bluuebunny/crossref_metadata_2025 huggingface dataset:
Side-by-side comparison of parent vs. technician-collected respiratory swabs in low-income, multilingual, urban communities in the United States
Authors: Chaves Sandra S. , Park Ju-Hyeong , Prill Mila M. , Whitaker Brett , Park Reena , Chew Ginger L.
Published: January 2022

Background

Home-based swabbing has not been widely used. The objective of this analysis was to compare respiratory swabs collected by mothers of 7–12-year-olds living in low-income, multilingual communities in the United States with technician collected swabs.

Methods

Retrospective data analysis of respiratory samples collected at home by mothers compared to technicians. Anterior nasal and throat specimens collected using flocked swabs were combined in dry tubes. Test was done using TaqMan array cards for viral and bacterial pathogens. Cycle threshold (Ct) values of ribonuclease P (RNP) gene were used to assess specimen quality. Ct < 40 was interpreted as a positive result. Concordance of pathogen yield from mother versus technician collected swabs were analyzed using Cohen’s Kappa coefficients. Correlation analysis, paired t-test, and Wilcoxon signed-rank test for paired samples were used for RNP Ct values.

Results

We enrolled 36 households in Cincinnati (African American) and 44 (predominately Chinese or Latino) in Boston. In Cincinnati, eight of 32 (25%) mothers did not finish high school, and 11 (34%) had finished high school only. In Boston, 13 of 44 (30%) mothers had less than a high school diploma, 23 (52%) had finished high school only. Mother versus technician paired swabs (n = 62) had similar pathogen yield (paired t-test and Wilcoxon signed rank test p-values = 0.62 and 0.63, respectively; 95% confidence interval of the difference between the two measurements = − 0.45–0.75). Median Ct value for RNP was 22.6 (interquartile range, IQR = 2.04) for mother-collected and 22.4 (IQR = 2.39) for technician-collected swabs (p = 0.62). Agreement on pathogen yield between samples collected by mothers vs. technicians was higher for viruses than for bacterial pathogens, with high concordance for rhinovirus/enterovirus, human metapneumovirus, and adenovirus (Cohen’s kappa coefficients ≥80%, p < 0.0001). For bacterial pathogens, concordance was lower to moderate, except for Chlamydia pneumoniae, for which kappa coefficient indicated perfect agreement.

Conclusion

Mothers with a range of education levels from low-income communities were able to swab their children equally well as technicians. Home-swabbing using dry tubes, and less invasive collection procedures, could enhance respiratory disease surveillance.
Vaccination against tuberculosis, polio and hepatitis B at birth in Podor health district, Northern Senegal: cross-sectional study of vaccination coverage and its associated factors
Authors: Bassoum Oumar , Sougou Ndeye Mareme , Ba Mouhamadou Faly , Anne Malick , Bocoum Mamoudou , Dieye Alioune , Sokhna Cheikh , Tal-Dia Anta
Published: January 2022

Background

In Senegal, studies focusing specifically on vaccination coverage with the Bacille de Calmette et Guérin (BCG) vaccine, the birth dose of oral polio vaccine (OPV zero dose) and the birth dose of hepatitis B (HepB-BD) vaccine are insufficient. This study aimed to highlight vaccination coverages with birth doses and factors associated with timely vaccination in Podor health district.

Methods

A cross-sectional study was carried out from June 19 to 22, 2020. The study population consisted of children aged 12 to 23 months of which 832 were included. A stratified two-stage cluster survey was carried out. The sources of data were home-based records (HBR), health facility registries (HFR) and parental recalls. Timely vaccination refers to any vaccination that has taken place within 24 h after birth. Descriptive analyzes, the chi-square test and logistic regression were performed.

