bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Well-being: The Quest for Wholeness and Purpose in Education
Authors: Shirley Dennis
Published: August 2020

Purpose:

This article develops a critique of contemporary understandings and practices related to well-being in education. It proposes a fuller development of wholeness and purpose that supplements and goes beyond the new well-being agenda.

Design/Approach/Methods:

This article draws upon a document analysis of conceptual and policy frameworks related to well-being. It builds its critique of well-being with reference to a qualitative study consisting of 222 interviews with educators in the Canadian province of Ontario with regard to their understandings of well-being. It includes references to the research and development work in the U.S., Germany, and Norway.

Findings:

The inclusion of well-being in policy agendas is an important step forward in the field of educational change, but this indication of progress is in danger of being reified through simplistic understandings of life satisfaction and other frameworks that evade the complexity of human development. Wholeness and purpose are concepts that include but also go beyond well-being that should be addressed by educators.

Originality/Value:

Most of the criticisms of the new well-being agenda in educational policies and research simply assume its status as a summum bonum for human development. This essay acknowledges the importance of well-being but expands beyond it to define wholeness and purpose as an alternative set of constructs with their own independent integrity that should not simply be subsumed into current well-being agendas.
Internationalization of Canadian Teacher Education: Teacher Candidates’ Experiences and Perspectives
Authors: Guo (郭燕) Yan , Guo (郭世宝) Shibao
Published: August 2020

Purpose:

Informed by social imaginary, Canadian exceptionalism, and social inclusion, this study explores how teacher candidates experience and interpret internationalization at home at one university in Canada.

Design/Approach/Methods:

Data were collected from three sources: (a) policy analyses of public documents related to internationalization in Canada and at the university; (b) a student survey on the internationalization of higher education; and (c) individual interviews with 12 teacher candidates. Eight interviewees were local, four White and four racialized minorities, and four were international.

Findings:

Findings indicate that most participants relate internationalization to student mobility. They present the Canadian society and themselves as open, tolerant, and accepting. Such an imaginary of Canadian exceptionalism does not necessarily coincide with everyday realities of international and racialized teacher candidates. They reported that they experienced Eurocentric curricula, different forms of exclusion, and racism. Some participants enacted agency to disrupt the dominance of White perspectives.

Originality/Value:

This research addresses knowledge gaps related to internationalization policy as teacher candidates’ voices are not often heard in internationalization initiatives. The study suggests that the internationalization of teacher education requires decolonization of curriculum, bridging with anti-racism education, and the internationalization of teacher educators.
Surgical Outcomes of C1-2 Posterior Stabilization in Patients With Chiari Malformation Type 1
Authors: Arslan Ali , Olguner Semih Kivanc , Acik Vedat , İstemen İsmail , Arslan Barış , Ökten Ali İhsan , Gezercan Yurdal
Published: August 2020

Study Design:

Retrospective chart review.

Objectives:

Chiari malformation (CM) is characterized by a downward displacement of the cerebellar tonsils through the foramen magnum. This tonsillar herniation may sometimes be accompanied by syringomyelia and/or basilar invagination (BI). In this study, we examined the surgical outcomes of patients by underwent C1-2 reduction + fixation (C1-2RF), which is a new method defined by Goel, in the literature.

Methods:

Between 2015 and 2018, 21 patients (mean age and duration of follow-up: 39 years and 20 months, respectively) with CM were treated with atlantoaxial fixation. We found syringomyelia in all patients and BI in 9 of them. In all cases, radiography, computed tomography, and magnetic resonance imaging were performed radiologically. C1-2RF was performed in all patients. Preoperative and postoperative clinical Japanese Orthopaedic Association scores were obtained. Syrinx size and cerebrospinal fluid flow rate were compared radiologically.

Results:

All patients were treated with C1-2RF. None of the patients underwent foramen magnum decompression or intervention for the syrinx. Occipital bone and subaxial spinal structures were not included in the fixation. In addition to significant clinical improvement, significant improvement in syringomyelia and cerebrospinal fluid flow rate was seen on the radiographs of all patients.

Conclusions:

Although posterior fossa decompression and/or duraplasty is a common treatment modality in CM, we propose that the C1-2RF method described by Goel is a radiologically and clinically effective treatment method, whether or not BI and/or syringomyelia in CM are present. This article is the first article of central and axial atlantoaxial dislocation, except for Goel’s writings in the literature.
Ehrlichiosis-Induced Atrial Flutter: An Unusual Cause of Atrial Flutter
Authors: Kunnumpurath Anthony , Kamoga Gilbert-Roy
Published: August 2020

