bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted DNase treatment of obstructive lung disease: a pilot randomised controlled trial
Authors: Negewo Netsanet A. , Niessen Natalie M. , Baines Penelope J. , Williams Evan J. , Fibbens Naomi , Simpson Jodie L. , McDonald Vanessa M. , Berthon Bronwyn S. , Gibson Peter G. , Baines Katherine J.
Published: October 2024

Background

Sputum extracellular DNA (eDNA) is associated with disease severity in asthma and COPD and therefore emerging as a potential therapeutic target. The aim of this study was to investigate the effect of 10 days of recombinant human DNase (rhDNase) treatment of eDNA-high asthma and COPD on sputum eDNA levels, neutrophil-related inflammation, lung function and symptoms.

Methods

Adults with asthma (n=80) or COPD (n=66) were screened for the presence of high (>20 µg·mL−1) sputum eDNA and those eligible (n=18 asthma, n=17 COPD) were randomised to a two-period crossover controlled trial consisting of daily nebulised rhDNase (2.5 mg/2.5 mL) or placebo (5 mL 0.9% saline) for 10 days, with a 2-week washout period. The primary outcome was sputum eDNA, and secondary outcomes included sputum neutrophil extracellular trap (NET)-related biomarkers, inflammatory cell counts, lung function and respiratory symptoms.

Results

At screening, high eDNA was associated with significantly higher sputum total cell count, sputum colour score and inflammation (HNP1-3, LL-37 and interleukin-1β) in both asthma and COPD compared to low eDNA groups. In asthma, participants with high eDNA were older and had poorer lung function and asthma control compared to low eDNA. Administration of nebulised rhDNase significantly reduced sputum eDNA levels in both asthma (median (Q1–Q3) Pre: 48.4 (22.1–74.1); Post: 17.0 (5.0–31.0) µg·mL−1; p=0.022) and COPD (median (Q1–Q3) Pre: 39.3 (36.7–55.6); Post: 25.4 (11.3–38.6) µg·mL−1; p=0.044) compared to placebo. Symptoms, lung function and NET biomarkers remained unchanged. In asthma, there was a reduction in banded blood neutrophils (3.2 (0–7.7) to 0.0 (0.0–1.5); p=0.044).

Conclusion

Targeted rhDNase treatment for 10 days effectively reduced sputum eDNA in eDNA-high asthma and COPD.
A Review on Combined Strategy of Non-invasive Brain Stimulation and Robotic Therapy
Authors: Zhang Leiyu , Chang Yawei , Zhang Feiran , Li Jianfeng
Published: October 2024

Stroke is a major cause of death and disability among adults in China, and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation. The non-invasive brain stimulation (NBS) can modulate the excitability of the cerebral cortex and provide after-effects apart from immediate effects to regain extremity motor functions, whereas robotic therapy provides high-intensity and long-duration repetitive movements to stimulate the cerebral cortex backward. The combined strategy of the two techniques is widely regarded as a promising application for stroke patients with dyskinesia. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) are important methods of NBS. Their recovery principles, stimulation parameters, and clinical applications have been summarized. The combined treatments of rTMS/tDCS and robotic therapy are analyzed and discussed to overcome the application barriers of the two techniques. The future development trend and the key technical problems are expounded for the clinical applications.
Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity
Authors: Huang Zhuoan , Yao Junyu , Nie Lingdi , Nie Xinchen , Xiong Xuechunhui , Kõks Sulev , Quinn John P. , Kanhere Aditi , Wang Minyan
Published: October 2024

Background

Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively.

Methods

A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone. The role of SFKs antagonism on light aversion was assessed by the total time the mouse stays in the light and transition times between the dark and light compartments. To gain insight to the preventive mechanism of SFKs antagonism, hypothalamic neuropeptides levels were assessed using enzyme linked immunofluorescent assay and trigeminal ganglion activity were assessed using RNA-sequencing and qPCR analysis.

Results

SFKs antagonism by a clinically relevant SFKs inhibitor saracatinib reduced the total time in light and transition times in male mice, but not in females, suggesting SFKs play a crucial role in photophobia progressing and exhibit a male-only effect. SFKs antagonism had no effect on hypothalamic calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide levels of all mice investigated, suggesting the gender-different effect of saracatinib on light aversion appears to be independent of these hypothalamic neuropeptide levels. In trigeminal ganglion of male mice, photophobia is associated with profound alteration of differentially expressed genes, part of which were reversed by SFKs antagonism. Subsequent qPCR analysis showed SFKs antagonism displayed gender-different modulation of expression in some candidate genes, particularly noteworthy those encoding ion channels (trpm3, Scn8a), ATPase signaling (crebbp, Atp5α1) and kinase receptors (Zmynd8, Akt1).

