bluuebunny/crossref_metadata_2025 huggingface dataset:
Carfilzomib Prescribing Patterns and Outcomes for Relapsed or Refractory Multiple Myeloma: A Real-World Analysis
Authors: Kaur Gurbakhash , Dong Sharlene , Banerjee Rahul , Khan Adeel , Wang Mengru , Wang Xiaoliang , Afghahi Anosheh , Afrough Aimaz , Janakiram Murali , Wang Bo , Cowan Andrew , Sperling Adam , Anderson Larry , Rajkumar S
Published: October 2024

Despite the widespread use of carfilzomib (K) in relapsed/refractory multiple myeloma (RRMM), there is no consensus on optimal K dose in milligrams per square meter (mg/m2) or dosing schedule. We assessed three modern K prescribing patterns in RRMM using a large United States electronic health record-derived database. Our final cohort (n = 486) included 136 patients (28.0%) who received K 56 mg/m2 once weekly (K56-1x), 86 (17.7%) who received 56 mg/m2 twice weekly (K56-2x), and 264 (54.3%) who received 70 mg/m2 once weekly (K70-1x). Between 2016 and 2023, once-weekly dosing became more common: K70-1x proportions changed from 21.1% in 2016 to 50.6% in 2023, K56-1x from 15.8% to 37.0%, and K56-2x from 63.2% to 12.3%. Median real-world progression-free survival was 13.0 months [95% confidence interval (CI) 11.2-20.7] for K56-1x, 13.2 months (95% CI 9.0-28.1 months) for K56-2x, and 10.9 months (95% CI 9.9-15.3 months) for K70-1x; these differences were not statistically significant (log-rank p = 0.46). The prevalence of heart failure was comparable (<5% in all cohorts). In summary, our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of time toxicity from frequent infusions.
Brain Metabolism in Pre-frontal Cortex and Insula Areas in Patients With Occlusal Splint for Temporomandibular Muscle Disorders
Authors: Cabezas-Bernhardt Gerson Oswaldo , Villavicencio-Caparo Ebingen , Tay Lidia Yileng
Published: October 2024

Background: There is a relationship between anxiety/depression and the development of disorders in the temporomandibular joint (TMJ), but it is unknown whether treatment for these conditions could have any effect on emotional symptoms. The aim of the present study was to compare brain metabolism in the prefrontal cortex and insula before and after occlusal splint placement in patients with TMJ muscle disorders with anxiety and/or depression. Methods: An experimental study evaluated 23 patients with anxiety and/or depression confirmed by the Hospital Anxiety and Depression Scale (HADS) questionnaire and with TMJ muscle disorders diagnosed by means of clinical examination and the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire. (RDC/TMD), an occlusal splint was then made for condylar decompression 2 mm greater than the mandibular rest space, as confirmed by panoramic radiography before and after the placement of the occlusal splint. Brain metabolism in response to a positive or negative stimulus was evaluated by functional magnetic resonance imaging (fMRI), both with and without occlusal splints.
Results: In both the prefrontal cortex and insula, a statistically significant difference (p <0.001 Wilcoxon test) was found between the stimulus reading without a splint and the stimulus reading with an occlusal splint.
Conclusion: There was a significant difference in brain metabolism in both the prefrontal cortex and insula area, either with positive or negative stimulation before and after occlusal splint placement, between patients with TMJ muscle disorders.
TCF7L2 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through activating the PI3K/AKT signaling pathway in colorectal carcinoma
Authors: Cheng Yong , Tang Kang , Gong Jianping , Li Yang
Published: October 2024

Hypoxia is a critical pathogenic factor in cancer development and metastasis. The pivotal role of hypoxia-inducible factor 1α (HIF-1α) in tumor progression under hypoxic conditions is well-documented. However, the specific mechanisms by which HIF-1α contributes to colorectal cancer (CRC) progression remain inadequately elucidated. In this study, we observed an upregulation of Transcription Factor 7-like 2 (TCF7L2) in CRC cells under hypoxic conditions. Meanwhile, hypoxia-induced overexpression of TCF7L2 plays a pivotal role in the proliferation, apoptosis, cell cycle arrest, migration, invasion, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) characteristics of colorectal cancer (CRC) cells in vitro. Additionally, our findings indicate that the inhibition of TCF7L2 results in a significant reduction of tumor growth in vivo. Mechanistically, hypoxia-induced up-regulation of TCF7L2 expression occurs in a HIF-1α-dependent manner. Chromatin immunoprecipitation (ChIP) assays demonstrated increased HIF-1α binding to the promoter sequence of TCF7L2 following hypoxic stimulation. Furthermore, our findings indicate that TCF7L2 plays an oncogenic role in colorectal cancer (CRC) by activating the PI3K/AKT signaling pathway. Additionally, we observed that elevated expression levels of both HIF-1α and TCF7L2 in CRC specimens are associated with aberrant clinicopathological features. Co-expression of TCF7L2 and HIF-1α predicts a poor prognosis in CRC patients. Targeting TCF7L2 is a promising approach to colorectal cancer therapy.
Establishment of a nomogram prediction model for severe primary lower limb lymphedema
Authors: Li Xingpeng , Zhang Yimeng , Liu Mengke , Wang Jingru , Guo Jia , Ren Jie , Shen Wenbin , Yue Yunlong , Wang Rengui
Published: October 2024