Tick-borne illness has been increasingly on the rise, since the first human case was reported in the late 1980s. Ehrlichia chaffeensis is one of the most common reported causes of tick-borne illness, particularly in the southern states of the United States. The clinical picture presents as a paradigm to the clinician, often missing the diagnosis without an appropriate history being taken and sometimes mistreated for other conditions. With the number of cases on the rise, new manifestations and clinical presentations due to E chaffeensis continue to be reported. Our case report is one such case in a 46-year-old male from Arkansas, with known exposure to multiple tick bites who presented with classical symptoms and laboratory values of tick-borne illness leading to atrial flutter. This unusual manifestation of atrial flutter due to tick-borne illness is rare and poorly understood. Further studies on tick-borne illness due to E chaffeensis may be needed to understand the systemic causes of the bacteria. In addition, in our case report, we bring to attention the standard presentation (symptoms, signs, and laboratory values) of tick-borne illness due to E chaffeensis along with the current standard for diagnosis and treatment.
Drug-Drug Interactions Between Cannabidiol and Lithium
Authors: Singh Rani K. , Dillon Brittany , Tatum David A. , Van Poppel Katherine C. , Bonthius Daniel J.
Published: August 2020

Epidiolex® (Cannabidiol- CBD) is approved for epilepsy associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients over 2 years of age. Common side effects include somnolence and diarrhea. Recent studies have demonstrated interactions between cannabidiol and several other antiseizure medications. However, little is known regarding interactions between cannabidiol and other classes of medications. We discuss an autistic patient with LGS and significant psychiatric comorbidities who was being treated with multiple antiseizure and psychiatric medications, including lithium, when CBD was added to his medical regimen. Several weeks after initiating CBD therapy, he developed hypersomnolence, ataxia and decreased oral intake and was found to have lithium toxicity. Lithium was discontinued and his symptoms resolved. He remains on CBD and 2 other antiseizure medications, seizure-free with improved behavior. We review mechanisms of action and pharmacokinetics of CBD and discuss possible explanations for lithium toxicity in this patient.
Early use of acute medication for preventing migraine attacks: Results from a diary-based cohort study
Authors: Termini Susanna Di , Wöber Christian , Brannath Werner
Published: August 2020

Background:

Treating migraine attacks early may improve outcome. The aim of this analysis was to investigate whether certain premonitory symptoms could be indicators for taking acute medication.

Methods:

We analyzed 3-month diary data recorded by 271 patients with episodic migraine and looked at all migraine-free intervals. For investigating the interaction between acute medication and neck discomfort associated with sensitivity to lights, noises, or odors, we used a marginal structural model and a Cox regression analysis adjusted for moderate or severe headache.

Results:

The patients (mean age 43 ± 15.4 years, 88% women) recorded a total of 20,219 diary days without migraine. In the marginal structural model analysis, the risk for occurrence of a migraine attack on the subsequent day was reduced when acute medication was used in the presence of neck discomfort associated with sensitivity to lights (hazard ratio 0.4; 95% confidence interval 0.2–0.7), noises (0.4; 0.3–0.7), or odors (0.2; 0.1–0.4). The marginal structural model showed lower risk of migraine attacks than the Cox regression analysis adjusted for moderate or severe headache in the majority of the cases.

Conclusion:

Migraine attacks may be prevented when acute medication is used in the presence of neck discomfort associated with sensitivity to lights, noises, or odors. The results of this study may stimulate further prospective trials.
Prevention Science as a Platform for Solving Major Societal Problems and Improving Population Health
Authors: Herman Keith C. , Reinke Wendy M. , Thompson Aaron M.
Published: August 2020

The article describes a prevention science approach to impacting population health. We use activities of the Missouri Prevention Science Institute that address youth mental health concerns with a public health approach to illustrate the approach. In particular, we focus on several lessons that may be relevant for advancing the success of prevention and health promotion scholars in addressing major societal problems: connecting small ideas to big solutions, matching intervention targets with goals, developing reliable and systemic monitoring data streams, ensuring data and prevention efforts account for cultural context, and helping people/systems change.
Observations about the seismic response of RC buildings in Mexico City
Authors: Alcocer Sergio , Behrouzi Anahid , Brena Sergio , J Elwood Kenneth , Irfanoglu Ayhan , Kreger Michael , Lequesne Rémy , Mosqueda Gilberto , Pujol Santiago , Puranam Aishwarya , Rodriguez Mario , Shah Prateek , Stavridis Andreas , Wood Richard
Published: August 2020

Over 2000 buildings were surveyed by members of the Colegio de Ingenieros (CICM) and Sociedad Mexicana de Ingenieria Estructural (SMIE) in Mexico City following the Puebla-Morelos Earthquake of 2017. This inventory of surveyed buildings included nearly 40 collapses and over 600 buildings deemed to have structural damage. Correlation of damage with peak ground acceleration (PGA), peak ground velocity (PGV), predominant spectral period, building location, and building properties including height, estimated stiffness, and presence of walls or retrofits was investigated for the surveyed buildings. The evidence available suggests that (1) ground motion intensity (PGV) drove the occurrence of damage and (2) buildings with more infill and stiff retrofit systems did better than other buildings.
Induced earthquake damage assessment methodology for potential hydraulic fracturing sites: Application to Manaus, Brazil
Authors: Silva Andréia HA , Pita Gonzalo L , Inaudi José A , Vieira Luiz CM
Published: August 2020

