bluuebunny/crossref_metadata_2025 huggingface dataset:
The emotional impact of uncomplicated urinary tract infections in women in China and Japan: a qualitative study
Authors: Yun Zhao , Powell Danielle , Mulgirigama Aruni , Miyazaki Jun
Published: February 2024

Background

Uncomplicated urinary tract infections (uUTIs) are one of the most common community-acquired infections, particularly among women. Common symptoms of UTI include dysuria, urinary urgency and increased frequency, and lower abdominal pain. With appropriate treatment, symptoms may resolve in a few days. However, there is a lack of research on the emotional impact of this disease. We conducted a qualitative, interview-based study to gain a greater understanding of the emotional impact of uUTIs in women in China and Japan.

Methods

A qualitative, exploratory, in-depth, interview-based study was conducted between 19 November 2020 and 25 February 2021. Women aged ≥ 18 years who experienced ≥ 1 uUTI and received antibiotic treatment in the past year were eligible for inclusion. Participants must have experienced ≥ 1 of the following symptoms during a uUTI episode: urinary urgency, frequency, dysuria, or lower abdominal/suprapubic pain. Participants who reported back pain or fever (indicative of complicated UTI) were excluded. Participants with recurrent or sporadic UTIs were included, with specific screening criteria used to ensure capture of both groups. Following a screening call, a structured, in-depth telephone interview (~ 30 min in duration) was conducted by three female external moderators trained in qualitative interviewing, assisted by an interview guide. Interviews were analysed individually and thematically, with the results presented within the identified themes.

Results

A total of 65 women with uUTI completed the in-depth telephone interview: 40 (62%) from China and 25 (38%) from Japan. Participants reported that the symptoms of uUTI affected multiple aspects of their lives, and described feelings of embarrassment, frustration, guilt, dread, and loneliness associated with symptoms that interfered with relationships, work and daily activities, and sleep. Participants reported seeking healthcare from several different points of contact, from local pharmacies to hospitals.

Conclusions

Our analysis highlights the profound emotional impact of uUTIs in women in China and Japan, and the journey these participants take before their initial interaction with a healthcare professional. These insights emphasise the need to better understand the full impact of uUTI, and the role of healthcare professionals in improved patient education and support.
Trainee-supervisor collaboration, progress-visualisation, and coaching: a survey on challenges in assessment of ICU trainees
Authors: Scholte Johannes B. J. , Strehler Johannes C. , Dill Tatjana , van Mook Walther N. K. A.
Published: February 2024

Background

Assessing trainees is crucial for development of their competence, yet it remains a challenging endeavour. Identifying contributing and influencing factors affecting this process is imperative for improvement.

Methods

We surveyed residents, fellows, and intensivists working in an intensive care unit (ICU) at a large non-university hospital in Switzerland to investigate the challenges in assessing ICU trainees. Thematic analysis revealed three major themes.

Results

Among 45 physicians, 37(82%) responded. The first theme identified is trainee-intensivist collaboration discontinuity. The limited duration of trainees’ ICU rotations, large team size operating in a discordant three-shift system, and busy and unpredictable day-planning hinder sustained collaboration. Potential solutions include a concise pre-collaboration briefing, shared bedside care, and post-collaboration debriefing involving formative assessment and reflection on collaboration.

The second theme is the lack of trainees’ progress visualisation, which is caused by unsatisfactory familiarisation with the trainees’ development. The lack of an overview of a trainee’s previous achievements, activities, strengths, weaknesses, and goals may result in inappropriate assessments. Participants suggested implementing digital assessment tools, a competence committee, and dashboards to facilitate progress visualisation.

The third theme we identified is insufficient coaching and feedback. Factors like personality traits, hierarchy, and competing interests can impede coaching, while high-quality feedback is essential for correct assessment. Skilled coaches can define short-term goals and may optimise trainee assessment by seeking feedback from multiple supervisors and assisting in both formative and summative assessment.

Based on these three themes and the suggested solutions, we developed the acronym “ICU-STAR” representing a potentially powerful framework to enhance short-term trainee-supervisor collaboration in the workplace and to co-scaffold the principles of adequate assessment.

Conclusions

According to ICU physicians, trainee-supervisor collaboration discontinuity, the lack of visualisation of trainee’s development, and insufficient coaching and feedback skills of supervisors are the major factors hampering trainees’ assessment in the workplace. Based on suggestions by the survey participants, we propose the acronym “ICU-STAR” as a framework including briefing, shared bedside care, and debriefing of the trainee-supervisor collaboration at the workplace as its core components. With the attending intensivists acting as coaches, progress visualisation can be enhanced by actively collecting more data points.