Background
The International Society of Lymphology (ISL) guidelines have established grading criteria for primary lower limb lymphedema (PLEL), but there is a lack of model on a unified standard for assessing the severity of the disease.
Purpose
The aim of this study was to establish and validate a predictive model for evaluating severe PLEL.
Methods and Materials:
This retrospective study included 226 patients with unilateral PLEL from 2018 to 2023, who were divided into non-severe (143 cases) and severe (83 cases) groups according to the ISL grading criteria. The two groups of patients had a total of 26 MRI and 15 clinical features recorded. One-way ANOVA was performed first, followed by multi-factor ANOVA, and logistic regression was used to construct a nomogram prediction model. The model’s performance was evaluated via the area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis, and internal validation.
Results
The predictive model identified six independent risk factors associated with the severity of PLEL, including the parallel line sign, crescent sign, longitudinal range, band sign thickness, fat area, and fat diameter. The nomogram model established based on the above six factors predicts a training set AUC of 0.908 (95% CI: 0.868–0.947) for severe PLEL, with a sensitivity of 0.868, specificity of 0.832, accuracy of 0.845, precision of 0.75. The AUC of the validation set was 0.891 (95% CI: 0.847 ~ 0.935), the sensitivity was 0.831, the specificity was 0.825, the accuracy was 0.827, the precision was 0.734. In decision curve analysis, more net benefit can be achieved when the threshold probability is between 1% and 90%.
Conclusions
The severity risk prediction model based on MRI and clinical practice has good discriminatory power and accuracy in evaluating the severity of PLEL which can provide a reference for individualized clinical prediction of PLEL.
Two dramatically different clinical scenarios of neonatal Echovirus-11 infection in late preterm male twins: a case report and review of the literature
Authors: Perniciaro Simona , Proietti Caterina , bossi Angela , maragliano Roberta , facco Carla , novazzi Federica , mancini Nicasio , agosti Massimo Agostino
Published: October 2024

Background
Enterovirus is a well-known cause of infection in all age groups, with particular importance for neonates with both vertically and horizontally transmission. Neonatal clinical manifestations are highly variable and mostly is asymptomatic, but severe infections are described such as myocarditis, meningitis, encephalitis, hepatitis, coagulopathy, pneumonia and viral sepsis.
Since 2022, The World Health Organization (WHO) has recently reported an increasing number of severe neonatal infection associated with a new variant of Echovirus 11 (E-11).
Many of the infants described with E-11infections in a case reports series were preterm, male and twins. Despite the criticality of neonatal disease, the clinical management remains primarily supportive and therapeutic options are unfortunately few.
Case presentation
We present the case of male dichorionic diamniotic (DCDA) late-preterm twins, born in December 2023 at Filippo del Ponte Hospital in Varese (Northen Italy) with early Echovirus 11 infection. They had two dramatically different clinical scenarios and one of them developed a severe and fatal hemorrhage-hepatitis syndrome.
Conclusion
Our experience has the purpose to emphasize public health attention to Echovirus 11 neonatal infections and their rare dramatically neonatal clinical presentations. Prematurity, host genetic predisposition and vertical transmission seem to be strong risk factors for severe infections, but it still need to be elucidated. According toprevious Italian report, a surveillance protocols in all cases with unexpected clinical presentations and sequencing complete genome in order to better understand typing and molecular characterization of emerging and re-emerging pathogenic variants and new strains are strongly recommend in Italy.
ECMO support may be associated with improved survival in tuberculosis associated severe ARDS
Authors: Nalbant Bahar , Buhlmann Alix , Wild Lennart , Bode Christian , David Sascha , Seeliger Benjamin , Stahl Klaus
Published: October 2024

Background
Data describing outcome of extracorporeal membrane oxygenation (ECMO) support in Tuberculosis (Tbc)-associated acute respiratory distress syndrome (ARDS) remain sparce and are mostly confined to singular case reports. The aim of this case series was to analyze intensive care unit (ICU) survival in patients with Tbc-associated ARDS receiving ECMO support and to compare those to patients not receiving ECMO.
Case presentation
ICU survival was analyzed retrospectively in 14 patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years, of which eight patients received additional veno-venous (vv) ECMO support and six standard care only.
ICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n=5/8) compared to those that did not (16.7%, n=1/6) (p=0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023-0.689), p=0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11-26) and 37 (27-53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients.
Discussion and Conclusions:
This retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery.
What patients and their families want to know before and after ICU tour for lung cancer surgery: a qualitative study
Authors: CHEN Dihong , DIAO Li , YANG Qianxue , PENG Tingting , FAN Yaxu , YUAN Lei , LIU Yan , TIAN Yongming , TAO Wenjuan
Published: October 2024

