bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Clinical Impact of Coronal Malalignment Following Circumferential Minimally Invasive Surgery (CMIS) for Adult Spinal Deformity Correction
Authors: Tanasansomboon Teerachat , Khandehroo Babak , Limthongkul Worawat , Yingsakmongkol Wicharn , Anand Neel
Published: October 2024

Study Design

Retrospective study.

Objectives

To determine prevalence and clinical importance of patients who had postoperative CM after CMIS for ASD correction.

Methods

We reviewed patients who underwent CMIS technique. Inclusion criteria were patients who were diagnosed with ASD, which is defined as having at least one of the following: coronal Cobb angle >20, SVA >50 mm, PI-LL >10, PT >20. They underwent >4 spinal levels fusion with CMIS technique and had at least 1-year follow-up. Preoperative and 1-year postoperative radiographs and clinical outcome measures (VAS, ODI, and SRS-22 scores) were used to make the comparisons.

Results

120 patients were included. Radiographic outcomes, including CVA, coronal Cobb angle, LSF curve, SVA, LL, and PI-LL, and clinical outcomes, were significantly improved postoperatively in each of the 3 preoperative subgroups (Bao type A, B, and C). At 1-year post-operation, 10 patients (12.4 %) of type A turned out to be CM, 4 patients (21.1%) of type B, and 8 patients (40%) of type C remained CM. Comparing coronally aligned (CA) to coronally mal-aligned patients at 1-year follow-up in each coronal subtype revealed that clinical and radiographic outcomes were comparable.

Conclusions

CMIS technique significantly improves radiographic and clinical outcomes for ASD patients. Incidence rates of postoperative CM were similar to open surgery. Type C patients were at risk of postoperative CM than types A and B. However, most 1-year outcomes were not significantly different between postoperative CA and CM patients regardless of the preoperative coronal alignment characteristics except ODI scores in type A.
Colorectal SIG Goals 2024–2025
Authors: Kluger Sharon
Published: October 2024

The Colorectal SIG seeks to enhance the knowledge and promote discussion of pediatric colorectal topics. The goal is to provide education, peer support, multi-institutional collaboration and encourage development of colorectal care for all patients across the world. We are looking forward to what we can accomplish together in 2025.
Magnitude of Septic Shock and its Associated Factors Among Critically Ill COVID-19 Patients at Addis Ababa COVID-19 Care Centers, Ethiopia
Authors: Tiruneh Kasie Gebeyehu , Mekonnen Migbar Sibhat , Tsegaw Melsew Getnet , Ashine Taye Mezgebu , Mesfin Edmialem Getahun , Sane Asaminew Habtamu , Beyene Hailu Asmare , Mengstie Melkie Ambaw , Zewude Wuletaw Chane
Published: October 2024

Background

The coronavirus disease (COVID-19) pandemic imposed a major public health impact. Septic shock is one of the frequent complications encountered among critically ill COVID-19 patients, leading to poor healthcare outcomes. This study aimed at assessing the magnitude of septic shock and its associated factors.

Methods and materials

An institution-based cross-sectional study was conducted retrospectively on 242 randomly selected COVID-19 patients admitted to three Addis Ababa COVID-19 care centers from September 2020 to October 2021. Septic shock was defined as a Sequential Organ Failure Assessment (SOFA) score ≥2 points and persisting hypotension requiring vasopressors to maintain a mean arterial pressure of ≥65 mmHg despite adequate volume resuscitation. Variables in the bivariate analysis were fitted to multiple regression analysis to eliminate confounders and determine independent risk factors for septic shock. In the multivariable analysis, statistical significance was declared at P < .05

Results

The prevalence of septic shock was found to be 39.3% (95% confidence interval [CI]: 33.1, 45.7). Advanced age (≥60 years) [AOR = 7.9; 95% CI: 2.3, 26.8], intensive care unit stay above 7 days [AOR = 6.2; 95%CI: 2.1, 18.7], invasive ventilation [AOR = 10; 95% CI: 3, 37], and chronic obstructive pulmonary disease (COPD) [AOR = 18; 95% CI: 7, 45] were significantly associated with increased septic shock among COVID-19 patients. Meanwhile, diabetes [AOR = 0.24; 95% CI: 0.08, 0.71] and cardiovascular diseases [AOR = 0.17; 95% CI: 0.07, 0.44] were associated with a decrease risk of septic shock.

