bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke knowledge in Malta: A mixed methods study
Authors: Grech Reuben , Grech Paulann
Published: November 2024

Background

Stroke is a major cause of morbidity and mortality worldwide. Despite advances in acute treatments, timely intervention remains crucial. This study assessed stroke knowledge in Malta to identify gaps that could contribute to treatment delays.

Methods

A mixed methods approach was used, starting with qualitative interviews of stroke patients, relatives, and bystanders, followed by a quantitative survey among the general Maltese population and healthcare workers. The online survey included demographics, stroke knowledge, and stroke response questions. Data were analysed using descriptive and inferential statistics to identify knowledge gaps and influencing factors.

Results

The study surveyed 1872 participants, representing the Maltese population. Significant knowledge gaps were found in stroke symptoms, risk factors, and appropriate responses. Younger participants, males, non-Maltese, urban residents, those with higher education, and higher-income individuals showed better stroke knowledge and response. Healthcare workers scored higher than the general public. A strong positive correlation was found between stroke knowledge and appropriate response actions.

Conclusions

The study highlights the need for targeted educational interventions to improve stroke awareness and response, especially among older adults, women, rural residents, and lower-income groups. Recommendations include comprehensive public education campaigns, culturally tailored materials, and ongoing professional development for healthcare workers. Addressing these gaps could enhance stroke prevention and management, reducing stroke-related morbidity and mortality.
Epistemic Marginalization and Methodology 50 Years after The Death of White Sociology
Authors: Johnson Odis
Published: November 2024

In its original form, the following essay was the closing keynote address of the annual meeting of the Sociology of Education Association (SEA), held in Monterey, California on February 20, 2023. That year was the 50th anniversary of both the founding of SEA and the publication of the landmark volume, The Death of White Sociology. In commemorating these events and assessing how the field of sociology has changed 50 years later, this essay juxtaposes the promise of critical quantitative and computational methods (CritQCM) with the problems of epistemic marginalization highlighted in the volume. After describing the rich theoretical diversity foregrounding the critical quantitative and computational movement, the discussion elaborates on three epistemic threats to the aim of the movement to develop and practice counter-hegemonic methodologies. These threats include (1) the qualitative-quantitative divide, (2) White norms and Black epistemic rigor, and (3) normative theory privileging. The essay concludes by contextualizing these epistemic threats with the nation’s current challenge of anomie, which has destabilized normative processes of knowledge recognition, and considers ways CritQCM might respond.
Communication and coordination in the 2023 Kahramanmaras earthquakes
Authors: Comfort Louise K , Celik Suleyman , Basbug Erkan Burcak , Lee Seunghyun
Published: November 2024

The interaction between communication and coordination is central to mobilizing response operations, but the processes vary under critical time constraints, creating disparities in complex operations in practice. To explore conditions that facilitate or hinder the interaction between these processes, we identify networks of organizations engaged in communication and coordination that functioned in response to the 6 February 2023, Kahramanmaras earthquakes in Turkey. Framed in the theory of complex adaptive systems, this study focuses on decision-making among organizations that operated during this event and the flow of information within and among organizations that guided collective action. Using exploratory case-study methods, we undertook four tasks to: (1) characterize the context in which the earthquakes occurred—public awareness, policies, and practice to reduce seismic risk; (2) identify technical communication networks that functioned during the first 3 weeks of response operations; (3) identify organizational coordination networks and flow of information that guided technical networks, including principal nodes of connection and missing links in the process; and (4) identify gaps between knowledge and action as organizations struggled to operate in a disaster-degraded context. Study findings revealed limits in both technical and organizational networks and offer insights into how these sociotechnical networks could be scaled and strengthened to function more effectively in large-scale, extreme events.
DsbA-L activates TGF-β1/SMAD3 signaling and M2 macrophage polarization by stimulating AKT1 and NLRP3 to promote pulmonary fibrosis
Authors: Wang Juan , Xia Zhenkun , Qing Bei , Chen Ying , Gu Linguo , Chen Hongzuo , Ge Zhenglian , Yuan Yunchang
Published: November 2024

Background

Pulmonary fibrosis (PF) is a progressive and difficult-to-heal lung disease that poses a significant threat to human life and health. This study aimed to investigate the potential pathological mechanisms of PF and to identify new avenues for the treatment of PF.

Methods

Clinical samples were collected to assess the effect of disulfide-bond A oxidoreductase-like protein (DsbA-L) on PF. TGF-β1-induced MLE-12 cell model and bleomycin (BLM)-induced mice model were established. Changes in physiological morphology and fibrosis were observed in the lung tissues. The degree of apoptosis and the mitochondrial function was analyzed. The expression of relative cytokines was examined. The CD68+/CD206+ ratio was determined to indicate M2 macrophage polarization.

Results

The expression of DsbA-L was upregulated in patients with PF and PF-like models. In vitro, DsbA-L overexpression exacerbated TGF-β1-induced the deposition of extracellular matrix (ECM), apoptosis, inflammation, and mitochondrial damage, whereas DsbA-L silencing exerted the opposite effects. DsbA-L silencing inhibited the activation of AKT1, NLRP3, and SMAD3 by TGF-β1. MLE-12 cells silencing DsbA-L limited the polarization of RAW264.7 cells towards the M2 phenotype. AKT1 agonist or NLRP3 agonist reversed the role of DsbA-L silencing in inhibiting the TGF-β1/SMAD3 pathway and M2 macrophage polarization. In vivo, DsbA-L knockout protected mice from PF-like pathological damage caused by BLM.

