses upon AIT in HDM‐allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM‐specific IgE, IgG2, and IgG4 in serum could be used as follow‐up combined markers to support decision as to AIT continuation and/or adaptation.
Association between obstructive sleep apnea and male serum testosterone: A systematic review and meta‐analysis
Authors: Su Liang , Meng Yu‐Hang , Zhang Si‐Zheng , Cao Yan , Zhu Jian , Qu Hua , Jiao Yong‐Zheng
Published: September 2021

Background

Currently, there is no consensus on the effect of obstructive sleep apnea on male serum testosterone levels. This systematic review and meta‐analysis aimed to determine the association between obstructive sleep apnea and male serum testosterone level.

Methods

The literature related to obstructive sleep apnea and male serum testosterone in the PubMed, Embase, and Cochrane Library databases were searched from their inception to June 10, 2021. Data were pooled using the Stata 15 software. We performed a subgroup analysis of studies after matching the age and body mass index, as well as according to the severity of obstructive sleep apnea.

Results

Eighteen studies involving 1823 men were included in the systematic review and meta‐analysis. A significant inverse association between obstructive sleep apnea and male serum testosterone (SMD = −0.76; 95% CI: −1.18, −0.33; p = 0.001) was found. After adjusting for age and body mass index, this inverse association still existed (SMD = −0.8; 95% CI = −1.41, −0.18, p = 0.012). According to the subgroup analysis of obstructive sleep apnea severity, our results showed that serum testosterone was not significantly decreased in mild (SMD = −0.58; 95% CI = −1.88, 0.73, p = 0.386) and moderate obstructive sleep apnea patients (SMD = −0.94; 95% CI = −2.04, 0.15, p = 0.092), whereas it was significantly reduced in patients with severe obstructive sleep apnea (SMD = −1.21; 95% CI = −2.02, −0.41, p = 0.003).

Conclusions

Obstructive sleep apnea is inversely associated with male serum testosterone levels, independent of body mass index and age. Notably, the severity of obstructive sleep apnea is also correlated with male serum testosterone, which is significantly reduced in patients with severe obstructive sleep apnea.
Busulfan impairs blood–testis barrier and spermatogenesis by increasing noncollagenous 1 domain peptide via matrix metalloproteinase 9
Authors: Jiang Shuyi , Xu Ying , Fan Yunxia , Hu Ying , Zhang Qiang , Su Wenhui
Published: September 2021

Backgrounds

Sterility induced by anti‐cancer treatments has caused significant concern, yet the mechanism and treatment exploration are little for male infertility after cancer therapy. Busulfan, the antineoplastic that was widely applied before bone marrow transplantation, was known to induce male reproductive disorder.

Objectives

To investigate the effect of busulfan on blood–testis barrier function in adult rats and determine whether noncollagenous 1 domain peptide, the biologically active fragment proteolyzed from the collagen α3 chain (IV) by matrix metalloproteinase 9, was involved during this process.

Materials and methods

Adult male rats were treated with one‐dose or double‐dose of busulfan (10 mg/kg) before euthanized at day 35. Blood–testis barrier integrity assay, HE staining, immunofluorescence, and Western blot were used to validate the effect of busulfan on blood–testis barrier permeability and spermatogenesis. JNJ0966 was applied to specifically inhibit the matrix metalloproteinase 9 activity. The polymerization activity of F‐actin/G‐actin and microtubule/tubulin in the testis were assessed by using commercial kits.

Results

A noteworthy blood–testis barrier injury and significant up‐regulation of matrix metalloproteinase 9 activity and noncollagenous 1 level after a single‐dose busulfan (10 mg/kg) treatment in adult rat testis were revealed. The application of JNJ0966 was found to decrease noncollagenous 1 level and rescue the busulfan‐induced blood–testis barrier injury including the mis‐localization of junction proteins across the seminiferous epithelium, by recovering the organization and polymerization of both F‐actin and microtubule. The busulfan‐induced spermatogenesis impairment was also improved by JNJ0966.

