bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and reporting of stratified cluster randomized trials—a systematic survey
Authors: Borhan Sayem , Papaioannou Alexandra , Ma Jinhui , Adachi Jonathan , Thabane Lehana
Published: November 2020

Background

In order to correctly assess the effect of intervention from stratified cluster randomized trials (CRTs), it is necessary to adjust for both clustering and stratification, as failure to do so leads to misleading conclusions about the intervention effect. We have conducted a systematic survey to examine the current practices about analysis and reporting of stratified CRTs.

Method

We used the search terms to identify the stratified CRTs from MEDLINE since the inception to July 2019. In phase 1, we screened the title and abstract for English-only studies and selected, including the main results paper of the identified protocols, for the next phase. In phase 2, we screened the full text and selected studies for data abstraction. The data abstraction form was piloted and developed using the REDCap. We abstracted data on multiple design and methodological aspects of the study including whether the primary method adjusted for both clustering and stratification, reporting of sample size, randomization, and results.

Results

We screened 2686 studies in the phase 1 and selected 286 studies for phase 2—among them 185 studies were selected for data abstraction. Most of the selected studies were two-arm 140/185 (76%) and parallel-group 165/185 (89%) trials. Among these 185 studies, 27 (15%) of them did not provide any sample size or power calculation, while 105 (57%) studies did not mention any method used for randomization within each stratum. Further, 43 (23%) and 150 (81%) of 185 studies did not provide the definition of all the strata, while more than 60% of the studies did not include all the stratification variable(s) in the flow chart or baseline characteristics table. More than half 114/185 (62%) of the studies did not adjust the primary method for both clustering and stratification.

Conclusion

Stratification helps to achieve the balance among intervention groups. However, to correctly assess the intervention effect from stratified CRTs, it is important to adjust the primary analysis for both stratification and clustering. There are significant deficiencies in the reporting of methodological aspects of stratified CRTs, which require substantial improvements in several areas including definition of strata, inclusion of stratification variable(s) in the flow chart or baseline characteristics table, and reporting the stratum-specific number of clusters and individuals in the intervention groups.
The tumor suppressor Zinc finger protein 471 suppresses breast cancer growth and metastasis through inhibiting AKT and Wnt/β-catenin signaling
Authors: Tao Chunfang , Luo Juan , Tang Jun , Zhou Danfeng , Feng Shujun , Qiu Zhu , Putti Thomas C. , Xiang Tingxiu , Tao Qiao , Li Lili , Ren Guosheng
Published: November 2020

Background

Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, and molecular mechanisms in breast cancer.

Methods

We examined ZNF471 expression by RT-PCR and qPCR. Methylation-specific PCR determined its promoter methylation. Its biological functions and related molecular mechanisms were assessed by CCK-8, clonogenicity, wound healing, Transwell, nude mice tumorigenicity, flow cytometry, BrdU-ELISA, immunohistochemistry and Western blot assays.

Results

ZNF471 was significantly downregulated in breast cell lines and tissues due to its promoter CpG methylation, compared with normal mammary epithelial cells and paired surgical-margin tissues. Ectopic expression of ZNF471 substantially inhibited breast tumor cell growth in vitro and in vivo, arrested cell cycle at S phase, and promoted cell apoptosis, as well as suppressed metastasis. Further knockdown of ZNF471 verified its tumor-suppressive effects. We also found that ZNF471 exerted its tumor-suppressive functions through suppressing epithelial-mesenchymal transition, tumor cell stemness and AKT and Wnt/β-catenin signaling.

Conclusions

ZNF471 functions as a tumor suppressor that was epigenetically inactivated in breast cancer. Its inhibition of AKT and Wnt/β-catenin signaling pathways is one of the mechanisms underlying its anti-cancer effects.
Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis
Authors: De Lillo Antonella , Pathak Gita A. , De Angelis Flavio , Di Girolamo Marco , Luigetti Marco , Sabatelli Mario , Perfetto Federico , Frusconi Sabrina , Manfellotto Dario , Fuciarelli Maria , Polimanti Renato
Published: November 2020

Hereditary transthyretin (TTR) amyloidosis (hATTR) is a rare life-threatening disorder caused by amyloidogenic coding mutations located inTTRgene. To understand the high phenotypic variability observed among carriers ofTTRdisease-causing mutations, we conducted an epigenome-wide association study (EWAS) assessing more than 700,000 methylation sites and testing epigenetic difference ofTTRcoding mutation carriersvs. non-carriers. We observed a significant methylation change at cg09097335 site located inBeta-secretase 2(BACE2) gene (standardized regression coefficient = −0.60,p = 6.26 × 10–8). This gene is involved in a protein interaction network enriched for biological processes and molecular pathways related to amyloid-beta metabolism (Gene Ontology: 0050435,q = 0.007), amyloid fiber formation (Reactome HSA-977225,q = 0.008), and Alzheimer’s disease (KEGG hsa05010,q = 2.2 × 10–4). Additionally,TTRandBACE2share APP (amyloid-beta precursor protein) as a validated protein interactor. WithinTTRgene region, we observed that Val30Met disrupts a methylation site, cg13139646, causing a drastic hypomethylation in carriers of this amyloidogenic mutation (standardized regression coefficient = −2.18,p = 3.34 × 10–11). Cg13139646 showed co-methylation with cg19203115 (Pearson’sr2 = 0.32), which showed significant epigenetic differences between symptomatic and asymptomatic carriers of amyloidogenic mutations (standardized regression coefficient = −0.56,p = 8.6 × 10–4). In conclusion, we provide novel insights related to the molecular mechanisms involved in the complex heterogeneity of hATTR, highlighting the role of epigenetic regulation in this rare disorder.
Assessment of MGMT methylation status using high-performance liquid chromatography in newly diagnosed glioblastoma
Authors: Hanihara Mitsuto , Miyake Kunio , Watanabe Atsushi , Yamada Yuriko , Oishi Naoki , Kawataki Tomoyuki , Inukai Takeshi , Kondo Tetsuo , Kinouchi Hiroyuki
Published: November 2020

