bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial mutualistic fungus Suillus luteus provided excellent buffering insurance in Scots pine defense responses under pathogen challenge at transcriptome level
Authors: Wen Zilan , Manninen Minna J. , Asiegbu Fred O.
Published: January 2025

Background

Mutualistic mycorrhiza fungi that live in symbiosis with plants facilitates nutrient and water acquisition, improving tree growth and performance. In this study, we evaluated the potential of mutualistic fungal inoculation to improve the growth and disease resistance of Scots pine (Pinus sylvestris L.) against the forest pathogen Heterobasidion annosum.

Results

In co-inoculation experiment, Scots pine seedlings were pre-inoculated with mutualistic beneficial fungus (Suillus luteus) prior to H. annosum infection. The result revealed that inoculation with beneficial fungus promoted plant root growth. Transcriptome analyses revealed that co-inoculated plants and plants inoculated with beneficial fungus shared some similarities in defense gene responses. However, pathogen infection alone had unique sets of genes encoding pathogenesis-related (PR) proteins, phenylpropanoid pathway/lignin biosynthesis, flavonoid biosynthesis, chalcone/stilbene biosynthesis, ethylene signaling pathway, JA signaling pathway, cell remodeling and growth, transporters, and fungal recognition. On the other hand, beneficial fungus inoculation repressed the expression of PR proteins, and other defense-related genes such as laccases, chalcone/stilbene synthases, terpene synthases, cytochrome P450s. The co-inoculated plants did not equally enhance the induction of PR genes, chalcone/stilbene biosynthesis, however genes related to cell wall growth, water and nutrient transporters, phenylpropanoid/lignin biosynthesis/flavonoid biosynthesis, and hormone signaling were induced.

Conclusion

S. luteus promoted mutualistic interaction by suppressing plant defense responses. Pre-inoculation of Scots pine seedlings with beneficial fungus S. luteus prior to pathogen challenge promoted primary root growth, as well as had a balancing buffering role in plant defense responses and cell growth at transcriptome level.
Prenatal diagnosis of mucopolysaccharidosis type I on hepatosplenomegaly and coarse features: a case-report
Authors: Agranier Maxime , Demurger Florence , Dubourg Christele , Fromageot Jerome , Dufour Anne-Sophie Cabaret , Launay Erika , Gournay Magalie , Lefèvre Charles , Froissart Roseline , Pettazzoni Magali , Rollier Paul
Published: January 2025

Background

Mucopolysaccharidosis type I (MPS I - IDUA gene) is a rare autosomal recessive lysosomal storage disorder. Clinical symptoms, including visceral overload, are progressive and typically begin postnatally. Descriptions of hepatosplenomegaly associated with lysosomal pathology are uncommon during the prenatal period. The most prevalent etiologies are infections, anemia, and neoplasms.

Case presentation

A pregnant woman at 26.5 gestational weeks was referred to our center for fetal ultrasound findings of hepatosplenomegaly, distinct facial features, and liver, spleen and thymus echogenic spots. Whole exome sequencing after amniocentesis identified two likely pathogenic IDUA gene variants (in trans), raising suspicion of a diagnosis of MPS I. MPS I was confirmed by the deficiency of α-L-iduronidase activity in amniotic cells. A medical pregnancy termination was carried out due to the severe prognosis. After termination of pregnancy, external examination of the fetus confirmed hepatosplenomegaly and coarse dysmorphic features.

Conclusion

Lysosomal storage diseases (LSD) are a rare cause of prenatal hepatosplenomegaly, but this has not been described in MPS I according to our literature search. The genetic variants identified in this case prompted early diagnosis through genome-wide studies. This rare presentation of MPS I highlights the expanding role of genomic analyses in diagnosing conditions during pregnancy.
Through-tunnel reconstruction with Ligament Augmentation and Reconstruction System (LARS) for managing post-arthroplasty patellofemoral instability
Authors: Chang Jung-Hsiu , Chen Chih-Hui , Li Yi-An
Published: January 2025

Background

Despite advancements in prosthetic designs and surgical techniques, patellar dislocation remains a rare but significant complication following total knee arthroplasty, with an incidence ranging between 0.15% and 0.5%. This condition often requires revision surgery to alleviate discomfort and restore joint function. Among the methods to address patellofemoral instability, medial patellofemoral ligament reconstruction has gained attention. In this case, we present the first report of using the synthetic Ligament Augmentation and Reconstruction System (LARS; Surgical Implants and Devices, Arc-sur-Tille, France) for medial patellofemoral ligament reconstruction following patellar dislocation after total knee arthroplasty, offering a novel approach to avoid donor site morbidity.

Case presentation

An 87-year-old man with no significant comorbidities underwent NexGen posterior-stabilized-total knee arthroplasty (Zimmer Biomet, Warsaw IN) for advanced osteoarthritis in his left knee. Three months postoperatively, he experienced a persistent giving-way sensation and swelling in the knee after a fall. Physical examination revealed patellar subluxation, confirmed by imaging studies. A computed tomography scan showed no malrotation of the femoral or tibial components. The patient was diagnosed with a medial patellar retinacular tear and medial patellofemoral ligament rupture. He underwent medial patellofemoral ligament reconstruction using a Ligament Augmentation and Reconstruction System (LARS; Surgical Implants and Devices, Arc-sur-Tille, France) synthetic ligament, and the medial retinaculum was repaired. After a year of follow-up, the patient reported satisfactory knee stability, with no recurrence of patellar dislocation.