Conclusion

These findings thus demonstrate that the elevation in matrix metalloproteinase 9 and noncollagenous 1 might participate in busulfan‐induced blood–testis barrier disruption in adult male rats. As such, busulfan‐induced male infertility could possibly be managed through interventions on noncollagenous 1 production.
Very preterm infants admitted to a tertiary neonatal unit in central Vietnam showed poor postnatal growth
Authors: Tran Hoang Thi , Le Thao Dieu , Skinner Alyson , Narchi Hassib
Published: September 2021

Aim

We aimed to evaluate the postnatal growth of very preterm infants.

Methods

This was a cross‐sectional observational study of neonates born before 32 weeks of gestation and admitted to the neonatal unit at Da Nang Hospital for Women and Children, Vietnam, between 1 February 2020 and 30 September 2020. Morbidities, therapies, nutrition modalities and growth status were recorded from admission to discharge.

Results

The 78 infants (51% female) were born at a median of 29 weeks and mean birth weight of 1247 grams. The mean weight gain velocity from regaining their birth weight until discharge was 12.7 ± 4.9 g/kg/d. At discharge, the Z‐scores for weight, length, both weight and length and weight for length were lower than at birth in 94%, 67%, 64% and 95% of infants and the Delta Z‐scores were less than −1 in 73%, 44%, 39% and 82%. Late‐onset sepsis (LOS) and bronchopulmonary dysplasia (BPD) were significantly associated with growth failure, with adjusted odds ratios of 3.6 and 20.1, respectively.

Conclusion

The high rate of poor growth among the very preterm infants in our study indicates the need to reduce LOS and BPD and ensure the availability of human milk fortifier, vitamin and mineral supplements.
Terrorism Risk and the Mediating Role of Manager Experience: Empirical Evidence*
Authors: Mazhar Ummad
Published: September 2021

Firms in developing countries face security risks and suffer from weak institutional support. In theory, managerial talent is pivotal in firms' assessment of external risks and implementing operational changes in response. Using managers' experience as a proxy for managerial talent, this study estimates its mediating role in determining firms' security costs in a threatened environment. The study uses survey data from 1700 formal firms covering 13 sectors and 17 locations in Pakistan. The nonlinear effects are estimated at different percentiles of the distribution of managerial experience. The main finding is a positive effect of the risk of terrorism on firm security costs, which is decreasing in managerial experience. This effect is robust against alternative specifications. The issue of endogeneity of the variables of interest is tackled using the instrumental variables approach. The implications and limitations of the findings are noted.
Political Instability, Civil War and Cost Efficiency of Banking Firms: A Case Study in Sri Lanka*
Authors: Seelanatha Lalith
Published: September 2021

This paper investigates the effects of political instability resulting from successive regime changes and the 30‐year civil war on the cost efficiency of local banks in Sri Lanka. A translog cost function was used to estimate bank cost efficiency, and a multivariate regression model was used to investigate the determinants of bank cost inefficiency. On average, the cost efficiency of banks in Sri Lanka during the study period was relatively high. Sri Lankan banks performed more efficiently during the second political regime (2001–2004), which had more liberal political and economic policies to promote the private sector compared with other regimes. During this period, the government was involved in peace talks, leading to a ceasefire agreement that temporarily stopped the violence. Furthermore, the positive coefficients for the dummy variables representing the third and fourth political regimes showed that more restrictive economic policies can increase bank cost inefficiencies. The results also indicate that immediately following the civil war, Sri Lankan banks recorded a decline in cost efficiency. Cost inefficiency was positively associated with banks' risk aversion, credit risk, market share, interest rate risk and increase in GDP and negatively associated with non‐earning assets, liquidity, bank size and concentration.
Grassland reclamation of a copper mine tailings facility: Long‐term effects of biosolids on plant community responses
Authors: Gagnon Alyson , Ploughe Laura W , Harris Michelle P , Gardner Wendy C , Pypker Thomas , Fraser Lauchlan H
Published: September 2021

Aim

We explore long‐term plant community responses 17 years after a one‐time application of biosolids (0, 50, 100, 150, 200, 250 dry Mg/ha) to determine: (a) whether the land application of biosolids on mine tailings, seeded with an agronomic grass‐legume mixture, affects long‐term plant community responses; (b) how application rates and soil texture influenced plant community responses and community structure; and (c) whether native plant species have colonized and contributed to the reclaimed plant community.