The number of seismic events induced by the exploitation of unconventional oil and gas reservoirs has escalated considerably in the last decade. This has raised concerns in several sectors of society, and in consequence, research efforts have been launched to ascertain the risk associated with induced seismicity. This article presents a procedure to quantify potential damages caused by induced seismicity to the built infrastructure of a region. The technique adapts the probabilistic seismic hazard analysis framework to the features of induced seismicity. The risk is then evaluated by the probability of exceeding economic loss. Estimates of potential injuries or loss of life caused by buildings’ interior components are fundamental policymaking inputs, but were not considered in this initial study which is focused on assessing direct damage. In a future study, however, these factors will be addressed. The procedure is applied in a case study in Manaus, a city located on a large shale gas basin which is potentially exploitable. The results of the study indicate that the tectonic parameter ( b) of the adjusted Gutenberg–Richter model is a governing driver in the loss analysis. Two damage mitigation strategies are proposed: one that limits volume injected setting loss thresholds and other that restricts injection locations based on damage modeling estimates. Insights from the case study emphasize that these type of activities should be avoided near urban areas where seismic standard anticipates low natural seismicity, and with a high proportion of poorly built residential infrastructure. The study contributes to the literature a technique to inform the decision-making associated with establishing unconventional oil and gas exploitation projects that is applicable to several places and situations.
HAK/KUP/KT family potassium transporter genes are involved in potassium deficiency and stress responses in tea plants (Camellia sinensis L.): expression and functional analysis
Authors: Yang Tianyuan , Lu Xin , Wang Yan , Xie Yunxia , Ma Jingzhen , Cheng Xunmin , Xia Enhua , Wan Xiaochun , Zhang Zhaoliang
Published: August 2020

Background

Tea plant is one of the most important non-alcoholic beverage crops worldwide. While potassium (K+) is an essential macronutrient and greatly affects the growth and development of plants, the molecular mechanism underlying K+ uptake and transport in tea plant root, especially under limited-K+ conditions, is still poorly understood. In plants, HAK/KUP/KT family members play a crucial role in K+ acquisition and translocation, growth and development, and response to stresses. Nevertheless, the biological functions of these genes in tea plant are still in mystery, especially their roles in K+ uptake and stress responses.

Results

In this study, a total of 21 non-redundant HAK/KUP/KT genes (designated as CsHAKs) were identified in tea plant. Phylogenetic and structural analysis classified the CsHAKs into four clusters (I, II, III, IV), containing 4, 8, 4 and 5 genes, respectively. Three major categories of cis-acting elements were found in the promoter regions of CsHAKs. Tissue-specific expression analysis indicated extremely low expression levels in various tissues of cluster I CsHAKs with the exception of a high root expression of CsHAK4 and CsHAK5, a constitutive expression of clusters II and III CsHAKs, and a moderate cluster IV CsHAKs expression. Remarkably, the transcript levels of CsHAKs in roots were significantly induced or suppressed after exposure to K+ deficiency, salt and drought stresses, and phytohormones treatments. Also notably, CsHAK7 was highly expressed in all tissues and was further induced under various stress conditions. Therefore, functional characterization of CsHAK7 was performed, and the results demostrated that CsHAK7 locates on plasma membrane and plays a key role in K+ transport in yeast. Taken together, the results provide promising candidate CsHAKs for further functional studies and contribute to the molecular breeding for new tea plants varieties with highly efficient utilization of K+.

Conclusion

This study demonstrated the first genome-wide analysis of CsHAK family genes of tea plant and provides a foundation for understanding the classification and functions of the CsHAKs in tea plants.
Differences in patient population and service provision between nurse practitioner and general practitioner consultations in Swiss primary care: a case study
Authors: Gysin Stefan , Meier Rahel , van Vught Anneke , Merlo Christoph , Gemperli Armin , Essig Stefan
Published: August 2020

Background

Primary care systems around the world have implemented nurse practitioners (NPs) to ensure access to high quality care in times of general practitioner (GP) shortages and changing health care needs of a multimorbid, ageing population. In Switzerland, NPs are currently being introduced, and their exact role is yet to be determined. The aim of this study was to get insight into patient characteristics and services provided in NP consultations compared to GP consultations in Swiss primary care.

Methods

This case study used retrospective observational data from electronic medical records of a family practice with one NP and two GPs. Data on patient-provider encounters were collected between August 2017 and December 2018. We used logistic regression to assess associations between the assignment of the patients to the NP or GP and patient characteristics and delivered services respectively.

Results

Data from 5210 patients participating in 27,811 consultations were analyzed. The average patient age was 44.3 years (SD 22.6), 47.1% of the patients were female and 19.4% multimorbid. 1613 (5.8%) consultations were with the NP, and 26,198 (94.2%) with the two GPs. Patients in NP consultations were more often aged 85+ (OR 3.43; 95%-CI 2.70–4.36), multimorbid (OR 1.37; 95%-CI 1.24–1.51;p < 0.001) and polypharmaceutical (OR 1.28; 95%-CI 1.15–1.42; p < 0.001) in comparison to GP consultations. In NP consultations, vital signs (OR 3.05; 95%-CI 2.72–3.42;p < 0.001) and anthropometric data (OR 1.33; 95%-CI 1.09–1.63; p 0.005) were measured more frequently, and lab tests (OR 1.16; 95%-CI 1.04–1.30; p 0.008) were ordered more often compared to GP consultations, independent of patient characteristics. By contrast, medications (OR 0.35; 95%-CI 0.30–0.41; p < 0.001) were prescribed or changed less frequently in NP consultations.

