bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of transjugular liver biopsy in acute liver failure – a real-world analysis
Authors: Nalbant Bahar , Pape Thorben , Schneider Andrea , Seeliger Benjamin , Schirmer Paul , Heidrich Benjamin , Taubert Richard , Wedemeyer Heiner , Lenzen Henrike , Stahl Klaus
Published: August 2024

Background

Histopathological characterization obtained by transjugular liver biopsy (TJLB) may theoretically contribute to clarification of the exact aetiology of acute liver failure (ALF). It's unclear whether the histopathological information from TJLB, due to the small specimen size, significantly contributes to diagnosing ALF causes, guiding therapy decisions, or predicting overall prognosis. This retrospective study aimed to analyse safety and clinical significance of TJLB in patients with ALF.

Methods

This retrospective, monocentric study investigated safety and efficacy of TJLB in patients with ALF over a ten-year period at a tertiary care transplant-center. The predictive value of various clinical and laboratory characteristics as well as histopathological findings obtained by TJLB on 28-day liver-transplant-free survival were evaluated by calculating uni- and multivariate Cox-proportional hazard regression models. Additional univariate logistic regression analyses were performed to explore the influence of degree of intrahepatic necrosis on the secondary endpoints intensive-care-unit (ICU) admission, need for endotracheal intubation, renal replacement therapy and high-urgency listing for LTX.

Results

A total of 43 patients with ALF receiving TJLB were included into the study. In most cases (n = 39/43 cases) TJLB confirmed the initially already clinically presumed ALF aetiology and the therapeutic approach was unchanged by additional histological examination in the majority of patients (36/43 cases). However, in patients with a high suspicion for aetiologies potentially treatable by medical immunosuppression (e.g. AIH, GvHD), TJLB significantly influenced further treatment planning and/or adjustment. While the degree of intrahepatic necrosis showed significance in the univariate analysis (p = 0.04), it did not demonstrate a significant predictive effect on liver transplant-free survival in the multivariate analysis (p = 0.1). Only consecutive ICU admission was more likely with higher extent of intrahepatic necrosis (Odds ratio (OR) 1.04 (95% CI 1–1.08), p = 0.046).

Conclusions

Performance of TJLB in ALF led to a change in suspected diagnosis and to a significant change in therapeutic measures only in those patients with a presumed high risk for aetiologies potentially responsive to immunosuppressive therapy. Clinical assessment alone was accurate enough, with additional histopathological examination adding no significant value, to predict overall prognosis of patients with ALF.
HPV vaccine behaviors and intentions among a diverse sample of women aged 27-45 years: implications for shared clinical decision-making
Authors: Allen Jennifer D. , Abuelezam Nadia N. , Rose Raviv , Isakoff Katelin , Zimet Gregory , Fontenot Holly B.
Published: August 2024

Background

The Advisory Committee on Immunization Practices issued a shared clinical decision-making (SCDM) recommendation for HPV vaccination in persons aged 27–45. Since expanded eligibility for the vaccine was issued, little information has been available about HPV vaccine behaviors and intentions among women in this age group.

Methods

We conducted a cross-sectional online survey among women aged 27–45 years recruited through a Qualtrics™ respondent panel (N = 324) to answer the following questions (1) What is the prevalence of HPV vaccination among a diverse sample of adult women aged 27–45 years? (2) What are the characteristics of those who have or have not previously been vaccinated? and (3) What factors are associated with the intention to obtain the HPV vaccine among those who had never been vaccinated? Multivariable logistic regression analyses estimated adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs).

Results

Only 31.1% had at least one dose of the HPV vaccine. In multivariable analyses, those more likely to have been vaccinated were younger and were more likely to believe that the vaccine was effective. Of those unvaccinated or unsure, 54.8% indicated they were likely to get vaccinated in the future. Factors associated with future vaccine intention (compared to those not intending) included beliefs about vaccine testing, perceived likelihood of HPV infection, greater comfort in asking one’s provider for vaccination, and prior negative healthcare experiences.

Conclusions

Our findings suggest that many women in this age group are interested in HPV vaccination. While the recommendation is for SCDM rather than routine vaccination for all women in this age group, efforts to promote informed decision-making among mid-adult women may include educating women about the rigorous vaccine testing and approval process, their risk factors for HPV infection, and encouraging them to engage in SCDM with their medical providers. Targeted efforts to reach women who have had negative experiences with healthcare may also be needed.
Acceptability of HPV vaccination for cervical cancer prevention amongst emerging adult women in rural Mysore, India: a mixed-methods study
Authors: Coursey Kate , Muralidhar Kiranmayee , Srinivas Vijaya , Jaykrishna Poornima , Begum Fazila , Ningaiah Nagalambika , Lee Sung-Jae , Madhivanan Purnima
Published: August 2024

Background

India has the highest number of estimated deaths from cervical cancer globally, with most cases attributed to Human papillomavirus (HPV). The World Health Organization recommends primary HPV vaccination for girls ages 9–14, with catch-up vaccination for young women ≥ 15 if feasible. India authorized a new, inexpensive HPV vaccine in 2022; given anticipated vaccine expansion, we conducted a mixed-methods study exploring acceptability of HPV catch-up vaccination for young emerging adult women in rural Mysore, India.