Results

The crude vaccination coverages with BCG, OPV zero dose and HepB-BD were 95.2%, 88.3% and 88.1%, respectively. Vaccination coverages within 24 h after birth were estimated at 13.9%, 30% and 42.1%, respectively. The factors associated with timely HepB-BD are delivery in a health facility (AOR = 1.55; 95% CI = 1.02–2.40), access to television (AOR = 1.63; 95% CI = 1.16–2.29), weighing (AOR = 3.92; 95% CI = 1.97–8.53) and hospitalization of the newborn immediately after birth (AOR = 0.42; 95% CI = 0.28–0.62).

Conclusion

Timely administration of birth doses is a challenge in the Podor health district. The solutions would be improving geographic access to health facilities, involving community health workers, raising awareness and integrating health services.
Assessing the implementation of community-based learning in public health: a mixed methods approach
Authors: Leblanc Pierre , Occelli Pauline , Etienne Jerome , Rode Gilles , Colin Cyrille
Published: January 2022

Background

The French government has set up a community-based learning programme on health promotion for undergraduate health students to involve them in key public health objectives. At the University of Lyon, students first underwent formal instruction, including e-learning, lectures, and interactive seminars, and then became health educators for school pupils. The main objective of the present study was to assess the process of implementing this programme during the 2018–2019 academic year.

Methods

The satisfaction and perception of medical and midwife students with community-based learning experiences were assessed by a questionnaire, semi-directive interviews, and observations. Replies to the questionnaire were described by median and interquartile range or by proportion. A paired Wilcoxon-Mann–Whitney test was used to compare self-evaluated students’ competence scores before and after the seminars (alpha risk of 5%). Thematic analyses using grounded theory were performed on recorded and transcribed interviews, and on transcribed notes taken during the observations.

Results

Over time the students have evolved from a negative perception of the community-based learning to a positive one. The students were mostly satisfied by interactive seminars that allowed them to gain confidence and competencies in health education. Their involvement in the programme increased their self-esteem. They became more aware of their educative responsibilities regarding public health issues as future professionals.

Conclusions

The students had a positive perception of the implementation of a community-based learning programme in our University, as it appeared a pertinent strategy to raise their awareness of prevention and health education issues.
Prediction and risk stratification from hospital discharge records based on Hierarchical sLDA
Authors: Yu Guanglei , Zhang Linlin , Zhang Ying , Zhou Jiaqi , Zhang Tao , Bi Xuehua
Published: January 2022

Background

The greatly accelerated development of information technology has conveniently provided adoption for risk stratification, which means more beneficial for both patients and clinicians. Risk stratification offers accurate individualized prevention and therapeutic decision making etc. Hospital discharge records (HDRs) routinely include accurate conclusions of diagnoses of the patients. For this reason, in this paper, we propose an improved model for risk stratification in a supervised fashion by exploring HDRs about coronary heart disease (CHD).

Methods

We introduced an improved four-layer supervised latent Dirichlet allocation (sLDA) approach called Hierarchical sLDA model, which categorized patient features in HDRs as patient feature-value pairs in one-hot way according to clinical guidelines for lab test of CHD. To address the data missing and imbalance problem, RFs and SMOTE methods are used respectively. After TF-IDF processing of datasets, variational Bayes expectation-maximization method and generalized linear model were used to recognize the latent clinical state of a patient, i.e., risk stratification, as well as to predict CHD. Accuracy, macro-F1, training and testing time performance were used to evaluate the performance of our model.

Results

According to the characteristics of our datasets, i.e., patient feature-value pairs, we construct a supervised topic model by adding one more Dirichlet distribution hyperparameter to sLDA. Compared with established supervised algorithm Multi-class sLDA model, we demonstrate that our proposed approach enhances training time by 59.74% and testing time by 25.58% but almost no loss of average prediction accuracy on our datasets.

Conclusions

A model for risk stratification and prediction of CHD based on sLDA model was proposed. Experimental results show that Hierarchical sLDA model we proposed is competitive in time performance and accuracy. Hierarchical processing of patient features can significantly improve the disadvantages of low efficiency and time-consuming Gibbs sampling of sLDA model.
Validation of the Helsinki University Hospital prevent pressure Injury Risk Assessment Tool: a prospective observational study
Authors: Heikkilä Anniina , Kotila Jaana , Junttila Kristiina
Published: January 2022

Background

Pressure injures are a common adverse event in a hospital, and they are one of the most important quality indicators of patient care. Risk assessment is recommended as the first step in the prevention of pressure injuries. A Prevent Pressure Injury Risk Assessment Tool is a new tool for risk assessment that was developed by the Helsinki University Hospital.

