bluuebunny/crossref_metadata_2025 huggingface dataset:
“Practicing care in qualitative organizational research: moral responsibility and legitimacy in a study of immigration management”
Authors: Okkonen Ida , Takala Tuomo , Bell Emma
Published: March 2021

Purpose

The purpose of this paper is to provide insight into the reciprocal relations between the caregiving imparted by immigration centre managers and the role of the researcher in responding to the care that is given by managerial caregivers. To enable this, we draw on a feminist theory of care ethics that considers individuals as relationally interdependent.

Design/methodology/approach

The analysis draws on a semi-structured interview study involving 20 Finnish immigration reception centre managers.

Findings

Insight is generated by reflecting on moments of care that arise between research participants and the researcher in a study of immigration centre management. We emphasise the importance of mature care, receptivity and engrossment in building caring relationships with research participants by acknowledging the care they give to others. Our findings draw attention to the moral and epistemological responsibility to practice care in organizational research.

Originality/value

The paper highlights the relationality between practicing care in immigration centre management and doing qualitative organizational research, both of which rely on mature care, receptivity and engrossment in order to meet the other morally. We draw attention to the moral responsibility to care which characterises researcher–researched relationships and emphasise the importance of challenging methodological discourses that problematise or dismiss care in qualitative organizational research.
Body size and shape responses to warming and resource competition
Authors: Tan Hanrong , Hirst Andrew G. , Atkinson David , Kratina Pavel
Published: March 2021

Body size is a fundamental trait that impacts many aspects of species biology and ecology. It is, in turn, influenced by a suite of environmental factors, and often decreases with warming. Although environmental conditions can also impact body shape, which is another functional trait that influences locomotion, resource acquisition and potentially physiological processes, such responses are poorly understood and rarely quantified.

We experimentally tested the independent and combined effects of environmental temperature, resource level and interspecific competition on the body shape and size responses of two model protist species. We also tested the degree to which these individual‐level phenotypic responses are associated with population densities and species coexistence.

Body shape was strongly influenced by resource competition, whereas body size changes were mainly driven by environmental temperature. In both species, lower resource levels resulted in body shape elongation, suggesting that relatively more elongate individuals with potentially higher swimming speed were advantaged in the resource scarce environment. However, competition had contrasting influence on the body shape of the two species. Competition decreased the population densities of Blepharisma japonicum, which exhibited relative body shape elongation, similar to the response at low resource levels. In contrast, competition increased the population densities of Paramecium aurelia, which exhibited reduced elongation similar to body shape response at high resource levels. Hence, body shape responses could be indicative of changes in resource availability, aiding our understanding of competitive hierarchies and species interactions.

Coexistence was observed in all treatment combinations, likely because body size of both species decreased similarly under warming, potentially maintaining constant per capita competitive intensity. These findings, along with recent research on phytoplankton, diverse pelagic invertebrates, and birds highlight the importance of body shape and morphology across different taxonomic groups. Hence, we call for body size and shape to be considered in concert when investigating ecological consequences of climate warming.

A free Plain Language Summary can be found within the Supporting Information of this article.
“You are here”: Assessing the inclusion of maps in a campus emergency alert system
Authors: Cain Lauren , Herovic Emina , Wombacher Kevin
Published: March 2021

Emergency alerts are typically sent through mobile devices and email and are a means by which to notify students of threats or hazards on campus. Alerts that include maps help illustrate the significance of a threat and improve understanding when designed correctly. This study of a college campus examines how maps can clarify who should take protective action by specifying the location of the threat in relation to the user, and whether maps affect risk perception, intended action, and trust in the message source. Results indicate a significant difference in perceptions of risk susceptibility between participants exposed to a long‐distance map, a short‐distance map, and no map, and participants exposed to the shooting condition reported significantly higher measures of negative emotions, risk susceptibility, risk severity, and behavioural intention. Findings indicate that while personalized maps improve risk susceptibility, they cannot work alone in affecting other message response factors and may be most useful when paired with highly specific warning messages. The results of this study are useful to practitioners developing or improving emergency alert systems.
Conservative management of spontaneous intra‐abdominal abscess in Crohn's disease: Outcome and prognostic factors
Authors: Waked Bruno , Holvoet Tom , Geldof Jeroen , Baert Filip , Pattyn Piet , Lobatón Triana , Hindryckx Pieter
Published: March 2021

Objective

To compare the outcomes of different treatments for spontaneous intra‐abdominal abscesses (IAA) in active Crohn's disease (CD).

