bluuebunny/crossref_metadata_2025 huggingface dataset:
Confounding factors in profiling of locus-specific human endogenous retrovirus (HERV) transcript signatures in primary T cells using multi-study-derived datasets
Authors: Hamann Martin V. , Adiba Maisha , Lange Ulrike C.
Published: April 2023

Background

Human endogenous retroviruses (HERV) are repetitive sequence elements and a substantial part of the human genome. Their role in development has been well documented and there is now mounting evidence that dysregulated HERV expression also contributes to various human diseases. While research on HERV elements has in the past been hampered by their high sequence similarity, advanced sequencing technology and analytical tools have empowered the field. For the first time, we are now able to undertake locus-specific HERV analysis, deciphering expression patterns, regulatory networks and biological functions of these elements. To do so, we inevitable rely on omics datasets available through the public domain. However, technical parameters inevitably differ, making inter-study analysis challenging. We here address the issue of confounding factors for profiling locus-specific HERV transcriptomes using datasets from multiple sources.

Methods

We collected RNAseq datasets of CD4 and CD8 primary T cells and extracted HERV expression profiles for 3220 elements, resembling most intact, near full-length proviruses. Looking at sequencing parameters and batch effects, we compared HERV signatures across datasets and determined permissive features for HERV expression analysis from multiple-source data.

Results

We could demonstrate that considering sequencing parameters, sequencing-depth is most influential on HERV signature outcome. Sequencing samples deeper broadens the spectrum of expressed HERV elements. Sequencing mode and read length are secondary parameters. Nevertheless, we find that HERV signatures from smaller RNAseq datasets do reliably reveal most abundantly expressed HERV elements. Overall, HERV signatures between samples and studies overlap substantially, indicating a robust HERV transcript signature in CD4 and CD8 T cells. Moreover, we find that measures of batch effect reduction are critical to uncover genic and HERV expression differences between cell types. After doing so, differences in the HERV transcriptome between ontologically closely related CD4 and CD8 T cells became apparent.

Conclusion

In our systematic approach to determine sequencing and analysis parameters for detection of locus-specific HERV expression, we provide evidence that analysis of RNAseq datasets from multiple studies can aid confidence of biological findings. When generating de novo HERV expression datasets we recommend increased sequence depth ( > = 100 mio reads) compared to standard genic transcriptome pipelines. Finally, batch effect reduction measures need to be implemented to allow for differential expression analysis.
Human cells with osteogenic potential in bone tissue research
Authors: Dvorakova Jana , Wiesnerova Lucie , Chocholata Petra , Kulda Vlastimil , Landsmann Lukas , Cedikova Miroslava , Kripnerova Michaela , Eberlova Lada , Babuska Vaclav
Published: April 2023

Bone regeneration after injury or after surgical bone removal due to disease is a serious medical challenge. A variety of materials are being tested to replace a missing bone or tooth. Regeneration requires cells capable of proliferation and differentiation in bone tissue. Although there are many possible human cell types available for use as a model for each phase of this process, no cell type is ideal for each phase. Osteosarcoma cells are preferred for initial adhesion assays due to their easy cultivation and fast proliferation, but they are not suitable for subsequent differentiation testing due to their cancer origin and genetic differences from normal bone tissue. Mesenchymal stem cells are more suitable for biocompatibility testing, because they mimic natural conditions in healthy bone, but they proliferate more slowly, soon undergo senescence, and some subpopulations may exhibit weak osteodifferentiation. Primary human osteoblasts provide relevant results in evaluating the effect of biomaterials on cellular activity; however, their resources are limited for the same reasons, like for mesenchymal stem cells. This review article provides an overview of cell models for biocompatibility testing of materials used in bone tissue research.
The magnitude and associated factors of coagulation abnormalities among liver disease patients at the University of Gondar Comprehensive Specialized Hospital Northwest, Ethiopia, 2022
Authors: Melkamu Abateneh , Woldu Berhanu , Sitotaw Chomaw , Seyoum Masresha , Aynalem Melak
Published: April 2023

Background

Liver disease is any condition that affects the liver cells and their function. It is directly linked to coagulation disorders since most coagulation factors are produced by the liver. Therefore, this study aimed to assess the magnitude and associated factors of coagulation abnormalities among liver disease patients.

