bluuebunny/crossref_metadata_2025 huggingface dataset:
How I Teach It: Per Oral Endoscopic Myotomy (POEM)
Authors: Hashimoto Daniel A. , Lyons Joshua , Marks Jeffrey M.
Published: September 2022

Per oral endoscopic myotomy (POEM) is an endoscopic procedure for the management of achalasia. The basic steps of POEM include (1) diagnostic esophagogastroduodenoscopy, (2) mucosotomy, (3) submucosal tunneling, (4) myotomy, and (5) mucosal closure. An educational pathway composed of observation, simulation, intraoperative education, and proctorship can allow endoscopists to safely learn POEM for independent practice.
Functional and radiological outcomes after treatment of congenital pseudarthrosis of the tibia using the Ilizarov technique: a retrospective single-center study
Authors: Zayda Ahmed Ibrahim , Mesregah Mohamed Kamal , Zalalo Soliman Hassan , Sakr Samy Abdel-Hady
Published: September 2022

Background

Congenital pseudarthrosis of the tibia (CPT) is a challenging problem in orthopedic practice, with high rates of non-union, refracture, and residual deformities. After union, long-term follow-up is required to manage late post-union complications. This study aimed to assess the outcomes of the Ilizarov technique in the management of CPT.

Materials and methods

This retrospective study included patients with CPT treated with the Ilizarov method between 2005 and 2018. Intramedullary rods were used in 9 cases and iliac bone graft was used in 12 cases. An orthosis was applied till the end of follow-up in all cases. The American Orthopaedic Foot and Ankle Society (AOFAS) scale was used for the evaluation of the functional outcomes.

Results

This study included 16 patients, 11 males and 5 females, with an average age of 5.4 ± 2.8 years. Seven cases had multiple previous surgeries. Six patients had neurofibromatosis. The mean follow-up period was 5.8 ± 3.4 years. The average AOFAS score improved significantly from 47.5 ± 7.6 preoperatively to 78.9 ± 8.9 at the latest follow-up.

Union was achieved in 15 cases, and persistent non-union occurred in one case. The clinical results were excellent in one patient, good in seven cases, fair in 6, and poor in 2 cases. The radiological results were excellent in one patient, good in seven cases, fair in seven, and poor in one case.

Conclusions

The Ilizarov technique combined with intramedullary rod and primary or secondary bone graft provides a high union rate of CPT and can achieve simultaneous effective management of problems related to pseudarthrosis, including non-union, deformity, limb shortening, and adjacent joint contracture and subluxation.

Level of evidence Level IV.
Local data commons: the sleeping beauty in the community of data commons
Authors: Jeong Jong Cheol , Hands Isaac , Kolesar Jill M. , Rao Mahadev , Davis Bront , Dobyns York , Hurt-Mueller Joseph , Levens Justin , Gregory Jenny , Williams John , Witt Lisa , Kim Eun Mi , Burton Carlee , Elbiheary Amir A. , Chang Mingguang , Durbin Eric B.
Published: September 2022

Background

Public Data Commons (PDC) have been highlighted in the scientific literature for their capacity to collect and harmonize big data. On the other hand, local data commons (LDC), located within an institution or organization, have been underrepresented in the scientific literature, even though they are a critical part of research infrastructure. Being closest to the sources of data, LDCs provide the ability to collect and maintain the most up-to-date, high-quality data within an organization, closest to the sources of the data. As a data provider, LDCs have many challenges in both collecting and standardizing data, moreover, as a consumer of PDC, they face problems of data harmonization stemming from the monolithic harmonization pipeline designs commonly adapted by many PDCs. Unfortunately, existing guidelines and resources for building and maintaining data commons exclusively focus on PDC and provide very little information on LDC.

Results

This article focuses on four important observations. First, there are three different types of LDC service models that are defined based on their roles and requirements. These can be used as guidelines for building new LDC or enhancing the services of existing LDC. Second, the seven core services of LDC are discussed, including cohort identification and facilitation of genomic sequencing, the management of molecular reports and associated infrastructure, quality control, data harmonization, data integration, data sharing, and data access control. Third, instead of commonly developed monolithic systems, we propose a new data sharing method for data harmonization that combines both divide-and-conquer and bottom-up approaches. Finally, an end-to-end LDC implementation is introduced with real-world examples.

