bluuebunny/crossref_metadata_2025 huggingface dataset:
The antibody drug conjugate VLS-101 targeting ROR1 is effective in CAR T-resistant mantle cell lymphoma
Authors: Jiang Vivian Changying , Liu Yang , Jordan Alexa , McIntosh Joseph , Li Yijing , Che Yuxuan , Jessen Katti A. , Lannutti Brian J. , Wang Michael
Published: August 2021

Mantle cell lymphoma (MCL) is a rare, aggressive and incurable subtype of non-Hodgkin’s B-cell lymphoma. The principal barrier is frequent clinical relapse to multiple lines of therapies, including new FDA-approved biologics and cell therapy. Brexucabtagene autoleucel, the first and only FDA approved chimeric antigen receptor (CAR) T product in MCL, demonstrated unprecedented efficacy in overcoming resistance to Bruton’s tyrosine kinase inhibitors. However, relapses have inevitably occurred and once relapsed these patients display a very poor clinical outcome. Currently, there is no optional therapy specifically designed for these patients. The development of tailored and more efficacious therapies is therefore critical and represents a new medical need. We found that while the receptor tyrosine kinase-like orphan receptor 1 (ROR1) is expressed across most of the MCL cells, it is significantly elevated in CAR T-relapsed MCL tumors. To see whether this aberrant ROR1 expression contributed to CAR T resistance, we targeted ROR1 using VLS-101, a monomethyl auristatin E conjugated anti-ROR1 antibody. VLS-101 showed potent anti-MCL activity in vitro in ROR1-expressing MCL cell lines and ex vivo in primary patient samples. Importantly, VLS-101 safely induced tumor regression in PDX models resistant to CAR T-cell therapy, ibrutinib and/or venetoclax. These data advocate for targeting ROR1 as a viable approach in the treatment of ROR1-positive MCL tumors, especially those with failure to prior therapies. These data also provide strong evidence for future enrollment of post-CD19 CAR T-cell relapsed MCL patients in a first in-human phase 1b VLS-101 trial. The upcoming testing in a clinical setting will provide important insights on this new therapeutic development aiming to overcome the CAR T resistance via targeting ROR1, which is a rising unmet clinical need in MCL.
The HIF1α-PDGFD-PDGFRα axis controls glioblastoma growth at normoxia/mild-hypoxia and confers sensitivity to targeted therapy by echinomycin
Authors: Peng Gong , Wang Yin , Ge Pengfei , Bailey Christopher , Zhang Peng , Zhang Di , Meng Zhaoli , Qi Chong , Chen Qian , Chen Jingtao , Niu Junqi , Zheng Pan , Liu Yang , Liu Yan
Published: September 2021

Background

Glioblastoma multiforme (GBM), a lethal brain tumor, remains the most daunting challenge in cancer therapy. Overexpression and constitutive activation of PDGFs and PDGFRα are observed in most GBM; however, available inhibitors targeting isolated signaling pathways are minimally effective. Therefore, better understanding of crucial mechanisms underlying GBM is needed for developing more effective targeted therapies.

Methods

Target genes controlled by HIF1α in GBM were identified by analysis of TCGA database and by RNA-sequencing of GBM cells with HIF1α knockout by sgRNA-Cas9 method. Functional roles of HIF1α, PDGFs and PDGFRs were elucidated by loss- or gain-of-function assays or chemical inhibitors, and compared in response to oxygen tension. Pharmacological efficacy and gene expression in mice with intracranial xenografts of primary GBM were analyzed by bioluminescence imaging and immunofluorescence.

Results

HIF1α binds the PDGFD proximal promoter and PDGFRA intron enhancers in GBM cells under normoxia or mild-hypoxia to induce their expression and maintain constitutive activation of AKT signaling, which in turn increases HIF1α protein level and activity. Paradoxically, severe hypoxia abrogates PDGFRα expression despite enhancing HIF1α accumulation and corresponding PDGF-D expression. Knockout of HIF1A, PDGFD or PDGFRA in U251 cells inhibits cell growth and invasion in vitro and eradicates tumor growth in vivo. HIF1A knockdown in primary GBM extends survival of xenograft mice, whereas PDGFD overexpression in GL261 shortens survival. HIF1α inhibitor Echinomycin induces GBM cell apoptosis and effectively inhibits growth of GBM in vivo by simultaneously targeting HIF1α-PDGFD/PDGFRα-AKT feedforward pathway.

Conclusions

HIF1α orchestrates expression of PDGF-D and PDGFRα for constitutive activation of AKT pathway and is crucial for GBM malignancy. Therefore, therapies targeting HIF1α should provide an effective treatment for GBM.
Prevalence of musculoskeletal injury and pain of UK‐based podiatrists and the impact of enforced altered working practices
Authors: Adams Robert , Branthwaite Helen , Chockalingam Nachiappan
Published: September 2021

Background

Occupational musculoskeletal injuries are prevalent in healthcare workers and are reported to be profession‐specific. There is, however, a paucity of information around the injuries sustained from working as a podiatrist. This paper looks at the incidence of injury from working as a podiatrist, the aggravating factors to sustain these injuries and whether the changes in workload due to the COVID‐19 pandemic altered the incidence.