Methods

A cross-sectional study was conducted from August to October 2022 among 307 consecutively selected study participants at the University of Gondar Comprehensive Specialized Hospital. Sociodemographic and clinical data were collected using a structured questionnaire and data extraction sheet, respectively. About 2.7 mL of venous blood were collected and analyzed by the Genrui CA51 coagulation analyzer. Data were entered into Epi-data and exported to STATA version 14 software for analysis. The finding was described in terms of frequencies and proportions. Factors associated with coagulation abnormalities were analyzed by bivariable and multivariable logistic regression.

Result

In this study, a total of 307 study participants were included. Of them the magnitude of prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were 68.08% and 63.51%, respectively. The presence of anaemia (AOR = 2.97, 95% CI: 1.26, 7.03), a lack of a vegetable feeding habit (AOR = 2.98, 95% CI: 1.42, 6.24), no history of blood transfusion (AOR = 3.72, 95% CI: 1.78, 7.78), and lack of physical exercise (AOR = 3.23, 95% CI: 1.60, 6.52) were significantly associated with prolonged PT. While the presence of anaemia (AOR = 3.02; 95% CI: 1.34, 6.76), lack of vegetable feeding habit (AOR = 2.64; 95% CI: 1.34, 5.20), no history of blood transfusion (AOR = 2.28; 95% CI: 1.09, 4.79), and a lack of physical exercise (AOR = 2.35; 95% CI: 1.16, 4.78) were significantly associated with abnormal APTT.

Conclusion

Patients with liver disease had substantial coagulation problems. Being anemic, having a transfusion history, lack of physical activity, and lack of vegetables showed significant association with coagulopathy. Therefore, early detection and management of coagulation abnormalities in liver disease patients are critical.
Monetary valuation of COVID-19 informal care: caregivers’ willingness to pay and willingness to accept
Authors: Ramezani-Doroh Vajiheh , Karimi Faride , Rangchian Maryam , Hamidi Yadolah
Published: April 2023

Background

Informal care can reduce hospitalization frequency and time, elevate bed turnover, and increase the health systems' capacity. This type of care has shown meaningful value in managing many cases through the COVID-19 pandemic. The present study aimed to identify determinants of monetary valuation of informal care and the burden of this care on the COVID-19 patients’ caregivers.

Methods

Through a cross-sectional phone survey from June to September 2021 in Sanandaj city, the west of Iran, COVID-19 patients and their caregivers (Each Group No. 425) were separately interviewed. A simple probabilistic sampling method was applied. Two questionnaires were developed and used after validation. Monetary valuation of informal caregivers was done using Willingness to pay (WTP) and willingness to accept (WTA). Double hurdle regressions were used to determine related variables to WTP/WTA. R software was used for the data analysis.

Results

The total mean (Standard Deviation) of WTP and WTA were $12.02(28.73), $10.30(15.43) USD. Most respondents put a zero value on informal care by WTA (243(57.18%) and WTP [263 (61.88%)]. Caregivers’ Employment, and being spouse/child of the care recipient increased the probability of reporting a positive value for WTP (p-value < 0.0001, p-value = 0.011 respectively) and WTA (p-value = 0.004, p-value < 0.0001 respectively). An increase in the number of caring days decreased the probability of reporting positive WTA (p-value = 0.001) and increased the mean of lnWTP (p-value = 0.044). Perceived difficulty in doing indoor activities and perceived difficulty in doing outdoor activities decreased lnWTA mean (p-value = 0.002) and lnWTP mean (p-value = 0.043) respectively.

Conclusions

Increasing caregivers’ self-efficacy and facilitating their involvement in the caring process could be facilitated through flexible work status, educational programs, and interventions on decreasing their burnout.
Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning
Authors: Du Yang , Qiu Rui , Chen Lei , Chen Yuewen , Zhong Zhifeng , Li Peng , Fan Fangcheng , Cheng Yong
Published: April 2023

Background

Remote ischemic preconditioning (RIPC) refers to a brief episode of exposure to potential adverse stimulation and prevents injury during subsequent exposure. RIPC has been shown to increase tolerance to ischemic injury and improve cerebral perfusion status. Exosomes have a variety of activities, such as remodeling the extracellular matrix and transmitting signals to other cells. This study aimed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection.