Methods

A retrospective analysis of patients with CD between January 2007 and December 2018 was performed in two Belgian inflammatory bowel disease centers. Successful conservative management was defined as complete resolution of abscesses without the need for bowel resection. The primary outcome was suboptimal evolution, defined as a composite outcome of recurrence of abscess, postoperative complications or the need for a non‐elective resection.

Results

Forty CD patients presenting with 43 independent episodes of spontaneous IAA development were included. One underwent immediate bowel resection. In all other 42 cases a conservative approach was taken, which led to a complete abscess resolution rate of 28.6% (12/42). The remaining abscesses required bowel resection. Anti‐tumor necrosis factor (TNF) agent use was associated with successful conservative management (odds ratio [OR] 13.36, 95% confidence interval [CI] 11.19‐15.52, P = 0.006), while the opposite trend was found for corticosteroids (OR 0.14, 95% CI 0.02‐1.26, P = 0.055). There was a trend towards suboptimal evolution in case of previous bowel resection (OR 4.77, 95% CI 0.77‐29.66, P = 0.094) or in patients aged above 50 years (OR 5.17, 95% CI 0.86‐30.91, P = 0.072).

Conclusions

Bowel resection appears to be inevitable in most CD patients presenting with IAA. An attempt at conservative treatment may be particularly successful with anti‐TNF agents in younger patients who have not undergone previous bowel resection. Large‐scale prospective studies are needed to confirm these findings.
GPR12 inhibits migration and promotes apoptosis in esophageal cancer and hypopharyngeal cancer cells
Authors: Zhang Minfa , Yang Xiaoqi , Chen Shuai , Jia Wenming , Ma Xiaojie , Wang Juan , Qian Ye , Lei Dapeng , Liu Heng , Pan Xinliang
Published: March 2021

Background

G protein‐coupled receptor 12 (GPR12) is an orphan receptor with no confirmed endogenous ligands. It plays important roles in both physiological and pathological conditions such as neurogenesis and neural inflammation. However, it remains unclear whether GPR12 regulates carcinogenesis and progression in head and neck squamous cell carcinoma (HNSCC), such as esophageal cancer (EC) and hypopharyngeal cancer (HC).

Methods

The Cancer Genome Atlas (TCGA) database was applied to explore the expression of GPR12. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of GPR12 in cancer tissues. Wound healing and transwell assays were carried out to verify the effect of GPR12 on cell migration. Flow cytometric analysis and caspase‐Glo 3/7 assay were carried out to verify the influence of GPR12 on cell apoptosis. Western blotting was used to measure the expression of proteins related to migration and apoptosis.

Result

The qRT‐PCR analyses showed that the expression of GPR12 decreased in EC and HC than that in their paired adjacent normal tissues. Wound healing assay and transwell assay demonstrated that GPR12 inhibited tumor cell migration. Flow cytometry analysis and Caspase‐Glo 3/7 Assay suggested that GPR12 promoted apoptosis. The mechanism of GPR12 may function via modulating caspase‐7, E‐cadherin, and α‐catenin in EC and HC cells.

Conclusion

In conclusion, GPR12 induced apoptosis by activating caspase‐7 and inhibited migration through epithelial‐to‐mesenchymal transition (EMT) in EC and HC. Our findings demonstrated that GPR12 as a potential tumor suppressor mediated cell migration and apoptosis in EC and HC.
Effects of moderate alcohol levels on default mode network connectivity in heavy drinkers
Authors: Fang Xiaojing , Deza‐Araujo Yacila I. , Petzold Johannes , Spreer Maik , Riedel Philipp , Marxen Michael , O’Connor Sean J. , Zimmermann Ulrich S. , Smolka Michael N.
Published: March 2021

Background

It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self‐related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol‐induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self‐initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol‐related changes.

Methods

We investigated resting‐state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single‐blind crossover design.

Results

Intranetwork connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus during acute alcohol exposure. Moreover, follow‐up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory internetwork connectivity analyses of the DMN with other resting‐state networks showed no significant alcohol‐induced changes, but suffered from low statistical power.

Conclusions

Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self‐referential processes commonly observed during alcohol intoxication. Future resting‐state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN‐related connectivity changes are associated with alcohol‐induced impairments or craving.
Blau syndrome with pulmonary nodule in a child
Authors: Su Jinping , Liu Donghua
Published: March 2021

Blau syndrome (BS) is a rare monogenic disease caused by mutation of NOD2/CARD15 gene. A case of Blau syndrome in a 4‐year‐old Chinese boy c.1001G > A(p.R334Q) mutation in the NOD2 genes reported. Imaging revealed a nodule at the tip of the right lung.
Association between electrocardiographic features and mortality in COVID‐19 patients
Authors: Antwi‐Amoabeng Daniel , Beutler Bryce D. , Singh Sahajpreet , Taha Moutaz , Ghuman Jasmine , Hanfy Ahmed , Manasewitsch Nicholas T. , Ulanja Mark B. , Ghuman Joban , Awad Munadel , Gullapalli Nageshwara , Gbadebo T. David
Published: March 2021

Background

Cardiovascular events have been reported in the setting of coronavirus disease‐19 (COVID‐19). It has been hypothesized that systemic inflammation may aggravate arrhythmias or trigger new‐onset conduction abnormalities. However, the specific type and distribution of electrocardiographic disturbances in COVID‐19 as well as their influence on mortality remain to be fully characterized.