Methods

Between September 2022-April 2023, participants were recruited with assistance from community health workers. In the qualitative phase, gender-stratified, audio-recorded focus group discussions (FGDs) were conducted in Kannada with emerging adults ages 18–26. FGDs were transcribed, translated, and analyzed using rapid approach to identify key HPV vaccination attributes. In the quantitative phase, a conjoint analysis was conducted to assess the impact of seven vaccination attributes on likelihood to vaccinate (LTV). Women ages 18–26 ranked LTV in eight hypothetical vaccination scenarios, and the relative impact of each attribute on LTV was calculated. All participants received education about cervical cancer, HPV, and HPV vaccination.

Results

Fifty-two young adults (female = 31, male = 21) participated in seven FGDs, and 101 women participated in the conjoint analysis. Average age of the 153 participants was 22.5 years, 66.7% had married, and all had completed high school. Only 17.9% had heard of cervical cancer, and 2.7% knew of the HPV vaccine. FGDs identified seven HPV vaccination attributes: cost, vaccination location, family support, peer influence, dose number, side effects, and risk of acquiring HPV. In the conjoint analysis, all attributes except dose number significantly impacted LTV. Family support (impact score = 19.37, p < 0.0001) and peer influence (impact score = 18.01, p < 0.0001) had the greatest influence, followed by cost (impact score = 16.64, p < 0.0001) and HPV risk (impact score = 12.31, p < 0.0001). Vaccination location (government centers preferred) and side effects were also significant.

Conclusion

Participants had poor knowledge of cervical cancer and HPV. Social attributes (family support, peer influence) had greatest impacts on LTV, and future studies should explore family-based interventions and peer education. Providing free vaccines at government centers through India’s national immunization program would maximize catch-up HPV vaccination for rural young women.
Significance of scattered small echogenic foci floating in urinary bladder as ultrasonography finding in dogs
Authors: Moosavian Hamidreza , Masoudifard Majid , Zareh Maede Beiki , Jamshidi Shahram , Tamai Iraj Ashrafi
Published: August 2024

Background

Despite the prevalence of echogenic foci floating in the urinary bladder seen in ultrasonography in dogs, surprisingly little has been written on its significance, including its potential association with urinalysis. The objective of the study was to determine the diagnostic value of the echogenic foci floating in urinary bladders in dogs.

Results

- Cystosonography was performed on 45 dogs. Bladder contents were examined and divided into positive (containing echogenic particles) and negative (absent echogenic particles) groups according to the presence and absence of floating echogenic particles. Five mL of urine was collected via cystocentesis. Urine analysis and culture were done and the relationship between ultrasound evaluation and urinalysis results was investigated. In dogs with bladder echogenic particles in ultrasonography, the prevalence of hematuria, pyuria, bacteriuria, and lipiduria were 88.9%, 92.6%, 29.6%, and 70.3%, respectively. However, in dogs in which echogenic particles were not observed in their bladders, the prevalence of hematuria, pyuria, bacteriuria, and lipiduria was 77%, 50%, 5.5%, and 77%, respectively. There was a significant association between bladder debris and positive urine culture, with an odds ratio of 7.15 (95% confidence interval: 0.81–63.28) compared with matched controls. Furthermore, there was a significant relationship between the presence of floating echogenic particles with pyuria, and urine color ( p ≤ 0.05).

Conclusion

In conclusion, the present results showed the detection of bladder debris on ultrasound can be a predictor for pyuria and positive urine culture in dogs.
Evaluation of axillary lymph nodes in breast cancer patients with clinically negative axilla using contrast enhanced ultrasonography
Authors: Jain Roshit , Khanna Rahul , Verma Ashish , Mishra Shashi Prakash , Meena Ram Niwas , Khanna Seema , Khanna Siddharth
Published: August 2024

Contrast enhanced ultrasonography enables dynamic evaluation of the microvasculature down to the capillaries when using high resolution ultrasound probes. It’s application in the evaluation of axillary lymph nodes in breast cancer patients with clinically negative axilla has been studied in 42 patients. The results of pre operative CEUS evaluation was correlated with histopathology status of axillary nodes after the harvesting of nodes during modified radical mastectomy or sentinel node biopsy. Heterogeneous enhancement with micro bubbles of the axillary nodes was found to be the most distinguishing criteria for malignant nodes.
Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid
Authors: Kamalian Aida , Shirzadeh Barough Siavash , Ho Sara G. , Albert Marilyn , Luciano Mark G. , Yasar Sevil , Moghekar Abhay
Published: August 2024

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer’s disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.
Pozelimab for CHAPLE disease: results from in-trial interviews and clinical outcome assessments
Authors: Litcher-Kelly Leighann , Ozen Ahmet , Ollis Sarah , Feldman Hagit Baris , Yaworsky Andrew , Medrano Paolo , Chongsrisawa Voranush , Brackin Taylor , Perlee Lorah , Walker Marisa , Pradeep Sharanya , Lenardo Michael J. , Harari Olivier A. , Jalbert Jessica J.
Published: August 2024

Background

CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634).