Conclusions

In conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine.
Effectiveness of community-based Baduanjin exercise intervention for older adults with varying frailty status: a randomized controlled trial
Authors: Tou Nien Xiang , Goh Siew Fong , Harding Susana , Tsao Mary Ann , Ng Tze Pin , Wee Shiou-Liang
Published: October 2024

Background

Due to poorer exercise tolerance, it may be challenging for frail older adults to engage in moderate- or vigorous-intensity exercise. While low-intensity exercise interventions may be more feasible, its effectiveness for such population group remains unclear. We examined the effectiveness and implementation of community-based Baduanjin Qigong, a low-intensity exercise program in older adults with varying frailty status.

Methods

A two-arm, multicenter assessor-blind parallel group randomized controlled trial was conducted at three local senior activity centers. Fifty-six community-dwelling older adults with low handgrip strength were randomly allocated to either the intervention (IG) or wait-list control (CG) group. The IG underwent a supervised 16-week Baduanjin exercise program at a frequency of 2–3 × 60 min sessions/week. The CG was instructed to maintain their usual activity and received a monthly health education talk. The primary outcome measures were knee extension strength, vital exhaustion, and fear of falling. Secondary outcome measures include physiological falls risk, handgrip strength, gait speed, timed up and go test, 30-second sit-to-stand, quality of life, depression, and frailty. All outcome measures were assessed at baseline and 4-month follow-up.

Results

Overall, there were no statistically significant differences in all outcome measures between CG and IG at 4-month follow-up. However, in exploratory compliance analysis, a statistically significant group x time interaction was found for vital exhaustion (B = -3.65, 95% CI [-7.13, -0.16], p = .047) among participants with at least 75% attendance. In post-hoc within-group comparisons, IG showed improved vital exhaustion by 4.31 points (95% CI [1.41, 7.20], d = 0.60). The average participant attendance rate was 81.3%. No major adverse events occurred, and all participants reported positive experiences with the exercise intervention.

Conclusions

Our study demonstrated that Baduanjin is a safe, feasible, and acceptable exercise program that can be successfully implemented in community settings for older adults with varying frailty status. With good adherence, Baduanjin exercise could potentially be effective in alleviating vital exhaustion. However, the effectiveness of Baduanjin on physical performance, psychological measures and frailty in community-dwelling older adults remains equivocal.

Trial registration

ClinicalTrials.gov NCT04549103. Registered September 16, 2020.
Rapid growth rate of Enterobacter sp. SM3 determined using several methods
Authors: Pollack-Milgate Sophie , Saitia Sanchi , Tang Jay X.
Published: October 2024

Background

Bacterial growth rate, commonly reported in terms of doubling time, is frequently determined by one of two techniques: either by measuring optical absorption of a growing culture or by taking samples at different times during their growth phase, diluting them, spreading them on agar plates, incubating them, and counting the colonies that form. Both techniques require measurements of multiple repeats, as well careful assessment of reproducibility and consistency. Existing literature using either technique gives a wide range of growth rate values for even the most extensively studied species of bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and  Staphylococcus aureus. This work aims to apply several methods to reliably determine the growth rate of a recently identified species of Enterobacteriaceae, called Enterobacter sp. SM3, and to compare that rate with that of a well-known wildtype E. coli strain KP437.

Results

We extend conventional optical density (OD) measurements to determine the growth rate of Enterobacter sp. SM3. To assess the reliability of this technique, we compare growth rates obtained by fitting the OD data to exponential growth, applying a relative density method, and measuring shifts in OD curves following set factors of dilution. The main source of error in applying the OD technique is due to the reliance on an exponential growth phase with a short span. With proper choice of parameter range, however, we show that these three methods yield consistent results. We also measured the SM3 division rate by counting colony-forming units (CFU) versus time, yielding results consistent with the OD measurements. In lysogeny broth at 37oC, SM3 divides every 21 ± 3 min, notably faster than the RP437 strain of E. coli, which divides every 29 ± 2 min.

Conclusion

The main conclusion of this report is that conventional optical density (OD) measurements and the colony-forming units (CFU) method can yield consistent values of bacterial growth rate. However, to ensure the reproducibility and reliability of the measured growth rate of each bacterial strain, different methods ought to be applied in close comparison. The effort of checking for consistency among multiple techniques, as we have done in this study, is necessary to avoid reporting variable values of doubling time for particular species or strains of bacteria, as seen in the literature.
Effects of dexamethasone on the EC50 of remifentanil combined with dexmedetomidine achieving analgesia during pancreatic extracorporeal shockwave lithotripsy: a prospective, randomized and controlled study
Authors: Guo Yu , Lu Jun , Li Bo , Wang Chang-Li , Wang Jia-Feng , Deng Xiao-Ming
Published: October 2024

Background

In addition to their classic genomic effects, glucocorticoids also manifest rapid non genomic effects. We speculate that dexamethasone has the potential prompt onset of analgesic effects. The objective of this study is to investigate the influence of a single preoperative dose of dexamethasone on the half maximal effective concentration (EC50) of remifentanil when combined with dexmedetomidine for pain relief during pancreatic extracorporeal shockwave lithotripsy (P-ESWL).

