bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a patient reported experience measure for experimental cancer medicines (PREM-ECM) and their carers (PREM-ECM-Carer)
Authors: Sawyer Chelsea S. , Taylor Sally , Carter Louise , Stanworth Melissa , Davies Michelle , Thistlethwaite Fiona , Taylor Jo , Eastwood Charlotte , Yorke Janelle
Published: April 2024

Background

Our aim was to develop a validated Patient Reported Experience Measure (PREM) to capture patient and carer experience during participation in experimental cancer medicine trials (ECM): called PREM-ECM.

Methods

Mixed method design, consisting of four stages. Questionnaire items were produced for both patients and carers using interviews, focus groups, and cognitive interviews with patients and carers separately. For both patient and carer PREMs, a cross-sectional questionnaire study was conducted to identify final items for inclusion using hierarchical item reduction and Rasch analysis. Questionnaire validity and reliability were assessed, including administration feasibility.

Results

Initial interview participants suggested the need for three PREMs, two specific to patients: (i) a ‘prior’ questionnaire that captured experiences of trial introduction, screening, consenting, and early trial experience (< 6 weeks post consent); and (ii) ‘on-trial’ that captured experiences of ongoing consent and trial participation; and (iii) a PREM specific for carers. The draft 25-item ‘prior’ questionnaire was completed by 162 patients and 162 patients completed the draft 35-item ‘on-trial’ questionnaire. Hierarchical and Rasch analysis produced a 14-item ‘prior’ list and a 15-item list for ‘on-trial’. Both patient PREM’s demonstrated a good fit to the Rasch model following Bonferroni correction (X2p = 0.008). The carer 34-draft item questionnaire was completed by 102 participants. Hierarchical and Rasch analysis produced a 13-item list for PREM-ECM-Carer, with good fit to the Rasch model ( X2p = 0.62). The pilot testing demonstrated the feasibility of all the PREMs in capturing patient and caregiver experiences in routine clinical settings.

Conclusions

The three PREM-ECM questionnaires will be the first validated experience measures for ECM trial patients and their carers. These questionnaires may be used to assess patients’ and their carers’ experiences of ECM and enable robust comparisons across cancer trial units highlighting areas for service improvement.
Germline mutations in BRCA1 and BRCA2 among Brazilian women with ovarian cancer treated in the Public Health System
Authors: de Oliveira Ferreira Caroline , Carneiro Vandré Cabral Gomes , Araujo Mariz Carolline
Published: April 2024

Background

Germline mutations in BRCA1 and BRCA2 genes are among the main causes of hereditary ovarian cancer. Identifying these mutations may reduce cancer risk, facilitate early detection, and enable personalized treatment. However, genetic testing is limited in the Brazilian Public Health System, and data regarding germline mutations in many regions are scarce. Therefore, the study aimed to investigate the prevalence of germline mutations in BRCA1 and BRCA2 in women with ovarian cancer treated in the Public Health System in Pernambuco, Brazil.

Methods

A cross-sectional study was conducted in the Hereditary Cancer Program from two reference oncological centers in Pernambuco. Women (n = 45) with high-grade serous ovarian cancer underwent genetic counseling and DNA sequencing for BRCA1 and BRCA2 genes.

Results

The prevalence of deleterious mutations in the BRCA1 and BRCA2 genes was 33%. Of the 15 germline mutations found, 13 were in BRCA1 and 2 in BRCA2; two mutations of unknown clinical significance were also found in BRCA2. Mutations c.5266dupC and c.2215 A > T were the most frequent; each was mutation observed in three patients. Additionally, the mutations c.7645dupT and c.921dupT were reported for the first time.

Conclusion

One in three women showed a pathogenic mutation, demonstrating a significant prevalence of germline mutations in this sample. Additionally, the small sample revealed an interesting number of mutations, indicating the need to explore more regions of the country.
The comorbid network characteristics of anxiety and depressive symptoms among Chinese college freshmen
Authors: Luo Jie , Bei Dong-Li , Zheng Chuanzhang , Jin Jie , Yao Chengkui , Zhao Jianhua , Gong Jie
Published: April 2024

Background

This study aimed to investigate the interplay between anxiety and depressive symptoms in Chinese college freshmen using the causal system perspective (CSP), which differs from the traditional common cause perspective (CCP) by providing an alternative explanation by attributing comorbidity to direct interactions among symptoms.

Methods

A convenience sample of 2,082 Chinese college freshmen (39.51% male, Mage = 18.61) from a normal university completed the Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9). Network analysis was conducted and evaluated as to centrality, stability, node predictability, and bridging features. Moreover, the moderated network model (MNM) was utilized to detect the moderation effects of gender in the comorbidity network.

Results

The network of anxiety and depressive symptoms exhibited stability, characterized by the core symptoms of “restlessness”, “lack of energy”, and “excessive worry about control”, as well as the bridging symptoms of “fearfulness”, “sad mood”, and “irritability”. Notably, the nodes representing “uncontrollable worry” and “difficulty in relaxation” demonstrated the highest predictive power. Gender did not exert any moderating effects on the anxiety and depressive symptom network.