Aim

The aim of this study was to evaluate the predictive validity and the concurrent validity of the Prevent Pressure Injury Risk Assessment Tool in acute care.

Method

The prospective observational study was conducted in 19 in-patient wards representing internal medicine, neurology, and surgery during 2017–2018. The participants’ inclusion criteria were: age ≥18 years old, no pressure injury on admission to the hospital and consenting to participate. The data collected by physical assessment of patients was combined with data from electronic patient records. Each patient was assessed by two different nurses with the Prevent Pressure Injury Risk Assessment Tool and the Braden Scale at patient admission. Furthermore, skin condition was observed throughout the hospital stay.

Results

Of the 637 patients accepted for the study, 10 (1.6%) developed a pressure injury during the hospital stay. Poisson regression analysis showed that pressure injuries were more likely in high–risk patients compared to those with low-risk. The sensitivity of the Prevent Pressure Injury Risk Assessment Tool was adequate (75%), while specificity was poor (40%). A moderate correlation was found between the Prevent Pressure Injury Risk Assessment Tool and the Braden Scale.

Conclusions

The Prevent Pressure Injury Risk Assessment Tool may be useful for identifying the adult pressure injury risk patients in acute care. Further research is needed to evaluate interrater reliability, and usability and validity with different patient populations.
Attitude toward second opinions in Germany – a survey of the general population
Authors: Könsgen Nadja , Prediger Barbara , Schlimbach Anna , Bora Ana-Mihaela , Hess Simone , Caspers Michael , Pieper Dawid
Published: January 2022

Background

Second medical opinions (SOs) can assist patients in making informed treatment decisions and improve the understanding of their diagnosis. In Germany, there are different approaches to obtain a structured SO procedure: SO programs by health insurers and SOs according to the SO Directive. Through a direct survey of the population, we aimed to assess how structured SOs should be provided to fulfil patients’ needs.

Methods

A stratified sample of 9990 adults (≥18 years) living in the federal states of Berlin and Brandenburg (Germany) were initially contacted by post in April and sent a reminder in May 2020. The survey results were analyzed descriptively.

Results

Among 1349 participants (response rate 14%), 56% were female and the median age was 58 years (interquartile range (IQR) 44–69). Participants wanted to be informed directly and personally about the possibility of obtaining an SO (89%; 1201/1349). They preferred to be informed by their physician (93%; 1249/1349). A majority of participants would consider it important to obtain an SO for oncological indications (78%; 1049/1349). Only a subset of the participants would seek an SO via their health insurer or via an online portal (43%; 577/1349 and 16%; 221/1349). A personally delivered SO was the preferred route of SO delivery, as 97% (1305/1349) would (tend to) consider this way of obtaining an SO. Participants were asked to imagine having moderate knee pain for years, resulting in a treatment recommendation for knee joint replacement. They were requested to rate potential qualification criteria for a physician providing the SO. The criteria rated to be most important were experience with the recommended diagnosis/treatment (criterion (very) important for 93%; 1257/1349) and knowledge of the current state of research (criterion (very) important for 86%; 1158/1349). Participants were willing to travel 60 min (median; IQR 60–120) and wait 4 weeks (median; IQR 2–4) for their SO in the hypothetical case of knee pain.

Conclusion

In general, SOs were viewed positively. We found that participants have clear preferences regarding SOs. We propose that these preferences should be taken into account in the future design and development of SO programs.
First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain
Authors: Matt Eva , Kaindl Lisa , Tenk Saskia , Egger Anicca , Kolarova Teodora , Karahasanović Nejla , Amini Ahmad , Arslan Andreas , Sariçiçek Kardelen , Weber Alexandra , Beisteiner Roland
Published: January 2022

Background

With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior.