Methods

Sixty adult male military personnel participants were divided into the control group (n = 30) and the RIPC group (n = 30). We analyzed the differential metabolites and proteins in the serum exosomes of RIPC participants and control subjects.

Results

Eighty-seven differentially expressed serum exosomal metabolites were found between the RIPC and control groups, which were enriched in pathways related to tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, and multiple neurodegeneration diseases. In addition, there were 75 differentially expressed exosomal proteins between RIPC participants and controls, which involved the regulation of insulin-like growth factor (IGF) transport, neutrophil degranulation, vesicle-mediated transport, etc. Furthermore, we found differentially expressed theobromine, cyclo gly-pro, hemopexin (HPX), and apolipoprotein A1 (ApoA1), which are associated with neuroprotective benefits in ischemia/reperfusion injury. In addition, five potential metabolite biomarkers, including ethyl salicylate, ethionamide, piperic acid, 2, 6-di-tert-butyl-4-hydroxymethylphenol and zerumbone, that separated RIPC from control individuals were identified.

Conclusion

Our data suggest that serum exosomal metabolites are promising biomarkers for RIPC, and our results provide a rich dataset and framework for future analyses of cerebral ischemia‒reperfusion injury under ischemia/reperfusion conditions.
Unexpectedly high incidence of Kawasaki Disease in a Canadian Atlantic Province- an 11-year retrospective descriptive study
Authors: Alkanhal Abdulrahman , Saunders Joseph , Altammar Fajer , Huber Adam M. , Lynk Andrew , MacLeod Alison , Ortiz-Alvarez Oliva , Adams Meighan , Ramsey Suzanne , Stringer Elizabeth , Warren Andrew , Lang Bianca
Published: April 2023

Background

Kawasaki Disease (KD) is the leading cause of acquired heart disease in children in developed countries with a variable incidence worldwide. Previous studies reported an unexpectedly high incidence of KD in the Canadian Atlantic Provinces. The goals of our study were to validate this finding in the province of Nova Scotia and to carefully review patients’ characteristics and disease outcomes.

Methods

This was a retrospective review of all children < 16 years old from Nova Scotia diagnosed with KD between 2007–2018. Cases were identified using a combination of administrative and clinical databases. Clinical information was collected retrospectively by health record review using a standardized form.

Results

Between 2007–2018, 220 patients were diagnosed with KD; 61.4% and 23.2% met the criteria for complete and incomplete disease, respectively. The annual incidence was 29.6 per 100,000 children < 5 years. The male to female ratio was 1.3:1 and the median age was 3.6 years. All patients diagnosed with KD in the acute phase received intravenous immunoglobulin (IVIG); 23 (12%) were refractory to the first dose. Coronary artery aneurysms were found in 13 (6%) patients and one patient died with multiple giant aneurysms.

Conclusion

We have confirmed an incidence of KD in our population which is higher than that reported in Europe and other regions of North America despite our small Asian population. The comprehensive method to capture patients may have contributed to the detection of the higher incidence. The role of local environmental and genetic factors also deserves further study. Increased attention to regional differences in the epidemiology of KD may improve our understanding of this important childhood vasculitis.
TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder
Authors: You Yun-Fan , Chen Man , Tang Yue , Yu Wen-Xiang , Pang Xiao-Wei , Chu Yun-Hui , Zhang Hang , Shang Ke , Deng Gang , Zhou Luo-Qi , Yang Sheng , Wang Wei , Xiao Jun , Tian Dai-Shi , Qin Chuan
Published: April 2023

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination.

