bluuebunny/crossref_metadata_2025 huggingface dataset:
Range of motion at 6 weeks is an independent risk factor for non-healing at 6 months after arthroscopic supraspinatus repair.
Authors: Nabergoj Marko , Laedermann Alexandre , Bothorel Hugo , Pernoud Anthony , Collin Philippe , Martinho Tiago
Published: February 2024

PURPOSE: This study aimed to analyze the effect of the range of motion (ROM) progression pattern on healing after supraspinatus (SSN) repair.

HYPOTHESIS: We hypothesized that a faster ROM recovery in the immediate postoperative period would be detrimental for tendon healing.

Methods:

This was a retrospective study of prospective collected data. All primary arthroscopic SSN repairs for full-thickness tears, with retraction Patte grade < 2, fatty infiltration Goutallier grade < 3 and no glenohumeral osteoarthritis were eligible. Patients who did not attend all follow-ups were excluded. One surgeon performed all arthroscopic repairs using a double-row technique. All patients followed the same rehabilitation protocol with an abduction pillow and passive ROM for 6 weeks. One observer assessed all patients preoperatively and at 1.5, 3 and 6 months postoperatively. Collected outcome measures included: ROM, Visual Analogue Scale (VAS) for pain and Constant Score (CS). Repair integrity was evaluated at 6 months by ultrasound. 2 groups were established based on repair integrity (healed/non-healed). A multivariable analysis was performed to assess potential confounding factors and ROC curve analysis was used to identify predictive thresholds for non-healing.

Results:

Of 1397 consecutive SSN repairs, 169 were excluded and 1207 were finally included. The overall healing rate was 87.3%. All preoperative outcome measures were similar between groups. Non-healed repairs at 6 months were slightly younger (57.8±7.9 vs 61.6±8.8, p < 0.001) and had a faster postoperative ROM recovery pattern. This difference was most distinct at 6 weeks in passive anterior elevation (AE) (143±22 vs 128±26, p < 0.001) and external rotation (ER) (32±17 vs 23±17,p < 0.001) but was fully compensated by 6 months. VAS pain and CS at each follow-up were similar between groups. Multivariable analysis confirmed 6-weeks passive EA (OR:1.36) and ER (OR:1.16) as independent risk factors for non-healing. The non-healing rate increased when 6-weeks passive EA >140° (20.4 vs 7.9%) and ER > 30° (18.4 vs 8.8%).

Conclusions:

In a large cohort of isolated arthroscopic SSN repairs treated with the same surgical technique and rehabilitation protocol, a faster postoperative ROM progression pattern, reflected by higher 6-weeks AE and ER, was associated with an increased rate of non-healing. This study illustrates the benefit of a conservative rehabilitation protocol on tendon healing without affecting ROM at 6 months.
We Should Know Everything Shouldn’t We?: Children of Soldiers on What and How War Should Be Taught
Authors: Gibbs Brian
Published: February 2024

Taken from a larger qualitative multi-case study, this article centers the voices of high school students who are from military affiliated families and how they want war to be taught to them. Using heritage history and difficult knowledge as theoretical frames, this article argues that military affiliated students seek a more robust teaching of war. Students demonstrated an interest in developing a deeper understanding of the community in which they live. Students requested a pedagogy that was inquiry and discussion based with teachers not telling them what or how to think about war, a curriculum that was thematic in nature, teaching that was connected to the present, and teaching that was mindful of the personal connections students had to the subject of war through their family.
Using Technology to Support Students with Disabilities in Inclusive Music Classrooms
Authors: Draper Ellary A.
Published: February 2024

Students with disabilities may require specific assistive technology to use their strengths to compensate for a weakness or need caused by the disability, including both “devices” and “services.” As a result, teachers need to be able to use and support students while using assistive technology during instruction. Teachers also can use technology during instruction to support students with and without disabilities. This article summarizes the different types of assistive technology students may use in the inclusive music classroom as well as ways music teachers can use other technology to support students with disabilities.
Social Emotional Learning and Music Education: Be sure to Be Kind to Yourself, Too
Authors: Varner Edward
Published: February 2024