Methods

Electrocardiograms (ECGs) were obtained from 186 COVID‐19‐positive patients at a large tertiary care hospital in Northern Nevada. The following arrhythmias were identified by cardiologists: sinus bradycardia, sinus tachycardia, atrial fibrillation (A‐Fib), atrial flutter, multifocal atrial tachycardia (MAT), premature atrial contraction (PAC), premature ventricular contraction (PVC), atrioventricular block (AVB), and right bundle branch block (RBBB). The mean PR interval, QRS duration, and corrected QT interval were documented. Fisher's exact test was used to compare the ECG features of patients who died during the hospitalization with those who survived. The influence of ECG features on mortality was assessed with multivariable logistic regression analysis.

Results

A‐Fib, atrial flutter, and ST‐segment depression were predictive of mortality. In addition, the mean ventricular rate was higher among patients who died as compared to those who survived. The use of therapeutic anticoagulation was associated with reduced odds of death; however, this association did not reach statistical significance.

Conclusion

The underlying pathogenesis of COVID‐19‐associated arrhythmias remains to be established, but we postulate that systemic inflammation and/or hypoxia may induce potentially lethal conduction abnormalities in affected individuals. Longitudinal studies are warranted to evaluate the risk factors, pathogenesis, and management of COVID‐19‐associated cardiac arrhythmias.
Operative experience in essential emergency general surgery procedures: is autonomy achievable during surgical training?
Authors: Belvedere Shane , Joh Daniel , Furlong Tim , Dennett Elizabeth , Loveday Benjamin P. T.
Published: March 2021

Background

Readiness for practice is an ongoing concern in surgery. Surgeons who have completed general surgery training are expected to be proficient in performing common emergency procedures. The aim of this study was to assess the experience and autonomy of general surgery trainees in New Zealand in 10 emergency general surgery procedures, and identify factors associated with reaching primary operator (PO) thresholds.

Methods

Operative logbook data from all New Zealand general surgery trainees from 2013 to 2017 were analysed. Data for 10 emergency general surgery procedures were extracted to determine PO and autonomous PO (mentor not scrubbed) rates. A threshold of 70% for PO and APO rates was used to define two levels of proficiency.

Results

A total of 120 trainees performed 40 865 included procedures. Trainees met the PO threshold for all procedures by Surgical Education and Training (SET) 5. The APO threshold was met for three of 10 procedures (appendicectomy, drainage of perianal abscess and perforated peptic ulcer repair). Final APO rates for the other procedures ranged from 18% to 58%. On multivariate analysis, SET year and case volume were associated with increased odds of meeting the PO and APO thresholds. Female trainees were less likely to reach the PO and APO thresholds for three of 10 and four of 10 procedures, respectively.

Conclusion

Trainees had increasing PO and autonomous PO rates over the course of their training. Graduating New Zealand general surgeons likely have sufficient operative experience in emergency general surgery procedures. However, rates of autonomy are lower, and further research is needed to determine whether this affects readiness for independent practice.
Plasma long‐chain omega‐3 fatty acid status and risk of recurrent early spontaneous preterm birth: a prospective observational study
Authors: Goodfellow Laura , Care Angharad , Harrold Jane , Sharp Andrew , Ivandic Jelena , Poljak Borna , Roberts Devender , Alfirevic Ana , Müller‐Myhsok Bertram , Gibson Robert , Makrides Maria , Alfirevic Zarko
Published: March 2021

Introduction

A 2018 Cochrane review found that omega‐3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega‐3 fatty acid status. However, the contemporary omega‐3 fatty acid status of pregnant women in the UK is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega‐3 fatty acid status of a UK pregnant population and determine the association between the long‐chain omega‐3 fatty acids and recurrent spontaneous early preterm birth.

Material and methods

A total of 283 high‐risk women with previous early preterm birth were recruited to the prospective observational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth ≥39+0 weeks in the index pregnancy provided a low‐risk population sample. Within the high‐risk group we assessed the odds ratio of recurrent early preterm birth compared with birth at ≥37+0 weeks of gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15–22 weeks of gestation.