Background:Information asymmetry between healthcare providers and patients leads to low treatment participation and compliance, low admission satisfaction, and medical disputes. To provide a comprehensive understanding of the information needs of patients who undergoing lung cancer surgery before entering the intensive care unit (ICU), as well as the information needs from their caregivers.Methods:Under a qualitative study design, 27 lung cancer surgery patients and their family members in the Lung Cancer Center of West China Hospital of Sichuan University were selected by purposive sampling for semi-structured interviews. Content analysis was employed using NVivo12.0 software.Results: By extracting the important nodes in the semi-structured interview, the information needs of patients with lung cancer surgery and their family members were divided into two first-level nodes, four second-level nodes, and 13 third-level nodes to construct the ICU pre-experience information demand model.Conclusion:Patients undergoing lung cancer surgery and their families have limited access to ICU information, and medical personnel happen to be the main source of information support.Implications:Based on the findings of this study, an ICU pre-experience model will beexplored and established based on the information needs of patients and their families during the peri-ICU period as the benchmark and the key nodes of patients' treatment in the ICU as the time axis to decrease the anxiety of patients and their families, reduce medical disputes, and bolster their satisfaction with ICU nursing work.Reporting Method (if applicable):This study adhered the SRQR guidelines.Patient or Public Contribution:Overall,27 lung cancer patients and their family members were selected through purposive sampling.
Clinical predictive model of new-onset atrial fibrillation in patients with acute myocardial infarction after percutaneous coronary intervention
Authors: Wu Xiao-Dan , zhao Wei , Wang Quan-Wei , Yang Xin-Yu , Wang Jing-Yue , Yan Shuo , Tong Qian
Published: October 2024

Background
New-onset atrial fibrillation (NOAF) is associated with increased morbidity and mortality. Despite identifying numerous factors contributing to NOAF, the underlying mechanisms remain uncertain. This study introduces the triglyceride-glucose index (TyG index) as a predictive indicator and establishes a clinical predictive model.
Materials and Methods
We included 551 patients with acute myocardial infarction (AMI) without a history of atrial fibrillation (AF). These patients were divided into two groups based on the occurrence of postoperative NOAF during hospitalization: the NOAF group (n = 94) and the sinus rhythm (SR) group (n = 457). We utilized a regression model to analyze the risk factors of NOAF and to establish a predictive model. The predictive performance, calibration, and clinical effectiveness were evaluated using the receiver operational characteristics (ROC), calibration curve, decision curve analysis, and clinical impact curve.
Results
94 patients developed NOAF during hospitalization. TyG was identified as an independent predictor of NOAF and was significantly higher in the NOAF group. Left atrial (LA) diameter, age, the systemic inflammatory response index (SIRI), and creatinine were also identified as risk factors for NOAF. Combining these with the TyG to build a clinical prediction model resulted in an area under the curve (AUC) of 0.780 (95% CI: 0.888, 0.358). The ROC, calibration curve, decision curve, and clinical impact curve demonstrated that the performance of the new nomogram was satisfactory.
Conclusion
By incorporating the TyG index into the predictive model, NOAF after AMI during hospitalization can be effectively predicted. Early detection of NOAF can significantly improve the prognosis of AMI patients.
Association between the monocyte-to-high-density lipoprotein cholesterol ratio and adult psoriasis: evidence from the NHANES
Authors: xue zhiwei , Liu Peng , Cao Jian , Mou Jian-Hui , Wang Rui
Published: October 2024

Background
Psoriasis is a representative chronic inflammatory and hereditary disease. There was a significant association between the monocyte to high-density lipoprotein cholesterol (MHR) ratio and the psoriasis area and severity index (PASI) score. The correlation between MHR and psoriasis has not been well investigated. The authors sought to examine the correlation between the MHR and psoriasis in adult individuals living in the U.S.
Methods
This study used cross-sectional data from the NHANES conducted between 2009 and 2014. The data included information on persons aged 20 years or older in the U.S. Sample-weighted logistic regression and stratified subgroup analysis were employed.
Results
This study analyzed a total of 15,895 participants. There is a positive correlation between an increased MHR and a greater occurrence of psoriasis. When other confounding variables were controlled for, a significant correlation between the MHR and psoriasis was found (OR,1.364;95%CI，1.026-1.815). Based on subgroup analysis and interaction testing (p for interaction > 0.05), no statistically significant association was seen between sex, education level, diabetes, race, smoking status, coronary artery disease, age, congestive heart failure, and stroke.
Conclusion
The results revealed a positive association between the MHR and psoriasis. These findings suggest that the MHR could serve as a useful tool for identifying individuals who are more susceptible to developing psoriasis.
Symptom networks of multidimensional symptom experiences in breast cancer survivors: A network analysis
Authors: Muhetaer Sulaiman , Mijiti Peierdun , Aierken Kaibinuer , Jingjing Wei
Published: October 2024