Conclusions

Although LDCs are an optimal place to identify and address data quality issues, they have traditionally been relegated to the role of passive data provider for much larger PDC. Indeed, many LDCs limit their functions to only conducting routine data storage and transmission tasks due to a lack of information on how to design, develop, and improve their services using limited resources. We hope that this work will be the first small step in raising awareness among the LDCs of their expanded utility and to publicize to a wider audience the importance of LDC.
Genetic architecture of berry aroma compounds in a QTL (quantitative trait loci) mapping population of interspecific hybrid grapes (Vitis labruscana × Vitis vinifera)
Authors: Koyama Kazuya , Kono Atsushi , Ban Yusuke , Bahena-Garrido Sharon Marie , Ohama Tomoko , Iwashita Kazuhiro , Fukuda Hisashi , Goto-Yamamoto Nami
Published: September 2022

Background

Although grapes accumulate diverse groups of volatile compounds, their genetic regulation in different cultivars remains unelucidated. Therefore, this study investigated the volatile composition in the berries of an interspecific hybrid population from a Vitis labruscana ‘Campbell Early’ (CE) × Vitis vinifera ‘Muscat of Alexandria’ (MA) cross to understand the relationship among volatile compounds and their genetic regulation. Then, a quantitative trait locus (QTL) analysis of its volatile compounds was conducted.

Results

While MA contained higher concentrations of monoterpenes and norisoprenoids, CE contained higher concentrations of C6 compounds, lactones and shikimic acid derivatives, including volatiles characteristic to American hybrids, i.e., methyl anthranilate, o-aminoacetophenone and mesifurane. Furthermore, a cluster analysis of volatile profiles in the hybrid population discovered ten coordinately modulated free and bound volatile clusters. QTL analysis identified a major QTL on linkage group (LG) 5 in the MA map for 14 monoterpene concentrations, consistent with a previously reported locus. Additionally, several QTLs detected in the CE map affected the concentrations of specific monoterpenes, such as linalool, citronellol and 1,8-cineol, modifying the monoterpene composition in the berries. As for the concentrations of five norisoprenoids, a major common QTL on LG2 was discovered first in this study. Several QTLs with minor effects were also discovered in various volatile groups, such as lactones, alcohols and shikimic acid derivatives.

Conclusions

An overview of the profiles of aroma compounds and their underlying QTLs in a population of interspecific hybrid grapes in which muscat flavor compounds and many other aroma compounds were mixed variously were elucidated. Coordinate modulation of the volatile clusters in the hybrid population suggested an independent mechanism for controlling the volatiles of each group. Accordingly, specific QTLs with significant effects were observed for terpenoids, norisoprenoids and some volatiles highly contained in CE berries.
Increased risk of preterm delivery with high cortisol during pregnancy is modified by fetal sex: a cohort study
Authors: Oaks Brietta M. , Adu-Afarwuah Seth , Ashorn Per , Lartey Anna , Laugero Kevin D. , Okronipa Harriet , Stewart Christine P. , Dewey Kathryn G.
Published: September 2022

Background

Previous studies show an association between maternal plasma and salivary cortisol and preterm birth but have been primarily conducted in high-income countries. It is unknown whether salivary cortisol is a risk factor for preterm birth in Ghana. Our objective was to determine whether maternal salivary cortisol during pregnancy was associated with pregnancy duration and preterm delivery in Ghana.

Methods

We conducted a cohort study of 783 pregnant women in Ghana. We measured salivary cortisol at baseline (mean 16 wk), 28 wk., and 36 wk. gestation. Pregnancy duration was determined primarily by ultrasound. We used adjusted linear regression models to examine the association between cortisol and pregnancy duration and Poisson regression models to determine the risk of preterm delivery among women with high cortisol at baseline or 28 wk. gestation.

Results

Mean pregnancy duration was 39.4 ± 1.8 wk. and 6.6% had a preterm delivery. Mean maternal cortisol increased throughout pregnancy, from 4.9 ± 2.7 nmol/L at baseline (16 wk) to 6.4 ± 3.2 nmol/L at 28 wk. and 7.9 ± 3.0 nmol/L at 36 wk. gestation. In adjusted analyses, higher cortisol concentrations at baseline (β = − 0.39, p = .002) and 28 wk. (β = − 0.49, p = .001), but not 36 wk. (β = − 0.23, p = .084) were associated with a shorter pregnancy duration. Women with high cortisol at baseline (> 6.3 nmol/L) had an increased relative risk of preterm delivery (RR (95% CI): 1.96 (1.13, 3.40)), but the association between high cortisol at 28 wk. and preterm delivery was not significant. There was a significant interaction with fetal sex (p-for-interaction = 0.037): among women carrying male fetuses, high cortisol at baseline increased the risk of preterm delivery threefold (3.18 (1.51, 6.71)) while there was no association (1.17 (0.50, 2.74)) among women carrying female fetuses.

Conclusion

Higher maternal cortisol is associated with a shorter pregnancy duration and an increased risk of preterm delivery. Subgroup analysis by fetal sex revealed that this association is evident primarily among women carrying male fetuses. Future studies of cortisol and preterm delivery should include consideration of fetal sex as a potential effect modifier.
Association between dietary knowledge and overweight/obesity in Chinese children and adolescents aged 8–18 years: a cross-sectional study
Authors: Wang Lihong , Zhuang Jielian , Zhang Heng , Lu Weijuan
Published: September 2022

Background

A lack of adequate dietary knowledge may result in poor health. The purpose of this study was to study the association between dietary knowledge and overweight/obesity in children and adolescents. 

