bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-L1-expression patterns in large-cell neuroendocrine carcinoma of the lung: potential implications for use of immunotherapy in these patients: the GFPC 03-2017 “EPNEC” study
Authors: Arpin Dominique , Charpentier Marie-Christine , Bernardi Marie , Monnet Isabelle , Boni Aurelie , Watkin Emmanuel , Goubin-Versini Isabelle , Lamy Régine , Gérinière Laurence , Geier Margaux , Forest Fabien , Gervais Radj , Madrosyk Anne , Guisier Florian , Serrand Cécile , Locher Chrystèle , Decroisette Chantal , Fournel Pierre , Auliac Jean-Bernard , Jeanfaivre Thierry , Letreut Jacques , Doubre Hélène , Francois Geraldine , Piton Nicolas , Chouaïd Christos , Damotte Diane
Published: July 2020

Background:

Few data are available on programmed cell-death-protein-1–ligand-1 (PD-L1) expression on large-cell neuroendocrine carcinomas of the lung (LCNECs). We analyzed PD-L1 expression on tumor (TCs) and inflammatory cells (ICs) from LCNEC patients to assess relationships between this expression, clinical characteristics, and disease outcomes.

Methods:

PD-L1 expression was determined by immunohistochemistry with monoclonal antibody 22C3 in consecutive LCNEC patients managed in 17 French centers between January 2014 and December 2016.

Results:

After centralized review, only 68 out of 105 (64%) patients had confirmed LCNEC diagnoses. Median overall survival (OS) (95% CI) was 11 (7–16) months for all patients, 7 (5–10), 21 (10–not reached) and not reached months for metastatic, stage III and localized forms ( p = 0.0001). Respectively, 11% and 75% of the tumor samples were TC+ and IC+, and 66% had a TC–/IC+ profile. Comparing IC+ versus IC– metastatic LCNEC, the former had significantly longer progression-free survival [9 (4–13) versus 4 (1–8) months; p = 0.03], with a trend towards better median OS [12 (7–18) versus 9.5 (4–14) months; p = 0.21]. Compared to patients with TC– tumors, those with TC+ LCNECs tended to have non-significantly shorter median OS [4 (1–6.2) versus 11 (8–18) months, respectively]. Median OS was significantly shorter for patients with TC+/IC– metastatic LCNECs than those with TC–IC+ lesions (2 versus 8 months, respectively; p = 0.04).

Conclusion:

TC–/IC+ was the most frequent PD-L1–expression profile for LCNECs, a pattern quite specific compared with non-small-cell lung cancer and small-cell lung cancer. IC PD-L1 expression seems to have a prognostic role.
miR-30a-5p Inhibits Epithelial-to-Mesenchymal Transition by Targeting CDK6 in Nasal Polyps
Authors: Zhang Ting , Zhou Yong , You Bo , You Yiwen , Yan Yongbing , Zhang Jie , Pei Yinyin , Zhang Wei , Chen Jing
Published: July 2020

Background

Epithelial-to-Mesenchymal Transition (EMT) is considered as a crucial event in disease development and dysregulation of microRNAs (miRNAs) is involved in the regulation of EMT in various human diseases. Emerging evidences congregated over the years have demonstrated that miR-30a-5p was decreased in diseases and its overexpression inhibited the process of diseases via attenuating EMT. Although aberrant expression of miRNAs and occurrence of EMT were previously reported in Nasal Polyps (NPs), the role of miR-30a-5p in EMT of NPs is still remains unclear.

Objective

The purpose of our present study was to explore the expression and potential function of miR-30a-5p in EMT of NPs.

Methods

The expression of miR-30a-5p and mRNA expression level were detected by quantitative real-time PCR (qRT-PCR) in transforming growth factor β1 (TGF-β1) - induced EMT model and NPs patients. Western Blot (WB) and immunohistochemistry (IHC) were performed to evaluate the protein expression level of EMT markers. The cells mobility was assessed by Wound-Healing assay. Luciferase reporter assay was utilized to verify the relationship between Cyclin-dependent kinase 6 (CDK6) and miR-30a-5p.

Results

Firstly, we observed that miR-30a-5p was down-regulated notably, accompanying with the alteration of EMT markers expression in NPs tissues and EMT model induced by TGF-β1 in primary Human Nasal Epithelial Cells (pHNECs) and A549 cells in vitro. Moreover, the functional assays demonstrated that overexpression of miR-30a-5p significantly inhibited EMT and cells mobility. Subsequently, CDK6 was validated as a direct target of miR-30a-5p. Finally, we performed the rescue experiments indicating that overexpression of CDK6 eliminated the suppressive effects of miR-30a-5p in TGF-β1-induced EMT in pHNECs and A549 cells.