Conclusion

DsbA-L exhibited a significant profibrotic effect in lung epithelial cells and mice, which increased the levels of AKT1 and NLRP3 to activate the TGF-β1/SMAD3 pathway and M2 macrophage polarization. These findings could shed light on new clues for comprehension and treatment of PF.
The most effective combination of pharmacological therapy for heart failure with reduced ejection fraction: a network meta-analysis of randomized controlled trials
Authors: Tang Huilin , Germinal Kimberly , Milfort Alexandra , Chen Wei-Han , Chang Shao-Hsuan , Huang Wenxi , Li Yujia , Lu Ying , Ahmed Mustafa M. , Kimmel Stephen E. , Bian Jiang , Guo Jingchuan
Published: November 2024

Background

Evidence for the efficacy of pharmacological therapies for heart failure with reduced ejection fraction (HFrEF) is growing. However, there is no consensus on the most effective treatment for HFrEF. This study aimed to evaluate the most effective combination of pharmacological therapy in patients with HFrEF.

Methods

We systematically searched Medline, Embase, and CENTRAL up to Feb 2022, to include randomized controlled trials (RCTs) that evaluated the efficacy of pharmacological treatment among adults (≥ 18 years) with a diagnosis of HFrEF (defined by a left ventricular ejection fraction ≤ 45%). The outcomes of interest included all-cause death, cardiovascular (CV) death, and hospitalization for heart failure (HHF). A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) and rank the treatments.

Results

We included 49 RCTs involving 90,529 participants with HFrEF. For reducing all-cause mortality, the combination of angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) was most effective (RR, 0.46; 95% CI, 0.32–0.66). For CV death, the combination of ACEI, BB, MRA, and Vericiguat showed the highest efficacy (RR, 0.34; 95% CI, 0.12–0.90). Regarding reducing HHF, the combination of ACEI, BB, MRA, and SGLT2i as well as the combination of ACEI, BB, MRA, and Ivabradine were equally the most effective (both RR, 0.27; 95% CI, 0.18–0.39).

Conclusion

This study provides robust evidence supporting the use of combination therapies in HFrEF management, with newer agents offering incremental benefits when added to established guideline-directed medical therapy.
The role of the estimand framework in the analysis of patient-reported outcomes in single-arm trials: a case study in oncology
Authors: Thomassen Doranne , Roychoudhury Satrajit , Amdal Cecilie Delphin , Reynders Dries , Musoro Jammbe Z. , Sauerbrei Willi , Goetghebeur Els , le Cessie Saskia ,   SISAQOL-IMI Work Package 3, Kamalakar Rajesh , Sail Kavita , Basch Ethan , Reijneveld Jaap , Keating Karen , Su Yun , Alanya Ahu , Rumpold Gerhard , Sasseville Maxime , Black Jennifer , Molenberghs Geert , Rantell Khadija , Schlichting Michael , Regnault Antoine , Ness David , ten Seldam Silene , Reksten Tove Ragna , Schiel Anja , Falk Ragnhild Sorum , Campbell Alicyn , Cappelleri Joseph C. , Russell-Smith Alexander , Calvert Melanie , Cruz Rivera Samantha , Aiyegbusi Olalekan Lee , Liu Limin , Van Lancker Kelly , Rutherford Claudia , Bhatnagar Vishal , Chen Ting-Yu , Fiero Mallorie , Kluetz Paul
Published: November 2024

Background

Patient-reported outcomes (PROs) play an increasing role in the evaluation of oncology treatments. At the same time, single-arm trials are commonly included in regulatory approval submissions. Because of the high risk of biases, results from single-arm trials require careful interpretation. This benefits from a clearly defined estimand, or target of estimation. In this case study, we demonstrated how the ICH E9 (R1) estimand framework can be implemented in SATs with PRO endpoints.

Methods

For the global quality of life outcome in a real single-arm lung cancer trial, a range of possible estimands was defined. We focused on the choice of the variable of interest and strategies to deal with intercurrent events (death, treatment discontinuation and disease progression). Statistical methods were described for each estimand and the corresponding results on the trial data were shown.

Results

Each intercurrent event handling strategy resulted in its own estimated mean global quality of life over time, with a specific interpretation, suitable for a corresponding clinical research aim. In the setting of this case study, a ‘while alive’ strategy for death and a ‘treatment policy’ strategy for non-terminal intercurrent events were deemed aligned with a descriptive research aim to inform clinicians and patients about expected quality of life after the start of treatment.

Conclusions

The results show that decisions made in the estimand framework are not trivial. Trial results and their interpretation strongly depend on the chosen estimand. The estimand framework provides a structure to match a research question with a clear target of estimation, supporting specific clinical decisions. Adherence to this framework can help improve the quality of data collection, analysis and reporting of PROs in SATs, impacting decision making in clinical practice.
Exercise-based telerehabilitation in chronic low back pain – a scoping review
Authors: Sivertsson Jenny , Sernert Ninni , Åhlund Kristina
Published: November 2024

Background

Low back pain is a major global health problem. Physiotherapy involving exercises is considered first-line treatment. In recent years digital tools including telerehabilitation have increased, but the interventions are diverse. The aim of this study was to map how telerehabilitation approaches are used in studies evaluating exercise-based rehabilitation in patients with chronic low back pain.