Method

Data from the China Health and Nutrition Survey (CHNS) 2004, 2006, 2009, 2011, and 2015 were used in this cross-sectional study. The dietary knowledge of children and adolescents was evaluated by the questionnaire in the database. The overweight and obesity status was evaluated by body mass index (BMI). Cluster analysis was performed to establish different groups based on dietary knowledge level. Logistic regression analysis and subgroup analysis were conducted.

Results

A total of 2,701 children and adolescents were finally selected. Cluster A (n = 837, 30.99%), Cluster B (n = 1,264, 46.80%) and Cluster C (n = 600, 22.21%) were high, medium and low dietary knowledge level, respectively. Participants with high dietary knowledge levels [OR = 0.56 (95%CI: 1.40–0.78)] may be negatively associated with overweight and obesity. Similar results were found among adolescents, males, females, people living in eastern and northeastern China, and rural areas, after adjusting for age, gender, geographic region, maternal education level, alcohol consumption, waist-to-hip ratio, systolic blood pressure and diastolic blood pressure.

Conclusion

Improving the dietary knowledge level of children and adolescents was associated with decreased risk of overweight and obesity. Our study provided a theoretical basis for the relationship between dietary knowledge and overweight/obesity in Chinese children and adolescents and suggested strengthening the publicity and popularization of dietary knowledge in schools and communities.
The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study
Authors: Brynte Christoffer , Aeschlimann Myriam , Barta Csaba , Begeman Alex Hendikus Abraham , Bäcker Amanda , Crunelle Cleo Lina , Daigre Constanza , De Fuentes-Merillas Laura , Demetrovics Zsolt , Dom Geert , López Lara Grau , Icick Romain , Johnson Brian , Joostens Peter , Kapitány-Fövény Máté , Karsinti Emily , Kiefer Falk , Konstenius Maija , Levin Frances R. , Luderer Mathias , Markus Wiebren , Matthys Frieda , Moggi Franz , Palma-Alvarez Raul Felipe , Paraskevopoulou Maria , Ramos-Quiroga J. Antoni , Schellekens Arnt , Soravia Leila M. , Therribout Norman , Thomas Anil , van de Glind Geurt , van Kernebeek Michiel Willem , Vollstädt-Klein Sabine , Vorspan Florence , van den Brink Wim , Franck Johan
Published: September 2022

Background

Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD.

Aims

This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes.

This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months.

Results

A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%.

Conclusions

The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes.

Trial registration

ISRCTN15998989 20/12/2019.
An analysis of time trends in breast and prostate cancer mortality rates in Lithuania, 1986–2020
Authors: Everatt Rūta , Gudavičienė Daiva
Published: September 2022

Background

Breast cancer (BC) and prostate cancer (PC) mortality rates in Lithuania remain comparatively high despite the ongoing BC and PC screening programmes established in 2006. The aim of this study was to investigate time trends in BC and PC mortality rates in Lithuania evaluating the effects of age, calendar period of death, and birth-cohort over a 35-year time span.

Methods

We obtained death certification data for BC in women and PC in men for Lithuania during the period 1986–2020 from the World Health Organisation database. Age-standardised mortality rates were analysed using Joinpoint regression. Age-period-cohort models were used to assess the independent age, period and cohort effects on the observed mortality trends.

Results

Joinpoint regression analysis indicated that BC mortality increased by 1.6% annually until 1996, and decreased by − 1.2% annually thereafter. The age-period-cohort analysis suggests that temporal trends in BC mortality rates could be attributed mainly to cohort effects. The cohort effect curvature showed the risk of BC death increased in women born prior to 1921, remained stable in cohorts born around 1921–1951 then decreased; however, trend reversed in more recent generations. The period effect curvature displayed a continuous decrease in BC mortality since 1991–1995. For PC mortality, after a sharp increase by 3.0%, rates declined from 2007 by − 1.7% annually. The period effect was predominant in PC mortality, the curvature displaying a sharp increase until 2001–2005, then decrease.

Conclusions

Modestly declining recent trends in BC and PC mortality are consistent with the introduction of widespread mammography and PSA testing, respectively, lagging up to 10 years. The study did not show that screening programme introduction played a key role in BC mortality trends in Lithuania. Screening may have contributed to favourable recent changes in PC mortality rates in Lithuania, however the effect was moderate and limited to age groups < 65 years. Further improvements in early detection methods followed by timely appropriate treatment are essential for decreasing mortality from BC and PC.
Selected coffee (Coffea arabica L.) extracts inhibit intestinal α-glucosidases activities in-vitro and postprandial hyperglycemia in SD Rats
Authors: Mitiku Haimanot , Kim Tae Yang , Kang Hanna , Apostolidis Emmanouil , Lee Jung-Yun , Kwon Young-In
Published: September 2022