Methods

Interviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change.

Results

Ten patients (aged 3–19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (≥ 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from “mild” to “very severe” at baseline to “no signs or symptoms” at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores.

Conclusions

Patients with CHAPLE disease treated with pozelimab for 24 weeks experienced complete resolution of core signs and symptoms. Mixed-methods approaches can contextualize the patient experience (how patients feel and function) in rare disease trials.

Trial registration

Clinicaltrials.gov, NCT04209634, registered December 24, 2019, https://classic.clinicaltrials.gov/ct2/show/NCT04209634.
Flexural Behavior Evaluation for Seismic, Durability and Structure Performance Improvement of Aged Bridge According to Reinforcement Methods
Authors: Kim Tae-Kyun , Park Jong-Sup
Published: August 2024

Among infrastructure, concrete bridges are the most exposed to various environmental effects. Structural degradation occurs due to natural and artificial influences shortening the lifespan of the structure. Therefore, bridges need to be reinforced over time. The structures used in this study are re-formed using aged bridge floor decks that have been used for 50 years, approximately. The fiber-reinforced polymer (FRP) adhesion method, using sheets and plate forms, was selected among various reinforcement methods to investigate the performance of reinforced structures. We have tested various reinforcement scenarios including one and two layers FRP sheets and FRP plates. The mechanical properties of the reinforced structures were evaluated experimentally through tensile strength and flexural test experiments. In contrast to most available literature focused on model-based studies, our present work represents an experimental test validation of structural reinforcement on an actual bridge. Our results indicate that fiber-based reinforcement in sheet form exhibits higher performances of the reinforced structure compared to reinforcement using the plate form. This study is intended to provide sufficient data for reinforcing bridge floors that could be used for reference at future construction sites.
Proteomic stable isotope probing with an upgraded Sipros algorithm for improved identification and quantification of isotopically labeled proteins
Authors: Xiong Yi , Mueller Ryan S. , Feng Shichao , Guo Xuan , Pan Chongle
Published: August 2024

Background

Proteomic stable isotope probing (SIP) is used in microbial ecology to trace a non-radioactive isotope from a labeled substrate into de novo synthesized proteins in specific populations that are actively assimilating and metabolizing the substrate in a complex microbial community. The Sipros algorithm is used in proteomic SIP to identify variably labeled proteins and quantify their isotopic enrichment levels (atom%) by performing enrichment-resolved database searching.

Results

In this study, Sipros was upgraded to improve the labeled protein identification, isotopic enrichment quantification, and database searching speed. The new Sipros 4 was compared with the existing Sipros 3, Calisp, and MetaProSIP in terms of the number of identifications and the accuracy and precision of atom% quantification on both the peptide and protein levels using standard E. coli cultures with 1.07 atom%, 2 atom%, 5 atom%, 25 atom%, 50 atom%, and 99 atom% 13C enrichment. Sipros 4 outperformed Calisp and MetaProSIP across all samples, especially in samples with ≥ 5 atom% 13C labeling. The computational speed on Sipros 4 was > 20 times higher than Sipros 3 and was on par with the overall speed of Calisp- and MetaProSIP-based pipelines. Sipros 4 also demonstrated higher sensitivity for the detection of labeled proteins in two 13C-SIP experiments on a real-world soil community. The labeled proteins were used to trace 13C from 13C-methanol and 13C-labeled plant exudates to the consuming soil microorganisms and their newly synthesized proteins.

Conclusion

Overall, Sipros 4 improved the quality of the proteomic SIP results and reduced the computational cost of SIP database searching, which will make proteomic SIP more useful and accessible to the border community.
What caused the record-low frequency of western North Pacific tropical cyclones in autumn 2023?
Authors: Song Jinjie , Klotzbach Philip J. , Wei Na , Duan Yihong
Published: August 2024

September–November (e.g., autumn) 2023 produced the fewest western North Pacific (WNP) tropical cyclones (TCs) since 1951, likely as a joint response to El Niño and a warm phase of the North Pacific Mode (NPM). Decreases in both TC genesis frequency and two genesis potential indices (GPIs) over the western WNP were likely the result of El Niño-induced and warm NPM-induced negative low-level relative vorticity anomalies. Over the eastern WNP, TC genesis and GPI reductions were also associated with vorticity decreases over the eastern WNP, where the TC-suppressing effect of the warm NPM surpassed the TC-favoring effect of El Niño. The changes in vorticity were further linked to anomalous anticyclones centered over the South China Sea and the midlatitude central North Pacific. A linear combination of the responses to El Niño and a warm NPM can explain the changes in TC genesis and low-level circulation over most of the WNP in 2023, except east of 160°E where other climate modes may have played more of a role.
Reckoning of antiurolithiatic effect of Flemingia Strobilifera R. BR using ethylene glycol-induced urolithiatic animal model: demystifying traditional medicine
Authors: Kumar Anil , V. Anil Kumar K. , Rani Swaroopa , Rao Suguna , B S. Girish , Johns Joel M.
Published: August 2024

Background

Urolithiasis is a painful condition and current treatment doesn’t assure the prevention of recurrence. This research aims to demonstrate the scientific reliability of Chloroform leaf extract ofFlemingia StrobiliferaR.Br. (CEFS) for antiurolithiatic activity using ethylene glycol-induced urolithiasis model.