Methods

A total of 60 patients undergoing P-ESWL were enrolled and randomized at 1:1 ratio into the dexamethasone (DXM) group and the placebo group. Before anesthesia induction, patients in DXM group received an intravenous injection of 8 mg dexamethasone, while subjects in placebo group received an equal dose of physiological saline. Monitored anesthesia care (MAC) was performed based on remifentanil in combination with dexmedetomidine. Remifentanil was administered by TCI with an initial target concentration of 2.5 µg/mL for both groups. A positive response was defined as that VAS score > 3 by the patient at any time during the procedure. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.3 ng/mL intervals, based on the response of the previous patient. The EC50 of remifentanil for pain relief during P-ESWL treatment was calculated using Dixon’s up-and-down method. Hemodynamic variables, oxygen saturation and adverse events were also recorded.

Results

Dixon up-and-down method revealed that the EC50 of remifentanil was significantly higher in placebo group (2.65 ± 0.28 ng/mL) than in DXM group (2.02 ± 0.23 ng/ml) (P < 0.001). Hemodynamic parameter exhibited a significant decrease in mean arterial pressure (MAP) and heart rate (HR) before and after induction in placebo group; however, data of the two groups were comparable (P>0.05). Less adverse events occurred in DXM group, including the incidence of postoperative nausea and vomiting (PONV) and analgesia requirement with in the first 24 h following the procedure at ward.

Conclusion

Dexamethasone exerted analgesic effects with a rapid onset, and patients received dexamethasone 8 mg preoperative had a lower required EC50 of remifentanil during P-ESWL. It is also associated with reduced PONV in addition to reduced postoperative analgesic consumption in the first postoperative 24 h.

Trial registration

Registered in the Chinese Clinical Trial Registry (ChiCTR2300078171) on 30/11/2023.
The distinct functional brain network and its association with psychotic symptom severity in men with methamphetamine-associated psychosis
Authors: Hwang Zhen-An , Hsu Ai-Ling , Li Chia-Wei , Wu Changwei W. , Chen Chun-Hsin , Chan Wing P. , Huang Ming-Chyi
Published: October 2024

Background

Individuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis.

Methods

We recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity.

Results

The MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN.

Conclusion

MUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group.
Mandibular second molar impaction: introducing a novel and validated 3D classification system
Authors: Barone Selene , Cevidanes Lucia , Bocchino Tecla , Michelotti Ambra , Borelli Massimo , Giudice Amerigo
Published: October 2024

Background

Mandibular second molar (M2M) impaction is a clinically significant manifestation of eruption disturbance in dental development. The primary aim of this study was to investigate the impact of the three-dimensional (3D) characterization on clinical and therapeutic decisions for M2M impaction. The secondary aim was to introduce a validated 3D classification system incorporating both surgical and orthodontic parameters.

Methods

Bidimensional (2D) and 3D radiological records of 15 impacted M2M were collected and deidentified. Ten experienced clinicians (5 oral surgeons;5 orthodontists) categorized each case, first based on 2D records and then with 3D scans. The degree of orthodontic and surgical difficulty in treating impacted M2M was evaluated using a novel classification system based on anatomical and radiological features. The primary outcome variable was the assessment of differences in diagnosis and decision-making protocol using 2D or 3D records, where clinical relevance ranged from 0 to 4. The secondary outcome variable was the validation analysis of the proposed 3D classification system to determine the concordance among the clinicians. Descriptive statistics and multivariable inferential analysis based on Akaike information criterion (AIC) were performed (α = 0.05).

Results

3D examination allowed a better visualization of M2M impaction with higher clinical relevance for diagnosis of M2M root relationship to alveolar nerve and lingual plate, height to alveolar crest, depth, and inclination relative to the first molar and position relative to the third molar (range:2.69–3.43). The proposed 3D classification of M2M impaction changed clinical decisions regarding surgical-orthodontic approach, biomechanics, patient education, and treatment time estimate (range:2.59–3.33). In the validation analysis of the classification, no evidence of inter- or intra-group (surgeon/orthodontist) bias in score attribution occurred: the model with the minimum AIC was the null model (AIC = 718.04).