Graphical Abstract
Effects of backward walking exercise using lower body positive pressure treadmill on knee symptoms and physical function in individuals with knee osteoarthritis: a protocol for RCT
Authors: Almutairi Sattam M. , Almutairi Marzouq K. , Alotaibi Mansour M. , Alshehri Mohammed , Alenazi Aqeel M.
Published: April 2023

Objectives

The primary aim is to compare the effects of backward walking exercise to forward walking exercise on knee pain, knee functions, and thigh muscle strength in individuals with mild to moderate knee osteoarthritis using lower body positive pressure, in addition to mobility functions, balance, and self-reported health status.

Methods

The study is a single blind randomized clinical trial with two independent groups. This study will enroll 26 participants with mild to moderate knee osteoarthritis. The participants will be randomized into either experimental group (backward walking exercise) or control group (forward walking exercise). Both groups will use lower body positive pressure treadmill for walking exercise. Both groups will perform regular conventional exercise and worm-up exercise before walking exercise. The treatment will be three times a week for six weeks. Walking session will be up to 30 min each session. Data collection will be collected during pre- and post- intervention including primary outcomes including numeric pain rating scale (NPRS), knee injury and osteoarthritis outcome score (KOOS), and thigh muscle strength test. The secondary outcomes include five times sit to stand test (FTSTS), 3-meter backward walk test (3MBWT), timed up and go test (TUG), four square step test (FSST), functional reach test (FRT), 10-meter walk test (10-MWT), six minute walk test (6MWT), medical outcomes study short form 12 (SF-12), patient health questionnaire -9 (PHQ-9), and rapid assessment of physical activity (RAPA). An independent t-test will be used to evaluate the effect of treatment on the outcome measures.

Results

Not applicable.

Conclusion

Using lower body positive pressure may have promising results against knee osteoarthritis. Moreover, walking backward exercise using lower body positive pressure might add more benefits to individuals with knee osteoarthritis and help clinicians in decision making.

Trial registration: This study was registered in ClinicalTrails.gov (ID: NCT05585099).
Psychosocial model of burnout among humanitarian aid workers in Bangladesh: role of workplace stressors and emotion coping
Authors: Foo Cheryl Yunn Shee , Tay Alvin Kuowei , Yang Yexinyu , Verdeli Helen
Published: April 2023

Background

While trauma exposure is an established predictor of poor mental health among humanitarian aid workers (HAWs), less is known about the role of psychosocial work-related factors. This study aims to establish a psychosocial model for burnout and psychological distress in HAWs that tests and compares the effects of adversity exposure and workplace stressors in combination, and explores the potential mediating role of individual coping styles.

Methods

Path analysis and model comparison using cross-sectional online survey data were collected from full-time international and local HAWs in Bangladesh between December 2020 and February 2021. HAWs self-reported on exposure to adversities, workplace psychosocial stressors (Third Copenhagen Psychosocial Questionnaire), coping styles (Coping Inventory for Stressful Situations), burnout (Maslach Burnout Inventory—Human Services Survey), and psychological distress (Kessler-6).

Results

Among N = 111 HAWs, 30.6%, 16.4%, 12.7%, and 8.2% screened positive for moderate psychological distress (8 ≤ Kessler-6 ≤ 12), emotional exhaustion (EE ≥ 27), depersonalization (DP ≥ 13), and severe psychological distress (K-6 ≥ 13), respectively. 28.8% reported a history of mental disorder. The preferred model showed distinct pathways from adversity exposure and workplace stressors to burnout, with negative emotion-focused coping and psychological distress as significant intervening variables. While greater exposure to both types of stressors were associated with higher levels of burnout and distress, workplace stressors had a stronger association with psychological outcomes than adversity exposure did (β = .52, p ≤ .001 vs. β = .20, p = .032). Workplace stressors, but not adversities, directly influenced psychological distress (β = .45, p ≤ .001 vs. β = −.01, p = .927). Demographic variables, task-focused and avoidance-focused coping were not significantly associated with psychological outcomes.

Conclusions

Compared to exposure to adversities, workplace stressors primarily influenced occupational stress syndromes. Reducing workplace stressors and enhancing adaptive coping may improve psychological outcomes in humanitarian staff.
Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice
Authors: Taylor Peter N. , Lansdown Andrew , Witczak Justyna , Khan Rahim , Rees Aled , Dayan Colin M. , Okosieme Onyebuchi
Published: April 2023

Background

Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice.