Results

Ethylene glycol (EG) was used to induce hyperoxaluria in male Wistar rats. The rats were grouped into 7-groups containing six each. Group I and II served as negative and positive control, group III received standard treatment, whereas Group IV to VII served as testing groups. CEFS of 30 mg/kg body-weight and 60 mg/kg body-weight was used as a preventive and curative regimen. The urine biochemistry was analysed for the presence of calcium, magnesium, phosphate, and oxalate. The rats were sacrificed for histopathological examination and LDH detection. The 24-hours urine volume was increased in both EG-treated groups as well as CEFS-treated groups, indicating the diuretic activity of plant. CEFS dose-dependently inhibited urine excretion of phosphate, calcium, and oxalate compared to the positive-control group. The histopathological examination of CEFS-treated rats’ kidneys had reduced loss of renal structure and lessened deposition of calcium oxalate crystals.

Conclusion

CEFS exhibited significant antiurolithiatic activity by reducing supersaturation of urine and excretion of stone forming components.
Decoying the enemy: soluble receptor for advanced glycation end products and cognitive impairment in neurodegenerative diseases—a systematic review and meta-analysis
Authors: Mahayana Ngakan Putu Krishna , Yadmika Ni Putu Wulandari Putri , Aryaweda Made Dhiyo Wiweka , Mahardana Made Dwinanda Prabawa , Mamangdean Christo Timothy , Dewi Ni Nyoman Ayu , Wirawan Chandra , Laksmidewi Anak Agung Ayu Putri
Published: August 2024

Background

Accumulation of advanced glycation end products (AGEs) has contribution in development of Alzheimer’s disease (AD), vascular dementia (VAD), and mild cognitive impairment (MCI). AGEs activate several signaling pathways that have roles in development of those diseases via receptor for advanced glycation end product (RAGE), this receptor has its soluble form called sRAGE which has ability to bind AGEs but could not induce molecular signaling. Based on this property, sRAGE could work as RAGE decoy and prevent pathological effect of AGEs accumulation. This meta-analysis is aimed to evaluate correlation between sRAGE plasma level and risk of AD, VAD, and MCI.

Methods

Standardized mean difference with 95% coincidence interval was used as effect size. Inverse variance was used as analysis method with random effect model. Egger test and funnel plot were used to assess publication bias.

Results

We found 424 articles through database searching. Among those articles, 15 articles that fulfilled our eligibility criteria. After selection based on inclusion and exclusion criteria, only 5 articles were included in this meta-analysis. Our analysis found that AD and VAD patients have lower levels of plasma sRAGE when compared to healthy control. Significant correlation between low sRAGE plasma level and MCI was not found. However, publication bias is found in MCI group. Publication bias of VAD group could not be assessed due to limited number of studies.

Conclusions

Here, we show inverse relationship between sRAGE and the incidence of AD alongside VAD suggests that lower sRAGE plasma levels may be associated with a higher incidence of AD and VAD. However, some limitations in sample size and minimal studies may introduce bias into our results.
Knowledge, perceived benefits, perceived concerns, and predisposition to use telehealth services in Bangladesh: a cross-sectional survey
Authors: Kabir Humayun , Hasan Md. Kamrul , Jamil Safayet , Chowdhury Saifur R. , Mitra Dipak Kumar
Published: August 2024

Background

Telehealth services are essential to expand healthcare coverage for all in the era of modern technology. Knowledge, willingness, and involvement with the service are also significantly important in the utilization of the service. This study investigated factors associated with knowledge, perceived benefits, perceived concerns, and predisposition to use telehealth services in Bangladesh. This web-based survey was conducted among 1266 adults in Bangladesh. Respondents were enrolled by following a convenience sampling technique.

Results

Demographic, telehealth service, and perceived health related information were significantly associated with respondents’ knowledge, perceived benefits, perceived concerns, and predispositions. The knowledge was significantly positively correlated with the perceived benefit (p <0.05) and predisposition of telehealth (p <0.05). Albeit, knowledge was significantly negatively correlated with perceived concerns of telehealth (p <0.05).