Conclusion

Taken together, our results suggested that EMT was involved in NPs, and overexpression of miR-30a-5p could attenuate EMT via repressing the expression of the CDK6 in pHNECs and A549 cells.
“They should have followed the rules”: Trade-offs Between Fairness and Authority Values Predict Judgments of Social Justice Protests
Authors: Monroe Andrew E. , Wyngaarden James B. , Plant E. Ashby
Published: July 2020

In 2017, Colin Kaepernick drew global attention by kneeling during the national anthem before a football game. The protest divided the country into two groups: those who supported Kaepernick’s stand against inequality and those who believed it was disrespectful. The current study investigates whether differences in moral values (i.e., fairness vs. respect for authority) predict an individual’s opinion of the protestors and whether priming one of those values influences opinions on social justice protests more broadly. Our data support the moral trade-off hypothesis by demonstrating that when values are in conflict, the degree to which individuals value fairness versus authority predicts their opinions of the protesters. These differences in fairness versus authority also extended to judgments of other kinds of social justice protests. These findings support the moral foundations theory as a useful tool for investigating the influence of moral values on perceptions of social issues and subsequent behavior.
Medical management of a suspected atrial myxoma in a nonagenarian
Authors: Kawall Jessica , Seecheran Rajeev , Seecheran Valmiki , Persad Sangeeta , Maharaj Stefan , Seecheran Naveen Anand
Published: July 2020

Cardiac myxomas are the most frequently encountered tumors of the heart. However, they are unusual to be newly diagnosed in the geriatric population. Myxomas are among the great mimickers, with a myriad of clinical presentations related to heart failure, embolic events, and constitutional symptoms. We describe a rare case of a giant atrial myxoma in a nonagenarian presenting with heart failure, which was medically managed.
The global prevalence of Barrett’s esophagus: A systematic review of the published literature
Authors: Marques de Sá Inês , Marcos Pedro , Sharma Prateek , Dinis‐Ribeiro Mário
Published: July 2020

Background

Determining the prevalence of Barrett’s esophagus is important for defining screening strategies. We aimed to synthesize the available data, determine Barrett’s esophagus prevalence, and assess variability.

Methods

Three databases were searched. Subgroup, sensitivity, and meta‐regression analyses were conducted and pooled prevalence was computed.

Results

Of 3510 studies, 103 were included. In the general population, we estimated a prevalence for endoscopic suspicion of Barrett’s esophagus of (a) any length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.85–1.07), (b) ≥1 cm of length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.75–1.18) and (c) for any length with histologic confirmation of columnar metaplasia as 3.89% (95% confidence interval: 2.25–5.54). By excluding studies with high‐risk of bias, the prevalence decreased to: (a) 0.70% (95% confidence interval: 0.61–0.79) and (b) 0.82% (95% confidence interval: 0.63–1.01). In gastroesophageal reflux disease patients, we estimated the prevalence with afore‐mentioned criteria to be: (a) 7.21% (95% confidence interval: 5.61–8.81) (b) 6.72% (95% confidence interval: 3.61–9.83) and (c) 7.80% (95% confidence interval: 4.26–11.34). The Barrett’s esophagus prevalence was significantly influenced by time period, region, Barrett’s esophagus definition, Seattle protocol, and study design. There was a significant gradient East‐West and North‐South. There were minimal to no data available for several countries. Moreover, there was significant heterogeneity between studies.

Conclusion

There is a need to reassess the true prevalence of Barrett’s esophagus using the current guidelines in most regions. Having knowledge about the precise Barrett’s esophagus prevalence, diverse attitudes from educational to screening programs could be taken.
Cutaneous horn arising from the scrotum
Authors: John Jeff , Mngqi Noma , Morse Nicole , Lazarus John , Kesner Ken
Published: July 2020

A cutaneous horn, cornu cutaneum, is a hard, conical projection composed of compacted keratin that resembles the horns of animals. They commonly occur on sun-exposed areas, including the head, ears, forearms and hands. Cutaneous horns are extremely rare. Although most are benign in nature, a significant portion may harbour a malignant or pre-malignant lesion, and histopathological analysis of the base of the lesion is imperative to categorise it as one of benign aetiology or one of a more sinister pathology. We present a case of a 46-year-old male who presented with a 2-month history of a painless, firm, rapidly growing conical projection arising from his scrotum. Clinically, a non-tender curved, yellow-brown, horn-like projection was observed arising from the median raphe of his scrotum. With informed consent, a full-thickness excision, with adequate excision of the base of the horn, was performed under local anaesthesia. Macroscopically, the exophytic keratinous lesion was 7.5 cm long and 1.8 cm wide, with the length of the horn far outweighing the width at its base. Histopathological analysis confirmed the presence of a cutaneous horn arising from a condyloma acuminatum as evidenced by a verruciform architecture with tiers of parakeratosis in association with hypergranulosis and koilocytes. No dysplastic or malignant changes were present in the epithelium. According to our knowledge, this is the first case in the English literature of a cutaneous horn arising from the scrotal skin.
Critical Cyanosis in a Neonate With Unusual Congenital Tricuspid Valve Lesion
Authors: Boshnakov Ventsislav , Lazarov Stojan D. , Mitev Plamen , Mitev Ivaylo , Konstantinov George , Pechilkov Dimitar
Published: July 2020

We describe a case of a low birth weight neonate who presented on second day of life with progressive cyanosis and oxygen saturation of 60% by pulse oximetry. The echocardiography examination revealed a large tumor-like mass connected to the tricuspid valve, with severe obstruction of the right ventricular inflow and massive right-to-left shunt through the distended foramen ovale. A large vegetation-like lesion with calcifications was discovered intraoperatively and was debrided by shave excision technique under deep hypothermic circulatory arrest. Follow-up showed normal function of the tricuspid valve and preserved biventricular function.
Combination of PGE1 and Pulmonary Vasodilator Therapy in Managing a Challenging Case of Severe PAH Secondary to CDH
Authors: Aljohani Othman A. , Rao Rohit , Mackie Duncan , Haldeman Shylah , Karamlou Tara
Published: July 2020

