bluuebunny/crossref_metadata_2025 huggingface dataset:
Aboard the Smile Train: Outcomes of Primary Cleft Palate Repair at a Tertiary Care Center: À bord du Smile Train : les résultats cliniques de réparations de fentes palatines dans un centre de soins tertiaires
Authors: Khan Daniyal A. , Farooq Ayesha , Jiwani Uswa , Ahsan Muhammad Asif , Shahzad Farooq , Rahman Mohammad Fazlur
Published: June 2020

Introduction:

Cleft palate repair is considered to be a safe procedure, yet still carries a 5% to 30% risk of complications. This study sought to assess the outcomes of this procedure in a high-burden Asian country that partners with the Smile Train to perform cleft surgeries.

Methods:

The Aga Khan University medical records database was queried for pediatric patients undergoing cleft surgery between 2014 and 2017. Data were abstracted from the patient medical records, and details of the clinical, demographic factors, and postoperative outcomes were assessed.

Results:

Among 142 patients with orofacial clefts, 102 (72%) underwent primary cleft palate repair, one-third (n = 36, 35%) of whom were operated as part of the Smile Train. The median preoperative hemoglobin was 11.4 g/dL (interquartile range: 10.7-12.0 g/dL), whereas the median weight was 8.3 kg (7.7-11.4 kg). Nearly two-thirds (n = 64, 63%) of the cohort underwent preoperative cardiology screening, with only a minority undergoing orthodontic treatment (n = 6, 6%). Approximately 15% (n = 15) of patients experienced a postoperative complication, most often a fistula (n = 11, 73%). On multivariable analysis, with each unit increase in hemoglobin levels, there was a 50% reduction in the odds of experiencing a complication (odds ratio: 0.51, 95% CI: 0.28-0.87). There were no in-patient deaths among the cohort.

Conclusion:

The results of the current study provide useful information to key stakeholders including patients, plastic surgeons, and policy makers on the outcomes of cleft palate repair in a developing country.
Governing India: Evolution of Programmatic Welfare in Andhra Pradesh
Authors: Mukherji Rahul , Zarhani Seyed Hossein
Published: June 2020

How can clientelistic politics be transformed into programmatic politics in a subnational state with a well-recorded history of patronage politics? We explore institutional pathways away from clientelism by systematically explicating clientelistic propensities with programmatic citizen-oriented ones in undivided Andhra Pradesh. This paper engages with a paradigm shift in policy from clientelistic to programmatic service delivery in rural development by exploring three major rural welfare programmes in undivided Andhra Pradesh: need-based redistribution, evolution of self-help groups and implementation of the right to work in India through the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) scheme. We argue that the capacity of the state to deliver owes a great deal to bureaucratic puzzling and political powering over developmental ideas. We combine powering and puzzling within the state to argue the case for how these ideas tip after evolving in a path-dependent way.
Book review: Raheel Dhattiwala, Keeping the Peace: Spatial Differences in Hindu–Muslim Violence in Gujarat in 2002
Authors: Corbridge Stuart
Published: June 2020

Raheel Dhattiwala, Keeping the Peace: Spatial Differences in Hindu–Muslim Violence in Gujarat in 2002. Cambridge University Press. 2019. 193 pages. ₹695.
Gastric Inflammatory Fibroid Polyp: A Rare Cause of Occult Upper Gastrointestinal Bleeding
Authors: Inayat Faisal , Ur Rahman Asad , Wahab Ahsan , Riaz Amir , Zahid Effa , Bejarano Pablo , Pimentel Ronnie
Published: June 2020

Inflammatory fibroid polyps (IFPs) are rare mesenchymal lesions that can arise throughout the gastrointestinal tract. These tumors represent less than 0.1% of all gastric polypoid lesions and are frequently found incidentally on endoscopic evaluation. While presenting symptoms depend on the location of the tumor, gastric polyps commonly present with epigastric pain and early satiety. We hereby delineate the case of a middle-aged female who presented with chronic iron deficiency anemia and a positive fecal occult blood test. She underwent an upper endoscopy, which revealed an actively oozing umbilicated lesion in the gastric antrum. Endoscopic ultrasound divulged the submucosal origin of the lesion. It was subsequently excised using endoscopic mucosal resection. Pathologic examination of the resected specimen confirmed the diagnosis of gastric IFP. Furthermore, we conducted a systematic literature search of the MEDLINE database centered on gastric IFPs from January 2000 till March 2020. The data on patient demographics, clinical features, endoscopic findings, lesion site and size, and treatment approaches were collected and analyzed. This article illustrates the overarching need for clinicians to be vigilant of gastric IFPs presenting with initial clinical symptoms suggestive of occult upper gastrointestinal bleeding. Prompt diagnosis and management of gastric IFPs carry paramount importance to combat chronic unexplained iron deficiency anemia following occult bleeding in such patients. A concoction of endoscopy, biopsy, and immunohistochemical examination can be employed toward their prompt detection. Although gastric IFPs have conventionally been treated with surgery, endoscopic resection is now emerging as a safe and efficient therapeutic modality.
Proactive Health Support: Exploring Face-to-Face Start-Up Sessions Between Participants and Registered Nurses at the Onset of Telephone-Based Self-Management Support
Authors: Winther Susanne , Fredens Mia , Hansen Marie Brund , Benthien Kirstine Skov , Nielsen Camilla Palmhøj , Grønkjær Mette
Published: June 2020