Conclusion

These results reinforce that certain anxiety or depressive symptoms are more central than others, and thus play a more vital role in the comorbid network. These findings highlight underlying potential targeting symptoms to consider in future interventions.
Associations between Life’s Essential 8 and abdominal aortic calcification among US Adults: a cross-sectional study
Authors: Liu Quanjun , Xiang Hong , Chen Shuhua , Ouyang Jie , Liu Huiqin , Zhang Jing , Chai Yanfei , Gao Peng , Zhang Xiao , Fan Jianing , Zheng Xinru , Lu Hongwei
Published: April 2024

Background

Cardiovascular health (CVH) and abdominal aortic calcification (AAC) are closely linked to cardiovascular disease (CVD) and related mortality. However, the relationship between CVH metrics via Life’s Essential 8 (LE8) and AAC remains unexplored.

Methods

The study analyzed data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) cohort, which included adults aged 40 or above. The research used the LE8 algorithm to evaluate CVH. Semi-quantitative AAC-24 scoring techniques were employed to assess AAC, categorized into no calcification, mild to moderate calcification, and severe calcification.

Results

The primary analysis involved 2,478 participants. Following adjustments for multiple factors, the LE8 score exhibited a significant association with ACC risk (Mild-moderate ACC: 0.87, 95% CI: 0.81,0.93; Severe ACC: 0.77, 95% CI: 0.69,0.87, all P < 0.001), indicating an almost linear dose–response relationship. Compared to the low CVH group, the moderate CVH group showed lower odds ratios (OR) for mild-moderate and severe calcification (OR = 0.78, 95% CI: 0.61–0.99, P = 0.041; OR = 0.68, 95% CI: 0.46–0.99, P = 0.047, respectively). Moreover, the high CVH group demonstrated even lower ORs for mild-moderate and severe calcification (OR = 0.46, 95% CI: 0.31, 0.69, P < 0.001; OR = 0.29, 95% CI: 0.14, 0.59, P = 0.001, respectively). Interactions were found between chronic kidney disease (CKD) condition, history of CVD, marital status and CVH metrics to ACC. Participants without CKD exhibited a more pronounced negative association between the CVH metric and both mild-moderate and severe ACC. Those lacking a history of CVD, and never married/widowed/divorced/separated showed a stronger negative association between the CVH metric and severe ACC.

Conclusions

The novel CVH metrics demonstrated an inverse correlation with the risk of AAC. These findings suggest that embracing improved CVH levels may assist in alleviating the burden of ACC.
How different attributes are weighted in professionals’ decision-making in Pediatric Dentistry—a protocol for guiding discrete choice experiment focused on shortening the evidence-based practice implementation for dental care
Authors: Machado Gabriela Manco , Luca Ana Clara Falabello , Pereira Renata Paz Leal , Fernandez Ana Yne , Rodrigues Lucas Gabriel Santini , Leite Isabella Petroline , Cenci Maximiliano Sergio , Cenci Tatiana Pereira , Santos Ana Paula Pires , Oliveira Branca Heloisa , Nadanovsky Paulo , Lima Marina Deus Moura , Moura Marcoeli Silva , Lucena Edson Hilan Gomes , Lenzi Tathiane Larissa , Crispim Ana Carla , Carrer Fernanda Campos Almeida , Gabriel Mariana , Lira Claudia Cazal , Gurgel Carla Vecchione , Pinheiro Helder Henrique Costa , Pucca Gilberto Alfredo , Martins Fábio Carneiro , Calvasina Paola Gondim , Tricoli Maria Fernanda Montezuma , Branco Camila Menezes Costa Castelo , Freitas Raiza Dias , Imparato José Carlos Pettorossi , Raggio Daniela Prócida , Tedesco Tamara Kerber , Mendes Fausto Medeiros , Braga Mariana Minatel
Published: April 2024

Background

Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that.

Methods

This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals’ perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice.

Discussion

Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals’ decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals.

Trial registration

https://osf.io/bhncv.
Encapsulation of propolis extracted with methylal in the chitosan nanoparticles and its antibacterial and cell cytotoxicity studies
Authors: Vaseghi Akbar , Parchin Reza Ashrafi , Chamanie Kosar Rezaee , Herb Marc , Maleki Hajar , Sadeghizadeh Majid
Published: April 2024