Music educators often advocate for the benefits of music education, such as leadership, self-expression, and creativity. Or, for some, music education for music education’s sake. Consider accomplishing this by teaching students to be self-aware and socially aware musicians. When student awareness improves, so does the music and the community of musicians. Social Emotional Learning (SEL) competency development should not be viewed as something taking time from musical instruction. Instead, view SEL competency skills as being learned through musical instruction. SEL alignments need to be intentional, explicit, consistent, and structured. This column suggests three embedded SEL techniques and encourages four focus activities to help foster personal, emotional, and physical well-being for music teachers and their students.
Development of a multilayer film for the first US Food and Drug Administration cleared aseptically-produced intravenous solution bags with a short history of key medical device milestones
Authors: Czuba Len
Published: February 2024

Flexible intravenous solution containers (IV bags) were introduced to the marketplace in the early 1970s. These new containers were designed to replace glass IV bottles and were quickly adopted widely for delivering medical solutions to patients throughout the world. The 40 years during which commercially available IV solutions in glass bottles were used, the healthcare industry grew dramatically with better patient outcomes while also reducing operational costs. These early developments then led to the rapid expansion of new medical devices that have been further developed to improve healthcare and reduce overall costs of the products and devices. It is not an exaggeration to suggest that the medical device industry was founded on the development of the flexible poly (vinyl chloride) (PVC) plastic IV tubing and bag. After the IV bag product lines grew to serve many markets, a new unmet need was discovered for an aseptically produced premixed drug container. This article will review how a new film was developed and used to produce the required aseptically made IV premixed drug product. It was, after the Food and Drug Administration (FDA) gave “clearance to market”, a ground-breaking product, never before thought possible for the highly FDA-regulated and controlled industry.
Clinical–imaging–pathological correlation in pulmonary hypertension associated with left heart disease
Authors: van de Veerdonk Marielle C. , Roosma Lize , Trip Pia , Gopalan Deepa , Vonk Noordegraaf Anton , Dorfmüller Peter , Nossent Esther J.
Published: February 2024

Pulmonary hypertension (PH) is highly prevalent in patients with left heart disease (LHD) and negatively impacts prognosis. The most common causes of PH associated with LHD (PH-LHD) are left heart failure and valvular heart disease. In LHD, passive backward transmission of increased left-sided filling pressures leads to isolated post-capillary PH. Additional pulmonary vasoconstriction and remodelling lead to a higher vascular load and combined pre- and post-capillary PH. The increased afterload leads to right ventricular dysfunction and failure. Multimodality imaging of the heart plays a central role in the diagnostic work-up and follow-up of patients with PH-LHD. Echocardiography provides information about the estimated pulmonary artery pressure, morphology and function of the left and right side of the heart, and valvular abnormalities. Cardiac magnetic resonance imaging is the gold standard for volumetric measurements and provides myocardial tissue characterisation. Computed tomography of the thorax may show general features of PH and/or LHD and is helpful in excluding other PH causes. Histopathology reveals a spectrum of pre- and post-capillary vasculopathy, including intimal fibrosis, media smooth muscle cell hyperplasia, adventitial fibrosis and capillary congestion. In this paper, we provide an overview of clinical, imaging and histopathological findings in PH-LHD based on three clinical cases.
kalis: a modern implementation of the Li & Stephens model for local ancestry inference in R
Authors: Aslett Louis J. M. , Christ Ryan R.
Published: February 2024

Background

Approximating the recent phylogeny of N phased haplotypes at a set of variants along the genome is a core problem in modern population genomics and central to performing genome-wide screens for association, selection, introgression, and other signals. The Li & Stephens (LS) model provides a simple yet powerful hidden Markov model for inferring the recent ancestry at a given variant, represented as an $$N \times N$$

N
×
N

distance matrix based on posterior decodings.