Congenital diaphragmatic hernia (CDH) is a rare disease, which affects 1 in 2,500 newborns. Congenital diaphragmatic hernia can interfere with the normal development of the pulmonary parenchyma and vascular bed, and in severe cases, it can lead to the development of severe pulmonary arterial hypertension (PAH) and right ventricular failure. We present a neonate with CDH who developed severe PAH and right ventricular dysfunction and was managed with a unique strategy combining venoarterial extracorporeal membrane oxygenation, prostaglandin E1, and a variety of PAH therapies.
Combined Transcatheter Tricuspid and Pulmonary Valve Replacement
Authors: Small Adam J. , Aksoy Olcay , Levi Daniel S. , Salem Morris M. , Yang Eric H. , Aboulhosn Jamil A.
Published: July 2020

Background:

For patients with combined tricuspid and pulmonary valve disease, operative intervention carries high mortality risk. Published reports of combined transcatheter tricuspid and pulmonary valve replacement have been limited to single cases.

Methods:

A retrospective chart review was performed including all patients undergoing combined transcatheter tricuspid and pulmonary valve replacement at the Ahmanson/UCLA Adult Congenital Heart Disease Center.

Results:

Combined transcatheter tricuspid and pulmonary valve replacement was undertaken in five adult patients (median age: 46 years; range: 24-64 years). Three had congenital heart disease and two had carcinoid syndrome. Four patients had previous surgical tricuspid valve replacement and one had a surgical incomplete annuloplasty ring. Four patients had previous surgical pulmonary valve replacement and one had a right ventricle-to-pulmonary artery homograft conduit. Two patients underwent Medtronic Melody valve implantation in both tricuspid and pulmonary positions and three underwent Edwards Sapien S3 implantation in both tricuspid and pulmonary positions. Valve implantation was successful in all. Follow-up ranged from 0.9 to 3.0 years. One patient underwent redo transcatheter tricuspid valve replacement 12 months after the first transcatheter intervention for progressive regurgitation of a Melody valve. This patient died 2.5 years after combined valve placement of complications from refractory heart failure. The remaining patients were alive and free of valve reintervention at follow-up.

Conclusions:

Combined transcatheter tricuspid and pulmonary valve replacement can be performed successfully, with an acceptable complication rate. This strategy is a feasible option for appropriately selected patients.
Visualization of the Cervicothoracic Junction With EOS Imaging Is Superior to Conventional Lateral Cervical Radiographs
Authors: Hirsch Brandon P. , Vaynrub Max , Siow Matthew , Zou Anthony , Anil Utkarsh , Montes Dennis Vasquez , Protopsaltis Themistocles S.
Published: July 2020

Study Design:

Single-center retrospective review.

Objectives:

The cervicothoracic junction (CTJ) is typically difficult to visualize using traditional radiographs. Whole-body stereoradiography (EOS) allows for imaging of the entire axial skeleton in a weightbearing position without parallax error and with lower radiation doses. In this study we sought to compare the visibility of the vertebra of the CTJ on lateral EOS images to that of conventional cervical lateral radiographs.

Methods:

Two fellowship-trained spine surgeons evaluated the images of 50 patients who had both lateral cervical radiographs and EOS images acquired within a 12-month period. The number of visible cortices of the vertebral bodies of C6-T2 were scored 0-4. Patient body mass index and the presence of spondylolisthesis >2 mm at each level was recorded. The incidence of insufficient visibility to detect spondylolisthesis at each level was also calculated for both modalities.

Results:

On average, there were more visible cortices with EOS versus XR at T1 and T2, whereas visible cortices were equal at C6 and C7. Patient body mass index was inversely correlated with cortical visibility on XR at T2 and on EOS at T1 and T2. There was a significant difference in the incidence of insufficient visibility to detect spondylolisthesis on EOS versus XR at C7-T1 and T1-2, but not at C6-7.

Conclusions:

EOS imaging is superior at imaging the vertebra of the CTJ. EOS imaging deserves further consideration as a diagnostic tool in the evaluation of patients with cervical deformity given its ability to produce high-quality images of the CTJ with less radiation exposure.
Incidence of Proximal Junctional Kyphosis With Pedicle Screws at Upper Instrumented Vertebrae in Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Authors: Ogura Yoji , Glassman Steven D. , Sucato Daniel , Hresko M. Timothy , Carreon Leah Y.
Published: July 2020

Study Design:

Longitudinal cohort.

Objectives:

Posterior spinal fusion (PSF) using all-pedicle screw constructs has become the standard procedure in the treatment of adolescent idiopathic scoliosis (AIS). However, there have been several reports that all-pedicle screw constructs or the use of pedicle screws at the upper instrumented vertebrae (UIV) increases the incidence of proximal junctional kyphosis (PJK). We aimed to evaluate the impact of instrumentation type on the incidence of PJK following PSF for AIS.

Methods:

We performed a stratified random sampling from 3654 patients enrolled in a multicenter database of surgically treated AIS to obtain a representative sample from all Lenke types. Patients were then allocated into 3 groups based on the instrumentation type: all-pedicle screw (PS), hook at UIV with pedicle screws distally (HT), and hybrid constructs (HB). We measured proximal junctional angle (PJA) and defined PJK as PJA ≥ 10° and PJA progression of >10° at the final follow-up.

Results:

Fifteen (4.3%) of 345 cases had PJK. PJK was significantly more common in PS (11%) compared with HB (1%) and HT (0%) ( P < .001). PJK patients were similar to non-PJK patients regarding age, sex, curve type, UIV, and preoperative coronal Cobb angle. Thoracic kyphosis was significantly higher in the PJK group before surgery. Patients who developed PJK had a statistically significantly larger negative sagittal balance compared with the non-PJK group.