In this study we develop novel type of antibacterial chitosan-propolis NPs to improve theantimicrobial activity against various pathogens. To this aim, we primarily extracted propolis with methylal and ethanol as green solvents and its encapsulation with chitosan NPs. The developed propolis loaded chitosan NPs indicated antimicrobial and anti-biofilm properties against various gram positive and negative. FTIR revealed the successful encapsulation of the propolis extract with Ethanol (PE) and Methylal (PM) into the chitosan nano career matrix. HPLC and GC-MASS also confirmed the presence of flavonoids and phenols compounds of propolis extracted with both solvents. In addition, we confirmed the total phenolic and flavonoid compounds in propolis by calorimetric method of Folin–Ciocalteu and aluminum trichloride complex formation assays, respectively. PE-CH and PM-CH were optimized regarding physicochemical properties such as particle size, zeta potential, and poly dispersity index (PDI) index. DLS and SEM micrographs confirmed a spherical morphology in a range of 360–420 nm with Z potential values of 30–48 mV and PDI of 0.105–0.166 for PE-CH and PM-CH, respectively. The encapsulation efficiency was evaluated using colorimetric analysis, with median values ranging from 90 to 92%. The MIC values within the range of 2 to 230 µg/ml and MBC values between 3 to 346 μg/ml against both gram-positive and negative bacteria. While both PE and PM showed a significant reduction in the number of E. coli, S. aureus, and S. epidermidis, the use of PE-CH and PM-CH led to a statistically significant and greater reduction in number of E. coli, S. aureus, and S. epidermidis strains on the biofilm, pre-formed biofilm and planktonic phases. Besides, the DPPH assay showed significant antioxidant activity for these NPs within the range of 36 to 92%. MTT assay for MHFB-1, HFF, L929, MDF, and MCF-7 cells exhibited statistically significant differences in each other that show the IC50 between 60–160 µg/ml for normal cells and 20 for cancer cells. Finally the present study indicated that both PM and PM-CH greater than PE and PE-CH in which contain high flavonoid and phenolic contents with a high antioxidation potential antioxidant properties, which could be beneficial for cell proliferation and antibiotic and anticancer applications.
An insight into the use of telemedicine technology for cancer patients during the Covid-19 pandemic: a scoping review
Authors: Toni Esmaeel , Ayatollahi Haleh
Published: April 2024

Background

The use of telemedicine technology has significantly increased in recent years, particularly during the Covid-19 pandemic. This study aimed to investigate the use of telemedicine technology for cancer patients during the Covid-19 pandemic.

Methods

This was a scoping review conducted in 2023. Various databases including PubMed, Web of Science, Scopus, Cochrane Library, Ovid, IEEE Xplore, ProQuest, Embase, and Google Scholar search engine were searched. All quantitative, qualitative, and mixed-method studies published in English between 2020 and 2022 were included. Finally, the needed data were extracted, and the results were synthesized and reported narratively.

Results

A total of 29 articles were included in this review. The results showed that teleconsultation, televisit, and telerehabilitation were common telemedicine services, and video conferencing and telephone were common technologies used in these studies. In most cases, patients and healthcare providers preferred these services compared to the face-to-face consultations due to their convenience and advantages. Furthermore, the findings revealed that in terms of clinical outcomes, telemedicine could effectively reduce anxiety, pain, sleep disorders, and hospital admission rates.

Conclusion

The findings provided valuable insights into the various telemedicine technologies, services, users’ perspectives, and clinical outcomes in cancer patients during the Covid-19 pandemic. Overall, the positive outcomes and users’ satisfaction showed that the use of telemedicine technology can be expanded, particularly in cancer care. Future research needs to investigate both clinical and non-clinical effectiveness of using various telemedicine services and technologies for improving cancer care delivery, which can help to develop more successful strategies for implementing this technology.
Quality indicators for hospital burn care: a scoping review
Authors: Suzuki Denise R. Rabelo , Santana Levy Aniceto , Ávila Juliana Elvira H. Guerra , Amorim Fábio Ferreira , Modesto Guilherme Pacheco , Gottems Leila Bernarda Donato , Maldaner Vinicius
Published: April 2024

Background

Burn treatments are complex, and for this reason, a specialised multidisciplinary approach is recommended. Evaluating the quality of care provided to acute burn patients through quality indicators makes it possible to develop and implement measures aiming at better results. There is a lack of information on which indicators to evaluate care in burn patients. The purpose of this scoping review was to identify a list of quality indicators used to evaluate the quality of hospital care provided to acute burn patients and indicate possible aspects of care that do not have specific indicators in the literature.

Method

A comprehensive scoping review (PRISMA-ScR) was conducted in four databases (PubMed, Cochrane Library, Embase, and Lilacs/VHL) between July 25 and 30, 2022 and redone on October 6, 2022. Potentially relevant articles were evaluated for eligibility. General data and the identified quality indicators were collected for each included article. Each indicator was classified as a structure, process, or outcome indicator.

Results

A total of 1548 studies were identified, 82 were included, and their reference lists were searched, adding 19 more publications. Thus, data were collected from 101 studies. This review identified eight structure quality indicators, 72 process indicators, and 19 outcome indicators listed and subdivided according to their objectives.

Conclusion

This study obtained a list of quality indicators already used to monitor and evaluate the hospital care of acute burn patients. These indicators may be useful for further research or implementation in quality improvement programs.

