bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigating into the unknown: exploring the experience of exposure to prehospital emergency stressors: a sequential explanatory mixed-methods
Authors: Afshari Ali , Torabi Mohammad , Navkhasi Sasan , Aslani Marzieh , Khazaei Afshin
Published: November 2023

Introduction

The unpredictability of prehospital emergencies combined with constantly changing circumstances can lead to increased stress and mental health issues among Emergency Medical Technicians (EMTs). To accurately determine the stress-inducing factors in the prehospital environment, it is important to first identify the stressful events that occur in this environment. Therefore, this study strives to provide a thorough analysis of the stressors in the prehospital environment.

Methods

Sequential explanatory mixed methods were conducted in Hamadan prehospital emergency centers in 2022. The study included 251 EMTs, who were selected through a method in the quantitative phase. The quantitative part used a questionnaire consisting of basic information and the Posttraumatic Stress Questionnaire (PCL-5). In the qualitative phase, 17 with extensive experience in dealing with prehospital stressors were selected based on their PCL-5 scores (above 33). The qualitative phase analysis was carried out using the contractual content method using the Graneheim and Ladman's approach. Statistical analyzes for the quantitative and qualitative phases were performed using SPSS 21 and maxqda 10, respectively.

Results

The study revealed that the EMTs had an average PTSD score of 21. 60 ± 11. 45. Multivariate linear regression analysis showed that the number of shifts had a statistically significant relationship with PTSD scores (t = 26.38, P < 0.001). The qualitative phase of the study included 17 interviews, resulting in 14 subcategories, which consisted of four categories: “the overall impact of the stress crisis on technicians,” “missing links in the communication network in incident management,” "professional shortcomings in pre-hospital care,” and “the complex and multifaceted context of stressful pre-hospital emergencies.” Additionally, the study's theme was centered around “surveying the experiences of EMTs in stressful environments.”

Conclusion

As the number of shifts increased, the primary cause of the high prevalence of PTSD in EMTs was revealed. Prehospital emergency stress can be reduced and managed more skillfully by adjusting various factors such as shortening workdays, offering continuous training, augmenting workforce, supplying ambulance equipment insurance, refraining from hiring personnel devoid of clinical training, hiring psychologists, hiring midwives in an emergency, updating prehospital protocols and guidelines, encouraging cooperation between EMTs and other relief groups, and utilizing cutting-edge technologies.
Living with polypharmacy: a narrative interview study with older Pakistanis in East London
Authors: Sultan Najia , Swinglehurst Deborah
Published: November 2023

Background

Polypharmacy is a growing and major public health issue. It can be burdensome and risky for patients and costly to healthcare systems. Older adults and those from ethnic minority backgrounds are disproportionately affected by polypharmacy. This study focuses on medication practices among Urdu-speaking Pakistani patients, a significant ethnic group in the UK. Most existing research on medication practices within South-Asian communities centres on adherence, leaving the social and moral dimensions of polypharmacy unpacked. Understanding how British Pakistani patients understand and manage polypharmacy in the context of their daily lives is crucial to avoiding harmful polypharmacy.

Methods

In-depth narrative interviews were conducted with 15 first-generation Pakistani patients using the Biographical Narrative Interview Method. Participants were recruited from GP practices in East London. All participants were prescribed ten or more regular medications (a pragmatic marker of ‘higher risk’ polypharmacy) and were aged over 50. Interviews were conducted with a bilingual researcher at home and were designed to elicit narratives of patients’ experiences of polypharmacy in the context of their biographies and daily lives.

Results

Polypharmacy is enacted through networks of interpersonal and socio-material relationships. The doctor-patient relationship and the family network held particular significance to study participants. In addition, participants described emotional bonds between themselves and their medicines, identifying them as ‘forces for good’—substances which allowed them to maintain their health through the intercession of God. Meanings attributed to medicines and enacted through these social, emotional, and spiritual relationships contributed to emerging and sustaining polypharmacy.