Conclusion

The prevalence of septic shock in critically ill COVID-19 patients was high and a major concern in this study, and it is independently associated with advanced age, prolonged stay in the intensive care unit, and COPD. Based on these findings, healthcare professionals should closely monitor and manage patients with COVID-19 who have a history of COPD, are older, or prolonged intensive care unit (ICU) stays to prevent septic shock and improve patient outcomes.
The Effect of Jacobson Relaxation Technique on Sleep Quality of Patients With Cancer Under Chemotherapy: A Randomized Clinical Trial
Authors: Kahreh Fatemeh Safari , Abdi Alireza , Khatony Alireza , Salari Nader , Paveh Behnam Khaledi- , Aznab Mozaffar , Naghibzadeh Amirhossein , Mohammadi Mohammad
Published: October 2024

Introduction

Sleep is one of the most crucial basic human needs in Maslow's hierarchy, while sleep disorders are the most commonly occurring complications of chemotherapy.

Objective

This study was conducted to determine the effect of progressive muscle relaxation techniques on the sleep quality of patients with cancer undergoing chemotherapy.

Methods

This study was a randomized clinical trial performed on patients with cancer undergoing chemotherapy. Ninety cancer patients were selected by the convenience sampling method and randomly assigned into two groups; the progressive muscle relaxation group and the control group. Before the intervention, the Pittsburgh Sleep Quality Questionnaire (PSQQ) was completed for patients in both groups. In the intervention group, progressive muscle relaxation was performed for 4 weeks (twice daily and 20 min each time). In the control group, patients only received routine care. After the intervention, the PSQQ was completed again for patients in both groups. The data were analyzed using SPSS version 23.

Results

The mean and standard deviation of age were 45.95 ± 10.26 years. The samples of the intervention and control groups were homogeneous in terms of demographic characteristics. The results showed a significant improvement in the Pittsburgh Sleep Quality Index in the intervention group before and after the intervention ( P < .001, Z = 5.09). However, this rate was not different in the control group. The sleep level of the intervention and control groups was not different at the beginning of the study. However, at the end of the study, the sleep score in the intervention group had decreased significantly ( P < .001, Z = 3.52).

Conclusion

The results of the present study showed that progressive muscle relaxation improves the sleep quality of patients with cancer undergoing chemotherapy. Therefore, relaxation can be considered a useful and effective intervention for improving sleep quality of patients with cancer.
Combatting Burnout Culture and Imposter Syndrome in Medical Students and Healthcare Professionals: A Future Perspective
Authors: Faizan Siddiqui Mohd , Azaroual Mouna
Published: October 2024

It is the year 2050, and the world of medicine has undergone significant changes. With the advent of advanced technology and medical breakthroughs, medical schools have become even more competitive. Medical students are now required to have an exceptional academic record, outstanding research experience, and a perfect social media presence. However, with the rise of social media, a new phenomenon has emerged, one that has been plaguing medical students for years - imposter syndrome.
Evaluating the Effectiveness of Indigenous Health Curricula: Validation and Application of the NOSM CAST Instrument
Authors: Maar Marion , Urajnik Diana , Hudson Geoffrey L. , Manitowabi Darrel , McGregor Lorrilee , Senecal Sam , Strasser Roger , Warry Wayne , Jacklin Kristen
Published: October 2024

OBJECTIVES

In recent years, Indigenous health curricula have been integrated into medical education in response to international calls to improve Indigenous health care. Instruments to evaluate Indigenous health education are urgently needed. We set out to validate a tool to measure self-reported medical student preparedness to provide culturally safe care to Indigenous Peoples. We then applied the tool to evaluate the effectiveness of the Northern Ontario School of Medicine University's (NOSM U) Indigenous health curriculum.

METHODS

We conducted psychometric testing of a 46-item draft NOSM Cultural Competency and Safety Tool (CAST). Testing included principal components analysis, subscale and item analysis, and the use of paired sample t-tests to examine pre- and posttest change to measure learner outcomes. The NOSM CAST was transposed to create a retrospective pre–posttest survey with single-point-in-time scoring.

RESULTS

Respondents included five cohorts of first-year undergraduate medical students, with 305 of 320 participating (response rate of 95.3%). The validated survey subscales included knowledge, confidence/preparedness, attitudes, intentions for advocacy, antidiscrimination, and self-reflective practice, measured using 36 scale items. Cronbach's alpha showed good to excellent internal consistency for the scales ( α range = 0.82–0.91). Composite reliability values were acceptable. The pre–posttest analysis showed statistically significant increases on four scales: knowledge [ t(254) = 15.10, P < .001], confidence/preparedness [ t(254) = 15.85, P < .001], intentions for advocacy [ t(251) = 3.32, P = .001], and self-reflective practice [ t(254) = 8.04, P < .001]. The largest mean increases were for knowledge ( d = 1.07) and confidence/preparedness ( d = 1.15).