One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes, α-amylase, and α-glucosidases, in the digestive organs. Coffee consumption has been reported to beneficial effects for controlling calorie and cardiovascular diseases, however, the clear efficacy and mode of action are yet to be proved well. Therefore, in this study we evaluated in- vitro rat intestinal α-glucosidases and porcine α-amylase inhibitory activities as well as in vivo (Sprague–Dawley rat model) blood glucose lowering effects of selected coffee extracts. The water extracted Sumatra coffee (SWE) showed strong α-glucosidase inhibitory activity (IC50, 4.39 mg/mL) in a dose-dependent manner followed by Ethiopian water extract (EWE) (IC50, 4.97) and Guatemala water extract (GWE) (IC50, 5.19). Excepted for GWE all the coffee types significantly reduced the plasma glucose level at 0.5 h after oral intake (0.5 g/kg-body weight) in sucrose and starch-loaded SD rats. In sucrose loading test SWE (p < 0.001) and EWE (p < 0.05) had significantly postprandial blood glucose reduction effect, when compared to control. The maximum blood glucose levels (Cmax) of EWE administration group were decreased by about 18% (from 222.3 ± 16.0 to 182.5 ± 15.4, p < 0.01) and 19% (from 236.2 ± 25.1 to 191.3 ± 13.2 h·mg/dL, p < 0.01) in sucrose and starch loading tests, respectively. These results indicate that selected coffee extract may improve exaggerated postprandial spikes in blood glucose via inhibition of intestinal sucrase and thus delays carbohydrate absorption. These in vitro and in vivo studies therefore could provide the biochemical rationale for the benefit of coffee-based dietary supplement and the basis for further clinical study.
Exploring healthcare workers’ perspectives of video feedback for training in the use of powered air purifying respirators (PAPR) at the onset of the COVID-19 pandemic
Authors: Wyer Mary , Barratt Ruth , Hor Su-yin , Ferguson Patricia E. , Gilbert Gwendolyn L.
Published: September 2022

Background

With the advent of COVID-19, many healthcare workers (HWs) in Australia requested access to powered air purifying respirators (PAPR) for improved respiratory protection, comfort and visibility. The urgency of the response at our hospital required rapid deployment of innovative training to ensure the safe use of PAPRs, in particular, a video-feedback training option to prepare HWs for PAPR competency.

Aim

To explore the feasibility, acceptability, and utility of video-feedback in PAPR training and competency assessment.

Methods

Semi-structured interviews were conducted with 12 HWs, including clinicians from Intensive Care, Anaesthetics and Respiratory Medicine, at a large teaching hospital in Australia.

Findings

Participants believed that the use of video-feedback in PAPR training was feasible, acceptable and useful. They described a variety of benefits to learning and retention, from a variety of ways in which they engaged with the personal video-feedback. Participants also described the impact of reviewing personalised practice footage, compared to generic footage of an ideal performance.

Conclusion

By conceptualising video-feedback using a pedagogical approach, this study contributes to knowledge around optimising methods for training HWs in PPE use, particularly when introducing a new and complex PPE device during an infectious disease outbreak.
Community perspectives on ideal bacterial STI testing services for gay, bisexual, and other men who have sex with men in Toronto, Canada: a qualitative study
Authors: Rana Jayoti , Burchell Ann N. , Wang Susan , Logie Carmen H. , Lisk Ryan , Gesink Dionne
Published: September 2022

Background

Innovation is needed to produce sustained improvements in bacterial sexually transmitted infections (STI) testing given suboptimal access and uptake among sexually active gay, bisexual or other men who have sex with men (GBM). Yet, the STI testing processes and technologies that best address local testing barriers among GBM in Toronto is unknown. We aimed to explore men’s perspectives regarding STI testing services for GBM to identify and prioritize new STI testing interventions in Toronto, Ontario, Canada.

Methods

We conducted four focus groups with twenty-seven GBM in 2017: two with cisgender men living with HIV, one with cisgender HIV-negative men, and one with transgender men. Twenty-seven men participated in the focus groups with 40% 18–30 years of age, 48% self-identifying as white, and the remainder self-identifying as Middle Eastern, Latino/Hispanic, Asian/Pacific Islander, South Asian, First Nations, African/Caribbean/Black, or mixed race. 59% of participants self-identified as living with HIV. Participants were asked about their STI testing experiences in Toronto, barriers and facilitators to testing, and ideal STI testing process. Focus groups were audio recorded, transcribed verbatim, and analyzed using thematic analysis.

Results

Core concepts included how clinical context, bacterial STI testing delivery, and interactions with healthcare providers can create barriers and recommendations for ways to improve. Regarding clinical context, participants desired more clinics with accessible locations/hours; streamlined testing that minimized use of waiting rooms and wait times; and improved clinic ambience. Bacterial STI testing delivery recommendations included standardization to ensure consistency in sexual history intake, tests offered, follow-up and public health reporting between clinics. Men also recommended reducing the multistep process testing by offering components such as lab requisitions and results online. Participants also recommended interactions with healthcare providers be professional and non-judgmental, offer compassionate and competent care with destigmatizing and lesbian, gay, bisexual and trans (LGBT) affirming communication.