Conclusions

Patients make sense of and manage treatments in culturally specific ways. Developing an understanding of how medication practices in different communities are enacted is important for informing meaningful and effective conversations with patients about their medicines. Our findings contribute to enabling the integration of culturally sensitive approaches to prescribing.
Rapid implementation of home oxygen treatment and remote monitoring for COVID-19 patients at the verge of the Omicron wave in Turku, Finland
Authors: Hänninen Janne , Anttalainen Ulla , Kilpeläinen Maritta , Hohenthal Ulla , Broman Niklas , Palmén Jenni , Oksi Jarmo , Feuth Thijs
Published: November 2023

Background

In Turku, Finland, we introduced a home oxygen treatment and app-based monitoring program for hospitalized COVID-19 patients to facilitate an early discharge during the Omicron wave. In this case series we explore the clinical parameters of patients enrolled in the program and evaluate the cost–benefit and safety issues of the program.

Methods

Hospitalized COVID-19 patients with marked hypoxemia but otherwise in stable condition were screened from Turku City Hospital and Turku University Hospital by treating doctors for eligibility in the program. Peripheral oxygen saturation of > 92% and breathing frequency < 30/min in rest with oxygen supplementation were among the criteria. All patients actively participating in the program between 10th of January 2022 and 30th of September 2022 were included in this case series. Clinical data of hospitalization and monitoring were analysed, and cost–benefit evaluation was based on the number of saved hospitalization days.

Results

Nineteen COVID-19 patients were included in this case series and recruited from three different hospital departments in the Turku city region, South-West Finland. All patients were male, the median age was 59 years and the median duration of hospitalization before enrolment in the program was 6 days (range 3—20 days). The median duration of home oxygen treatment was 13 days (range 3—72 days) and the median duration of home monitoring was 18 days (range 7—41 days). A total of 210,5 hospital days were prevented, resulting in savings of €144,490 of healthcare expenditure (on average 9 days and €7,605 per patient). No major safety issues were reported during the program.

Conclusions

In our case series, home oxygen treatment combined with home monitoring was safe and economically beneficial. Application based monitoring could be considered in other post-acute pulmonary conditions to reduce hospitalization and healthcare costs.
Confirmatory validation of the french version of the Duchenne Muscular Dystrophy module of the pediatric quality of life inventory (PedsQLTM3.0DMDfv)
Authors: Wallach Elisabeth , Ehlinger Virginie , Biotteau Maelle , Walther-Louvier Ulrike , Péréon Yann , Vuillerot Carole , Fontaine Stephanie , Sabouraud Pascal , Espil-Taris Caroline , Cuisset Jean-Marie , Laugel Vincent , Baudou Eloïse , Arnaud Catherine , Cances Claude
Published: November 2023

Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease that inevitably leads to total loss of autonomy. The new therapeutic strategies aim to both improve survival and optimise quality of life. Evaluating quality of life is nevertheless a major challenge. No DMD-specific quality of life scale to exists in French. We therefore produced a French translation of the English Duchenne Muscular Dystrophy module of the Pediatric Quality of Life Inventory (PedsQLTMDMD) following international recommendations. The study objective was to carry out a confirmatory validation of the French version of the PedsQLTMDMD for paediatric patients with DMD, using French multicentre descriptive cross-sectional data. The sample consisted of 107 patients. Internal consistency was acceptable for proxy-assessments, with Cronbach's alpha coefficients above 0.70, except for the Treatment dimension. For self-assessments, internal consistency was acceptable only for the Daily Activities dimension. Our results showed poor metric qualities for the French version of the PedsQLTMDMD based on a sample of about 100 children, but these results remained consistent with those of the original validation. This confirms the interest of its use in clinical practice.
Cognitive Remediation in Bipolar (CRiB2): study protocol for a randomised controlled trial assessing efficacy and mechanisms of cognitive remediation therapy compared to treatment as usual
Authors: Tsapekos Dimosthenis , Strawbridge Rebecca , Cella Matteo , Goldsmith Kimberley , Kalfas Michail , Taylor Rosie H. , Swidzinski Samuel , Marwaha Steven , Grey Libby , Newton Elizabeth , Shackleton Julie , Harrison Paul J. , Browning Michael , Harmer Catherine , Hartland Hannah , Cousins David , Barton Stephen , Wykes Til , Young Allan H.
Published: November 2023

Background

A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects.

Methods

CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30–40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models.

Discussion

This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action.