Trial registration

N/A.
The effectiveness of using situational awareness and case-based seminars in a comprehensive nursing skill practice course for undergraduate nursing students: a quasi-experimental study
Authors: Sun Yuanhao , Li Xiangdong , Liu Haiyang , Li Yuqing , Gui Jiaofeng , Zhang Xiaoyun , Li Xiaoping , Sun Lu , Zhang Lin , Wang Congzhi , Li Jing , Liu Mingming , Zhang Dongmei , Gao Jingyi , Kang Xuefeng , Lei Yunxiao , Yuan Ting
Published: February 2024

Background

Nurses play an important role in healthcare development. The increasing demands for nurses mean that nursing schools at the undergraduate level have the responsibility to ensure patient safety and quality care through a well-designed curriculum. This research aimed to evaluate the effect of the teaching method combined with situational awareness and case-based seminars in a comprehensive nursing skills practice course on the level of self-directed learning, professional identity, academic self-efficacy, theoretical scores, practical scores, teaching satisfaction, and student competence among nursing students.

Methods

The research population comprised was of the grades of 2019 and 2020 at Wannan Medical College in Anhui Province, China (n = 169, response rate 77.88%). The observation group from grade 2020 used the teaching method combined with situational awareness and case-based seminars, whereas the control group from grade 2019 used the traditional teaching mode. General information, self-directed learning, a professional identity, and academic self-efficacy were compared between the two groups. This research used means and standard deviations, chi-square, the Shapiro–Wilk test, and an independent sample t-test for statistical analyses.

Results

Compared with the control group, the total scores for self-directed learning, professional identity, and academic self-efficacy were higher in the observation group (78.80 ± 7.89 vs 60.21 ± 7.44, 63.39 ± 7.87 vs 52.35 ± 7.68, and 22.31 ± 3.30 vs 21.28 ± 2.31, respectively, with P < 0.05 for all scores). More significant improvements were made in the observation group on the level of theoretical scores (81.39 ± 3.32 vs 76.28 ± 5.90) and practical scores (93.32 ± 4.70 vs 90.67 ± 5.09) (P < 0.05). Meanwhile, teaching satisfaction, which includes teaching method (66/18 vs 32/53) and teacher-student interaction (72/12 vs 34/51), and student competence, which includes team cooperation (67/17 vs 39/46), critical thinking (60/24 vs 31/54), and communication skills (67/17 vs 38/47) after the intervention (P < 0.05). There was no significant difference in social persuasion (P > 0.05).

Conclusion

The teaching method combined with situational awareness and case-based seminars in a comprehensive nursing skills practice course has the potential to improve the level of self-directed learning, professional identity, and academic self-efficacy, and it increases theoretical scores, practical scores, teaching satisfaction, and student competence.
Establishment of a risk prediction model for bowel necrosis in patients with incarcerated inguinal hernia
Authors: Zhou Jiajie , Yuan Xiaoming
Published: February 2024

Introduction

Incarceration occurred in approximately 5% to 15% of inguinal hernia patients, with around 15% of incarcerated cases progressing to intestinal necrosis, necessitating bowel resection surgery. Patients with intestinal necrosis had significantly higher mortality and complication rates compared to those without necrosis.The primary objective of this study was to design and validate a diagnostic model capable of predicting intestinal necrosis in patients with incarcerated groin hernias.

Methods

We screened the clinical records of patients who underwent emergency surgery for incarcerated inguinal hernia between January 1, 2015, and December 31, 2022. To ensure balanced representation, the enrolled patients were randomly divided into a training set (n = 180) and a validation set (n = 76) using a 2:1 ratio. Logistic regression analysis was conducted using the rms package in R software, incorporating selected features from the LASSO regression model, to construct a predictive model.

Results

Based on the results of the LASSO regression analysis, a multivariate logistic regression model was developed to establish the predictive model. The predictors included in the model were Abdominal effusion, Hernia Sac Effusion, and Procalcitonin. The area under the receiver operating characteristic (ROC) curve for the nomogram graph in the training set was 0.977 (95% CI = 0.957–0.992). In the validation set, the AUC for the nomogram graph was 0.970. Calibration curve and decision curve analysis (DCA) verified the accuracy and practicability of the nomogram graph in our study.

Conclusion

Bowel necrosis in patients with incarcerated inguinal hernia was influenced by multiple factors. The nomogram predictive model constructed in this study could be utilized to predict and differentiate whether incarcerated inguinal hernia patients were at risk of developing bowel necrosis.
Prediction the prognosis of the poisoned patients undergoing hemodialysis using machine learning algorithms
Authors: Rahimi Mitra , Afrash Mohammad Reza , Shadnia Shahin , Mostafazadeh Babak , Evini Peyman Erfan Talab , Bardsiri Mohadeseh Sarbaz , Ramezani Maral
Published: February 2024

Background

Hemodialysis is a life-saving treatment used to eliminate toxins and metabolites from the body during poisoning. Despite its effectiveness, there needs to be more research on this method precisely, with most studies focusing on specific poisoning. This study aims to bridge the existing knowledge gap by developing a machine-learning prediction model for forecasting the prognosis of the poisoned patient undergoing hemodialysis.