CONCLUSIONS

The NOSM CAST tracks student progress in Indigenous health curricula. NOSM U's classroom and immersion-based Indigenous health curriculum enhanced students’ self-reported preparedness for culturally safe care. NOSM CAST implemented together with an assessment of Indigenous patient experiences with the same learners constitutes a rigorous evaluation approach to Indigenous health curricula.
Indeterminate DC histiocytosis is distinct from LCH and often associated with other hematopoietic neoplasms
Authors: Ozkaya Neval , Melloul Benizri Sarah , Venkataraman Girish , Karai Laszlo J. , Fraitag Sylvie , Razanamahery Jérôme , Pittaluga Stefania , Battistella Maxime , Pack Svetlana , Le Pelletier François , Xi Liqiang , Moreau Anne , Lee Ina , Hélias-Rodzewicz Zofia , Donadieu Jean , Haroche Julien , Raffeld Mark , Jaffe Elaine S. , Emile Jean-François
Published: October 2024

Indeterminate dendritic cell histiocytosis (IDCH) is a rare and poorly understood entity characterized by accumulation of CD1a+/S100+ histiocytes (as Langerhans cell histiocytosis [LCH]) but with reduced-absent expression of Langerin/CD207. We assembled 43 cases of IDCH (defined by CD1a+/CD207<20% immunophenotypic profile) examining the clinical, pathologic, and molecular landscape. Median age at presentation was 70 years (interquartile range, 44-80) with cutaneous (31/43; 72%) and nodal (11/43; 26%) involvement predominating. Eighteen (42%) individuals had an associated nonhistiocytic hematopoietic neoplasm (“secondary” IDCH) whereas 7 of 43 (16%) had a concurrent non-IDCH histiocytosis (“mixed” histiocytosis). Most cases exhibited morphology indistinguishable from LCH but with a CD1c+/CSF1R(CD115)− phenotype, mirroring the signature of normal indeterminate cells and conventional DC type 2. Mutational analysis revealed frequent KRAS (13/32; 41%) and BRAF p.V600E (11/36, 31%) mutations that were nearly mutually exclusive. RNA-sequencing analysis uncovered ETV3::NCOA2 fusion in 6 other patients presenting as a sole genetic alteration without any other concurrent histiocytic or hematopoietic neoplasm. BRAF and MAP2K1 alterations were significantly associated with partial/retained (1%-20%) Langerin expression (P = .005) and mixed histiocytosis (P = .002). Remarkably, myeloid alterations (DNMT3A, TET2, and SRSF2) co-occurred in IDCH tissues of several individuals. Paired sequencing of IDCH and concurrent non-IDCH hematopoietic neoplasm in 4 individuals revealed shared mutations. Age at diagnosis and any nodal involvement at diagnosis predicted inferior overall survival, but BRAF/RAS pathway alterations did not affect outcome. These data have implications for the diagnostic evaluation, classification, and therapeutic management of IDCH.
Pathogenic variants inCFAP46,CFAP54,CFAP74andCFAP221cause primary ciliary dyskinesia with a defective C1d projection of the central apparatus
Authors: Wohlgemuth Kai , Hoersting Niklas , Koenig Julia , Loges Niki Tomas , Raidt Johanna , George Sebastian , Cindrić Sandra , Schramm Andre , Biebach Luisa , Lay Simon , Dougherty Gerard W. , Olbrich Heike , Pennekamp Petra , Dworniczak Bernd , Omran Heymut
Published: October 2024

Background

Primary ciliary dyskinesia is a rare genetic disorder caused by insufficient mucociliary clearance leading to chronic airway infections. The diagnostic guideline of the European Respiratory Society primarily recommends an evaluation of the clinical history (e.g.by the PICADAR prediction tool), nasal nitric oxide production rate measurements, high-speed videomicroscopy analysis of ciliary beating and an assessment of ciliary axonemesviatransmission electron microscopy. Genetic testing can be implemented as a last step.

Aims

In this study, we aimed to characterise primary ciliary dyskinesia with a defective C1d projection of the ciliary central apparatus and we evaluated the applicability of the European Respiratory Society diagnostic guideline to this primary ciliary dyskinesia type.