Methods

A modified work based musculoskeletal injury questionnaire was distributed in the UK via podiatry led social media platforms. Open and Closed questions explored the demographics of the sample, perceived injury 12 months prior to the COVID‐19 pandemic and then 6 months into the lockdown. Pre and post COVID‐19 data were analysed for differences and thematic analysis was included to categorise reported experiences.

Results

148 podiatrists representing 3 % of HCPC registered practitioners responded to the questionnaire. Employment status altered as a result of the COVID‐19 pandemic with a 13 % reduction in those working full time. Environments also changed with domiciliary and telehealth significantly increasing (p > 0.00) and non‐clinical roles being extended (p > 0.002). Pain frequency and intensity significantly (p > 0.04) increased as a result of the pandemic with shoulder pain being most frequent before lockdown altering to the neck during the lockdown. Two main themes were identified that were attributed to the causes of pain including physical demands and working in awkward spaces.

Conclusions

Work‐related musculoskeletal pain in podiatrists is common with the shoulder and neck being the most frequently affected. Changes in work practices due to the restrictions enforced from the COVID‐19 pandemic increased the frequency and intensity of pain mostly associated with increased domiciliary and telehealth working environments.
“More air—better performance—faster recovery”: study protocol for randomised controlled trial of the effect of post-stroke inspiratory muscle training for adults
Authors: Sørensen Susanne Lillelund , Kjeldsen Simon Svanborg , Mortensen Sine Secher , Hansen Ulla Torp , Hansen Dorthe , Pedersen Asger Roger , Pallesen Hanne
Published: August 2021

Background

Stroke results in varying physical, cognitive, emotional and/or social disabilities in the short and long term alike. Motor impairments are important, persistent consequences of stroke and include, among others, decreased respiratory muscle function, decreased ability to expand the thorax and postural dysfunction. These deficits affect the patient’s ability to perform daily activities, produce fatigue and reduce endurance and quality of life. Inspiratory muscle training (IMT) aims to improve the strength and endurance of the diaphragm and the external intercostal muscles. The objectives of this study are to investigate the effect of 3 weeks of IMT on (i) maximal inspiratory pressure (MIP) in adults having suffered a stroke, as well as (ii) functional activities and expiratory measurements.

Methods/design

This is a randomised controlled trial (RCT) comparing IMT with conventional neurorehabilitation (usual practice). The trial will include 80 patients with reduced MIP hospitalised at a specialised neurorehabilitation hospital in Denmark. The intervention group will receive IMT sessions, exercising at 30% of MIP. Patients in the intervention group will perform two daily sessions (one session of IMT with Threshold IMT consisting of two times 15 inspirations at normal breathing rhythm (5–10 min)), 7 days a week for 3 weeks. Training can be with or without physiotherapist supervision. Study outcomes: MIP assessed by the Power Breath, Functional Independence Measurement, The 6-min walk test, the Fatigue Severity Scale and average voice volume. Expiratory function will be assessed using spirometry. All assessments will be conducted at baseline and 3 weeks (at termination of the intervention) and 3 months after the intervention has concluded.

Discussion

IMT is a promising and partly self-managed tool for rehabilitation to improve respiratory function. The introduction of IMT in combination with traditional physical therapy may enhance faster recovery after stroke and may at the same time demand little personnel resources to increase training intensity. This trial will provide further evidence of IMT to clinicians, patients and health managers. Hereby, this study accepts the call for further research.

Trial registration

ClinicalTrials.govNCT04686019. Registered on 28 December 2020.
A novel protist parasite, Salmoxcellia vastator n. gen., n. sp. (Xcelliidae, Perkinsozoa), infecting farmed salmonids in Norway
Authors: Karlsbakk Egil , Nystøyl Cecilie Flatnes , Plarre Heidrun , Nylund Are
Published: August 2021

Background

In Norway, x-cell parasites associated with disease in farmed salmonids have been known as a rare phenomenon for two decades. These parasites cause systemic infections in farmed rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar), but have so far not been characterized and described.

Methods

The x-cells from several cases of diseased fish were studied using light and electron microscopy, and by phylogenetic analysis based on small subunit ribosomal RNA (SSU rRNA) gene sequences.

Results

We describe here the x-cell parasite as a new species in a new genus, Salmoxcellia vastator n. gen., n. sp. Phylogenetic analyses placed Salmoxcellia n. gen. together with Gadixcellia among the xcelliids, a group of perkinsozoan alveolates. The new genus and species were found to have vacuolate plasmodial x-cells filled with lipid droplets, and an electron-dense alveolar pellicle. Electron-dense cytoplasmic inclusions, which are characteristic of the other xcelliid genera Xcellia and Gadixcellia, are lacking in Salmoxcellia n. gen. These x-cell plasmodia divide by plasmotomy and occur as aggregates in the host tissues, particularly in blood-rich tissues such as those of the kidney, red musculature, heart and liver. Host reaction and the refractive lipid droplets in the x-cells result in S. vastator n. gen., n. sp. aggregates appearing as white patches in the tissues.

Conclusions

We describe a new genus and species of xcelliid protist parasites from two very important farmed fish species and provide molecular methods for detection. The new parasite is associated with disease, but more importantly it has a spoiling effect on farmed salmonid fillets, rendering them unsuitable for sale. Consequently, this parasite represents a threat to the aquaculture industry.