Methods

Using a registry database from 2016 to 2022, this study conducted a retrospective cohort study at Loghman Hakim Hospital. First, the relief feature selection algorithm was used to identify the most important variables influencing the prognosis of poisoned patients undergoing hemodialysis. Second, four machine learning algorithms, including extreme gradient boosting (XGBoost), histgradient boosting (HGB), k-nearest neighbors (KNN), and adaptive boosting (AdaBoost), were trained to construct predictive models for predicting the prognosis of poisoned patients undergoing hemodialysis. Finally, the performance of paired feature selection and machine learning (ML) algorithm were evaluated to select the best models using five evaluation metrics including accuracy, sensitivity, specificity the area under the curve (AUC), and f1-score.

Result

The study comprised 980 patients in total. The experimental results showed that ten variables had a significant influence on prognosis outcomes including age, intubation, acidity (PH), previous medical history, bicarbonate (HCO3), Glasgow coma scale (GCS), intensive care unit (ICU) admission, acute kidney injury, and potassium. Out of the four models evaluated, the HGB classifier stood out with superior results on the test dataset. It achieved an impressive mean classification accuracy of 94.8%, a mean specificity of 93.5 a mean sensitivity of 94%, a mean F-score of 89.2%, and a mean receiver operating characteristic (ROC) of 92%.

Conclusion

ML-based predictive models can predict the prognosis of poisoned patients undergoing hemodialysis with high performance. The developed ML models demonstrate valuable potential for providing frontline clinicians with data-driven, evidence-based tools to guide time-sensitive prognosis evaluations and care decisions for poisoned patients in need of hemodialysis. Further large-scale multi-center studies are warranted to validate the efficacy of these models across diverse populations.
Spanish transcultural adaptation of the 4AT score for the evaluation of delirium in the emergency department: a prospective diagnostic test accuracy study
Authors: Morales-Puerto Marta , Ruiz-Díaz María , García-Mayor Silvia , León-Campos Álvaro , Morales-Asencio José Miguel , Canca-Sánchez José Carlos , Gavira-Guerra Sonia , Toledo-Fernandez Cecilia , Aranda-Gallardo Marta
Published: February 2024

Background

Delirium is one of the most common adverse events in older people during hospitalization, especially in the emergency department. Reliable, easy-to-use instruments are necessary to properly manage delirium in this setting. This study aims to evaluate the diagnostic validity of the Spanish version of the 4 ‘A’s Test (4AT) in the ED.

Methods

A diagnostic accuracy study was conducted in patients over 65 years old admitted to the Emergency Department who did not have a formal diagnosis of dementia or a severe mental health disorder. Face and content validity were evaluated by an expert panel. Emergency nurses performed the evaluation with 4AT, whilst blinded and trained researchers assessed patients with the Revised Delirium Rating Scale as the gold standard. The content validity index, sensitivity, specificity, positive and negative predictive values, likelihood ratios, Youden’s Index and ROC curves were calculated to evaluate the diagnostic accuracy of the instrument.

Results

Of 393 eligible patients, 380 were finally analyzed. Content validity yielded a median content validity index of 4 (interquartile range: 0). The Spanish 4AT sensitivity (95.83%; 95% ECI: 78.9–99.9%), specificity (92.98%; 95% CI: 89.8–95.4%), positive predictive value (47.92%) and negative predictive value (99.7%) were satisfactory. Youden’s index was 0.89. Positive likelihood ratio was 13.65, and negative likelihood ratio 0.045. The area under the curve was 0.97.

Conclusions

The Spanish version of the 4AT for use in the Emergency Departments is easy-to-use and applicable. The validation results indicate that it is a valid instrument with sufficient predictive validity to identify patients at risk of delirium in the Emergency Departments. Moreover, it is a tool that facilitates the management of an adverse event that is associated with increased mortality and morbidity.
Nurses’ views of patient- and family-centered care and its practices in peri-operative contexts in hospitals in Northern Ghana
Authors: Adugbire Bernard Atinyagrika , Jordan Portia Janine , Cornelle Young
Published: February 2024

Background

The purpose of the study was to explore the views of nurses on the concept of patient- and family-centered care (PFCC) and its practices in a peri-operative context in Northern Ghanaian hospitals.

Methods

The study, using a qualitative explorative, descriptive, and contextual research design was conducted at six selected hospitals located in the Northern part of Ghana. Purposive sampling was used to recruit participants for individual and focus group interviews. Data were generated between March and May 2022. Data saturation was reached with 27 participants comprising 15 individuals and 12 members from two focus group interviews. All interviews were digitally recorded and transcribed verbatim and the data analyzed using thematic analysis.

Results

Two themes emerged from the study, namely nurses’ understanding of the concept of PFCC and how they see the benefits of PFCC in a peri-operative context. Subthemes of the nurses’ understanding of PFCC included their perceptions of PFCC, the need for collaboration, supporting the patient’s family for better post-operative and effective communication, and PFCC practices in the peri-operative context. Subthemes for benefits of PFCC in the peri-operative context included nurse-related benefits, patient- and family-related benefits, and healthcare system-related benefits.