Conclusion

This case demonstrates the successful use of a synthetic Ligament Augmentation and Reconstruction System for Medial patellofemoral ligament reconstruction in managing post-arthroplasty patellar dislocation. It offers a less invasive alternative to autograft harvesting, reducing donor site morbidity while providing effective stabilization of the extensor mechanism. This approach could have significant clinical implications, particularly for elderly patients with compromised bone healing capacity.
Crafting dental specialities in Iran: insights from a qualitative study
Authors: Rojhanian Tayebe , Aryan Kya Michael , Yazdani Shahram , Jadidfard Mohammad-Pooyan
Published: January 2025

Background

Different countries have varying dental specialities, shaped by diverse factors. The determinants influencing the development of these specialities differ between developed and developing countries. This study aimed to explore the factors contributing to the establishment of dental specialities in Iran, a developing country with a wide range of recognised dental specialities.

Methods

A qualitative case study was carried out, involving the review of 25 in-depth interviews and 47 documents. The data were organised using Atlas.ti (version 7.57) software and analysed through content analysis. This process included transcribing the interviews, identifying meaning units, abstracting content, categorising codes, and developing themes.

Results

The results identified three key factors influencing the development of dental specialities in Iran: stakeholders, contextual factors, and the specialisation process. Stakeholders encompass influential figures such as abroad-trained specialists, the government, the Ministry of Health and Medical Education, and scientific associations, along with their position, perceptions, and power. Contextual factors include cultural norms, sociopolitical relationships, political shifts, economic conditions, and academic disciplines. The process of establishing new dental specialities revealed several gaps, including the absence of formal needs assessments, advocacy plans, career planning, effective partnerships, and adequate evaluation mechanisms.

Conclusion

Contextual factors have played a crucial role in shaping dental specialisation in Iran, driving the formation of ideas in this field. Key players, including dentists trained abroad, have significantly influenced this process, often motivated by the desire to mirror practices in other countries. However, it did not address the specific oral health needs of the Iranian population. Due to limited awareness and the cost disparity between specialised and general services, there has been little public demand for dental specialisation. However, the process of establishing these specialities faces significant gaps that need to be addressed.
Sustainable reduction in sound levels on intensive care units through noise management - an implementation study
Authors: Witek Sandra , Schmoor Claudia , Montigel Fabian , Grotejohann Birgit , Ziegler Sven
Published: January 2025

Background

The noise levels in intensive care units usually exceed the recommended limits in (inter)national recommendations. Such noise levels can affect both the recovery of intensive care patients and the performance of staff. The aim of this study was to reduce ward-based noise levels in three intensive care units (anesthesiological, neurological, and neonatological).

Methods

The implementation of a setting-specific intervention bundle consisting of (a) ward-specific guide to noise management, (b) further noise reduction and prevention measures and (c) the use of “noise traffic lights” was evaluated in an implementation study with a pre-post design. Our primary endpoint was changes in sound level (equivalent continuous sound pressure (LAeq)) 12 weeks after the intervention, and the secondary endpoint was sound level (LAeq), peak sound pressure and maximum sound level at different time points, including changes at 24-week follow-up.

Results

After the intervention phase, we observed a significant overall reduction in the sound level of 0.77 decibels (A-weighted) (dB (A)), 95%-CI [0.06, 1.49], p = 0.034 with post-intervention measurements of LAeq1h 56.43 dB (A) compared to pre-intervention measurements of 57.21 dB (A). The difference was particularly large (2.21 dB (A) [p < 0.0001] in one of the three intensive care units. After adjusting our analysis for the intensity of nursing workload, the sound level reduction was smaller. Comparisons of LAeq1h between measurement times during the daytime periods showed a post-interventional difference of 58.28 dB(A) to 58.84 dB(A) baseline during the day of 0.57 dB(A), 95%-CI [-0.07, 1.21], p = 0.08 and at night of 53.36 dB(A) post-interventionally to 54.48 dB(A) baseline a difference of 1.11 dB(A) 95%-CI [0.19, 2.04], p = 0.02. In follow-up, baseline sound levels became realigned and we noted a rise in sound level of 0.81 dB (A) [p = 0.01].

Conclusions

Our implementation study indicates that a bundle of interventions can reduce noise levels in intensive care units, although the clinical relevance of the measured effect must be questioned. Sufficient resources and a participatory approach using an implementation framework should therefore be employed to manage sustainable noise abatement.

Trial registration

German Clinical Trials Register (DRKS): trial registration number: DRKS00025835; Date of registration: 12.08.2021.
Factors influencing trust among colleagues in hospital settings: a systematic review
Authors: Varga Andreea Isabela , Spehar Ivan , Veggeland Frode , Skirbekk Helge
Published: January 2025

Background

Many studies show positive results of collegial trust in the workplace, e.g. performance, innovation and collaboration. However, no systematic review on collegial trust in hospital settings exists. This study aimed to provide the missing overview of factors that positively and negatively influence this trust relationship between healthcare providers.