Objectives
We aimed to construct a symptom network for breast cancer patients, identify its core symptoms, and explore symptom clusters. This network approach may provide valuable insights for precise interventions to improve the overall quality of life in breast cancer patients.
Methods
A total of 462 eligible breast cancer patients were recruited. The severity of patients' symptoms was measured using the EORTC QLQ-C30 Chinese version scale and Zung Self-Rating Depression and Anxiety Scale. A regularized partial correlation network was established, and central symptoms were identified using Strength centrality.
Results
The strongest associations were observed between NV-AP (weight = 0.39), Dep-Anx (weight = 0.38), PA-DY (weight = 0.21), and Anx-SL (weight = 0.20). Fatigue was the most prevalent symptom among breast cancer patients, and fatigue was consistently the central symptom in the network, in addition to anxiety, appitie loss, and pain. DAG indicated that fatigue might influence overall symptoms in breast cancer patients. Three syomtom clusters were indentified: emotional symptoms (depression, anxiety, and insomnia), gastrointestinal symptoms (nausea/vomiting, diarrhea, and loss of appetite), and somatic symptoms (fatigue, pain, and dyspnea).
Conclusions
Fatigue, depression, and anxiety are highly prevalent and central symptoms in breast cancer patients. It is crucial to screen and provide early treatment for these symptoms to effectively manage them and enhance the overall quality of life for breast cancer patients. Future studies should focus on conducting longitudinal research to establish dynamic networks and investigate causal relationships between these symptoms.
Differentiating PCOS from Anovulatory Cycles in Adolescents: A Comprehensive Evaluation of FAI, SHBG, and LH/FSH Ratio
Authors: OZER Emre , TAŞ Demet , GÜNDOĞAN Seçil ÇAKIR , BOYRAZ Mehmet , GÜRBÜZ Fatih
Published: October 2024

Background
Menstrual irregularities are common among adolescents, often linked to anovulatory cycles. This study aims to establish diagnostic cut-off values for Polycystic Ovary Syndrome (PCOS) and differentiate these from anovulatory dysfunction in adolescents. Additionally, we assessed the sensitivity of using the Free Androgen Index (FAI) and Sex Hormone Binding Globulin (SHBG) in diagnosing PCOS.
Methods
This study included 305 adolescents presenting with oligomenorrhea at a tertiary center. Data were analyzed statistically and Receiver operating characteristic (ROC) curves were plotted to evaluate diagnostic performance.
Results
Of the 305 patients, 229 (75%) had anovulatory cycles and 36 (11.8%) had PCOS. The mean FAI values for anovulatory cycles, PCOS, and hyperinsulinism were 3.5 ± 2, 8.0 ± 5, and 8.3 ± 4, respectively (p < 0.001). A significant positive correlation was found between FAI and both HOMA-IR (r = 0.389; p < 0.001) and BMI (r = 0.499; p < 0.001). ROC analysis determined the LH threshold of 9.7 U/L and LH/FSH ratio threshold of 2.62 as predictive markers for PCOS.
Conclusions
Anovulatory cycles are the most frequent cause of menstrual irregularities in adolescents, with hyperandrogenism being crucial for diagnosing PCOS. The FAI may be unreliable for PCOS diagnosis due to similar values in adolescents with hyperinsulinemia and obesity. Lower SHBG levels in hyperinsulinemic obese adolescents further complicate the use of FAI, indicating that glucose/insulin metabolism significantly influences FAI/SHBG levels. Comprehensive diagnostic criteria, including androgen levels, LH/FSH ratio, SHBG, FAI levels, and ovarian ultrasound, are essential for accurate PCOS diagnosis.
More similarity than difference: comparison of within- and between-sex variance in early adolescent brain structure
Authors: Torgerson Carinna , Bottenhorn Katherine , Ahmadi Hedyeh , Choupan Jeiran , Herting Megan M.
Published: October 2024

Background
Adolescent neuroimaging studies of sex differences in the human brain predominantly examine mean differences between males and females. This focus on between-groups differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain.
Methods
We aimed to characterize the variance in brain macro- and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=7,723). Specifically, for global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within- and between-sex variance, overlap between male and female distributions, inhomogeneity of variance via the Fligner-Killeen test, and an analysis of similarities (ANOSIM). For completeness, we examined these sex differences using both uncorrected (raw) brain estimates and residualized brain estimates after using mixed-effects modeling to account for age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable.
Results
The overlap between male and female distributions was universally greater than the difference (overlap coefficient range: 0.585 - 0.985) and the ratio of within-sex and between-sex differences was similar (ANOSIM R range: -0.001 - 0.117). All cortical and subcortical volumes showed significant inhomogeneity of variance, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Inhomogeneity of variance was reduced after accounting for other sources of variance. Overlap coefficients were larger and ANOSIM R values were smaller for residualized outcomes, indicating greater within- and smaller between-sex differences once accounting for other covariates.
Conclusions
Reported sex differences in early adolescent human brain structure may be driven by disparities in variance, rather than binary, sex-based phenotypes. Contrary to the popular view of the brain as sexually dimorphic, we found more similarity than difference between sexes in all global and regional measurements of brain structure examined. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure.
Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum: A Cross-sectional Study
Authors: Yilmaz Nevin , Bakirci Isil Turan , Sahin Busra , Bolluk Gokhan , Can Esra , Dedeakayogullari Huri
Published: October 2024