Methods

A systematic literature search was conducted in PubMed, Cinahl and Cochrane Central between January 2017 and January 2024 for original studies on adults, 18 years or older, with chronic low back pain who received exercise-based telerehabilitation.

Results

The database search resulted in 1019 articles. Out of 37 full texts that were screened 28 articles were included in the analysis. The included studies showed a wide variation regarding technological solutions, interventions and outcome measures. The exercise-based telerehabilitation was usually delivered asynchronously via a smartphone application. The most common clinical outcome measure was pain and disability/physical function. Telerehabilitation compared to conventional exercise therapy showed similar clinical improvements.

Conclusions

This scoping review confirms the heterogeneity within this research area but also contributes by mapping and demonstrating some knowledge gaps in the literature. Further research focusing on synchronous and group interventions are needed. The new technologies described in the included studies provide added value through functional improvements and task redesign.

Trial registration

OSF https//doi.org/10.17605/OSF.IO/EMKCG.
Regenerative endodontic therapy in immature teeth using photobiomodulation and photodynamic therapy; a histomorphological study in canine model
Authors: Fouad Eman M. , Fawzy Mervat I. , Saafan Ali M. , Elhousiny Maha A.
Published: November 2024

Background

Regenerative endodontic therapy (RET) is still coming up short to demonstrate histological evidence for true regeneration with clinically feasible protocol of cell homing in single visit approach.

Aim

The aim of the present study is to evaluate the regenerative potential of photobiomodulation (PBM) on RET in immature roots when photodynamic therapy (PDT) protocol is implemented for root canal disinfection in canine model.

Materials and methods

Seventy-two root canals were recruited, with sixty assigned to experimental groups and twelve to positive and negative controls. Following the induction of pulp necrosis and apical periodontitis, the roots were divided into two experimental groups: Group I received RET followed by PBM (seven sessions with an 808 nm diode laser at 300 mW for 90 s), and Group II received RET without PBM. Follow-ups were conducted at 1, 2, and 3 months (subgroups A, B, and C respectively). Qualitative and quantitative assessment was carried out histologically. All data were statistically analyzed with the Mann-Whitney U test and Bonferroni’s adjustment, as well as Chi square test.

Results

The newly formed hard tissue highly resembled true dentine where the dentinal tubules looked well organized lined by poly layers palisading pattern of rounded odontoblast-like cells with cytoplasmic processes extending through the predentine layer. GI exhibited statistically significantly higher scores of vital tissue infiltration and hard tissue deposition in subgroups A and B (P ≤ 0.05). The inflammatory cells scores were significantly lower in GI than in GII at all time intervals. However, no significance could be detected regarding apical closure.

Conclusion

The disinfection protocol of PDT and subsequent irradiation with low power laser in PBM protocol pose a promising potential for regenerative endodontics in immature teeth.
Effect of saliva on accuracy of digital dental implant transfer using two different materials of intraoral scan bodies with different exposed lengths
Authors: Tawfik Mohamed Hesham Ahmed , EL Torky Ibrahim Ramadan , El Sheikh Mohamed Maamoun
Published: November 2024

Background

The accuracy of digital implant transfer is currently under investigation in relation to the effect of saliva, scan body material, and exposed length.

Methods

Six completely edentulous casts with four implant fixtures were fabricated. The four implant fixtures in each cast were placed below the crest of the ridge of the casts by 1.5 mm. The four implant fixtures were alternately attached to four implant scan bodies (PEEK) Group (I) and (TITANIUM) Group (II). For each cast, two flexible polyurethane layers with varying thicknesses were fabricated and molded on the six 3D printed identical casts after the placement of the implant fixtures in each cast for the soft tissue moulage in the cast. The six casts were alternately covered with a 2 mm and 4 mm thick layer. The six reference casts were recorded using a coordinate measurement machine (CMM) and subsequently scanned with an Intraoral scanner (MEDIT I 700). The scanning was conducted under both dry and wet conditions, with artificial saliva applied. The scanning platform consisted of two transparent acrylic boxes, and the process followed standardized scanning conditions using a digital lux meter (n = 48). The mean difference and standard deviation values (± SD) between the implant scan bodies measured on the reference and experimental scans were calculated using the inspection software program (Medit design). Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). The Kolmogorov-Smirnov test and Shapiro-Wilk test were used to verify the normality of distribution. Quantitative data mean and standard deviation. The significance of the obtained results was determined at the 5% level. The student t-test for normally distributed quantitative variables was used to compare the two groups studied.

Results

Statistically significant differences in wettability condition discrepancies were found between groups (I) and (II) (p < 0.05). In addition, there were statistically significant differences in intraoral scan body (ISB) length between the two groups (p < 0.05). Regarding the intraoral scan body material, statistically significant differences were found between the two groups (p < 0.05).