Proactive Health Support (PaHS) is a large-scale intervention in Denmark carried out by registered nurses (RNs) who provide self-management support to people at risk of hospital admission to enhance their health, coping, and quality of life. PaHS is initiated with a face-to-face session followed by telephone conversations. We aimed to explore the start-up sessions, including if and how the relationship between participants and RNs developed at the onset of PaHS. We used an ethnographic design including observations and informal interviews. Data were analyzed using a phenomenological–hermeneutical approach. The study showed that contexts such as hospitals and RNs legitimized the intervention. Face-to-face communication contributed to credibility, just as the same RN throughout the intervention ensured continuity. We conclude that start-up sessions before telephone-based self-management support enable a trust-based relationship between participants and RNs. Continuous contact with the same RNs throughout the session promoted participation in the intervention.
Patients’ Experiences With Illness, Treatment, and Decision-Making for Esophageal Cancer: A Qualitative Study in a Danish Hospital Setting
Authors: Larsen Malene Kaas , Schultz Helen , Mortensen Michael Bau , Birkelund Regner
Published: June 2020

Patients with curable esophageal cancer or cancer in the esophageal junction face several challenges during the course of their treatment because of the burden of uncertainty in their prognoses and complexity and side effects of the treatment. The aim of this study is to explore patient experiences with illness, treatment, and decision-making in the context of esophageal cancer. A qualitative approach using phenomenological–hermeneutical methodology was used. Data consisted of participant observations and interviews. We analyzed the data based on Ricoeur’s theory of interpretation. The results show that patients with esophageal cancer are putting their ordinary lives on hold and experiencing the meal as a battleground during treatment. Patients strive to maintain autonomy, gain control, and take ownership. The results emphasize the need for a systematic approach to establish an ongoing dialogue with patients throughout the course of treatment.
Biomarkers and antithrombotic treatment in cervical artery dissection – Design of the TREAT-CAD randomised trial
Authors: Traenka Christopher , Gensicke Henrik , Schaedelin Sabine , Luft Andreas , Arnold Marcel , Michel Patrik , Kägi Georg , Kahles Timo , Nolte Christian H , Kellert Lars , Rosenbaum Sverre , Sztaizel Roman , Brehm Alex , Stippich Christoph , Psychogios Marios , Lyrer Philippe , Engelter Stefan T ,   for the TREAT-CAD investigators
Published: June 2020

Introduction

The type of antithrombotic treatment in cervical artery dissection patients is still a matter of debate. Most physicians prefer anticoagulants over antiplatelet agents for stroke prevention. However, this approach is not evidence-based and antiplatelets might be as safe and as effective. The ‘Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection’ (‘TREAT-CAD’) trial (clinicaltrials.gov: NCT02046460) compares Aspirin to oral anticoagulants (vitamin K antagonists) with regard to efficacy and safety by using both clinical and imaging surrogate outcome measures. TREAT-CAD tests the hypothesis, that aspirin is as safe and effective as vitamin K antagonists.

Patients and methods

TREAD-CAD is a Prospective, Randomised controlled, Open-labelled, multicentre, non-inferiority trial with Blinded assessment of outcome Events (PROBE-design). Key eligibility criteria are (i) clinical symptoms attributable to cervical artery dissection and (ii) verification of the cervical artery dissection diagnosis by established magnetic resonance imaging criteria. Patients are randomised to receive either Aspirin 300 mg daily or vitamin K antagonists for 90 days.

Results

Primary outcomes are assessed at 14 ± 10 days (magnetic resonance imaging and clinical examination) and at 90 ± 30 days (clinical examinations). The primary endpoint is a composite outcome measure – labelled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) – and includes (i) occurrence of any stroke (including retinal infarction), (ii) new ischaemic lesions on diffusion-weighted magnetic resonance imaging, (iii) any major extracranial haemorrhage, (iv) any symptomatic intracranial haemorrhage, (v) any new haemorrhagic lesion visible on paramagnetic-susceptible sequences and (vi) death.

Discussion

After database closure, (i) central verification of cervical artery dissection diagnosis will be done by two experienced raters, (ii) adjudication of outcome events will be performed by independent adjudication committees, separately for clinical and imaging outcomes. The primary analysis will be done on the per protocol data set. The targeted sample size consists of 169 evaluable patients in the per protocol data set.