Conclusion

Concrete and practical solutions for improving existing sexual health services and facilitating optimal STI testing include streamlining testing options and providing patient-centred, LGBT-affirming care to enable optimal STI testing.
The taTME learning curve for mid-low rectal cancer: a single-center experience in China
Authors: Xu Fengming , Zhang Yiqiao , Yan Jiafu , Xu Bowen , Wu Guocong , Yang Zhengyang , Sun Liting , Zhang Xiao , Yao Hongwei , Zhang Zhongtao
Published: September 2022

Purpose

As transanal total mesorectal excision (taTME) is performed worldwide, the optimization of existing training and guidance programs to enhance new taTME learners’ competence in performing this procedure is warranted. This study aimed to evaluate the taTME learning curve in patients with mid-low rectal cancer.

Methods

Patients who underwent taTME for mid-low rectal cancer between October 2015 and August 2021 at a single center were included. A cumulative sum (CUSUM) learning curve analysis was performed with the total operation time as the study outcome. The learning curve was analyzed using risk-adjusted CUSUM analysis, with postoperative complications and anastomotic leakage (AL) as outcomes.

Results

In total, 104 consecutive patients were included in this study. The CUSUM learning curve for total operative time started declining after 42 cases (309.1 ± 84.4 vs. 220.2 ± 46.4, P < 0.001). The risk-adjusted CUSUM (RA-CUSUM) learning curve for postoperative complications fluctuated in cases 44–75 and declined significantly after case 75. The RA-CUSUM learning curve for AL declined after 68 cases.

Conclusions

taTME had learning curves of 42, 75, and 68 cases for total operative time, postoperative complications, and AL, respectively. A surgeon may require 42 and 75 cases to achieve “proficiency” and “mastery” in taTME procedures, respectively.
Prognostic significance of tumor deposits in radically resected gastric cancer: a retrospective study of a cohort of 1915 Chinese individuals
Authors: Zhou Menglong , Yang Wang , Zou Wei , Yang Jianing , Zhou Changming , Zhang Zhiyuan , Wang Yaqi , Zhang Jing , Wang Yan , Li Guichao , Zhang Zhen , Xia Fan
Published: September 2022

Background

Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients.

Methods

We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted.

Results

The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance.

Conclusions

The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.
Factors leading to falls in transfemoral prosthesis users: a case series of sound-side stumble recovery responses
Authors: Eveld Maura E. , King Shane T. , Zelik Karl E. , Goldfarb Michael
Published: September 2022

Background

Transfemoral prosthesis users’ high fall rate is related to increased injury risk, medical costs, and fear of falling. Better understanding how stumble conditions (e.g., participant age, prosthesis type, side tripped, and swing phase of perturbation) affect transfemoral prosthesis users could provide insight into response deficiencies and inform fall prevention interventions.

Methods

Six unilateral transfemoral prosthesis users experienced obstacle perturbations to their sound limb in early, mid, and late swing phase. Fall outcome, recovery strategy, and kinematics of each response were recorded to characterize (1) recoveries versus falls for transfemoral prosthesis users and (2) prosthesis user recoveries versus healthy adult recoveries.

Results

Out of 26 stumbles, 15 resulted in falls with five of six transfemoral prosthesis users falling at least once. By contrast, in a previously published study of seven healthy adults comprising 214 stumbles using the same experimental apparatus, no participants fell. The two oldest prosthesis users fell after every stumble, stumbles in mid swing resulted in the most falls, and prosthesis type was not related to strategy/fall outcomes. Prosthesis users who recovered used the elevating strategy in early swing, lowering strategy in late swing, and elevating or lowering/delayed lowering with hopping in mid swing, but exhibited increased contralateral (prosthetic-side) thigh abduction and trunk flexion relative to healthy controls. Falls occurred if the tripped (sound) limb did not reach ample thigh/knee flexion to sufficiently clear the obstacle in the elevating step, or if the prosthetic limb did not facilitate a successful step response after the initial sound-side elevating or lowering step. Such responses generally led to smaller step lengths, less anterior foot positioning, and more forward trunk flexion/flexion velocity in the resulting foot-strikes.