Location

Two tailings deposits (sand and silt loam) generated by a copper–molybdenum (Cu–Mo) mine in southern British Columbia, Canada.

Methods

Plant communities were sampled by visual evaluation of cover percentage to the lowest taxonomic level possible. Vegetation surveys were completed on two mine tailings deposits within the storage facility that have different soil textures (sand and silt loam).

Results

Results showed that the interaction of biosolids applications and soil texture impacted multiple community plant responses, including increasing plant cover at both sites, and increasing richness, evenness and diversity at the sandy site. Biosolids application enhanced the performance of spontaneously established species (volunteer species) and non‐native/naturalized grasses.

Conclusion

Our study demonstrated that biosolids application facilitates ecological succession by enhancing the establishment of non‐native volunteer species over the long term, which increases vegetative cover on both deposits and promotes plant communities’ diversity on sites with sandy soil texture.
A matching procedure for sequential experiments that iteratively learns which covariates improve power
Authors: Kapelner Adam , Krieger Abba
Published: September 2021

We propose a dynamic allocation procedure that increases power and efficiency when measuring an average treatment effect in sequential randomized trials exploiting some subjects' previous assessed responses. Subjects arrive sequentially and are either randomized or paired to a previously randomized subject and administered the alternate treatment. The pairing is made via a dynamic matching criterion that iteratively learns which specific covariates are important to the response. We develop estimators for the average treatment effect as well as an exact test. We illustrate our method's increase in efficiency and power over other allocation procedures in both simulated scenarios and a clinical trial dataset. An R package “SeqExpMatch” for use by practitioners is available on CRAN.
Health care provider support and factors associated with breastfeeding beyond infancy: A cross‐national study
Authors: Keim Sarah A. , Tchaconas Alexis , Ford Jane B. , Nickel Nathan C. , Heffern Debbi , Adesman Andrew
Published: September 2021

Background

Breastfeeding beyond infancy (12 months) remains atypical in the United States, United Kingdom, Canada, and Australia, and the role of health care providers is unclear. The objective of this study was to compare women's perceptions of provider support and other factors affecting breastfeeding beyond infancy across countries, among women who had each successfully breastfed at least one child that long.

Methods

Women completed an online questionnaire distributed via La Leche League, USA (2013), about sources and ratings of support for breastfeeding for their oldest child who was breastfed at least 12 months and participant demographics. Multivariable log‐binomial regression was used to compare ratings of health care provider support and the importance of 13 factors by country.

Results

Some similarities and many differences were observed across countries in support received from providers, whereas modest or no differences were observed in the importance women placed on factors like health benefits and enjoyment of breastfeeding. Of 59 581 women, less than half discussed their decision to breastfeed beyond infancy with their child's provider. United Kingdom women rated their comfort in discussing breastfeeding beyond 12 months with their providers and the support received as lower than United States women. Canadian women gave lower ratings than United States women, but inconsistently. Australian women rarely differed from United States women in their responses. Providers’ recommendations were not important to the decision to breastfeed beyond infancy, especially for United Kingdom women.