Trial registration

Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry:
https://www.isrctn.com/ISRCTN10362331. Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting.
Comparison of 2D, 2.5D, and 3D segmentation networks for maxillary sinuses and lesions in CBCT images
Authors: Yoo Yeon-Sun , Kim DaEl , Yang Su , Kang Se-Ryong , Kim Jo-Eun , Huh Kyung-Hoe , Lee Sam-Sun , Heo Min-Suk , Yi Won-Jin
Published: November 2023

Background

The purpose of this study was to compare the segmentation performances of the 2D, 2.5D, and 3D networks for maxillary sinuses (MSs) and lesions inside the maxillary sinus (MSL) with variations in sizes, shapes, and locations in cone beam CT (CBCT) images under the same constraint of memory capacity.

Methods

The 2D, 2.5D, and 3D networks were compared comprehensively for the segmentation of the MS and MSL in CBCT images under the same constraint of memory capacity. MSLs were obtained by subtracting the prediction of the air region of the maxillary sinus (MSA) from that of the MS.

Results

The 2.5D network showed the highest segmentation performances for the MS and MSA compared to the 2D and 3D networks. The performances of the Jaccard coefficient, Dice similarity coefficient, precision, and recall by the 2.5D network of U-net +  + reached 0.947, 0.973, 0.974, and 0.971 for the MS, respectively, and 0.787, 0.875, 0.897, and 0.858 for the MSL, respectively.

Conclusions

The 2.5D segmentation network demonstrated superior segmentation performance for various MSLs with an ensemble learning approach of combining the predictions from three orthogonal planes.
Effect of educational intervention on medication reconciliation practice of hospital pharmacists in a developing country – A non-randomised controlled trial
Authors: Aje Akinniyi A. , Showande Segun J. , Adisa Rasaq , Fakeye Titilayo O. , Olutayo Oluwakemi A. , Adebusoye Lawrence A. , Olowookere Olufemi O.
Published: November 2023

Background

Medication reconciliation is an evidence-based practice that reduces medication-related harm to patients. This study evaluated the effect of educational intervention on medication reconciliation practice of pharmacists among ambulatory diabetes and hypertensive patients.

Methods

A non-randomized clinical trial on medication reconciliation practice was carried out among 85 and 61 pharmacists at the intervention site and control site, respectively. Medication reconciliation was carried out among 334 (intervention-183; control-151) diabetes and/or hypertensive patients by the principal investigator to indirectly evaluate pharmacists’ baseline medication reconciliation practice at both sites. A general educational intervention was carried out among intervention pharmacists. Medication reconciliation was carried out by the principal investigator among another cohort of 96 (intervention-46; control-50) and 90 (intervention-44; control-46) patients at three and six months postintervention, respectively, to indirectly assess pharmacists’ postintervention medication reconciliation practice. Thereafter, a focused educational intervention was carried out among 15 of the intervention pharmacists. Three experts in clinical pharmacy analysed the medication reconciliation form filled by the 15 pharmacists after carrying out medication reconciliation on another cohort of 140 patients, after the focused intervention. Data was summarized with descriptive (frequency, percentage, mean ± standard deviation) and inferential (Pearson product-moment correlations analysis, independent-samples t-test and one-way ANOVA) statistics with level of significance set at p<0.05.

Key findings

Baseline medication reconciliation practice was poor at both sites. Post-general educational intervention, medication discrepancy was significantly reduced by 42.8% at the intervention site (p<0.001). At the intervention site, a significant increase of 54.3% was observed in patients bringing their medication packs for clinic appointments making medication reconciliation easier (p=0.003), at 6-months postintervention. Thirty-five, 66 and 48 drug therapy problems were detected by 31 (43.1%), 33 (66.0%) and 32 (71.1%) intervention pharmacists at 1-, 3- and 6-month post-general educational intervention, respectively. Post-focused educational intervention, out of a total of 695 medications prescribed, 75 (10.8%) medication discrepancies were detected and resolved among 42 (30%) patients by the 15 pharmacists.

Conclusions

The educational interventions improved pharmacists’ medication reconciliation practice at the intervention site. It is expected that this research would help create awareness on medication reconciliation among pharmacists in developing countries, with a view to reducing medication-related patient harm.
Through the eyes of nurses: a content analysis of nurses’ experiences in caring for COVID-19 patients
Authors: Broujeni Razieh Beigi , Kamalzadeh Hesamaddin , Ahmadi Zakieh , Abedini Samireh
Published: November 2023

Background

In the current global climate, the nursing staff has placed a significant emphasis on developing effective self-protection strategies and implementing measures to prevent the transmission of infectious diseases, with a particular focus on the highly communicable COVID-19 virus. Ensuring the safety and well-being of both healthcare providers and patients has made it imperative to incorporate this aspect into healthcare provision.