Results

Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long‐chain omega‐3 status and recurrent early preterm birth (n = 51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38–2.15, p = 0.83) for women in the lowest, compared with the highest three quintiles of EPA+DHA.

Conclusions

In the majority of our participants, levels of long‐chain omega‐3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega‐3 “replete”; or else omega‐3 levels may be of lesser importance in recurrent early preterm birth.
Ranibizumab in retinopathy of prematurity – one‐year follow‐up of ophthalmic outcomes and two‐year follow‐up of neurodevelopmental outcomes from the CARE‐ROP study
Authors: Stahl Andreas , Bründer Marie‐Christine , Lagrèze Wolf A. , Molnár Fanni E. , Barth Teresa , Eter Nicole , Guthoff Rainer , Krohne Tim U. , Pfeil Johanna M. ,   the CARE‐ROP Study Group
Published: March 2021

Purpose

The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE‐ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1‐ and 2‐year follow‐up data focusing on long‐term functional outcomes and safety.

Methods

The CARE‐ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double‐blind, controlled study design. Sixteen patients entered the follow‐up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients.

Results

Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1‐year follow‐up (first seen at PMA 75 weeks). Mean spherical equivalents were −1.9 diopters (D) and −0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms.

Conclusion

Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long‐term safety. Late reactivation of ROP, however, represents a challenge during the follow‐up phase and it is of utmost importance that regular follow‐ups are maintained.
Retinal oxygen saturation is associated with HbA1c but not with short‐term diabetes control, internal environment, smoking and mild retinopathy ‐ ROXINEGLYD study
Authors: Mlčák Petr , Chlup Rudolf , Kudlová Pavla , Krystyník Ondřej , Král Michal , Kučerová Veronika , Spurná Jaromíra , Titzová Simona , Hübnerová Petra , Vláčil Ondřej , Šínová Irena , Karhanová Marta , Zapletalová Jana , Šín Martin
Published: March 2021

Purpose

Purpose of this prospective uncontrolled single‐centre pilot study was to find an association of retinal oxygen saturation (SatO2) with acid–base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions.

Methods

Forty‐one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1–36) years, BMI 29.4 ± 6.3 kg/m2, and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4‐day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro®2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2.

Results

Wilcoxon signed‐rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found.

Conclusion

This study confirmed the association of venous SatO2 with long‐term but not with short‐term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.
Parapapillary deep‐layer microvasculature dropout is only found near the retinal nerve fibre layer defect location in open‐angle glaucoma
Authors: Son Ki Young , Han Jong Chul , Kee Changwon
Published: March 2021

Purpose

We aimed to investigate the topographic correspondence between deep‐layer microvasculature dropout (MvD) and retinal nerve fibre layer (RNFL) defects in eyes with open‐angle glaucoma (OAG) using spectral‐domain optical coherence tomography (SD‐OCT) and optical coherence tomography angiography (OCT‐A).

Methods

Microvasculature dropout width and location were determined using OCT‐A, RNFL thickness, RNFL defect width and location were revealed using SD‐OCT. The association between MvD and RNFL widths and that between the location of the MvD and RNFL defects were investigated. In addition, patients with OAG were divided into two groups: the RNFL defect in one hemiretina (RNFLD‐HR) group (n = 24 eyes) and the RNFL defects in both hemiretinas (RNFLD‐BR) group (n = 25 eyes). The presence, width and location of MvDs were compared between the two groups.

Results

Forty‐nine eyes were included. In 24 RNFLD‐HR eyes, all MvDs were found in the inferior area, corresponding with the location of the RNFL defect. Meanwhile, in 25 RNFLD‐BR eyes, 18 MvDs (72%) were found in the inferior hemiretina, two (8%) were found in the superior hemiretina, and five (20%) were found in both hemiretinas. In RNFLD‐BR eyes, the average RNFL thickness was thinner in a location with MvD than a location without MvD.