Methods

Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed.

Results

Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area.

Conclusions

TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.
Point-of-care cell therapy manufacturing; it’s not for everyone
Authors: Stroncek David F. , Somerville Robert P. T. , Highfill Steven L.
Published: January 2022

The use of cellular therapies to treat cancer, inherited immune deficiencies, hemoglobinopathies and viral infections is growing rapidly. The increased interest in cellular therapies has led to the development of reagents and closed-system automated instruments for the production of these therapies. For cellular therapy clinical trials involving multiple sites some people are advocating a decentralized model of manufacturing where patients are treated with cells produced using automated instruments at each participating center using a single, centrally held Investigational New Drug Application (IND). Many academic centers are purchasing these automated instruments for point-of-care manufacturing and participation in decentralized multiple center clinical trials. However, multiple site manufacturing requires harmonization of product testing and manufacturing in order to interpret the clinical trial results. Decentralized manufacturing is quite challenging since all centers should use the same manufacturing protocol, the same or comparable in-process and lot release assays and the quality programs from each center must work closely together. Consequently, manufacturing cellular therapies using a decentralized model is in many ways more difficult than manufacturing cells in a single centralized facility. Before an academic center decides to establish a point-of-care cell processing laboratory, they should consider all costs associated with such a program. For many academic cell processing centers, point-of-care manufacturing may not be a good investment.
Evaluation of a breastmilk hand expression toolkit: the M.I.L.K survey study
Authors: Alibhai Kameela Miriam , Murphy Malia S. Q. , Dunn Sandra , Keely Erin , O’Meara Paloma , Anderson Josdalyne , El-Chaâr Darine
Published: January 2022

Background

Breastmilk hand expression (BMHE) is recommended to promote lactation, relieve breast engorgement, and collect milk for future infant feedings. Resources to teach this skill are limited and infrequently developed in partnership with the obstetrical population. In collaboration with maternity care experts and individuals with recent breastfeeding experience, we designed a one-page toolkit that describes the process of BMHE and includes step-by-step instructions and images to illustrate the technique. This study aimed to evaluate the readability, clarity of content, layout, and informational value of this BMHE toolkit.

Methods

Individuals who intended to breastfeed, were currently breastfeeding, or had recently breastfed were electronically surveyed and completed a two-part survey that consisted of radio, multi-select, Likert scale, and open-ended questions. Part one captured sociodemographic factors, obstetrical history, and breastfeeding practices. Part two collected feedback on the BMHE toolkit. Participants were recruited electronically through social media and posters were circulated in antenatal and postnatal care settings in Ottawa, Canada between November 2020 and February 2021.

Results

Of the 123 participants, 117 (95.1%) had heard of hand expression prior to reviewing the toolkit and 99 (80.5%) had hand expressed before. Among the 48 participants who were no longer exclusively breastfeeding at the time of the survey, 22 (45.8%) had exclusively breastfed their infant for at least six months and 7 (14.6%) had discontinued exclusive breastfeeding within the first month. When asked about the BMHE toolkit, 118 (95.9%) participants said it was informative, 115 (93.5%) said it was easy to understand, and 114 (92.7%) said it was well laid-out. When asked about information seeking behaviours, participants indicated a preference for online resources (58.5%) and video resources (22.0%).