Background

The utility of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status as a prognostic marker in patients with glioblastoma (GBM) has been established. However, the number of CpG sites that must be methylated to cause transcriptional silencing remains unclear, and no significant consensus exists on the optimal method of assessing MGMT methylation. We developed a new high-performance liquid chromatography (HPLC) method that enables accurate analysis of DNA methylation levels using long PCR products. In the present study, we analyzed the MGMT methylation status of 28 isocitrate dehydrogenase–wild-type GBMs treated with temozolomide using ion-exchange HPLC and set the optimal cutoff values.

Results

We designed three primers for separate regions (regions 1–3) that had 21 to 38 CpGs for PCR and validated the MGMT promoter methylation status using frozen samples. There was a strong correlation between HPLC and bisulfite sequencing results (R = 0.794). The optimal cutoff values for MGMT methylation in HPLC were determined to allow differentiation of patient prognosis by receiver operating characteristic curve analysis. The cutoff values were 34.15% for region 1, 8.84% for region 2, and 36.72% for region 3. Kaplan–Meyer curve analysis estimated that the most differentiated prognosis was enabled in the setting of 8.84% methylation of MGMT in region 2. Progression-free survival and overall survival were significantly longer for patients in this setting of region 2 methylation (p = 0.00365 and p = 0.00258, respectively).

Conclusions

The combination of our HPLC method and the original primer setting provides a new standard method for determination of MGMT methylation status in patients with GBM and is useful for refining MGMT-based drug selection.
Prevalence and risk factors for lung involvement on low-dose chest CT (LDCT) in a paucisymptomatic population of 247 patients affected by COVID-19
Authors: Castelli Maxime , Maurin Arnaud , Bartoli Axel , Dassa Michael , Marchi Baptiste , Finance Julie , Lagier Jean-Christophe , Million Matthieu , Parola Philippe , Brouqui Philippe , Raoult Didier , Cortaredona Sebastien , Jacquier Alexis , Gaubert Jean-Yves , Habert Paul
Published: November 2020

Background

Low-dose chest CT (LDCT) showed high sensitivity and ability to quantify lung involvement of COVID-19 pneumopathy. The aim of this study was to describe the prevalence and risk factors for lung involvement in 247 patients with a visual score and assess the prevalence of incidental findings.

Methods

For 12 days in March 2020, 250 patients with RT-PCR positive tests and who underwent LDCT were retrospectively included. Clinical and imaging findings were recorded. The extent of lung involvement was quantified using a score ranging from 0 to 40. A logistic regression model was used to explore factors associated with a score ≥ 10.

Results

A total of 247 patients were analyzed; 138 (54%) showed lung involvement. The mean score was 4.5 ± 6.5, and the mean score for patients with lung involvement was 8.1 ± 6.8 [1–31]. The mean age was 43 ± 15 years, with 121 males (48%) and 17 asymptomatic patients (7%). Multivariate analysis showed that age > 54 years (odds ratio 4.4[2.0–9.6] p < 0.001) and diabetes (4.7[1.0–22.1] p = 0.049) were risk factors for a score ≥ 10. Multivariate analysis including symptoms showed that only age > 54 years (4.1[1.7–10.0] p = 0.002) was a risk factor for a score ≥ 10. Rhinitis (0.3[0.1–0.7] p = 0.005) and anosmia (0.3[0.1–0.9] p = 0.043) were protective against lung involvement. Incidental imaging findings were found in 19% of patients, with a need for follow-up in 0.6%.

Conclusion

The prevalence of lung involvement was 54% in a predominantly paucisymptomatic population. Age ≥ 55 years and diabetes were risk factors for significant parenchymal lung involvement. Rhinitis and anosmia were protective against LDCT abnormalities.
AiZynthFinder: a fast, robust and flexible open-source software for retrosynthetic planning
Authors: Genheden Samuel , Thakkar Amol , Chadimová Veronika , Reymond Jean-Louis , Engkvist Ola , Bjerrum Esben
Published: November 2020

We present the open-source AiZynthFinder software that can be readily used in retrosynthetic planning. The algorithm is based on a Monte Carlo tree search that recursively breaks down a molecule to purchasable precursors. The tree search is guided by an artificial neural network policy that suggests possible precursors by utilizing a library of known reaction templates. The software is fast and can typically find a solution in less than 10 s and perform a complete search in less than 1 min. Moreover, the development of the code was guided by a range of software engineering principles such as automatic testing, system design and continuous integration leading to robust software with high maintainability. Finally, the software is well documented to make it suitable for beginners. The software is available at http://www.github.com/MolecularAI/aizynthfinder.
Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina modulates the functions of chicken dendritic cells to boost Th1 type immune response and stimulates autologous CD4+ T cells differentiation in-vitro
Authors: Lakho Shakeel Ahmed , Haseeb Muhammad , Huang Jianmei , Yang Zhang , Hasan Muhammad Waqqas , Aleem Muhammad Tahir , Naqvi Muhammad Ali-ul-Husnain , Memon Muhammad Ali , Song XiaoKai , Yan RuoFeng , Xu Lixin , Li XiangRui
Published: November 2020