Graphical abstract
Diversity of midgut bacteria in larvae and females of Aedes aegypti and Aedes albopictus from Gampaha District, Sri Lanka
Authors: Ranasinghe Koshila , Gunathilaka Nayana , Amarasinghe Deepika , Rodrigo Wasana , Udayanga Lahiru
Published: August 2021

Background

The midgut microbiota of mosquitoes maintain basal immune activity and immune priming. In recent years, scientists have focused on the use of microbial communities for vector control interventions. In the present study, the midgut bacteria of larvae and adults of Aedes aegypti and Ae. albopictus were assessed using both field-collected and laboratory-reared mosquitoes from Sri Lanka.

Methods

Adults and larvae of Ae. aegypti and Ae. albopictus were collected from three selected areas in Gampaha Medical Officer of Health area, Gampaha District, Western Province, Sri Lanka. Bacterial colonies isolated from mosquito midgut dissections were identified by PCR amplification and sequencing of partial 16S rRNA gene fragments.

Results

Adults and larvae of Ae. aegypti and Ae. albopictus harbored 25 bacterial species. Bacillus endophyticus and Pantoea dispersa were found more frequently in field-collected Ae. aegypti and Ae. albopictus adults, respectively. The midgut bacteria of Ae. aegypti and Ae. albopictus adults (X2 = 556.167, df = 72, P < 0.001) and larvae (X2 = 633.11, df = 66, P < 0.001) were significantly different. There was a significant difference among the bacterial communities between field-collected adults (X2 = 48.974, df = 10, P < 0.001) and larvae (X2 = 84.981, df = 10, P < 0.001). Lysinibacillus sphaericus was a common species in adults and larvae of laboratory-reared Ae. aegypti. Only P. dispersa occurred in the field-collected adults of Ae. aegypti and Ae. albopictus. Species belonging to genera Terribacillus, Lysinibacillus, Agromyces and Kocuria were recorded from Aedes mosquitoes, in accordance with previously reported results.

Conclusions

This study generated a comprehensive database on the culturable bacterial community found in the midgut of field-collected (Ae. aegypti and Ae. albopictus) and laboratory-reared (Ae. aegypti) mosquito larvae and adults from Sri Lanka. Data confirm that the midgut bacterial diversity in the studied mosquitoes varies according to species, developmental stage and strain (field vs laboratory).

Graphical abstract
Improved vector control of Triatoma infestans limited by emerging pyrethroid resistance across an urban-to-rural gradient in the Argentine Chaco
Authors: Gaspe María Sol , Cardinal Marta Victoria , Fernández María del Pilar , Vassena Claudia Viviana , Santo-Orihuela Pablo Luis , Enriquez Gustavo Fabián , Alvedro Alejandra , Laiño Mariano Alberto , Nattero Julieta , Alvarado-Otegui Julián Antonio , Macchiaverna Natalia Paula , Cecere María Carla , Freilij Héctor , Gürtler Ricardo Esteban
Published: August 2021

Background

The sustainable elimination of Triatoma infestans in the Gran Chaco region represents an enduring challenge. Following the limited effects of a routine pyrethroid insecticide spraying campaign conducted over 2011–2013 (first period) in Avia Terai, an endemic municipality with approximately 2300 houses, we implemented a rapid-impact intervention package to suppress house infestation across the urban-to-rural gradient over 2015–2019 (second period). Here, we assess their impacts and whether persisting infestations were associated with pyrethroid resistance.

Methods

The 2011–2013 campaign achieved a limited detection and spray coverage across settings (< 68%), more so during the surveillance phase. Following community mobilization and school-based interventions, the 2015–2019 program assessed baseline house infestation using a stratified sampling strategy; sprayed all rural houses with suspension concentrate beta-cypermethrin, and selectively sprayed infested and adjacent houses in urban and peri-urban settings; and monitored house infestation and performed selective treatments over the follow-up.

Results

Over the first period, house infestation returned to pre-intervention levels within 3–4 years. The adjusted relative odds of house infestation between 2011–2013 and 2015–2016 differed very little (adj. OR: 1.17, 95% CI 0.91–1.51). Over the second period, infestation decreased significantly between 0 and 1 year post-spraying (YPS) (adj. OR: 0.36, 95% CI 0.28–0.46), with heterogeneous effects across the gradient. Mean bug abundance also dropped between 0 and 1 YPS and thereafter remained stable in rural and peri-urban areas. Using multiple regression models, house infestation and bug abundance at 1 YPS were 3–4 times higher if the house had been infested before treatment, or was scored as high-risk or non-participating. No low-risk house was ever infested. Persistent foci over two successive surveys increased from 30.0 to 59.3% across the gradient. Infestation was more concentrated in peridomestic rather than domestic habitats. Discriminating-dose bioassays showed incipient or moderate pyrethroid resistance in 7% of 28 triatomine populations collected over 2015–2016 and in 83% of 52 post-spraying populations.

Conclusions

The intervention package was substantially more effective than the routine insecticide spraying campaign, though the effects were lower than predicted due to unexpected incipient or moderate pyrethroid resistance. Increased awareness and diagnosis of vector control failures in the Gran Chaco, including appropriate remedial actions, are greatly needed.