Conclusion

TREAT-CAD is testing the non-inferiority of Aspirin versus vitamin K antagonists treatment in patients with symptomatic cervical artery dissection by combined clinical and magnetic resonance imaging outcomes.
Philological connotations among various manuscripts of Xianluoguan Yiyu
Authors: Zheng Wei , Li Chenyu
Published: June 2020

Xianluoguan Yiyu is a series of Siamese-Chinese vocabularies compiled by the Ming and Qing government for translation or interpretation teachings. In choosing transcription characters, the compilers emphasized the agreement on initials and main vowels more than distinctions between voiced and unvoiced consonants. Various manuscripts reflect some phonetic characteristics in different periods during two centuries, in which it is proved that the sound changes of ʔb- > b- > m- and ʔd- > d- > l- were completed no later than the later period of the 17th century.
Reliability of and Minimal Detectable Changes in Gait Performance Tests in Patients With Chronic Hemiplegic Stroke
Authors: Hayakawa Jun , Ochi Mitsuhiro , Yano Yudai , Matsugaki Ryutaro , Ogata Yuto , Murakami Takeshi , Kuhara Satoshi , Itoh Hideaki , Hachisuka Kenji , Saeki Satoru
Published: June 2020

Purpose: This study aimed to determine the inter- and intra-rater reliability of and minimal detectable changes (MDCs) at the 95% confidence interval in gait performance tests in patients with chronic hemiplegic stroke who can walk independently.

Materials and Methods: Thirty patients with chronic hemiplegic stroke (24 men, 6 women, mean age 62.5 ± 11.6 years) were enrolled. Physical therapists (mean clinical experience: 9.1 ± 9.3 years) performed the timed up and go test (TUG), 10-m walk test (10MWT), and 6-min walk test (6MWT) 1 day apart. Reliability was evaluated using the intraclass correlation coefficient (ICC) and Bland–Altman analysis.

Results: The ICC was ≥0.9 for all tests, and no systematic bias was found. MDC at the 95% confidence interval was 1.9 s for the TUG, 0.16 m/s for the 10MWT, and 28.4 m for the 6MWT.

Discussion: We demonstrated excellent intra- and inter-rater reliability of all tests. These results suggest that gait performance tests are reliable.

Conclusion: These commonly used gait performance tests demonstrated high reliability and can be recommended to evaluate clinically meaningful improvements in patients with chronic hemiplegic stroke who can walk independently.
Women’s employment, income and divorce in West Germany: a causal approach
Authors: Brüggmann Daniel
Published: June 2020

In this paper, I assess the employment and income effect of divorce for women in West Germany between 2000 and 2005. With newly available administrative data that allows me to adopt a causal approach, I find strong negative employment effects with respect to marginal employment and strong positive effects with respect to regular employment. However, in sum, the overall employment rate (marginal and regular employment combined) is not affected. Furthermore, the lower the labor market attachment before separation is, the more pronounced employment effects are. In addition, I also estimate the impact of divorce on daily gross incomes. I find no convincing evidence for an income effect. I conclude that a divorce might have a pure labor supply effect only.
Pseudoscorpion Wolbachia symbionts: diversity and evidence for a new supergroup S
Authors: Lefoulon Emilie , Clark Travis , Borveto Fanni , Perriat-Sanguinet Marco , Moulia Catherine , Slatko Barton E. , Gavotte Laurent
Published: June 2020

Background

Wolbachia are the most widely spread endosymbiotic bacteria, present in a wide variety of insects and two families of nematodes. As of now, however, relatively little genomic data has been available. The Wolbachia symbiont can be parasitic, as described for many arthropod systems, an obligate mutualist, as in filarial nematodes or a combination of both in some organisms. They are currently classified into 16 monophyletic lineage groups (“supergroups”). Although the nature of these symbioses remains largely unknown, expanded Wolbachia genomic data will contribute to understanding their diverse symbiotic mechanisms and evolution.

Results

This report focuses on Wolbachia infections in three pseudoscorpion species infected by two distinct groups of Wolbachia strains, based upon multi-locus phylogenies. Geogarypus minor harbours wGmin and Chthonius ischnocheles harbours wCisc, both closely related to supergroup H, while Atemnus politus harbours wApol, a member of a novel supergroup S along with Wolbachia from the pseudoscorpion Cordylochernes scorpioides (wCsco). Wolbachia supergroup S is most closely related to Wolbachia supergroups C and F. Using target enrichment by hybridization with Wolbachia-specific biotinylated probes to capture large fragments of Wolbachia DNA, we produced two draft genomes of wApol. Annotation of wApol highlights presence of a biotin operon, which is incomplete in many sequenced Wolbachia genomes.

Conclusions

The present study highlights at least two symbiont acquisition events among pseudoscorpion species. Phylogenomic analysis indicates that the Wolbachia from Atemnus politus (wApol), forms a separate supergroup (“S”) with the Wolbachia from Cordylochernes scorpioides (wCsco). Interestingly, the biotin operon, present in wApol, appears to have been horizontally transferred multiple times along Wolbachia evolutionary history.
A novel VPS13B mutation in Cohen syndrome: a case report and review of literature
Authors: Momtazmanesh Sara , Rayzan Elham , Shahkarami Sepideh , Rohlfs Meino , Klein Christoph , Rezaei Nima
Published: June 2020

Background

Cohen syndrome, an autosomal recessive syndrome, is a rare syndrome with diverse clinical manifestations including failure to thrive, hypotonia, hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, neutropenia and a friendly character. It is associated with mutations of the vacuolar protein sorting 13 homolog B (VPS13B) gene, which is involved in the development of the ocular, hematological and central nervous systems. This gene encodes a transmembrane protein playing a crucial role in preserving the integrity of the Golgi complex. To date, more than 150 mutations of VPS13B have been reported in over 200 Cohen syndrome patients. Missense or nonsense mutations are the most common mutations.