Methods

Ten information sources (Web of Science, Embase, MEDLINE, APA PsycInfo, CINAHL, Scopus, EconLit, Taylor & Francis Online, SAGE Journals and Springer Link) were searched from database inception up until October 21st, 2022. Empirical studies included were written in English, undertaken in a hospital or similar setting, and addressed collegial trust relationships between healthcare professionals, without date restrictions. Studies were excluded if they only explored trust between healthcare professionals on different hierarchical levels. Theoretical studies, systematic reviews, conceptually unclear papers and anecdotal case studies were also excluded. Records were independently screened for eligibility by at least two researchers. A narrative synthesis technique was adopted to explore and discuss the influencing factors of trust between colleagues identified across both quantitative and qualitative studies. This method was chosen given the inclusion of studies with different research designs and the unsuitability of the data for a meta-analysis or meta-ethnography. Risk of bias was assessed independently by at least two researchers using four critical appraisal tools.

Results

Eight thousand two hundred sixty-eight studies were screened and 11 studies were included. Seven were qualitative and four were quantitative. Themes identified were professional competence, elements of communication, such as tacit knowledge sharing, and ethical conduct, such as honesty, confidentiality and accountability. Moreover, trust among colleagues was seen to thrive in work environments characterised by psychological safety. The results of the quality assessment show that most studies were of an acceptable quality, with some associated risk of bias. One of the limitations was represented by the lack of a definition for trust in some studies, and some inconsistency for those studies that did define trust.

Conclusions

Professionalism, communication and ethics were seen as the most important factors enhancing trust. However, these concepts were defined differently in the studies.

Trial registration

PROSPERO; CRD42023433021.
Associations between class-level factors and student physical activity during physical education lessons in China
Authors: Zhou Yulan , Wang Lijuan , Chen Ruzhuan , Wang Bingnan
Published: January 2025

Background

The purpose of this study is to explore the association between class-level factors, such as lesson start time, class size, lesson location, PE content, and PE context, and student engagement in moderate-to-vigorous physical activity (MVPA) during PE lessons in both elementary and middle schools.

Methods

A total of 284 PE lessons from ten schools in Shanghai, Eastern China, were included in the study. Students’ MVPA during PE lessons was recorded using accelerometry, and lesson context was evaluated using the System for Observing Fitness Instruction Time (SOFIT). Mixed linear regression analysis was applied to assess the association between class-level factors and MVPA during elementary and middle school PE lessons.

Results

Students in elementary school spent 40.3 ± 8.1% of PE lesson time in MVPA, while middle school students spent 40.5 ± 7.1%. Significant relationships were found between MVPA and class-level factors like lesson location, PE content, and PE context. Specifically, elementary school students recorded a higher percentage of MVPA during lessons with team games, individual games, individual activities, and more time spent on skill practice and game play context. In middle schools, higher MVPA was connected to outdoor lessons, a focus on individual games, and more time devoted to fitness context.

Conclusions

Class-level factors may affect students’ MVPA differently depending on the school level, and these modifiable factors should be targeted to increase MVPA time in elementary and middle school PE classes. Future studies should investigate ways to modify these factors, strategically plan lesson time across different contexts, and optimizing PE content to boost MVPA in PE lessons.
Transmantle pressure under the influence of free breathing: non-invasive quantification of the aqueduct pressure gradient in healthy adults
Authors: Liu Pan , Owashi Kimi , Monnier Heimiri , Metanbou Serge , Capel Cyrille , Balédent Olivier
Published: January 2025

Background

The pressure gradient between the ventricles and the subarachnoid space (transmantle pressure) is crucial for understanding CSF circulation and the pathogenesis of certain neurodegenerative diseases. This pressure can be approximated by the pressure difference across the aqueduct (ΔP). Currently, no dedicated platform exists for quantifying ΔP, and no research has been conducted on the impact of breathing on ΔP. This study aims to develop a post-processing platform that balances accuracy and ease of use to quantify aqueduct resistance and, in combination with real-time phase contrast MRI, quantify ΔP driven by free breathing and cardiac activities.

Methods

Thirty-four healthy participants underwent 3D balanced fast field echo (BFFE) sequence and real-time phase contrast (RT-PC) imaging on a 3T scanner. We used the developed post-processing platform to analyse the BFFE images to quantify the aqueduct morphological parameters such as resistance. RT-PC data were then processed to quantify peak flow rates driven by cardiac and free breathing activity (Qc and Qb) in both directions. By multiplying these Q by resistance, ΔP driven by cardiac and breathing activity was obtained (ΔPc and ΔPb). The relationships between aqueduct resistance and flow rates and ΔP driven by cardiac and breathing activity were analysed, including a sex difference analysis.

Results

The aqueduct resistance was 78 ± 51 mPa·s/mm³. The peak-to-peak cardiac-driven ΔP (Sum of ΔPc+ and ΔPc−) was 24.2 ± 11.4 Pa, i.e., 0.18 ± 0.09 mmHg. The peak-to-peak breath-driven ΔP was 19 ± 14.4 Pa, i.e., 0.14 ± 0.11 mmHg. Males had a longer aqueduct than females (17.9 ± 3.1 mm vs. 15 ± 2.5 mm, p < 0.01) and a larger average diameter (2.0 ± 0.2 mm vs. 1.8 ± 0.3 mm, p = 0.024), but there was no gender difference in resistance values (p = 0.25). Aqueduct resistance was negatively correlated with stroke volume and the peak cardiac-driven flow (p < 0.05); however, there was no correlation between aqueduct resistance and breath-driven peak flow rate.