Conclusions

The study revealed that the concept of PFCC is unfamiliar to the Ghanaian peri-operative context despite the positive perceptions exhibited by the nurses in terms of their understanding of PFCC and its related benefits to nurses, patients, and families as well as the healthcare system.
Registered nurses’ experiences regarding operational factors influencing the implementation of HIV care services in the mobile health clinics of eThekwini Municipality in KwaZulu-Natal
Authors: Ngcobo Silingene Joyce , Makhado Lufuno , Sehularo Leepile Alfred
Published: February 2024

Background

Registered nurses working in the mobile health clinics (MHCs) play an important role in enabling HIV care access to populations in remote areas through Nurse Initiated Antiretroviral Therapy program (NIMART).

Aim

To explore and describe the nurses’ experiences regarding operational factors influencing the implementation of HIV care services in the mobile health clinics (MHCs) of eThekwini Municipality in KwaZulu Natal.

Methods

Qualitative Exploratory Descriptive (QED) method was used after permission was granted from North-West University Human Research Ethics Committee provincial and local health authorities. Data saturation informed sample size of thirteen MHCs nurses were purposefully sampled to participate. Audio-recorded, semi-structured, online, one-on-one interviews guided by open-ended questions were done for data collection, and including demographic profile. The interview transcripts were analysed using Atlas-TI and SPSS descriptive statistics was used for demographics.

Results

Eleven subthemes emerged under patient-related, nurse-related, and organisational-related themes which influence the operational factors in the MHCs, namely: patient defaulting treatment, lack of privacy, unavailability of phones, stressful and demotivating MHCs, nurses feel unsafe, lack of support from management, lack of budget, unavailability of computers, shortage of medical equipment, shortage of nursing staff and absence of data capturers.

Conclusion

Structured contextual coaching and support program for nurses is imperative to ensure effective and strengthened operations in MHCs, further supported by improvement in human resource for health allocation for MHCs in light of expanding health care programs

Contributions

Evaluation of health care programmes, and human resource for health quality improvement needs in the clinical practice of HIV care of MHCs nurses which advocate for specific policy formulations.
Family members’ experiences of everyday caregiving for a family member living with Parkinson’s disease: a qualitative thematic analysis study
Authors: Fekonja Zvonka , Irgolič Nadja , Vrbnjak Dominika
Published: February 2024

Background

In the daily life of individuals living with Parkinson's disease, their loved ones are crucial. Adapting family members to the patient's condition, support in providing care, and psychosocial adaptations is essential.

Aim

To explore family members' perception of everyday caregiving for a family member living with Parkinson's disease and to describe their role in the care and everyday life.

Methods

In a descriptive, qualitative thematic analysis study, semi-structured interviews were conducted with ten people between the ages of 20 and 70, the closest family members of people living with Parkinson's disease. The analysis of the collected data was carried out using thematic analysis.

Results

We generated the main theme: "Living with a family member with Parkinson’s disease", with associated secondary-level sub-themes: “Response”, “Change”, “Care”, and “Support”. Family members of individuals living with Parkinson's disease frequently encounter similar life situations. The most notable transformation in their daily lives primarily revolves around adapting to various activities.

Conclusions

Family members are the ones who most often take on the role of caregiver and provide help to their loved ones. Many of them accept the disease as a part of everyday life and learn to live with it. It is of fundamental importance that we offer family members the necessary support, knowledge, and involvement in holistic treatment and care.
Organizational characteristics of nursing practice environments related to registered nurses’ professional autonomy and job satisfaction in two Finnish Magnet-aspiring hospitals: structural equation modeling study
Authors: Pursio Katja , Kankkunen Päivi , Mikkonen Santtu , Kvist Tarja
Published: February 2024

Background

Nurses are leaving their profession because of poor personal job satisfaction, heavy workload, and unfavorable work environments with low professional autonomy. Professional autonomy involves the possibility to influence one’s work and have a sense of control – the ability to contribute to a workplace culture and influence how decisions are made. This study explores registered nurses’ perceptions of the nursing practice environment, using the Nursing Work Index-Revised (NWI-R), and its relationships with professional autonomy and job satisfaction.

Methods

A cross-sectional study along with instrument re-validation was conducted using a web-based survey for nurses in two Magnet-aspiring hospitals in Finland in September 2021 (n = 586). Structural equation modeling was used to find out the relationships of the NWI-R components with professional autonomy and job satisfaction.