Conclusion

3D evaluation of impacted M2Ms could enhance diagnostic accuracy, and a classification system was proposed and validated by a group of experienced surgeons and orthodontists with high concordance.
Healthcare professionals’ experiences of providing palliative care for patients with diabetes – a qualitative study
Authors: Seim Signe , Monsen Ragnhild Elisabeth , Kolltveit Beate-Christin Hope , Graue Marit
Published: October 2024

Background

At present, there are no specific guidelines for the treatment of diabetes in palliative care in Norway. The aim of this study was therefore to explore healthcare professionals’ experiences of providing palliative care to individuals with diabetes in specialist as well as primary care settings.

Methods

We interviewed 12 healthcare professionals from two palliative care units in specialist healthcare, one hospice unit in a nursing home, and one dietary care unit providing counselling in the municipality in the eastern part of Norway. Thematic analysis was used to analyze the data.

Results

Our analysis generated three main themes: 1) “Quality of life is the main focus”, which showed that the healthcare professionals’ main focus was on comforting patients through engagement and communication; 2) “An individualized approach”, emphasizing that the treatment was tailored to the unique circumstances of each individual and considered factors such as life expectancy, difficult blood glucose control, and multidisciplinary collaboration, and 3) “Diabetes in the background”, which highlighted that they had a modest focus on diabetes. Diabetes was seen as another aspect of health that they had to be aware of, but their limited knowledge of diabetes guidelines, technical tools, and treatment choices underscored that attentiveness to the diabetes treatment was not prominent.

Conclusion

The findings show that a lack of guidelines allowed for diverse approaches to the treatment of patients with diabetes in palliative care. Attentiveness to diabetes was based on the individual healthcare professionals’ experience and expertise, professional views, and the circumstances of each individual.
Co-designing an interprofessional digital education resource on delirium: a student-led approach
Authors: Wilson Christine Brown , Anderson Tara , Graham Margaret , Murphy Jill , Mitchell Gary , Tuohy Dympna , Barry Heather E. , Boland Pauline , Birch Matt , Tierney Audrey , Stark Patrick , McCurtin Arlene , Creighton Laura , Henderson Elizabeth , Craig Stephanie , McConnell Hannah , Guttridge Heather , Cook Lana , Cunningham Emma , Curran Geoffrey M. , Coffey Alice
Published: October 2024

Background

Interprofessional education is crucial for healthcare students to develop collaborative skills and provide effective patient care. However, opportunities for interprofessional learning are often limited in healthcare curricula. The present study aimed to engage students from different health professions in co-designing an educational resource on delirium recognition and management through an interprofessional lens and explore their experiences of this process.

Methods

Two co-design workshops were conducted with students from medicine, nursing, pharmacy, and occupational therapy programmes at two universities across the island of Ireland. Focus groups were held following these workshops to explore students’ experiences of the co-design process. The workshops involved a range of activities, including theme generation, scenario development, resource creation (podcasts, simulations), and focus group discussions. Data from focus groups were analysed thematically.

Results

A total of 19 students participated across the two workshops. Three themes were identified: (1) Relationship development, where students identified the benefits of co-creating the resource and valued the flexibility, collaboration, and social aspects of the co-design approach; (2) Interprofessional collaboration, which challenged students’ assumptions about other disciplines, fostered teamwork and communication, and highlighted the need for early and continuous interprofessional learning; (3) Professional growth, with students reporting increased confidence in managing delirium, working with other professions, and engaging in novel experiences like podcasting and simulation.

Conclusions

The co-design process facilitated interprofessional collaboration, peer learning, and personal growth among healthcare students. Students appreciated the opportunity to co-create an educational resource while developing interprofessional skills. The study demonstrates the potential of co-design as a methodology for enhancing interprofessional education and promoting effective teamwork in healthcare.
An educational intervention study on mandatory reporting of intimate partner violence: changes in knowledge and attitudes among healthcare providers
Authors: Brevik Thea Beate , Laake Petter , Bjørkly Stål , Leer-Salvesen Kjartan , Vatnar Solveig Karin Bø
Published: October 2024

Background

Intimate partner violence (IPV) is a major public health concern. Healthcare providers can play a crucial role in reporting cases of IPV or suspected IPV injuries to the police or the criminal justice system, commonly referred to as mandatory reporting. However, mandatory reporting of intimate partner violence (MR-IPV) is a debated topic that can pose complex challenges for healthcare providers. This underscores the importance of training programs to ensure that healthcare providers can fulfill their MR-IPV obligations.

Methods

We developed an educational intervention on MR-IPV and assessed its impact on healthcare providers’ knowledge and attitudes. The study used a pre- and post-test design with three measurement points: baseline (T0), immediately after the intervention (T1), and six months later (T2). The intervention was conducted at a university college in Norway, with data collected between October 2022 and May 2023. The intervention was delivered to 37 healthcare providers who were currently part-time students in mental healthcare. Changes in knowledge and attitudes between T0 and T1, and T0 and T2 were analyzed through nonparametric tests on related samples using the Marginal homogeneity (Stuart–Maxwell) test. Risk differences (RD), along with their corresponding 95% confidence intervals (CI), were calculated for selected categories.