Trial Registration

Protocol was registered on the Open Science Framework platform on June 27, 2022 (https://doi.org/10.17605/OSF.IO/NAW85).
Variability in the prevalence of depression among adults with chronic pain: UK Biobank analysis through clinical prediction models
Authors: Chen Lingxiao , Ashton-James Claire E , Shi Baoyi , Radojčić Maja R , Anderson David B , Chen Yujie , Preen David B , Hopper John L , Li Shuai , Bui Minh , Beckenkamp Paula R , Arden Nigel K , Ferreira Paulo H , Zhou Hengxing , Feng Shiqing , Ferreira Manuela L
Published: April 2024

Background

The prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain.

Methods

Participants were from the UK Biobank. The primary outcome was a “lifetime” history of depression. The model’s performance was evaluated using discrimination (optimism-corrected C statistic) and calibration (calibration plot).

Results

Analyses included 24,405 patients with chronic pain (mean age 64.1 years). Among participants with chronic widespread pain, the prevalence of having a “lifetime” history of depression was 45.7% and varied (25.0–66.7%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.66; good calibration on the calibration plot) included age, BMI, smoking status, physical activity, socioeconomic status, gender, history of asthma, history of heart failure, and history of peripheral artery disease. Among participants with chronic regional pain, the prevalence of having a “lifetime” history of depression was 30.2% and varied (21.4–70.6%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.65; good calibration on the calibration plot) included age, gender, nature of pain, smoking status, regular opioid use, history of asthma, pain location that bothers you most, and BMI.

Conclusions

There was substantial variability in the prevalence of depression among patients with chronic pain. Clinically relevant factors were selected to develop prediction models. Clinicians can use these models to assess patients’ treatment needs. These predictors are convenient to collect during daily practice, making it easy for busy clinicians to use them.
Successful management of pulmonary edema secondary to accidental electrocution in a young dog
Authors: Díaz Eduardo A. , Sáenz Carolina , Torres Diana , Silva Andrés , Segnini Gilberto
Published: April 2024

Background

Human records describe pulmonary edema as a life-threatening complication of electric shock. Successful management requires prompt recognition and intensive care. However, in companion animals, electrocutions are rarely reported, even though domestic environments are full of electrical devices and there is always the possibility of accidental injury. Therefore, it is important for veterinarians to know more about this condition in order to achieve successful patient outcomes.

Case presentation

A 3-month-old male Labrador Retriever was presented with a history of transient loss of consciousness after chewing on a household electrical cord. On admission, the puppy showed an orthopneic position with moderate respiratory distress. Supplemental oxygen via nasal catheter was provided, but the patient showed marked worsening of respiratory status. Point-of-care ultrasound exams suggested neurogenic pulmonary edema due to electrical shock close to the central nervous system and increased B-lines without evidence of cardiac abnormalities. Mechanical ventilation of the patient was initiated using volume-controlled mode with a tidal volume of 9 to 15 ml/kg until reaching an end-tidal carbon dioxide ≤ 40 mm Hg, followed by a stepwise lung-recruitment maneuver in pressure-controlled mode with increases of the peak inspiratory pressure (15 to 20 cm H2O) and positive end-expiratory pressure (3 to 10 cm H2O) for 30 min, and return to volume-controlled mode with a tidal volume of 15 ml/kg until reaching a peripheral oxygen saturation ≥ 96%. Weaning from the ventilator was achieved in six hours, and the patient was discharged two days after admission without neurological or respiratory deficits.

Conclusions

We present a rather unusual case of a neurogenic pulmonary edema subsequent to accidental electrocution in a dog. Timely diagnosis by ultrasound and mechanical ventilation settings are described. Our case highlights that pulmonary edema should be considered a potentially life-threatening complication of electrical shock in small animal emergency and critical care medicine.
Design of a multi-epitope-based vaccine candidate against Bovine Genital Campylobacteriosis using a reverse vaccinology approach
Authors: Silva Marta Filipa , Pereira Gonçalo , Mateus Luísa , da Costa Luís Lopes , Silva Elisabete
Published: April 2024

Background

Bovine Genital Campylobacteriosis (BGC), a worldwide distributed venereal disease caused by Campylobacter fetus subsp. venerealis (Cfv), has a relevant negative economic impact in cattle herds. The control of BGC is hampered by the inexistence of globally available effective vaccines. The present in silico study aimed to develop a multi-epitope vaccine candidate against Cfv through reverse vaccinology.

Results

The analysis of Cfv strain NCTC 10354 proteome allowed the identification of 9 proteins suitable for vaccine development. From these, an outer membrane protein, OmpA, and a flagellar protein, FliK, were selected for prediction of B-cell and T-cell epitopes. The top-ranked epitopes conservancy was assessed in 31 Cfv strains. The selected epitopes were integrated to form a multi-epitope fragment of 241 amino acids, which included 2 epitopes from OmpA and 13 epitopes from FliK linked by GPGPG linkers and connected to the cholera toxin subunit B by an EAAAK linker. The vaccine candidate was predicted to be antigenic, non-toxic, non-allergenic, and soluble upon overexpression. The protein structure was predicted and optimized, and the sequence was successfully cloned in silico into a plasmid vector. Additionally, immunological simulations demonstrated the vaccine candidate’s ability to stimulate an immune response.