Conclusions

Quantitative data from pilot projects provide valuable insights into NP tasks and activities in Swiss primary care. Our results provide first indications that NPs might have a focus on and could offer care to the growing number of multimorbid, polypharmaceutical elderly in Swiss primary care.
Interaction between lead and noradrenergic genotypes affects neurocognitive functions in attention-deficit/hyperactivity disorder: a case control study
Authors: Choi Jae-Won , Jung A-Hyun , Nam Sojeong , Kim Kyoung Min , Kim Jun Won , Kim Soo Yeon , Kim Bung-Nyun , Kim Jae-Won
Published: August 2020

Background

Lead is known to be associated with attention-deficit/hyperactivity disorder (ADHD) even at low concentrations. We aimed to evaluate neurocognitive functions associated with lead in the blood and the interactions between lead and dopaminergic or noradrenergic pathway-related genotypes in youths with ADHD.

Methods

A total of 259 youths with ADHD and 96 healthy controls (aged 5–18 years) enrolled in this study. The Korean Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime version was conducted for psychiatric diagnostic evaluation. Blood lead levels were measured, and their interaction with dopaminergic or noradrenergic genotypes for ADHD; namely, the dopamine transporter (DAT1), dopamine receptor D4 (DRD4), and alpha-2A-adrenergic receptor (ADRA2A) genotypes were investigated. All participants were assessed using the ADHD Rating Scale-IV (ADHD-RS). Participants also completed the continuous performance test (CPT) and Stroop Color-Word Test (SCWT). Analysis of covariance was used for comparison of blood lead levels between ADHD and control groups. A multivariable linear regression model was used to evaluate the associations of blood lead levels with the results of ADHD-RS, CPT, and SCWT; adjusted for intelligence quotient (IQ), age, and sex. A path analysis model was used to identify the mediating effects of neurocognitive functions on the effects of blood lead on ADHD symptoms. To evaluate the effect of the interaction between blood lead and genes on neuropsychological functions, hierarchical regression analyses were performed.

Results

There was a significant difference in blood lead levels between the ADHD and control groups (1.4 ± 0.5 vs. 1.3 ± 0.5 μg/dL, p = .005). Blood lead levels showed a positive correlation with scores on omission errors(r = .158, p = .003) and response time variability (r = .136, p = .010) of CPT. In the multivariable linear regression model, blood lead levels were associated with omission errors (B = 3.748, p = .045). Regarding the effects of lead on ADHD symptoms, hyperactivity-impulsivity was mediated by omission errors. An interaction effect was detected between ADRA2A DraI genotype and lead levels on omission errors (B = 5.066, p = .041).

Conclusions

Our results indicate that neurocognitive functions at least partly mediate the association between blood lead levels and ADHD symptoms, and that neurocognitive functions are affected by the interaction between blood lead levels and noradrenergic genotype.
The effect of bone cement distribution on the outcome of percutaneous Vertebroplasty: a case cohort study
Authors: Tan Lei , Wen Bingtao , Guo Zhaoqing , Chen Zhongqiang
Published: August 2020

Background

To analyze the effect of different types of bone cement distribution after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fracture (OVCF).

Methods

One hundred thirty seven patients with single level OVCF who underwent PVP were retrospectively analyzed. The patients were divided into two groups according to bone cement distribution. Group A: bone cement contacted both upper and lower endplates; Group B: bone cement missed at least one endplate. Group B was divided into 3 subgroups. Group B1: bone cement only contacted the upper endplates; Group B2: bone cement only contacted the lower endplates; Group B3: bone cement only located in the middle of vertebral body. The visual analogue scale (VAS) score at 24 h post operation and last follow-up, anterior vertebral height restoration ratio (AVHRR), anterior vertebral height loss ratio (AVHLR), local kyphotic angle change and vertebral body recompression rate were compared.

Results

24 h post operation, the pain of all groups were significantly improved. The average follow-up time was 15.3 ± 6.3 (6–24) months. At last follow-up, the VAS score of group A was lower than that of group B. There were 14 cases (10.2%) of adjacent vertebral fracture, 5 cases (8.6%) in group A and 9 cases (11.4%) in group B. There were 9 cases (6.6%) of cement leakage, 4 cases (6.9%) in group A and 5 cases (6.3%) in group B. At last follow-up, there were 16 cases (11.7%) of vertebral body recompression, including 3 cases (5.2%) in group A and 13 cases (16.5%) in group B. There was no significant difference in AVHRR between two groups. Local kyphotic angle change was significant larger in group B. At last follow-up, AVHLR in group B was higher than that in group A. Analysis in subgroup B revealed no significant difference in VAS score, local kyphotic angle change, vertebral recompression rate, AVHRR or AVHLR.