Conclusion

Considering that MvD is only observed at the location of the RNFL defect in RNFLD‐HR eyes and is usually found in the location of more severe RNFL defects in RNFLD‐BR eyes, MvD seems to be a sign that accompanies glaucomatous damage in OAG eyes.
Glomerular filtration and shrunken pore syndrome in children and adults
Authors: Grubb Anders
Published: March 2021

A major function of the kidney is to, by glomerular filtration, maintain the overall steady‐state of 5–30 kDa proteins, many of which are signalling molecules. This function of the kidney has been overlooked, since predominantly low‐molecular‐mass substances <1 kDa have been used to measure or estimate glomerular filtration rate (GFR). The use of cystatin C (13 kDa) as a marker of GFR has allowed the discovery that the filtration of 5–30 kDa molecules can be selectively impaired defining the shrunken pore syndrome. The discovery, pathophysiology, morbidity (mainly cardiovascular manifestations) and mortality of this syndrome are described.
Thyroid function in postpartum psychosis: An exploratory study
Authors: Sethy Rati Ranjan , Garg Shobit , Ram Daya , Tikka Sai Krishna
Published: March 2021

The study aimed to compare thyroid function between psychosis with postpartum onset (PPO), psychosis without postpartum onset (PWPO), and normal postpartum females (HC). Twenty women were recruited in each of the three groups. The PPO group had significantly greater psychopathology and shorter episodes compared to the PWPO group. The PPO group was found to have significantly greater right lobe volume than the other groups. The PPO group also had significantly higher FT4 levels than the HC group. We conclude that isolated increase in FT4 and thyroid lobe volumetric changes could be more specifically associated with psychosis of post‐partum onset.
The city‐island‐state, wounding cascade, and multi‐level vulnerability explored through the lens of Malta
Authors: Main Geoff , Schembri John , Speake Janet , Gauci Ritienne , Chester David
Published: March 2021

In this paper, we introduce the concept of “city‐island‐state” into a discussion of small highly urbanised islands. We place the “city” at the forefront of our analysis by bringing together the geographies of the “city” and “state,” together with a wider discussion of factors that may cause both the wounding of the city and an increase in the precariousness of the “island.” We apply this concept to the advanced city‐island‐state of Malta (Central Mediterranean), which is a densely populated, urbanised small island archipelago with about 500,000 inhabitants and operates as a single city with an urban core, suburbs, and a rural hinterland that is rapidly decreasing in size. This city‐island‐state is frequently considered as being “safe” from external geophysical, climatic, and anthropogenic wounding, but, in reality, Malta, as a city, an island, and an independent nation‐state, is faced with multiple internal and external pressures that increase its precariousness and vulnerability to such externalities. Some of these are socio‐economic, but others are environmental. We argue that the potential for wounding is particularly marked in Malta, that it is exacerbated by the contemporary globalised neoliberal world of flows and interconnectivities, and that this represents a multi‐level wounding cascade: wounding the city wounds the island and, by extension, the state.
Women's evaluation of costs and benefits in public versus private spheres: The role of gender ideology
Authors: Villanueva‐Moya Laura , Expósito Francisca
Published: March 2021

Gender equality's progress in the public sphere has not expanded to the private sphere, where women are primarily responsible for housework, which seems to affect them at individual, family, and social levels. We investigated how women perceive contextual (society), intrapersonal (decision‐making), or interpersonal (romantic relationship) factors could affect them (cost and benefits) at these levels; considering women's gender ideology as moderator. In Study 1, women (N = 94) rated the associated costs and benefits of a context (equal vs. unequal) and a decision (work vs. family). Findings showed that an equal context and the decision to invest in work benefited women at the individual level; investing in work benefited women at the social level but not at the family level. Moreover, women's gender ideology affected their evaluation. The Study 2 focused on the private sphere, women (N = 91) rated the associated costs and benefits of an egalitarian (vs. traditional) partner. Women perceived more benefits at all levels in an egalitarian (vs. traditional) partner. The effect a partner's ideology had on women's perception was stronger than the women's ideology. These findings highlight that—although women progress in the public sphere—certain factors in the private sphere seem to affect them.
Evaluation of the protective effect of lycopene on growth performance, intestinal morphology, and digestive enzyme activities of aflatoxinB1 challenged broilers
Authors: Sarker Md Touhiduzzaman , Wang Zhi Yue , Yang Haiming , Wan Xiaoli , Emmanuel Asare
Published: March 2021