Conclusion

The findings of the study may assist policymakers in implementing telehealth services by addressing the associated factors of knowledge, perceived benefits, perceived concerns, and predispositions.
Challenges to the real-world delivery of brief alcohol interventions in the custody suite: qualitative study
Authors: Jarrett Manuela , Mills Thomas , Mallion Jaimee , Sykes Susie , Wills Jane , Chaplin Eddie
Published: August 2024

Aims and method

The aim was to evaluate an innovative pathway in police custody suites that aimed to specifically address alcohol-related health needs through screening and brief interventions by police custody staff. This paper presents a qualitative investigation of challenges involved in implementing the pathway. Qualitative interviews were carried out with 22 staff involved with commissioning and delivering the pathway; thematic analysis of interview data was then undertaken.

Results

An overarching theme highlights the challenges and uncertainties of delivering brief alcohol interventions in the custody suite. These include challenges related to the setting, the confidence and competence of the staff, identifying for whom a brief intervention would be of benefit and the nature of the brief intervention.

Clinical implications

Our findings show that there is a lack of clarity over how alcohol-related offending can be identified in police custody, whose role it is to do that and how to intervene.
Natural Language Processing Accurately Differentiates Cancer Symptom Information in Electronic Health Record Narratives
Authors: Albashayreh Alaa , Bandyopadhyay Anindita , Zeinali Nahid , Zhang Min , Fan Weiguo , Gilbertson White Stephanie
Published: August 2024

PURPOSE

Identifying cancer symptoms in electronic health record (EHR) narratives is feasible with natural language processing (NLP). However, more efficient NLP systems are needed to detect various symptoms and distinguish observed symptoms from negated symptoms and medication-related side effects. We evaluated the accuracy of NLP in (1) detecting 14 symptom groups (ie, pain, fatigue, swelling, depressed mood, anxiety, nausea/vomiting, pruritus, headache, shortness of breath, constipation, numbness/tingling, decreased appetite, impaired memory, disturbed sleep) and (2) distinguishing observed symptoms in EHR narratives among patients with cancer.

METHODS

We extracted 902,508 notes for 11,784 unique patients diagnosed with cancer and developed a gold standard corpus of 1,112 notes labeled for presence or absence of 14 symptom groups. We trained an embeddings-augmented NLP system integrating human and machine intelligence and conventional machine learning algorithms. NLP metrics were calculated on a gold standard corpus subset for testing.

RESULTS

The interannotator agreement for labeling the gold standard corpus was excellent at 92%. The embeddings-augmented NLP model achieved the best performance (F1 score = 0.877). The highest NLP accuracy was observed in pruritus (F1 score = 0.937) while the lowest accuracy was in swelling (F1 score = 0.787). After classifying the entire data set with embeddings-augmented NLP, we found that 41% of the notes included symptom documentation. Pain was the most documented symptom (29% of all notes) while impaired memory was the least documented (0.7% of all notes).

CONCLUSION

We illustrated the feasibility of detecting 14 symptom groups in EHR narratives and showed that an embeddings-augmented NLP system outperforms conventional machine learning algorithms in detecting symptom information and differentiating observed symptoms from negated symptoms and medication-related side effects.
Toward a Framework to Assess the Financial and Economic Burden of Cervical Cancer in Low- and Middle-Income Countries: A Systematic Review
Authors: Fuady Ahmad , Setiawan Didik , Man Irene , de Kok Inge M.C.M. , Baussano Iacopo
Published: August 2024

PURPOSE

To review the economic burden assessment of cervical cancer in low- and middle-income countries (LMICs) and use the findings to develop a pragmatic, standardized framework for such assessment.

METHODS

We first systematically reviewed articles indexed in scientific databases reporting the methodology for collecting and calculating costs related to the cervical cancer burden in LMICs. Data on study design, costing approach, cost perspective, costing period, and cost type (direct medical costs [DMC], direct nonmedical costs [DNMC], and indirect costs [IC]) were extracted. Finally, we summarized the reported limitations in the methodology and used the solutions to inform our framework.

RESULTS

Cervical cancer treatment costs across LMICs vary greatly and can be extremely expensive, up to 70,968 International US dollars. Economic and financial assessment methods also vary greatly across countries. Of the 28 reviewed articles, 25 studies reported DMC for cervical cancer treatment by extracting cost information from billing or insurance databases (eight studies), conducting surveys (five), and estimating the costs (12). Only 11 studies—mainly through surveys—reported DNMC and IC. The economic burden assessment framework includes health care/payer and societal perspectives (DMC, DNMC, IC, and human capital loss) across the cervical cancer screening and treatment continuum. To assess health care/payer costs, we recommend combining the predefined treatment standards with actual local treatment practices, multiplied by unit costs. To assess societal costs, we recommend conducting a cost survey in line with a standardized yet adaptable protocol.