Conclusions

The presence of saliva significantly affects the accuracy of the digital implant transfer. Additionally, using a longer intraoral scan body improves the accuracy of digital implant impressions. The titanium scan body had a greater level of precision on the implant impression scan.
The potential for attractive toxic sugar baits to complement core malaria interventions strategies: the need for more evidence
Authors: Zembere Kennedy
Published: November 2024

Despite its success, the increased use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has contributed to the development of insecticide resistance in malaria vectors and shifts in biting patterns of the primary malaria vectors. The limitations portrayed by ITNs and IRS suggest that their use alone will not reduce malaria to elimination levels as the remaining untargeted vectors continue to sustain residual malaria transmission (RMT). RMT is a big challenge to malaria elimination because even at 100% ITN and IRS coverage, malaria transmission persists as outdoor vectors avoid or reduce contact with such interventions. With the recent increase in the outdoor biting Anopheles arabiensis (hard to control using routine tools), in most African countries, including Malawi, novel tools such as the attractive toxic sugar baits (ATSBs), targeting outdoor biting vectors in addition to controlling indoor vectors are greatly needed to complement current tools, and could facilitate sustainable malaria control. The ATSB is one potential tool that has been tested in different settings with promising results, and more trials are ongoing in other African countries. ATSBs have been attributed to reductions of mosquito densities and malaria incidence with over 80% and 50%, respectively, and there is hope that by 2025, ATSBs would be considered for the World Health Organization prequalification listing as a complementary tool for mosquito control. This article highlights evidence that ATSBs can advance malaria elimination by complementing indoor-based tools. However, for effective control programmes and elimination campaigns, the use of ATSBs alone might not be adequate, and this article recommends the combined use of ATSBs with either IRS or ITNs.
Dendritic cells under the control of the preimplantation embryo secretome: an in vitro study
Authors: Kyvelidou Christiana , Haselrieder Sofia , von Gierke Maria , Gostner Johanna M. , Biasio Wolfgang , Wirleitner Barbara , Heufler Christine , Toth Bettina , Hofer-Tollinger Susanne
Published: November 2024

Objective

To study the crosstalk between maternal immune cells and the developing embryo by investigating the immunogenic properties of human blastocyst spent media (SM) on dendritic cells.

Methods

In this prospective multicenter experimental study, human preimplantation embryo spent media were collected after blastocyst formation, grouped based on successful or unsuccessful implantation, and analyzed by protein array or used to stimulate monocyte derived dendritic cells (moDC). The immunomodulatory properties of SM on moDC were investigated by analyzing changes in phenotype, cytokine secretion, indoleamine 2,3-dioxygenase (IDO) activity, and ability to activate T cells.

Results

A plethora of cytokines and growth factors secreted from preimplantation embryos was detected. Exposure to embryo SM altered the phenotype of moDC in a manner dependent on the implantation outcome. Specifically, SM from non-implanted embryos increased the expression of co-stimulatory molecules and activation markers on moDC. Furthermore, SM treated dendritic cells secreted low levels of cytokines and growth factors and were able to stimulate naïve T cells. Activation of IDO was decreased in moDC after stimulation with SM.

Conclusions

Our findings show that human preimplantation embryos secrete an abundance of molecules with the ability to significantly affect and even regulate immune cells in their environment.
Effects of sodium-glucose cotransporter-2 inhibitors on chronic kidney disease progression: a multi-state survival model
Authors: Tansawet Amarit , Looareesuwan Panu , Teza Htun , Boongird Sarinya , McKay Gareth J. , Attia John , Pattanaprateep Oraluck , Thakkinstian Ammarin
Published: November 2024

Background

Current guidelines recommend good glycemic control in patients with type 2 diabetes (T2D) to limit the progression of associated complications with combination therapies. This study aimed to compare the rate of chronic kidney disease (CKD) progression between patients who did or did not receive sodium-glucose cotransporter-2 inhibitors (SGLT2i) using a multistate model with two intermediate states (i.e., CKD stage 4 (CKD4) and 5 (CKD5)) and one absorbing state (i.e., death).

Methods

Data from patients with T2D and CKD stage 3 (CKD3) were retrieved for analysis. Patients treated with SGLT2i were matched 1:2 by prescription date with non-SGLT2i patients. The multistate model was constructed from Cox survival regression models specific to each transition stage. Cumulative failure and transition probabilities were estimated from bootstrapping.

Results

Data from 6582 patients (2194 and 4388 patients in the SGLT2i and non-SGLT2i groups, respectively) were analyzed. At 10-year follow-up, patients in the SGLT2i group were more likely to remain at CKD3 compared to the non-SGLT2i group: 82.3% (95% CI 79.9%, 84.6%) vs 60.4% (57.6%, 63.4%). Transition probabilities to CKD4, CKD5, and death were lower in the SGLT2i group than non-SGLT2i group: 11.3% (9.5%, 13.3%) vs 19.8% (17.4%, 22.2%), 2.4% (1.5%, 3.4%) vs 7.4% (5.8%, 9.0%), and 4.1% (2.9%, 5.3%) vs 12.4% (10.3%, 14.6%), respectively.

Conclusion

SGLT2i may delay the decline in renal function and slow CKD progression compared to standard care without SGLT2i.
Bromodomain proteins as potential therapeutic targets for B-cell non-Hodgkin lymphoma
Authors: Zou Dan , Feng Sitong , Hu Bowen , Guo Mengya , Lv Yan , Ma Rong , Du Yuxin , Feng Jifeng
Published: November 2024

Background

B-cell non-Hodgkin lymphoma (B-NHL) is the most common type of lymphoma and is significantly heterogeneous among various subtypes. Despite of considerable advancements in treatment strategies for B-NHL, the prognosis of relapsed/refractory patients remains poor.