Conclusions

This study developed a novel vaccine candidate suitable for further in vitro and in vivo experimental validation, which may become a useful tool for the control of BGC.
Reduced mortality associated with pulmonary embolism response team consultation for intermediate and high-risk pulmonary embolism: a retrospective cohort study
Authors: Gardner Tiffany A. , Fuher Alexandra , Longino August , Sink Eric M. , Jurica James , Park Bryan , Lindquist Jonathan , Bull Todd M. , Hountras Peter
Published: April 2024

Background

The management of acute pulmonary embolism (PE) has become increasingly complex with the expansion of advanced therapeutic options, resulting in the development and widespread adoption of multidisciplinary Pulmonary Embolism Response Teams (PERTs). Much of the literature evaluating the impact of PERTs has been limited by pre- postimplementation study design, leading to confounding by changes in global practice patterns over time, and has yielded mixed results. To address this ambiguity, we conducted a retrospective cohort study to evaluate the impact of the distinct exposures of PERT availability and direct PERT consultation.

Methods

At a single tertiary center, we conducted propensity-matched analyses of hospitalized patients with intermediate or high-risk PE. To assess the impact of PERT availability, we evaluated the changes in 30-day mortality, hospital length of stay (HLOS), time to therapeutic anticoagulation (TAC), in-hospital bleeding complications, and use of advanced therapies between the two years preceding and following PERT implementation. To evaluate the impact of direct PERT consultation, we conducted the same analyses in the post-PERT era, comparing patients who did and did not receive PERT consultation.

Results

Six hundred eighty four patients were included, of which 315 were pre-PERT patients. Of the 367 postPERT patients, 201 received PERT consultation. For patients who received PERT consultation, we observed a significant reduction in 30-day mortality (5% vs 20%, OR 0.38, p = 0.0024), HLOS.

(-5.4 days, p < 0.001), TAC (-0.25 h, p = 0.041), and in-hospital bleeding (OR 0.28, p = 0.011).

These differences were not observed evaluating the impact of PERT presence in pre-vs postimplementation eras.

Conclusions

We observed a significant reduction in 30-day mortality, hospital LOS, TAC, and in-hospital bleeding complications for patients who received PERT consultation without an observed difference in these metrics when comparing the pre- vs post-implementation eras. This suggests the benefits stem from direct PERT involvement rather than the mere existence of PERT. Our data supports that PERT consultation may provide benefit to patients with acute intermediate or high-risk PE and can be achieved without a concomitant increase in advanced therapies.
Structural determinants for activation of the Tau kinase CDK5 by the serotonin receptor 5-HT7R
Authors: Ackmann Jana , Brüge Alina , Gotina Lizaveta , Lim Sungsu , Jahreis Kathrin , Vollbrecht Anna-Lena , Kim Yun Kyung , Pae Ae Nim , Labus Josephine , Ponimaskin Evgeni
Published: April 2024

Background

Multiple neurodegenerative diseases are induced by the formation and deposition of protein aggregates. In particular, the microtubule-associated protein Tau leads to the development of so-called tauopathies characterized by the aggregation of hyperphosphorylated Tau within neurons. We recently showed that the constitutive activity of the serotonin receptor 7 (5-HT7R) is required for Tau hyperphosphorylation and aggregation through activation of the cyclin-dependent kinase 5 (CDK5). We also demonstrated physical interaction between 5-HT7R and CDK5 at the plasma membrane suggesting that the 5-HT7R/CDK5 complex is an integral part of the signaling network involved in Tau-mediated pathology.

Methods

Using biochemical, microscopic, molecular biological, computational and AI-based approaches, we investigated structural requirements for the formation of 5-HT7R/CDK5 complex.

Results

We demonstrated that 5-HT7R domains responsible for coupling to Gs proteins are not involved in receptor interaction with CDK5. We also created a structural model of the 5-HT7R/CDK5 complex and refined the interaction interface. The model predicted two conserved phenylalanine residues, F278 and F281, within the third intracellular loop of 5-HT7R to be potentially important for complex formation. While site-directed mutagenesis of these residues did not influence Gs protein-mediated receptor signaling, replacement of both phenylalanines by alanine residues significantly reduced 5-HT7R/CDK5 interaction and receptor-mediated CDK5 activation, leading to reduced Tau hyperphosphorylation and aggregation. Molecular dynamics simulations of 5-HT7R/CDK5 complex for wild-type and receptor mutants confirmed binding interface stability of the initial model.

Conclusions

Our results provide a structural basis for the development of novel drugs targeting the 5-HT7R/CDK5 interaction interface for the selective treatment of Tau-related disorders, including frontotemporal dementia and Alzheimer’s disease.
Bone health and physical activity in adolescents with juvenile idiopathic arthritis: a cross-sectional case-control study
Authors: Vasil Egi , M. Nesbitt Colleen , Toomey Clodagh , Kuntze Gregor , Esau Shane , A. Emery Carolyn , Gabel Leigh
Published: April 2024

Background

Adolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for bone development and reduced physical activity may detrimentally effect bone health. Thus, we examined differences in total body bone mineral content (BMC) and areal bone mineral density (aBMD) between adolescents with JIA and adolescent controls without JIA. We also examined associations between moderate-to-vigorous physical activity (MVPA), lean mass, and bone outcomes.