Results

We provide a high-performance engine to make these posterior decodings readily accessible with minimal pre-processing via an easy to use package kalis, in the statistical programming language . kalis enables investigators to rapidly resolve the ancestry at loci of interest and developers to build a range of variant-specific ancestral inference pipelines on top. kalis exploits both multi-core parallelism and modern CPU vector instruction sets to enable scaling to hundreds of thousands of genomes.

Conclusions

The resulting distance matrices accessible via kalis enable local ancestry, selection, and association studies in modern large scale genomic datasets.
Trends in low-value GP care during the COVID-19 pandemic: a retrospective cohort study
Authors: Müskens Joris L. J. M. , Olde Hartman Tim C. , Schers Henk J. , Akkermans Reinier P. , Westert Gert P. , Kool Rudolf B. , van Dulmen Simone A.
Published: February 2024

Background

Several studies showed that during the pandemic patients have refrained from visiting their general practitioner (GP). This resulted in medical care being delayed, postponed or completely forgone. The provision of low-value care, i.e. care which offers no net benefit for the patient, also could have been affected. We therefore assessed the impact of the COVID-19 restrictions on three types of low-value GP care: 1) imaging for back or knee problems, 2) antibiotics for otitis media acuta (OMA), and 3) repeated opioid prescriptions, without a prior GP visit.

Methods

We performed a retrospective cohort study using registration data from GPs part of an academic GP network over the period 2017–2022. The COVID-19 period was defined as the period between April 2020 to December 2021. The periods before (January 2017 to April 2020) and after the COVID-19 period (January 2022 to December 2022) are the pre- and post-restrictions periods. The three clinical practices examined were selected by two practicing GPs from a top 30 of recommendations originating from the Dutch GP guidelines, based on their perceived prevalence and relevance in practice (van Dulmen et al., BMC Primary Care 23:141, 2022). Multilevel Poisson regression models were built to examine changes in the incidence rates (IR) of both registered episodes and episodes receiving low-value treatment.

Results

During the COVID-19 restrictions period, the IRs of episodes of all three types of GP care decreased significantly. The IR of episodes of back or knee pain decreased by 12%, OMA episodes by 54% and opioid prescription rate by 13%. Only the IR of OMA episodes remained significantly lower (22%) during the post-restrictions period. The provision of low-value care also changed. The IR of imaging for back or knee pain and low-value prescription of antibiotics for OMA both decreased significantly during the COVID-restrictions period (by 21% and 78%), but only the low-value prescription rate of antibiotics for OMA remained significantly lower (by 63%) during the post-restrictions period. The IR of inappropriately repeated opioid prescriptions remained unchanged over all three periods.

Conclusions

This study shows that both the rate of episodes as well as the rate at which low-value care was provided have generally been affected by the COVID-19 restrictions. Furthermore, it shows that the magnitude of the impact of the restrictions varies depending on the type of low-value care.

This indicates that deimplementation of low-value care requires tailored (multiple) interventions and may not be achieved through a single disruption or intervention alone.
Micropulse transscleral cyclophotocoagulation (MP-CPC): efficacy endpoints for the treatment of refractory paediatric glaucoma - a retrospective case-series
Authors: Balbaid Nasser , AlJodai Mohammed , Fairaq Ghadeer , AlEnzi Maram , AlShahwan Sami
Published: February 2024

Background

This study evaluates the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-CPC) in paediatric patients.

Methods

This retrospective case-series recruited 44 eyes for glaucoma patients who were younger than 17 years and were treated with MP-CPC and followed for at least one year. Pre- and post-intervention intraocular pressure (IOP) was compared out to at least one year postoperatively. Success rates at 6 months and 1 year postoperatively were assessed. P < 0.05 was considered statistically significant.

Results

There were 35 (79.5%) eyes with a history of glaucoma surgery. IOP decreased statistically significantly from a baseline of 32.7 (standard deviation:8.7 mmHg) to 23.2 (8.6) and 21.7 (7.9) mmHg at the 6 months and 1-year follow-up, respectively (P < 0.0001, all comparisons). Overall success was noted in 19 (47.5%) eyes at the 6 months follow-up, and 23 (53.5%) eyes at 1 year.