Graphical abstract
Seeing the forest through the trees: prioritising potentially functional interactions from Hi-C
Authors: Liu Ning , Low Wai Yee , Alinejad-Rokny Hamid , Pederson Stephen , Sadlon Timothy , Barry Simon , Breen James
Published: August 2021

Eukaryotic genomes are highly organised within the nucleus of a cell, allowing widely dispersed regulatory elements such as enhancers to interact with gene promoters through physical contacts in three-dimensional space. Recent chromosome conformation capture methodologies such as Hi-C have enabled the analysis of interacting regions of the genome providing a valuable insight into the three-dimensional organisation of the chromatin in the nucleus, including chromosome compartmentalisation and gene expression. Complicating the analysis of Hi-C data, however, is the massive amount of identified interactions, many of which do not directly drive gene function, thus hindering the identification of potentially biologically functional 3D interactions. In this review, we collate and examine the downstream analysis of Hi-C data with particular focus on methods that prioritise potentially functional interactions. We classify three groups of approaches: structural-based discovery methods, e.g. A/B compartments and topologically associated domains, detection of statistically significant chromatin interactions, and the use of epigenomic data integration to narrow down useful interaction information. Careful use of these three approaches is crucial to successfully identifying potentially functional interactions within the genome.
A transcriptome-wide association study of Alzheimer’s disease using prediction models of relevant tissues identifies novel candidate susceptibility genes
Authors: Sun Yanfa , Zhu Jingjing , Zhou Dan , Canchi Saranya , Wu Chong , Cox Nancy J. , Rissman Robert A. , Gamazon Eric R. , Wu Lang
Published: September 2021

Background

Genome-wide association studies (GWAS) have identified over 56 susceptibility loci associated with Alzheimer’s disease (AD), but the genes responsible for these associations remain largely unknown.

Methods

We performed a large transcriptome-wide association study (TWAS) leveraging modified UTMOST (Unified Test for MOlecular SignaTures) prediction models of ten brain tissues that are potentially related to AD to discover novel AD genetic loci and putative target genes in 71,880 (proxy) cases and 383,378 (proxy) controls of European ancestry.

Results

We identified 53 genes with predicted expression associations with AD risk at Bonferroni correction threshold (P value < 3.38 × 10−6). Based on fine-mapping analyses, 21 genes at nine loci showed strong support for being causal.

Conclusions

Our study provides new insights into the etiology and underlying genetic architecture of AD.
Innovative method of alopecia treatment by autologous adipose-derived SVF
Authors: Kim Sun Jong , Kim Myung Jin , Lee Young Jun , Lee Joo Chan , Kim Ji Hyang , Kim Do Ha , Do Young Hoo , Choi Jun Woo , Chung Sung Ill , Do Byung-Rok
Published: August 2021

Background

Alopecia refers to a condition developed by gradual reduction of hair loss by various abnormal causes such as endocrine system, genetic factors, and stress. Stromal vascular fraction (SVF) isolated from the fat is one of the latest innovative solutions in the field of regeneration therapy. We focused on presenting effectiveness of clinical cases to improve AGA through transplantation of autologous SVF into the scalp.

Objective

To confirm the efficacy of the autologous SVF usage to the patients with AGA.

Methods

Nine patients (age range 43–64 years; 4 men, grade IV to V and 5 women, grade I to III), who are suffering from androgenic alopecia (AGA), were treated with single transplantation of autologous SVF in the upper scalp. Autologous SVF was isolated and characterized prior to the injection of live 7–9 × 106 cells into the patients’ treatment site. The hair loss improvement effect was assessed by three test criteria: hair skin quality, hair thickness and hair density 3 and 6 months after post-injection compared to pre-injection status.

Results

Hair density of SVF-treated side was significantly increased after 3 and 6 months of transplantation compared to non-treated side (P = 0.01 and P = 0.009 per each). And significant improvement in the score of the keratin on the scalp was seen in the injected area as compared to the non-injected area 6 months after transplantation (P = 0.032). Although thickness increase was observed at 3 and 6 months after transplantation, there was no statistical significance (P = 0.142 and 0.155, respectively).

Conclusions

One transplantation of autologous SVF for the AGA patients, hair density and score for the keratin were significantly increased within 6 months. This study shows that SVF is a very effective way to treat hair loss and most of subjects are satisfied with the result after treatment.
Correlation of in vivo imaging to morphomolecular pathology in translational research: challenge accepted
Authors: Ballke Simone , Heid Irina , Mogler Carolin , Braren Rickmer , Schwaiger Markus , Weichert Wilko , Steiger Katja
Published: August 2021

Correlation of in vivo imaging to histomorphological pathology in animal models requires comparative interdisciplinary expertise of different fields of medicine. From the morphological point of view, there is an urgent need to improve histopathological evaluation in animal model-based research to expedite translation into clinical applications. While different other fields of translational science were standardized over the last years, little was done to improve the pipeline of experimental pathology to ensure reproducibility based on pathological expertise in experimental animal models with respect to defined guidelines and classifications. Additionally, longitudinal analyses of preclinical models often use a variety of imaging methods and much more attention should be drawn to enable for proper co-registration of in vivo imaging methods with the ex vivo morphological read-outs. Here we present the development of the Comparative Experimental Pathology (CEP) unit embedded in the Institute of Pathology of the Technical University of Munich during the Collaborative Research Center 824 (CRC824) funding period together with selected approaches of histomorphological techniques for correlation of in vivo imaging to morphomolecular pathology.
Three broad classifications of acute respiratory failure etiologies based on regional ventilation and perfusion by electrical impedance tomography: a hypothesis-generating study
Authors: He Huaiwu , Chi Yi , Long Yun , Yuan Siyi , Zhang Rui , Yang Yingying , Frerichs Inéz , Möller Knut , Fu Feng , Zhao Zhanqi
Published: August 2021

Background

The aim of this study was to validate whether regional ventilation and perfusion data measured by electrical impedance tomography (EIT) with saline bolus could discriminate three broad acute respiratory failure (ARF) etiologies.