Dendritic cells (DCs) play a pivotal role to amplify antigen-specific immune responses. Antigens that sensitize T cells via antigen-presentation by DCs could enhance the capacity of host immunity to fight infections. In this study, we tested the immunogenic profiles of chicken DCs towards Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina (EaGAPDH). Immunoblot analysis showed that recombinant EaGAPDH (rEaGAPDH) protein was successfully recognized by rat sera generated against rEaGAPDH. Interaction and internalisation of rEaGAPDH by chicken splenic-derived DCs (chSPDCs) was confirmed by immunofluorescence analysis. Flow cytometry revealed that chSPDCs upregulated MHCII, CD1.1, CD11c, CD80, and CD86 cell-surface markers. Moreover, mRNA expressions of DC maturation biomarkers (CCL5, CCR7, and CD83) and TLR signalling genes (TLR15 and MyD88) were also upregulated whereas those of Wnt signalling were non-significant compared to negative controls. rEaGAPDH treatment induced IL-12 and IFN-γ secretion in chSPDCs but had no effect on IL-10 and TGF-β. Likewise, DC-T cell co-culture promoted IFN-γ secretion and the level of IL-4 was unaffected. Proliferation of T cells and their differentiation into CD3+/CD4+ T cells were triggered in chSPDCs-T cells co-culture system. Taken together, rEaGAPDH could promote Th1 polarization by activating both host DCs and T cells and sheds new light on the role of this important molecule which might contribute to the development of new DCs-based immunotherapeutic strategies against coccidiosis.
Causes of stress and conflict in the veterinary professional workplace – a perspective from Poland
Authors: Wojtacka Joanna , Grudzień Wojciech , Wysok Beata , Szarek Józef
Published: November 2020

Background

The problems of burnout and the moral and ethical distress resulting from various kinds of conflict have been raised in the veterinary profession. However, their sources and inter-relationships have not been thoroughly recognized mainly due to the multidimensional nature of human interactions related to animal breeding, farming, welfare, prophylaxis and therapy. For the first time in Poland, an analysis of conflict and conflict-causing factors in veterinary practice has been conducted with the participation of veterinarians of various specialties and the owners of different animal species.

Results

Conflict in the course of work is most often experienced by young veterinarians. The problems associated with communication between veterinarians and animal owners and unforeseen random situations are the general causes of conflict. Approved Veterinarians were identified by animal owners as the most common professional group associated with the conflict experienced .

Conclusions

There is a lack of professional preparation by veterinary surgeons to cope with unpredicted stressful situations at work, resulting from an absence of appropriate educational input in this area. The animal owners do not understand the role and duties of Approved Veterinarians.
Smooth adversarial examples
Authors: Zhang Hanwei , Avrithis Yannis , Furon Teddy , Amsaleg Laurent
Published: November 2020

This paper investigates the visual quality of the adversarial examples. Recent papers propose to smooth the perturbations to get rid of high frequency artifacts. In this work, smoothing has a different meaning as it perceptually shapes the perturbation according to the visual content of the image to be attacked. The perturbation becomes locally smooth on the flat areas of the input image, but it may be noisy on its textured areas and sharp across its edges.This operation relies on Laplacian smoothing, well-known in graph signal processing, which we integrate in the attack pipeline. We benchmark several attacks with and without smoothing under a white box scenario and evaluate their transferability. Despite the additional constraint of smoothness, our attack has the same probability of success at lower distortion.
The gender gap and healthcare: associations between gender roles and factors affecting healthcare access in Central Malawi, June–August 2017
Authors: Azad Amee D. , Charles Anthony G. , Ding Qian , Trickey Amber W. , Wren Sherry M.
Published: November 2020

Background

Women in low and middle-income countries (LMICs) do not have equal access to resources, such as education, employment, or healthcare compared to men. We sought to explore health disparities and associations between gender prioritization, sociocultural factors, and household decision-making in Central Malawi.

Methods

From June–August 2017, a cross-sectional study with 200 participants was conducted in Central Malawi. We evaluated respondents’ access to care, prioritization within households, decision-making power, and gender equity which was measured using the Gender-Equitable Men (GEM) scale. Relationships between these outcomes and sociodemographic factors were analyzed using multivariable mixed-effect logistic regression.

Results

We found that women were less likely than men to secure community-sourced healthcare financial aid (68.6% vs. 88.8%, p < 0.001) and more likely to underutilize necessary healthcare (37.2% vs. 22.4%, p = 0.02). Both men and women revealed low GEM scores, indicating adherence to traditional gender norms, though women were significantly less equitable (W:16.77 vs. M:17.65, p = 0.03). Being a woman (Odds Ratio (OR) 0.41, 95% confidence interval (CI) 0.21–0.78) and prioritizing a woman as a decision-maker for large purchases (OR 0.38, CI 0.15–0.93) were independently associated with a lower likelihood of prioritizing women for medical treatment and being a member of the Chewa tribal group (OR 3.87, CI 1.83–8.18) and prioritizing women for education (OR 4.13, CI 2.13–8.01) was associated with a higher odds.