Main text

It has been indicated that epigenetic dysregulation is critically associated with the pathogenesis of most hematological malignancies, resulting in the clinical targeting of epigenetic modifications. Bromodomain (BRD) proteins are essential epigenetic regulators which contain eight subfamilies, including BRD and extra-terminal domain (BET) family, histone acetyltransferases (HATs) and HAT-related proteins, transcriptional coactivators, transcriptional mediators, methyltransferases, helicases, ATP-dependent chromatin-remodeling complexes, and nuclear-scaffolding proteins. Most pre-clinical and clinical studies on B-NHL have focused predominantly on the BET family and the use of BET inhibitors as mono-treatment or co-treatment with other anti-tumor drugs. Furthermore, preclinical models of B-NHL have revealed that BET degraders are more active than BET inhibitors. Moreover, with the development of BET inhibitors and degraders, non-BET BRD protein inhibitors have also been designed and have shown antitumor activities in B-NHL preclinical models. This review summarized the mechanism of BRD proteins and the recent progress of BRD protein-related drugs in B-NHL. This study aimed to collect the most recent evidences and summarize possibility on whether BRD proteins can serve as therapeutic targets for B-NHL.

Conclusion

In summary, BRD proteins are critical epigenetic regulatory factors and may be potential therapeutic targets for B-NHL.
High flow nasal cannula and low level continuous positive airway pressure have different physiological effects during de novo acute hypoxemic respiratory failure
Authors: Tuffet Samuel , Boujelben Mohamed Ahmed , Haudebourg Anne-Fleur , Maraffi Tommaso , Perier François , Labedade Pascale , Moncomble Elsa , Gendreau Ségolène , Lacheny Matthieu , Vivier Emmanuel , Mekontso-Dessap Armand , Carteaux Guillaume
Published: November 2024

Background

Large tidal volumes during de novo acute hypoxemic respiratory failure (AHRF) may promote patient self-inflicted lung injury. Tidal volume assessment under high flow nasal cannula (HFNC) is not routinely feasible at the bedside. Our objective was to determine whether tidal volume during low-level continuous positive airway pressure (CPAP) could predict tidal volume during HFNC and to compare the physiological effects of HFNC and low-level CPAP.

Methods

Prospective, single-center study including 29 de novo AHRF patients treated with HFNC (50 to 60 L.min− 1). Patients were monitored using electrical impedance tomography during HFNC then CPAP at 4 cmH2O. Tidal volume during HFNC was calculated based on tidal impedance variation. The ability of tidal volume under low-level CPAP to predict tidal volume under HFNC was explored using Bland-Altman analysis. CPAP and HFNC were compared in terms of tidal volume, minute ventilation, respiratory comfort, dyspnea, oxygenation, ventilation distribution, end-expiratory lung volume, thoraco-abdominal asynchrony and recruitment.

Results

Under HFNC, patients had a tidal volume of 6.6 (5.9–8.7) mL.kg− 1 PBW. 20 (69%) patients exhibited a tidal volume between 4 and 8 mL.kg− 1 PBW, while in 5 (17%) patients it exceeded 9 mL.kg− 1 PBW. Tidal volume under CPAP was higher (9.4 (8.3–11) mL.kg− 1 PBW, p < 0.001). Tidal volumes under CPAP and under HFNC were modestly correlated (Spearman r = 0.50, p = 0.005). Bland-Altman analysis showed a bias of 2.4 mL.kg− 1, with limits of agreement ranging from − 1.1 mL.kg− 1to 5.9 mL.kg− 1. Nevertheless, a larger (> 11.5 mL.kg− 1 PBW ) tidal volume under low-level CPAP predicted a larger (> 9 mL.kg− 1 PBW ) tidal volume under HFNC with 80% sensitivity and 96% specificity. Low-level CPAP was associated with increased minute ventilation, end-expiratory lung volume, and oxygenation as compared to HFNC. It decreased signs of respiratory distress in the most severe patients but was associated with lower comfort compared to HFNC.

Conclusion

Among ICU patients with de novo AHRF, tidal volume under HFNC was mostly protective. Tidal volume during CPAP at 4 cmH2O did not predict tidal volume during HFNC. Such low-level CPAP was associated with increased tidal volume, minute ventilation, end-expiratory volume, and oxygenation.

Trial registration

ClinicalTrials.gov ID NCT03919331. Registration date: 2019-03-26.
From fixing to connecting: parents’ experiences supporting adult children with eating disorders
Authors: Geller J. , Fernandes A. , Marshall S. , Srikameswaran S.
Published: November 2024

Background

Unlike evidence-based guidelines that exist for families of youth with eating disorders, little is known about the optimal role for families of adult patients. Given issues of patient autonomy and confidentiality, it is common for family members to report high levels of distress, confusion about how to offer support, and feelings of exclusion. Nevertheless, interactions with parents play a critical role in the recovery process. The purpose of this research was to increase understanding of support experiences of parents of adult children while identifying what they believe to be the most beneficial forms of support.

Methods

Sixteen parents of adults who were either recovered or actively engaged in intensive eating disorders treatment participated in semi-structured interviews. Participants were asked to describe the nature of their relationship, beliefs about their child’s support needs, and factors that challenged or facilitated their capacity to offer what they deemed as optimal support.

Results

In the context of receiving support and practicing self-care, parents’ aspiration shifted from fixing the eating disorder to prioritizing a relational goal of unrelenting connection with their child. Achieving this involved three key skills: managing reactions and expectations, learning boundaries, and practicing validation.