Methods

Perfusion image was generated from EIT-based impedance–time curves caused by 10 ml 10% NaCl injection during a respiratory hold. Ventilation image was captured before the breath holding period under regular mechanical ventilation. DeadSpace%, Shunt% and VQMatch% were calculated based on lung perfusion and ventilation images. Ventilation and perfusion maps were divided into four cross-quadrants (lower left and right, upper left and right). Regional distribution defects of each quadrant were scored as 0 (distribution% ≥ 15%), 1 (15% > distribution% ≥ 10%) and 2 (distribution% < 10%). Data percentile distributions in the control group and clinical simplicity were taken into consideration when defining the scores. Overall defect scores (DefectV, DefectQ and DefectV+Q) were the sum of four cross-quadrants of the corresponding images.

Results

A total of 108 ICU patients were prospectively included: 93 with ARF and 15 without as a control. PaO2/FiO2 was significantly correlated with VQMatch% (r = 0.324, P = 0.001). Three broad etiologies of ARF were identified based on clinical judgment: pulmonary embolism-related disease (PED, n = 14); diffuse lung involvement disease (DLD, n = 21) and focal lung involvement disease (FLD, n = 58). The PED group had a significantly higher DeadSpace% [40(24)% vs. 14(15)%, PED group vs. the rest of the subjects; median(interquartile range); P < 0.0001] and DefectQ score than the other groups [1(1) vs. 0(1), PED vs. the rest; P < 0.0001]. The DLD group had a significantly lower DefectV+Q score than the PED and FLD groups [0(1) vs. 2.5(2) vs. 3(3), DLD vs. PED vs. FLD; P < 0.0001]. The FLD group had a significantly higher DefectV score than the other groups [2(2) vs. 0(1), FLD vs. the rest; P < 0.0001]. The area under the receiver operating characteristic (AUC) for using DeadSpace% to identify PED was 0.894 in all ARF patients. The AUC for using the DefectV+Q score to identify DLD was 0.893. The AUC for using the DefectV score to identify FLD was 0.832.

Conclusions

Our study showed that it was feasible to characterize three broad etiologies of ARF with EIT-based regional ventilation and perfusion. Further study is required to validate clinical applicability of this method.

Trial registration clinicaltrials, NCT04081142. Registered 9 September 2019—retrospectively registered, https://clinicaltrials.gov/show/NCT04081142.
An online algorithm for echo cancellation, dereverberation and noise reduction based on a Kalman-EM Method
Authors: Cohen Nili , Hazan Gershon , Schwartz Boaz , Gannot Sharon
Published: August 2021

Many modern smart devices are equipped with a microphone array and a loudspeaker (or are able to connect to one). Acoustic echo cancellation algorithms, specifically their multi-microphone variants, are essential components in such devices. On top of acoustic echos, other commonly encountered interference sources in telecommunication systems are reverberation, which may deteriorate the desired speech quality in acoustic enclosures, specifically if the speaker distance from the array is large, and noise. Although sub-optimal, the common practice in such scenarios is to treat each problem separately. In the current contribution, we address a unified statistical model to simultaneously tackle the three problems. Specifically, we propose a recursive EM (REM) algorithm for solving echo cancellation, dereverberation and noise reduction. The proposed approach is derived in the short-time Fourier transform (STFT) domain, with time-domain filtering approximated by the convolutive transfer function (CTF) model. In the E-step, a Kalman filter is applied to estimate the near-end speaker, based on the noisy and reveberant microphone signals and the echo reference signal. In the M-step, the model parameters, including the acoustic systems, are inferred. Experiments with human speakers were carried out to examine the performance in dynamic scenarios, including a walking speaker and a moving microphone array. The results demonstrate the efficiency of the echo canceller in adverse conditions together with a significant reduction in reverberation and noise. Moreover, the tracking capabilities of the proposed algorithm were shown to outperform baseline methods.
Emergent technologies, divergent frames: differences in regulator vs. developer views on innovation
Authors: Keisler Jeffrey M. , Trump Benjamin D. , Wells Emily , Linkov Igor
Published: August 2021

Technology innovation is inherently uncertain. The risk–benefit divide for such innovation is a classical debate within scholarly literature and is often framed on a monetary scale where innovation approval is granted if benefit outweighs risk. However, such discussion leaves out a critical yet subjective vein of discussion within the innovation evaluation process — stakeholder context. Specifically, regulators and technology developers are often described as having respective motivations that are often at odds with one another. In theory, efforts towards balancing risk and benefit for technology evaluation should be driven by relatively efficient, inexpensive, robust methods, and processes. In practice, however, technology evaluation is often expensive, slow, and often of questionable quality for new and emerging technologies. Literature often frames the innovation-regulation tradeoff as a zero-sum game driven by regulators and developers that are inherently at odds with one another. However, we argue that such a relationship is actually worse than zero-sum and is a classic framing problem as described by Kahneman and Tversky. Specifically, the divergent frames adopted by regulators and technology developers, respectively, can drastically affect their perception of risk and tolerance for further development and commercialization of a given technology. There are known and natural solutions to such problems that can smooth the path towards realizing the societal potential of emerging technologies.
The impact of COVID-19 on eating disorder referrals and admissions in Waikato, New Zealand
Authors: Hansen Sara J. , Stephan Alice , Menkes David B.
Published: August 2021