Objective

The study aimed to describe the experiences of nurses in providing care for patients infected with COVID-19.

Methodology

This qualitative content analysis study, following COREQ guidelines, involved 18 nurses who were taking care of COVID-19 patients at Shahid Mohamadi Hospital, a general hospital in Bandar Abbas, Hormozgan Province. The hospital is affiliated with Hormozgan University of Medical Sciences and the research was conducted in 2022.The sampling method was purposive, and unstructured interviews were used. Data collection continued until data saturation was achieved. Data analysis was performed continuously and concurrently through the collection of data using conventional content analysis methods.

Findings

The qualitative analysis of the data revealed three main themes centered on challenges related to nurses’ self-care, patient care, and the healthcare delivery system.

Conclusion

Overall, to address the challenges faced by healthcare providers caring for COVID-19 patients, their needs must be prioritized. This includes establishing a prepared healthcare system, implementing strategies to protect their well-being, and learning from their experiences for future disease outbreaks and disasters.
Psychometric testing of the 10-item perceived stress scale for Chinese nurses
Authors: Du Xiaoyu , Liu Xiqin , Zhao Yajun , Wang Song
Published: November 2023

Background

Nurses bear a lot of stressors at work. The 10-item Perceived Stress Scale (PSS-10) is a widely used self-reported scale for measuring the global perception of stress. However, there is a lack of use of the PSS-10 in Chinese nurses. This study aimed to test the psychometric properties of the PSS-10 among Chinese nurses.

Methods

A total of 708 Chinese nurses completed the PSS-10, the Big Five Inventory (BFI), and the Depression Anxiety and Stress Scale (DASS). Confirmatory factor analysis (CFA) tested the factor structure of the PSS-10. Cronbach’s α and test-retest correlation examined the scale reliability. Pearson correlation and hierarchical regression analyses tested the convergent, discriminant and criterion validity of the PSS-10.

Results

CFA revealed that a two-factor model fits the structure of the PSS-10 in Chinese nurses (χ2/df = 6.25,p < 0.001; comparative fit index [CFI] = 0.94, non-normal fit index [NNFI] = 0.92, Tucker-Lewis index [TLI] = 0.91, root mean square error of approximation [RMSEA] = 0.08, standardized root mean square residual [SRMR] = 0.05). The scale demonstrated adequate internal consistency (α = 0.86) and test-retest reliability (r = 0.66,p < 0.001), satisfactory convergent and discriminant validity with relations to Big Five personalities, as well as good criterion validity such that the PSS-10 score could explain incremental variance in predicting anxiety, depression and stress.

Conclusions

Our findings suggest that PSS-10 is a reliable and valid measure of perceived stress among Chinese nurses and can be used in future research and practice on stress management and coping in Chinese nurses.
Home-based initiatives for acute management of COVID-19 patients needing oxygen: differences across The Netherlands
Authors: Boeijen Josi A. , van de Pol Alma C. , van Uum Rick T. , Smit Karin , Ahmad Abeer , van Rijswijk Eric , van Apeldoorn Marjan J. , van Thiel Eric , de Graaf Netty , Menkveld R. Michiel , Mantingh Martijn R. , Geertman Silke , Couzijn Nicolette , van Groenendael Leon , Schers Henk , Bont Jettie , Bonten Tobias N. , Rutten Frans H. , Zwart Dorien L. M.
Published: November 2023

Objective

During the COVID-19 pandemic new collaborative-care initiatives were developed for treating and monitoring COVID-19 patients with oxygen at home. Aim was to provide a structured overview focused on differences and similarities of initiatives of acute home-based management in the Netherlands.

Methods

Initiatives were eligible for evaluation if (i) COVID-19 patients received oxygen treatment at home; (ii) patients received structured remote monitoring; (iii) it was not an ‘early hospital discharge’ program; (iv) at least one patient was included. Protocols were screened, and additional information was obtained from involved physicians. Design choices were categorised into: eligible patient group, organization medical care, remote monitoring, nursing care, and devices used.