Results

The number of participants knowing the MR law increased from 2.9% at baseline to 62.9% at T1 (RD = 0.60, 95% CI: 0.41—0.79) and to 31.4% at T2 (RD = 0.29, 95% CI: 0.11–0.46). The number of participants reporting knowing relevant criteria increased from 0.0% at baseline to 68.6% at T1 (RD = 0.69, 95% CI: 0.50–0.87) and to 34.3% at T2 (RD = 0.34, 95% CI: 0.16—0.53). We observed several persistent changes in healthcare providers' attitudes towards MR, including finding MR to be a useful instrument and generally complying with MR requirements.

Conclusions

The findings suggest that this educational intervention can have a positive impact on healthcare providers' attitudes and compliance with MR-IPV. Before the intervention, few participants reported knowing the MR law and its application criteria, demonstrating the importance of continuous learning and evidence-based training programs.
The juggling act of pharmacists in Sweden: a qualitative study on balancing healthcare professionalism and retail employment
Authors: Hagsten Kenneth , Eriksson Andrea , Svensson Ingrid , Palm Kristina
Published: October 2024

Background

Community pharmacies in Sweden merge a state-funded professional community service with a retail business. While previous research has recognized its challenges, less attention has been paid to the potential conflict of interest it could result in regarding the work of pharmacists. This study aims to increase understanding of how pharmacists in Sweden combine their healthcare ambitions and obligations with those concerning being employees in a retail business.

Methods

Semi-structured interviews were conducted with 28 pharmacists employed by pharmacy chains in Sweden. The data were thematically analysed.

Results

In the analysis, three themes were formulated: Different interests, The conflict between professional work & business work, and Strategies to manage the conflicts. The analysis of the data reveals that pharmacists in Sweden experience a conflict of interest. They grapple with balancing being healthcare professionals with a focus on patient care and being valued retail employees that also focus on financial results. This conflict manifests in various situations, such as time management, communication focus, preferred behaviours, and different tasks. The different strategies applied by individual pharmacists to manage the work are results of job crafting. Pharmacists employ strategies such as compromise, mandate stretching, avoidance, and acceptance to manage the conflict. However, these strategies lead to compromises in their work.

Conclusion

This study aimed to understand how pharmacists combine their healthcare ambitions and obligations with those of being employees in a retail business. The study demonstrated that Swedish community pharmacists need to perform a juggling act to be both professional healthcare workers and viewed as valuable retail employees. In situations when the conflict of interest occurs, the pharmacists use different strategies when determining how to prioritize between the professional work and the business work. The conflict of interest in the pharmacists’ work need to be taken into consideration when discussing pharmacists practices, the profession, or role it’s in the healthcare system.
Translating restrictive law into practice: An ethnographic exploration of the systemic processing of legally restricted health care access for asylum seekers in Germany
Authors: Ziegler Sandra , Bozorgmehr Kayvan
Published: October 2024

Background

Access to health services for asylum seekers is legally restricted in Germany. The law is subject to interpretation, therefore the chance of receiving care is not equally distributed among asylum seekers. What services are provided to whom is ultimately decided by health professionals and government employees. The respective prioritization processes and criteria are not transparent. We sought to understand how legal restrictions are translated into daily practices and how this affects the health system. We aimed to outline the complex process of cost coverage for health services for asylum seekers and provide insights into common decision-making criteria.

Methods

We conducted an ethnographic exploration of routines in two outpatient clinics in two federal states over the course of three months, doing participant and non-participant observation. Additionally, we interviewed 21 professionals of health care and government organizations, and documented 110 applications for cost coverage of medical services and their outcome. In addition to qualitative data analysis and documentation, we apply a system-theoretical perspective to our findings.

Results

To perform legal restrictions a cross-sectoral prioritization process of medical services has been implemented, involving health care and government institutions. This changes professional practices, responsibilities and (power) relations. Involved actors find themselves at the intersection of several, oftentimes conflicting priorities, since “doing it right” might be seen differently from a legal, medical, economic, or political perspective. The system-theoretical analysis reveals that while actors have to bring different rationales into workable arrangements this part of the medical system transforms, giving rise to a sub-system that incorporates migration political rationales.