Methods

Participants included 21 adolescents with JIA (14 females, 7 males) and 21 sex- and age-matched controls aged 10–20 years. Assessments included: height; weight; triple-single-leg-hop distance (TSLH); MVPA by accelerometry; and total body BMC, aBMD, and lean mass measured using dual X-ray absorptiometry. Height-adjusted z-scores were calculated for BMC and aBMD and used for all analyses. Multiple linear mixed effects models examined group differences in BMC and aBMD, adjusting for sex, maturity, MVPA, TSLH, and lean mass. Participants clusters, based on sex and age (within 18 months), were considered random effects.

Results

Adolescents with JIA had lower total body aBMD z-scores [β (95% CI); -0.58 (-1.10 to -0.07), p = 0.03] and BMC z-scores [-0.47 (-0.91 to -0.03), p = 0.04] compared with controls. Mean daily MVPA was 22.0 min/day lower in adolescents with JIA than controls; however, MVPA was not associated with aBMD [-0.01 (-0.01 to 0.01), p = 0.32] or BMC [0.00 (-0.01 to 0.00), p = 0.39]. Lean mass was positively associated with aBMD [0.05 (0.01 to 0.09) g/cm2, p = 0.03] and BMC [0.06 (0.03 to 0.10) g, p < 0.001].

Conclusion

Adolescents with JIA had lower total body aBMD and BMC compared with sex- and age-matched controls without JIA. Group differences in bone outcomes were not associated with the lower MVPA participation of adolescents with JIA. Despite this, physical activity should still be encouraged as it promotes physical well-being.
A quantitative and qualitative analysis of patient group narratives suggests common biopsychosocial red flags of undiagnosed rare disease
Authors: Al-Attar Mariam , Butterworth Sondra , McKay Lucy
Published: April 2024

Background

The ‘diagnostic odyssey’ is a common challenge faced by patients living with rare diseases and poses a significant burden for patients, their families and carers, and the healthcare system. The diagnosis of rare diseases in clinical settings is challenging, with patients typically experiencing a multitude of unnecessary tests and procedures. To improve diagnosis of rare disease, clinicians require evidence-based guidance on when their patient may be presenting with a rare disease. This study aims to identify common experiences amongst patients with rare diseases, to inform a series of ‘red flags’ that can aid diagnosis of rare diseases in non-specialist settings.

A questionnaire was developed by Medics for Rare Diseases, informed by the experiences of clinicians, rare disease patients and patient advocates, and was shared with UK-based rare disease patient groups. Study participants were engaged via social media platforms, blogs and email newsletters of three umbrella rare disease organisations. The questionnaire, comprising 22 questions, was designed to identify typical experiences relating to physical and psychosocial manifestations and presentation of disease, patient interactions with healthcare providers, and family history.

Results

Questionnaire responses were received from 79 different rare disease patient groups and the common experiences identified were used to inform seven red flags of rare disease: multi-system involvement (3 or more); genetic inheritance pattern; continued presentation throughout childhood and adulthood; difficulties at school, especially relating to absences, difficulty participating in physical education and experiences of bullying or social isolation; multiple specialist referrals; extended period with unexplained symptoms; and misdiagnosis. In light of the red flags identified, recommendations for primary care and education settings have been proposed, focusing on the need for holistic assessment and awareness of both physical and psychosocial factors.

Conclusions

This study identified key commonalities experienced by patients with rare disease across physical and psychosocial domains, in addition to understanding patients’ history and experiences with healthcare providers. These findings could be used to develop a clinical decision‑making tool to support non-specialist practitioners to consider when their patient may have an undiagnosed rare condition, which may minimise the challenges of the ‘diagnostic odyssey’ and improve the patient experience.
Cervicovaginal microbiota: a promising direction for prevention and treatment in cervical cancer
Authors: Shen Jie , Sun Hao , Chu Jing , Gong Xiaodi , Liu Xiaojun
Published: April 2024

Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.
Minimum information and guidelines for reporting a multiplexed assay of variant effect
Authors: Claussnitzer Melina , Parikh Victoria N. , Wagner Alex H. , Arbesfeld Jeremy A. , Bult Carol J. , Firth Helen V. , Muffley Lara A. , Nguyen Ba Alex N. , Riehle Kevin , Roth Frederick P. , Tabet Daniel , Bolognesi Benedetta , Glazer Andrew M. , Rubin Alan F.
Published: April 2024

Multiplexed assays of variant effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines have led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs.
Exploring relationship of poor sleeping habits with prenatal stress among pregnant women in Pakistan: a cross-sectional study
Authors: Waqas Ahmed , Siddique Irfan , Ahsen Mehroz , Zubair Muhammad , Naeem Mehak , Memon Aamir Raoof , Naveed Sadiq
Published: April 2024

Objective

Pregnancy is a complex phenomenon accompanied by biological, physiological and psychosocial changes for a mother. It is also regarded as a stressful life event where a woman’s role, identity and interpersonal relationships are restructured. The present study from Pakistan explores the association of sleep quality and poor sleeping habits with prenatal stress using Pittsburgh Sleep quality Index.