Methods

Using a high-throughput sequencing approach of genes encoding C1d components, we identified pathogenic variants in the novel primary ciliary dyskinesia genesCFAP46andCFAP54, and the known primary ciliary dyskinesia geneCFAP221. To fully assess this primary ciliary dyskinesia type, we also analysed individuals with pathogenic variants inCFAP74.

Results

Careful evaluation revealed that C1d-defective primary ciliary dyskinesia is associated with normal situs composition, normal nasal nitric oxide production rates, normal ciliary ultrastructure by transmission electron microscopy and normal ciliary beating by high-speed videomicroscopy analysis. Despite chronic respiratory disease, PICADAR does not reliably detect this primary ciliary dyskinesia type. However, we could show byin vitrociliary transport assays that affected individuals exhibit insufficient ciliary clearance.

Conclusions

Overall, this study extends the spectrum of primary ciliary dyskinesia genes and highlights that individuals with C1d-defective primary ciliary dyskinesia elude diagnosis when using the current diagnostic algorithm. To enable diagnosis, genetic testing should be prioritised in future diagnostic guidelines.
Fungal lung disease
Authors: Jaggi Tavleen Kaur , Agarwal Ritesh , Tiew Pei Yee , Shah Anand , Lydon Emily C. , Hage Chadi A. , Waterer Grant W. , Langelier Charles R. , Delhaes Laurence , Chotirmall Sanjay H.
Published: October 2024

Fungal lung disease encompasses a wide spectrum of organisms and associated clinical conditions, presenting a significant global health challenge. The type and severity of disease are determined by underlying host immunity and infecting fungal strain. The most common group of diseases are associated with the filamentous fungusAspergillusspecies and include allergic bronchopulmonary aspergillosis, sensitisation, aspergilloma and chronic and invasive pulmonary aspergillosis. Fungal lung disease remains epidemiologically heterogenous and is influenced by geography, environment and host comorbidities. Diagnostic modalities continue to evolve and now include novel molecular assays and biomarkers; however, persisting challenges include achieving rapid and accurate diagnosis, particularly in resource-limited settings, and in differentiating fungal infection from other pulmonary conditions. Treatment strategies for fungal lung diseases rely mainly on antifungal agents but the emergence of drug-resistant strains poses a substantial global threat and adds complexity to existing therapeutic challenges. Emerging antifungal agents and increasing insight into the lung mycobiome may offer fresh and personalised approaches to diagnosis and treatment. Innovative methodologies are required to mitigate drug resistance and the adverse effects of treatment. This state-of-the-art review describes the current landscape of fungal lung disease, highlighting key clinical insights, current challenges and emerging approaches for its diagnosis and treatment.
Lung structure and longitudinal change in cardiac structure and function: the MESA COPD Study
Authors: Hermann Emilia A. , Sun Yifei , Hoffman Eric A. , Allen Norrina B. , Ambale-Venkatesh Bharath , Bluemke David A. , Carr J. Jeffrey , Kawut Steven M. , Prince Martin R. , Shah Sanjiv J. , Smith Benjamin M. , Watson Karol E. , Lima Joao A.C. , Barr R. Graham
Published: October 2024

Background

Lung structure and cardiac structure and function are associated cross-sectionally. The classic literature suggests relationships of airways disease to cor pulmonale and emphysema to reduced cardiac output (CO) but longitudinal data are lacking.

Methods

The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study was a multicentre longitudinal COPD case–control study of participants 50–79 years with ≥10 pack-years smoking without clinical cardiovascular disease. Segmental airway wall area (WA) and percent emphysema were measured on computed tomography. Right and left ventricle parameters were assessed on cardiac magnetic resonance imaging (cMRI) in exams 6 years apart. Longitudinal and period cross-sectional associations were evaluated with mixed models adjusted for demographics, body size and smoking.

Results

The 187 participants with repeated cMRI were 67±7 years old; 42% had COPD; 22% currently smoked; and the race/ethnicity distribution was 54% White, 30% Black, 14% Hispanic and 3% Asian. Greater WA at enrolment was associated with longitudinal increase in right ventricular (RV) mass (3.5 (95% CI 1.1–5.9) g per 10 mm2WA). Greater percent emphysema was associated with stably lower left ventricular (LV) end-diastolic volume (−7.8 (95% CI −10.3– −3.0) mL per 5% emphysema) and CO (−0.2 (95% CI −0.4– −0.1) L·min−1per 5% emphysema).