Conclusions

The highly automated post-processing software developed in this study effectively balances ease of use and accuracy for quantifying aqueduct resistance, providing technical support for future research on cerebral circulation physiology and the exploration of new clinical diagnostic methods. By integrating real-time phase contrast MRI, this study is the first to quantify the aqueduct pressure difference under the influence of free breathing. This provides an important physiological reference for further studies on the impact of breathing on transmantle pressure and cerebral circulation mechanisms.
SMORE: spatial motifs reveal patterns in cellular architecture of complex tissues
Authors: Samadi Zainalabedin , Hao Kai , Askary Amjad
Published: January 2025

Deciphering the link between tissue architecture and function requires methods to identify and interpret patterns in spatial arrangement of cells. We present SMORE, an approach to detect patterns in sequential arrangements of cells and examine their associated gene expression specializations. Applied to retina, brain, and embryonic tissue maps, SMORE identifies novel spatial motifs, including one that offers a new mechanism of action for type 1b bipolar cells. Structural signatures detected by SMORE also form a basis for classifying tissues. Together, our method provides a new framework for uncovering spatial complexity in tissue organization and offers novel insights into tissue function.
Developing a knowledge transfer and exchange strategy for a clinical trials unit
Authors: South Annabelle , Terré Torras Berta , Rush Hannah , Goodman Anna , Love Sharon
Published: January 2025

Need for a strategic approach to knowledge transfer and exchange

Late-phase clinical trials and systematic reviews find results that have the potential to improve health outcomes for people. However, there are often delays in these results influencing clinical practice. We developed a knowledge transfer and exchange strategy to support research teams, aiming to identify activities along the research process to maximise and accelerate the research impact.

Our knowledge transfer and exchange strategy

The strategy has five strands of activity across the life-course of our research:

1. Partnerships with external stakeholders (including patient and public involvement, charities, policymakers, healthcare professionals, professional bodies, regulators and industry)

2. Communication (including the development of research impact strategies and use of communication tools and channels)

3. Maximising the scientific value of our studies (including open access, data and sample sharing, and incorporating multi-disciplinary components within studies)

4. Strengthening capacity (including building internal and partner capacity to communicate effectively, and strengthening the capacity of external stakeholders to understand and apply our research).

5. Learning and sharing (evaluating the impact of research, sharing lessons learnt internally and externally)

The strategy has helped trial teams think systematically about impact and was easy to use.

Conclusions

Our strategy helps researchers systematically identify activities which may improve the usefulness and uptake of their study results. While developed in a single trials unit, we think it may be of use to others.
Diagnostic value of dual-layer spectral detector CT parameters for differentiating high- from low-grade bladder cancer
Authors: Chen Li , Xu Lili , Zhang Xiaoxiao , Zhang Jiahui , Bai Xin , Peng Qianyu , Guo Erjia , Lu Xiaomei , Yu Shenghui , Jin Zhengyu , Zhang Gumuyang , Xie Yi , Xue Huadan , Sun Hao
Published: January 2025

Objectives

This study aimed to investigate the diagnostic value of spectral parameters of dual-layer spectral detector computed tomography (DLCT) in distinguishing between low- and high-grade bladder cancer (BCa).

Methods

This single-center retrospective study included pathologically confirmed BCa patients who underwent preoperative contrast-enhanced DLCT. Patients were divided into low- and high-grade groups based on pathology. We measured and calculated the following spectral CT parameters: iodine density (ID), normalized ID (NID), arterial enhancement fraction (AEF), extracellular volume (ECV) fraction, virtual non-contrast (VNC), slope of the attenuation curve, and Z effective (Zeff). Univariate and multivariable logistic regression analyses were used to determine the best predictive factors in differentiating between low- and high-grade BCa. We used receiver operating characteristic curve analysis to assess diagnostic performance and decision curve analysis to determine the net benefit.

Results

The study included 64 patients (mean age, 64 ± 11.0 years; 46 men), of whom 42 had high-grade BCa and 22 had low-grade BCa. Univariate analysis revealed that differences in ID and NID in the corticomedullary phase, AEF, ECV, VNC, and Zeff images were statistically significant (p = 0.001–0.048). Multivariable analysis found that AEF was the best predictor of high-grade tumors (p = 0.006). With AEF higher in high-grade BCa, AEF results were as follows: area under the curve (AUC), 0.924 (95% confidence interval, 0.861–0.988); sensitivity, 95.5%; specificity, 81.0%; and accuracy, 85.9%. The cutoff valve of AEF for predicting high-grade BCa was 67.7%.

Conclusion

Using DLCT AEF could help distinguish high-grade from low-grade BCa.

Critical relevance statement

This research demonstrates that the arterial enhancement fraction (AEF), a parameter derived from dual-layer spectral detector CT (DLCT), effectively distinguishes between high- and low-grade bladder cancer, thereby aiding in the selection of appropriate clinical treatment strategies.

Key Points

This study investigated the value of dual-layer spectral detector CT in the assessment of bladder cancer (BCa) histological grade.

The spectral parameter arterial enhancement fraction could help determine BCa grade.

Our results can help clinicians formulate initial treatment strategies and improve prognostications.

Graphical Abstract
Introducing an index on prediction of post-revascularization cerebral infarction using preoperative CT perfusion parameters in moyamoya disease
Authors: Hao Xiaojun , Zhang Chao , Yang Chen , Zhao Xintong , Zhou Yunfeng , Wang Juan
Published: January 2025

Objective

To determine the value of preoperative CT perfusion (CTP) parameters for prediction of post-revascularization cerebral infarction (post-CI) in adults with moyamoya disease (MMD).