Conclusions

If the bone cement fully contacted both the upper and lower endplates, it can better restore the strength of the vertebral body and maintain the height of the vertebral body, reduce the risk of the vertebral body recompression and long-term pain.
Transient osteoporosis of the hip and subclinical hypothyroidism: an unusual dangerous duet? Case report and pathogenetic hypothesis
Authors: Paoletta Marco , Moretti Antimo , Liguori Sara , Bertone Matteo , Toro Giuseppe , Iolascon Giovanni
Published: August 2020

Background

Transient osteoporosis of the hip (TOH) is a rare and temporary clinical condition characterised by bone marrow edema (BME), severe pain, and functional limitation. It commonly occurs in middle-aged men or in women in the last trimester of pregnancy. TOH usually resolves with conservative therapy but may predispose to hip fracture or progression to avascular necrosis (AVN). Etiology is still unclear, although several pathophysiological mechanisms underpinning this condition has been proposed. We describe the management of an unusual case of TOH occurred in a patient with subclinical hypothyroidism.

Case presentation

A clinical case of a 46-year-old man with severe pain in the left anterior thigh is presented. After a comprehensive clinical and radiological approach, a TOH was diagnosed. Moreover, biochemical assessment suggested the presence of subclinical hypothyroidism. After 3 months of treatment with clodronate, physical therapy and hormone replacement therapy (HRT) a significant improvement of clinical and radiological outcomes was observed.

Conclusion

Several pathological conditions have been related to development of TOH. In our case, we suggested for the first time a role of subclinical hypothyroidism as novel contributory factor for the onset of this condition, providing pathophysiological mechanisms and a scientific rationale for pharmacological treatment.
Reengineering anthrax toxin protective antigen for improved receptor-specific protein delivery
Authors: Becker Lukas , Verdurmen Wouter P. R. , Plückthun Andreas
Published: August 2020

Background

To increase the size of the druggable proteome, it would be highly desirable to devise efficient methods to translocate designed binding proteins to the cytosol, as they could specifically target flat and hydrophobic protein-protein interfaces. If this could be done in a manner dependent on a cell surface receptor, two layers of specificity would be obtained: one for the cell type and the other for the cytosolic target. Bacterial protein toxins have naturally evolved such systems. Anthrax toxin consists of a pore-forming translocation unit (protective antigen (PA)) and a separate protein payload. When engineering PA to ablate binding to its own receptor and instead binding to a receptor of choice, by fusing a designed ankyrin repeat protein (DARPin), uptake in new cell types can be achieved.

Results

Prepore-to-pore conversion of redirected PA already occurs at the cell surface, limiting the amount of PA that can be administered and thus limiting the amount of delivered payload. We hypothesized that the reason is a lack of a stabilizing interaction with wild-type PA receptor. We have now reengineered PA to incorporate the binding domain of the anthrax receptor CMG2, followed by a DARPin, binding to the receptor of choice. This construct is indeed stabilized, undergoes prepore-to-pore conversion only in late endosomes, can be administered to much higher concentrations without showing toxicity, and consequently delivers much higher amounts of payload to the cytosol.

Conclusion

We believe that this reengineered system is an important step forward to addressing efficient cell-specific delivery of proteins to the cytosol.
Assessing inequalities and regional disparities in child nutrition outcomes in India using MANUSH – a more sensitive yardstick
Authors: Jain Ayushi , Agnihotri Satish B.
Published: August 2020

Background

India is strongly committed to reducing the burden of child malnutrition, which has remained a persistent concern. Findings from recent surveys indicate co-existence of child undernutrition, micronutrient deficiency and overweight/obesity, i.e. the triple burden of malnutrition among children below 5 years. While considerable efforts are being made to address this challenge, and several composite indices are being explored to inform policy actions, the methodology used for creating such indices, i.e., linear averaging, has its limitations. Briefly put, it could mask the uneven improvement across different indicators by discounting the ‘lagging’ indicators, and hence not incentivising a balanced improvement. Signifying negative implications on policy discourse for improved nutrition. To address this gap, we attempt to develop a composite index for estimating the triple burden of malnutrition in India, using a more sensitive measure, MANUSH.

Methodology

Data from publicly available nation-wide surveys - National Family Health Survey (NFHS) and Comprehensive National Nutrition Survey (CNNS), was used for this study. First, we addressed the robustness of MANUSH method of composite indexing over conventional aggregation methods. Second, using MANUSH scores, we assessed the triple burden of malnutrition at the subnational level over different periods NHFS- 3(2005–06), NFHS-4 (2015–16) and CNNS (2106–18). Using mapping and spatial analysis tools, we assessed neighbourhood dependency and formation of clusters, within and across states.

Result

MANUSH method scores over other aggregation measures that use linear aggregation or geometric mean. It does so by fulfilling additional conditions of Shortfall and Hiatus Sensitivity, implicitly penalising cases where the improvement in worst-off dimension is lesser than the improvement in best-off dimension, or where, even with an overall improvement in the composite index, the gap between different dimensions does not reduce. MANUSH scores helped in revealing the gaps in the improvement of nutrition outcomes among different indicators and, the rising inequalities within and across states and districts in India. Significant clusters (p < 0.05) of high burden and low burden districts were found, revealing geographical heterogeneities and sharp regional disparities. A MANUSH based index is useful in context-specific planning and prioritising different interventions, an approach advocated by the newly launched National Nutrition Mission in India.