Conclusions

The BMHE toolkit was well received by participants and the feedback was favourable overall. The survey feedback will be used to create a revised version of the toolkit that has been validated by the obstetrical patient population. Future research should focus on identifying implementation strategies to optimize the use of the toolkit and increase its effectiveness as an educational resource to teach participants correctly BMHE.
WSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections
Authors: Sartelli Massimo , Coccolini Federico , Kluger Yoram , Agastra Ervis , Abu-Zidan Fikri M. , Abbas Ashraf El Sayed , Ansaloni Luca , Adesunkanmi Abdulrashid Kayode , Augustin Goran , Bala Miklosh , Baraket Oussama , Biffl Walter L. , Ceresoli Marco , Cerutti Elisabetta , Chiara Osvaldo , Cicuttin Enrico , Chiarugi Massimo , Coimbra Raul , Corsi Daniela , Cortese Francesco , Cui Yunfeng , Damaskos Dimitris , de’Angelis Nicola , Delibegovic Samir , Demetrashvili Zaza , De Simone Belinda , de Jonge Stijn W. , Di Bella Stefano , Di Saverio Salomone , Duane Therese M. , Fugazzola Paola , Galante Joseph M. , Ghnnam Wagih , Gkiokas George , Gomes Carlos Augusto , Griffiths Ewen A. , Hardcastle Timothy C. , Hecker Andreas , Herzog Torsten , Karamarkovic Aleksandar , Khokha Vladimir , Kim Peter K. , Kim Jae Il , Kirkpatrick Andrew W. , Kong Victor , Koshy Renol M. , Inaba Kenji , Isik Arda , Ivatury Rao , Labricciosa Francesco M. , Lee Yeong Yeh , Leppäniemi Ari , Litvin Andrey , Luppi Davide , Maier Ronald V. , Marinis Athanasios , Marwah Sanjay , Mesina Cristian , Moore Ernest E. , Moore Frederick A. , Negoi Ionut , Olaoye Iyiade , Ordoñez Carlos A. , Ouadii Mouaqit , Peitzman Andrew B. , Perrone Gennaro , Pintar Tadeja , Pipitone Giuseppe , Podda Mauro , Raşa Kemal , Ribeiro Julival , Rodrigues Gabriel , Rubio-Perez Ines , Sall Ibrahima , Sato Norio , Sawyer Robert G. , Shelat Vishal G. , Sugrue Michael , Tarasconi Antonio , Tolonen Matti , Viaggi Bruno , Celotti Andrea , Casella Claudio , Pagani Leonardo , Dhingra Sameer , Baiocchi Gian Luca , Catena Fausto
Published: January 2022

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.

Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs.

An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.
Anatomical study for the treatment of proximal humeral fracture through the medial approach
Authors: Xiang Hao , Wang Yan , Yang Yongliang , Liu Fanxiao , Lu Qingsen , Kong Lingpeng , Li Mingzhen , Han Yong , Wang Fu
Published: January 2022

Background

The treatment of complex 3- and 4-part proximal humeral fractures has been controversial due to numerous postoperative complications. With the further study of medial support and blood supply of humeral head, new techniques and conception are developing. The study aims to illustrate the medial approach of the proximal humeral fracture through cadaver autopsy.

Method

Upper limbs from 19 cadavers have been dissected to expose the shoulder joint. We selected the coracoid process as the bony reference. Vernier caliper will be used to measure the following data, including distance from coracoid process to circumflex brachial artery, distance between anterior humeral circumflex artery (ACHA) and posterior circumflex brachial artery (PCHA) and their diameters. Assessment included the characteristics of the vascular supply around the humeral head, identification of the structures at risk, quality of exposure of the bony structures, and feasibility of fixation.

Results

The medial approach is appropriate in 86.84% anatomical patterns. Between the lower part of the shoulder capsule and the insertion of conjoined tendon, the bony surface exposed was limited by the interval between ACHA and PCHA. An interval of 2 to 3 cm (24.29 ± 3.42 mm) was available for medial plate. ACHA (49.35 ± 8.13 mm, 35.14–68.53 mm) and PCHA (49.62 ± 7.82 mm, 37.67–66.76 mm) were about 5 cm away from the coracoid process. Risk structures including ACHA and PCHA originate in common, PCHA originated from the deep brachial artery (DBA), the presence of perforator vessels, musculocutaneous nerve intersects with ACHA, the diameter of PCHA: ACHA < 1.5. In 13.15% anatomical patterns, this risk structure should be taken seriously.