Conclusion

Cardiac associations varied by lung structure over 6 years in this multi-ethnic study. Greater WA at enrolment was associated with longitudinal increases in RV mass, whereas greater percent emphysema was associated with stable decrements in LV filling and CO.
Acetylxylan esterase is the key to the host specialization of wood-decay fungi predicted by random forest machine-learning algorithm
Authors: Hasegawa Natsuki , Sugiyama Masashi , Igarashi Kiyohiko
Published: October 2024

Wood-decay fungi produce extracellular enzymes that metabolize wood components such as cellulose, hemicellulose and lignin. Each fungus has a preference of wood species as the host, but identification of these preferences requires a huge amount of cultivation data. Here, we developed a method of predicting the wood species preference, Angiosperm specialist or Gymnosperm specialist or generalist, of wood-decay fungi using the random forest machine-learning algorithm, trained on the numbers of families associated with host specialization in the Carbohydrate-Active enZymes database. The accuracy of the prediction was about 80%, which is lower than that of the classification of white- and brown-rot fungi (more than 98%) by the same method, but the reason for this may be the ambiguity of the definition of “preference” and “generalists”. Carbohydrate esterase (CE) family 1 acetylxylan esterase was the most significant contributor to the prediction of host specialization, followed by family 1 carbohydrate-binding module and CE family 15, mainly containing glucuronoyl esterases. These results suggest that the ability to degrade glucuronoacetylxylan, a major hemicellulose of Angiosperm, is the key factor determining the host specialization of wood-decay fungi.
Autistic and schizotypal traits exhibit similarities in their impact on mentalization and adult attachment impairments: a cross-sectional study
Authors: Sörnyei Dániel , Vass Ágota , Németh Dezső , Farkas Kinga
Published: October 2024

Background

Deficits in mentalizing and attachment occur in the autism and schizophrenia spectrum, and their extended traits in the general population. Parental attachment and the broader social environment highly influence the development of mentalizing. Given the similarities in the symptomatology and neurodevelopmental correlates of autism spectrum disorder (ASD) and schizophrenia (SCH), it is crucial to identify their overlaps and differences to support screening, differential diagnosis, and intervention.

Methods

This cross-sectional study utilized questionnaire data from 2203 adults (65.1% female, mean age[SD] = 37.98[9.66]), including participants diagnosed with ASD, SCH, and those exhibiting subclinical traits to investigate the associations between mentalizing, attachment, and perceived social support during adolescence across the autistic and schizotypy spectrum.

Results

It was revealed that both autistic and schizotypal traits have comparable effects on insecure adult attachment, primarily through challenges in mentalizing. The impact of mentalizing deficits on adult attachment slightly varies between autistic and schizotypal traits. Conversely, perceived social support during adolescence relates to improved mentalizing and secure adult attachment as a protective factor during development.

Conclusions

These outcomes highlight the significance of supportive therapeutic relationships and community care while suggesting directions for further research and collaborative treatments addressing ASD and SCH, considering the differential impact of mentalizing on adult attachment.
A preventive integrated eHealth approach for individuals with a low socioeconomic position: protocol for a realist evaluation
Authors: Israel Adriana M.C. , van Lenthe Frank J. , Beenackers Mariëlle A.
Published: October 2024

Background

Adoption of standalone eHealth tools is low among persons in lower socioeconomic groups. The preventive integrated eHealth approach combines blended care with an active and personal approach to facilitate access to local care, tailored to the needs of the participant. We describe the four step preventive integrated eHealth approach for individuals with a low socioeconomic position and the realist evaluation protocol of the intervention and implementation. The realist evaluation centers around the question, ‘what works for whom in what circumstances and why’.

Methods

The study population will consist of adult individuals with a low socioeconomic position, who participate in the preventive integrated eHealth approach in one of the participating locations in the Netherlands. The four-step intervention consists of: (1) a proactive invitation of participants by care professionals, (2) the use of an eHealth tool that produces a personalized health report, (3) a personal consultation with a care professional to discuss the personalized health report and set a goal to work on, and (4) active referral to local social and health care. An initial program theory theorized from literature and stakeholder involvement is presented. Qualitative and quantitative data collection and analysis with participants (survey at zero, three and twelve months and focus groups at six months) and professionals (interviews at three months) will inform the realist evaluation and serves to test and refine the initial program theory.