Background

Several countries have reported increased demand for eating disorder services during the COVID-19 pandemic, particularly for adolescents. Within New Zealand, anecdotal and media reports suggest similar changes but are limited in scope and detail. We assessed eating disorder service demand in the Waikato district in relation to the COVID-19 pandemic.

Methods

We retrospectively analysed records of eating disorder admissions and referrals for both children (< 18 years) and adults (≥ 18 years) during 2019 and 2020 in the Waikato, a mixed urban–rural province in northern New Zealand (population 435,000). We analysed medical admission and outpatient referral rates, and referral acuity, in relation to the COVID-19 pandemic using Welch’s t- and chi-square tests.

Results

106 medical admissions met inclusion criteria (n = 37 in 2019; 69 in 2020). Admissions for eating disorders increased markedly following nationwide lockdown in March 2020 (RR = 1.7, p = 0.01), largely driven by increases in adult admissions (RR 2.0, p = 0.005). The proportion of ‘new patient’ admissions showed comparable increases for both children (RR = 2.0, p = 0.02) and adults (RR = 2.3, p = 0.03). Following lockdown, outpatient referrals increased in acuity (RR = 1.8, p = 0.047) and volume (RR = 1.6, p = 0.076) for children but not for adults.

Conclusions

Our study confirms a pandemic-related increase in demand for eating disorder services in the Waikato region of New Zealand, consistent with findings reported overseas. We observed contrasting increases in admissions for adults and outpatient referrals for children, exacerbating resource constraints for already stretched services and compromising provision of timely care.

Plain English summary

The COVID-19 pandemic has been linked to increased numbers and worsening severity of eating disorders in several settings. In New Zealand, similar trends have been noted anecdotally. We assessed clinical records to calculate rates of eating disorder-related hospital admissions and outpatient referrals during 2019 and 2020. We found significant increases in hospital admissions related to COVID-19, particularly for adults, and greater proportions of both children and adults having a first-ever eating disorder-related admission. In outpatient services, young people were referred more frequently during the pandemic and were more physically unwell when referred. These results indicate increased demand for eating disorder services as a result of the pandemic and complement findings reported overseas.
Implementing a formative assessment model at the secondary schools: attitudes and challenges
Authors: Rahman Kh. Atikur , Hasan Md. Kamrul , Namaziandost Ehsan , Ibna Seraj Prodhan Mahbub
Published: September 2021

This paper aims at exploring the issues related to implementing a formative assessment model namely School-Based Assessment (SBA) at secondary schools in Bangladesh. A qualitative study employing interviews with English teachers of grade 8 and the head teachers and FGDs with students from twelve secondary schools was conducted. Moreover, field notes and document analysis provided valuable data. The findings from the qualitative content analysis showed a dismal condition of implementing SBA in Bangladesh. Some distinct reasons posed challenges to implementing SBA. These are teachers’ insufficient orientation towards SBA, teachers’ negative attitude towards SBA, teachers’ heavy workloads, large class size, large contents of syllabus, no reflection of the marks of SBA in public examinations, lack of honesty and fairness in teachers, lack of validity and reliability of SBA as an assessment tool, poor socio-economic conditions of teachers, and the absence of monitoring and supervision by concerned authorities. This study also provides a comprehensive understanding of how teachers conceptualize and apply strategies of SBA in their classrooms, along with some recommendations and, hence, bears implications for the policy makers, teacher trainers, and other stakeholders involved in the Bangladeshi school education system and elsewhere.
Mini Hyrax vs Hyrax expanders in the rapid palatal expansion in adolescents with posterior crossbite: a randomized controlled clinical trial
Authors: Silveira Giordani Santos , Abreu Lucas Guimarães , Palomo Juan Martin , da Matta Cid Pinto Larissa Salgado , de Sousa Adriana Alkmim , Gribel Bruno Frazão , Oliveira Dauro Douglas
Published: September 2021

Purpose

The aim of this study was to compare the dental effects, impact on quality of life, and pain perception of adolescents wearing Mini Hyrax and Hyrax expanders in rapid palatal expansion.

Methods

Thirty-four adolescents aged 11 to 16 years, with maxillary transverse deficiency (unilateral or bilateral posterior crossbite), were randomly allocated into two groups, Mini Hyrax group and Hyrax group (1:1 ratio). Dental effects were evaluated by digitally superimposed pretreatment and postretention three-dimensional intraoral scans on the palatal rugaes using the software 3DSlicer. Impact on quality of life was assessed with the OHIP-14 questionnaire applied in the pretreatment, posttreatment and postretention. Visual analog scale was applied 24, 48, and 72 h and 7 days after the first activation of the expander.