Results

There were a total of 516 women (mean age = 29.82 years), with more than half reporting poor sleep quality. Ethnically, a majority (395, 76.6%) were natives of the Punjab province while rest were non-natives. A high percentage of respondents reported poor subjective sleep quality (22.1%), sleep latency (44.1%), habitual sleep efficiency (27.5%), sleep disturbance (30.1%), use of medications (7.1%) and daytime dysfunction (29.5%). According to logistic regression analysis, respondents with poor sleep quality were 2.24 (95% CI = 1.55–3.22,P < 0.001) times more likely to have high stress levels (P < 0.001).
Effect of soil contamination and additives on fermentative profile, microbial community and iron bioaccessibility of alfalfa silage
Authors: Jia Tingting , Luo Ying , Wang Lei , Yu Zhu
Published: April 2024

Background

During alfalfa harvesting and preservation, it is important to minimize losses and preserve dry matter and nutrients. Soil contamination of alfalfa forage is a common issue that occurs during the ensiling process. Soil contamination can adversely influence the quality of silage, potentially altering the fermentation process, microbial composition, and iron content.

Results

In this study, different levels of soil (0, 1.5% or 7.5% contamination on a wet basis; silt loam soil) and two types of additives (LP, Lactobacillus plantarum inoculant alone; MLP, combination addition of molasses and Lactobacillus plantarum) were added to alfalfa and subjected to anaerobic fermentation for 45 days to evaluate the iron content as well as the alpha diversity and relative abundance of bacterial and fungal communities. Soil-contaminated alfalfa contained lower levels of LA (14.2–41.8 g kg−1 DM) and higher levels of AN (50.0–156.4 g kg−1 DM) compared to uncontaminated alfalfa. Soil contamination of alfalfa forage increased the abundance of Clostridia, Actinobacteria, and Alphaproteobacteria in silage. The application of LP or MLP in soil-contaminated silage increased the abundance of Lactobacillus and inhibited the growth of Enterococcus faecium, Pediococcus pentosaceus, unclassified_f_Enterobacteriaceae, and Weissella cibaria. In addition, as the level of soil contamination increased, both the total and bioaccessible iron contents in alfalfa silage increased. The dominant bacteria Lactobacillus plantarum exhibited a positive relationship with LA and bioaccessible iron contents and a negative relationship with pH, AN and BA. The dominant fungi Neocosmospora rubicola showed a positive relationship with total iron, BA, AN and pH.

Conclusions

Soil contamination of alfalfa increased the abundance of Clostridia, Actinobacteria, and Alphaproteobacteria and it also increased the total and bioaccessible iron content in silage. The addition of LP and MLP improved the fermentation quality of soil-contaminated silage by increasing LA production and reducing the relative abundance of Enterococcus faecium, Pediococcus pentosaceus, unclassified_f_Enterobacteriaceae, and Weissella cibaria.

Graphical Abstract
Knowledge Translation Task Force for core measures clinical practice guideline: a short report on the process and utilization
Authors: Bland Marghuretta D. , Moore Jennifer L. , Anderl Elizabeth , Eikenberry Megan , McCarthy Arlene , Olivier Geneviève N. , Rice Tracy , Siles Amelia , Zeleznik Hallie , Romney Wendy
Published: April 2024

Background

As part of the 2018 Clinical Practice Guideline (CPG): A Core Set of Outcome Measures for Adults with Neurologic Conditions Undergoing Rehabilitation, a Knowledge Translation (KT) Task Force was convened. The purpose of this short report was to (1) demonstrate the potential impact of a CPG KT Task Force through a practical example of efforts to implement a CPG into neurologic physical therapy practice and (2) describe the process to convene a KT Task Force and develop products (KT Toolkit) to facilitate implementation of the CPG.

Methods

To describe the process used by the KT Task Force to develop and review a KT Toolkit for implementation of the CPG.

Results

Utilizing the Knowledge-To-Action Cycle framework, eight tools were developed as part of the KT Toolkit and are available with open access to the public. Findings indicate that the Core Outcome Measures Homepage, which houses the KT Toolkit, has had greater than 70,000 views since its publication.

Conclusions

This short report serves as an example of the efforts made to implement a CPG into physical therapy practice. The processes to facilitate KT and the tools developed can inform future implementation efforts and underscore the importance of having a KT Task Force to implement a CPG. Moving forward, KT Task Forces should be convened to implement new or revised guidelines.

Trial registration

N/A.
Exploring the co-occurrence of depression, anxiety and insomnia symptoms, diagnoses and treatments in primary care: observational study using UK primary care data
Authors: Nimmons Danielle , Bazo-Alvarez Juan Carlos , Avgerinou Christina , Hayes Joseph , Osborn David , Cooper Claudia , Petersen Irene , Walters Kate
Published: April 2024

Background

Depression, anxiety and insomnia often co-occur. However, there is a lack of research regarding how they cluster and how this is related to medication used to treat them.