Discussion

Rates of breastfeeding beyond infancy are low in these countries; improving provider support may help achieve global breastfeeding goals.
Intravitreous treatment of severe ocular von Hippel–Lindau disease using a combination of the VEGF inhibitor, ranibizumab and PDGF inhibitor, E10030: Results from a phase 1/2 clinical trial
Authors: Hwang Christopher K. , Chew Emily Y. , Cukras Catherine A. , Keenan Tiarnan D. L. , Wong Wai T. , Linehan W. Marston , Chittiboina Prashant , Pacak Karel , Wiley Henry E.
Published: September 2021

Background

Treatment options for severe ocular von Hippel–Lindau (VHL) disease are limited. This trial evaluated preliminary safety and potential efficacy of combination intravitreous injection with ranibizumab, a vascular endothelial growth factor (VEGF) inhibitor, and E10030, a PDGF inhibitor, for eyes with VHL disease‐associated retinal hemangioblastoma (RH) not amenable or responsive to thermal laser photocoagulation.

Methods

This was a prospective, single‐arm, open‐label phase 1/2 study, comprised of three adults with VHL‐associated RH and vision loss. Intravitreous injections of ranibizumab (0.5 mg) and E10030 (1.5 mg) were given unilaterally every 4 weeks in the study eye through 16 weeks, then every 8 weeks through 48 weeks. Supplementary standard care therapies were allowed without restriction after 40 weeks. The primary outcome was the ocular and systemic adverse effect profile at 52 weeks. Secondary outcomes included changes in best‐corrected visual acuity (BCVA), RH size, exudation, epiretinal proliferation and retinal traction, and need for ablative treatment of RH or ocular surgery at week 52.

Results

Three participants each received nine injections prior to week 52 and were followed for 104 weeks. One participant manifested mild episodic ocular hypertension in the study eye. Change in BCVA in the study eye at week 52 for the three participants was −5, −12 and +2 letters. No reduction in RH size was measured at 52 weeks. Variable mild improvements in exudation in two participants at week 16 were not sustained through week 52.

Conclusions

Combination intravitreous injection with ranibizumab and E10030 demonstrated a reasonable preliminary safety profile, but limited treatment effect.
Trends in risk factors of anastomotic leakage after colorectal cancer surgery (2011–2019): A Dutch population‐based study
Authors: Arron Melissa N. N. , Greijdanus Nynke G. , ten Broek Richard P. G. , Dekker Jan Willem T. , van Workum Frans , van Goor Harry , Tanis Pieter J. , de Wilt Johannes H. W.
Published: September 2021

Aim

Anastomotic leakage (AL) after colon cancer (CC) and rectal cancer (RC) surgery often requires reintervention. Prevalence and morbidity may change over time with evolutions in treatment strategies and changes in patient characteristics. This nationwide study aimed to evaluate changes in the incidence, risk factors and mortality from AL during the past nine years.

Methods

Data of CC and RC resections with primary anastomosis were extracted from the Dutch Colorectal Audit (2011–2019). AL was registered if requiring reintervention. Three consecutive cohorts were compared using logistic regression analysis.

Results

Incidence of AL after CC surgery decreased from 6.6% in 2011–2013 to 4.8% in 2017–2019 and increased from 8.6% to 11.9% after RC surgery. In 2011–2013, male sex, ASA ≥3, (y)pT3‐4, neoadjuvant therapy, emergency surgery and multivisceral resection were identified as risk factors for AL after CC surgery. In 2017–2019, only male sex and ASA ≥3 were risk factors for AL. For RC patients, male sex and neoadjuvant therapy were a risk factor for AL in 2011–2013. In 2017–2019, transanal approach was also a risk factor for AL. Postoperative mortality rate after AL was 12% (CC) and 2% (RC) in 2017–2019, without significant changes over time.

Conclusion

Contradictory trends in incidence and mortality for AL were observed among CC and RC surgery with changing risk factors over the past 9 years. High mortality after AL is only observed after CC surgery and remains unchanged. Continued efforts should be made to improve early detection and treatment of AL for these patients.
Acute kidney injury is a common and significant complication following ileostomy formation
Authors: Loria Anthony , Melucci Alexa , Speranza Jenny , Cellini Christina , Salloum Rabih , Temple Larissa K. , Fleming Fergal J. , Justiniano Carla F.
Published: September 2021

Aim

The aim was to characterize the incidence and short‐term prognostic value of an acute kidney injury (AKI) during the admission where an ileostomy is formed.