Main text

There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures.

Conclusion

Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals.
Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry
Authors: Marchesi Francesco , Salmanton-García Jon , Buquicchio Caterina , Itri Federico , Besson Caroline , Dávila-Valls Julio , Martín-Pérez Sonia , Fianchi Luana , Rahimli Laman , Tarantini Giuseppe , Grifoni Federica Irene , Sciume Mariarita , Labrador Jorge , Cordoba Raul , López-García Alberto , Fracchiolla Nicola S. , Farina Francesca , Ammatuna Emanuele , Cingolani Antonella , García-Bordallo Daniel , Gräfe Stefanie K. , Bilgin Yavuz M. , Dargenio Michelina , González-López Tomás José , Guidetti Anna , Lahmer Tobias , Lavilla-Rubira Esperanza , Méndez Gustavo-Adolfo , Prezioso Lucia , Schönlein Martin , Van Doesum Jaap , Wolf Dominik , Hersby Ditte Stampe , Magyari Ferenc , Van Praet Jens , Petzer Verena , Tascini Carlo , Falces-Romero Iker , Glenthøj Andreas , Cornely Oliver A. , Pagano Livio
Published: April 2023

Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.
PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation
Authors: Marranci Andrea , Prantera Antonella , Masotti Simona , De Paolo Raffaella , Baldanzi Caterina , Podda Maurizio S. , Mero Serena , Vitiello Marianna , Franchin Cinzia , Laezza Mariavittoria , Comelli Laura , Arrigoni Giorgio , Cervelli Tiziana , Del Pozzo Giovanna , Poliseno Laura
Published: April 2023

In human cells BRAF oncogene is invariably expressed as a mix of two coding transcripts: BRAF-ref and BRAF-X1. These two mRNA isoforms, remarkably different in the sequence and length of their 3′UTRs, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the X1 3′UTR in melanoma cells. Mechanistically, PARP1 Zinc Finger domain down-regulates BRAF expression at the translational level. As a consequence, it exerts a negative impact on MAPK pathway, and sensitizes melanoma cells to BRAF and MEK inhibitors, both in vitro and in vivo. In summary, our study unveils PARP1 as a negative regulator of the highly oncogenic MAPK pathway in melanoma, through the modulation of BRAF-X1 expression.
Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma
Authors: Ramzy George M. , Norkin Maxim , Koessler Thibaud , Voirol Lionel , Tihy Mathieu , Hany Dina , McKee Thomas , Ris Frédéric , Buchs Nicolas , Docquier Mylène , Toso Christian , Rubbia-Brandt Laura , Bakalli Gaetan , Guerrier Stéphane , Huelsken Joerg , Nowak-Sliwinska Patrycja
Published: April 2023

Background

We propose a new approach for designing personalized treatment for colorectal cancer (CRC) patients, by combining ex vivo organoid efficacy testing with mathematical modeling of the results.

Methods

The validated phenotypic approach called Therapeutically Guided Multidrug Optimization (TGMO) was used to identify four low-dose synergistic optimized drug combinations (ODC) in 3D human CRC models of cells that are either sensitive or resistant to first-line CRC chemotherapy (FOLFOXIRI). Our findings were obtained using second order linear regression and adaptive lasso.

Results

The activity of all ODCs was validated on patient-derived organoids (PDO) from cases with either primary or metastatic CRC. The CRC material was molecularly characterized using whole-exome sequencing and RNAseq. In PDO from patients with liver metastases (stage IV) identified as CMS4/CRIS-A, our ODCs consisting of regorafenib [1 mM], vemurafenib [11 mM], palbociclib [1 mM] and lapatinib [0.5 mM] inhibited cell viability up to 88%, which significantly outperforms FOLFOXIRI administered at clinical doses. Furthermore, we identified patient-specific TGMO-based ODCs that outperform the efficacy of the current chemotherapy standard of care, FOLFOXIRI.