Conclusions

Health care restrictions for asylum seekers are implemented through an organizational linking of care provision and government administration, resulting in a bureaucratization of practice. Power structures at this intersection of health and migration policy, that are uncommon in other parts of the health system are thereby normalized. Outpatient clinics provide low-threshold access to health services, but paradoxically they may unintentionally stabilize health inequities, if prioritization criteria and power dynamics are not made transparent. Health professionals should openly reflect on conflicting rationales. Training, research and professional associations need to empower them to stay true to professional ethical principles and international conventions.
Patients with low prognosis in ART: a Delphi consensus to identify potential clinical implications and measure the impact of POSEIDON criteria
Authors: Alviggi Carlo , Humaidan Peter , Fischer Robert , Conforti Alessandro , Dahan Michael H. , Marca Antonio La , Orvieto Raoul , Polyzos Nikolaos P. , Roque Matheus , Sunkara Sesh K. , Ubaldi Filippo Maria , Vuong Lan , Yarali Hakan , D’Hooghe Thomas , Longobardi Salvatore , Esteves Sandro C.
Published: October 2024

Background

Currently, there is no consensus on the optimal management of women with low prognosis in ART. In this Delphi consensus, a panel of international experts provided real-world clinical perspectives on a series of literature-supported consensus statements regarding the overall relevance of the POSEIDON criteria for women with low prognosis in ART.

Methods

Using a Delphi-consensus framework, twelve experts plus two Scientific Coordinators discussed and amended statements and supporting references proposed by the Scientific Coordinators (Round 1). Statements were distributed via an online survey to an extended panel of 53 experts, of whom 36 who voted anonymously on their level of agreement or disagreement with each statement using a six-point Likert-type scale (1 = Absolutely agree; 2 = More than agree; 3 = Agree; 4 = Disagree; 5 = More than disagree; 6 = Absolutely disagree) (Round 2). Consensus was reached if > 66% of participants agreed or disagreed.

Results

The extended panel voted on seventeen statements and subcategorized them according to relevance. All but one statement reached consensus during the first round; the remaining statement reached consensus after rewording. Statements were categorized according to impact, low-prognosis validation, outcomes and patient management. The POSEIDON criteria are timely and clinically sound. The preferred success measure is cumulative live birth and key management strategies include the use of recombinant FSH preparations, supplementation with r-hLH, dose increases and oocyte/embryo accumulation through vitrification. Tools such as the ART Calculator and Follicle-to-Oocyte Index may be considered. Validation data from large, prospective studies in each POSEIDON group are now needed to corroborate existing retrospective data.

Conclusions

This Delphi consensus provides an overview of expert opinion on the clinical implications of the POSEIDON criteria for women with low prognosis to ovarian stimulation.
Acute postnatal inflammation alters adult microglial responses to LPS that are sex-, region- and timing of postnatal inflammation-dependent
Authors: Nikodemova Maria , Oberto Jose R. , Kaye Ethan L. , Berschel Mackenzie R. , Michaelson Alysha L. , Watters Jyoti J. , Mitchell Gordon S.
Published: October 2024

Background

Adverse events in early life can have impact lasting into adulthood. We investigated the long-term effects of systemic inflammation during postnatal development on adult microglial responses to lipopolysaccharide (LPS) in two CNS regions (cortex, cervical spinal cord) in male and female rats.

Methods

Inflammation was induced in Sprague-Dawley rats by LPS (1 mg/kg) administered intraperitoneally during postnatal development at P7, P12 or P18. As adults (12 weeks of age), the rats received a second LPS dose (1 mg/kg). Control rats received saline. Microglia were isolated 3 h post-LPS followed by gene expression analysis via qRT-PCR for pro-inflammatory (IL-6, iNOS, Ptgs2, C/EBPb, CD14, CXCL10), anti-inflammatory (CD68, Arg-1), and homeostatic genes (P2Y12, Tmemm119). CSF-1 and CX3CL1 mRNAs were analyzed in microglia-free homogenates.

Results

Basal gene expression in adult microglia was largely unaffected by postnatal inflammation. Adult cortical microglial pro-inflammatory gene responses to LPS were either unchanged or attenuated in rats exposed to LPS during postnatal development. Ptgs2, C/EBPb, CXCL10 and Arg-1 were the most affected genes, with expression significantly downregulated vs. rats without postnatal LPS. Spinal microglia were affected most by LPS at P18, with mixed and sometimes opposing effects on proinflammatory genes in males vs. females. Overall, male cortical vs. spinal microglia were more affected by postnatal LPS. Females were affected in both cortex and spinal cord, but the effect was dependent on timing of postnatal LPS. Overall, inflammatory challenge at P18 had greater effect on adult microglia vs. challenge at P12 or P7.