Results

Nine initiatives were screened for eligibility; five were included. Three initiatives included low-risk patients and two were designed specifically for frail patients. Emergency department (ED) visit for an initial diagnostic work-up and evaluation was mandatory in three initiatives before starting home management. Medical responsibility was either assigned to the general practitioner or hospital specialist, most often pulmonologist or internist. Pulse-oximetry was used in all initiatives, with additional monitoring of heart rate and respiratory rate in three initiatives. Remote monitoring staff’s qualification and authority varied, and organization and logistics were covered by persons with various backgrounds. All initiatives offered remote monitoring via an application, two also offered a paper diary option.

Conclusions

We observed differences in the organization of interprofessional collaboration for acute home management of hypoxemic COVID-19 patients. All initiatives used pulse-oximetry and an app for remote monitoring. Our overview may be of help to healthcare providers and organizations to set up and implement similar acute home management initiatives for critical episodes of COVID-19 (or other acute disorders) that would otherwise require hospital care.
F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
Authors: Ye Lin , Wang Yizhong , Xiao Fangfei , Wang Xufei , Li Xiaolu , Cao Rong , Zhang Jiayue , Zhang Ting
Published: November 2023

Background

Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice.

Results

Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor β (TGF-β) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1).

Conclusion

Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.
Surface curvature-induced oriented assembly of sushi-like Janus therapeutic nanoplatform for combined chemodynamic therapy
Authors: Ma Yanming , Liu Minchao , Hou Mengmeng , Kou Yufang , Wang Wenxing , Zhao Tiancong , Li Xiaomin
Published: November 2023

Background

Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency.

Results

Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform.

Conclusions

In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.
Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis
Authors: Liu Senrui , Cheng Shengwen , Chen Bowen , Xiao Pengcheng , Zhan Jingdi , Liu Jiacheng , Chen Zhuolin , Liu Junyan , Zhang Tao , Lei Yiting , Huang Wei
Published: November 2023

Background

Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence.

Result

We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs.

Conclusion

The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA.
A novel two-step administration of XPO-1 inhibitor may enhance the effect of anti-BCMA CAR-T in relapsed/refractory extramedullary multiple myeloma
Authors: Wang Di , Fu Haiying , Que Yimei , Ruan Haitao , Xu Menglei , Long Xiaolu , Yu Qiuxia , Li Chunhui , Li Zhe , Cai Songbai , Chen Wei , Sun Cong , Hu Guang , Wang Shuai , He Donggou , Mei Jianming , Wang Wen , Li Chunrui
Published: November 2023

Background

Extramedullary disease usually implies a dismal outcome in relapsed/refractory multiple myeloma patients, and requires novel treatment approaches. We designed a trial using Selinexor, a nuclear export protein 1 inhibitor, together with anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell product CT103A to treat these patients, and describe the first two cases in this report.

Methods

Selinexor was administered with a novel two-step schedule in bridging therapy and in maintenance. The clinical responses and adverse events were recorded after CAR-T infusion and Selinexor administration. In vitro analysis of the influence of Selinexor on CAR-T cell function was performed using myeloma cell lines.

Results

After infusion, both patients achieved stringent complete remission (sCR), and were maintained in sCR at data-cutoff, with survival over 13 and 10 months, respectively. Neither immune effector cell-associated neurotoxicity syndrome nor over grade 2 cytokine release syndrome was observed. Meanwhile, the patients showed good tolerance to the combination. In addition, we demonstrated that low dose of Selinexor could upregulate the expression of BCMA on plasma cell lines and subsequently enhance the function of CAR-T cell in vitro.

Conclusions

The combination of Selinexor and CT103A exerts preliminary synergistic effect, and can be developed as a promising strategy for relapsed/refractory extramedullary myeloma.
Notch-based gene signature for predicting the response to neoadjuvant chemotherapy in triple-negative breast cancer
Authors: Omar Mohamed , Nuzzo Pier Vitale , Ravera Francesco , Bleve Sara , Fanelli Giuseppe Nicolò , Zanettini Claudio , Valencia Itzel , Marchionni Luigi
Published: November 2023

Background

While the efficacy of neoadjuvant chemotherapy (NACT) in treating triple-negative breast cancer (TNBC) is generally accepted, not all patients derive benefit from this preoperative treatment. Presently, there are no validated biomarkers to predict the NACT response, and previous attempts to develop predictive classifiers based on gene expression data have not demonstrated clinical utility. However, predictive models incorporating biological constraints have shown increased robustness and improved performance compared to agnostic classifiers.