Conclusion

MANUSH based index emphasises balanced development in nutritional outcomes and is hence relevant for diverse and unevenly developing economy like India.
Osteofibrous dysplasia-like adamantinoma treated via intercalary segmental resection with partial cortex preservation using pedicled vascularized fibula graft: a case report
Authors: Yamamura Yuji , Emori Makoto , Takahashi Nobuyuki , Chiba Mitsumasa , Shimizu Junya , Murahashi Yasutaka , Sugita Shintaro , Iba Kousuke , Hasegawa Tadashi , Yamashita Toshihiko
Published: August 2020

Background

Morphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity.

Case presentation

We report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed.

Conclusion

This case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.
Correction to: Platelets promote breast cancer cell MCF-7 metastasis by direct interaction: surface integrin α2β1-contacting-mediated activation of Wnt-β-catenin pathway
Authors: Zuo Xiao-xiao , Yang Ya , Zhang Yue , Zhang Zhi-gang , Wang Xiao-fei , Shi Yong-gang
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
A monocentric, open-label randomized standard-of-care controlled study of XONRID®, a medical device for the prevention and treatment of radiation-induced dermatitis in breast and head and neck cancer patients
Authors: Ingargiola Rossana , De Santis Maria Carmen , Iacovelli Nicola Alessandro , Facchinetti Nadia , Cavallo Anna , Ivaldi Eliana , Dispinzieri Michela , Franceschini Marzia , Giandini Carlotta , Romanello Domenico Attilio , Di Biaso Simona , Sabetti Michela , Locati Laura , Alfieri Salvatore , Bossi Paolo , Guglielmo Mauro , Macchi Fabio , Lozza Laura , Valdagni Riccardo , Fallai Carlo , Pignoli Emanuele , Orlandi Ester
Published: August 2020

Background

This study was an open-label, 2-arms, monocentric, randomized clinical trial comparing Xonrid®, a topical medical device, versus standard of care (SOC) in preventing and treating acute radiation dermatitis (ARD) in Head and Neck Cancer (HNC) and Breast Cancer (BC) patients undergoing radiotherapy (RT).

Methods

Eligible HNC and BC patients were randomized 1:1 to receive Xonrid® + SOC or SOC during RT. Patients were instructed to apply Xonrid® on the irradiated area three times daily, starting on the first day of RT and until 2 weeks after RT completion or until the development of grade ≥ 3 skin toxicity. The primary endpoint was to evaluate the proportion of patients who developed an ARD grade < 2 at the 5th week in both groups. Secondary endpoints were median time to grade 2 (G2) skin toxicity onset; changes in skin erythema and pigmentation and trans-epidermal water loss (TEWL); patient-reported skin symptoms. All patients were evaluated at baseline, weekly during RT and 2 weeks after treatment completion. The evaluation included: clinical toxicity assessment; reflectance spectrometry (RS) and TEWL examination; measurement of patients’ quality of life (QoL) through Skindex-16 questionnaire.

Results

Eighty patients (40 for each cancer site) were enrolled between June 2017 and July 2018. Groups were well balanced for population characteristics. All BC patients underwent 3-Dimensional Conformal RT (3D-CRT) whereas HNC patients underwent Volumetric-Modulated Arc Therapy (VMAT). At week 5 the proportion of BC patients who did not exhibit G2 ARD was higher in Xonrid® + SOC group (p = 0.091). In the same group the onset time of G2 ARD was significantly longer than in SOC-alone group (p < 0.0491). For HNC groups there was a similar trend, but it did not reach statistical significance. For both cancer sites, patients’ QoL, measured by the Skindex-16 score, was always lower in the Xonrid® + SOC group.

Conclusion

Despite the failure to achieve the primary endpoint, this study suggests that Xonrid® may represent a valid medical device in the prevention and treatment of ARD at least in BC patients, delaying time to develop skin toxicity and reducing the proportion of patients who experienced G2 ARD during RT treatment and 2 weeks later.

Trial registration

The study was approved by the Ethical Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT 52/14 - NCT02261181). Registered on ClinicalTrial.gov on 21st August 2017.
ETV4 promotes late development of prostatic intraepithelial neoplasia and cell proliferation through direct and p53-mediated downregulation of p21
Authors: Cosi Irene , Pellecchia Annamaria , De Lorenzo Emanuele , Torre Eugenio , Sica Michela , Nesi Gabriella , Notaro Rosario , De Angioletti Maria
Published: August 2020

Background

ETV4 is one of the ETS proteins overexpressed in prostate cancer (PC) as a result of recurrent chromosomal translocations. In human prostate cell lines, ETV4 promotes migration, invasion, and proliferation; however, its role in PC has been unclear. In this study, we have explored the effects of ETV4 expression in the prostate in a novel transgenic mouse model.

Methods

We have created a mouse model with prostate-specific expression of ETV4 (ETV4 mice). By histochemical and molecular analysis, we have investigated in these engineered mice the expression of p21, p27, and p53. The implications of our in vivo findings have been further investigated in human cells lines by chromatin-immunoprecipitation (ChIP) and luciferase assays.