The current study was conducted to investigate the protective efficiency of dietary lycopene (LYC) supplementation on growth performance, intestinal morphology, and digestive enzyme activities aflatoxinB1 (AFB1) challenged broilers. A total of 240 days old Arber across male broiler chicks were randomly allocated in five treatments and six replicates (eight birds per replicate); feed and water were provided ad libitum during the 42 days experiment. The treatment diets were as follows: (i) Basal diet (control), (ii) Basal diet + 100 µg/kg AFB1 contaminated diet, (iii) Basal diet + 100 µg/kg AFB1 + 100 mg/kg LYC1, (iv) Basal diet + 100 µg/kg AFB1 + 200 mg/kg LYC2, and (v) Basal diet + 100 µg/kg AFB1 + 400 mg/kg LYC3. The results showed that the addition of LYC to AFB1 contaminated broiler diets significantly increased (p < .05) average daily gain (ADG) and decreased feed conversion ratio (FCR) compared to the AFB1 diet. AFB1 diet decreased the intestinal villus height (VH) and crypt depth ratio (VCR) while increasing the crypt depth (CD). However, dietary LYC supplemented diets relieved the intestinal morphological alterations. Dietary LYC supplementation (200 and 400 mg/kg) significantly improved (p < .05) intestinal digestive enzyme amylase and lipase activities with AFB1 contaminated diet. These findings suggested that LYC is a promising feed supplement in the broiler industry, alleviating the harmful effects of AFB1.
Zinc supplementation as an adjunct therapy for COVID‐19: Challenges and opportunities
Authors: Chinni Vidyasagar , El‐Khoury John , Perera Marlon , Bellomo Rinaldo , Jones Daryl , Bolton Damien , Ischia Joseph , Patel Oneel
Published: March 2021

An outbreak of a novel coronavirus (COVID‐19 or 2019‐CoV) infection has posed significant threats to international health and the economy. Patients with COVID‐19 are at risk of cytokine storm, acute respiratory distress syndrome (ARDS), reduced blood oxygenation, mechanical ventilation, and a high death rate. Although recent studies have shown remdesivir and dexamethasone as treatment options, there is an urgent need to find a treatment to inhibit virus replication and to control the progression of the disease. Essential biometal zinc has generated a lot of excitement as one of the promising candidates to reduce the severity of COVID‐19 infection. Several published observations outlined in the review are the reasons why there is a global enthusiasm that zinc therapy could be a possible therapeutic option. However, the biggest challenge in realising the therapeutic value of zinc is lack of optimal treatment modalities such as dose, duration of zinc supplementation and the mode of delivery. In this review, we discuss the regulatory mechanism that hinges upon the bioavailability of zinc. Finally, we propose that intravenous zinc could circumvent the confounding factors affecting the bioavailability of zinc and allow zinc to achieve its therapeutic potential. If successful, due to advantages such as lack of toxicity, low cost and ease of availability, intravenous zinc could be rapidly implemented clinically.
The effect of interleukin‐17F on vasculogenic mimicry in oral tongue squamous cell carcinoma
Authors: Almahmoudi Rabeia , Salem Abdelhakim , Hadler‐Olsen Elin , Svineng Gunbjørg , Salo Tuula , Al‐Samadi Ahmed
Published: March 2021

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin‐17F (IL‐17F) correlates with better disease‐specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL‐17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC‐3 and SAS) form tube‐like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC‐25) did not form any VM structures. Droplet‐digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC‐3 cells expressed VE‐cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL‐17F inhibited the formation of VM structures in vitro by HSC‐3 and reduced almost all VM‐related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL‐17F through its effect on the VM. Therefore, targeting IL‐17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC.
Ppp6c haploinsufficiency accelerates UV‐induced BRAF(V600E)‐initiated melanomagenesis
Authors: Kanazawa Kosuke , Kishimoto Kazuhiro , Nomura Miyuki , Kurosawa Koreyuki , Kato Hiroyuki , Inoue Yui , Miura Koh , Fukui Katsuya , Yamashita Yoji , Sato Ikuro , Tsuji Hiroyuki , Watanabe Toshio , Tanaka Takuji , Yasuda Jun , Tanuma Nobuhiro , Shima Hiroshi
Published: March 2021

According to TCGA database, mutations in PPP6C (encoding phosphatase PP6) are found in c. 10% of tumors from melanoma patients, in which they coexist with BRAF and NRAS mutations. To assess PP6 function in melanoma carcinogenesis, we generated mice in which we could specifically induce BRAF(V600E) expression and delete Ppp6c in melanocytes. In these mice, melanoma susceptibility following UVB irradiation exhibited the following pattern: Ppp6c semi‐deficient (heterozygous) > Ppp6c wild‐type > Ppp6c‐deficient (homozygous) tumor types. Next‐generation sequencing of Ppp6c heterozygous and wild‐type melanoma tumors revealed that all harbored Trp53 mutations. However, Ppp6c heterozygous tumors showed a higher Signature 1 (mitotic/mitotic clock) mutation index compared with Ppp6c wild‐type tumors, suggesting increased cell division. Analysis of cell lines derived from either Ppp6c heterozygous or wild‐type melanoma tissues showed that both formed tumors in nude mice, but Ppp6c heterozygous tumors grew faster compared with those from the wild‐type line. Ppp6c knockdown via siRNA in the Ppp6c heterozygous line promoted the accumulation of genomic damage and enhanced apoptosis relative to siRNA controls. We conclude that in the presence of BRAF(V600E) expression and UV‐induced Trp53 mutation, Ppp6c haploinsufficiency promotes tumorigenesis.
Tournament incentives and performance: Evidence from the WNBA
Authors: Hill Brian
Published: March 2021