Conclusions

This research highlights the ongoing challenges faced by parents, indicating that interventions aimed at supporting their own well-being and fostering connection with their child may be of benefit.
Treatment utilization among people with drug use disorders in prison: a national longitudinal cohort study
Authors: Lokdam Nicoline Toresen , Stavseth Marianne Riksheim , Skjaervø Ingeborg , Bukten Anne
Published: November 2024

Background

Drug use disorders are highly prevalent among people in prison. Nevertheless, treatment coverage for individuals with drug use disorders in prison remains understudied and unknown. The aim of this study was to estimate treatment coverage among a sample of people with harmful and likely drug dependence before entering prison and to investigate the factors associated with treatment utilization.

Methods

This was a longitudinal cohort study using baseline survey data linked to registry data on imprisonment and treatment utilization. The study is based on the Norwegian Offender Mental Health and Addiction (NorMA) cohort (n = 733) recruited in 2013–2014 from 57 Norwegian prisons. At baseline, participants reported drug use the year before imprisonment, using the Drug Use Disorder Identification Test (DUDIT). The outcome of interest was DUD treatment, defined as at least one DUD treatment episode from the specialized health services during baseline imprisonment.

Results

40% of the sample had DUDIT scores that indicated likely drug dependence (≥ 25) and a need for treatment. Among this group, 64% received DUD treatment while imprisoned. Longer imprisonment (> 12 months; aOR = 8.87, p < 0.001), Nordic country of birth (aOR = 2.85, p = 0.003), daily/almost daily injecting drug use (aOR = 2.58, p < 0.001) and polydrug use (aOR = 2.19, p = 0.002) were positively associated with treatment utilization in prison.

Conclusions

Most people with likely drug dependence before entering prison in Norway received DUD treatment during their time in prison. More severe drug use (Injecting drug use and polydrug use), longer imprisonments and being born in the Nordics were positively associated with treatment utilization. People in prison must have access to adequate treatment during imprisonment, and further studies should investigate the possible individual or structural barriers resulting in treatment gaps, especially for people who are foreign born and people with short sentences.
Personalized circulating tumor DNA analysis for sensitive disease monitoring and detection of relapse in neuroblastoma
Authors: Rahmqvist Ida , Engström Enya , Mellström Elisabeth , Ibrahim Raghda R. , Pujol-Calderón Fani , Dahlstrand Rudin Agnes , Ordqvist Redfors Anna , Rostamzadeh Niki , Di Rienzo Rita , Franssila Wilma , Khashan Robert , Xylander Moe , Karlsson Christin , Ek Torben , Andersson Daniel , Österlund Tobias , Gaarder Jennie , Fagman Henrik , Fransson Susanne , Martinsson Tommy , Ståhlberg Anders , Dalin Martin
Published: November 2024

Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma. We generated personalized sequencing panels targeting 10 tumor-specific single nucleotide variants (SNVs) for each patient and performed ctDNA analysis of 136 plasma samples collected longitudinally in 13 children with neuroblastoma. ctDNA was detected using ultra-deep next generation sequencing with unique molecular identifiers to eliminate polymerase-induced errors. We found that the levels of ctDNA at diagnosis correlated with risk group and decreased gradually during effective treatment. All samples collected during follow-up in patients without disease relapse were ctDNA-negative. All four relapses were associated with elevated ctDNA levels, and a majority of the analyzed SNVs were detected at time of relapse. In one case, ctDNA became positive 78 days before the relapse was diagnosed with routine assessment and increased by over a thousandfold before the start of additional treatment. Overall, ctDNA was more uniformly elevated at diagnosis, showed less putative false positive results, and was more sensitive for detection of relapse compared to five serum or urine tumor markers used in clinical routine. In conclusion, personalized ctDNA analysis is suitable for clinical monitoring of tumor burden and may be used in all neuroblastoma patients regardless of risk group or tumor genetics.
MACC1 revisited – an in-depth review of a master of metastasis
Authors: Schöpe Paul Curtis , Torke Sebastian , Kobelt Dennis , Kortüm Benedikt , Treese Christoph , Dumbani Malti , Güllü Nazli , Walther Wolfgang , Stein Ulrike
Published: November 2024

Cancer metastasis remains the most lethal characteristic of tumors mediating the majority of cancer-related deaths. Identifying key molecules responsible for metastasis, understanding their biological functions and therapeutically targeting these molecules is therefore of tremendous value. Metastasis Associated in Colon Cancer 1 (MACC1), a gene first described in 2009, is such a key driver of metastatic processes, initiating cellular proliferation, migration, invasion, and metastasis in vitro and in vivo. Since its discovery, the value of MACC1 as a prognostic biomarker has been confirmed in over 20 cancer entities. Additionally, several therapeutic strategies targeting MACC1 and its pro-metastatic functions have been developed. In this review, we will provide a comprehensive overview on MACC1, from its clinical relevance, towards its structure and role in signaling cascades as well as molecular networks. We will highlight specific biological consequences of MACC1 expression, such as an increase in stem cell properties, its immune-modulatory effects and induced therapy resistance. Lastly, we will explore various strategies interfering with MACC1 expression and/or its functions. Conclusively, this review underlines the importance of understanding the role of individual molecules in mediating metastasis.
Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing
Authors: Noack Darius , Wach Johannes , Barrantes-Freer Alonso , Nicolay Nils H. , Güresir Erdem , Seidel Clemens
Published: November 2024