Results

ETV4 mice, from two independent transgenic lines, have increased cell proliferation in their prostate and two-thirds of them, by the age of 10 months, developed mouse prostatic intraepithelial neoplasia (mPIN). In these mice,cdkn1aand its p21 protein product were reduced compared to controls; p27 protein was also reduced. By ChIP assay in human prostate cell lines, we show that ETV4 binds to a specific site (-704/-696 bp upstream of the transcription start) in theCDKN1Apromoter that was proven, by luciferase assay, to be functionally competent. ETV4 further controlsCDKN1Aexpression by downregulating p53 protein: this reduction of p53 was confirmed in vivo in ETV4 mice.

Conclusions

ETV4 overexpression results in the development of mPIN but not in progression to cancer. ETV4 increases prostate cell proliferation through multiple mechanisms, including downregulation ofCDKN1Aand its p21 protein product: this in turn is mediated through direct binding of ETV4 to theCDKN1Apromoter and through the ETV4-mediated decrease of p53. This multi-faceted role of ETV4 in prostate cancer makes it a potential target for novel therapeutic approaches that could be explored in this ETV4 transgenic model.
Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes
Authors: Poran Asaf , Harjanto Dewi , Malloy Matthew , Arieta Christina M. , Rothenberg Daniel A. , Lenkala Divya , van Buuren Marit M. , Addona Terri A. , Rooney Michael S. , Srinivasan Lakshmi , Gaynor Richard B.
Published: August 2020

Background

The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2.

Methods

We leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from theCoronaviridaefamily and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8+T cell responses.

Results

We first validated HLA-I and HLA-II predictions onCoronaviridaefamily epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8+T cells in healthy human donor peripheral blood mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be potential targets for T cell immunity.

Conclusions

Using our bioinformatics platform, we identify multiple putative epitopes that are potential targets for CD4+and CD8+T cells, whose HLA binding properties cover nearly the entire population. We also confirm that our binding predictors can predict epitopes eliciting CD8+T cell responses from multiple SARS-CoV-2 proteins. Protein expression and population HLA allele coverage, combined with the ability to identify T cell epitopes, should be considered in SARS-CoV-2 vaccine design strategies and immune monitoring.
Proteomic analysis revealed common, unique and systemic signatures in gender-dependent hepatocarcinogenesis
Authors: Li Huiling , Rong Zhuona , Wang Hong , Zhang Nan , Pu Chunwen , Zhao Yi , Zheng Xu , Lei Chuanyi , Liu Yang , Luo Xiaoqin , Chen Jun , Wang Fujin , Wang Aiguo , Wang Jingyu
Published: August 2020

Hepatocellular carcinoma (HCC) is the most common liver cancer and is highly malignant. Male prevalence and frequent activation of the Ras signaling pathway are distinct characteristics of HCC. However, the underlying mechanisms remain to be elucidated. By exploringHras12Vtransgenic mice showing male-biased hepatocarcinogenesis, we performed a high-throughput comparative proteomic analysis based on tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the tissue samples obtained from HCC (T) and their paired adjacent precancerous (P) ofHras12Vtransgenic male and female mice (Ras-Tg) and normal liver (W) of wild-type male and female mice (Non-Tg). The further validation and investigation were performed using quantitative real-time PCR and western blot. Totally, 5193 proteins were quantified, originating from 5733 identified proteins. Finally, 1344 differentially expressed proteins (DEPs) (quantified in all examined samples; |ratios| ≥ 1.5,p< 0.05) were selected for further analysis. Comparison within W, P, and T of males and females indicated that the number of DEPs in males was much higher than that in females. Bioinformatics analyses showed the common and unique cluster-enriched items between sexes, indicating the common and gender-disparate pathways towards HCC. Expression change pattern analysis revealed HCC positive/negative-correlated andrasoncogene positive/negative-correlated DEPs and pathways. In addition, it showed that therasoncogene gradually and significantly reduced the responses to sex hormones from hepatocytes to hepatoma cells and therefore shrunk the gender disparity between males and females, which may contribute to the cause of the loss of HCC clinical responses to the therapeutic approaches targeting sex hormone pathways. Additionally, gender disparity in the expression levels of key enzymes involved in retinol metabolism and terpenoid backbone/steroid biosynthesis pathways may contribute to male prevalence in hepatocarcinogenesis. Further, the biomarkers, SAA2, Orm2, and Serpina1e, may be sex differences. In conclusion, common and unique DEPs and pathways toward HCC initiated byrasoncogene from sexually dimorphic hepatocytes provide valuable and novel insights into clinical investigation and practice.
Large-scale production of recombinant miraculin protein in transgenic carrot callus suspension cultures using air-lift bioreactors
Authors: Park Yun-Ji , Han Jong-Eun , Lee Hyoshin , Jung Yu-Jin , Murthy Hosakatte Niranjana , Park So-Young
Published: August 2020