Background
This study aimed to assess maternal serum survivin levels in women with placenta previa, with and without placenta accreta spectrum (PAS), to understand its role in abnormal placental adherence and invasion.
Methods
In this prospective cross-sectional study, we enrolled 84 pregnant women categorized into control (n = 42), placenta previa (n = 24), and PAS (n = 28) groups. Serum survivin levels were quantitatively determined using ELISA, and statistical analyses were performed using ANOVA and post-hoc tests.
Results
A significant elevation in serum survivin levels was observed in the placenta previa and PAS groups compared to the controls (p < 0.05), suggesting that survivin plays a role in the pathophysiological response to abnormal placental adherence and invasion.
Conclusions
Elevated serum survivin levels may serve as an early biomarker for the diagnosis and management of placenta previa and PAS, aiding in the planning and timing of surgical interventions and the selection of appropriate surgical centers.
Central nervous system relapse after allogeneic HCT in FLT3-mutated AML
Authors: Kouidri Khouloud , Acker Fabian , Toenges Rosa , Pfaff Saskia , Lindner Sarah , Riemann Julia , Werth Marek , Ajib Salem , Lang Fabian , Steffen Björn , Oellerich Thomas , Serve Hubert , Cremer Anjali , Bug Gesine
Published: October 2024

Central nervous system (CNS) relapse in acute myeloid leukemia (AML) is rare, but prognostically extremely unfavorable and associated with very high mortality rates. Aim of our single-center study was to define risk factors for CNS relapse in patients with FLT3-mutated AML after allogeneic hematopoietic cell transplantation (HCT) and to determine the impact of pre-emptive or salvage therapy with FLT3-inhibitors (FLT3i) on occurrence of CNS relapse and overall prognosis. We analyzed 39 FLT3-mutated AML patients who were treated with intensive induction therapy and consecutively underwent HCT at our institution. We observed that the remission status before HCT was strongly associated with relapse probability. Notably, FLT3-mutated AML showed a high propensity for CNS relapse with a cumulative incidence of 50% (95% confidence interval [CI], 16–77) at 2 years in non-responders pre-HCT compared to 0% in responders (cause-specific hazard ratio, 24.5, 95% CI, 2.9-206.2; p = 0.003). This was not abrogated by pre-emptive or salvage therapy with FLT3i in first relapse. Targeted therapies prior to transplant, use of intrathecal chemoprophylaxis or closer monitoring may be considered in patients with FLT3-mutated AML with active disease prior to HCT in order to prevent CNS relapse. Additionally, CNS directed induction therapies may be indicated.
A Combined School Survey and Reactive Case Detection Reveals Minimal Local Transmission of Malaria in the Highlands Region of Papua New Guinea 2019
Authors: Seidahmed Osama , Kurumop Serah , Wawaga Elizabeth , Kualawi Melvin , Siba Valentine , Jamea Sharon , Ura Yangta , Makita Leo , Pomat William , Hetzel Manuel W.
Published: October 2024

Background
The Highlands of Papua New Guinea are non-endemic for malaria compared to the rest of the country. This study aimed to explore the local transmission of malaria in the Highlands through a cross-sectional school survey coupled with reactive case detection.
Methods
Between July and November 2019, 5575 students and 1048 household members were screened for malaria using Rapid Diagnostic Tests, subsequently validated by light microscopy. In addition, an analysis of malaria cases (2017 to 2019) was conducted across 33 health facilities within the catchment areas of the surveyed schools and households.
Results
Thirteen individuals were diagnosed with malaria: eleven with Plasmodium falciparum (five students, six household members) and two with P. vivax (one student, one household member); all were aged ten years or older. Malaria prevalence was 0.09% [95% CI: 0.03, 0.3] among students and 1.7% [95% CI: 0.3, 9.1] among household members. Eleven positive individuals (84%) reported recent travel, mainly to lower-altitude endemic areas. Long-Lasting Insecticidal Nets were used by 34.8% [95% CI: 28.7, 40.8] of household members. The average annual malaria incidence in the catchment areas was 3.7 cases per 1000 [95% CI: 2.6, 5.3] among the general population, while children under 15 years accounted for 19% [95% CI: 14, 27] of the positive cases.
Conclusions
Local malaria transmission appears to be minimal in the surveyed Highlands areas. Strengthening surveillance-response system to control imported cases and stop local foci could support malaria elimination in PNG. However, effective operational triggers for re-active case finding remain to be determined.
Assessment of Cardio-Oncology Knowledge and Practice among Healthcare Providers in Saudi Arabia: A Comprehensive Nationwide Survey
Authors: Badreldin Hisham A. , Alsuhebany Nada , Alfehaid Lama , Alzahrani Mohammed , Aldoughaim Maha , Alrajhi Abdullah M. , Alsufyani Jumanah , Elsherif Dania , Alshammari Kanan
Published: October 2024