Discussion

Our mixed-methods realist evaluation on the effect and implementation of a personal and active blended care approach will elucidate what elements trigger the mechanisms and responses of how individuals with a low socioeconomic position experience the preventive integrated eHealth approach. This will inform the way a preventative health check incorporating eHealth can be used to its full potential for low socioeconomic positioned groups to help close the digital divide and contribute to reduce health disparities.
Impact of refrigeration of different Resin composite restorative materials on the marginal adaptation in class II restorations
Authors: El-Maksoud Omar Abd , Hamama Hamdi , Wafaie Ramy Ahmed , El-Wassefy Noha , Mahmoud Salah Hasab
Published: October 2024

Background

The pre-polymerization temperature of resin composite restorative materials could influence their adaptation to cavity details. As a current debate is existing about the refrigeration of resin composite restorative materials, this study was designed to assess the effect of refrigeration of 3 types of resin composite restorative materials with different matrix systems on their marginal adaptation in Class II restorations.

Methods

Forty-two sound maxillary molars, each with two separated Class II cavities, were used in this study. The teeth were assigned into 3 main groups (n = 14) according to the restorative /adhesive system used; an Ormocer-based composite (Admira Fusion/Futurabond M+, Voco GmbH, Cuxhaven, Germany), a methacrylate modified Ormocer-based (Ceram.X SphereTEC One/Prime&Bond Universal, Dentsply Sirona GmbH Konstanz, Germany), and a methacrylate-based (Tetric N-Ceram/Tetric N-Bond Universal, Ivoclar Vivadent AG, Schaan, Liechtenstein). Each group was then divided into 2 subgroups (n = 14) according to the gingival margin location; 1 mm above and 1 mm below the cemento-enamel junction (C.E.J). Each subgroup was further divided into 2 categories (n = 7) according to the storage temperature; stored at room temperature or stored in refrigerator at 4°- 5° C. Epoxy resin replicas were observed under scanning electron microscope (SEM) to examine the marginal gaps. A gab scoring system was used to assess the marginal adaptation of each restoration by giving scores on the basis of measurements of the maximum marginal gaps. The data obtained were statistically analyzed using the Chi-square test at a significance level of p < 0.05.

Results

None of the tested groups exhibited 100% gap-free margins irrespective of margin location or storage temperature. For both storage temperatures, no statistically significant difference was observed among all tested groups either with margins located above or below C.E.J (p > 0.05). As well, there was no statistically significant difference when comparing both marginal locations for each material (p > 0.05). Regarding the effect of storage temperature, statistically significant difference was only observed between the room-temperature stored groups with margins located above C.E.J and their corresponding groups stored in refrigerator (p < 0.05).

Conclusion

The refrigeration of resin composite restorative materials prior to the restorative procedures revealed a deleterious effect on marginal adaptation of the restorations with margins located in enamel regardless the type of material used.
Expiratory flow limitation development index (ELDI): a novel method of assessing respiratory mechanics in COPD
Authors: Dean James , Fowler Stephen J. , Singh Dave , Beech Augusta
Published: October 2024

Background

Expiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI).

Methods

A retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance.

Results

The mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment.

Conclusions

COPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.
Working in a relational way is everything: Perceptions of power and value in a drug policy-making network
Authors: Zakimi Naomi , Bouchard Martin , Ritter Alison , Greer Alissa
Published: October 2024

Background

The development of drug policies has been a major focus for policy-makers across North America in light of the ongoing public health emergency caused by the overdose crisis. In this context, the current study examined stakeholders’ experiences and perceptions of power and value in a drug policy-making process in a North American city using qualitative, questionnaire, and social network data.

Methods

We interviewed 18 people who participated in the development of a drug policy proposal between October 2021 and March 2022. They represented different groups and organizations, including government (n = 3), people who use drugs-led advocacy organizations (n = 5), other drug policy advocacy organizations (n = 5), research (n = 3) and police (n = 2). Most of them identified as men (n = 8) and white (n = 16), and their ages ranged between 30 and 80 years old (median = 50). Social network analysis questionnaires and semi-structured qualitative interviews were administered via Zoom. Social network data were analysed using igraph in R, and qualitative data were analysed using thematic analysis. The analyses explored perceptions of value and power within a drug policy-making network.

Results

The policy-making network showed that connections could be found across participants from different groups, with government officials being the most central. Qualitative data showed that inclusion in the network and centrality did not necessarily translate into feeling powerful or valued. Many participants were dissatisfied with the process despite having structurally advantageous positions or self-reporting moderately high quantitative value scores. Participants who viewed themselves as more valued acknowledged many process shortcomings, but they also saw it as more balanced or fair than those who felt undervalued.