CDKN2A/B deletions are prognostically relevant in low- and high-grade gliomas. Data on this is derived from heterogeneous series, an accurate estimation of survival risk from homozygous CDKN2A/B deletion is missing. Besides genetic testing, p16-immunohistochemistry (IHC) as a less cost intensive means for indirect detection of CDKN2A/B alterations is possible but not validated in larger datasets. The present meta-analysis aimed to (1) reconstruct individual patient data (IPD) and estimate overall survival (OS) stratified by CDKN2A/B status from all literature and to (2) determine accuracy of p16 testing for CDKNA2/B detection from published studies. For survival analysis according to CDKN2A/B status 460 records were screened, four articles with 714 participants were included. In IDH-wildtype (IDH-wt) gliomas, 57.07% harbored the deletion compared to 9.76% in IDH-mutant (IDH-mut) gliomas. Median OS of patients with IDH-wt gliomas and homozygous CDKN2A/B deletion was 13.0 months compared to 18.0 months with non-deleted CDKN2A/B (p = 0.014, Log-Rank). With homozygous deletion of CDKN2A/B the risk of death was increased by 1.5 (95%-CI 1.1–2.1). Median OS in patients with IDH-mut gliomas without CDKN2A/B deletion was 92.0 months compared to 40.0 months with CDKN2A/B deletion (p < 0.001, Log-Rank). CDKN2A/B deletions were associated with a significantly shorter OS (HR = 3.2; 95%-CI 2.2–5.5). For p16 IHC analysis, 10 eligible studies with 1087 examined samples were included. The cut-off for retention differed between the studies. In 588/662 p16 retained cases CDKN2A/B deletions was not detected, implying a negative predictive value (NPV) of p16 staining of 88.8%. Conversely, 279/425 p16 absent cases showed a CDKN2A/B deletion resulting in a positive predictive value (PPV) of 65.6%. Sensitivity of p16 staining for CDKN2A/B detection was 79.0%, specificity 80.1%. Highest diagnostic accuracy of p16 IHC was reached with a cut-off of > 5% and within IDH-mut glioma.
Treatment of a left inguinal hernia with incarceration of the scope during colonoscopy: a case report and literature review
Authors: Numoto Ryo , Taniguchi Kohei , Imai Yoshiro , Asakuma Mitsuhiro , Tomiyama Hideki , Fujiwara Shinya , Nakanishi Yoshihiko , Hamaguchi Takuya , Masubuchi Shinsuke , Inoue Hitoshi , Kawai Masaru , Kinoshita Takashi , Morita Shinsho , Hayashi Michihiro , Lee Sang-Woong
Published: November 2024

Background

Colonoscopy is widely performed. However, reports of colonoscopic incarceration within inguinal hernias are rare. Incarceration during colonoscopy is a critical condition, and attempting forced reduction may exacerbate complications; therefore, a careful approach is required. Here, we present a case of colonoscopic incarceration of a left inguinal hernia that was successfully reduced under fluoroscopic guidance, followed by elective endoscopic surgery.

Case presentation

A 74-year-old man presented for colonoscopy at a primary care clinic and was referred to our hospital for the incarceration of the colonoscope within the inguinal hernia. On arrival, the colonoscope remained in situ through the anus. Laboratory tests and imaging studies confirmed the absence of perforation. Manual pressure was applied under fluoroscopic guidance to successfully reduce the hernia and allow for scope extraction. No evidence of perforation was revealed in the follow-up fluoroscopic examination using a gastrografin enema. Six weeks later, the patient underwent definitive surgery for total extraperitoneal hernia repair.

Conclusions

A complication of colonoscopy is the incarceration of the colonoscope within the inguinal hernia, particularly in older men. Therefore, inquiring about the patient’s history of inguinal hernia, particularly those accompanied by scrotal swelling, besides assessing the surgical history before performing a colonoscopy, is critical. Furthermore, recent trends include attempts at incarceration reduction under fluoroscopic guidance, with emergency surgery reserved for irreducible cases.
Association Between Inter-Limb Asymmetry and Determinants of Middle- and Long-distance Running Performance in Healthy Populations: A Systematic Review
Authors: D’Hondt Joachim , Chapelle Laurent , Bishop Chris , Aerenhouts Dirk , De Pauw Kevin , Clarys Peter , D’Hondt Eva
Published: November 2024

Background

The presence of inter-limb asymmetry in the human body has traditionally been perceived to be detrimental for athletic performance. However, a systematic review addressing and comprehensively assessing the association of asymmetry between the lower limbs and middle- and long-distance running performance-related metrics is currently lacking.

Objective

The main purpose of this systematic review was to examine the relationship between lower inter-limb asymmetry and determinants of running performance in healthy middle- and long-distance runners. The secondary objective was to identify possible avenues for further research in this area.

Methods

PubMed, Web of Science and SPORTDiscus were systematically searched for studies investigating the relationship between lower inter-limb asymmetry and (determinants of) running performance in healthy and injury-free middle- and long-distance runners. The quality of studies eligible for inclusion was assessed using the Downs and Black Quality Index Tool.

Results

Out of 4817 articles screened, 8 studies were included in this review which assessed the association between functional, morphological, kinematic and kinetic asymmetry and running performance-related metrics. The quality score of the included research varied between 5/10 and 9/10. Our results revealed mixed findings, showing both significant negative (n = 16) and positive (n = 1) associations as well as no significant associations (n = 30) between inter-limb asymmetry and running performance-related metrics.