Methods

Adults with a baseline serum creatinine measurement discharged alive after ileostomy formation from 2014 to 2016 were included. All patients had daily basic metabolic panels and the Kidney Diseases Improving Global Outcomes criteria were used to determine the presence and severity of any AKI. Dehydration was defined by a single urine abnormality or clinical criteria combined with an objective abnormality in vitals or basic metabolic panels.

Results

Of 262 patients, 19.4% sustained an AKI (74.5% Stage I, 15.7% Stage II, 9.8% Stage III) during the index admission. Predictors of incident AKI were increasing age, male sex, higher baseline creatinine and open surgery. Patients with AKI had significantly longer length of stay and 45% had creatinine <1.0 mg/dl at discharge. Of the total cohort, 11% were readmitted with dehydration and the independent predictors were AKI during the index admission, high ileostomy output, age >65 years, male sex and prior ileostomy. Of those readmitted with dehydration, 79% had AKI at readmission.

Conclusions

Nearly 20% of patients with ileostomies develop an AKI during the index admission with almost half resolving by discharge. Patients with AKIs are at high risk for 30‐day dehydration‐related readmission and AKI is present in nearly 80% of those readmitted with dehydration. Since AKI is objective, based on routine laboratory measures, and has known prognostic value it is probably a more robust outcome than dehydration for researchers, surgeons and patients.
Do terrorist attacks matter to dividend policy?
Authors: Do Trung K.
Published: September 2021

Research Question/Issue

Motivated by the importance of dividend policy in corporate finance as well as the rising frequency and severity of terrorism in society, this study aims to investigate whether and how dividend policy is influenced by terrorist attacks.

Research Findings/Insights

Using a comprehensive sample of terrorist attacks occurring in the United States between 1994 and 2015, we find that relative to firms located in safety areas (nonimpact firms), firms headquartered in terrorism‐affected areas (impact firms) are more likely to pay dividends and pay higher amount of cash dividends. We further find that the effect of terrorist attacks on dividends is driven by agency costs of free cash flow.

Theoretical/Academic Implications

We contribute to the literature by shedding light on how terrorism affects firms' dividend preferences. We highlight that uncertainty caused by terrorism heightens the need for dividend payouts in the presence of free cash flow. Our paper also adds to the existing literature by showing that better corporate governance quality as defined by a more independent board featuring CEO–chairman separation and greater presence of independent directors coupled with larger institutional ownership has a crucial role in mitigating the impact of terrorism on corporate payout policy.

Practitioner/Policy Implications

Public firms should regard dividend policy as a governance tool that reduces agency costs during times of uncertainty. The results of this study strengthen the idea that institutional investors can play a key role in corporate governance. As such, for investors, as far as agency costs are concerned, investments in firms that have a higher proportion of institutional holdings are sensible.
Early versus delayed feeding after therapeutic endoscopic procedures: Meta‐analysis of randomized controlled trials
Authors: Kan Sheau Wen , Huang Ting‐Yun , Ma Hon‐Ping , Tay Ming Zhe , Tam Ka‐Wai , Tsai Tung‐Yao
Published: September 2021

Introduction

Early feeding was previously considered to increase the risk of postprocedural bleeding. However, many trials have demonstrated the benefits of early feeding after therapeutic endoscopic procedures. We conducted a meta‐analysis of randomized controlled trials to evaluate the safety and outcomes between early feeding and delayed feeding after therapeutic endoscopic procedures.

Methods

Medline (PubMed), Embase, Google Scholar, the Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials that met our inclusion criteria. The pooled data for the mortality rate, postprocedural bleeding rate, and length of hospital stay were analyzed.

Results

A total of seven trials consisting of 717 patients were reviewed. These seven trials examined various therapeutic endoscopic procedures. Three trials included patients undergoing endoscopic hemostasis for upper gastrointestinal bleeding, two included patients undergoing esophageal variceal ligation, and two included patients with gastric neoplasm treated with endoscopic submucosal dissection. Although no significant differences were observed in the postprocedural bleeding rate or the mortality rate between patients who received early feeding and those who received delayed feeding, early feeding resulted in shorter hospital stays (weighted mean difference −1.04, 95% confidence interval −1.45 to 0.63).