Miraculin, derived from the miracle fruit (Synsepalum dulcificum), is a taste-regulating protein that interacts with human sweet-taste receptors and transforms sourness into sweet taste. Since miracle fruit is cultivated in West Africa, mass production of miraculin is limited by regional and seasonal constraints. Here, we investigated mass production of recombinant miraculin in carrot (Daucus carota L.) callus cultures using an air-lift bioreactor. To increase miraculin expression, the oxidative stress-inducible SWPA2 promoter was used to drive the expression of miraculin gene under various stress treatments. An 8 h treatment of hydrogen peroxide (H2O2) and salt (NaCl) increased the expression of miraculin gene by fivefold compared with the untreated control. On the other hand, abscisic acid, salicylic acid, and methyl jasmonate treatments showed no significant impact on miraculin gene expression compared with the control. This shows that since H2O2 and NaCl treatments induce oxidative stress, they activate the SWPA2 promoter and consequently up-regulate miraculin gene expression. Thus, the results of this study provide a foundation for industrial-scale production of recombinant miraculin protein using transgenic carrot cells as a heterologous host.
Correction to: Transient expression of SbDhr2 and MeHNL in Gossypium hirsutum for herbivore deterrence assay with Spodoptera litura
Authors: MAHAJAN Chavi , NASER Rafiuddin , RAWAL Shuban , PYATI Prashant , PANDA Bhuban , LOMATE Purushottam , GUPTA Shantikumar
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Immune Landscape of Pituitary Tumors Reveals Association Between Macrophages and Gonadotroph Tumor Invasion
Authors: Principe Moitza , Chanal Marie , Ilie Mirela Diana , Ziverec Audrey , Vasiljevic Alexandre , Jouanneau Emmanuel , Hennino Ana , Raverot Gerald , Bertolino Philippe
Published: August 2020

Purpose

Pituitary neuroendocrine tumors (PitNETs) are frequent intracranial neoplasms that present heterogenic characteristics. Little is known about the immune cell network that exists in PitNETs and its contribution to their aggressive behavior.

Methods

Here we combined flow cytometry, t-SNE analysis, and histological approaches to define the immune landscape of surgically resected PitNETs. Xenografts of rodent pituitary tumor cells and resected PitNETs were performed in Rag2KO mice, in combination with in vitro analysis aimed at dissecting the role of pituitary tumor-cells in monocyte recruitment.

Results

We report that gonadotroph PitNETs present an increased CD68+ macrophage signature compared to somatotroph, lactotroph, and corticotroph PitNETs. Transcriptomic and histological characterizations confirmed gonadotroph infiltrating macrophages expressed CD163, MRC-1, ARG1, and CSF1R M2 macrophage markers. Use of growth hormone (GH)3/GH4 somatotroph and LβT2/αT3.1 gonadotroph cells drove THP1 macrophage migration through respective expression of CCL5 or CSF1. Although both LβT2 and GH3 cells recruited F4/80 macrophages following their engraftment in mice, only LβT2 gonadotroph cells showed a capacity for M2-like polarization. Similar observations were performed on patient-derived xenografts from somatotroph and gonadotroph tumors. Analysis of clinical data further demonstrated a significant correlation between the percentage of CD68+ and CD163+ infiltrating macrophages and the invasive character of gonadotroph tumors.

Conclusions

Gonadotroph tumor drive the recruitment of macrophages and their subsequent polarization to an M2-like phenotype. More importantly, the association between infiltrating CD68+/CD163+ macrophages and the invasiveness of gonadotroph tumors points to macrophage-targeted immunotherapies being a potent strategy to limit the progression of gonadotroph PitNETs.
Cellular Pathophysiology of Mutant Voltage-Dependent Ca2+ Channel CACNA1H in Primary Aldosteronism
Authors: Gürtler Florian , Jordan Katrin , Tegtmeier Ines , Herold Janina , Stindl Julia , Warth Richard , Bandulik Sascha
Published: August 2020

The physiological stimulation of aldosterone production in adrenocortical glomerulosa cells by angiotensin II and high plasma K+ depends on the depolarization of the cell membrane potential and the subsequent Ca2+ influx via voltage-activated Ca2+ channels. Germline mutations of the low-voltage activated T-type Ca2+ channel CACNA1H (Cav3.2) have been found in patients with primary aldosteronism. Here, we investigated the electrophysiology and Ca2+ signaling of adrenal NCI-H295R cells overexpressing CACNA1H wildtype and mutant M1549V in order to understand how mutant CACNA1H alters adrenal cell function. Whole-cell patch-clamp measurements revealed a strong activation of mutant CACNA1H at the resting membrane potential of adrenal cells. Both the expression of wildtype and mutant CACNA1H led to a depolarized membrane potential. In addition, cells expressing mutant CACNA1H developed pronounced action potential–like membrane voltage oscillations. Ca2+ measurements showed an increased basal Ca2+ activity, an altered K+ sensitivity, and abnormal oscillating Ca2+ changes in cells with mutant CACNA1H. In addition, removal of extracellular Na+ reduced CACNA1H current, voltage oscillations, and Ca2+ levels in mutant cells, suggesting a role of the partial Na+ conductance of CACNA1H in cellular pathology. In conclusion, the pathogenesis of stimulus-independent aldosterone production in patients with CACNA1H mutations involves several factors: i) a loss of normal control of the membrane potential, ii) an increased Ca2+ influx at basal conditions, and iii) alterations in sensitivity to extracellular K+ and Na+. Finally, our findings underline the importance of CACNA1H in the control of aldosterone production and support the concept of the glomerulosa cell as an electrical oscillator.