Conclusions

Introducing training (e.g., muscle strength or task-specific motor skill) and/or modifying assistive devices (e.g., lower-limb prostheses or exoskeletons) may improve responses for transfemoral prosthesis users. Specifically, training or exoskeleton assistance could help facilitate sufficient thigh/knee flexion for elevating; training or prosthesis assistance could provide support-limb counteracting torques to aid in elevating; and training or prosthesis assistance could help initiate and safely complete prosthetic swing.
Preclinical assessment of synergistic efficacy of MELK and CDK inhibitors in adrenocortical cancer
Authors: Laha Dipranjan , Grant Robert R.C. , Mishra Prachi , Boufraqech Myriem , Shen Min , Zhang Ya-Qin , Hall Matthew D. , Quezado Martha , De Melo Michelly Sampaio , Del Rivero Jaydira , Zeiger Martha , Nilubol Naris
Published: September 2022

Background

Adrenocortical cancer (ACC) is a rare and aggressive cancer with dismal 5-year survival due to a lack of effective treatments. We aimed to identify a new effective combination of drugs and investigated their synergistic efficacy in ACC preclinical models.

Methods

A quantitative high-throughput drug screening of 4,991 compounds was performed on two ACC cell lines, SW13 and NCI-H295R, based on antiproliferative effect and caspase-3/7 activity. The top candidate drugs were pairwise combined to identify the most potent combinations. The synergistic efficacy of the selected inhibitors was tested on tumorigenic phenotypes, such as cell proliferation, migration, invasion, spheroid formation, and clonogenicity, with appropriate mechanistic validation by cell cycle and apoptotic assays and protein expression of the involved molecules. We tested the efficacy of the drug combination in mice with luciferase-tagged human ACC xenografts. To study the mRNA expression of target molecules in ACC and their clinical correlations, we analyzed the Gene Expression Omnibus and The Cancer Genome Atlas.

Results

We chose the maternal embryonic leucine zipper kinase (MELK) inhibitor (OTS167) and cyclin-dependent kinase (CDK) inhibitor (RGB-286638) because of their potent synergy from the pairwise drug combination matrices derived from the top 30 single drugs. Multiple publicly available databases demonstrated overexpression of MELK, CDK1/2, and partnering cyclins mRNA in ACC, which were independently associated with mortality and other adverse clinical features. The drug combination demonstrated a synergistic antiproliferative effect on ACC cells. Compared to the single-agent treatment groups, the combination treatment increased G2/M arrest, caspase-dependent apoptosis, reduced cyclins A2, B1, B2, and E2 expression, and decreased cell migration and invasion with reduced vimentin. Moreover, the combination effectively decreased Foxhead Box M1, Axin2, glycogen synthase kinase 3-beta, and β-catenin. A reduction in p-stathmin from the combination treatment destabilized microtubule assembly by tubulin depolymerization. The drug combination treatment in mice with human ACC xenografts resulted in a significantly lower tumor burden than those treated with single-agents and vehicle control groups.

Conclusions

Our preclinical study revealed a novel synergistic combination of OTS167 and RGB-286638 in ACC that effectively targets multiple molecules associated with ACC aggressiveness. A phase Ib/II clinical trial in patients with advanced ACC is therefore warranted.
A novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae regulates inflammasome activation through the TLR4–ROS–NLRP3 pathway
Authors: Xu Jingyun , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Xiong Lang , Peng Xuerong , Yang Guangyou
Published: September 2022

Background

Giant pandas (Ailuropoda melanoleuca) are the obligate host of the parasitic roundworm Baylisascaris schroederi. The infection of giant pandas with B. schroederi is very common. At present, little is known about the mechanism of immune interaction between B. schroederi and the host. As an important component of innate immunity, the NOD-like receptor 3 (NLRP3) inflammasome plays an important role in host immune response and the occurrence and development of infectious diseases.

Methods

We analyzed the regulation of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) by the recombinant B. schroederi migratory larvae cysteine protease inhibitor rBsCPI-1, knowing from a previous study that the CPI-1 is highly expressed in B. schroederi migratory larvae. We first determined the effects of rBsCPI-1 and excretory–secretory products of B. schroederi migratory larvae on cell proliferation using the CCK-8 and LDH release assays. We then analyzed NLRP3 inflammasome activation, pyroptosis and pro-inflammatory cytokine release by quantitative-PCR, western blotting and enzyme-linked immunosorbent assay. The signaling pathway of rBsCPI-1 to activate NLRP3 inflammasomes was analyzed in activation and inhibition experiments. Finally, the effects of rBsCPI-1 on inflammasome activation in mice immunized with rBsCPI-1 were analyzed.

Results

The activation and inhibition experiments revealed that rBsCPI-1 induced inflammasome activation through the TLR4–ROS–NLRP3 signaling pathway, with reactive oxygen species (ROS) not only functioning as an activator of the NLRP3 inflammasome, but also an activation product of the NLRP3 inflammasome. rBsCPI-1 promoted the activation and assembly of the NLRP3 inflammasome, which further converted the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 into mature active forms. At the same time, caspase-1 cleaved gasdermin D to trigger cell pyroptosis. The results of animal immunization experiments further confirmed that rBsCPI-1 could induce the activation of the NLRP3 inflammasome.