Conclusions

MP-CPC reduces IOP and the burden of medications in paediatric patients with glaucoma. Additionally, its safety profile favours the use of MP-CPC as an adjunctive modality for refractory glaucoma.
Hepatitis B vaccine effectiveness among vaccinated children in Africa: a systematic review and meta-analysis
Authors: Geta Mekuanint , Yizengaw Endalew , Manyazewal Tsegahun
Published: February 2024

Background

Globally, 257 million people have chronic hepatitis. Even though a safe and effective prophylactic vaccine against HBV infection has been available, it causes significant morbidity and mortality. HBV vaccines were designed to improve or modulate the host immune responses. The effectiveness of the vaccine is determined by measuring serum hepatitis B surface antibody (Anti-HBs) level. Therefore, this systematic review aimed to evaluate the effectiveness of hepatitis B vaccine among vaccinated children.

Methods

Preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines was applied for systematically searching of different databases. Only cross-section studies measuring the level of anti-HBs of vaccinated children were included. The seroprotective level with anti-HBs > 10mIU/ml was extracted. The meta-analysis was performed using statistical software for data sciences (STATA) version 14. Effectiveness estimates were reported as a proportion of anti-HBs level. The heterogeneity between studies was evaluated using the I2 test, and I2 > 50% and/or P < 0.10 was considered significant heterogeneity. Significant publication bias was considered when Egger’s test P-value < 0.10. The new castle Ottawa scale was used to assess the quality of the studies.

Results

A pooled sample size of the included papers for meta-analysis was 7430. The pooled prevalence of seroprotected children was 56.95%, with a heterogeneity index (I2) of 99.4% (P < 0.001). 35% of the participants were hypo-responders (10-99mIU/ml) and 21.46% were good responders (> 100mIU/ml). Based on subgroup analysis using country of studies conducted, the highest prevalence of anti-HBs was 87.00% (95% CI: 84.56, 89.44), in South Africa, and the lowest was 51.99% (95% CI: 20.41–83.58), with a heterogeneity index I2 = 70.7% (p = 0.009) in Ethiopia.

Conclusion and recommendations

Hepatitis B vaccine seroprotective level in the current pooled analysis have suboptimal, which failed to demonstrate consistent effectiveness for global hepatitis B virus elimination plan in 2030. Using consistent age group may have a significant value for the decision of the HB vaccine effectiveness. A significant heterogeneity was observed both in studies conducted in Ethiopia and Egypt. Therefore, the impact of HB vaccination on the prevention of hepatitis B virus infection should be assessed regularly in those countries. Future meta-analysis is needed to investigate all possible vaccines in a separate way of reviewing, which will lead to a strong conclusion and recommendations.
Avoidable emergency department visits among palliative care cancer patients: novel insights from Saudi Arabia and the Middle East
Authors: Salama Hagir , Omer Mohamed H. , Shafqat Areez , Binahmed Ahmed , Alghamdi Ghadah Muhammed , Saeed Mohammed , Alfagi Mohamed Madani , Alqahtany Bayan Saeed , Alshoshan Feda , Salih Dalia , Hashim Ahmed , Alkaiyat Mohammad , Algarni Abdullah
Published: February 2024

Background

Several studies emerging from developed countries have highlighted a significant number of potentially avoidable emergency department (ED) visits by cancer patients during the end-of-life period. However, there is a paucity of information from developing nations regarding palliative care practices and the utilization of the ED by palliative care patients. Herein, we aim to characterize ED admissions among patients receiving palliative care at our tertiary center in Saudi Arabia.

Methods

This is a retrospective, cross-sectional study evaluating ED visits amongst adult patients with advanced cancer who were receiving treatment under the palliative care department. This study took place over a period of 12 months from July 2021 through to July 2022. Three palliative care specialist physicians independently and blindly reviewed each patient’s ED visits and determined whether the visit was avoidable or unavoidable.