Introduction: The evolving field of oncology necessitates effective management of cancer-related cardiovascular diseases. In Saudi Arabia, the incidence of cancer is rising, and there is a critical need for cardio-oncology services to address cancer treatment-related cardiovascular toxicity. This study aimed to evaluate the knowledge and practices of healthcare providers (HCPs) in Saudi Arabia regarding cardio-oncology.
Methods: A cross-sectional study was conducted from January to April 2024 using an online survey targeting cardiologists, oncologists, and clinical pharmacists. The survey assessed demographics, perceptions of cardio-oncology, availability of services, and current practices. Data were analyzed using descriptive statistics, chi-squared tests, and bivariate analyses.
Results: The survey received responses from 116 HCPs, including cardiologists (63.79%), oncologists (23.28%), and clinical pharmacists (12.93%). Most participants had over six years of experience, and only one had formal cardio-oncology training. While 84.48% recognized the importance of managing cardiac complications in cancer patients, only 42.24% were familiar with existing guidelines. Limited training programs and institutional resources were significant barriers to implementing cardio-oncology services. Despite agreement on the need for cardiotoxicity management, only one-third recommended cardioprotective agents as standard care.
Conclusion: There is a notable deficiency in formal training and resources for cardio-oncology in Saudi Arabia. To bridge this gap, integrating cardio-oncology into training programs, establishing institutional guidelines, and adopting multidisciplinary care models are crucial. These measures will enhance the quality of care for cancer patients and improve their cardiovascular outcomes.
3D in vitro Modelling of Post-Partum Cardiovascular Health reveals Unique Characteristics and Signatures following Hypertensive Disorders in Pregnancy
Authors: Ming Clara Liu Chung , Pienaar Dillan , Ghorbanpour Sahar , Chen Hao , Roberts Lynne Margaret , Cole Louise , McGrath Kristine C , Padula Matthew P , Henry Amanda , Gentile Carmine , McClements Lana
Published: October 2024

Background
Hypertensive disorders of pregnancy (HDP) affect 2–8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.
Methods
Human iPSC-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were tri-cultured to form cardiac spheroids (CS) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum (n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE). Plasma-treated CS were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).
Results
Contraction frequency (CF) was increased in PE-treated CS (CF:45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CS (CF:45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/minute). Only PE-treated CS presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analysis identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control (p < 0.05).
Conclusions
Using innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.
Impact of extraction and RT-PCR protocols on stool RNA detection: A study on CRC- associated immune-genes in various patient groups
Authors: Omran Thura Akrem , Madsø Inger Line , Saether Per Christian , Bemanian Vahid , Tunsjø Hege Smith
Published: October 2024

There is a growing interest in using fecal mRNA transcripts as biomarkers for non-invasive detection of colorectal cancer (CRC). The following study compares different RNA extraction and reverse transcription PCR (RT-PCR) methods for mRNA detection in stool and identifies a robust and sensitive protocol.
A combination of the Stool total RNA purification kit (Norgen) and the Superscript III one-step RT-PCR kit (Invitrogen) provided high RNA purity and sensitive and consistent mRNA detection, making them well-suited candidates for large-scale studies. We tested the protocol by detecting the mRNA of several immune genes (CXCL1, IL8, IL1B, IL6, PTGS2, and SPP1) in 22 CRCs, 24 adenomatous polyps, and 22 control stool samples. All these inflammatory markers, except for CXCL1, showed a strong association with CRC. Cancer stool samples showed increased levels of IL1B, IL8, and PTGS2 transcripts compared to polyp and control groups.Thus, this work supports the potential use of fecal mRNA for CRC biomarker detection.
Mendelian Randomization Reveals Causal Links Between Vertigo Types and structural characteristics of specific brain regions
Authors: Huang Junwei , Zhu Xiao , Yao Jingxin , Lu Wei , Zhu Zhenhua
Published: October 2024

Background
Vertigo is a common clinical symptom that involves multiple neurobiological processes; however, its exact mechanism remains elusive. In neuroimaging studies focusing on vertigo and its central correlation, potential reverse causality and unmeasured confounding factors frequently introduce biases. Furthermore, the causal relationship between vertigo and specific neuroimaging features is not yet established. Employing the Mendelian randomization (MR) method can provide a more precise understanding of the causal relationships between vertigo and changes in brain structure and function.
Methods
Based on the large-scale genome-wide association study data from UK Biobank, this study employed bidirectional MR analysis to explore the causal relationships between brain MRI features associated with vertigo and the condition itself. The research focuses on brain imaging-derived phenotypes (IDPs) such as whole brain volume, and the volumes of both gray matter and white matter.
Results
In this study, MR analysis revealed that for benign paroxysmal positional vertigo (BPV), an increase in specific brain regions such as BA-exvivo lh volume BA2, aparc-Desikan rh area rostralmiddlefrontal, IDP dMRI TBSS L2 Corticospinal tract R, and rfMRI connectivity (ICA100 edge 1323) was significantly correlated with a reduction in BPV risk. Conversely, an increase in IDP dMRI TBSS MD Cingulum hippocampus L and rfMRI connectivity (ICA100 edge 82 and 357) was associated with an increased risk of BPV. For peripheral vertigo (PERIPHVERTIGO), an increase in aparc-a2009s rh volume Pole-occipital significantly increased the risk. For general vertigo (VERTIGO), increases in IDP dMRI TBSS FA Superior fronto-occipital fasciculus R and rfMRI connectivity (ICA100 edge 236) were associated with increased risk, while a decrease in rfMRI connectivity (ICA100 edge 184) was associated with decreased risk. For central vertigo (VERTIGOCENT), an increase in rfMRI connectivity (ICA100 edge 1387) and BA-exvivo rh thickness BA4a significantly reduced the risk, whereas an increase in aparc-Desikan rh area annularcingulate significantly increased the risk.
Conclusion
The genetic susceptibility of the vertigo network, extending from the vestibular labyrinth in the cerebellum and brainstem to the cerebral cortex, is causally related to an increase in white matter volume and total brain volume. Volume changes in several cortical regions may suggest a higher risk of vertigo; thus, further studies of causal inference at the sub-brain regional level are strongly recommended. Our results offer genetic evidence that helps elucidate the underlying pathophysiological mechanisms of neuroanatomical abnormalities related to vertigo.
Postoperative recurrence of atypical odontoma: a case report
Authors: Qin Han , Gong Yong-qing
Published: October 2024