Conclusion

The medial approach opens a new perspective in the optimal management of complex fractures of proximal humerus. Anatomical research proves that the medial approach is feasible. The interval between ACHA and PCHA is suitable for placement. Anatomical pattern and indication have been discussed, and we hypothesized that ACHA has been destroyed in complex PHFs. With further studies on the anatomy and mechanism of injury, the development of more clinical cases will be an important work of our institution in the future.
Anti-high-mobility group box-1 (HMGB1) mediates the apoptosis of alveolar epithelial cells (AEC) by receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway in the rats of crush injuries
Authors: Zhang Bin-Fei , Song Wei , Wang Jun , Wen Peng-Fei , Zhang Yu-Min
Published: January 2022

Objectives

The lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model.

Methods

Seventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses.

Results

Nine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups.

Conclusion

The remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.
5-ALA-mediated fluorescence of musculoskeletal tumors in a chick chorio-allantoic membrane model: preclinical in vivo qualification analysis as a fluorescence-guided surgery agent in Orthopedic Oncology
Authors: Guder Wiebke K. , Hartmann Wolfgang , Buhles Clarissa , Burdack Maike , Busch Maike , Dünker Nicole , Hardes Jendrik , Dirksen Uta , Bauer Sebastian , Streitbürger Arne
Published: January 2022

Background

Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) and other contrast agents has shown its efficacy in improving resection margins, local recurrence and survival rates in several medical disciplines. It is the objective of this study to analyze the engraftment rate of musculoskeletal tumor specimens on the chick chorio-allantoic membrane (CAM), the rate of tumor fluorescence (PDD), and the effects of photodynamic therapy (PDT) after exposure of tumors to 5-ALA in an in vivo environment.

Methods

A total of 486 CAMs were inoculated with macroscopic tumor grafts (n = 26; n = 478 eggs) and primary cell culture suspensions (n = 2; n = 8 eggs) from 26 patients on day 10 of egg development. On day 16, 2 mg/200 µl 5-ALA were topically applied per egg. After 4 h of incubation, Protoporphyrin IX was excited using blue light (420 ± 10 nm). Tumor fluorescence (PDD) was photo-documented. A subgroup of specimens was additionally exposed to red light (635 nm ± 10 nm; PDT). After the termination of the experiment, CAM-grown tumors were histopathologically analyzed.

Results

Benign and borderline tumors (chondroblastoma, giant cell tumor of bone and atypical chondrogenic tumor) presented with high rates of detectable fluorescence. Comparable results were found for chondrosarcoma, osteosarcoma and Ewing’s sarcoma among bone and dedifferentiated liposarcoma, myxofibrosarcoma and undifferentiated pleomorphic sarcoma among soft tissue sarcomas. Overall, tumor fluorescence was negative for 20.2%, single-positive (+) for 46.9% and double-positive (++) for 32.9% of macroscopic xenografts, and negative in 20% and (+) in 80% of primary cell culture tumors. Macroscopic tumor xenografts (n = 478) were identified as viable in 14.8%, partially viable in 2.9% and partially to completely regressive in 45.2%. All (n = 8) tumors grown from primary cell culture were viable. After PDT, tumor samples were found viable in 5.5%, partially viable in 5.5% and partially to completely regressive in 68%. Egg survival increased with decreasing PDT doses.

Conclusions

The CAM model proves to be a suitable in vivo model for the investigation of short-term observation questions in musculoskeletal tumors. The findings of this study warrant further investigation of PDT effects on musculoskeletal tumors and a possible incorporation of 5-ALA FGS in clinical Orthopedic Oncology care.
Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension
Authors: Yu Zhijie , Xiao Jun , Chen Xiao , Ruan Yi , Chen Yang , Zheng Xiaoyuan , Wang Qiang
Published: January 2022

Pulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH.

Graphical Abstract
Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains
Authors: Bigley Tarin M. , Xiong Monica , Ali Muhammad , Chen Yun , Wang Chao , Serrano Javier Remolina , Eteleeb Abdallah , Harari Oscar , Yang Liping , Patel Swapneel J. , Cruchaga Carlos , Yokoyama Wayne M. , Holtzman David M.
Published: January 2022

Background

The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition.