Conclusions

While participation can make stakeholders and communities feel valued and empowered, our findings highlight that inclusion, position and diversity of connections in a drug policy-making network do not, in and of itself, guarantee these outcomes. Instead, policy-makers must provide transparent terms of reference guidelines and include highly skilled facilitators in policy discussions. This is particularly important in policy processes that involve historical power imbalances in the context of a pressing public health emergency.
Hyperspectral imaging for pest symptom detection in bell pepper
Authors: Krüger Marvin , Zemanek Thomas , Wuttke Dominik , Dinkel Maximilian , Serfling Albrecht , Böckmann Elias
Published: October 2024

Background

The automation of pest monitoring is highly important for enhancing integrated pest management in practice. In this context, advanced technologies are becoming increasingly explored. Hyperspectral imaging (HSI) is a technique that has been used frequently in recent years in the context of natural science, and the successful detection of several fungal diseases and some pests has been reported. Various automated measures and image analysis methods offer great potential for enhancing monitoring in practice.

Results

In this study, the use of hyperspectral imaging over a wide spectrum from 400 to 2500 nm is investigated for noninvasive identification and the distinction of healthy plants and plants infested with Myzus persicae (Sulzer) and Frankliniella occidentalis (Pergande) on bell peppers. Pest infestations were carried out in netted areas, and images of single plants and dissected leaves were used to train the decision algorithm. Additionally, a specially modified spraying robot was converted into an autonomous platform used to carry the hyperspectral imaging system to take images under greenhouse conditions. The algorithm was developed via the XGBoost framework with gradient-boosted trees. Signals from specific wavelengths were found to be associated with the damage patterns of different insects. Under confined conditions, M. persicae and F. occidentalis infestations were distinguished from each other and from the uninfested control for single leaves. Differentiation was still possible when small whole plants were used. However, application under greenhouse conditions did not result in a good fit compared to the results of manual monitoring.

Conclusion

Hyperspectral images can be used to distinguish sucking pests on bell peppers on the basis of single leaves and intact potted bell pepper plants under controlled conditions. Wavelength reduction methods offer options for multispectral camera usage in high-grown vegetable greenhouses. The application of automated platforms similar to the one tested in this study could be possible, but for successful pest detection under greenhouse conditions, algorithms should be further developed fully considering real-world conditions.
Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study
Authors: Sardh Eliane , Balwani Manisha , Rees David C. , Anderson Karl E. , Jia Gang , Sweetser Marianne T. , Wang Bruce
Published: October 2024

Background

Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18–65 years who completed part C of the Phase 1 givosiran study (NCT2452372).

Methods

Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint.

Results

Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed.

Conclusions

In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria.
Different diseases, different needs: Patient preferences for gene therapy in lysosomal storage disorders, a probabilistic threshold technique survey
Authors: Corazolla Eleonore M. , Eskes Eline C. B. , Veldwijk Jorien , Brands Marion M. M. G. , Dekker Hanka , van de Mheen Erica , Langeveld Mirjam , Hollak Carla E. M. , Sjouke Barbara
Published: October 2024

Background

Gene therapy is currently in development for several monogenetic diseases including lysosomal storage disorders. Limited evidence is available on patient preferences for gene therapy in this population. In this study, we compare gene therapy-related risk tolerance between people affected by three lysosomal storage diseases currently faced with different therapeutic options and prognoses.

Methods

A survey including the probabilistic threshold technique was developed in which respondents were asked to choose between gene therapy and the current standard of care. The attributes included to establish participants’ risk tolerance were previously identified in focus groups of affected people or their representatives, namely: risk of mild side effects, severe side effects, the need for additional medication, and the likelihood of long-term effectiveness. The survey was distributed among people receiving outpatient care for type 1 Gaucher disease (good prognosis with current treatment options), Fabry disease (varying prognosis with current treatment options, XY-genotype on average more severely affected than XX), and parents representing people with severe forms of mucopolysaccharidosis type III A/B (poor prognosis, no disease-specific therapy available).

Results

A total of 85 surveys were completed (15 Gaucher disease respondents, 62 Fabry disease respondents (17 self-identifying male), eight parents of ten people with mucopolysaccharidosis type III). Disease groups with higher disease severity trended towards higher risk tolerance: Gaucher disease respondents were most cautious and predominantly preferred the current standard of care as opposed to MPS III representatives who were more risk tolerant. Respondents with Fabry disease were most heterogeneous in their risk tolerance, with male participants being more risk tolerant than female participants. Long-term effectiveness was the attribute in which respondents tolerated the least risk.