Results

Thirty of the 34 adolescents recruited completed the study. There were no statistically significant differences in dentoalveolar effects between groups. OHIP-14 scores across time among Mini Hyrax wearers were similar to those of the Hyrax wearers. The inter-group comparisons showed no difference between groups with respect to the OHIP-14 scores in posttreatment and postretention (p > 0.05). There were no differences in pain perception between groups. Considering intra-group comparison, the reduction in pain perception among adolescents in the Mini Hyrax group was gradual. Among adolescents in the Hyrax group, a statistically significant reduction between 48 and 72 h was observed.

Conclusion

There were no significant differences in dental effects, impact on quality of life and pain perception between adolescents wearing Mini Hyrax and Hyrax expanders in rapid palatal expansion.
Data-driven gated PET/CT: implications for lesion segmentation and quantitation
Authors: Thomas M. Allan , Pan Tinsu
Published: August 2021

Background

Data-driven gating (DDG) can improve PET quantitation and alleviate many issues with patient motion. However, misregistration between DDG-PET and CT may occur due to the distinct temporal resolutions of PET and CT and can be mitigated by DDG-CT. Here, the effects of misregistration and respiratory motion on PET quantitation and lesion segmentation were assessed with a new DDG-PET/CT method.

Methods

A low-dose cine-CT was acquired in misregistered regions to enable both average CT (ACT) and DDG-CT. The following were compared: (1) baseline PET/CT, (2) PET/ACT (attenuation correction, AC = ACT), (3) DDG-PET (AC = helical CT), and (4) DDG-PET/CT (AC = DDG-CT). For DDG-PET, end-expiration (EE) data were derived from 50% of the total PET data at 30% from end-inspiration. For DDG-CT, EE phase CT data were extracted from cine-CT data by lung Hounsfield unit (HU) value and body contour. A total of 91 lesions from 16 consecutive patients were assessed for changes in standard uptake value (SUV), lesion glycolysis (LG), lesion volume, centroid-to-centroid distance (CCD), and DICE coefficients.

Results

Relative to baseline PET/CT, median changes in SUVmax ± σ for all 91 lesions were 20 ± 43%, 26 ± 23%, and 66 ± 66%, respectively, for PET/ACT, DDG-PET, and DDG-PET/CT. Median changes in lesion volume were 0 ± 58%, − 36 ± 26%, and − 26 ± 40%. LG for individual lesions increased for PET/ACT and decreased for DDG-PET, but was not different for DDG-PET/CT. Changes in mean HU from baseline PET/CT were dramatic for most lesions in both PET/ACT and DDG-PET/CT, especially for lesions with mean HU < 0 at baseline. CCD and DICE were both affected more by motion correction with DDG-PET than improved registration with ACT or DDG-CT.

Conclusion

As misregistration becomes more prominent, the impact of motion correction with DDG-PET is diminished. The potential benefits of DDG-PET toward accurate lesion segmentation and quantitation could only be fully realized when combined with DDG-CT. These results impress upon the necessity of ensuring both misregistration and motion correction are accounted for together to optimize the clinical utility of PET/CT.
Effect of crown-to-implant ratio and crown height space on marginal bone stress: a finite element analysis
Authors: da Rocha Ferreira José Joaquim , Machado Luís Filipe Meira , Oliveira José Manuel , Ramos João Carlos Tomás
Published: September 2021

Background

Crown-to-implant ratio and crown height space, associated with the use of short implants, have been related with marginal bone loss. However, it is unclear which of the two entities would play the most important role on the bone remodelling process. Using a finite element analysis, the present work aims to help clarifying how those two factors contribute for the stress generation at the marginal bone level. A numerical model (reference model), with a crown-to-implant ratio of 4, was double validated and submitted to a numerical calculation. Then, it was modified in two different ways: (a) by decreasing the prosthetic height obtaining crown-to-implant ratios of 3, 2.5 and 2 and (b) by increasing the implants length obtaining a crown-to-implant ratio of 2.08. The new models were also submitted to numerical calculations.

Results

The reference model showed a marginal bone stress of 96.9 MPa. The increase in the implants’ length did not show statistically significant differences in the marginal bone stress (p-value = 0.2364). The decrease in the prosthetic height was accompanied with a statistically significant decrease in the marginal bone stresses (p-value = 2.2e− 16).

Conclusions

The results represent a paradigm change as the crown height space appears to be more responsible for marginal bone stress than the high crown-to-implant ratios or the implants’ length. New prosthetic designs should be attempted to decrease the stress generated at the marginal bone level.
Differences in gene expression and variable splicing events of ovaries between large and small litter size in Chinese Xiang pigs
Authors: Ran Xueqin , Hu Fengbin , Mao Ning , Ruan Yiqi , Yi Fanli , Niu Xi , Huang Shihui , Li Sheng , You Longjiang , Zhang Fuping , Tang Liangting , Wang Jiafu , Liu Jianfeng
Published: September 2021

Background

Although lots of quantitative trait loci (QTLs) and genes present roles in litter size of some breeds, the information might not make it clear for the huge diversity of reproductive capability in pig breeds. To elucidate the inherent mechanisms of heterogeneity of reproductive capability in litter size of Xiang pig, we performed transcriptome analysis for the expression profile in ovaries using RNA-seq method.

Results

We identified 1,419 up-regulated and 1,376 down-regulated genes in Xiang pigs with large litter size. Among them, 1,010 differentially expressed genes (DEGs) were differently spliced between two groups with large or small litter sizes. Based on GO and KEGG analysis, numerous members of genes were gathered in ovarian steroidogenesis, steroid biosynthesis, oocyte maturation and reproduction processes.