Methods

This retrospective study included 92 adults with MMD who underwent surgical revascularization. Preoperative quantitative CTP parameters, including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to drain (TTD), and transit time to maximum of the residue function (Tmax), along with clinical data, were compared between the groups with and without post-CI. Predictors of post-CI were identified and assessed using multivariable logistic regression and receiver-operating characteristic curve analyses.

Results

Post-CI occurred in 11 patients (12.0%). In univariate analysis, preoperative mean values for CBF, MTT, TTD, Tmax, initial presentation, infarction within the 2 months before surgery, surgical side, and modified Rankin Scale score on admission were associated with post-CI (all p < 0.05). Multivariable logistic regression revealed that the preoperative mean Tmax (OR 2.342, 95% CI: 1.267–4.330, p = 0.007) and infarction within the 2 months before surgery (OR 14.345, 95% CI: 2.108–97.638, p = 0.006) were independent predictors of post-CI. The preoperative mean Tmax produced the largest area under the curve (0.955, 95% CI: 0.914–0.997) with a cutoff of 3.590 s (sensitivity, 100%; specificity, 87.7%).

Conclusions

Adults with MMD are at risk of post-CI when the preoperative mean Tmax is > 3.590 s. Cerebral infarction during the 2 months before revascularization is also a risk factor for post-CI.

Critical relevance statement

Post-CI is a serious complication for adults with MMD following surgical revascularization. The risk of post-CI can be predicted using preoperative CTP parameters, which will assist neurosurgeons with surgical decisions and implementing individualized prophylactic strategies.

Key Points

Predicting the risk of post-CI in MMD patients is beneficial to their prognosis.

The preoperative mean Tmax was an excellent perfusion parameter for predicting post-CI.

Preoperative CTP evaluation can help clinicians make cautious surgical decisions.

Graphical Abstract
Using low-discrepancy points for data compression in machine learning: an experimental comparison
Authors: Göttlich S. , Heieck J. , Neuenkirch A.
Published: January 2025

Low-discrepancy points (also called Quasi-Monte Carlo points) are deterministically and cleverly chosen point sets in the unit cube, which provide an approximation of the uniform distribution. We explore two methods based on such low-discrepancy points to reduce large data sets in order to train neural networks. The first one is the method of Dick and Feischl (J Complex 67:101587, 2021), which relies on digital nets and an averaging procedure. Motivated by our experimental findings, we construct a second method, which again uses digital nets, but Voronoi clustering instead of averaging. Both methods are compared to the supercompress approach of (Stat Anal Data Min ASA Data Sci J 14:217–229, 2021), which is a variant of the K-means clustering algorithm. The comparison is done in terms of the compression error for different objective functions and the accuracy of the training of a neural network.
Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia
Authors: Yang Tingting , Dong Yetian , Zhang Mingming , Feng Jingjing , Fu Shan , Xiao Pingnan , Hong Ruimin , Xu Huijun , Cui Jiazhen , Huang Simao , Wei Guoqing , Kong Delin , Geng Jia , Chang Alex H. , Huang He , Hu Yongxian
Published: January 2025

Background

Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited.

Methods

This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS).

Results

Twenty-three patients with a median age of 58.1 years (range 25.9–75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7–45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively.

Conclusions

Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients.
A machine learning-based model to predict POD24 in follicular lymphoma: a study by the Chinese workshop on follicular lymphoma
Authors: Zha Jie , Chen Qinwei , Zhang Wei , Jing Hongmei , Ye Jingjing , Liu Huanhuan , Yu Haifeng , Yi Shuhua , Li Caixia , Zheng Zhong , Xu Wei , Li Zhifeng , Lin Zhijuan , Ping Lingyan , He Xiaohua , Zhang Liling , Xie Ying , Chen Feili , Sun Xiuhua , Su Liping , Zhang Huilai , Yang Haiyan , Zhao Weili , Qiu Lugui , Li Zhiming , Song Yuqin , Xu Bing
Published: January 2025

Background

Disease progression within 24 months (POD24) significantly impacts overall survival (OS) in patients with follicular lymphoma (FL). This study aimed to develop a robust predictive model, FLIPI-C, using a machine learning approach to identify FL patients at high risk of POD24.

Methods

A cohort of 1,938 FL patients (FL1-3a) from seventeen centers nationwide in China was randomly divided into training and internal validation sets (2:1 ratio). XGBoost was utilized to construct the POD24-predicting model, which was internally validated in the validation set and externally validated in the GALLIUM cohort. Key predictors of POD24 included lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) > ULN, low hemoglobin (Hb), elevated beta-2 microglobulin (β2-MG), maximum standardized uptake value (SUVmax), and lymph node involvement. The FLIPI-C model assigned 2 points to LMR and 1 point to each of the other variables.

Results

The FLIPI-C model demonstrated superior accuracy (AUC) for predicting POD24 and 3-year overall survival (OS) in both the internal (AUC POD24: 0.764, OS: 0.700) and external validation cohorts (AUC POD24: 0.703, OS: 0.653), compared to existing models (FLIPI, FLIPI-2, PRIMA-PI, FLEX). Decision curve analysis confirmed the superior net benefits of FLIPI-C.