Results

Principal component analysis and confirmatory factor analysis supported seven components with 34 items. Collegial nurse–doctor relationships, organization’s quality standards, and nursing involvement and expertise sharing (means of 3.23, 2.96, and 2.66, respectively) demonstrated a favorable nursing practice environment; professional nursing standards, nurse management and leadership, staffing and resource adequacy, and professional advancement (means of 2.38, 2.18, 2.15, and 2.13, respectively) demonstrated an unfavorable nursing practice environment. The presented model (RMSEA 0.068, CFI 0.987, TLI 0.946) indicated that nursing involvement and expertise sharing, organization’s quality standards, nurse management and leadership, and collegial nurse–doctor relationships were related to professional autonomy. Nurse management and leadership, staffing and resource adequacy, and organization’s quality standards were related to job satisfaction. Moreover, professional autonomy was related to job satisfaction.

Conclusion

Nurses’ professional autonomy is important due to its relationship with job satisfaction. When factors that increase professional autonomy are taken into account and attention is paid to the promotion of autonomy, it is possible to improve nurses’ job satisfaction. These issues cannot be solved at the unit level; investment is needed at the organizational and political levels. The results introduce nurses, managers, researchers, and stakeholders to improvements in the nursing practice environment toward an organizational culture where nurses may utilize their professional autonomy to its full potential.
Repurposing phone booths into COVID-19 sampling stations: medical operator experiences
Authors: Schoch Martin , Lawanyawatna Sunaree
Published: February 2024

This study investigated the repurposing of phone booths into COVID-19 sampling stations and assessed medical operator experiences in twelve healthcare facilities in Thailand. Amidst the pandemic, these facilities became sampling stations as an emergency measure to enhance medical staff protection. The stations, repurposed from decommissioned phone booths, aimed to reduce COVID-19 infection risks among healthcare workers and patients. After 13 to 16 months of use, a review collected user satisfaction information from each facility. Results indicated high user satisfaction in addressing protection concerns and increasing swab testing participation. This study discusses station design, operational characteristics, and social benefits, emphasizing their adaptability in resource-limited settings. Findings underscore the potential for repurposing infrastructure in public health emergencies and suggest avenues for future research in sustainable healthcare solutions.
Comparison of one-hole split endoscopic discectomy and microendoscopic discectomy in the treatment of lumbar disk herniation: a one-year retrospective cohort study
Authors: Liu Chen , Zhang Wencan , Wang Chongyi , Hu Bingtao , Wang Kaibin , Feng Yunze , Li Le , Xu Wanlong , Si Haipeng
Published: February 2024

Background

We aim to compare and assess the surgical parameters and follow-up information of one-hole split endoscopic discectomy (OSE) and microendoscopic discectomy (MED) in the treatment of LDH.

Methods

This study included 154 patients with degenerative lumbar disk disease. Sixty-eight patients underwent OSE and 86 patients MED. The VAS score for lower back and lower limb radiation pain, ODI score, modified MacNab score, estimated blood loss (EBL), length of the incision, amount of C-reactive protein, and recurrence and complication rates were examined as indicators for clinical outcomes and adverse events.

Results

After surgery, the VAS and ODI scores in the two groups significantly decreased. On the third day after surgery, the VAS and ODI scores of the OSE group were significantly better than those of the MED group. The VAS and ODI scores preoperatively and at 1 month, 3 months, 6 months, and 12 months following the procedure did not substantially vary between the two groups. There was less EBL and a shorter incision with OSE than with MED. There was no significant difference in the rate of complications between the two groups.

Conclusion

Compared with MED, OSE is a new alternative option for LDH that can achieve similar and satisfactory clinical outcomes. Furthermore, OSE has many advantages, including less EBL and a smaller incision. Further clinical studies are needed to confirm the effectiveness of OSE.
Effect of remote ischemic preconditioning on postoperative cognitive dysfunction in adult patients with general anesthesia: a meta-analysis
Authors: Han Mengnan , Du Yanru , Li Jianli , Li Yi , Han Shuang , Li Chong
Published: February 2024

Background

Remote ischemic preconditioning (RIPC) is proven to have neuroprotective protective effects. Nevertheless, the impact of RIPC on postoperative cognitive dysfunction (POCD) in patients undergoing general anesthesia is controversial. This meta-analysis of randomized controlled trials (RCTs) aimed to assess the effect of RIPC on POCD in adults after general anesthesia.

Methods

Relevant literature was obtained by searching Embase, PubMed, Web of Science, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases in July 2022. RCTs were included to assess the influences of RIPC on POCD in adults following general anesthesia. Two investigators independently performed literature screening, data extraction, and quality assessment based on the inclusion and exclusion criteria. The incidence of POCD, operation time, and hospital stay were analyzed by Review manager5.4 software.

Results

Thirteen RCTs with 1122 participants were selected for this meta-analysis. Compared to the control group, RIPC decreased the incidence of POCD (OR = 0.50, 95% CI 0.31–0.82), as well as reduced the duration of hospitalization (MD = − 0.98, 95% CI − 1.69 to − 0.27), but did not prolong operative time (MD = − 2.65, 95% CI − 7.68 to 2.37).