Conclusion:

The incidence of PJK was 4.3% and was more common in all-pedicle screw constructs. Using hooks at UIV might be a treatment strategy to limit PJK.
Constructing Good Nursing Practice for Medical Assistance in Dying in Canada: An Interpretive Descriptive Study
Authors: Pesut Barbara , Thorne Sally , Schiller Catharine , Greig Madeleine , Roussel Josette , Tishelman Carol
Published: July 2020

Nurses play a central role in Medical Assistance in Dying (MAiD) in Canada. However, we know little about nurses’ experiences with this new end-of-life option. The purpose of this study was to explore how nurses construct good nursing practice in the context of MAiD. This was a qualitative interview study using Interpretive Description. Fifty-nine nurses participated in semi-structured telephone interviews. Data were analyzed inductively. The findings illustrated the ways in which nurses constructed artful practice to humanize what was otherwise a medicalized event. Registered nurses and nurse practitioners described creating a person-centered MAiD process that included establishing relationship, planning meticulously, orchestrating the MAiD death, and supporting the family. Nurses in this study illustrated how a nursing gaze focused on relationality crosses the moral divides that characterize MAiD. These findings provide an in-depth look at what constitutes good nursing practice in MAiD that can support the development of best practices.
Trauma-Informed Care in the Childcare and Family Placement Process: Miracle Foundation’s Approach Within Alternative Care in India
Authors: Choudhury Audria
Published: July 2020

Trauma-informed care (TIC) is critical in institutional settings to address not only the trauma of experiences that lead children to be enrolled into alternative care, such as childcare institutions (CCIs), but also the inherent trauma that comes from a child being separated from her or his family. This article looks at how Miracle Foundation applies principles of TIC at every stage: from intake and care at a CCI while awaiting placement, to preparing children and families for transition, and finally to supporting post-placement.

Following a brief background of the trauma surrounding institutional settings and its damage on children’s development drawn from existing literature, the article defines the principles of TIC: safety, choice, collaboration, trustworthiness and empowerment. The narrative then illustrates how these principles are applied with children, families and CCI staff through capacity building, access to counselling and mental health resources and dedicated guidance by Miracle team members throughout the childcare and placement process. Training government officials through a train-the-trainer model equips them to practise a strength-based approach with children and families. This also positions us for a systematic change when it comes to developing all members of the social workforce through system strengthening.
The Implementation of the Convention on the Rights of Children in Seven South Asian Countries
Authors: Adamcheck Amanda , Carville Kaya , Cilingiroglu Senem , Clements Rachael , Ford Stacy , Ingham Louisa , Macris Lucy , Peddada Yamini , Pham Hau , Sarmah Aditya , Schreur Hanneke , Signy Katherine , Steval Katie , Tunstall Lauren , Weber Ingram , Wells Andrew
Published: July 2020

This year marks thirty years since the Convention on the Rights of the Child (the Convention) entered into force and ten years since the Guidelines for the Alternative Care of Children (the Guidelines) were adopted. The term ‘alternative care’ refers to the placing of children in the care of someone other than a parent. Although the seven South Asian countries – Afghanistan, Bangladesh, Bhutan, India, Nepal, Pakistan and Sri Lanka – have ratified the Convention, each of the jurisdictions has reflected the Convention and Guidelines through domestic law in different ways and to different degrees. This article examines the extent to which two key child rights principles enshrined in the Convention have been incorporated into the domestic law of these countries: (a) the obligation to undertake active measures to prevent the unnecessary separation of children from their families and (b) the placing of a child in alternative care as a measure of last resort. While progress has been made across all jurisdictions, effective implementation of policies envisioned by the Convention remains elusive.
Essence and Scope of Strengthening Community-Based Preventive Child Care and Protection Systems in India
Authors: Panda Ranjan Kanti , Mullick Lopamudra , Adhikari Subhadeep , Basu Neepa , Kumari Archana
Published: July 2020

This article reflects different programmes and resource components that may be promoted to keep children with either their own family or within alternative family care, satisfying the rights of their overall development. In India, the concept of promoting family-based care mechanisms through government systems has not been fully realised, owing to lack of synergy between resource allocation and existing government programmes, policies and plans of action for child protection. Additionally, the common public discourse is that Child Care Institutions (CCIs) offer suitable care and protection for children outside the parental care. CCIs continue to be identified as the ultimate and the most common response for children at risk. This practice nullifies the scope to explore opportunities for the child to live with their family or in any alternative family care mechanisms. Child in Need Institute (CINI), 1 1 CINI is a national level development organization working on establishing child-friendly communities through its work on health, nutrition, child protection and education for the last forty-five years in India. partnering with Hope and Homes for Children, have analysed the vulnerability factors that led children to arrive at the selected CCIs in Ranchi and Khunti districts of Jharkhand in India. While working with children in the communities, CINI endeavoured to understand the drivers and vulnerabilities leading to family/child separation and what mechanisms could address the vulnerabilities at source and prevent separation. CINI promoted a participatory governance process with the involvement of community-level institutions along with children’s and women’s groups, incubating safe spaces for children that aided in identifying, tracking and promoting multi-sectoral development plans for children at risk.
An Interview With Dr. Barbara Rogoff About Perspectives on Learning
Authors: Petrone Robert
Published: July 2020