Results

A total of 243 patients were included in the final analysis, of which 189 (78.1%) patients had unavoidable visits and 53 (21.9%) patient visits were classified as avoidable. A significantly higher proportion of breast cancer patients presented with unavoidable admissions (14.3% vs. 3.8%, P = 0.037) compared to other cancer types. The incidence of dyspnea (23.8% vs. 5.7%, P < 0.001) and fevers/chills (23.3% vs. 5.7%, P = 0.005) was significantly higher in patients with unavoidable visits. Patients with avoidable visits had a significantly greater proportion of visits for dehydration (13.2% vs. 2.1%, P = 0.002). Notably, although hospital stay was significantly longer in the unavoidable group (P = 0.045), mortality for palliative care patients—regardless of whether their ED visit was avoidable or unavoidable—was not statistically different (P=-0.069).

Conclusion

To our knowledge, this is the largest and most comprehensive study from Saudi Arabia and the Middle East providing insights into the utilization of palliative care services in the region and the propensity of advanced cancer patients towards visiting the ED. Future studies ought to explore interventions to reduce the frequency of avoidable ED visits.
The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors
Authors: Henderson Tara O. , Allen Mary Ashley , Mim Rajia , Egleston Brian , Fleisher Linda , Elkin Elena , Oeffinger Kevin , Krull Kevin , Ofidis Demetrios , Mcleod Briana , Griffin Hannah , Wood Elizabeth , Cacioppo Cara , Weinberg Michelle , Brown Sarah , Howe Sarah , McDonald Aaron , Vukadinovich Chris , Alston Shani , Rinehart Dayton , Armstrong Gregory T. , Bradbury Angela R.
Published: February 2024

Background

Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. TheENGaging andActivating cancer survivors inGenetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing.

Methods

The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services.

Discussion

With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine.

Trial registration

This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.
Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors
Authors: Park Yong-Moon Mark , Jung Wonyoung , Yeo Yohwan , Park Sang Hyun , Fradley Michael G. , Malapati Sindhu J. , Tarun Tushar , Raj Vinay , Lee Hong Seok , Naqvi Tasneem Z. , Henry-Tillman Ronda S. , Mehta Jawahar L. , Schootman Mario , Amick Benjamin C. , Han Kyungdo , Shin Dong Wook
Published: February 2024

Background

The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment.

Methods

Using data from the Korean Health Insurance Service database (2010–2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities.

Results

BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00–1.13), but the association disappeared over time. Younger BCS (age < 40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98–3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older BCS, especially those aged > 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28–1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40–2.69 in those aged ≤ 50 years).

Conclusions

Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS.

Graphical Abstract
Exposure to chemical pollutants and biological aerosol in indoor facilities for recreational and sport horses
Authors: Rodzyń Izabela , Karpińska Katarzyna , Bis-Wencel Hanna , Wlazło Łukasz , Ossowski Mateusz , Strzelec Katarzyna , Jaguszewski Sebastian , Nowakowicz-Dębek Bożena
Published: February 2024

Background

Due to the increasing prevalence of equine non-infectious respiratory disease, the air contamination in equine housing (Stables A-C) and training facilities (indoor riding arenas A - C) was investigated. The aim of the study was to monitor gaseous pollutants, bioaerosols, and dust concentrations at three different sites (stables and riding halls), where different floor materials were used in the riding halls.

Materials and methods

Air quality was monitored in housing for horses and in riding halls in terms of dust concentration, the presence of gaseous chemical pollutants, and concentrations of biological aerosol. Statistical analysis was performed using analysis of variance (ANOVA). The levels obtained were compared with acceptable limits.

Results

Among the gaseous pollutants identified, the highest concentration was obtained for ammonia in stables B and C (16.37 and 22.39 mg/m3, respectively). Standards for total dust were exceeded in stables B and C and in riding halls B and C. The highest numbers of bacteria and fungi were recorded in stables A and C and in riding hall B. Ulocladium sp. had the highest percentage share among the moulds identified.