Conclusions

Developed using a machine learning approach, the FLIPI-C model offers superior predictive accuracy and utilizes simple, widely available markers. It holds promise for informing treatment decisions and prognostic assessments in clinical practice for FL patients at high risk of POD24.
The hidden rhythms of epilepsy: exploring biological clocks and epileptic seizure dynamics
Authors: Niu Ruili , Guo Xuan , Wang Jiaoyang , Yang Xiaofeng
Published: January 2025

Epilepsy, characterized by recurrent seizures, is influenced by biological rhythms, such as circadian, seasonal, and menstrual cycles. These rhythms affect the frequency, severity, and timing of seizures, although the precise mechanisms underlying these associations remain unclear. This review examines the role of biological clocks, particularly the core circadian genes Bmal1, Clock, Per, and Cry, in regulating neuronal excitability and epilepsy susceptibility. We explore how the sleep-wake cycle, particularly non-rapid eye movement sleep, increases the risk of seizures, and discuss the circadian modulation of neurotransmitters like gamma-aminobutyric acid and glutamate. We explore clinical implications, including chronotherapy which refers to the practice of timing medical treatments to align with the body's natural biological rhythms, such as the circadian rhythm. Chronotherapy aligns anti-seizure medication administration with biological rhythms. We also discuss rhythm-based neuromodulation strategies, such as adaptive deep brain stimulation, which may dynamically change stimulation in response to predicted seizures in patients, provide additional therapeutic options. This review emphasizes the potential of integrating biological rhythm analysis into personalized epilepsy management, offering novel approaches to optimize treatment and improve patient outcomes. Future research should focus on understanding individual variability in seizure rhythms and harnessing technological innovations to enhance seizure prediction, precision treatment, and long-term management.
Millets in India: exploring historical significance, cultural heritage and ethnic foods
Authors: Ankita  , Seth Upasna
Published: January 2025

This review paper offers a comprehensive exploration of the historical significance of millets in India, their role in preserving cultural heritage and embodiment in a diverse array of ethnic foods. In-depth online literature searches were conducted to assess the data, and the information was retrieved from official government reports, journals and books. The study explores the archaeological evidence and historical records of millet cultivation in India, highlighting their importance in Vedic era, ancient civilizations and Mughal rule. Studies showed a diversity of cultures in India and the importance of millets in religious ceremonies, festivals, literature, and folklore, showcasing their deep-rooted presence in Indian traditions. Further, the inclusion of millets in various ethnic dishes of different states demonstrates the diverse culinary applications of millets in India. Recent processing technologies for millet need to be studied for producing various millet-based food products. Additionally, the paper briefly discusses the challenges of millet consumption and promotion in India along with its future prospects. The study suggests that promoting millets and reviving traditional millet-based ethnic food and cultural practices can help preserve India’s rich heritage.
Out of place: thoracic splenosis—a case report
Authors: Becherano Gaston , Podgaetz Eitan , Ahmed Shair , Ringenberg Sigrid , Schwartz Gary
Published: January 2025

Background

Thoracic splenosis is a rare condition where there is ectopic autotransplantation of splenic tissue, typically after traumatic injury of the spleen or splenectomy with or without history of diaphragmatic injury. This diagnosis is noteworthy, as fewer than 100 cases have been documented since its initial description in 1896. Additionally, the patient’s oncological background further complicated the diagnostic process.

Case presentation

We present a case of an asymptomatic 37-year-old male with a past medical history of a right testicular seminoma and a surgical history of splenectomy and left pneumothorax due to a motorcycle accident 18 years prior. During oncological surveillance, a computed tomography (CT) scan of the chest revealed a mediastinal mass, which raised concern for metastatic seminoma or a primary tumor. Surgical removal via a robotic-assisted thoracoscopic approach demonstrated thoracic splenosis.

Conclusions

Thoracic splenosis should be considered as a differential diagnosis of mediastinal masses in patients with history of traumatic spleen injury or splenectomy. Surgical resection may be necessary in oncological cases to rule out metastasis.
PSSR2: a user-friendly Python package for democratizing deep learning-based point-scanning super-resolution microscopy
Authors: Stites Hayden C. , Manor Uri
Published: January 2025

Background

To address the limitations of large-scale high quality microscopy image acquisition, PSSR (Point-Scanning Super-Resolution) was introduced to enhance easily acquired low quality microscopy data to a higher quality using deep learning-based methods. However, while PSSR was released as open-source, it was difficult for users to implement into their workflows due to an outdated codebase, limiting its usage by prospective users. Additionally, while the data enhancements provided by PSSR were significant, there was still potential for further improvement.

Methods

To overcome this, we introduce PSSR2, a redesigned implementation of PSSR workflows and methods built to put state-of-the-art technology into the hands of the general microscopy and biology research community. PSSR2 enables user-friendly implementation of super-resolution workflows for simultaneous super-resolution and denoising of undersampled microscopy data, especially through its integrated Command Line Interface and Napari plugin. PSSR2 improves and expands upon previously established PSSR algorithms, mainly through improvements in the semi-synthetic data generation (“crappification”) and training processes.

Results

In benchmarking PSSR2 on a test dataset of paired high and low resolution electron microscopy images, PSSR2 super-resolves high-resolution images from low-resolution images to a significantly higher accuracy than PSSR. The super-resolved images are also more visually representative of real-world high-resolution images.