Background: The purpose of this study was to analyze a case of recurrent atypical odontoma after surgical resection, in order to provide some references for the etiology analysis and treatment of this disease.
Methods：The detailed clinical data and history of related clinical symptoms of this patient were retrieved at first visit. Intraoral examination showed permanent dentition, no left maxillary first premolar (24). However, there were several anomalous tooth-like tissues in the affected area. Imaging studies showed several small, highly dense image aggregates above tooth 24. The erupting and un-erupting teeth-like tissues were removed in accordance with the surgical method of extraction of supernumerary teeth under local anesthesia. The patient was returned to our clinic one month later, and periapical radiography examination showed irregular and unorganized radiopaque mass surrounded by a clear thin radiographic halo above the crown of tooth 24. The imaging data indicated that this was a typical manifestation of odontoma. After full communication with the child's parents, the second surgical resection was performed to remove the cyst wall and the hard tissue inside the capsule.
Results: When the patient returned 3 months after the second operation, the intraoral examination showed tooth 24 had erupted normally, and periapical radiography examination showed no abnormal root development.
Conclusion: The case gives us three inspirations: atypical odontoma is easy to cause misdiagnosis and lead to incomplete resection and postoperative recurrence; Intraoperative stimulation can promote the rapid growth of odontoma. Young permanent teeth can erupt normally after removing mechanical blockages without special treatment.
Indocyanine Green Dyed Gauze-Guided Minimum Invasive Surgery for Anatomical Landmarks and Preventing Gauze Remnants: A Pilot Study
Authors: Tashiro Yoshihiko , Aoki Takeshi , Yasunaga Hidekazu , Ando Shinji
Published: October 2024

Purpose
We aimed to develop a novel fluorescent surgical gauze dyed with indocyanine green (ICG) to guide surgeons to the target anatomical destination during surgery for real-time navigation and to prevent gauze remnants after surgery.
Methods
Surgical gauze was dyed with an aqueous solution of ICG (5.0 × 10− 5 mol L− 1 for Steraze, 1.5 × 10− 4 mol L− 1 for BK-Opeze ) at 132°C (inside pressure: 2.82 atm, 286 kPa) for 15 min using an autoclave, followed by washing with distilled water, drying at room temperature, and sterilizing at 132°C for 8 min before surgery. Fluorescence (FL) intensity was examined preclinically in the resected specimens using the SPY PHI (Stryker) system. Fourteen patients who underwent laparoscopic- and robotic-assisted gastroenterological surgery at Showa University Hospital were included.
Results
Fluorescent emission of ICG-dyed gauze was clearly observed through resected specimens with a thickness of approximately 10 mm or more. In a clinical trial, the ICG-dyed gauze was detected earlier with near-infrared (near-IR) FL imaging than under white light during seven cases of laparoscopic and robotic surgery, which could become a precise marker for surgeons to locate the dissection site despite overlaying tissues and nearby disturbances. Additionally, no seepage of ICG from the gauze was observed in all surgical fields.
Conclusion
We successfully developed ICG-dyed gauze exhibiting bright near-IR FL which can guide surgeons to the target anatomical destination and prevent gauze remnants during surgery. This invention would be a powerful support for real-time navigation surgery.
Diagnostic Utility of Fluorescence and Diffuse Reflectance Imaging in Gastrointestinal Luminal Pathology
Authors: Padikala John Anto , Subhash N , George Phebe , Manogli Sandeep P , Suvarnadas Rinoy , Raveendranadh Ajay , Mathew Stanley
Published: October 2024