Conclusion

RIPC reduced the incidence of POCD in adult patients after general anesthesia and accelerated their discharge.
Quantification of Proteus syndrome-associated lung disease
Authors: Ours Christopher A. , Buser Anna , Hodges Mia B. , Chen Marcus Y. , Sapp Julie C. , Gochuico Bernadette R. , Biesecker Leslie G.
Published: February 2024

Background

Proteus syndrome is an ultra-rare mosaic overgrowth disorder. Individuals with Proteus syndrome can develop emphysematous and cystic changes of the lung that may lead to progressive respiratory symptoms and require surgical intervention. This retrospective study seeks to quantify the radiographic features of Proteus syndrome-associated lung disease using computed tomography (CT) of the chest. The first method derives a Cystic Lung Score (CLS) by using a computer-aided diagnostic tool to quantify the fraction of cystic involvement of the lung. The second method yields a Clinician Visual Score (CVS), an observer reported scale of severity based on multiple radiographic features. The aim of this study was to determine if these measurements are associated with clinical symptoms, pulmonary function test (PFT) measurements, and if they may be used to assess progression of pulmonary disease.

Results

One hundred and thirteen imaging studies from 44 individuals with Proteus syndrome were included. Dyspnea and oxygen use were each associated with higher CLS (p = 0.001 and < 0.001, respectively) and higher CVS (p < 0.001 and < 0.001). Decreases in percent predicted FVC, FEV1, and DLCO each correlated with increased CLS and CVS. The annual increase of CLS in children, 5.6, was significantly greater than in adults, 1.6. (p = 0.03). The annual increase in CVS in children, 0.4, was similar to adults, 0.2 (p = 0.36).

Conclusions

Proteus syndrome-associated lung disease is progressive. The rate of cystic progression is increased in children. Increased scores in CLS and CVS were associated with clinical symptoms and decreased pulmonary function. Both methods were able to detect change over time and were associated with clinically meaningful outcomes which may enable their use in interventional studies.
Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders
Authors: Wayhelova Marketa , Vallova Vladimira , Broz Petr , Mikulasova Aneta , Smetana Jan , Dynkova Filkova Hana , Machackova Dominika , Handzusova Kristina , Gaillyova Renata , Kuglik Petr
Published: February 2024

Background

Neurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality of intellectual and social abilities and common daily functioning. The rapid development of exome sequencing (ES) techniques, together with trio-based analysis, nowadays leads to up to 50% diagnostic yield. Therefore, it is considered as the state-of-the-art approach in these diagnoses.

Results

In our study, we present the results of ES in a cohort of 85 families with 90 children with severe NDDs and MCAs. The interconnection of the in-house bioinformatic pipeline and a unique algorithm for variant prioritization resulted in a diagnostic yield of up to 48.9% (44/90), including rare and novel causative variants (41/90) and intragenic copy-number variations (CNVs) (3/90). Of the total number of 47 causative variants, 53.2% (25/47) were novel, highlighting the clinical benefit of ES for unexplained NDDs. Moreover, trio-based ES was verified as a reliable tool for the detection of rare CNVs, ranging from intragenic exon deletions (GRIN2A, ZC4H2 genes) to a 6-Mb duplication. The functional analysis using PANTHER Gene Ontology confirmed the involvement of genes with causative variants in a wide spectrum of developmental processes and molecular pathways, which form essential structural and functional components of the central nervous system.

Conclusion

Taken together, we present one of the first ES studies of this scale from the central European region. Based on the high diagnostic yield for paediatric NDDs in this study, 48.9%, we confirm trio-based ES as an effective and reliable first-tier diagnostic test in the genetic evaluation of children with NDDs.
Inhibition of choline metabolism in an angioimmunoblastic T-cell lymphoma preclinical model reveals a new metabolic vulnerability as possible target for treatment
Authors: Krug Adrien , Tosolini Marie , Madji Hounoum Blandine , Fournié Jean-Jacques , Geiger Roger , Pecoraro Matteo , Emond Patrick , Gaulard Philippe , Lemonnier François , Ricci Jean-Ehrland , Verhoeyen Els
Published: February 2024

Background

Angioimmunoblastic T-cell lymphoma (AITL) is a malignancy with very poor survival outcome, in urgent need of more specific therapeutic strategies. The drivers of malignancy in this disease are CD4+ follicular helper T cells (Tfh). The metabolism of these malignant Tfh cells was not yet elucidated. Therefore, we decided to identify their metabolic requirements with the objective to propose a novel therapeutic option.

Methods

To reveal the prominent metabolic pathways used by the AITL lymphoma cells, we relied on metabolomic and proteomic analysis of murine AITL (mAITL) T cells isolated from our established mAITL model. We confirmed these results using AITL patient and healthy T cell expression data.