This interview highlights and extends Dr. Barbara Rogoff’s keynote address at the 2019 annual convention. Specifically, in the interview, Dr. Rogoff discusses her framework for learning, Learning by Observing and Pitching In, as well as other aspects of learning, including notions of childhood, age-based social ordering, and conflict as an aspect of learning and community engagement.
Outcomes and Complications of Open Versus Posterior Arthroscopic Subtalar Arthrodesis: A Prospective Randomized Multicenter Study
Authors: Rungprai Chamnanni , Sripanich Yantarat , Jaroenarpornwatana Aekachai
Published: July 2020

Category:

Hindfoot; Other

Introduction/Purpose:

There remains a controversy for treatment of subtalar joint arthritis. Both open and arthroscopic techniques have been reported for successful treatment of subtalar arthritis; however, there is a little evidence to report prospective comparative outcomes between the two techniques. The purpose of this study was to compare clinical and functional outcomes including complications between the two techniques.

Methods:

A prospective, randomized collected data of 54 consecutive patients who were diagnosed with isolated subtalar joint arthritis and underwent either open (27 patients) or posterior arthroscopic (27 patients) subtalar arthrodesis between 2015 and 2019 in 2 institutions. A minimum follow-up to be included in the study was 12 months (mean, 24.2 months; range, 12 to 41 months). The primary outcome was union time. The secondary outcomes included visual analogue scale (VAS), Short Form-36 (SF-36), and FAAM, union rate, time to return to activity of daily living, sports, work, and complications. Pre- and post-operative SF-36, FAAM, and pain (Visual Analog Scale) were obtained and compared between the two groups using independent t-test and the same group with paired t-test.

Results:

There were 54 patients (42 male and 12 female) with mean age of 43.7 years (range, 21-68 years) and mean BMI of 25.7 kg/m2 (range, 18.3-33.6 kg/m2). Both techniques demonstrated significant improvement of post-operative functional outcomes (VAS, SF-36, and VAS (p < 0.001 all)) compared to pre-operative period; however, there was no significant difference between the two groups. The secondary outcomes between open and arthroscopic groups were time to return to activity of daily living (8.4 vs 10.8 weeks), works (10.6 vs 12.9 weeks), sports (24.9 vs 32.7 weeks), time to union using CT scan (9.4 vs 12.8 weeks), union rate (100% versus 96.3%), and complications included painful hardware (18.5% vs 22.2%), paresthesia (0 vs 7.4%), and no infection in both groups.

Conclusion:

Both open and arthroscopic techniques were demonstrated significant improvement in terms of functional outcomes as measured with the FAAM, SF-36, and VAS in patients with subtalar joint arthritis. Although there was no significant difference of short-term of functional outcomes measurement and complications, arthroscopic technique was better in term of fasten recovery time and time to union.
The Effect of CAM Boots on Contact Pressures of the Ankle and Hindfoot Joints
Authors: Smyth Niall A. , Abbasi Pooyan , de Cesar Netto Cesar , Michnick Stuart M. , Casscells Nicholas , Parks Brent , Schon Lew C.
Published: July 2020

Category:

Basic Sciences/Biologics; Ankle; Hindfoot

Introduction/Purpose:

The tall Controlled Ankle Motion (CAM) boot and the short CAM boot are commonly used devices to immobilize the foot and ankle. However, the effect of these devices on joint contact pressures is unknown. The objective of this study is to assess the effect of the tall CAM boot and short CAM boot on contact pressures of the ankle, subtalar, talonavicular, and calcaneocuboid joints. We hypothesize that both the tall CAM boot and short CAM boot will reduce contact pressures of the ankle and hindfoot joints, with the tall CAM boot having the greatest effect.

Methods:

Eight lower extremity cadaver specimens were mounted on a servohydraulic test frame. The specimens were loaded to 700 N at a cyclical frequency of 1 Hz with the posterior tibial, peroneus longus, peroneus brevis, flexor hallucis longus, flexor digitorum longus, and Achilles tendon physiologically tensioned. TekScan (TekScan, Boston, MA) pressure sensors were placed in the ankle, subtalar, talonavicular, and calcaneocuboid joints. In the sagittal plane, the specimens were loaded on a neutral surface, followed by 20o of dorsiflexion. Each specimen served as its own control, with contact pressures measured with no immobilization (control), followed by placement in a short CAM boot and tall CAM boot. In addition, contact pressures in the immobilized limbs were measured at muscle loads both equal to and half of the load applied to the control in order to account for decreased muscle activation during immobilization.

Results:

There was no difference in the average and peak contact pressures of the ankle, subtalar, talonavicular and calcaneocuboid joints when comparing the short CAM boot to no immobilization at equal tendon loads. The tall CAM boot significantly decreased average and peak contact pressures of the ankle, subtalar, and talonavicular joints when compared to no immobilization. The tall CAM decreased the contact pressures of the talonavicular and subtalar joint to a greater degree than the ankle joint. The reduction in contact pressures was accentuated when the load applied to the tendons was decreased in accordance with diminished muscle activation during immobilization. Neither immobilization device decreased the contact pressures of the calcaneocuboid joint at equal tendon loads. Neither CAM boot changed the center of pressure of any joint.