Conclusions

The results confirm that the wrong choice of bedding in the stable and indoor riding arenas may contribute, even in short training periods, to equine non-infectious respiratory disease (equine asthma). Bioaerosol suspended in the air together with released gaseous pollutants can exacerbate this phenomenon, which even in the case of short training periods can lead to equine asthma of varying degrees of severity. For this reason, the choice of floor material in riding halls should be treated as a priority, as the wrong decision can shorten the period during which the horse can be used for recreational purposes.
Associations between long-term ozone exposure and small airways function in Chinese young adults: a longitudinal cohort study
Authors: Feng Shurong , Yang Liu , Dou Siqi , Li Xinyuan , Wen Shuo , Yan Lailai , Huang Wenzhong , Zhang Yiwen , Ma Bin , Yuan Linghong , Li Shanshan , Lu Peng , Guo Yuming
Published: February 2024

Background

Increasing evidence is appearing that ozone has adverse effects on health. However, the association between long-term ozone exposure and lung function is still inconclusive.

Objectives

To investigate the associations between long-term exposure to ozone and lung function in Chinese young adults.

Methods

We conducted a prospective cohort study among 1594 college students with a mean age of 19.2 years at baseline in Shandong, China from September 2020 to September 2021. Lung function indicators were measured in September 2020 and September 2021, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow at the 25th, 50th, and 75th percentile of the FVC (FEF25, FEF50, and FEF75) and mean flow rate between 25% and 75% of the FVC (FEF25-75) were measured. Daily 10 km×10 km ozone concentrations come from a well-validated data-fusion approach. The time-weighted average concentrations in 12 months before the lung function test were defined as the long-term ozone exposure. The associations between long-term ozone exposure and lung function indicators in Chinese young adults were investigated using a linear mixed effects model, followed by stratified analyses regarding sex, BMI and history of respiratory diseases.

Results

Each interquartile range (IQR) (8.9 µg/m3) increase in long-term ozone exposure were associated with a -204.3 (95% confidence interval (CI): -361.6, -47.0) ml/s, -146.3 (95% CI: -264.1, -28.4) ml/s, and − 132.8 (95% CI: -239.2, -26.4) ml/s change in FEF25, FEF50, and FEF25-75, respectively. Stronger adverse associations were found in female participants or those with BMI ≥ 24 kg/m2 and history of respiratory diseases.

Conclusion

Long-term exposure to ambient ozone is associated with impaired small airway indicators in Chinese young adults. Females, participants with BMI ≥ 24 kg/m2 and a history of respiratory disease have stronger associations.
The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro
Authors: Matera Maria Gabriella , Rinaldi Barbara , Calabrese Cecilia , Belardo Carmela , Calzetta Luigino , Cazzola Mario , Page Clive
Published: February 2024

Background

Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.

Methods

We investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses.

Results

IL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction.

Conclusion

This study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.
Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment
Authors: Bao Xiaogang , Huo Shicheng , Wang Zhenhua , Yang Shengyan , Dou Linyun , Liu Yifei , Huang Jian , Cai Chang , Fang Bin , Xu Guohua
Published: February 2024

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.
TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy
Authors: Huang Yu , Xiong Zhiyong , Wang Jianjun , Gao Yafen , Cao Qi , Wang Decai , Shi Jian , Chen Zhixian , Yang Xiong
Published: February 2024

Background

Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear.

Methods

In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo.

Results

In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy.

Conclusions

Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.

Graphical Abstract
Towards a validated glossary of usability attributes for the evaluation of wearable robotic devices
Authors: Herrera-Valenzuela Diana , Meyer Jan T. , del-Ama Antonio J. , Moreno Juan C. , Gassert Roger , Lambercy Olivier
Published: February 2024

Background

Despite technical advances in the field of wearable robotic devices (WRD), there is still limited user acceptance of these technologies. While usability often comes as a key factor influencing acceptance, there is a scattered landscape of definitions and scopes for the term. To advance usability evaluation, and to integrate usability features as design requirements during technology development, there is a need for benchmarks and shared terminology. These should be easily accessible and implementable by developers.