Results

Strikingly, the mAITL Tfh cells were highly dependent on the second branch of the Kennedy pathway, the choline lipid pathway, responsible for the production of the major membrane constituent phosphatidylcholine. Moreover, gene expression data from Tfh cells isolated from AITL patient tumors, confirmed the upregulation of the choline lipid pathway. Several enzymes involved in this pathway such as choline kinase, catalyzing the first step in the phosphatidylcholine pathway, are upregulated in multiple tumors other than AITL. Here we showed that treatment of our mAITL preclinical mouse model with a fatty acid oxydation inhibitor, significantly increased their survival and even reverted the exhausted CD8 T cells in the tumor into potent cytotoxic anti-tumor cells. Specific inhibition of Chokα confirmed the importance of the phosphatidylcholine production pathway in neoplastic CD4 + T cells, nearly eradicating mAITL Tfh cells from the tumors. Finally, the same inhibitor induced in human AITL lymphoma biopsies cell death of the majority of the hAITL PD-1high neoplastic cells.

Conclusion

Our results suggest that interfering with choline metabolism in AITL reveals a specific metabolic vulnerability and might represent a new therapeutic strategy for these patients.
Galectin-3 and cancer immunotherapy: a glycobiological rationale to overcome tumor immune escape
Authors: Scafetta Giorgia , D’Alessandria Calogero , Bartolazzi Armando
Published: February 2024

Immunotherapy with checkpoint inhibitors (ICIs) has radically changed the landscape of therapeutic opportunities in oncology, but much still needs to be understood from a mechanistic point of view. There is space for further improving tumors’ response to ICIs, as supported by a strong biological rationale. For this achievement a detailed analysis of tumor cell phenotype with functional dissection of the molecular interactions occurring in the TME is required. Galectin-3 is a pleiotropic tumor relevant molecule, which deserves particular attention in immuno-oncology. Due to its ability to finely modulate immune response in vivo, Galectin-3 is a potential target molecule to be considered for overcoming tumor immune escape.
Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis
Authors: Hong Wangbing , Xiong Zhenfang , Wang Xin , Liao Xincheng , Liu Mingzhuo , Jiang Zhengying , Min Dinghong , Li Jiaqi , Guo Guanghua , Fu Zhonghua
Published: February 2024

Background

The prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs.

Methods

Diabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson’s trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells.

Results

The lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR‑126‑3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect.

Conclusion

Decreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.
Kimura’s disease: a case report
Authors: Anbessie Zablon Mesfin
Published: February 2024

Background

Kimura’s disease is a rare chronic inflammatory disorder of unknown etiology that is seen in people of Asian descent. It is characterized by head and neck subcutaneous nodules along with lymphadenopathy, which is usually solitary but can be generalized. It is diagnosed histopathologically by the proliferation of blood vessels and germinal centers in lymphoid follicles, along with variable degrees of fibrosis and extensive eosinophil infiltration. Its localized form is treated with surgical excision, while generalized lesions and those that do not respond to surgical excision can be managed with steroids or radiotherapy.

Case

In this report, we present the first case of Kimura’s disease in the Ethiopian literature in a 40-year-old Ethiopian man that presented with generalized pruritic subcutaneous nodules and lymphadenopathy, which were effectively managed with a tapering course of prednisolone, and a relapse that showed good sustained response with slow steroid taper.

Conclusion

We have demonstrated that, even though it is very rare in the African continent, Kimura’s disease is to be considered as a differential diagnosis for patients that present with subcutaneous nodules and lymphadenopathy. We also have demonstrated that relapses can be effectively managed with reinitiation of the same dose of steroids but with a very slow taper.
The image quality and feasibility of solitary delayed [68 Ga]Ga-PSMA-11 PET/CT using long field-of-view scanning in patients with prostate cancer
Authors: Yu Xiaofeng , Xu Lian , Huang Gang , Liu Jianjun , Chen Ruohua , Chen Yumei
Published: February 2024

Background

Previous studies have demonstrated that delayed [68 Ga]Ga-PSMA PET/CT imaging improves lesion detection compared to early [68 Ga]Ga-PSMA PET/CT in patients with prostate cancer. However, the sole use of delayed [68 Ga]Ga-PSMA PET/CT has been limited due to the insufficient number of photons obtained with standard PET/CT scanners. The combination of early and delayed [68 Ga]Ga-PSMA standard PET/CT may be considered, and it is challenging to incorporate into a high-demand clinical setting. Long field-of-view (LFOV) PET/CT scanners have higher sensitivity compared to standard PET/CT. However, it remains unknown whether the image quality of solitary delayed [68 Ga]Ga-PSMA LFOV PET/CT imaging is adequate to satisfy clinical diagnostic requirements. Therefore, the purpose of this study was to evaluate the image quality of delayed [68 Ga]Ga-PSMA LFOV PET/CT and examine the feasibility of utilizing delayed [68 Ga]Ga-PSMA LFOV PET/CT imaging alone in patients with prostate cancer.