Conclusions

rBsCPI-1 activates the inflammasome through the TLR4–ROS–NLRP3 signaling pathway and further induces the pyroptosis of MDMs and release of pro-inflammatory factors IL-1β and IL-18, thus promoting the occurrence and development of the inflammatory response in the host.

Graphical abstract
Association of Alzheimer’s disease polygenic risk scores with amyloid accumulation in cognitively intact older adults
Authors: Luckett Emma S. , Abakkouy Yasmina , Reinartz Mariska , Adamczuk Katarzyna , Schaeverbeke Jolien , Verstockt Sare , De Meyer Steffi , Van Laere Koen , Dupont Patrick , Cleynen Isabelle , Vandenberghe Rik
Published: September 2022

Background

Early detection of individuals at risk for Alzheimer’s disease (AD) is highly important. Amyloid accumulation is an early pathological AD event, but the genetic association with known AD risk variants beyond the APOE4 effect is largely unknown. We investigated the association between different AD polygenic risk scores (PRS) and amyloid accumulation in the Flemish Prevent AD Cohort KU Leuven (F-PACK).

Methods

We calculated PRS with and without the APOE region in 90 cognitively healthy F-PACK participants (baseline age 67.8 (52–80) years, 41 APOE4 carriers), with baseline and follow-up amyloid-PET (time interval 6.1 (3.4–10.9) years). Individuals were genotyped using Illumina GSA and imputed. PRS were calculated using three p-value thresholds (pT) for variant inclusion: 5 × 10−8, 1 × 10−5, and 0.1, based on the stage 1 summary statistics from Kunkle et al. (Nat Genet 51:414–30, 2019). Linear regression models determined if these PRS predicted amyloid accumulation.

Results

A score based on PRS excluding the APOE region at pT = 5 × 10−8 plus the weighted sum of the two major APOE variants (rs429358 and rs7412) was significantly associated with amyloid accumulation (p = 0.0126). The two major APOE variants were also significantly associated with amyloid accumulation (p = 0.0496). The other PRS were not significant.

Conclusions

Specific PRS are associated with amyloid accumulation in the asymptomatic phase of AD.
Constraints and prospects of utilising mountain pastures in Gilgit-Baltistan, Pakistan
Authors: Hameed Asif , Tariq Muhammad , Buerkert Andreas , Schlecht Eva
Published: September 2022

In the mountain regions of northern Pakistan, pasture-based animal husbandry is a substantial element of people’s livelihood. To study the implications of herding strategies on rangeland utilization patterns, individual interviews with 90 herders and 10 group interviews with five to eight herders per group, respectively, were conducted in three valleys each of Pakistan’s Gilgit-Baltistan region. Data collection targeted number and species of animals kept, livestock management practices and seasonal pasture use and included GIS-based participatory mapping of spring, summer, autumn and winter pastures of yak, small ruminants and cattle. Households kept 10 yaks on average, along with 4 cattle and 15 small ruminants. Herding practices varied between valleys and seasons and were influenced by topographic as well as social factors. Full-time herding led to a more uniform distribution of yaks on pastures than part-time herding and unattended grazing, but in small ruminants promoted higher animal numbers near campsites. Many livestock keepers perceived rangeland degradation as a veritable challenge and identified lack of herding labour as one important problem. Training programmes for young herders, strengthening of group herding schemes and prevention of lowland pasture conversion into farmland were suggested as effective countermeasures.
Identifying performance factors of long-term care facilities in the context of the COVID-19 pandemic: a scoping review protocol
Authors: Létourneau Josiane , Bélanger Emilie , Sia Drissa , Beogo Idrissa , Robins Stephanie , Kruglova Katya , Jubinville Maripier , Tchouaket Eric Nguemeleu
Published: September 2022

Background

Long-term care facilities (LTCFs) have been severely affected by the COVID-19 pandemic with serious consequences for the residents. Some LTCFs performed better than others, experiencing lower case and death rates due to COVID-19. A comprehensive understanding of the factors that have affected the transmission of COVID-19 in LTCFs is lacking, as no published studies have applied a multidimensional conceptual framework to evaluate the performance of LTCFs during the pandemic. Much research has focused on infection prevention and control strategies or specific disease outcomes (e.g., death rates). To address these gaps, our scoping review will identify and analyze the performance factors that have influenced the management of COVID-19 in LTCFs by adopting a multidimensional conceptual framework.

Methods

We will query the CINAHL, MEDLINE (Ovid), CAIRN, Science Direct, and Web of Science databases for peer-reviewed articles written in English or French and published between January 1, 2020 and December 31, 2021. We will include articles that focus on the specified context (COVID-19), population (LTCFs), interest (facilitators and barriers to performance of LTCFs), and outcomes (dimensions of performance according to a modified version of the Ministère de la santé et des services sociaux du Québec conceptual framework). Each article will be screened by at least two co-authors independently followed by data extraction of the included articles by one co-author and a review by the principal investigator.