Case presentation

A 4-year-old girl, born to consanguineous parents, was referred to the pediatric clinical immunology outpatient clinic for investigation of recurrent neutropenia with a history of recurrent infections in the past year. On physical examination, she had the characteristic facial features of Cohen syndrome, developmental delay and speech disorder. She had a cheerful disposition, and her mother gave a history of feeding difficulties in her first months of life. She did not present any ophthalmologic or cardiac abnormalities. Her lab results revealed moderate neutropenia. Serum IgG, IgM, IgA and IgE levels were normal. She fulfilled the clinical diagnostic criteria for Cohen syndrome. WES revealed a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49). Currently, she is not experiencing any severe problem, and she undergoes irregular medical treatment once her neutrophil count decreases under the normal limit. Her verbal and motor abilities have improved as a result of speech and occupational therapies.

Conclusion

We reported a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49) in a 4-year-old girl with Cohen syndrome. Cohen syndrome should be considered in differential diagnosis of any child with intellectual disability and neutropenia.
Analytical evaluation of the clonoSEQ Assay for establishing measurable (minimal) residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma
Authors: Ching Travers , Duncan Megan E. , Newman-Eerkes Tera , McWhorter Mollie M. E. , Tracy Jeffrey M. , Steen Michelle S. , Brown Ryan P. , Venkatasubbarao Srivatsa , Akers Nicholas K. , Vignali Marissa , Moorhead Martin E. , Watson Drew , Emerson Ryan O. , Mann Tobias P. , Cimler B. Melina , Swatkowski Pamela L. , Kirsch Ilan R. , Sang Charles , Robins Harlan S. , Howie Bryan , Sherwood Anna
Published: June 2020

Background

The clonoSEQ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) identifies and tracks unique disease-associated immunoglobulin (Ig) sequences by next-generation sequencing of IgH, IgK, and IgL rearrangements and IgH-BCL1/2 translocations in malignant B cells. Here, we describe studies to validate the analytical performance of the assay using patient samples and cell lines.

Methods

Sensitivity and specificity were established by defining the limit of detection (LoD), limit of quantitation (LoQ) and limit of blank (LoB) in genomic DNA (gDNA) from 66 patients with multiple myeloma (MM), acute lymphoblastic leukemia (ALL), or chronic lymphocytic leukemia (CLL), and three cell lines. Healthy donor gDNA was used as a diluent to contrive samples with specific DNA masses and malignant-cell frequencies. Precision was validated using a range of samples contrived from patient gDNA, healthy donor gDNA, and 9 cell lines to generate measurable residual disease (MRD) frequencies spanning clinically relevant thresholds. Linearity was determined using samples contrived from cell line gDNA spiked into healthy gDNA to generate 11 MRD frequencies for each DNA input, then confirmed using clinical samples. Quantitation accuracy was assessed by (1) comparing clonoSEQ and multiparametric flow cytometry (mpFC) measurements of ALL and MM cell lines diluted in healthy mononuclear cells, and (2) analyzing precision study data for bias between clonoSEQ MRD results in diluted gDNA and those expected from mpFC based on original, undiluted samples. Repeatability of nucleotide base calls was assessed via the assay’s ability to recover malignant clonotype sequences across several replicates, process features, and MRD levels.

Results

LoD and LoQ were estimated at 1.903 cells and 2.390 malignant cells, respectively. LoB was zero in healthy donor gDNA. Precision ranged from 18% CV (coefficient of variation) at higher DNA inputs to 68% CV near the LoD. Variance component analysis showed MRD results were robust, with expected laboratory process variations contributing ≤3% CV. Linearity and accuracy were demonstrated for each disease across orders of magnitude of clonal frequencies. Nucleotide sequence error rates were extremely low.

Conclusions

These studies validate the analytical performance of the clonoSEQ Assay and demonstrate its potential as a highly sensitive diagnostic tool for selected lymphoid malignancies.
Impact of obesity and metabolic health status in the development of non-alcoholic fatty liver disease (NAFLD): A United Kingdom population-based cohort study using the health improvement network (THIN)
Authors: Vusirikala A. , Thomas T. , Bhala N. , Tahrani A. A. , Thomas G. N. , Nirantharakumar K.
Published: June 2020

Background

With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records.

Methods

A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes.

Results

During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98–3.49), and 6.92 (6.40–7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97–2.61) or = < 2 (2.39, 1.99–2.87) metabolic abnormalities.