Methods

We used the preoperative transcriptomic profiles from 298 patients with TNBC to train and test a rank-based classifier, k-top scoring pairs, to predict whether the patient will have pathological complete response (pCR) or residual disease (RD) following NACT. To reduce overfitting and enhance the signature’s interpretability, we constrained the training process to genes involved in the Notch signaling pathway. Subsequently, we evaluated the signature performance on two independent cohorts with 75 and 71 patients. Finally, we assessed the prognostic value of the signature by examining its association with relapse-free survival (RFS) using Kaplan‒Meier (KM) survival estimates and a multivariate Cox proportional hazards model.

Results

The final signature consists of five gene pairs, whose relative ordering can be predictive of the NACT response. The signature has a robust performance at predicting pCR in TNBC patients with an area under the ROC curve (AUC) of 0.76 and 0.85 in the first and second testing cohorts, respectively, outperforming other gene signatures developed for the same purpose. Additionally, the signature was significantly associated with RFS in an independent TNBC patient cohort even after adjusting for T stage, patient age at the time of diagnosis, type of breast surgery, and menopausal status.

Conclusion

We introduce a robust gene signature to predict pathological complete response (pCR) in patients with TNBC. This signature applies easily interpretable, rank-based decision rules to genes regulated by the Notch signaling pathway, a known determinant in breast cancer chemoresistance. The robust predictive and prognostic performance of the signature make it a strong candidate for clinical implementation, aiding in the stratification of TNBC patients undergoing NACT.
DeepAutoGlioma: a deep learning autoencoder-based multi-omics data integration and classification tools for glioma subtyping
Authors: Munquad Sana , Das Asim Bikas
Published: November 2023

Background and objective

The classification of glioma subtypes is essential for precision therapy. Due to the heterogeneity of gliomas, the subtype-specific molecular pattern can be captured by integrating and analyzing high-throughput omics data from different genomic layers. The development of a deep-learning framework enables the integration of multi-omics data to classify the glioma subtypes to support the clinical diagnosis.

Results

Transcriptome and methylome data of glioma patients were preprocessed, and differentially expressed features from both datasets were identified. Subsequently, a Cox regression analysis determined genes and CpGs associated with survival. Gene set enrichment analysis was carried out to examine the biological significance of the features. Further, we identified CpG and gene pairs by mapping them in the promoter region of corresponding genes. The methylation and gene expression levels of these CpGs and genes were embedded in a lower-dimensional space with an autoencoder. Next, ANN and CNN were used to classify subtypes using the latent features from embedding space. CNN performs better than ANN for subtyping lower-grade gliomas (LGG) and glioblastoma multiforme (GBM). The subtyping accuracy of CNN was 98.03% (± 0.06) and 94.07% (± 0.01) in LGG and GBM, respectively. The precision of the models was 97.67% in LGG and 90.40% in GBM. The model sensitivity was 96.96% in LGG and 91.18% in GBM. Additionally, we observed the superior performance of CNN with external datasets. The genes and CpGs pairs used to develop the model showed better performance than the random CpGs-gene pairs, preprocessed data, and single omics data.

Conclusions

The current study showed that a novel feature selection and data integration strategy led to the development of DeepAutoGlioma, an effective framework for diagnosing glioma subtypes.
Use of complementary and alternative medicine in children affected by oncologic, neurologic and liver diseases: a narrative review
Authors: Casini Francesca , Scaltrito Francesca , Grimaldi Maria Teresa , Pop Tudor Lucian , Calcaterra Valeria , Zuccotti Gian Vincenzo , Pettoello-Mantovani Massimo , Ferrara Pietro , Corsello Giovanni , Fabiano Valentina
Published: November 2023

Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases.
Multisensory stimulation bundles on sleep and neurobehavioral development in the first year after birth in very preterm infants: a randomized crossover controlled study protocol
Authors: Tang Xiaoli , Sha Sha , Shen Nanping , Zhu Zhiyu , Qin Yanmin , Shen Junyi , Bei Fei
Published: November 2023

Background

Disrupted sleep is believed to contribute to short- and long-term neurodevelopmental problems in very preterm infants (VPIs). This study presents a protocol for an evaluator-blinded, randomized crossover trial. It aims to assess the sleep efficiency of hospitalized VPIs by providing multisensory stimulation bundles. Furthermore, it aims to observe the intervention impacts on sleep during hospitalization of the VPIs and their sleep and neurodevelopmental outcomes during the first year of post-discharge follow-up.