Conclusions

Combined with gene biological function, twelve genes were found out that might be related with the reproductive capability of Xiang pig, of which, eleven genes were recognized as hub genes. These genes may play a role in promoting litter size by elevating steroid and peptide hormones supply through the ovary and facilitating the processes of ovulation and in vivo fertilization.
Prevalence, awareness, and control of hypertension among Bangladeshi adults: an analysis of demographic and health survey 2017–18
Authors: Al Kibria Gulam Muhammed , Gupta Rajat Das , Nayeem Jannatun
Published: September 2021

Background

The prevalence of hypertension is increasing in Bangladesh, however, few recent studies investigated the proportion of people and factors associated with prevalence, awareness, and control of this condition in this country. This study investigated these among Bangladeshi adults.

Methods

Using Bangladesh Demographic and Health Survey 2017–18 data, a cross-sectional study was conducted. Multilevel logistic regression analysis was employed after descriptive analysis and prevalence estimation.

Results

Among 12,926 persons (mean age: 40 years, 57% women), the prevalence of hypertension was 27.4% (n = 3551), it was 28.4 and 26.2% among females and males, respectively. Among hypertensive people, about 42.4% (n = 1508) people were aware of having it, 48.7% among females and 33.5% among males. Of the 1313 people who were taking antihypertensive medication, only 33.8% (n = 443) had controlled hypertension, 34.7 and 31.7% among females and males, respectively.

Among the studied factors associated with hypertension, people with older age, female gender, overweight/obesity, diabetes, richer wealth quintiles, and residence in some administrative divisions had higher odds of hypertension (p < 0.05). However, the odds of awareness was lower among younger people, males, and people without overweight/obesity, diabetes, or richer wealth quintiles. Odds of controlled hypertension was also lower among people with older age and higher among college-educated people.

Conclusion

This study identified several important factors associated with prevalence, awareness, and control of hypertension. It is important to address these factors with nationwide prevention and control programs.
The use of digital storytelling of patients’ stories as an approach to translating knowledge: a scoping review
Authors: Park Elly , Forhan Mary , Jones C. Allyson
Published: August 2021

Background

A growing interest has centered on digital storytelling in health research, described as a multi-media presentation of a story using technology. The use of digital storytelling in knowledge translation (KT) is emerging as technology advances in healthcare to address the challenging tasks of disseminating and transferring knowledge to key stakeholders. We conducted a scoping review of the literature available on the use of patient digital storytelling as a tool in KT interventions.

Methods

We followed by Arksey and O’Malley (Int J Soc Res Methodol 8(1):19–32, 2005), and Levac et al. (Implement Sci 5(1):69, 2010) recommended steps for scoping reviews. Search strategies were conducted for electronic databases (Medline, CINAHL, Web of Science, ProQuest dissertations and theses global, Clinicaltrials.gov and Psychinfo). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) was used to report the review process.

Results

Of 4656 citations retrieved, 114 full texts were reviewed, and twenty-one articles included in the review. Included studies were from nine countries and focused on an array of physical and mental health conditions. A broad range of interpretations of digital storytelling and a variety of KT interventions were identified. Digital storytelling was predominately defined as a story in multi-media form, presented as a video, for selective or public viewing and used as educational material for healthcare professionals, patients and families.

Conclusion

Using digital storytelling as a tool in KT interventions can contribute to shared decision-making in healthcare and increase awareness in patients’ health related experiences. Concerns centered on the accuracy and reliability of some of the information available online and the impact of digital storytelling on knowledge action and implementation.
Fluorescein angiographic findings and Behcet's disease ocular attack score 24 (BOS24) as prognostic factors for visual outcome in patients with ocular Behcet's disease
Authors: Keorochana Narumon , Homchampa Nathamon , Vongkulsiri Sritatath , Choontanom Raveewan
Published: August 2021

Purpose

To determine the application of fluorescein angiographic (FA) findings and Behcet’s disease ocular attack score 24 (BOS24) scoring system in predicting poor visual outcome in patients with ocular Behcet’s disease.

Study design

Retrospective cohort study.

Methods

We included 73 eyes of 38 patients with ocular Behcet’s disease who underwent FA and reviewed FA images, anterior chamber cells, vitreous opacity, retinal and optic disc lesions, which are parameters in BOS24. The correlation between FA findings, BOS24, and visual acuity was assessed.

Results

Optic disc hyperfluoresence (74%), diffuse posterior pole leakage (52%) and diffuse peripheral leakage (52%) were the three most common findings. Common complications were peripheral capillary nonperfusion (29%), arterial narrowing (22%), and macular ischemia (19%). BOS24 scores of ≥ 6 (p < 0.0001), arterial narrowing (p < 0.0001), and severe posterior pole leakage (p = 0.004) were significantly associated with poor visual outcome. Combining significant FA findings: arterial narrowing and severe posterior pole leakage, to BOS24 ≥ 6 results in an increased relative risk of developing poor visual acuity from 7.30 to 10.43 and 1.89 to 2.02 respectively.

Conclusion

Fluorescein angiography is an important investigation for predicting poor visual outcome. BOS24 may be a useful alternative when fluorescein angiographic is unavailable.