Methods

An initial set of usability attributes (UA) was extracted from a literature survey on usability evaluation in WRD. The initial set of attributes was enriched and locally validated with seven developers of WRD through an online survey and a focus group. The locally validated glossary was then externally validated through a globally distributed online survey.

Results

The result is the Robotics Usability Glossary (RUG), a comprehensive glossary of 41 UA validated by 70 WRD developers from 17 countries, ensuring its generalizability. 31 of the UA had high agreement scores among respondents and 27 were considered highly relevant in the field, but only 11 of them had been included as design criteria by the respondents.

Conclusions

Multiple UA ought to be considered for a comprehensive usability assessment. Usability remains inadequately incorporated into device development, indicating a need for increased awareness and end-user perspective. The RUG can be readily accessed through an online platform, the Interactive Usability Toolbox (IUT), developed to provide context-specific outcome measures and usability evaluation methods. Overall, this effort is an important step towards improving and promoting usability evaluation practices within WRD. It has the potential to pave the way for establishing usability evaluation benchmarks that further endorse the acceptance of WRD.
Large-scale in-silico analysis of CSF dynamics within the subarachnoid space of the optic nerve
Authors: Rossinelli Diego , Fourestey Gilles , Killer Hanspeter Esriel , Neutzner Albert , Iaccarino Gianluca , Remonda Luca , Berberat Jatta
Published: February 2024

Background

Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer’s and Parkinson’s disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural alterations of the ONSAS, from first principles, with supercomputers.

Methods

Large-scale in-silico investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625 μm/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes.

Results

A physiological flow speed of 0.5 mm/s is achieved by imposing a hydrostatic pressure gradient of 0.37–0.67 Pa/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover, ONSAS trabeculae seem key players in mass transfer.

Conclusions

The present analysis suggests that a pressure drop of 0.1–0.2 mmHg over 4 cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome.
Bufei Yishen formula protects the airway epithelial barrier and ameliorates COPD by enhancing autophagy through the Sirt1/AMPK/Foxo3 signaling pathway
Authors: Jia Lidan , Liu Xuefang , Liu Xinguang , Guan Qingzhou , Tian Yange , Li Jiansheng , Zhao Peng
Published: February 2024

Object

Bufei Yishen formula (BYF), a traditional Chinese medicine alleviates COPD symptoms and suppresses airway epithelial inflammation. In this study, we determined whether BYF protects the airway epithelial barrier from destruction in COPD rats.

Methods

The protective effects of BYF on the airway epithelial barrier were examined in a rat COPD model. BEAS-2B epithelial cells were exposed to cigarette smoke extract (CSE) to determine the effect of BYF on epithelial barrier function. Transcriptomic and network analyses were conducted to identify the protective mechanisms.

Results

Oral BYF reduced the severity of COPD in rats by suppressing the decline in lung function, pathological changes, inflammation, and protected airway epithelial barrier function by upregulating apical junction proteins, including occludin (OCLN), zonula occludens (ZO)-1, and E-cadherin (E-cad). BYF treatment reduced epithelial permeability, and increased TEER as well as the apical junction proteins, OCLN, ZO-1, and E-cad in BEAS-2B cells exposed to CSE. Furthermore, 58 compounds identified in BYF were used to predict 421 potential targets. In addition, the expression of 572 differentially expressed genes (DEGs) was identified in CSE-exposed BEAS-2B cells. A network analysis of the 421 targets and 572 DEGs revealed that BYF regulates multiple pathways, of which the Sirt1, AMPK, Foxo3, and autophagy pathways may be the most important with respect to protective mechanisms. Moreover, in vitro experiments confirmed that nobiletin, one of the active compounds in BYF, increased apical junction protein levels, including OCLN, ZO-1, and E-cad. It also increased LC3B and phosphorylated AMPK levels and decreased the phosphorylation of FoxO3a.