Results

We will present the results both narratively and with visual aids (e.g., flowcharts, tables, conceptual maps).

Discussion

Our scoping review will provide a comprehensive understanding of the factors that have affected the performance of LTCFs during the COVID-19 pandemic. This knowledge can help inform the development of more effective infection prevention and control measures for future pandemics and outbreaks. The results of our review may lead to improvements in the care and safety of LTCF residents and staff.

Scoping review registration

Research Registry researchregistry7026
eHealth literacy measurement tools: a systematic review protocol
Authors: Délétroz Carole , Allen Marina Canepa , Sasseville Maxime , Rouquette Alexandra , Bodenmann Patrick , Gagnon Marie-Pierre
Published: September 2022

Background

Improving eHealth literacy (eHL) is one of the biggest challenges currently facing the global healthcare community. Indeed the use of digital services has the potential to engage patients in care as well as improve the effectiveness of chronic disease self-management, it remains highly dependent on a patient’s specific skills and experiences in the health care systems. Although eHealth literacy has gained momentum in the past decade, it remains an underresearched area, particularly eHealth literacy measurement. The aim of the review is to identify patient-reported outcome measures (PROMs) of eHealth literacy for adult populations and to summarize the evidence on their psychometric properties.

Methods

We will conduct a systematic literature review of the tools used to measure eHealth literacy for adult population. The search strategy aims to find published studies. A three-step search strategy will be used in this review. Published studies will be searched in CINAHL, PubMed, PsycINFO, and Web of Science from inception until end. Grey literature will be searched to find theses. Database search strategies will be formulated and tested with the assistance of an expert Health Sciences Librarian. The selection of studies will be done by two independent reviewers. Disagreements will be resolved through consensus, and a third reviewer will solve discrepancies. Furthermore, two reviewers will independently evaluate the methodological rigor of the instruments development and testing and assign a grade using the standardized Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist. Disagreements will be discussed with a third reviewer, expert in psychometrics.

Extracted data will be aggregated and analyzed to produce a set of synthesized findings that will be used to develop evidence-informed recommendations in regard of eHL instruments. We will present a synthesis of all instruments, their psychometric properties, and make recommendations for eHL instrument selection in practice. Reporting will be informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and a PRISMA flow diagram.

Discussion

This systematic review will summarize the evidence on the psychometric properties of PROMs instruments used to measure eHL and will help clinicians, managers, and policy-makers to select an appropriate instrument.

Systematic review registration

PROSPERO CRD42021232765
Combined left thoracoscopic and median sternotomy approach to resect aortopulmonary mediastinal paraganglioma following feeding artery embolization: a case report
Authors: Itagaki Kota , Notsuda Hirotsugu , Suzuki Tomoyuki , Tanaka Ryota , Kamada Hiroki , Omata Kei , Tezuka Yuta , Ota Hideki , Okada Yoshinori , Saiki Yoshikatsu
Published: September 2022

Background

Aortopulmonary mediastinal paragangliomas are rare. Complete resection of the tumor is desirable regardless of tumor size in view of the risk of sudden death induced by adjacent organ compression and poor prognosis after partial resection or untreated observation. Due to the hypervascularity of the tumor, the risk of intraoperative bleeding is significant, and cardiopulmonary bypass is often required for complete resection.

Case presentation

The patient was diagnosed as having bilateral carotid body tumors and supposedly an aortic body tumor at the age of 43 and eventually underwent resections of bilateral carotid body tumors at the age of 52. The pathology of the carotid body tumors was compatible with paraganglioma on both sides. A familial succinate dehydrogenase subunit D mutation was subsequently identified. Five years later, a contrast-enhanced computed tomography scan showed an enlarged tumor of 45 mm in size in the aortopulmonary mediastinum. Based on the previously known genetic mutation, the tumor was thought to be a paraganglioma. After confirming with an endocrinologist that the aortic body tumor was non-functional, radiologists performed preoperative embolization of the feeding vessels. Subsequently, a surgical team consisting of thoracic and cardiovascular surgeons resected the aortic body tumor using a video-assisted small left thoracotomy approach combined with a median sternotomy approach. The procedure was completed without cardiopulmonary bypass or blood transfusion. The patient was discharged home on postoperative day 9 uneventfully.

Conclusions

After conduction of preceding interventional embolization of multiple feeding vessels, we employed a video-assisted thoracoscopic surgical approach to dissect the aspects of the tumor adjacent to the esophagus, descending thoracic aorta, and left pulmonary artery, followed by a median sternotomy approach to dissect the other aspects of the tumor adjacent to the ascending aorta, aortic arch, right pulmonary artery, and trachea. There have been no reports on scheduled preoperative embolization of feeding vessels to an aortopulmonary mediastinal paraganglioma. Multidisciplinary approach was effective for complete resection of this challenging rare mediastinal tumor.