Conclusion:

Immobilization in a tall CAM boot decreases contact pressures of the ankle and hindfoot in both a neutral position and in dorsiflexion. A tall CAM boot should be used clinically if the goal of its use is to maximally reduce contact pressures of the ankle and hindfoot. The tall CAM boot is better at reducing the contact pressures of the subtalar and talonavicular joint than the ankle joint.
Navigating the Terrain of Entrepreneurship Education in Neoliberal Societies
Authors: Berglund Karin , Hytti Ulla , Verduijn Karen
Published: July 2020

This article offers reflections based on the special issue on unsettling entrepreneurship education (EEP 3(3)) in which contributions have resisted the tendency to see students as consumers with the ‘right’ to take part in entrepreneurship education (EE) so as to effectively shape their enterprising selves. Here we resume our editorial discussions of what unsettling entrepreneurship education could mean for us – as entrepreneurship researchers and as teachers – and seek to mark out new directions both for research and education by reflecting upon ethical perspectives, identity work, and how EE can be seen to create an affective and emotional workspace. These aspects not only invite us to ask new research questions, but may also challenge our position as teachers in EE and invite us to reflect upon our view of students. To frame the need of continuous reflection, when navigating the terrain of EE in neoliberal society, we both take off and arrive in the current Covid-19 pandemic and suggest that this crisis can teach us something as valuable as ‘standing still’, which helps us all to reconsider what kind of entrepreneurial society that we build together with our students in entrepreneurship education.
Profile of adverse events following immunization with measles rubella vaccine at a tertiary care hospital in East Delhi, India
Authors: Bhowmik Eshita , Singh Aaradhana , Sachan Ravi
Published: July 2020

Background:

As a part of a measles and rubella (MR) campaign, the MR vaccine replaced the two-dose measles vaccine at 9–12 months and 16–24 months of age under the Universal Immunization Program (UIP). Although adverse events following immunization (AEFIs) following the measles and MMR vaccine at 9 months of age have been studied, AEFIs following the MR vaccine at 9 months of age have not been studied. As the MR vaccine a is very recent introduction in the UIP for routine immunization at 9 months of age, we intend to investigate the AEFI profile of MR vaccination at 9 months of age by active surveillance.

Aim:

We aimed to study the profile of the AEFIs with MR vaccine at 9-12 months of age in children vaccinated at the immunization clinic at the Pediatrics Department of a tertiary care hospital in East Delhi, India.

Methods:

Our study was a prospective observational study (telephonic survey). Children who attended Pediatrics OPD for the first dose of the MR vaccine at 9–12 months of age were enrolled in the study. Demographic details of the children who received the first dose of MR vaccine at 9–12 months of age at the immunization clinic of the hospital were recorded in a case record form. A telephone survey was conducted on day 7 and day 30 post-vaccination for AEFIs.

Result:

A total of 278 children were enrolled in the study, but 7 were unavailable for the further telephone survey. A total of 42 (15.5%) AEFIs were reported, of which 39 (94%) were in the initial 7 days and 3 (6%) were in the following 21 days following immunization. Of the AEFIs reported, the most common symptom was fever (38%), followed by upper respiratory tract infection (30.9%), local swelling at injection site (26.1%), and skin rash (4%).

Conclusion:

MR vaccine introduced in National Immunization Schedule is found to be safe for use in children except for a few minor reactions.
Why Bayesian “Evidence for H1” in One Condition and Bayesian “Evidence for H0” in Another Condition Does Not Mean Good-Enough Bayesian Evidence for a Difference Between the Conditions
Authors: Palfi Bence , Dienes Zoltan
Published: July 2020

Psychologists are often interested in whether an independent variable has a different effect in condition A than in condition B. To test such a question, one needs to directly compare the effect of that variable in the two conditions (i.e., test the interaction). Yet many researchers tend to stop when they find a significant test in one condition and a nonsignificant test in the other condition, deeming this as sufficient evidence for a difference between the two conditions. In this Tutorial, we aim to raise awareness of this inferential mistake when Bayes factors are used with conventional cutoffs to draw conclusions. For instance, some researchers might falsely conclude that there must be good-enough evidence for the interaction if they find good-enough Bayesian evidence for the alternative hypothesis, H1, in condition A and good-enough Bayesian evidence for the null hypothesis, H0, in condition B. The case study we introduce highlights that ignoring the test of the interaction can lead to unjustified conclusions and demonstrates that the principle that any assertion about the existence of an interaction necessitates the direct comparison of the conditions is as true for Bayesian as it is for frequentist statistics. We provide an R script of the analyses of the case study and a Shiny app that can be used with a 2 × 2 design to develop intuitions on this issue, and we introduce a rule of thumb with which one can estimate the sample size one might need to have a well-powered design.
The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications
Authors: Ogiya Daisuke , Liu Jiye , Ohguchi Hiroto , Kurata Keiji , Samur Mehmet K. , Tai Yu-Tzu , Adamia Sophia , Ando Kiyoshi , Hideshima Teru , Anderson Kenneth C.
Published: July 2020