Conclusion

Women report greater barriers to healthcare and adhere to more traditional gender roles than men in this Central Malawian population. Women contribute to their own gender’s barriers to care and economic empowerment alone is not enough to correct for these socially constructed roles. We found that education and matriarchal societies may protect against gender disparities. Overall, internal and external gender discrimination contribute to a woman’s disproportionate lack of access to care.
Psychological interventions for depression in children and young people with an intellectual disability and/or autism: systematic review
Authors: Cameron Lauren A. , Phillips Katelyn , Melvin Glenn A. , Hastings Richard P. , Gray Kylie M.
Published: November 2020

Background

Children and young people with intellectual disability and/or Autism Spectrum Disorder (autism) experience higher rates of mental health problems, including depression, than their typically developing peers. Although international guidelines suggest psychological therapies as first-line intervention for children and young people, there is limited evidence for psychological therapy for depression in children and young people with intellectual disability and/or autism.

Aims

To evaluate the current evidence base for psychological interventions for depression in children and young people with intellectual disability and/or autism, and examine the experiences of children and young people with intellectual disability and/or autism, their families and therapists, in receiving and delivering psychological treatment for depression.

Method

Databases were searched up to 30 April 2020 using pre-defined search terms and criteria. Articles were independently screened and assessed for risk of bias. Data were synthesised and reported in a narrative review format.

Results

A total of 10 studies met the inclusion criteria. Four identified studies were clinical case reports and six were quasi-experimental or experimental studies. All studies were assessed as being of moderate or high risk of bias. Participants with intellectual disability were included in four studies. There was limited data on the experiences of young people, their families or therapists in receiving or delivering psychological treatment for depression.

Conclusions

Well-designed, randomised controlled trials are critical to develop an evidence base for psychological treatment for young people with intellectual disability and/or autism with depression. Future research should evaluate the treatment experiences of young people, their families and therapists.
Delays Experienced by Patients With Pediatric Cancer During the Health Facility Referral Process: A Study in Northern Tanzania
Authors: Maillie Luke , Masalu Nestory , Mafwimbo Judy , Maxmilian Mastidia , Schroeder Kristin
Published: November 2020

PURPOSE

It is estimated that 50%-80% of patients with pediatric cancer in sub-Saharan Africa present at an advanced stage. Delays can occur at any time during the care-seeking process from symptom onset to treatment initiation. Referral delay, the time from first presentation at a health facility to oncologist evaluation, is a key component of total delay that has not been evaluated in sub-Saharan Africa.

METHODS

Over a 3-month period, caregivers of children diagnosed with cancer at a regional cancer center (Bugando Medical Centre [BMC]) in Tanzania were consecutively surveyed to determine the number and type of health facilities visited before presentation, interventions received, and transportation used to reach each facility.

RESULTS

Forty-nine caregivers were consented and included in the review. A total of 124 facilities were visited before BMC, with 31% of visits (n = 38) resulting in a referral. The median referral delay was 89 days (mean, 122 days), with a median of two facilities (mean, 2.5 facilities) visited before presentation to BMC. Visiting a traditional healer first significantly increased the time taken to reach BMC compared with starting at a health center/dispensary (103 v 236 days; P = .02). Facility visits in which a patient received a referral to a higher-level facility led to significantly decreased time to reach BMC ( P < .0001). Only 36% of visits to district hospitals and 20.6% of visits to health centers/dispensaries yielded a referral, however.

CONCLUSION

The majority of patients were delayed during the referral process, but receipt of a referral to a higher-level facility significantly shortened delay time. Referral delay for pediatric patients with cancer could be decreased by raising awareness of cancer and strengthening the referral process from lower-level to higher-level facilities.
Accessory proteins of the zDHHC family of S-acylation enzymes
Authors: Salaun Christine , Locatelli Carolina , Zmuda Filip , Cabrera González Juan , Chamberlain Luke H.
Published: November 2020

Almost two decades have passed since seminal work in Saccharomyces cerevisiae identified zinc finger DHHC domain-containing (zDHHC) enzymes as S-acyltransferases. These enzymes are ubiquitous in the eukarya domain, with 23 distinct zDHHC-encoding genes in the human genome. zDHHC enzymes mediate the bulk of S-acylation (also known as palmitoylation) reactions in cells, transferring acyl chains to cysteine thiolates, and in so-doing affecting the stability, localisation and function of several thousand proteins. Studies using purified components have shown that the minimal requirements for S-acylation are an appropriate zDHHC enzyme–substrate pair and fatty acyl-CoA. However, additional proteins including GCP16 (also known as Golga7), Golga7b, huntingtin and selenoprotein K, have been suggested to regulate the activity, stability and trafficking of certain zDHHC enzymes. In this Review, we discuss the role of these accessory proteins as essential components of the cellular S-acylation system.
MRI for the display of autologous onlay bone grafts during early healing—an experimental study
Authors: Flügge Tabea , Ludwig Ute , Amrein Philipp , Kernen Florian , Vach Kirstin , Maier Johannes , Nelson Katja
Published: November 2020

Objectives:

Autologous bone grafts are the gold standard to augment deficient alveolar bone. Dimensional graft alterations during healing are not known as they are not accessible to radiography. Therefore, MRI was used to display autologous onlay bone grafts in vivo during early healing.