Players entering the Women's National Basketball Association (WNBA) are allocated to teams based on a draft where lower performing teams in the regular season earn the highest odds of selecting the best players, creating an incentive for teams to lose games. Using data from the 2000–2019 seasons, results indicate that WNBA teams are more likely to lose after they have been eliminated from postseason playoffs regardless of the gender of the coach or general manager. Evidence of tanking is concentrated in seasons after the WNBA made a draft lottery change in 2015, which was intended to reduce tanking.
A metabolomic analysis of thiol response for standard and modified N‐acetyl cysteine treatment regimens in patients with acetaminophen overdose
Authors: Dear James W , Ng Mei Li , Bateman D. Nicholas , Leroy Sivappiragasam Pakkiri , Choi Hyungwon , Khoo Benjamin Bing Jie , Ibrahim Baharudin , Drum Chester Lee
Published: March 2021

N‐acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol‐APAP)‐induced acute liver injury (ALI). The 3‐bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post‐start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post‐infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP‐metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP‐metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP‐induced ALI.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a TLR7 agonist prodrug RO6870868 in healthy volunteers
Authors: Grippo Joseph F. , Folitar Ilia , Passe Sharon , Jiang Qiudi , Rodriguez Ignacio , Fettner Scott H. , Calleja Elizabeth
Published: March 2021

RO6870868 is an oral prodrug of the toll‐like receptor 7 (TLR7) specific agonist, RO6871765. TLR7 agonists augment host immune activity and are in development to treat hepatitis B infection. We evaluated the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of RO6870868 in a first‐in‐human, phase I, randomized, single ascending oral dose study in 60 healthy volunteers at 6 dose levels (200–2000 mg). Single oral doses were generally well‐tolerated with a predictable safety profile associated with dose‐dependent increases in systemic interferon. No serious adverse events (AEs) were reported and no subject withdrew from the study due to an AE. No clinically significant changes were observed in vital signs, electrocardiograms, or laboratory parameters. Following oral RO6870868 doses, plasma RO6871765 concentrations increased rapidly, exhibiting mean terminal half‐life ranging 2–6 h across all cohorts, with area under the plasma concentration versus time curve extrapolated to infinity (AUC0‐∞) increasing proportionally with dose. A pattern of dose and time‐dependent PD activity was demonstrated consistent with engagement of the TLR7 system. Single RO6870868 doses activated components of the TLR innate immune system in a dose‐dependent manner with adequate safety and tolerability. Single‐dose data in healthy volunteers are useful to evaluate safety, PK, and PD activity of TLR7 agonists and help to guide dose and regimen selection for further trials in patients with chronic hepatitis B.
Regulatory guidelines do not accurately predict tolvaptan and metabolite interactions at BCRP, OATP1B1, and OAT3 transporters
Authors: Shoaf Susan E. , Bricmont Patricia , Repella Gordon Jennifer
Published: March 2021

Tolvaptan (TLV) was US Food and Drug Administration (FDA)‐approved for the indication to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease in 2018. In vitro, TLV was a breast cancer resistance protein (BCRP) inhibitor, whereas the oxobutyric acid metabolite of TLV (DM‐4013) was an inhibitor of organic anion transport polypeptide (OATP)1B1 and organic anion transporter (OAT)3. Based on the 2017 FDA guidance, potential for clinically relevant inhibition at these transporters was indicated for the highest TLV regimen. Consequently, two postmarketing clinical trials in healthy subjects were required. In trial 1, 5 mg rosuvastatin calcium (BCRP and OATP1B1 substrate) was administered alone, with 90 mg TLV or 48 h following 7 days of once daily 300 mg TLV (i.e., in the presence of DM‐4103). In trial 2, 40 mg furosemide (OAT3 substrate) was administered alone and in presence of DM‐4103. For BCRP, rosuvastatin geometric mean ratios (90% confidence intervals [CIs]) for maximum plasma concentration (Cmax) were 1.54 (90% CI 1.26–1.88) and for area under the concentration‐time curve from time 0 to the time of the last measurable concentration (AUCt) were 1.69 (90% CI 1.34–2.14), indicating no clinically significant interaction. DM‐4103 produced no clinically meaningful changes in rosuvastatin or furosemide concentrations, indicating no inhibition at OATP1B1 or OAT3. The BCRP prediction assumed the drug dose is completely soluble in 250 ml; TLV has solubility of ~0.01 g/250 ml. For OATP1B1/OAT3, if fraction unbound for plasma protein binding (PPB) is less than 1%, then 1% is assumed. DM‐4103 has PPB greater than 99.8%. Use of actual drug substance solubility and unbound fraction in plasma would have produced predictions consistent with the clinical results.
Model‐based approach to sampling optimization in studies of antibacterial drugs for infants and young children
Authors: Orito Yuji , Kakara Makoto , Okada Akira , Nagai Naomi
Published: March 2021