Methods

The study sample consisted of 56 prostate cancer patients who underwent [68 Ga]Ga-PSMA-11 LFOV PET/CT scanning between December 2020 and July 2021. All patients were subjected to early LFOV PET/CT imaging at 1-h post-injection as well as delayed LFOV PET/CT imaging at 3-h post-injection using [68 Ga]Ga-PSMA-11. The image quality and diagnostic efficiency of solitary delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT imaging was analyzed.

Results

The results showed that delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT yielded satisfactory image quality that fulfilled clinical diagnostic benchmarks. Compared to early imaging, delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT demonstrated heightened lesion SUVmax values (11.0 [2.3–193.6] vs. 7.0 [2.0–124.3], P < 0.001) and superior tumor-to-background ratios (3.3 [0.5–62.2] vs. 1.7 [0.3–30.7], P < 0.001). Additionally, delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT detected supplementary lesions in 14 patients (25%) compared to early imaging, resulting in modifications to disease staging and management plans.

Conclusions

In summary, the findings indicate that the image quality of delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT is satisfactory for meeting clinical diagnostic prerequisites. The use of solitary delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT imaging in prostate cancer simplifies the examination protocol and improves patient compliance, compared to [68 Ga]Ga-PSMA-11 standard PET/CT which necessitates both early and delayed imaging.
Risk of treatment-altering haematological toxicity and its dependence on bone marrow doses in peptide receptor radionuclide therapy
Authors: Persson Märta , Hindorf Cecilia , Ardenfors Oscar , Larsson Martin , Nilsson Joachim N.
Published: February 2024

Background

Peptide receptor radionuclide therapy is effective in treating neuroendocrine tumours, but treatment may be limited by kidney and bone marrow toxicity. In this work, the absorbed dose burden to the bone marrow was estimated using image-based dosimetry and its potential use for predicting treatment-altering toxicity was studied. Peripheral blood samples taken before and after 229 treatments with 177Lu-DOTATATE in 59 patients were studied. In connection to the treatments, a total of 940 blood sample occasions provided data on white blood cell, neutrophil granulocyte, platelet, erythrocyte and haemoglobin concentrations. SPECT/CT image data were collected at two or three time points after each treatment. Absorbed doses to bone marrow were calculated from the activity concentration in a metastasis-free lumbar vertebra. The rate of delayed and aborted treatments was analysed based on medical records.

Results

The average absorbed dose to the bone marrow was 0.42 Gy (median 0.33 Gy, SD 0.27 Gy) per treatment. Dose–response relationships between white blood cells, neutrophil granulocytes and haemoglobin concentrations were observed, most prominently at 31–45 days after each treatment. The correlations were stronger in patients with skeletal metastases. The rates of haematological toxicity-related delays and aborted treatments were 6% and 12%, respectively. None of the studied bone marrow dosimetric parameters could clearly predict treatment-related toxicity. However, patients with skeletal metastases had higher risk of treatment-altering toxicity (odds ratio = 6.0).

Conclusions

Treatment-altering haematological toxicity in peptide receptor radionuclide therapy is relatively rare and appears difficult to fully predict from post-therapeutic image-based dosimetry. However, for patients with skeletal metastases, the haematological dose–response relationships are stronger. Future studies may focus on this patient group, to further investigate the usefulness of dosimetry in predicting decreases in blood values.
Infinitely many solutions for quasilinear Schrödinger equation with concave-convex nonlinearities
Authors: Chen Lijuan , Chen Caisheng , Chen Qiang , Wei Yunfeng
Published: February 2024

In this work, we study the existence of infinitely many solutions to the following quasilinear Schrödinger equations with a parameter α and a concave-convex nonlinearity: $$\begin{aligned}& -\Delta _{p}u+V(x) \vert u \vert ^{p-2}u-\Delta _{p}\bigl( \vert u \vert ^{2\alpha}\bigr) \vert u \vert ^{2\alpha -2}u= \lambda h_{1}(x) \vert u \vert ^{m-2}u+h_{2}(x) \vert u \vert ^{q-2}u, \\& \quad x\in {\mathbb{R}}^{N}, \end{aligned}$$

−

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+
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(
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)
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−

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)

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−
2

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=
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1

(
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)
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u

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−
2

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+

h
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(
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)
|
u

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−
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,

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∈

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,

where $\Delta _{p}u=\operatorname{div}(|\nabla u|^{p-2}\nabla u)$

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=
div
(

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, $1< p< N$
1
<
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<
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, $\lambda \ge 0$
λ
≥
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, and $1< m< p<2\alpha p<q<2\alpha p^{*}=\frac{2\alpha pN}{N-p}$
1
<
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−
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. The functions $V(x)$
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(
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, $h_{1}(x)$

h
1

(
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, and $h_{2}(x)$

h
2

(
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)
satisfy some suitable conditions. Using variational methods and some special techniques, we prove that there exists $\lambda _{0}>0$

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>
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such that Eq. (0.1) admits infinitely many high energy solutions in $W^{1,p}({\mathbb{R}}^{N})$

W

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,
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provided that $\lambda \in [0,\lambda _{0}]$
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[
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.