Methods and materials:

Ten patients with alveolar bone atrophy and autologous onlay grafts were included. MRI was performed with a clinical MR system and an intraoral coil preoperatively (t0), 1 week (t1), 6 weeks (t2) and 12 weeks (t3) postoperatively, respectively. The graft volumes were assessed in MRI by manual segmentation by three examiners. Graft volumes for each time point were calculated and dimensional alteration was documented. Cortical and cancellous proportions of bone grafts were assessed. The intraobserver and interobserver variability were calculated. Statistical analysis was performed using a mixed linear regression model.

Results:

Autologous onlay bone grafts with cortical and cancellous properties were displayed in vivo in eight patients over 12 weeks. The fixation screws were visible as signal voids with a thin hyperintense fringe. The calculated volumes were between 0.12–0.74 cm3 (t1), 0.15–0.73 cm3 (t2), and 0.17–0.64 cm3 (t3). Median changes of bone graft volumes of −15% were observed. There was no significant difference between the examiners (p = 0.3).

Conclusions:

MRI is eligible for the display and longitudinal observation of autologous onlay bone grafts. Image artifacts caused measurements deviations in some cases and minimized the precise assessment of graft volume. To the knowledge of the authors, this is the first study that used MRI for the longitudinal observation of autologous onlay bone grafts.
Healthcare Resource Utilization Following a Discharge Against Medical Advice: An Analysis of Commercially Insured Adults
Authors: Gandhi Aakash Bipin , Onukwugha Eberechukwu , McRae Jacquelyn , Alfandre David
Published: November 2020

BACKGROUND

A discharge against medical advice (DAMA) is associated with adverse health outcomes. Its association with postdischarge healthcare resource utilization (HcRU) outside an inpatient setting is unknown. This information can help us understand how a DAMA may affect healthcare‐seeking behavior following a hospital stay. We evaluated the relationship between a DAMA and 30‐day postdischarge HcRU.

METHODS

This retrospective cohort study uses a 10% random sample of enrollees in the IQVIA PharMetrics® Plus database. We included individuals aged 18 to 64 years with an inpatient admission during 2007‐2015 and continuous insurance coverage. We defined comparison groups as DAMA and routine discharge. Both groups were matched on baseline covariates. We quantified the association between a DAMA and 30‐day HcRU, as well as 90‐day for sensitivity analysis, with use of generalized linear models for binary outcomes (inpatient readmissions, emergency department [ED] visits) and count outcomes (physician office visits, nonphysician outpatient encounters, prescription drug fills).

RESULTS

Of the 457,530 individuals in the unmatched sample, 2,245 (0.5%) had a DAMA. In the matched sample, a DAMA was positively associated with an ED visit (adjusted odds ratio, 2.28; 95% confidence interval, 1.90‐2.72) but not with an inpatient readmission. There were no differences between groups based on the count outcomes. A DAMA was positively associated with 90‐day HcRU (ie, inpatient readmission, ED visit, and prescription drug fills).

CONCLUSION

The relationship between a DAMA and HcRU varied with the HcRU category and postdischarge time interval. This examination of HcRU in the inpatient and outpatient settings provides important information about outcomes following a DAMA.
THE IMPACT OF LEADERSHIP EDUCATION AND CO-CURRICULAR INVOLVEMENT ON THE DEVELOPMENT OF SOCIALLY RESPONSIBLE LEADERSHIP OUTCOMES IN UNDERGRADUATE STUDENTS An Exploratory Study
Authors: Martinez Nicholas , Sowcik Matthew J. , Bunch James Charles
Published: November 2020

Socially responsible leadership (SRL) is a “purposeful, collaborative, values-based process that results in positive social change” (Komives, Wagner, & Associates, 2009, p. xii).This approach to leadership focuses on creating leaders that are capable of tackling the predicted wicked problems the world will face in the next few decades. As the number of leadership education programs continue to grow throughout higher education, it is important to assess the impact leadership education and co-curricular programs are having on students. Utilizing the Multi- Institutional Study of Leadership, this study aimed to better understand whether higher education leadership development, community service and study abroad programs are successfully developing students with self- perceived socially responsible leadership.
A NEW CONCEPTUAL MODEL: Integrating Ethical Leadership into the Assess, Challenge and Support (ACS) Model of Leader Development
Authors: Brown Shannon , Chikeleze Michael
Published: November 2020

Our paper discusses the need for continued focus on ethical leadership and the importance and benefits of ethical leadership development. We propose integrating ethical leadership development, that uses cognitive development theory, into the Center for Creative Leadership’s Assess, Challenge, and Support (ACS) leader development model to help address the continued failures of ethical leader development. Our extended framework includes values and morals as a component of the model, and ethical organizational culture as its backdrop, thereby incorporating an examination of ethical leadership into each component of the ACS model. We conclude with practical implications and suggestions for future research.
Should the femoral or brachial artery be used if radial artery cannulation is difficult?
Authors: McGuire Sean , Campbell Niamh , Carle Coralie
Published: November 2020

Current best practice in placement of arterial lines is to attempt to cannulate the radial artery in the first instance. However, if the radial artery is difficult to cannulate there is no consensus among clinicians on how best to proceed. This article looks at the evidence for the different options.
Lithium-associated hyperparathyroidism
Authors: Mifsud Simon , Cilia Kyle , Mifsud Emma L , Gruppetta Mark
Published: November 2020