Methods

The study will be conducted in the neonatology department of a tertiary pediatric teaching hospital. All the eligible VPIs will undergo two types of care in random order: “standard care” (2 weeks) and “standard care plus multisensory stimulation bundles,” each lasting 2 weeks. A generated list of random numbers will be used for case sequence allocation. Sleep outcomes will be evaluated using the Actiwatch-2 Actigraph. Moreover, the amplitude-integrated electroencephalography and the Griffiths Mental Development Scales will be used to measure the neurodevelopmental outcomes during hospitalization and in the first year of follow-up of the VPIs.

Discussion

The intervention protocol of this study differs from that of other traditional interventions by producing precise and consistent supportive stimulations, similar to maternal tactile, auditory, posture, and visual effects for hospitalized VPIs. This protocol could be an effective measure to facilitate sleep and early neurodevelopment of VPIs. The expected outcomes will help confirm the implementation and generalization of the multisensory stimulation bundles’ care protocol in neonatology departments. We expect that the study will positively impact hospitalized VPIs, especially in their sleep and early neurodevelopmental outcomes. It will also provide a new perspective regarding parent and infant interaction strategies, particularly for newborn intensive care units that limit visits because of the global spread of COVID-19.

Trial registration

Chinese Clinical Trial Registry ChiCTR 2200059099. Registered on 25 April 2022, https://www.chictr.org.cn/showproj.html?proj=166980; the Hospital Research Ethics Committee (approval number: SCMCIRB-K2021086-1, Version 01), approved on 21 January 2022.
Robot-assisted rehabilitation of people with breast cancer developing upper limb lymphedema: protocol of a randomized controlled trial with a 6-month follow‑up
Authors: Arippa Federico , Scribante Andrea , Rocca Barbara , Monticone Marco
Published: November 2023

Upper limb lymphedema (ULLy) is an external (and/or internal) manifestation of lymphatic system insufficiency and deranged lymph transport for more than 3 months and frequently affects people as a consequence of breast cancer (BC). ULLy is often underestimated despite diminished motor skills, mood, and cognitive-behavioral complaints negatively condition the health-related quality of life (HRQoL) of persons. BC can also metastasize to the jawbone, further impacting on the HRQoL. In time, the implementation of robot-assisted rehabilitation (RR) for neurological diseases has grown to improve HRQoL and pain. This study aims to evaluate the effectiveness of a RR program in the treatment of individuals who develop an ULLy; as a further analysis, the study will assess the effectiveness of the same program in people with jawbone metastases from BC who will also develop ULLy. A randomized, parallel-group superiority-controlled trial will be conducted. 44 participants will be randomly allocated to either the experimental (receiving a RR program) or the control group (regular rehabilitation). Both groups will follow individual-based programs three times a week for 10 weeks. The main outcome measure will be the Lymphedema Quality of Life Questionnaire. Secondary outcomes will be a pain intensity numerical rating scale and the Cranio-Facial Pain Disability Inventory. Evaluations are before and after training and 6 months later. Findings may provide evidence on the effectiveness of a RR program on inducing improvements in the HRQoL and pain of individuals with ULLy due to BC. People with ULLy and jawbone metastases from BC are expected for similar or higher improvements as per the same comparisons above. This trial might contribute towards defining guidelines for good clinical rehabilitation routines and might be used as a basis for health authorities’ endorsements.

Trial registration OSF REGISTRIES, osf-registrations-jz7ax-v1. Registered on 26 June 2023.
Efficacy of 3D screens for sustainable mosquito control: a semi-field experimental hut evaluation in northeastern Tanzania
Authors: Kathet Subam , Sudi Wema , Mwingira Victor , Tungu Patrick , Aalto Mikko , Hakala Tomi , Honkala Markku , Malima Robert , Kisinza William , Meri Seppo , Khattab Ayman
Published: November 2023

Background

A three-dimensional window screen (3D-Screen) has been developed to create a window double-screen trap (3D-WDST), effectively capturing and preventing the escape of mosquitoes. A 2015 laboratory study demonstrated the 3D-Screen's efficacy, capturing 92% of mosquitoes in a double-screen setup during wind tunnel assays. To further evaluate its effectiveness, phase II experimental hut trials were conducted in Muheza, Tanzania.