Conclusions

Our approach allows the optimization of patient-tailored synergistic multi-drug combinations within a clinically relevant timeframe.

Graphical Abstract
Tracheostomy timing and outcome in critically ill patients with stroke: a meta-analysis and meta-regression
Authors: Premraj Lavienraj , Camarda Christopher , White Nicole , Godoy Daniel Agustin , Cuthbertson Brian H. , Rocco Patricia R. M. , Pelosi Paolo , Robba Chiara , Suarez Jose I. , Cho Sung-Min , Battaglini Denise
Published: April 2023

Background

Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS.

Methods

We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients.

Results

Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0–3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = − 0.3, 95% CI = − 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS).

Conclusions

In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS.

Trial registration: PROSPERO—CRD42022351732 registered on 17th of August 2022.
Effects of 10 Hz individualized repetitive transcranial magnetic stimulation on patients with disorders of consciousness: a study protocol for an exploratory double-blind crossover randomized sham-controlled trial
Authors: Xu Chengwei , Zhu Zhaohua , Wu Wanchun , Zheng Xiaochun , Zhong Haili , Huang Xiyan , Xie Qiuyou , Qian Xinyi
Published: April 2023

Background

Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with “one size fits all” rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC.

Methods

Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days’ washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study.

Discussion

rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation.

Trial registration

ClinicalTrials.gov: NCT05187000. Registered on January 10, 2022.
Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial
Authors: Cold Isak Mazanti , Feinberg Joshua Buron , Brandes Axel , Davidsen Ulla , Dixen Ulrik , Dominguez Helena , Gang Uffe Jakob Ortved , Gluud Christian , Hadad Rakin , Kristensen Kit Engedal , van Le Doan Tuyet , Nielsen Emil Eik , Olsen Michael Hecht , Pedersen Ole Dyg , Raymond Ilan Esra , Sajadieh Ahmad , Soja Anne Merete Boas , Jakobsen Janus Christian
Published: April 2023

Background

A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis.

Methods

The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for “site,” type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues.

Discussion

This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial.

Trial registration

Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.
The impact of insulin resistance on the association between metabolic syndrome and lung function: the Kangbuk Samsung Health Study
Authors: Lee Jonghoo , Park Hye Kyeong , Kwon Min-Jung , Ham Soo-Youn , Gil Hyun-Il , Lim Si-Young , Song Jae-Uk
Published: April 2023

Background/Objective

Metabolic syndrome (MS) is related to lung dysfunction. However, its impact according to insulin resistance (IR) remains unknown. Therefore, we evaluated whether the relation of MS with lung dysfunction differs by IR.

Subject/Methods

This cross-sectional study included 114,143 Korean adults (mean age, 39.6 years) with health examinations who were divided into three groups: metabolically healthy (MH), MS without IR, and MS with IR. MS was defined as presence of any MS component, including IR estimated by HOMA-IR ≥ 2.5. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for lung dysfunction were obtained in MS, MS without IR, and MS with IR groups compared with the MH (reference) group.

Results

The prevalence of MS was 50.7%. The percent predicted forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) showed statistically significant differences between MS with IR and MH and between MS with IR and MS without IR (all P < 0.001). However, those measures did not vary between MH and MS without IR (P = 1.000 and P = 0.711, respectively). Compared to MH, MS was not at risk for FEV1% < 80% (1.103 (0.993–1.224), P = 0.067) or FVC% < 80% (1.011 (0.901–1.136), P = 0.849). However, MS with IR was clearly associated with FEV1% < 80% (1.374 (1.205–1.566) and FVC% < 80% (1.428 (1.237–1.647) (all p < 0.001), though there was no evident association for MS without IR (FEV1%: 1.078 (0.975–1.192, P = 0.142) and FVC%: 1.000 (0.896–1.116, p = 0.998)).