Conclusions

BYF protects the airway epithelial barrier in COPD by enhancing autophagy through regulation of the SIRT1/AMPK/FOXO3 signaling pathway.
The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway
Authors: Zhai Pan , Chen Qianyun , Wang Xunxun , Ouyang Xiaohu , Yang Mengling , Dong Yalan , Li Junyi , Li Yiming , Luo Shanshan , Liu Yue , Cheng Xiang , Zhu Rui , Hu Desheng
Published: February 2024

Background

Astragaloside IV (As-IV) and Tanshinone IIA (Ta-IIA) are the main ingredients of traditional Chinese medicinal Astragalus membranaceus (Fisch.) Bunge and Salvia miltiorrhiza Bunge, respectively, both of which have been employed in the treatment of cardiovascular diseases. Nevertheless, the efficacy of the combination (Co) of Ta-IIA and As-IV for cardiovascular diseases remain unclear and warrant further investigation. This study aimed to investigate the efficacy and the underlying molecular mechanism of Co in treating myocardial ischemia–reperfusion injury (MIRI).

Methods

In order to assess the efficacy of Co, an in vivo MIRI mouse model was created by temporarily blocking the coronary arteries for 30 min and then releasing the blockage. Parameters such as blood myocardial enzymes, infarct size, and ventricular function were measured. Additionally, in vitro experiments were conducted using HL1 cells in both hypoxia-reoxygenation model and oxidative stress models. The apoptosis rate, expression levels of apoptosis-related proteins, oxidative stress indexes, and release of inflammatory factors were detected. Furthermore, molecular docking was applied to examine the binding properties of Ta-IIA and As-IV to STING, and western blotting was performed to analyze protein expression of the STING pathway. Additionally, the protective effect of Ta-IIA, As-IV and Co via inhibiting STING was further confirmed in models of knockdown STING by siRNA and adding STING agonist.

Results

Both in vitro and in vivo data demonstrated that, compared to Ta-IIA or As-IV alone, the Co exhibited superior efficacy in reducing the area of myocardial infarction, lowering myocardial enzyme levels, and promoting the recovery of myocardial contractility. Furthermore, the Co showed more potent anti-apoptosis, antioxidant, and anti-inflammation effects. Additionally, the Co enhanced the inhibitory effects of Ta-IIA and As-IV on STING phosphorylation and the activation of STING signaling pathway. However, the administration of a STING agonist attenuated the protective effects of the Co, Ta-IIA, and As-IV by compromising their anti-apoptotic, antioxidant, and anti-inflammatory effects in MIRI.

Conclusion

Compared to the individual administration of Ta-IIA or As-IV, the combined treatment demonstrated more potent ability in inhibiting apoptosis, oxidative stress, inflammation, and the STING signaling pathway in the context of MIRI, indicating a more powerful protective effect against MIRI.

Graphical Abstract
DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study
Authors: Dubath Céline , Porcu Eleonora , Delacrétaz Aurélie , Grosu Claire , Laaboub Nermine , Piras Marianna , von Gunten Armin , Conus Philippe , Plessen Kerstin Jessica , Kutalik Zoltán , Eap Chin Bin
Published: February 2024

Background

Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip.

Results

A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10–16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10−8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10–8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association).

Conclusion

These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.
Successful microvascular surgery in patients with thrombophilia in head and neck surgery: a case series
Authors: Faber Julian , Schuster Frank , Hartmann Stefan , Brands Roman C. , Fuchs Andreas , Straub Anton , Fischer Markus , Müller-Richter Urs , Linz Christian
Published: February 2024

Background

In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss—which is most often caused by thrombosis—can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients.

Case presentation

We present three exemplary male Caucasian patients aged 53–57 years with free flap loss owing to an underlying, hidden thrombophilia.

Conclusion

We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.