CONCLUSION

Our standardized, pragmatic framework allows assessment of economic and financial burden of cervical cancer in LMICs despite the different levels of available resources across countries. This framework will facilitate global comparisons and monitoring and may also be applied to other cancers.
Strategy to Improve the Oral Pharmacokinetics of Cyclin-Dependent Kinase 4/6 Inhibitors: Enhancing Permeability and CYP450 Inhibition by a Natural Bioenhancer
Authors: Patil Prajakta Harish , Desai Mrunal Pradeep , Rao Rajat Radhakrishna , Mutalik Srinivas , Puralae Channabasavaiah Jagadish
Published: August 2024

Palbociclib and ribociclib an orally bioavailable, potent cyclin-dependent kinase 4/6 inhibitors, with low oral bioavailability due to substrate specificity towards CYP3A and P-glycoprotein. Thus, current research aims to examine the effect of a bioenhancer (naringin), on oral pharmacokinetics of palbociclib and ribociclib. Naringin’s affinity for CYP3A4 and P-glycoprotein was studied using molecular docking; its impact on palbociclib/ribociclib CYP3A metabolism and P-glycoprotein-mediated efflux was examined using in vitro preclinical models; and its oral pharmacokinetics in rats were assessed following oral administration of palbociclib/ribociclib in presence of naringin (50 and 100 mg/kg). Naringin binds optimally to both proteins with the highest net binding energy of − 1477.23 and − 1607.47 kcal/mol, respectively. The microsomal intrinsic clearance of palbociclib and ribociclib was noticeably reduced by naringin (5–100 µM), by 3.0 and 2.46-folds, respectively. Similarly, naringin had considerable impact on the intestinal transport and efflux of both drugs. The pre-treatment with 100 mg/kg naringin increased significantly (p < 0.05) the oral exposure of palbociclib (2.0-fold) and ribociclib (1.95-fold). Naringin's concurrent administration of palbociclib and ribociclib increased their oral bioavailability due to its dual inhibitory effect on CYP3A4 and P-glycoprotein; thus, concurrent naringin administration may represent an innovative strategy for enhancing bioavailability of cyclin-dependent kinase inhibitors.

Graphical Abstract
A Small Opening in the Storm Clouds: Overview of the Registry-based Study on the Management of Thyroid Storm
Authors: Duntas Leonidas H , Zarkovic Milos
Published: August 2024

Because of the high mortality rate of thyroid storm (TS), effective guidance for its diagnosis and treatment is essential. The diagnostic criteria introduced by the Japanese Thyroid Association in 2012, along with the Burch-Wartofsky Point Scale, constitute valuable tools for the diagnosis of TS. In 2016, Guidelines on the management of TS were produced by the Japanese Thyroid Association and the Japanese Endocrine Society. Recently, a prospective multicenter register-based study compared the prognosis and outcome of 110 new-onset TS patients with the results of previous comparable studies and evaluated the efficacy of the Guidelines. The study revealed higher Acute Physiology and Chronic Health Evaluation II scores and significant correlations between lower body mass index, postresuscitation shock, and fever with outcomes and, overall, improved TS prognosis. Most patients in the study received methimazole and potassium iodide, the timely administration of which was linked to lower fatality rates. Adherence to treatment guidelines correlates with lower mortality rates, emphasizing the importance of experienced multidisciplinary teams in intensive care unit settings and the necessity for periodic review of the guidelines to enhance therapeutic approaches and reduce mortality.
Aneurysm Wall Enhancement Can Predict Rupture Point in Intracranial Aneurysms With Multiple Blebs
Authors: Omodaka Shunsuke , Sugiyama Shin-ichiro , Sakata Hiroyuki , Funamoto Kenichi , Yamaguchi Takuhiro , Niizuma Kuniyasu , Endo Hidenori
Published: August 2024

BACKGROUND AND OBJECTIVES:

Ruptured aneurysms visualized by vessel wall MRI (VW-MRI) exhibit characteristic aneurysm wall enhancement (AWE). A secondary bulge of the aneurysmal wall, called a bleb, is often the site of rupture in ruptured aneurysms. We hypothesized that a higher degree of AWE would identify the rupture point in aneurysms with multiple blebs.

METHODS:

AWE was quantitatively analyzed in consecutive ruptured intracranial aneurysms with multiple blebs (31 aneurysms with a total of 72 blebs) using VW-MRI. A 3-dimensional T1-weighted fast spin-echo sequence was obtained after contrast media injection, and the contrast ratio of the aneurysm wall against the pituitary stalk (CRstalk) was calculated as the AWE indicator. Bleb characteristics, including CRstalk and wall shear stress (WSS), were compared between ruptured and unruptured blebs. Odds ratios with 95% confidence intervals for ruptures were calculated by conditional logistic regression analysis.

RESULTS:

Ruptured blebs had a higher CRstalk and lower WSS compared with unruptured blebs. CRstalk remained significantly associated with the bleb rupture status in the conditional logistic regression (adjusted odds ratio 3.9, 95% CIs 1.6-9.7).