Conclusion

The association of MS with lung function can be affected by IR. However, longitudinal follow-up studies are required to validate our findings.
Psychometric properties of the Arabic version of the Intuitive Eating Scale-2 (IES-2) in a sample of community adults
Authors: Fekih-Romdhane Feten , Jiang Chen , Obeid Sahar , Malaeb Diana , Chammas Nancy , Fawaz Mirna , Soufia Michel , Meng Runtang , Hallit Souheil
Published: April 2023

Background

There is a growing attention on intuitive eating (IE) styles in the Western world that has not yet reached Arab countries, which is likely due to the lack of psychometrically sound measures of the IE construct for Arabic-speaking people. The current study aims to examine the psychometric properties of an Arabic translation of the most widely used measure of IE—the Intuitive Eating Scale-2 (IES-2), in an Arabic-speaking community population from Lebanon.

Methods

Two samples of Arabic-speaking community adults from Lebanon (sample 1: n = 359, 59.9% females, age 22.75 ± 7.04 years; sample 2: n = 444, 72.7% females, age 27.25 ± 9.53 years) were recruited through online convenience sampling. The translation and back-translation method was applied to the IES-2 for linguistic validation. Factorial validity was investigated using an Exploratory Factor Analysis & Confirmatory Factor Analysis strategy. Composite reliability and sex invariance were examined. We also tested convergent and criterion-related validity through correlations with other theoretically plausible constructs.

Results

Nine out of the original 23 items were removed because they either loaded below 0.40 and/or cross-loaded too highly on multiple factors. This resulted in four domains (Unconditional Permission to Eat, Eating for Physical Rather than Emotional Reasons, Reliance on Hunger and Satiety Cues, and Body-Food Choice Congruence) and 14 items retained. Internal reliability estimates were excellent, with McDonald’s ω values ranging from 0.828 to 0.923 for the four factors. Multigroup analysis established configural, thresholds, metric, scalar, strict invariance across gender. Finally, higher IES-2 total scores were significantly correlated with lower body dissatisfaction scores and more positive eating attitudes, thus attesting to convergent and criterion-related validity of the scale.

Conclusions

The current findings provide preliminary evidence for the appropriate psychometric qualities of the Arabic 14-item, four-factor structure IES-2; thereby supporting its use at least among Arabic-speaking community adults.
Adequacy of energy and macronutrients intake in differently active slovenian adolescents
Authors: Vilhar Emanuela Čerček , Golja Petra , Starc Gregor , Seljak Barbara Koroušić , Kotnik Katja Zdešar
Published: April 2023

Objective

Evaluate the adequacy of energy/macronutrient intake in adolescents according to the Slovenian national recommendations adopted from the recommendations of the German Nutrition Society and to identify differences in energy/macronutrient intake between differently active adolescents.

Methods

Data on energy and macronutrient intake (24-hour dietary recall), physical activity (SHAPES questionnaire), and anthropometric characteristics (body mass and height) of adolescents were obtained on a representative sample of first-year secondary school students (average (SD) age: 15.3 (0.5) years; N = 341), who were included in the national survey The Analysis of Children’s Development in Slovenia (ACDSi) in 2013/14.

Results

75% of adolescents met the national recommendations for carbohydrates and proteins and 44% for fats, whereas only 10% of adolescents met the recommendations for energy intake. Energy/macronutrient intakes were significantly higher in vigorously physically active (VPA) boys compared to moderately (MPA) and less (LPA) physically active boys. No such differences were observed between girls of different physical activity levels.

Conclusion

Adolescents need to be encouraged to meet their energy needs according to gender and physical activity (especially VPA girls) and to reach for higher quality foods in adequate macronutrient proportions.
Introduction to this special section: Critical minerals exploration
Authors: Weiss Chester J. , Jones Alan G.
Published: April 2023