Conclusions

Long-lasting effects of postnatal inflammation on adult microglia depend on postnatal timing, CNS region and sex.
Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury
Authors: Wang Sudena , Weyer Marc-Philipp , Hummel Regina , Wilken-Schmitz Annett , Tegeder Irmgard , Schäfer Michael K. E.
Published: October 2024

Progranulin (PGRN), which is produced in neurons and microglia, is a neurotrophic and anti-inflammatory glycoprotein. Human loss-of-function mutations cause frontotemporal dementia, and PGRN knockout (KO) mice are a model for dementia. In addition, PGRN KO mice exhibit severe phenotypes in models of traumatic or ischemic central nervous system (CNS) disorders, including traumatic brain injury (TBI). It is unknown whether restoration of progranulin expression in neurons (and not in microglia) might be sufficient to prevent excessive TBI-evoked brain damage. To address this question, we generated mice with Nestin-Cre-driven murine PGRN expression in a PGRN KO line (PGRN-KONestinGrn) to rescue PGRN in neurons. PGRN expression analysis in primary CNS cell cultures from naïve mice and in (non-) injured brain tissue from PGRN-KONestinGrn revealed expression of PGRN in neurons but not in microglia. After experimental TBI, examination of the structural brain damage at 5 days post-injury (dpi) showed that the TBI-induced loss of brain tissue and hippocampal neurons was exacerbated in PGRN-KOGrnflfl mice (PGRN knockout with the mGrn fl-STOP-fl allele, Cre-negative), as expected, whereas the tissue damage in PGRN-KONestinGrn mice was similar to that in PGRN-WT mice. Analysis of CD68+ immunofluorescent microglia and Cd68 mRNA expression showed that excessive microglial activation was rescued in PGRN-KONestinGrn mice, and the correlation of brain injury with Cd68 expression suggested that Cd68 was a surrogate marker for excessive brain injury caused by PGRN deficiency. The results show that restoring neuronal PGRN expression was sufficient to rescue the exacerbated neuropathology of TBI caused by PGRN deficiency, even in the absence of microglial PGRN. Hence, endogenous microglial PGRN expression was not essential for the neuroprotective or anti-inflammatory effects of PGRN after TBI in this study.

Graphical Abstract
What validated instruments, that measure implementation outcomes, are suitable for use in the Paediatric Intensive Care Unit (PICU) setting? A systematic review of systematic reviews
Authors: Dodds Elizabeth , Redsell Sarah , Timmons Stephen , Manning Joseph C.
Published: October 2024

Background/aims

The measurement of implementation outcomes can establish the success of implementing evidence into practice. However, implementation outcomes are seldom measured in acute healthcare settings, such as Paediatric Intensive Care Units (PICU), and if they are used, are likely to be non-validated, site or intervention-specific measures. To address this literature gap, this systematic review of systematic reviews aims to identify validated instruments to measure implementation outcomes of new EBP interventions in a PICU setting.

Methods

A systematic review of systematic reviews was conducted in two phases. Phase One: Five electronic databases were searched between 06/10/22 and 14/10/22. Systematic reviews were selected using pre-determined eligibility criteria. Methodological quality was assessed using the Critical Appraisal Skills Programme tool and a data extraction table was used to allow further synthesis. Phase Two: Secondary eligibility criteria were used to extract and review instruments from the systematic reviews selected in Phase One. Instruments were analysed and mapped to the Consolidated Framework of Implementation Research (CFIR).

Results

Phase One: Searches resulted in 3195 unique papers. Five systematic reviews were eligible for inclusion. All examined the psychometric properties of each instrument, utilising different methods to do so; three considered their pragmatic or usability properties; and one identified instruments that were transferrable to different settings. Each systematic review identified that most included instruments had limited evidence of their validity or reliability and had poor psychometric properties. Phase two: 93 instruments were screened, and nine were eligible for analysis. After analysis and CFIR mapping, two instruments were identified as potentially adaptable to the PICU setting.

Conclusions

The methodological quality of implementation outcome measurement instruments is inadequate, warranting further validation research. Two instruments were identified that cover multiple CFIR domains and have scope to be adapted for use when implementing evidence-based practice into the PICU. Further work is needed to adapt and further validate an instrument for use in practice.

Trial registration

For transparency of procedures and methods, the protocol for this systematic review was registered with PROSPERO (registration number CRD42022361638L).
Improved detection of methylation in ancient DNA
Authors: Sawyer Susanna , Gelabert Pere , Yakir Benjamin , Llanos-Lizcano Alejandro , Sperduti Alessandra , Bondioli Luca , Cheronet Olivia , Neugebauer-Maresch Christine , Teschler-Nicola Maria , Novak Mario , Pap Ildikó , Szikossy Ildikó , Hajdu Tamás , Moiseyev Vyacheslav , Gromov Andrey , Zariņa Gunita , Meshorer Eran , Carmel Liran , Pinhasi Ron
Published: October 2024