Conclusions

A high heterogeneity across study methods and outcomes was apparent, making it difficult to draw a straightforward conclusion. Our results indicate that the majority of metrics of functional, morphological, kinematic and kinetic inter-limb asymmetry are negatively or not associated with running performance (and/or its determinants). Thus, a more extensive high-quality body of research using standardised asymmetry magnitude metrics is essential to determine whether, and to what extent asymmetry between the lower limbs could affect middle- and long-distance running performance. Future studies should establish potential trade-off values to help practitioners develop evidence-based training programs.

Key Points

In the majority of the metrics, the magnitude of lower inter-limb asymmetry was negatively or not associated with middle- and long-distance running performance.

Coaches, athletes and researchers should be attentive of the task, time- and metric-specificity as well as the inter- and intra- individual variability of magnitude outcomes, when assessing inter-limb asymmetries.
The impact of herd age structure on the performance of commercial sow-breeding farms
Authors: Sanz-Fernández Santos , Díaz-Gaona Cipriano , Simões João , Casas-Rosal José Carlos , Alòs Nuria , Tusell Llibertat , Quintanilla Raquel , Rodríguez-Estévez Vicente
Published: November 2024

Background

The herd age structure, i.e., distribution of sows within a farm based on their parity number, and its management are essential to optimizing farm reproductive efficiency. The objective of this study is to define different types of herd age structure using data from 623 Spanish commercial sow farms. Additionally, this study aims to determine which type of herd age structure can enhance reproductive efficiency at the farm level.

Results

Farms are classified into three groups according to the quadratic function fitted to the percentage of sows by parities. This classification unveils three types of herd structures: type 1 (HS1) exhibits a concave-downward trend, with a higher percentage of sows in intermediate parities (mean of 45.5% sows between the 3rd to 5th parity); type 2 (HS2) presents a trend curve that is close to a straight line, with a gradual decrease in the percentage of sows per parity (approximately 2% loss of sows census per parity); and type 3 (HS3) shows an upward concave trend curve, with an increase in the percentage of sows in later parities (19.0% of sows between 7th and ≥ 8th parity). Parametric tests assess productivity differences between the three types of herd structures (p < 0.01). HS1 farms have the best productive outcomes over a year, with 31.2 piglets weaned per sow and year (PWSY) and a farrowing rate of 87%, surpassing HS2 and HS3 farms (30.1 and 28.7 PWSY; 85.3% and 83.4% farrowing rates, respectively). HS1 also have the lowest percentage of sows returning to oestrus (11.8%) and the highest number of weaned piglets per litter (12.8), compared to HS2 (13.2% and 12.4 piglets weaned) and HS3 (15.1%, 11.9 piglets weaned). These differences show a medium effect size (η2 between 0.06 to < 0.14).

Conclusions

This study shows the importance of herd age structure on sow-breeding farms as a factor of reproductive efficiency. The results endorse the proposed classification based on the curvature of the trend parabola obtained with the quadratic function to categorize herd structures into three groups. Additionally, these findings highlight the importance of considering the herd age structure in farm decision-making.
Correlates of self-reported distress in end-stage kidney dialysis patients using the distress thermometer score
Authors: Yoowannakul Suree , Vongsanim Surachet , Tangvoraphonkchai Kamonwan , Davenport Andrew
Published: November 2024

Introduction

Haemodialysis patients self-report increased levels of anxiety and depression. We wished to determine the prevalence of distress in a multi-ethnic dialysis population and patient factors associated with distress.

Methods

We reviewed self-reported distress thermometer (DT) scores from 971 haemodialysis patients with corresponding laboratory investigations, bioimpedance body composition and hand grip strength (HGS).

Results

The median age was 66.0 (55–75) years, 62.9% were male, 46.5% were of white ethnicity and 45.4% were diabetic. The results showed that 57.4% were classified as having no/minimal, 34% moderate, and 8.7% severe distress. Frailty increased from 31.5% to 47.9% and 56%, in the none/minimal, mild to moderate and severe distress groups (χ2 17.6, p = 0.001), as did smoking (12.9% versus 16.7% versus 25%, χ2 12.5, p = 0.001), and more patients reporting severe distress had suffered a previous myocardial infarction (MI) (17.4% versus 16.7% versus 27.4%, χ2 7.1, p = 0.029). Haemoglobin decreased (109.6 ± 14.6 versus 107.6 ± 14.2 versus 103.5 ± 14.4 g/L, p < 0.001) as did HGS (18.9 (12.8–26.5) versus 17.1 (11.8–23.9) versus 15.4 (11.1–22.6) kg, p < 0.05). On ordinal multivariable analysis, increasing distress was associated with smoking (β 0.55, 95% confidence interval (CI) (0.17–0.92), p = 0.004), previous MI (β 0.47 (0.09–0.83), p = 0.015), serum calcium (β 1.11, (0.3–1.9), p = 0.007), lower age (β  −0.016, (−0.03 to −0.005), p = 0.003), haemoglobin (β  −0.014 (−0.02 to −0.004), p = 0.008) and HGS (β  −0.12 (−0.04 to −0.005), p = 0.013).

Conclusion

Younger age, higher calcium, lower haemoglobin and muscle strength, previous MI and smoking were associated with increasing levels of distress in this multi-ethnic dialysis population. Thus, both psychological and physical treatments are required to reduce stress levels for haemodialysis patients.