This special section of The Leading Edge focuses on the issue of critical minerals from the perspective of recent progress in mining exploration and anticipated future needs as the global energy economy transitions to higher use of, and reliance on, renewables. The definition of a “critical mineral” is itself context dependent. For example, minerals such as lithium, nickel, cobalt, manganese, and graphite each are essential to the development of modern, high-efficiency lithium-ion batteries, and any disruptions to these minerals — whether through supply chain issues or raw, geologic access — ultimately impacts the future of this now-pervasive, and increasingly necessary, energy storage technology. Similarly, rare earth elements (REEs) have long been central to the manufacture of permanent magnets, which themselves are key components of wind turbines and electric vehicles, the latter of which account for 14% of global passenger car sales in 2022, up from 9% in the previous year. In the United States alone, the market forecast for electric vehicles is expected to grow to roughly US$137 billion in 2028, up from $24 billion in 2020. Lastly, the more “common” but still “critical” minerals copper and aluminum are the backbone of the rapidly expanding global energy distribution systems upon which our modern society is built.
Women Have Greater Endothelin-B Receptor Function and Lower Mitochondrial Capacity Compared to Men With Type 1 Diabetes
Authors: Derella Cassandra C , Thomas Jeffery , Harris Ryan A
Published: April 2023

Context

Type 1 diabetes (T1D) negatively affects both the endothelin system and muscle oxidative capacity. The endothelin pathway is a critical regulator of microcirculatory function and may exhibit sexual dichotomy by which healthy premenopausal women have greater endothelin-B receptor (ETBR) function compared to men. Moreover, T1D may differentially alter muscle oxidative capacity in men and women; however, whether ETBR function is impaired in women compared to men with T1D and its relationship with muscle oxidative capacity has yet to be explored.

Objective

The purpose of this investigation was to determine if ETBR-mediated dilation is impaired in women compared to men with T1D and if this is related to their skeletal muscle oxidative capacity.

Methods

Men (n = 9; glycated hemoglobin A1c [HbA1c] = 7.8 ± 1.0%) and women (N = 10 women; HbA1c = 8.4 ± 1.3%) with uncomplicated T1D were recruited for this investigation. Near-infrared spectroscopy (NIRS) and intradermal microdialysis (750 nM BQ-123 + ET-1 [10−20–10−8 mol/L]) were used to evaluate skeletal muscle oxidative capacity and assess ETBR-mediated vasodilation, respectively.

Results

Skeletal muscle oxidative capacity was significantly lower (P = .031) in women compared with men with T1D. However, ETBR-mediated dilation induced a significantly greater (P = .012) vasodilatory response in women compared to men with T1D, and the area under the curve was negatively associated with skeletal muscle oxidative capacity (r = −.620; P = .042).

Conclusion

Compared to men with uncomplicated T1D, muscle oxidative capacity was lower and ETBR-mediated vasodilation was higher in women with uncomplicated T1D. ETBR-induced vasodilatory capacity was inversely related to skeletal muscle oxidative capacity, suggesting there may be compensatory mechanisms occurring to preserve microvascular blood flow in women with T1D.
Perioperative Care of Transgender and Gender-Diverse Patients: A Biopsychosocial Approach
Authors: Sanchez Kyle J. , Sanchez Raoul A. , Ben Khallouq Bertha , Ellis Dan B.
Published: April 2023

Transgender and gender-diverse (TGD) people endure numerous physical and mental health disparities secondary to lifelong stigma and marginalization, which are often perpetuated in medical spaces. Despite such barriers, TGD people are seeking gender-affirming care (GAC) with increased frequency. GAC facilitates the transition from the sex assigned at birth to the affirmed gender identity and is comprised of hormone therapy (HT) and gender-affirming surgery (GAS). The anesthesia professional is uniquely poised to serve as an integral support for TGD patients within the perioperative space. To provide affirmative perioperative care to TGD patients, anesthesia professionals should understand and attend to the biological, psychological, and social dimensions of health that are relevant to this population. This review outlines the biological factors that impact the perioperative care of TGD patients, such as the management of estrogen and testosterone HT, safe use of sugammadex, interpretation of laboratory values in the context of HT, pregnancy testing, drug dosing, breast binding, altered airway and urethral anatomy after prior GAS, pain management, and other GAS considerations. Psychosocial factors are reviewed, including mental health disparities, health care provider mistrust, effective patient communication, and the interplay of these factors in the postanesthesia care unit. Finally, recommendations to improve TGD perioperative care are reviewed through an organizational approach with an emphasis on TGD-focused medical education. These factors are discussed through the lens of patient affirmation and advocacy with the intent to educate the anesthesia professional on the perioperative management of TGD patients.