Conclusions

MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD.
An unusual presentation of developmental anomalies of the cardiovascular system including tetralogy of fallot, double outlet right ventricle, patent foramen ovale and persistent right aortic arch in a Friesian calf
Authors: McManus Aine , Moloney Tim , Kelly Pamela , Rowan Conor , Skelly Cliona , McAloon Catherine I.
Published: June 2020

Background

Congenital heart diseases are occasionally encountered in the bovine species. Ventricular septal defects (VSD) and atrial septal defects (ASD) are reported to be the most common; however, a vast collection have been reported [1, 2]. Congenital heart diseases is thought to represent less than 3% of all congenital abnormalities in calves [3]. Various cardiac anomalies arise due to defective embryologic development such as defects of the septae or the cardiac chambers [2]. The exact aetiology of these congenial heart anomalies remains to be fully elucidated [4]. VSDs appear to be the most common congenital cardiac anomaly in calves. Other diseases can be subdivided into cyanotic (e.g. ASD or patent ductus arteriosus) and non-cyanotic (e.g. tetralogy of fallot or eisenmengers complex) [5, 6]. An exceptional presentation of an array of congenital anomalies was identified in a Friesian heifer calf. To the authors’ knowledge this concurrent collection of congenital abnormalities has never been reported in this species.

Case presentation

A 3-day old Friesian heifer presented with a history since birth of regurgitation post feeding. The main finding on clinical examination was tachypnoea with a holosystolic murmur. Echocardiography identified a VSD, patent foramen ovale (PFO) (both with left to right blood flow) and tricuspid insufficiency. The calf was subsequently euthanised and underwent gross post-mortem examination. A persistent right aortic arch (PRAA) was identified. The cardiac anomalies identified on the echocardiogram were confirmed along with additional abnormalities; double outlet right ventricle (DORV), partial transposition of the great vessels, pulmonic stenosis, hypoplasia of the right branch of the pulmonary artery and right ventricular hypertrophy. The final diagnosis was Tetralogy of Fallot with DORV, PFO and PRAA. The lungs appeared oedematous and congested due to cardiac malfunction and cranioventral aspiration pneumonia. Free serous fluid was identified in the thoracic cavity. Unilateral renal agenesis of the left kidney was an incidental finding but is of note due to its coexistence with the cardiac abnormalities.

Conclusions

This is an unusual case as it features numerous congenital abnormalities that appeared to negate each other allowing capability with life. To the authors’ knowledge, this collection of concurrent cardiac anomalies has not been previously reported in bovines.
Global mental health: an improved measure of well-being in multiple languages
Authors: Graeff-Buhl-Nielsen Sophia , Garcia-Garzon Eduardo , Benzerga Amel , Folke Tomas , Ruggeri Kai
Published: June 2020

Background

An increasing number of international organisations and national governments have committed to well-being promotion. Unfortunately, important questions regarding how to assess well-being are still unresolved, making policy implementation and evaluation difficult.

Methods

This research expanded on Huppert and So’s (Soc Indic Res. 110, 837–861 2013) multidimensional subjective well-being framework by investigating the replicability of the model in two non-European regions (South America, represented by Brazil and Colombia, and Eastern Africa, represented by Uganda), and the United Kingdom. Additionally, previous limitations of the framework were also addressed.

ESS Round Six items were crucially improved in terms of temporal and response scale consistency. Bayesian approximate measurement invariance was applied on a sample of 381 young adult participants to test for consistency across countries.

Results

The Huppert & So (Soc Indic Res. 110, 837–861 2013) model was found to fairly replicate across non-European regions, where meaningful differences in well-being patterns across regions were observed. Additionally, estimated well-being was related with other well-being measures (Five Ways): Learn and Connect were the strongest predictors of general well-being, with Take Notice and Give being associated with specific aspects of it.

Conclusions

Based on this narrow sample of young adults, it appears the ten-item measure proposed by Huppert & So (Soc Indic Res. 110, 837–861 2013) is useful for assessing population mental health outside of Europe. This is only an initial attempt to assess qualities, so further testing should be done before applying at scale for identifying policy opportunities to address well-being of populations.
Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm
Authors: Jin Linling , Wu Zhenzhen , Wang Yanli , Zhao Xin
Published: June 2020

Background

Cancer stem cells (CSCs) are regarded as the root of tumor progression, thus representing an anti-cancer therapy through targeting this cell sub-population.

Methods

Non-small cell lung cancer (NSCLC) CSCs were enriched by non-adherent spheroid formation analysis. Lentivirus infection was used to stably change gene expression. Cell cycle, EdU incorporation, cell apoptosis, cell viability, ALDH1 activity, spheroid formation and in vivo tumor initiation assays were performed to detect the effects of Cryptotanshinone (CT), a traditional Chinese herb medicine, on the stemness of NSCLC cells. RNA-sequencing combined qRT-PCR and western blot analysis were constructed to explore the underlying mechanism contributing to CT-mediated effects.

Results

CT could attenuate the stemness of NSCLC CSCs, as evident by the reduced spheroid formation ability, stemness marker expression and ALDH1 activity. Additionally, CT provoked NSCLC CSCs entry into the cell cycle. RNA-sequencing analysis showed that Hippo signaling pathway was highly enriched in NSCLC CSCs with CT treatment. Further experiments disclosed that CT decreased TAZ (a regulatory master of Hippo pathway) expression via promoting its nuclear-cytoplasm translocation in NSCLC CSCs. Also, overexpression of TAZ partially saved the attenuation of CT on the stemness of NSCLC CSCs. Notably, CT enhanced the sensitivity of tyrosine kinase inhibitor (TKI) and chemotherapy in NSCLC CSCs.