Anti-CD38 monoclonal antibody (MoAb) treatments including daratumumab (DARA) are effective therapies for both newly diagnosed and relapsed multiple myeloma (MM). In this study, we examined the soluble factors that modulate CD38 expression and are associated with sensitivity to DARA-mediated antibody-dependent cellular cytotoxicity (ADCC) in the bone marrow (BM) microenvironment. Importantly, primary BM stromal cell (BMSC) culture supernatant (BMSC-sup) and interleukin-6 (IL-6) downregulated CD38 expression and reduced DARA-mediated ADCC. Both cytokine profiling of the BMSC-sup and genome-scale clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) knockout screening in MM cell lines identified and validated the JAK-STAT3 signaling pathway mediating CD38 downregulation, whereas the JAK-STAT1 pathway mediated CD38 upregulation. STAT3 knockdown abrogated BMSC-sup– and IL-6–induced CD38 downregulation on MM cell lines. We also confirmed that STAT3 and CD38 is negatively correlated in primary MM cells. To assess potential clinical relevance, pharmacological inhibition of the JAK-STAT pathway on BMSC-sup–induced CD38 downregulation was further examined. JAK inhibitor ruxolitinib inhibited STAT3 phosphorylation in MM cell lines, upregulated CD38 expression in MM cell lines and primary patient MM cells, and augmented DARA-mediated ADCC against MM cell lines. Taken together, our results suggest that CD38 expression on MM cells in the BM microenvironment is regulated by both STAT1 (positively) and STAT3 (negatively), and that inhibition of the JAK-STAT3 pathway represents a novel therapeutic option to enhance CD38 expression and anti-CD38 MoAb-mediated MM cytotoxicity.
Safety and efficacy of the combination of sonidegib and ruxolitinib in myelofibrosis: a phase 1b/2 dose-finding study
Authors: Gupta Vikas , Wolleschak Denise , Hasselbalch Hans , Vannucchi Alessandro Maria , Koschmieder Steffen , Cervantes Francisco , Li Yang , Dong Tuochuan , Wroclawska Monika , Bharathy Savita , Harrison Claire
Published: July 2020

The sonidegib and ruxolitinib combination was assessed in an open-label study in JAK inhibitor-naive patients with myelofibrosis (MF). The primary objective of phase 1b was to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and phase 2 was to assess spleen volume reduction at weeks 24 and 48. Fifty patients were enrolled. In the dose-escalation phase (n = 23), doses for sonidegib once daily/ruxolitinib twice daily were 400/10 mg (level 1, n = 8), 400/15 mg (level 2, n = 10), and 400/20 mg (level 3, n = 5). Two patients had dose-limiting toxicity at level 2: increased blood creatine phosphokinase (grades 3 and 4, n = 1 each). MTD/RP2D was determined as sonidegib 400 mg daily + ruxolitinib 20 mg twice daily. In phase 1b expansion and phase 2 stage 1 (n = 27), by weeks 24 and 48, ≥35% reduction in spleen volume was observed in 44.4% and 29.6% patients, respectively. By weeks 24 and 48, 42.0% and 26.0% patients had ≥50% reduction in Myelofibrosis Symptom Assessment Form total symptom score, respectively. Most common treatment-related adverse events (grade 3/4) were increased blood creatine phosphokinase (18%), anemia (14%), and thrombocytopenia (12%). Four deaths were reported due to multiple organ dysfunction syndrome (on-treatment; no relationship with study treatment), acute myeloid leukemia, MF progression, and aspiration pneumonia. Although well tolerated, this combination will not be further developed in MF patients due to modest overall benefit compared with historical ruxolitinib monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01787552.
Reducing catheter-associated urinary tract infections: a systematic review of barriers and facilitators and strategic behavioural analysis of interventions
Authors: Atkins Lou , Sallis Anna , Chadborn Tim , Shaw Karen , Schneider Annegret , Hopkins Susan , Bunten Amanda , Michie Susan , Lorencatto Fabiana
Published: July 2020

Background

Reducing the need for antibiotics is crucial in addressing the global threat of antimicrobial resistance. Catheter-associated urinary tract infection (CAUTI) is one of the most frequent device-related infections that may be amenable to prevention. Interventions implemented nationally in England target behaviours related to catheter insertion, maintenance and removal, but the extent to which they target barriers to and facilitators of these behaviours is unclear.

This strategic behavioural analysis applied behavioural science frameworks to (i) identify barriers to and facilitators of behaviours that lead to CAUTI (CAUTI-related behaviours) in primary, community and secondary care and nursing homes; (ii) describe the content of nationally adopted interventions; and (iii) assess the extent to which intervention content is theoretically congruent with barriers and facilitators.

Methods

A mixed-methods, three-phased study: (1) systematic review of 25 studies to identify (i) behaviours relevant to CAUTI and (ii) barriers to and facilitators of CAUTI-related behaviours, classified using the COM-B model and Theoretical Domains Framework (TDF); (2) content analysis of nationally adopted CAUTI interventions in England identified through stakeholder consultation, classified using the Behaviour Change Wheel (BCW) and Behaviour Change Techniques Taxonomy (BCTTv1); and (3) findings from 1 and 2 were linked using matrices linking COM-B and TDF to BCW/BCTTv1 in order to signpost to intervention design and refinement.

Results

The most frequently reported barriers to and facilitators of CAUTI-related behaviours related to ‘environmental context and resources’; ‘knowledge’; ‘beliefs about consequences’; ‘social influences’; ‘memory, attention and decision processes’; and ‘social professional role and identity.’

Eleven interventions aiming to reduce CAUTI were identifed. Interventions were primarily guidelines and included on average 2.3 intervention functions (1–5) and six BCTs (2–11), most frequently ‘education’, ‘training’ and ‘enablement.’ The most frequently used BCT was ‘information about health consequences’ which was used in almost all interventions. Social professional role and identity and environmental context and resources were targeted least frequently with potentially relevant BCTs.