Aims

To describe the frequencies and associations between depression, anxiety and insomnia, and treatment for these conditions in primary care.

Method

A retrospective cohort study using UK electronic primary care records. We included individuals aged between 18 and 99 years old with one or more records suggesting they had a diagnosis, symptom or drug treatment for anxiety, depression or insomnia between 2015 and 2017. We report the conditional probabilities of having different combinations of diagnoses, symptoms and treatments recorded.

Results

There were 1 325 960 records indicative of depression, anxiety or insomnia, for 739 834 individuals. Depression was the most common condition (n = 106 117 records), and SSRIs were the most commonly prescribed medication (n = 347 751 records). Overall, individuals with a record of anxiety were most likely to have co-occurring symptoms and diagnoses of other mental health conditions. For example, of the individuals with a record of generalised anxiety disorder (GAD), 24% also had a diagnosis of depression. In contrast, only 0.6% of those who had a diagnosis of depression had a diagnosis or symptom of GAD. Prescribing of more than one psychotropic medication within the same year was common. For example, of those who were prescribed an SNRI (serotonin-norepinephrine reuptake inhibitor), 40% were also prescribed an SSRI (selective serotonin reuptake inhibitor).

Conclusions

The conditional probabilities of co-occurring anxiety, depression and insomnia symptoms, diagnoses and treatments are high.
Comparative Anatomic Analysis of Neuronavigated Transmastoid-Infralabyrinthine Approaches for Jugular Fossa Pathologies: Short Anterior Rerouting Versus Nonrerouting and Tailored Nonrerouting Techniques
Authors: Cinibulak Zafer , Martinez Santos Jaime L. , Poggenborg Jörg , Schliwa Stefanie , Ostovar Nima , Keles Abdullah , Baskaya Mustafa K. , Nakamura Makoto
Published: April 2024

BACKGROUND AND OBJECTIVES:

Access to the jugular fossa pathologies (JFPs) via the transmastoid infralabyrinthine approach (TI-A) using the nonrerouting technique (removing the bone anterior and posterior to the facial nerve while leaving the nerve protected within the fallopian canal) or with the short-rerouting technique (rerouting the mastoid segment of the facial nerve anteriorly) has been described in previous studies. The objective of this study is to compare the access to Fisch class C lesions (JFPs extending or destroying the infralabyrinthine and apical compartment of the temporal bone with or without involving the carotid canal) between the nonrerouting and the short-rerouting techniques. Also, some tailored steps to the nonrerouting technique (NR-T) were outlined to enhance access to the jugular fossa (JF) as an alternative to the short-rerouting technique.

METHODS:

Neuronavigated TI-A was performed using the nonrerouting, tailored nonrerouting, and short-rerouting techniques on both sides of 10 human head specimens. Exposed area, horizontal distance, surgical freedom, and horizontal angle were calculated using vector coordinates for nonrerouting and short-rerouting techniques.

RESULTS:

The short-rerouting technique had significantly higher values than the NR-T (P < .01) for the exposed area (169.1 ± SD 11.5 mm2 vs 151.0 ± SD 12.4 mm2), horizontal distance (15.9 ± SD 0.6 mm vs 10.6 ± SD 0.5 mm2), surgical freedom (19 650.2 ± SD 722.5 mm2 vs 17 233.8 ± SD 631.7 mm2), and horizontal angle (75.2 ± SD 5.1° vs 61.7 ± SD 4.6°). However, adding some tailored steps to the NR-T permitted comparable access to the JF.

CONCLUSION:

Neuronavigated TI-A with the short-rerouting technique permits wider access to the JF compared with the NR-T. However, the tailored NR-T provides comparable access to the JF and may be a better option for class C1 and selected class C2 and C3 JFPs.
Mechanical stress combines with planar polarised patterning during metaphase to orient embryonic epithelial cell divisions
Authors: Blanchard Guy B. , Scarpa Elena , Muresan Leila , Sanson Bénédicte
Published: April 2024

The planar orientation of cell division (OCD) is important for epithelial morphogenesis and homeostasis. Here, we ask how mechanics and antero-posterior (AP) patterning combine to influence the first divisions after gastrulation in the Drosophila embryonic epithelium. We analyse hundreds of cell divisions and show that stress anisotropy, notably from compressive forces, can reorient division directly in metaphase. Stress anisotropy influences the OCD by imposing metaphase cell elongation, despite mitotic rounding, and overrides interphase cell elongation. In strongly elongated cells, the mitotic spindle adapts its length to, and hence its orientation is constrained by, the cell long axis. Alongside mechanical cues, we find a tissue-wide bias of the mitotic spindle orientation towards AP-patterned planar polarised Myosin-II. This spindle bias is lost in an AP-patterning mutant. Thus, a patterning-induced mitotic spindle orientation bias overrides mechanical cues in mildly elongated cells, whereas in strongly elongated cells the spindle is constrained close to the high stress axis.