Discussion

The improvements in PSSR2, in providing higher quality images, should improve the performance of downstream analyses. We note that for accurate super-resolution, PSSR2 models should only be applied to super-resolve data sufficiently similar to training data and should be validated against real-world ground truth data.
Explainable Machine Learning to Predict Treatment Response in Advanced Non–Small Cell Lung Cancer
Authors: Ahluwalia Vinayak S. , Parikh Ravi B.
Published: January 2025

PURPOSE

Immune checkpoint inhibitors (ICIs) have demonstrated promise in the treatment of various cancers. Single-drug ICI therapy (immuno-oncology [IO] monotherapy) that targets PD-L1 is the standard of care in patients with advanced non–small cell lung cancer (NSCLC) with PD-L1 expression ≥50%. We sought to find out if a machine learning (ML) algorithm can perform better as a predictive biomarker than PD-L1 alone.

METHODS

Using a real-world, nationwide electronic health record–derived deidentified database of 38,048 patients with advanced NSCLC, we trained binary prediction algorithms to predict likelihood of 12-month progression-free survival (PFS; 12-month PFS) and 12-month overall survival (OS; 12-month OS) from initiation of first-line therapy. We evaluated the algorithms by calculating the AUC on the test set. We plotted Kaplan-Meier curves and fit Cox survival models comparing survival between patients who were classified as low-risk (LR) for 12-month disease progression or 12-month mortality versus those classified as high-risk.

RESULTS

The ML algorithms achieved an AUC of 0.701 (95% CI, 0.689 to 0.714) and 0.718 (95% CI, 0.707 to 0.730) for 12-month PFS and 12-month OS, respectively. Patients in the LR group had lower 12-month disease progression (hazard ratio [HR], 0.47 [95% CI, 0.45 to 0.50];
P
< .001) and 12-month all-cause mortality (HR, 0.31 [95% CI, 0.29 to 0.34];
P
< .0001) compared with the high-risk group. Patients deemed LR for disease progression and mortality on IO monotherapy were less likely to progress (HR, 0.53 [95% CI, 0.46 to 0.61];
P
< .0001) or die (HR, 0.30 [95% CI, 0.24 to 0.37];
P
< .001) compared with the high-risk group.

CONCLUSION

An ML algorithm can more accurately predict response to first-line therapy, including IO monotherapy, in patients with advanced NSCLC, compared with PD-L1 alone. ML may better aid clinical decision making in oncology than a single biomarker.
Role of Social Media for Medical Oncologists and Medical Oncology Fellows (SMARTY): An Italian Cross-Sectional Study
Authors: Battaiotto Elena , Valenza Carmine , Garutti Mattia , Molendini Luigi Orlando , Bellio Elena , Trapani Dario , Puglisi Fabio , Pravettoni Gabriella , Buccoliero Luca , Curigliano Giuseppe , Mazza Manuelita
Published: January 2025

PURPOSE

The use of social media is transforming physician-patient communication, mainly in the field of medical oncology. The pattern of social media use by medical oncologists is poorly studied. Therefore, we developed a survey to understand the preferences, experiences, opinions, and expectations of Italian medical oncologists and oncology fellows regarding the use of social media in cancer medicine to identify the different profiles of social media users.

MATERIALS AND METHODS

This multicentric, cross-sectional, observational study included oncologists or oncology fellows from Italy, who were surveyed from July to December 2023 on their use of social media. Data were analyzed through K-means clustering, and the Hartigan-Wong algorithm was applied to identify different profiles of social media users among the participants.

RESULTS

Of the 245 participants who accepted the invitation, 116 completed the entire survey and were included in the cluster analysis. Three profiles of social media users were identified through clustering: the highly social, the social skeptic, and the moderately social, accounting for 31%, 31%, and 38% of the participants, respectively. In general, older age (
P
= .0001), being a specialized oncologist (
P
= .003), and a higher mean time spent on social media (
P
= .0001) were associated with a greater consideration of the professional use of social media.

CONCLUSION

The use of social media among medical oncologists and oncology fellows represents a spectrum ranging from the social skeptic user to the highly social. Age, professional status (specialist or fellow), and frequency on social media use were associated with different patterns, opinions, and behaviors related to social media use.
Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204
Authors: Huang Raymond Y. , Youssef Gilbert , Nelson Thomas , Wen Patrick Y. , Forsyth Peter , Hodi F. Stephen , Margolin Kim , Algazi Alain P. , Hamid Omid , Lao Christopher D. , Ernstoff Marc S. , Moschos Stergios J. , Atkins Michael B. , Postow Michael A. , Reardon David A. , Grootendorst Diederik J. , Leung David , Askelson Margarita , Ritchings Corey , Tawbi Hussein A.
Published: January 2025

PURPOSE

In CheckMate 204, nivolumab + ipilimumab showed high intracranial (IC) objective response rates (icORRs) in patients with melanoma brain metastases (MBMs). Using icORR as a surrogate for overall survival (OS) has prompted use of alternate response criteria. To set the stage for harmonized MBM trials, the aim of this exploratory analysis was to determine icORR using several response criteria and examine correlations of response with survival.

METHODS

Patients (N = 119) with ≥one unirradiated MBMs received nivolumab + ipilimumab every 3 weeks (four doses), followed by nivolumab every 2 weeks for ≤24 months. Blinded review icORR was assessed with modified RECIST (mRECIST), Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM; 5 mm and 10 mm cutoffs), and volumetric criteria (5 mm and 10 mm). Using a 6-week response landmark, IC progression-free survival (icPFS) and OS were compared for responders versus nonresponders.