CONCLUSION:

AWE is associated with the bleb rupture status independent of WSS. Contrast-enhanced VW-MRI may be a useful noninvasive tool for identifying the rupture point and guiding the treatment strategy.
DNAJA2 and Hero11 mediate similar conformational extension and aggregation suppression of TDP-43
Authors: Lam Andy Y.W. , Tsuboyama Kotaro , Tadakuma Hisashi , Tomari Yukihide
Published: August 2024

Many RNA-binding proteins (RBPs) contain low-complexity domains (LCDs) with prion-like compositions. These long intrinsically disordered regions regulate their solubility, contributing to their physiological roles in RNA processing and organization. However, this also makes these RBPs prone to pathological misfolding and aggregation that are characteristic of neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) forms pathological aggregates associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While molecular chaperones are well-known suppressors of these aberrant events, we recently reported that highly disordered, hydrophilic, and charged heat-resistant obscure (Hero) proteins may have similar effects. Specifically, Hero proteins can maintain the activity of other proteins from denaturing conditions in vitro, while their overexpression can suppress cellular aggregation and toxicity associated with aggregation-prone proteins. However, it is unclear how these protective effects are achieved. Here, we used single-molecule FRET to monitor the conformations of the aggregation-prone prion-like LCD of TDP-43. While we observed high conformational heterogeneity in wild-type LCD, the ALS-associated mutation A315T promoted collapsed conformations. In contrast, an Hsp40 chaperone, DNAJA2, and a Hero protein, Hero11, stabilized extended states of the LCD, consistent with their ability to suppress the aggregation of TDP-43. Our results link single-molecule effects on conformation to macro effects on bulk aggregation, where a Hero protein, like a chaperone, can maintain the conformational integrity of a client protein to prevent its aggregation.
Compact, energy efficient neutron source: Enabling Technology for Thorium Breeder and Accelerator Transmutation of Waste
Authors: Hershcovitch Ady , Roser Thomas
Published: August 2024

Background To fulfill need for large flux neutron sources, presently utilized and/or proposed large flux neutron sources are either nuclear reactor based or accelerator based. First method has shortcomings: in radioactive waste generation high proliferation risk. Accelerator based spallation neutron sources are complex, expensive and use large amounts of power. Method A novel neutron source comprising of a deuterium beam (energy of about 100 KeV) injected into a tube filled with tritium gas and/or tritium plasma that generates D-T fusion reactions, whose products are 14.06 MeV neutrons and 3.52 MeV alpha particles, is described. At the opposite end of the tube, the energy of deuterium ions that did not interact was recovered. Beryllium walls of appropriate thickness can be utilized to absorb 14 MeV neutrons and release 2 – 3 low-energy neutrons. Each ion source and tube forms a module. Larger systems can be formed using multiple units. Results Calculations indicate that this method is feasible and has multiple advantages. Relevance: among the possible applications of this neutron source concept are subcritical nuclear breeder reactors and transmutation of radioactive waste. Conclusion Due to its simplicity the idea can be tested using an inexpensive tabletop experiment.
Modelling drift of cold-stunned Kemp's ridley turtles stranding on the Dutch coast
Authors: Manral Darshika , Bos Ilse , de Boer Mark , van Sebille Erik
Published: August 2024

Background Every few years, juvenile Kemp’s ridley turtles (Lepidochelys kempii) are stranded on the Dutch coasts. The main population distribution of this critically endangered species primarily inhabits the Gulf of Mexico and the east coast of the United States. This study focuses on five reports from the Netherlands between 2007 and 2022, where juvenile turtles were reported to strand alive during the winter, albeit in a hypothermic state. At ambient ocean temperatures between 10°C and 13°C, Kemp’s ridley turtles begin to show an inability to actively swim and remain afloat on the ocean’s surface, a condition termed ‘cold stunning’. Understanding their transport in cold-stunned state can help improve the rehabilitation process of stranded turtles. Methods Cold-stunned turtles are back-tracked as passive, virtual particles from their stranding location using Lagrangian flow modelling. This study investigates when and where these juvenile turtles cross the threshold temperatures between 10° C and 14° C before stranding by tracking the temperature along the trajectories. Results As expected, the simulations show the transport of the cold-stunned turtles via the English Channel. More surprisingly, the analysis suggests they likely experience cold-stunning in the southern North Sea region and encounter temperatures below 10°C for only a few days to up to three weeks, and below 12°C for up to a month before stranding. Conclusions The estimate of cold-stunned drift duration of the turtles provides additional knowledge about their health status at the time of stranding. Adherence to rehabilitation protocols for Kemp’s ridley and post-release monitoring are recommended to improve their long-term survival.
Central territories of Tolyatti: history of formation and development prospects
Authors: Veretennikov Dmitry
Published: August 2024

For the first time, quantitative parameters of the growth and preservation of urban areas, the street and road network, and elements of the Tolyatti center system were obtained. A model of prospective development of the central territories of the city has been developed. Proposals have been formulated for the creation and functional filling of Tolyatti pedestrian zones. The developments on the creation of artistic decoration of the central territories of Tolyatti are presented. The directions of the development of the stylistics of the design of public spaces of the center system are proposed individually for each district of the city. The subject content of the public spaces of the central territories of Tolyatti has been determined.
It is intended for a wide range of specialists dealing with the problems of urban development and aspects of the design of their central territories, as well as for students and postgraduates of architectural universities in the fields of Architecture and Urban Planning.
Encounter as empowerment
Authors: Wilson Paul , Thoma Andrea , Loschavio dos Santos Maria Cecilia
Published: August 2024