Conclusions

People affected by a lysosomal storage disease associated with a poorer prognosis and less effective current treatment options trended towards more risk tolerance when choosing between gene therapy and the current standard of care. This study shows the importance of involvement of patient preferences before and during the development process of new treatment modalities such as gene therapy for rare diseases, to ensure that innovative therapies align with the wishes and needs of people affected by these diseases.
Analysis of binary mixture of oxytetracycline and bromohexine in their combined veterinary formulation by four simple spectrophotometric methods with greenness assessment
Authors: Sharkawi Marco M.Z. , Safwat Mark T. , Abdelwahab Nada S.
Published: October 2024

Tetracyclines family is considered as the first-line antibiotic drugs for food animals. Formulating bromhexine (BR) with oxytetracycline (OTC) improved the antibacterial activity of OTC, besides it is considered as a mucolytic agent. Four precise, rapid, and simple spectrophotometric methods were successfully developed for resolution of the overlapped spectra of OTC and BR in their pure form and in their pharmaceutical formulation. The proposed methods are absorption correction (AC), dual wavelength (DW), induced dual wavelength (IDW), and spectrum subtraction (SS) spectrophotometric methods. The developed methods were used for the determination of OTC and BR in the ranges of 2–50 µg/mL and 1–30 µg/mL, respectively for all methods. For (AC) and (SS) methods, OTC and BR were determined at 380 nm and 245.6 nm, respectively after spectral resolution steps. While for (DW) method, the absorbance difference between λ (271.8 –287.6 nm) and λ (245.6 –283.2 nm) were used for the determination of OTC and BR, in order. For IDW, it depended on using the absorbance difference between 271.8 nm and 245.6 nm as well as the equality factor (F) calculated for each drug at the selected wavelengths. In all methods, HCl was used as a solvent and they are validated according to ICH guidelines. Several green metric tools have been developed to evaluate the greenness of the analytical methods like National Environmental Methods Index (NEMI), Modified NEMI, Analytical Eco-scale, Green Analytical Procedure Index (GAPI) and Analytical GREEnness calculator (AGREE), and all ensured the low impact of the suggested approaches on health and environment. The proposed methods are highly selective, robust and precise. Additionally they are time and money effective and can be used in any analytical laboratory.
Epigenomic biomarkers insights in PBMCs for prognostic assessment of ECMO-treated cardiogenic shock patients
Authors: Hsiao Yi-Jing , Chiang Su-Chien , Wang Chih-Hsien , Chi Nai-Hsin , Yu Hsi-Yu , Hong Tsai-Hsia , Chen Hsuan-Yu , Lin Chien-Yu , Kuo Shuenn-Wen , Su Kang-Yi , Ko Wen-Je , Hsu Li-Ming , Lin Chih-An , Cheng Chiou-Ling , Chen Yan-Ming , Chen Yih-Sharng , Yu Sung-Liang
Published: October 2024

Objective

As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited.

Methods

Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses.

Results

The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test).

Conclusions

This study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes.
Biomarkers of bone metabolism in [223Ra] RaCl2 therapy - association with extent of disease and prediction of overall survival
Authors: Fosbøl Marie Øbro , Jørgensen Niklas Rye , Petersen Peter Meidahl , Kjaer Andreas , Mortensen Jann
Published: October 2024

Background

The alpha-emitting radionuclide therapy [223Ra]RaCl2 (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.

Methods

Prospective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.

Results

A total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7–16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1–4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1–2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3–5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1–13.9), P < 0.001).

Conclusion

BMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.

Trial registration

Clinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1.
Determining the effect of high hydrostatic pressure on the refrigerated stability of avocado puree
Authors: Uzunlu Sinan
Published: October 2024

The present study aimed to extend refrigerated stability of locally grown avocado fruit by applying High Hydrostatic Pressure (HHP) treatment. HHP was applied at 600 MPa for 3 min to avocado puree and stored at 4 °C for 28 days. Physicochemical (colour CIE L*, a*, b*, total oil amount, chlorophyll, pH, moisture) and microbiological (mesophilic, yeast-mould) analyses were performed at seven-day intervals on both control (untreated) and HHP-treated sample packs. It could be judged that HHP treatment effectively controlled the colour indices, preventing undesired changes during the cold storage period of avocado puree. In conclusion, this study demonstrated that HHP-processed avocado puree exhibited stability for 28 days compared to unprocessed puree at 4 °C. The shelf-life stability of avocado puree under chilled conditions was extended from 7 to 28 days.

Graphical Abstract