RESULTS

icORR was higher with mRECIST and volumetric criteria than with RANO-BM or RECIST. mRECIST and volumetric response also showed stronger correlations with icPFS and OS. mRECIST responders who were RANO-BM 5 mm nonresponders (n = 14) had similar OS to RANO-BM 5 mm responders (n = 41). Clinical deterioration affected RANO-BM icORR; however, when assessed only radiographically without deterioration, RANO-BM 5 mm performed similarly to mRECIST. Among 41 patients with target lesions all <10 mm, responder icPFS and OS were similar to those of responders in the total population, indicating that response could be accurately determined in these patients.

CONCLUSION

This analysis supports mRECIST or radiographic-only RANO-BM 5 mm as reliable assessment scales in MBM trials. Volumetric response correlated with survival, supporting its application in future trials. Response could be accurately determined in patients with MBMs all <10 mm, supporting the inclusion of patients with MBMs ≥5 mm in future trials.
Η ελευθερία στην παιδαγωγική σκέψη του John Dewey
Authors: Αλεξάκης Δημήτρης
Published: January 2025

Στην παρούσα εργασία αναλύουμε την ντιουιανή κατανόηση της ελευθερίας στο δημοκρατικό σχολείο αναδεικνύοντας τόσο τα γόνιμα στοιχεία όσο και τα όρια της. Αρχικά εστιάζουμε στην κριτική του Dewey στον αφηρημένο χαρακτήρα της ελευθερίας της βούλησης που υιοθετούν οι παιδοκεντρικές παιδαγωγικές προσεγγίσεις. Στη συνέχεια, επικεντρωνόμαστε στην προσπάθεια του Dewey να διαμορφώσει μια νέα κατανόηση της ελευθερίας, η οποία θα αναδεικνύει τον αντικειμενικό της χαρακτήρα συνδέοντάς την με τον πειραματικό αναστοχασμό και την ανάπτυξη του ατόμου, ενώ εξετάζουμε πως η προοδευτική αγωγή οφείλει να υιοθετήσει τη συγκεκριμένη αντίληψη περί ελευθερίας. Επίσης, επιμένουμε στη σύνδεση της ελευθερίας με τη δημοκρατική κοινότητα στην πολιτική και την παιδαγωγική σκέψη του Dewey, ώστε να αναδείξουμε αφενός την απόσταση του Dewey από τον ατομοκεντρικό φιλελευθερισμό και αφετέρου την αδυναμία του να συνδέσει τη δημοκρατική εκπαίδευση με την κατανόηση της ελευθερίας ως απελευθέρωση από τις καταπιεστικές κοινωνικές συνθήκες.
Ανθρωπόκαινο, δυστοπία και πλανητικός γραμματισμός στη Λογοτεχνία για παιδιά
Authors: Αγγελάκη Ρόζη-Τριανταφυλλιά
Published: January 2025

Το παρόν γεωλογικό χρονικό διάστημα χαρακτηρίζεται ως Ανθρωπόκαινο. Χαρακτηριστικά του είναι η ανθρώπινη κυριαρχία του πλανητικού οικοσυστήματος, η οποία έχει επιφέρει αρνητικές -και σε πολλές περιπτώσεις μη αναστρέψιμες- συνέπειες για τη Γη και τη βιόσφαιρα. Το Ανθρωπόκαινο απασχολεί επιστήμονες από διαφορετικά ερευνητικά πεδία, που προβληματίζονται αναφορικά με τις συνέπειες που θα κληθούν να αντιμετωπίσουν τα παιδιά του μέλλοντος. Στο πλαίσιο της παγκόσμιας κινητοποίησης για μια νέα, ηθική προσέγγιση του φυσικού περιβάλλοντος από τον άνθρωπο και τον κατακερματισμό της ηγεμονικής του θέσης μέσα σε αυτό, συγγραφείς για παιδιά επιχειρούν να καταστήσουν τους ανήλικους αναγνώστες πλανητικά εγγράμματους, εμφυσώντας τους μια ηθική αποστασιοποιημένη από τις οντολογικές και επιστημολογικές παραδοχές που αντιλαμβάνονται τον άνθρωπο ως τον μοναδικό διαμορφωτή του κόσμου. Πολλοί, ωστόσο, δεν επιλέγουν να ρομαντικοποιήσουν τη σχέση του ανθρώπου με τη Φύση, αλλά επιχειρούν να καταπολεμήσουν την περιβαλλοντική του αδρανοποίηση εκθέτοντας την αλήθεια. Στο παρόν άρθρο θα ερευνηθεί πώς σύγχρονοι συγγραφείς παιδικών βιβλία γνώσεων ενημερώνουν τους αναγνώστες για τις γεωλογικές και βιολογικές διεργασίες του πλανήτη και τις πτυχές της περιβαλλοντικής καταστροφής με στόχο να του καλλιεργήσουν περιβαλλοντική συνείδηση, ισορροπώντας μεταξύ δυστοπικής και ευτοπικής γραφής. Η έρευνα βασίζεται στην πρόσφατη βιβλιογραφία για τις μετα-ανθρωπιστικές προσεγγίσεις στην Παιδική Λογοτεχνία, στη θεωρία για τη διαντίδραση οπτικής και λεκτικής αφήγησης και σε εκείνη για τη σημειωτική της εικόνας, καθώς επίσης στην επιστημονική θέση για την ερμηνευτική ανταπόκριση του υπονοούμενου αναγνώστη.