BACKGROUND:
Cancer is a fatal disease with significant global mortality. Because cancer is so diverse and lacks biomolecular indicators, it is difficult to diagnose at an early stage using current histopathological diagnostic techniques. However, recent cutting-edge fluorescence and diffuse reflectance (DR) imaging techniques, which use sub-cellular spectral features, have proven beneficial in cancer diagnostics. This study aimed to investigate the diagnostic potential of these methods for discriminating malignant from normal gastrointestinal tissue in an ex vivo setting.
MATERIALS AND METHODS:
An experimental trial was conducted on 42 patients attending the Department of General Surgery, Kasturba Medical College, Manipal. Fluorescence and DR at 399 sites were measured using a handheld multimodal device. The spectral readings were taken immediately after the surgical resection of the specimen. Light-emitting diodes (LED) emitting at 375 nm, 545 nm, 575 nm, and 610 nm wavelengths were used for tissue illumination, and the backscattered light was analyzed using proprietary software. The DR ratio (R610/R545) intensity values were determined for all the different sites examined, and a scatter plot diagram was made to correlate with tissue pathology.
RESULTS:
Spectral readings of histologically confirmed malignant tissues were compared with those of histologically verified normal tissues and were used as controls. In total, 399 sites yielded 766 spectral findings. In an ex vivo context, our study demonstrated a sensitivity of 78.8% and specificity of 98.3% for differentiating between malignant and normal tissues. Additionally, the study showed a 90% specificity and 92% sensitivity for differentiating between benign and malignant tissues.
CONCLUSION:
The diagnostic utility of fluorescence and DR imaging demonstrates its potential to discriminate between normal tissues and pathological lesions of the gastrointestinal tract in real-time.
Identification of a immune-related genes signature for survival prediction in stage I lung adenocarcinoma
Authors: Zhang Xin , Li ShiNing , Luo SiSheng , Liu XinYu , Ao Yong , Zhong LeQi , Luo KongJia , Hu Yi
Published: October 2024

Background
With the popularization of low-dose spiral computed tomography (CT), an increasing number of stage I lung cancers have been discovered. Although most of the patients with stage I lung adenocarcinoma have a favorable prognosis, some patients still have a poor prognosis of recurrence and metastasis after surgery. The immune system has been shown to play an important role in the development of cancer. Our aim is to identify a reliable prognostic signature of immune-related genes that can predict prognosis and help in the individualized management of patients with stage I lung adenocarcinoma.
Methods
In this study, the immune-related genes were first extracted by the ImmPort database. Subsequently, these genes were screened using univariate Cox regression and LASSO regression to identify prognostic signatures, followed by construction of a prognostic model using multivariate Cox regression. A nomogram was developed to predict the prognosis of stage I lung adenocarcinoma and to evaluate the nomogram differentiation and accuracy using the receiver operating characteristic curve, clinical decision analysis and calibration curve. The model was validated in two independent data sets: GSE31210 and GSE30219. Then, patients were stratified based on median risk scores, and differential expression genes between the two groups were analyzed. Finally, the enrichment analysis and the immune infiltration analysis were performed.
Results
In this study, we found 29 immune-related genes and developed a gene signature with poor prognosis in stage I lung adenocarcinoma. Our model was validated using two independent datasets and demonstrated robust performance with good AUC values and clinical utility. Enrichment analysis indicated that immune-related genes signature has multifaceted effects on stage I lung adenocarcinoma, especially related to tumor development, proliferation, and metastasis. Patients in the high-risk group had higher tumor purity, lower matrix, estimated and immune scores, suggesting a potentially immunosuppressive tumor microenvironment.
Conclusion
This study constructed a gene signature related to immunity in stage I lung adenocarcinoma and analyzed its impact on tumor development and its relationship with the tumor microenvironment. The findings can contribute to a more precise survival risk stratification and personalized clinical management for stage I lung adenocarcinoma patients. Furthermore, we provide related opinions for future immune-related research by elucidating potential underlying mechanisms.
Study protocol for a prospective, longitudinal cohort study investigating the Intestinal permeability in critically ill patients
Authors: Hejazi Samin , Norouzy© Abdol Reza , Safarian Mohammad , Moghaddam Ahmad Bagheri , Alinezhad-Namaghi Maryam , Rezaiyan Majid Khadem , Dehbalaei Moazzameh Ghorbani , Dorchin Mohsen , Hasani Atefeh Sepehri
Published: October 2024

Aim: The research is a prospective cohort study focusing on assessing intestinal permeability in critically ill individuals. The primary aim of the study is to investigate the impact of intestinal permeability on disease severity and the 28-day and 60-day mortality rates among critically ill patients.
Introduction: Preserving the integrity of the gastrointestinal (GI) tract is essential for maintaining intestinal barrier function, as its compromise can result in the translocation of detrimental substances, such as bacteria. Critically ill patients are particularly vulnerable to changes in intestinal permeability (IP), which can elevate the chances of developing severe conditions like sepsis, multiple organ dysfunction syndrome (MODS), and systemic inflammatory response syndrome (SIRS), ultimately leading to mortality.
Method: The research will involve 73 ICU patients needing enteral feeding for a minimum of one day, who will undergo screening based on specific criteria for inclusion and exclusion. Small-bowel permeability will be assessed using the dual-sugar absorption method (lactulose and mannitol), a prevalent noninvasive technique in critically ill individuals, to determine their small-bowel permeability accurately.
Conclusion: Consequently, addressing altered intestinal permeability becomes a critical focus for therapeutic interventions and a pivotal factor influencing the outcomes of patients in the intensive care unit (ICU). Its straightforwardness, consistency, and reliability of this measuring make it ideal for routine clinical applications, enabling the quantification of intestinal permeability with ease and accuracy.