Methods

Three experimental hut trials were carried out between 2016 and 2017. Trial I tested two versions of the 3D-WDST in huts with open or closed eaves, with one version using a single 3D-Screen and the other using two 3D-Screens. Trial II examined the 3D-WDST with two 3D-Screens in huts with or without baffles, while Trial III compared handmade and machine-made 3D structures. Mosquito capturing efficacy of the 3D-WDST was measured by comparing the number of mosquitoes collected in the test hut to a control hut with standard exit traps.

Results

Trial I showed that the 3D-WDST with two 3D-Screens used in huts with open eaves achieved the highest mosquito-capturing efficacy. This treatment captured 33.11% (CI 7.40–58.81) of female anophelines relative to the total collected in this hut (3D-WDST and room collections) and 27.27% (CI 4.23–50.31) of female anophelines relative to the total collected in the control hut (exit traps, room, and verandahs collections). In Trial II, the two 3D-Screens version of the 3D-WDST captured 70.32% (CI 56.87–83.77) and 51.07% (CI 21.72–80.41) of female anophelines in huts with and without baffles, respectively. Compared to the control hut, the capturing efficacy for female anophelines was 138.6% (37.23–239.9) and 42.41% (14.77–70.05) for huts with and without baffles, respectively. Trial III demonstrated similar performance between hand- and machine-made 3D structures.

Conclusions

The 3D-WDST proved effective in capturing malaria vectors under semi-field experimental hut conditions. Using 3D-Screens on both sides of the window openings was more effective than using a single-sided 3D-Screen. Additionally, both hand- and machine-made 3D structures exhibited equally effective performance, supporting the production of durable cones on an industrial scale for future large-scale studies evaluating the 3D-WDST at the community level.

Graphical Abstract
Health-related quality of life in subjective cognitive decline and mild cognitive impairment: a longitudinal cohort analysis
Authors: Aye Sandar , Bouteloup Vincent , Tate Ashley , Wimo Anders , Handels Ron , Jean Delphine , Winblad Bengt , Jönsson Linus
Published: November 2023

Background

Health-related quality of life (HR-QoL) is an important outcome for patients and crucial for demonstrating the value of new treatments. Health utility estimates in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are limited, especially in biomarker-confirmed populations. Besides, little is known about the longitudinal HR-QoL trajectory. This study aims to provide health utility estimates for SCD and MCI and investigate the QoL trajectory along the disease continuum.

Methods

Longitudinal data from 919 SCD and 1336 MCI patients from the MEMENTO cohort were included. SCD was defined as clinical dementia rating (CDR) = 0, and MCI as CDR = 0.5. HR-QoL was measured using the EQ-5D-3L patient-reported instrument. Linear mixed-effect models (LMM) were used to assess the longitudinal change in HR-QoL and identify predictors of these changes.

Results

Baseline health utilities were 0.84 ± 0.16 and 0.81 ± 0.18, and visual analogue scale (VAS) were 75.8 ± 14.82 and 70.26 ± 15.77 in SCD and MCI. In amyloid-confirmed cases, health utilities were 0.85 ± 0.14 and 0.86 ± 0.12 in amyloid-negative and amyloid-positive SCD, and 0.83 ± 0.17 and 0.84 ± 0.16 in amyloid-negative and amyloid-positive MCI. LMM revealed an annual decline in health utility of − 0.015 (SE = 0.006) and − 0.09 (SE = 0.04) in moderate and severe dementia (P < 0.05). There was a negative association between clinical stage and VAS where individuals with MCI, mild, moderate, and severe dementia were on average 1.695 (SE = 0.274), 4.401 (SE = 0.676), 4.999 (SE = 0.8), and 15.386 (SE = 3.142) VAS points lower than individuals with SCD (P < 0.001). Older age, female sex, higher body mass index, diabetes, cardiovascular history, depression, and functional impairment were associated with poor HR-QoL. Amyloid positivity was associated with an annual decline of − 0.011 (SE = 0.004, P < 0.05) health utility over time.

Conclusions

Health utility estimates from this study can be used in economic evaluations of interventions targeting SCD and MCI. Health utility declines over time in moderate and severe dementia, and VAS declines with advancing clinical stages. Amyloid-positive patients show a faster decline in health utility indicating the importance of considering biomarker status in HR-QoL assessments. Future research is needed to confirm the longitudinal relationship between amyloid status and HR-QoL and to examine the level at which depression and IADL contribute to HR-QoL decline in AD.