Conclusions

Interventions incorporated half the potentially relevant content to target identifed barriers to and facilitators of CAUTI-related behaviours. There were missed opportunities for intervention as most focus on shaping knowledge rather than addressing motivational, social and environmental influences. This study suggests that targeting motivational, social and environmental influences may lead to more effective intervention design and refinement.
Metagenomic analysis of gut microbiome and resistome of diarrheal fecal samples from Kolkata, India, reveals the core and variable microbiota including signatures of microbial dark matter
Authors: De Rituparna , Mukhopadhyay Asish Kumar , Dutta Shanta
Published: July 2020

Background

Metagenomic analysis of the gut microbiome and resistome is instrumental for understanding the dynamics of diarrheal pathogenesis and antimicrobial resistance transmission (AMR). Metagenomic sequencing of 20 diarrheal fecal samples from Kolkata was conducted to understand the core and variable gut microbiota. Five of these samples were used for resistome analysis. The pilot study was conducted to determine a microbiota signature and the source of antimicrobial resistance genes (ARGs) in the diarrheal gut.

Results

16S rRNA amplicon sequencing was performed using Illumina MiSeq platform and analysed using the MGnify pipeline. The Genome Taxonomy Database (GTDB-Tk) was used for bacterial taxonomic identification. Diarrheal etiology was determined by culture method. Phylum Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were consistently present in 20 samples. Firmicutes was the most abundant phylum in 11 samples. The Bacteroidetes/Firmicutes ratio was less than 1 in 18 samples. 584 genera were observed. 18 of these were present in all the 20 samples. Proteobacteria was the dominant phylum in 6 samples associated with Vibrio cholerae infection. Conservation of operational taxonomic units (OTUs) among all the samples indicated the existence of a core microbiome. Asymptomatic carriage of pathogens like Vibrio cholerae and Helicobacter pylori was found. Signature of Candidate phyla or “microbial dark matter” occurred. Significant correlation of relative abundance of bacterial families of commensals and pathogens were found. Whole-genome sequencing (WGS) on Illumina MiSeq system and assembly of raw reads using metaSPAdes v3.9.1 was performed to study the resistome of 5 samples. ABRicate was used to assign ARG function. 491 resistance determinants were identified. In 80% of the samples tetracycline resistance was the most abundant resistance determinant. High abundance of ARGs against β-lactams, aminoglycosides, quinolones and macrolides was found. Eschericia sp. was the major contributor of ARGs.

Conclusions

This is the first comparative study of the gut microbiome associated with different diarrheal pathogens. It presents the first catalogue of different bacterial taxa representing the core and variable microbiome in acute diarrheal patients. The study helped to define a trend in the gut microbiota signature associated with diarrhea and revealed which ARGs are abundantly present and the metagenome-assembled genomes (MAGs) contributing to AMR.
Small lymphocytic lymphoma in true trilineage hematopoietic tissue within heterotopic ossification in an enucleated blind painful eye: a case report
Authors: Borgia Alfredo , Manara Sofia , Balzarotti Monica , Vinciguerra Paolo , Di Maria Alessandra
Published: July 2020

Background

The finding of hematological malignancies within bone marrow in heterotopic ossification has been reported only a handful of times previously in the literature. We described a case of true trilineage hematopoiesis in an excised area of heterotopic ossification from an enucleated blind painful eye.

Case presentation

A 70-year-old Caucasian man, positive for asymptomatic lymphoplasmacytic lymphoma, presented with a blind painful right eye in our ophthalmology department to evaluate enucleation bulbi. After enucleation, a histopathologic examination revealed the presence of intertrabecular infiltration in the metaplastic bone marrow of non-Hodgkin B lymphoma, with small lymphocytes, with similar characteristics to the already known disease.

Conclusion

This uncommon case reveals the possibility of the localization of malignant cells within bone metaplasia of intraocular ossification in an enucleated blind painful eye. From a practical point of view, a careful systematic histopathological examination of all resected tissues in patients with a history of malignant neoplastic pathology is necessary to confirm the diagnosis and exclude occult malignancies.
Phylogenetic analysis of Anguilla marmorata population in Thua Thien Hue, Vietnam based on the cytochrome C oxidase I (COI) gene fragments
Authors: Huyen Kieu Thi , Linh Nguyen Quang
Published: July 2020

The giant mottled eel is a species with high commercial value so overfishing, river management, and water pollution have negatively affected its movement and population numbers.Anguilla marmorata(eel) was listed in the Vietnam Red Data Book 2007 with a description of Vulnerability. This study used a barcode technique to analyze molecular characteristics and build genetic plants based on the cytochrome c oxidase I gene segment isolated from the mitochondrial genome of 48 individuals ofA. marmoratacollected in five different ecological regions of Thua Thien Hue, Vietnam. The isolated the cytochrome c oxidase I sequence has a length of 843 nucleotides, four base nucleotides of 30.03% Thymine, 25.15% Cytosine, 27.49% Adenine, and 17.43% Guanine. The percentage of Guanine + Cytosine content (42.58%) is acceptable, lower than the Adenine + Thymine content. The replacement capacity of Adenine and Guanine is 22.45% highest, the ratio between Thymine and Guanine; Cytosine and Guanine are the lowest at 2.72%. The establishment of genetically modified plants has shown the high genetic similarity of individuals in eel populations in Thua Thien Hue. The population ofAnguilla marmorataeels in Thua Thien Hue, Vietnam is divided into two separate groups that are guided by the migration process and specific ecological. This is particularly important in building strategies to conserve and develop the gene for eel in Vietnam and Thua Thien Hue.