Lithium is a mood stabiliser widely used in the treatment and prophylaxis of mania, bipolar disorders and recurrent depression. Treatment with lithium can give rise to various endocrine and metabolic abnormalities, including thyroid dysfunction, nephrogenic diabetes insipidus and hypercalcaemia. Lithium may induce hypercalcaemia through both acute and chronic effects. The initial acute effects are potentially reversible and occur as a result of lithium's action on the calcium-sensing receptor pathway and glycogen synthase kinase 3, giving rise to a biochemical picture similar to that seen in familial hypocalciuric hypercalcaemia. In the long term, chronic lithium therapy leads to permanent changes within the parathyroid glands by either unmasking hyperparathyroidism in patients with a subclinical parathyroid adenoma or possibly by initiating multiglandular hyperparathyroidism. The latter biochemical picture is identical to that of primary hyperparathyroidism. Lithium-associated hyperparathyroidism, especially in patients on chronic lithium therapy, is associated with increased morbidity. Hence, regular monitoring of calcium levels in patients on lithium therapy is of paramount importance as early recognition of lithium-associated hyperparathyroidism can improve outcomes. This review focuses on the definition, pathophysiology, presentation, investigations and management of lithium-associated hyperparathyroidism.
Consequences of prioritisation within long-term care in Denmark, England and Norway: towards increasing inequalities and poorer quality of care?
Authors: Ervik Rune , Lindén Tord Skogedal
Published: November 2020

Prioritisation concerns choosing something before something else, and in a welfare state context, this is about decisions on distribution, redistribution and rationing. This article investigates consequences of prioritisation within long-term care in Denmark, England and Norway. Analysing interviews with policy actors and policy documents, we find that prioritising home care, combined with increasing targeting of help and restricting institutionalised care towards those with the most severe needs, may reduce both service quality and equality for those not being prioritised. Moreover, monitoring and central control of service provision restrict individual discretion of care workers, with implications for service quality.
Quantitative measurement of mechanical properties in wound healing processes in a corneal stroma model by using vibrational optical coherence elastography (OCE)
Authors: Zhang Yilong , Ling Yuting , Zhang Duo , Wang Mingkai , Purslow Christine , Yang Ying , Li Chunhui , Huang Zhihong
Published: November 2020

Corneal wound healing, caused by frequent traumatic injury to the cornea and increasing numbers of refractive surgeries, has become a vital clinical problem. In the cornea, wound healing is an extremely complicated process. However, little is known about how the biomechanical changes in wound healing response of the cornea. Collagen-based hydrogels incorporating corneal cells are suitable for replicating a three-dimensional (3D) equivalent of the cornea in-vitro. In this study, the mechanical properties of corneal stroma models were quantitatively monitored by a vibrational optical coherence elastography (OCE) system during continuous culture periods. Specifically, human corneal keratocytes were seeded at 5 × 105 cells/mL in the hydrogels with a collagen concentration of 3.0 mg/mL. The elastic modulus of the unwounded constructs increased from 2.950 ± 0.2 kPa to 11.0 ± 1.4 kPa, and the maximum thickness decreased from 1.034 ± 0.1 mm to 0.464 ± 0.09 mm during a 15-day culture period. Furthermore, a traumatic wound in the construct was introduced with a size of 500 µm. The elastic modulus of the neo-tissue in the wound area increased from 1.488 ± 0.4 kPa to 6.639 ± 0.3 kPa over 13 days. This study demonstrates that the vibrational OCE system is capable of quantitative monitoring the changes in mechanical properties of a corneal stroma wound model during continuous culture periods and improves our understanding on corneal wound healing processes.
Laser-induced optical breakdown effects of micro-lens arrays and diffractive optical elements on ex vivo porcine skin after 1064 nm picosecond laser irradiation
Authors: Kim Hyeonsoo , Hwang Jewan Kaiser , Jung Minjung , Choi Jongman , Kang Hyun Wook
Published: November 2020

The current study aims to investigate the effects of micro-lens arrays (MLA) and diffractive optical elements (DOE) on skin tissue via intra-dermal laser-induced optical breakdown (LIOB) after irradiation of 1064-nm picosecond laser light at high energy settings. Irradiation with MLA and DOE was tested on dimming paper, tissue-mimicking phantom, and dark pigmented porcine skin to quantitatively compare distributions of micro-beams, micro-bubbles, and laser-induced vacuoles in the skin. DOE yielded more uniform distributions of the micro-beams on the paper and laser-induced micro-bubbles in the phantom, compared to MLA. The ex vivo skin test confirmed that the DOE-assisted irradiation accompanied more homogeneous generation of the micro-beams on the tissue surface (deviation of ≤ 3%) and a high density of small laser-induced vacuoles (∼78 µm) in the dermis than the MLA-assisted irradiation (deviation of ∼26% and ∼163 µm). The DOE-assisted picosecond laser irradiation may help to achieve deep and uniformly-generated vacuolization under the basal membrane after intra-dermal LIOB for effective fractional skin treatment.
Temporal quantum noise reduction acquired by an electron-multiplying charge-coupled-device camera
Authors: Li Fu , Li Tian , Agarwal Girish S.
Published: November 2020