Conclusion

Early feeding appears to be a safe management method for patients undergoing therapeutic endoscopic procedures. Therefore, we recommend early feeding for these patients.
Neurological impairment and disability in children in rural Kenya
Authors: Abuga Jonathan A , Kariuki Symon M , Abubakar Amina , Nyundo Christopher , Kinyanjui Samson M , Van Hensbroek Michael Boele , Newton Charles RJC
Published: September 2021

Aim

To investigate geographical change over time in the burden of neurological impairments in school‐aged children in a demographic surveillance area.

Method

We investigated changes in neurological impairment prevalence in five domains (epilepsy and cognitive, hearing, vision, and motor impairments) using similar two‐phase surveys conducted in 2001 (n=10 218) and 2015 (n=11 223) and determined changes in location‐level prevalence, geographical clustering, and significant risk factors for children aged 6 to 9 years (mean 7y 6mo, SD 1y) of whom 50.4% were males. Admission trends for preterm birth, low birthweight (LBW), and encephalopathy were determined using admission data to a local hospital.

Results

Overall prevalence for any neurological impairment decreased from 61 per 1000 (95% confidence interval [CI] 48.0–74.0) in 2001 to 44.7 per 1000 (95% CI 40.9–48.6) in 2015 (p<0.001). There was little evidence of geographical variation in the prevalence of neurological impairments in either survey. The association between neurological impairments and some risk factors changed significantly with year of survey; for example, the increased association of adverse perinatal events with hearing impairments (exponentiated coefficient for the interaction=5.94, p=0.03). Annual admission rates with preterm birth (rate ratio 1.08, range 1.07–1.09), LBW (rate ratio 1.08, range 1.06–1.10), and encephalopathy (rate ratio 1.08, range 1.06–1.09) significantly increased between 2005 and 2016 (p<0.001).

Interpretation

There was a significant decline in the prevalence of neurological impairments and differential changes in the associations of some risk factors with neurological impairments over the study period. Limited geographical variation suggests that similar interventions are appropriate across the defined area.
The Impact of Sanctions for Young Welfare Recipients on Transitions to Work and Wages, and on Dropping Out
Authors: van den Berg Gerard J. , Uhlendorff Arne , Wolff Joachim
Published: September 2021

The reintegration of young welfare recipients into the labour market is a major policy objective in many European countries. In this context, monitoring and sanctions are commonly used policy tools. We analyse the impact of strict sanctions for young welfare recipients whose institutional setting features sanctions for non‐compliance with job‐search requirements that effectively cancel benefits for a period of 3 months after detection. We consider effects on job‐search outcomes and on dropping out of the labour force, using administrative data on a large inflow sample. We estimate multivariate duration models taking selection on unobservables into account. Our results indicate an increased job entry rate at the expense of an increased withdrawal from the labour force and lower entry wages. Combining quantitative with qualitative evidence reveals that the latter side‐effects of sanctions can have dramatic consequences for the quality of life of the youths involved.
Aromatase and nonaromatase neurons in the zebra finch secondary auditory forebrain are indistinct in their song‐driven gene induction and intrinsic electrophysiological properties
Authors: de Bournonville Catherine , Mendoza Kyssia Ruth , Remage‐Healey Luke
Published: September 2021