Conclusions

This work reveals that CT attenuates NSCLC CSC stemness, implying the possibility of CT as an adjuvant therapy for NSCLC.
Novel 3D embryo implantation model within macroporous alginate scaffolds
Authors: Stern-Tal Dganit , Achache Hanna , Jacobs Catane Liora , Reich Reuven , Tavor Re’em Tali
Published: June 2020

Background

Implantation failure remains an unsolved obstacle in reproductive medicine. Previous studies have indicated that estrogen responsiveness, specifically by estrogen receptor alpha (ERα), is crucial for proper implantation. There is an utmost need for a reliable in vitro model that mimics the events in the uterine wall during the implantation process for studying the regulatory mechanisms governing the process. The current two-dimensional and hydrogel-based in vitro models provide only short-term endometrial cell culture with partial functionality.

Results

Endometrial biopsies showed an increase in E-cadherin expression on the typical window of implantation of fertile women, compared to negligible expression in recurrent implantation failure (RIF) patients. These clinical results indicated E-cadherin as a marker for receptivity. Three-dimensional (3D) macroporous alginate scaffolds were the base for epithelial endometrial cell-seeding and long-term culture under hormone treatment that mimicked a typical menstrual cycle. The RL95–2 epithelial cell culture in macroporous scaffolds was viable for 3 weeks and showed increased E-cadherin levels in response to estrogen. Human choriocarcinoma (JAR) spheroids were used as embryo models, seeded onto cell constructs and successfully adhered to the RL95–2 cell culture. Moreover, a second model of HEC-1A with low ERα levels, showed lower E-cadherin expression and no JAR attachment. E-cadherin expression and JAR attachment were recovered in HEC-1A cells that were transfected with ERα plasmid.

Conclusions

We present a novel model that enables culturing endometrial cells on a 3D matrix for 3 weeks under hormonal treatment. It confirmed the importance of ERα function and E-cadherin for proper implantation. This platform may serve to elucidate the regulatory mechanisms controlling the implantation process, and for screening and evaluating potential novel therapeutic strategies for RIF.
Partial trisomy 4q and monosomy 5p inherited from a maternal translocationt(4;5)(q33; p15) in three adverse pregnancies
Authors: Zhang Jingbo , Zhang Bei , Liu Tong , Xie Huihui , Zhai Jingfang
Published: June 2020

Background

Carriers of balanced reciprocal chromosomal translocations are at known reproductive risk for offspring with unbalanced genotypes and resultantly abnormal phenotypes. Once fertilization of a balanced translocation gamete with a normal gamete, the partial monosomy or partial trisomy embryo will undergo abortion, fetal arrest or fetal malformations. We reported a woman with chromosomal balanced translocation who had two adverse pregnancies. Prenatal diagnosis was made for her third pregnancy to provide genetic counseling and guide her fertility.

Case presentation

We presented a woman with chromosomal balanced translocation who had three adverse pregnancies. Routine G banding and CNV-seq were used to analyze the chromosome karyotypes and copy number variants of amniotic fluid cells and peripheral blood. The karyotype of the woman was 46,XX,t(4;5)(q33;p15). During her first pregnancy, odinopoeia was performed due to fetal edema and abdominal fluid. The umbilical cord tissue of the fetus was examined by CNV-seq. The results showed a genomic gain of 24.18 Mb at 4q32.3-q35.2 and a genomic deletion of 10.84 Mb at 5p15.2-p15.33 and 2.36 Mb at 15q11.1-q11.2. During her second pregnancy, she did not receive a prenatal diagnosis because a routine prenatal ultrasound examination found no abnormalities. In 2016, she gave birth to a boy. The karyotype the of the boy was 46,XY,der(5)t(4;5)(q33;p15)mat. The results of CNV-seq showed a deletion of short arm of chromosome 5 capturing regions 5p15.2-p15.33, a copy gain of the distal region of chromosome 4 at segment 4q32.3q35.2, a duplication of chromosome 1 at segment 1q41q42.11 and a duplication of chromosome 17 at segment 17p12. During her third pregnancy, she underwent amniocentesis at 17 weeks of gestation. Chromosome karyotype hinted 46,XY,der(5)t(4;5)(q33;p15)mat. Results of CNV-seq showed a deletion of short arm (p) of chromosome 5 at the segment 5p15.2p15.33 and a duplication of the distal region of chromosome 4 at segment 4q32.3q35.2.

Conclusions

Chromosomal abnormalities in three pregnancies were inherited from the mother. Preimplantation genetic diagnosis is recommended to prevent the birth of children with chromosomal abnormalities.
Identification of cell type-specific methylation signals in bulk whole genome bisulfite sequencing data
Authors: Scott C. Anthony , Duryea Jack D. , MacKay Harry , Baker Maria S. , Laritsky Eleonora , Gunasekara Chathura J. , Coarfa Cristian , Waterland Robert A.
Published: June 2020

Background

The traditional approach to studying the epigenetic mechanism CpG methylation in tissue samples is to identify regions of concordant differential methylation spanning multiple CpG sites (differentially methylated regions). Variation limited to single or small numbers of CpGs has been assumed to reflect stochastic processes. To test this, we developed software, Cluster-Based analysis of CpG methylation (CluBCpG), and explored variation in read-level CpG methylation patterns in whole genome bisulfite sequencing data.