Electron-multiplying charge-coupled-device cameras (EMCCDs) have been used to observe quantum noise reductions in beams of light in the transverse spatial degree of freedom. For the quantum noise reduction in the temporal domain, ‘bucket detectors,’ usually composed of photodiodes with operational amplifiers, are used to register the intensity fluctuations in beams of light within the detectors’ bandwidth. Here, we report on measurements of the temporal quantum noise reduction in bright twin beams using an EMCCD camera. The four-wave mixing process in an atomic rubidium vapor cell is used to generate the bright twin beams of light. We observe ∼ 25% of temporal quantum noise reduction with respect to the shot-noise limit in images captured by the EMCCD camera. The temporal images captured by our technique are potentially important in obtaining dynamical information on evolving systems.
Removal of ghost particles from the reconstruction of dusty plasma in integral photography by three-dimensional deconvolution
Authors: Sanpei Akio , Kai Eisaku , Kawade Yasutaka
Published: November 2020

The integral photography and deconvolution techniques have been applied to identify the three-dimensional (3D) positions of particles levitating in plasma. Artifacts in the light field, i.e. ghost particles, are removed by collating between results of integral photography and direct Richardson-Lucy deconvolution (RLD). Our reconstruction system is tested with known target particles and it is found that it works well in the range of our dust experiment. By applying the integral photography and RLD techniques to the obtained experimental image, we identified the 3D positions of dust particles floating in a radio-frequency plasma. Ghost particles are eliminated from the results by deconvolution and we succeeded in obtaining the 3D structure of a dusty plasma from a single-exposure image obtained from one view port.
Ultra-low-power nonvolatile integrated photonic switches and modulators based on nanogap-enhanced phase-change waveguides
Authors: Zhang Jieying , Zheng Jiajiu , Xu Peipeng , Wang Yanqun , Majumdar Arka
Published: November 2020

We propose a nanogap-enhanced phase-change waveguide with silicon PIN heaters. Thanks to the enhanced light-matter interaction in the nanogap, the proposed structure exhibits strong attenuation (Δα = ∼35 dB/µm) and optical phase (Δneff = ∼1.2) modulation at λ = 1550 nm when achieving complete phase transitions. We further investigate two active optical devices based on the proposed waveguide, including an electro-absorption modulator and a 1 × 2 directional-coupler optical switch. Finite-difference time-domain simulation of the proposed modulator shows a high extinction ratio of ∼17 dB at 1550 nm with an active segment of volume only ∼0.004λ3. By exploiting a directional coupler design, we present a 1 × 2 optical switch with an insertion loss of < 4 dB and a compact coupling length of ∼ 15 µm while maintaining small crosstalk less than −7.2 dB over an optical bandwidth of 50 nm. Thermal analysis shows that a 10 V pulse of 30 ns (1×1 modulator) and 55 ns (1×2 switch) in duration is required to raise the GST temperature of the phase-change waveguide above the melting temperature to induce the amorphization; however, the complete crystallization occurs by applying a 5 V pulse of 180 ns (1×1 modulator) and a 6 V pulse of 200 ns (1×2 switch), respectively.
Ultraviolet intracavity frequency-doubled Pr3+:LiYF4 orbital Poincaré laser
Authors: Srinivasa Rao A. , Miamoto Katsuhiko , Omatsu Takashige
Published: November 2020

Here we demonstrate intracavity frequency-doubling of an ultra-compact (cavity length < 20 mm) Pr3+:LiYF4 (YLF) orbital Poincaré laser, in which the fundamental modes are represented on an equivalent orbital Poincaré sphere (eOPS) and a singularities hybrid evolution nature sphere (SHENS). The generated ultraviolet (UV, 320 nm) output carries orbital angular momentum (OAM), and it typically exhibits an optical bottle beam with a 3-dimensional dark core, formed of a coherent superposition of eigen Laguerre-Gaussian (LG) modes. Such ultraviolet structured light beams with OAM offer many advanced applications from microscopy to materials processing.
Long-wave mid-infrared time-resolved dual-comb spectroscopy of short-lived intermediates
Authors: Luo Pei-Ling
Published: November 2020

In this Letter, an electro-optic dual-comb spectrometer with a central tunable range of 7.77–8.22 µm is demonstrated to perform transient absorption spectroscopy of the simplest Criegee intermediate (

C
H

2

O
O

), a short-lived species involved in many key atmospheric reactions, and its self-reaction product via comb-mode-resolved spectral sampling at microsecond temporal resolution. By combining with a Herriott-type flash photolysis cell,

C
H

2

O
O

can be probed with a detection limit down to

∼

1

×

10

11

m
o
l
e
c
u
l
e
s

c
m

−
3

. Moreover, pressure broadening of

C
H

2

O
O

absorption lines can be studied with spectrally interleaved dual-comb spectroscopy. This Letter holds promise for high-resolution precision measurements of transient molecules, especially for the study of large molecules in complex systems.
Influence of liquid nitrogen cooling on the spectral performance of BAC-P in bismuth-doped phosphosilicate fibers under liquid nitrogen temperature
Authors: Zhao Qiancheng , Hao Qun , Yu Changyuan , Tan Fengze , Luo Yanhua , Peng Gang-Ding
Published: November 2020