Reconstructing premortem DNA methylation levels in ancient DNA has led to breakthrough studies such as the prediction of anatomical features of the Denisovan. These studies rely on computationally inferring methylation levels from damage signals in naturally deaminated cytosines, which requires expensive high-coverage genomes. Here, we test two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. Bisulfite treatment shows the least reduction in DNA yields as well as the least biases during methylation conversion, demonstrating that this method can be successfully applied to ancient DNA.
Graphasing: phasing diploid genome assembly graphs with single-cell strand sequencing
Authors: Henglin Mir , Ghareghani Maryam , Harvey William T. , Porubsky David , Koren Sergey , Eichler Evan E. , Ebert Peter , Marschall Tobias
Published: October 2024

Haplotype information is crucial for biomedical and population genetics research. However, current strategies to produce de novo haplotype-resolved assemblies often require either difficult-to-acquire parental data or an intermediate haplotype-collapsed assembly. Here, we present Graphasing, a workflow which synthesizes the global phase signal of Strand-seq with assembly graph topology to produce chromosome-scale de novo haplotypes for diploid genomes. Graphasing readily integrates with any assembly workflow that both outputs an assembly graph and has a haplotype assembly mode. Graphasing performs comparably to trio phasing in contiguity, phasing accuracy, and assembly quality, outperforms Hi-C in phasing accuracy, and generates human assemblies with over 18 chromosome-spanning haplotypes.
Classifying physical activity levels using Mean Amplitude Deviation in adults using a chest worn accelerometer: validation of the Vivalink ECG Patch
Authors: Luckhurst Jim , Hughes Cara , Shelley Benjamin
Published: October 2024

Background

The development of readily available wearable accelerometers has enabled clinicians to objectively monitor physical activity (PA) remotely in the community, a superior alternative to patient self-reporting measures. Critical to the value of these monitors is the ability to reliably detect when patients are undergoing ambulatory activity. Previous studies have highlighted the strength of using mean amplitude deviation (MAD) as a universal measure for analysing raw accelerometery data and defining cut-points between sedentary and ambulatory activities. Currently however there is little evidence surrounding the use of chest-worn accelerometers which can provide simultaneous monitoring of other physiological parameters such as heart rate (HR), RR intervals, and Respiratory Rate alongside accelerometery data. We aimed to calibrate the accelerometery function within the VivaLink ECG patch to determine the cut-point MAD value for differentiating sedentary and ambulatory activities.

Methods

We recruited healthy volunteers to undergo a randomised series of 9 activities that simulate typical free-living behaviours, while wearing a VivaLink ECG Patch (Campbell, California). MAD values were applied to a Generalised Linear Mixed Model to determine cut-points between sedentary and ambulatory activities. We constructed a Receiver Operating Characteristic (ROC) curve to analyse the sensitivity and specificity of the cut-off MAD value.

Results

Eighteen healthy adults volunteered to the study and mean MAD values were collected for each activity. The optimal MAD cut-point between sedentary and ambulatory activities was 47.73mG. ROC curve analysis revealed an area under the curve of 0.99 (p < 0.001) for this value with a sensitivity and specificity of 98% and 100% respectively.

Conclusion

In conclusion, the MAD cut-point determined in our study is very effective at categorising sedentary and ambulatory activities among healthy adults and may be of use in monitoring PA in the community with minimal burden. It will also be useful for future studies aiming to simultaneously monitor PA with other physiological parameters via chest worn accelerometers.
LysoPE mediated by respiratory microorganism Aeromicrobium camelliae alleviates H9N2 challenge in mice
Authors: Yan Qingsong , Xing Junhong , Zou Ruonan , Sun Mingjie , Zou Boshi , Wang Yingjie , Niu Tianming , Yu Tong , Huang Haibin , Yang Wentao , Shi Chunwei , Yang Guilian , Wang Chunfeng
Published: October 2024

Influenza remains a severe respiratory illness that poses significant global health threats. Recent studies have identified distinct microbial communities within the respiratory tract, from nostrils to alveoli. This research explores specific anti-influenza respiratory microbes using a mouse model supported by 16S rDNA sequencing and untargeted metabolomics. The study found that transferring respiratory microbes from mice that survived H9N2 influenza to antibiotic-treated mice enhanced infection resistance. Notably, the levels of Aeromicrobium were significantly higher in the surviving mice. Mice pre-treated with antibiotics and then inoculated with Aeromicrobium camelliae showed reduced infection severity, as evidenced by decreased weight loss, higher survival rates, and lower lung viral titres. Metabolomic analysis revealed elevated LysoPE (16:0) levels in mildly infected mice. In vivo and in vitro experiments indicated that LysoPE (16:0) suppresses inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX2) expression, enhancing anti-influenza defences. Our findings suggest that Aeromicrobium camelliae could serve as a potential agent for influenza prevention and a prognostic marker for influenza outcomes.