Results

Analysis of both human and mouse whole genome bisulfite sequencing datasets reveals read-level signatures associated with cell type and cell type-specific biological processes. These signatures, which are mostly orthogonal to classical differentially methylated regions, are enriched at cell type-specific enhancers and allow estimation of proportional cell composition in synthetic mixtures and improved prediction of gene expression. In tandem, we developed a machine learning algorithm, Precise Read-Level Imputation of Methylation (PReLIM), to increase coverage of existing whole genome bisulfite sequencing datasets by imputing CpG methylation states on individual sequencing reads. PReLIM both improves CluBCpG coverage and performance and enables identification of novel differentially methylated regions, which we independently validate.

Conclusions

Our data indicate that, rather than stochastic variation, read-level CpG methylation patterns in tissue whole genome bisulfite sequencing libraries reflect cell type. Accordingly, these new computational tools should lead to an improved understanding of epigenetic regulation by DNA methylation.
Livestock owners’ worry and fear of tick-borne diseases
Authors: Johansson Maria , Mysterud Atle , Flykt Anders
Published: June 2020

Background

Recent global changes have led to an increase in distribution of ticks towards higher elevation and latitude in Europe and livestock are at increasing risk of contracting tick-borne diseases, but psychological aspects of how this affects human well-being are rarely assessed. Departing from the theory on emotional appraisal coming from psychology, this study investigates which factors that modulate worry and fear associated with the presence of ticks among livestock owners of sheep and/or cattle.

Methods

Survey data from 775 livestock owners in Norway were analysed by hierarchical multiple regression analysis with an index of fear of tick-borne diseases among livestock as the outcome variable.

Results

Twenty-nine per cent of the livestock owners reported worry and fear of tick-borne diseases among their livestock. The model explained 35% of the variance in worry and fear. There was a weak association between estimated incidences of tick-borne diseases in livestock and livestock owners’ worry and fear. Whereas previous personal experience of ticks and tick-borne diseases in livestock, and the livestock owners’ appraisals of the situation were more strongly associated with relatively stronger feelings of worry and fear.

Conclusions

Livestock owners’ worry and fear of tick-borne diseases in livestock can partly be understood as their appraisals of perceived personal relevance of the presence of ticks, its potential negative implications for their daily life at large, and what potential they have to cope by different strategies to adapt or adjust to the situation.
Correction to: The microbiome as a biosensor: functional profiles elucidate hidden stress in hosts
Authors: Zolti Avihai , Green Stefan J. , Sela Noa , Hadar Yitzhak , Minz Dror
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Creating inclusive classrooms by engaging STEM faculty in culturally responsive teaching workshops
Authors: O’Leary Erin Sanders , Shapiro Casey , Toma Shannon , Sayson Hannah Whang , Levis-Fitzgerald Marc , Johnson Tracy , Sork Victoria L.
Published: June 2020

Background

As higher education institutions strive to effectively support an increasingly diverse student body, they will be called upon to provide their faculty with tools to teach more inclusively, especially in science, technology, engineering, and mathematics (STEM) classrooms where recruitment and retention of students from underrepresented and disadvantaged groups present long-standing challenges. Pedagogical training approaches to creating inclusive classrooms involve interventions that raise awareness of student and instructor social identities and explore barriers to learning, such as implicit bias, microaggressions, stereotype threat, and fixed mindset. Such efforts should focus on embracing diversity as an asset leveraged to benefit all students in their learning. In this paper, we describe the impact of multiday, off-campus immersion workshops designed to impart faculty with these tools. Based on analysis of workshop participant data, we report the resulting changes in faculty knowledge of factors affecting classroom climate and student success in STEM, attitudes about students, and motivation to adopt new teaching practices aimed at fostering equitable and culturally responsive learning environments.

Results

Key findings indicate that attendees (1) increased their knowledge of social identities and the barriers to learning in STEM classrooms, particularly those faced by students from underrepresented groups in STEM or socioeconomically challenged backgrounds; (2) changed their attitudes about students’ abilities as science majors, shifting away from a fixed-mindset perspective in which characteristics, such as intelligence, are perceived as innate and unalterable; and (3) modified their teaching approaches to promote inclusivity and cultural responsiveness.

Conclusion

Faculty members, who are linchpins in the evolution of college classrooms into settings that provide students with equitable opportunities to succeed academically in STEM, can benefit from participating in immersion workshops structured to support their awareness of issues affecting classroom culture related to race/ethnicity, LGBTQ status, religious affiliation, ability, socioeconomic status, and other social identities that contribute to disparities in STEM achievement and persistence.
Environmentally sound Management of Ship Wastes: challenges and opportunities for European ports
Authors: Argüello Gabriela
Published: June 2020