The first results of the liquid nitrogen cooling effect on the spectral properties of a phosphor-related bismuth active center (BAC-P) have been presented. It is found that the small-signal absorption bands of BACs are mildly affected at liquid nitrogen temperature (LNT, 77 K), while the unsaturable absorption level is lowered moderately. Meanwhile, noticeable shape changes of luminescence spectra and enhanced luminescence intensity (∼ twice) of BAC bands were revealed at LNT upon excitation at 830 or 980 nm, which is contributed by the notable growth of BAC-P. In addition, the influence of cooling on the on-off gain performance of BACs is also explored. Furthermore, the laser-induced effect on the luminescence of BAC-P upon cooling at LNT is also investigated, revealing a noticeable increase (∼10%) instead of photobleaching. These experimental results bring new insights into the temperature-related spectral properties of BACs and provide an effective way for tuning the luminescence scheme for Bi-doped fibers by cryogenics for the desired spectral range 1.26-1.36 μm.
Budgerigars have complex sleep structure similar to that of mammals
Authors: Canavan Sofija V. , Margoliash Daniel
Published: November 2020

Birds and mammals share specialized forms of sleep including slow wave sleep (SWS) and rapid eye movement sleep (REM), raising the question of why and how specialized sleep evolved. Extensive prior studies concluded that avian sleep lacked many features characteristic of mammalian sleep, and therefore that specialized sleep must have evolved independently in birds and mammals. This has been challenged by evidence of more complex sleep in multiple songbird species. To extend this analysis beyond songbirds, we examined a species of parrot, the sister taxon to songbirds. We implanted adult budgerigars (Melopsittacus undulatus) with electroencephalogram (EEG) and electrooculogram (EOG) electrodes to evaluate sleep architecture, and video monitored birds during sleep. Sleep was scored with manual and automated techniques, including automated detection of slow waves and eye movements. This can help define a new standard for how to score sleep in birds. Budgerigars exhibited consolidated sleep, a pattern also observed in songbirds, and many mammalian species, including humans. We found that REM constituted 26.5% of total sleep, comparable to humans and an order of magnitude greater than previously reported. Although we observed no spindles, we found a clear state of intermediate sleep (IS) similar to non-REM (NREM) stage 2. Across the night, SWS decreased and REM increased, as observed in mammals and songbirds. Slow wave activity (SWA) fluctuated with a 29-min ultradian rhythm, indicating a tendency to move systematically through sleep states as observed in other species with consolidated sleep. These results are at variance with numerous older sleep studies, including for budgerigars. Here, we demonstrated that lighting conditions used in the prior budgerigar study—and commonly used in older bird studies—dramatically disrupted budgerigar sleep structure, explaining the prior results. Thus, it is likely that more complex sleep has been overlooked in a broad range of bird species. The similarities in sleep architecture observed in mammals, songbirds, and now budgerigars, alongside recent work in reptiles and basal birds, provide support for the hypothesis that a common amniote ancestor possessed the precursors that gave rise to REM and SWS at one or more loci in the parallel evolution of sleep in higher vertebrates. We discuss this hypothesis in terms of the common plan of forebrain organization shared by reptiles, birds, and mammals.
Inhibition of the de novo pyrimidine biosynthesis pathway limits ribosomal RNA transcription causing nucleolar stress in glioblastoma cells
Authors: Lafita-Navarro M. Carmen , Venkateswaran Niranjan , Kilgore Jessica A. , Kanji Suman , Han Jungsoo , Barnes Spencer , Williams Noelle S. , Buszczak Michael , Burma Sandeep , Conacci-Sorrell Maralice
Published: November 2020

Glioblastoma is the most common and aggressive type of cancer in the brain; its poor prognosis is often marked by reoccurrence due to resistance to the chemotherapeutic agent temozolomide, which is triggered by an increase in the expression of DNA repair enzymes such as MGMT. The poor prognosis and limited therapeutic options led to studies targeted at understanding specific vulnerabilities of glioblastoma cells. Metabolic adaptations leading to increased synthesis of nucleotides by de novo biosynthesis pathways are emerging as key alterations driving glioblastoma growth. In this study, we show that enzymes necessary for the de novo biosynthesis of pyrimidines, DHODH and UMPS, are elevated in high grade gliomas and in glioblastoma cell lines. We demonstrate that DHODH’s activity is necessary to maintain ribosomal DNA transcription (rDNA). Pharmacological inhibition of DHODH with the specific inhibitors brequinar or ML390 effectively depleted the pool of pyrimidines in glioblastoma cells grown in vitro and in vivo and impaired rDNA transcription, leading to nucleolar stress. Nucleolar stress was visualized by the aberrant redistribution of the transcription factor UBF and the nucleolar organizer nucleophosmin 1 (NPM1), as well as the stabilization of the transcription factor p53. Moreover, DHODH inhibition decreased the proliferation of glioblastoma cells, including temozolomide-resistant cells. Importantly, the addition of exogenous uridine, which reconstitutes the cellular pool of pyrimidine by the salvage pathway, to the culture media recovered the impaired rDNA transcription, nucleolar morphology, p53 levels, and proliferation of glioblastoma cells caused by the DHODH inhibitors. Our in vivo data indicate that while inhibition of DHODH caused a dramatic reduction in pyrimidines in tumor cells, it did not affect the overall pyrimidine levels in normal brain and liver tissues, suggesting that pyrimidine production by the salvage pathway may play an important role in maintaining these nucleotides in normal cells. Our study demonstrates that glioblastoma cells heavily rely on the de novo pyrimidine biosynthesis pathway to generate ribosomal RNA (rRNA) and thus, we identified an approach to inhibit ribosome production and consequently the proliferation of glioblastoma cells through the specific inhibition of the de novo pyrimidine biosynthesis pathway.