Methods

We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD.

Results

We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, −omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD.

Conclusion

Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.
DENA: training an authentic neural network model using Nanopore sequencing data of Arabidopsis transcripts for detection and quantification of N6-methyladenosine on RNA
Authors: Qin Hang , Ou Liang , Gao Jian , Chen Longxian , Wang Jia-Wei , Hao Pei , Li Xuan
Published: January 2022

Models developed using Nanopore direct RNA sequencing data from in vitro synthetic RNA with all adenosine replaced by N6-methyladenosine (m6A) are likely distorted due to superimposed signals from saturated m6A residues. Here, we develop a neural network, DENA, for m6A quantification using the sequencing data of in vivo transcripts from Arabidopsis. DENA identifies 90% of miCLIP-detected m6A sites in Arabidopsis and obtains modification rates in human consistent to those found by SCARLET, demonstrating its robustness across species. We sequence the transcriptome of two additional m6A-deficient Arabidopsis, mtb and fip37-4, using Nanopore and evaluate their single-nucleotide m6A profiles using DENA.
Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)—study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial
Authors: Maláska Jan , Stašek Jan , Duška František , Balík Martin , Máca Jan , Hruda Jan , Vymazal Tomáš , Klementová Olga , Zatloukal Jan , Gabrhelík Tomáš , Novotný Pavel , Demlová Regina , Kubátová Jana , Vinklerová Jana , Svobodník Adam , Kratochvíl Milan , Klučka Jozef , Gál Roman , Singer Mervyn ,   on behalf of the REMED Study Group
Published: January 2022

Background

Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids.

Methods

REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1–5, followed by dexamethasone 10 mg on days 6–10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic.

Discussion

We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety.

Trial registration

EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020
Blood flow restriction with different load levels in patients with knee osteoarthritis: protocol of a randomized controlled trial
Authors: Jardim Roger Andrey Carvalho , de Sousa Tamara Silva , dos Santos Wueyla Nicoly Nascimento , Matos Areolino Pena , Iosimuta Natália Camargo Rodrigues
Published: January 2022

Background

The effectiveness of blood flow restriction training (BFR) in elderly with knee osteoarthritis (OA) is comparable to performing high-intensity protocols (70 to 80% of 1 RM [repetition maximum]) that are known to be effective for improving the muscle strength of knee extensors, with the advantage of generating less particular rating of perceived exertion and pain immediately after training. However, despite being a promising alternative, little is known about the best way to apply the BFR, such as level of pressure and combination or not with other therapeutic modalities. The purpose of this study is to evaluate whether different levels of blood flow restriction with low load (BFR + LL) and no load (BFR + rest) are non-inferior to high-intensity resistance exercise (HIRE+BFRplacebo) for pain reduction in patients with knee OA.

Methods/design

This clinical trial is a non-inferiority, five-arm, randomized, active-controlled, single trial which will be carried out in 165 patients of both sexes with knee OA, aged 50 years and older. Participants will be randomly allocated into 5 exercise groups (40% of BFR + LL; 80% of BFR + LL; 40% of BFR + rest; 80% BFR + rest, and HIRE+BFR placebo). A mixed linear model will be used to examine the effect of group-by-time interaction on pain intensity on the WOMAC subscale (primary outcome) and on disease severity, physical functional data, balance data, quality of life, global perceived effect scale, and muscle strength (secondary outcomes). Participants will be analyzed for intention-to-treat, and the statistical assessor blinded to the groups. The collection of outcomes 72 h after completion of the 16 weeks of interventions will be the primary measurement point. Follow-up secondary timepoints will be collected at 20, 28, 40, 52, and 64 weeks after the end of interventions, except for pain during the training, which will be measured immediately at the end of each session. Only the comparison of the primary outcome between the HIRE group with each BFR group will be analyzed in the non-inferiority framework, the other comparisons between the BFR groups for the primary outcome, and all secondary outcomes will be interpreted in the superiority framework.