Ship wastes are incidentally regulated within the regime of marine pollution and the prevention of ship-source pollution is heavily reliant on the provision of adequate port reception facilities on land. However, the coordination between these facilities and further downstream management operations is still an unresolved issue. This paper examines from a legal perspective the challenges and opportunities related to the management of wastes generated on-board vessels after they are discharged to port reception facilities. Ship wastes are studied from a European Union (EU) law perspective and the author evaluates the integration of ship waste management within wider EU waste legislation and national waste management plans.
Review of protection and fault handling for a flexible DC grid
Authors: He Jinghan , Chen Keao , Li Meng , Luo Yiping , Liang Chenguang , Xu Yin
Published: June 2020

With the development of power electronics technology, the flexible DC grid will play a significant role in promoting the transformation and reformation of the power grid. It is immune to commutation failure and has high flexibility in power control and renewable energy grid integration. However, the protection and fault handling technology for a flexible DC grid is a big challenge because of the limited overcurrent capability of the converters. This paper summarizes the development of the flexible DC grid, and analyzes the fault characteristics in detail. Next, the applicability, advantages and disadvantages of the existing protection principle, fault isolation and recovery schemes are reviewed. Finally, the key problems and development trend of the future flexible DC grid are pointed out and forecasted respectively.
Tumor Molecular Profiling: Pediatric Results of the ProfiLER Study
Authors: Benezech Sarah , Saintigny Pierre , Attignon Valery , Pissaloux Daniel , Paindavoine Sandrine , Faure-Conter Cécile , Corradini Nadège , Marec-Berard Perrine , Bergeron Christophe , Cassier Philippe , Eberst Lauriane , Dufresne Armelle , Wang Qing , Agrapart Vincent , De La Fouchardière Arnaud , Perol David , Garin Gwenaëlle , Corset Véronique , Ben Abdesselem Leila , Chabaud Sylvie , Tredan Olivier , Blay Jean-Yves , Frappaz Didier
Published: June 2020

PURPOSE

The Program to Establish the Genetic and Immunologic Profile of Patient's Tumor for All Types of Advanced Cancer study (ClinicalTrials.gov identifier: NCT01774409 ) analyzed the genome of refractory cancers to identify a potential molecular-based recommended therapy (MBRT). The objectives of the pediatric substudy were to describe the incidence of genomic mutations, the MBRT, and the treatments undertaken with a molecular-targeted agent in a pediatric cohort.

METHODS

The tumor genome was analyzed within a 69-gene next-generation sequencing panel and an array comparative genomic hybridization assay. The results were evaluated by a multidisciplinary molecular board, and the targeted therapies were provided in the setting of a clinical trial or through compassionate use programs, when indicated.

RESULTS

Between November 2013 and June 2017, 50 patients younger than 19 years who were treated for a high-risk or relapsing tumor were included. Sarcomas (n = 24; 47%), CNS tumors (n = 14; 29%), and neuroblastomas (n = 5; 10%) were the most frequent tumor subtypes. Seven patients (14%) were excluded because no DNA could be recovered. Among the 43 remaining patients, 10 exhibited at least one targetable genomic alteration. Ultimately, four patients (8%) were treated with the recommended targeted therapy.

CONCLUSION

The results of this study confirm treatment with a targeted therapy for pediatric patients with cancer is still limited at present, as also is reported for adults.
Estrogen Versus FSH Effects on Bone Metabolism: Evidence From Interventional Human Studies
Authors: Khosla Sundeep
Published: June 2020

Provocative mouse studies and observational human data have generated considerable enthusiasm for modulating follicle-stimulating hormone (FSH) action in humans to prevent bone loss and, in addition, to treat obesity. This perspective summarizes the strengths and potential weaknesses of the mouse studies examining the skeletal phenotype of FSHβ or FSH receptor null mice, as well as more recent studies using FSH neutralizing antibodies. Although human observational studies do demonstrate correlation of serum FSH levels with postmenopausal bone loss, these studies cannot distinguish whether serum FSH is simply a better biomarker than estradiol or causally related to the bone loss. Establishing causality requires direct interventional studies either suppressing or infusing FSH in humans and to date, such studies have uniformly failed to demonstrate an effect of FSH on bone turnover independent of changes in sex steroid levels. In addition, suppression of FSH is unable to prevent increases in body fat following the induction of sex steroid deficiency, at least in men. Thus, although the preclinical mouse and human observational data are intriguing, there is currently no direct evidence from interventional studies that FSH regulates bone or fat metabolism in vivo in humans.
Transcendent Ephemera
Authors: Dugaw Dianne
Published: June 2020

This essay considers our response to printed ephemera, analyzing British examples of the seventeenth and eighteenth centuries, specifically elegies, broadside ballads, and the life story and advertised theatrical performing of the eighteenth-century female soldier Hannah Snell, using methods from folklore, musicology, and literary study. The formats of the ephemera, and their performative modes seemingly identify these expressions as impermanent; at the same time, examining them collectively, we recognize an ironic gesture for lasting universal human sentiment and meaning. The ubiquitousness of these recurring forms, conjoined with resistance to scholarly theorizing of expression popular across social ranks, leaves their conventions and parameters understudied and deserving of more exploration and analysis. As the psalmist observed, humans feel ourselves to be walking on a fleeting path. Ephemera speak to and from this experience of precarious temporality with a paradoxical coupling between representations of topical particularities on the one hand, and, on the other, oft-repeated patterns that invoke and formulaically echo a collective past.