Estrogens support major brain functions including cognition, reproduction, neuroprotection and sensory processing. Neuroestrogens are synthesized within some brain areas by the enzyme aromatase and can rapidly modulate local circuit functions, yet the cellular physiology and sensory‐response profiles of aromatase neurons are essentially unknown. In songbirds, social and acoustic stimuli drive neuroestrogen elevations in the auditory forebrain caudomedial nidopallium (NCM). In both males and females, neuroestrogens rapidly enhance NCM auditory processing and auditory learning. Estrogen‐producing neurons in NCM may therefore exhibit distinguishing profiles for sensory‐activation and intrinsic electrophysiology. Here, we explored these questions using both immunocyctochemistry and electrophysiological recordings. Immunoreactivity for aromatase and the immediate early gene EGR1, a marker of activity and plasticity, were quantified in NCM of song‐exposed animals versus silence‐exposed controls. Using whole‐cell patch clamp recordings from NCM slices, we also documented the intrinsic excitability profiles of aromatase‐positive and aromatase‐negative neurons. We observed that a subset of aromatase neurons were significantly activated during song playback, in both males and females, and in both hemispheres. A comparable population of non‐aromatase‐expressing neurons were also similarly driven by song stimulation. Membrane properties (i.e., resting membrane potential, rheobase, input resistance and multiple action potential parameters) were similarly indistinguishable between NCM aromatase and non‐aromatase neurons. Together, these findings demonstrate that aromatase and non‐aromatase neurons in NCM are indistinct in terms of their intrinsic electrophysiology and responses to song. Nevertheless, such similarities in response properties may belie more subtle differences in underlying conductances and/or computational roles that may be crucial to their function.
Inhibition, excitation and bilateral transfer following a unilateral complex finger‐tapping task in young and older adults
Authors: Nuzum Nathan D. , Teo Wei‐Peng , Macpherson Helen , Loughman Amy , Szymlek‐Gay Ewa A. , Hendy Ashlee
Published: September 2021

Neuroplasticity underpins motor learning, with abnormal neuroplasticity related to age‐associated motor declines. Bilateral transfer of motor learning, through rehabilitation, may mitigate these declines; however, the magnitude of transfer may be reduced in older populations. This study investigated excitatory and inhibitory pathways in the trained and untrained hemispheres following unilateral training of a complex finger‐tapping task across ageing. Fifteen young (26.2 ± 3.8 years) and 11 older adults (63.7 ± 15.4 years) received transcranial magnetic stimulation, although surface electromyography was recorded from the extensor digitorum communis (EDC) and abductor pollicis brevis (APB), before and after practicing a complex finger‐tapping task with the dominant hand. Excitability, inhibition (expressed as percent change scores from pre‐ to post‐training), motor task performance and bilateral transfer were assessed between groups. Investigation of hemispheric differences within each group was completed for measures that significantly differed between groups. There were no between‐group differences in task performance or bilateral transfer, with task performance improving post‐training irrespective of group for both hands (p < 0.05). Pre‐ to post‐inhibition change scores of the untrained EDC muscle increased (p = 0.034) in older compared with younger adults, indicating reduced inhibition in older adults. Inhibition change scores significantly differed between hemispheres for the young group only (p = 0.037). Only the younger group presented with hemispheric lateralisation, providing some support for the Hemispheric Asymmetry Reduction in OLDer adults (HAROLD) hypothesis. Whether this reduction is evidence of de‐differentiation or compensation will need to be confirmed with additional measures.
Declining mortality of cerebral venous sinus thrombosis with thrombocytopenia after SARS‐CoV‐2 vaccination
Authors: van de Munckhof Anita , Krzywicka Katarzyna , Aguiar de Sousa Diana , Sánchez van Kammen Mayte , Heldner Mirjam R. , Jood Katarina , Lindgren Erik , Tatlisumak Turgut , Putaala Jukka , Kremer Hovinga Johanna A. , Middeldorp Saskia , Levi Marcel , Arnold Marcel , Ferro José M. , Coutinho Jonathan M.
Published: September 2021

Background and purpose

High mortality rates have been reported in patients with cerebral venous sinus thrombosis (CVST) due to vaccine‐induced immune thrombotic thrombocytopenia (VITT) after vaccination with adenoviral vector SARS‐CoV‐2 vaccines. The aim of this study was to evaluate whether the mortality of patients with CVST‐VITT has decreased over time.