Clinical trials for pediatric indications and new pediatric drugs face challenges, including the limited blood volume due to the patients’ small bodies. In Japan, the Evaluation Committee on Unapproved or Off‐labeled Drugs with High Medical Needs has discussed the necessity of pediatric indications against the background of a lack of Japanese pediatric data. The limited treatment options regarding antibiotics for pediatric patients are associated with the emergence of antibiotic‐resistant bacteria. Regulatory guidelines promote the use of model‐based drug development to reduce practical and ethical constraints for pediatric patients. Sampling optimization is one of the key study designs for pediatric drug development. In this simulation study, we evaluated the precision of the empirical Bayes estimates of pharmacokinetic (PK) parameters based on the sampling times optimized by published pediatric population PK models. We selected three previous PK studies of cefepime and ciprofloxacin in infants and young children as paradigms. The number of sampling times was reduced from original full sampling times to two to four sampling times based on the Fisher information matrix. We observed that the precision of empirical Bayes estimates of the key PK parameters and the predicted efficacy based on the reduced sampling times were generally comparable to those based on the original full sampling times. The model‐based approach to sampling optimization provided a maximization of PK information with a minimum burden on infants and young children for the future development of pediatric drugs.
Application of MCAT questions as a testing tool and evaluation metric for knowledge graph–based reasoning systems
Authors: Fecho Karamarie , Balhoff James , Bizon Chris , Byrd William E. , Hang Sui , Koslicki David , Rensi Stefano E. , Schmitt Patrick L. , Wawer Mathias J. , Williams Mark , Ahalt Stanley C.
Published: March 2021

“Knowledge graphs” (KGs) have become a common approach for representing biomedical knowledge. In a KG, multiple biomedical data sets can be linked together as a graph representation, with nodes representing entities, such as “chemical substance” or “genes,” and edges representing predicates, such as “causes” or “treats.” Reasoning and inference algorithms can then be applied to the KG and used to generate new knowledge. We developed three KG‐based question‐answering systems as part of the Biomedical Data Translator program. These systems are typically tested and evaluated using traditional software engineering tools and approaches. In this study, we explored a team‐based approach to test and evaluate the prototype “Translator Reasoners” through the application of Medical College Admission Test (MCAT) questions. Specifically, we describe three “hackathons,” in which the developers of each of the three systems worked together with a moderator to determine whether the applications could be used to solve MCAT questions. The results demonstrate progressive improvement in system performance, with 0% (0/5) correct answers during the first hackathon, 75% (3/4) correct during the second hackathon, and 100% (5/5) correct during the final hackathon. We discuss the technical and sociologic lessons learned and conclude that MCAT questions can be applied successfully in the context of moderated hackathons to test and evaluate prototype KG‐based question‐answering systems, identify gaps in current capabilities, and improve performance. Finally, we highlight several published clinical and translational science applications of the Translator Reasoners.
Optimizing clinical phenotyping to better delineate the complex relationship between type 2 diabetes and Alzheimer’s disease
Authors: Hanson Angela J. , Rubinow Katya B.
Published: March 2021

Alzheimer’s disease (AD) is the most common form of dementia, and its prevalence is increasing rapidly. According to the Alzheimer’s Association, over 5 million adults in the United States over the age of 65 years currently have AD, and this number is expected to exceed 13 million by 2050 in the absence of novel, preventative strategies. Epidemiologic studies have implicated the presence of type 2 diabetes mellitus (T2DM) specifically at midlife as a key modifiable risk factor for AD, and AD may increase risk of dysglycemia and T2DM. However, data have been inconsistent with regard to the magnitude of AD risk attributable to T2DM, and the pathways underlying this apparent relationship remain poorly understood. Elucidating the impact of T2DM on AD risk and progression requires greater attention to the myriad facets of T2DM pathophysiology, its comorbid conditions, and attendant treatment modalities, all of which may differentially impact the relationships among T2DM, cognitive decline, and AD. This mini‐review will summarize the discrete facets of T2DM that may influence AD risk and highlight the importance of careful clinical phenotyping in both epidemiologic and interventional studies to better delineate the key pathways and mechanisms linking T2DM and AD.