Discussion

The results of this clinical trial can point out more clearly to ways to optimize the BFR training with the minimum of pain immediately after training, which will allow the offer of an effective and more adherent strengthening training to patients with knee OA.

Trial registration

Registro Brasileiro de Ensaios Clínicos, RBR-93rx9q. Registered on 23 July 2020. Version 1.0.
Association between life-course cigarette smoking and metabolic syndrome: a discovery-replication strategy
Authors: Wang Jingya , Bai Yang , Zeng Zihang , Wang Jun , Wang Ping , Zhao Yongai , Xu Weili , Zhu Yun , Qi Xiuying
Published: January 2022

Background

The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples.

Methods

Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged ≥ 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS.

Results

In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64–2.47) and 1.76 (95%CI: 1.44–2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged < 70 years (Pinteraction = 0.015). We were able to replicate the association between cigarette smoking and MetS in an independent adult sample (second tertile vs. never: OR = 1.30, 95%CI: 1.04–1.63). The interaction of smoking with age was also replicated.

Conclusions

Life-course cigarette smoking is associated with an increased odds of MetS, especially among individuals who aged < 70 years.
Adherence and persistence rates of major antidiabetic medications: a review
Authors: Lee David Seung U. , Lee Howard
Published: January 2022

The objective of this paper was to review the adherence and persistence rates of major antidiabetic medication classes (i.e., metformin, sulfonylureas, sodium glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, insulin, glucagon-like peptide-1 receptor agonists, and thiazolidinediones) by summarizing the major findings of the studies published since 2017. In addition, we reported the potential causes for low adherence and persistence of antidiabetic medications. Based on the literature, the highest rate of adherence and persistence was consistently observed in metformin users. Second to metformin were sodium glucose cotransporter-2 inhibitors. Injectable therapies such as insulin and glucagon-like peptide-1 receptor agonists trailed low on the adherence and persistence rates. To the best of our knowledge, no studies published since the year 2017 analyzed the adherence and persistence of thiazolidinediones independently. The most frequently cited cause for low adherence and persistence was the severity of adverse events. Baseline characteristics (e.g., baseline HbA1c level), demographic information (e.g., age, gender, or ethnicity), and comorbidity profiles also had significant impacts on adherence and persistence in patients with type 2 diabetes mellitus.
Occupational performance of children with autism spectrum disorder and quality of life of their mothers
Authors: Beheshti Seyedeh Zeinab , Hosseini Seyed-Sirvan , Maroufizadeh Saman , Almasi-Hashiani Amir
Published: January 2022

Objectives

Limited studies were found to investigate the occupational performance of autistic children and their parents’ quality of life. Therefore, this study aimed to investigate occupational performance of children with Autism Spectrum Disorder (ASD) and QoL of their mothers.

Results

In this study, 88 participants were selected from autism centers in Arak, Iran, 2020. The Canadian Occupational Performance Measure (COPM) and the parent version of Quality of Life in Autism Questionnaire (QoLA-P) were used to assess the occupational performance of ASD children and their mothers QoL. QoLA-P consists of parts A which is related to the quality of life and part-B related to the problems that these children have and are related to the parents or their caregivers. Regarding occupational performance, the first priority of mothers is self-care with frequency 64.8%. The finding suggested a significant correlation between total function score of COPM and the score of part-A (r = 0.227, p = 0.033) of QoLA-P. Also, the results revealed a significant correlation between the total satisfaction score of COPM and the score of part-A (r = 0.236, p = 0.026) and part-B of QoLA-P questionnaire (r = 0.231, p = 0.030). The mothers’ first priority is self-care and, the total satisfaction and function score of COPM showed a significant correlation with mothers’ QoL.
Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury
Authors: Li Xiangling , Guan Yanjun , Li Chaochao , Zhang Tieyuan , Meng Fanqi , Zhang Jian , Li Junyang , Chen Shengfeng , Wang Qi , Wang Yi , Peng Jiang , Tang Jinshu
Published: January 2022

Various immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.