Methods

The EudraVigilance database of the European Medicines Agency was used to identify cases of CVST with concomitant thrombocytopenia occurring within 28 days of SARS‐CoV‐2 vaccination. Vaccines were grouped based on vaccine type (adenoviral or mRNA). Cases with CVST onset until 28 March were compared to cases after 28 March 2021, which was the day when the first scientific paper on VITT was published.

Results

In total, 270 cases of CVST with thrombocytopenia were identified, of which 266 (99%) occurred after adenoviral vector SARS‐CoV‐2 vaccination (ChAdOx1 nCoV‐19, n = 243; Ad26.COV2.S, n = 23). The reported mortality amongst adenoviral cases with onset up to 28 March 2021 was 47/99 (47%, 95% confidence interval 37%–58%) compared to 36/167 (22%, 95% confidence interval 16%–29%) in cases with onset after 28 March (p < 0.001). None of the four cases of CVST with thrombocytopenia occurring after mRNA vaccination died.

Conclusion

The reported mortality of CVST with thrombocytopenia after vaccination with adenoviral vector‐based SARS‐CoV‐2 vaccines has significantly decreased over time, which may indicate a beneficial effect of earlier recognition and/or improved treatment on outcome after VITT.
Leveraging electrophysiologic correlates of word encoding to map seizure onset zone in focal epilepsy: Task‐dependent changes in epileptiform activity, spectral features, and functional connectivity
Authors: Saboo Krishnakant V. , Balzekas Irena , Kremen Vaclav , Varatharajah Yogatheesan , Kucewicz Michal , Iyer Ravishankar K. , Worrell Gregory A.
Published: September 2021

Objective

Verbal memory dysfunction is common in focal, drug‐resistant epilepsy (DRE). Unfortunately, surgical removal of seizure‐generating brain tissue can be associated with further memory decline. Therefore, localization of both the circuits generating seizures and those underlying cognitive functions is critical in presurgical evaluations for patients who may be candidates for resective surgery. We used intracranial electroencephalographic (iEEG) recordings during a verbal memory task to investigate word encoding in focal epilepsy. We hypothesized that engagement in a memory task would exaggerate local iEEG feature differences between the seizure onset zone (SOZ) and neighboring tissue as compared to wakeful rest (“nontask”).

Methods

Ten participants undergoing presurgical iEEG evaluation for DRE performed a free recall verbal memory task. We evaluated three iEEG features in SOZ and non‐SOZ electrodes during successful word encoding and compared them with nontask recordings: interictal epileptiform spike (IES) rates, power in band (PIB), and relative entropy (REN; a functional connectivity measure).

Results

We found a complex pattern of PIB and REN changes in SOZ and non‐SOZ electrodes during successful word encoding compared to nontask. Successful word encoding was associated with a reduction in local electrographic functional connectivity (increased REN), which was most exaggerated in temporal lobe SOZ. The IES rates were reduced during task, but only in the non‐SOZ electrodes. Compared with nontask, REN features during task yielded marginal improvements in SOZ classification.

Significance

Previous studies have supported REN as a biomarker for epileptic brain. We show that REN differences between SOZ and non‐SOZ are enhanced during a verbal memory task. We also show that IESs are reduced during task in non‐SOZ, but not in SOZ. These findings support the hypothesis that SOZ and non‐SOZ respond differently to task and warrant further exploration into the use of cognitive tasks to identify functioning memory circuits and localize SOZ.
Blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice
Authors: Ping Xingjie , Chai Zhi , Wang Weiping , Ma Cungen , White Fletcher A , Jin Xiaoming
Published: September 2021

Objective

Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis.

Methods

In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology.

Results

Undercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline‐treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb‐ or TAK242‐treated group (p < 0.001, when the RAGE mAb or TAK242 group is compared with the saline group). The lesioned cortical tissues of RAGE mAb‐ or TAK242‐treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67‐immunoreactive interneurons than the saline‐treated undercut group. Immunostaining to GFAP and Iba‐1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation.

Significance

RAGE and TLR4 signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.