This paper presents participatory design research conducted with marginalized young people from São Paulo, Brazil. The project consisted of two activities that used mapping and board games to explore instabilities and uncertainties in the participants' communities. The workshops aimed to foster encounters and highlight the capabilities and agency of young people. The resulting visual methods captured the participants' experiences of the urban landscape, demonstrating the potential for participatory design research to address social issues and empower marginalized communities.
STANDARD AND BIOPSYCHOSOCIAL OSTEOPATHIC MANAGEMENT FOR PATIENTS WITH NON-SPECIFIC LOW BACK PAIN (THE OSCAR STUDY): A SINGLE-CASE EXPERIMENTAL DESIGN
Authors: Draper-Rodi J , Abbey H , Brownhill K , Vogel S
Published: August 2024

Purpose and Background

Guidelines recommend biopsychosocial care for chronic, complex musculoskeletal conditions, including non-specific low back pain. The aims were: 1/ to assess how patients with low back pain respond to osteopathic treatment, both before and after an osteopath has completed a Biopsychosocial Pain Management (BPM) course; and 2/ to assess if it is feasible and acceptable for osteopath participants to receive weekly SCED data and use it to guide patient management.

Methods and Results

A multiple baseline single case experimental design trial (clinicaltrials.gov, on 18/10/2021, ID number NCT05120921) with 11 UK osteopaths was conducted. Patients were randomised to early, middle or late treatment start dates. Statistical analysis assessed the change between baseline, intervention and follow-up periods. Primary outcomes were the Numeric Pain Rating (NPR) and Patient Specific Function Scales (PSFS), measured during the baseline, the 6-week intervention, and during a 12-week follow-up period.

At baseline, the osteopaths reported stronger biopsychosocial attitudes to pain, compared to biomedical beliefs (PABS: 34 behavioural scale; 29 biomedical scale). Overall, patient participants showed daily increases in symptoms during the pre-treatment phase (+0.24/day, p<0.001), and daily decreases during treatment (−2.94 over the treatment phase, p<0.001), which continued post-treatment (−3.36 over 12 weeks, p=0.04). Similar improvements were observed for function.

Conclusion

Osteopathic care was shown to help patients with persistent low back pain. Patient recruitment was challenging because of the randomisation. With further development, the method shows feasibility as a means of enhancing research activity among practising clinicians.

Previous presentations or publications of the work

The protocol was published (https://doi.org/10.1016/j.ijosm.2023.100660) and presented at SBPR in 2022. The results were presented to an osteopathic conference in October 2023.

Ethics approval was received from the University College of Osteopathy Research Ethics Committee.

Conflicts of interests

Jerry Draper-Rodi receives fees from the sales of the e-learning course on the biopsychosocial management on the UCO CPD platform.

Sources of funding

The research was funded by the Osteopathic Foundation.
CONTRASTING CULTURES OF EMERGENCY DEPARTMENT CARE: A QUALITATIVE STUDY OF PATIENTS’ EXPERIENCES OF ATTENDING THE EMERGENCY DEPARTMENT FOR LOW BACK PAIN
Authors: Ryan C. , Pope C.J. , Roberts L.C.
Published: August 2024

Purpose and background

Although clinical guidelines recommend that low back pain (LBP) is best managed in primary or community care, in the UK and globally, LBP accounts for around 4% of emergency department (ED) attendances. Organising and delivering healthcare to be safe, effective, and acceptable requires hearing patients’ perspectives; this study therefore aimed to explore patients’ experiences of attending the ED for LBP.

Methods and results

This was a multisite qualitative interview study with 47 adults (aged 23–79 years) who, in the past six weeks, had attended one of four UK NHS emergency departments for LBP (all types and durations). Purposive sampling was used to gain variation in the recruiting site, and LBP and demographic characteristics. Data were collected using individual, semi-structured, telephone interviews (median 45mins). Interviews were audio-recorded, transcribed verbatim, and analysed thematically.

We identified significant variation in patients’ experiences of ED care for LBP, which we argue reflects contrasting cultures of ED care. We present three cultures, emergency screening only, ‘cynicism and neglect’, and ‘kindness’; these cultures differ in how they navigate the tension between the ED remit and patients’ perceived needs of care. We draw on Bourdieu's notions of field and habitus and professional identity theory to help explain these findings.

Conclusion

Our findings suggest unwarranted variation in ED care for LBP. Implications include the need for urgent access to primary and community care and clarity about best practice managing LBP in the ED; best practice guidance and strategies to implement this should be informed by notions of culture and professional identity.

No conflicts of interest

 

Sources of funding

Health Education England & National Institute of Health and Care Research (ICA-CDRF-2018-04-ST2-040)