bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous resection increases risk of chyle leak after total pancreatectomy for pancreatic tumors
Authors: Li Tianyu , Lin Chen , Zhao Bangbo , Li Zeru , Zhao Yutong , Han Xianlin , Dai Menghua , Guo Junchao , Wang Weibin
Published: June 2024

Background

Existing research on chyle leak (CL) after pancreatic surgery is mostly focused on pancreaticoduodenectomy and lacks investigation on total pancreatectomy (TP). This study aimed to explore potential risk factors of CL and develop a predictive model for patients with pancreatic tumor undergoing TP.

Methods

This retrospective study enrolled 90 consecutive patients undergoing TP from January 2015 to December 2023 at Peking Union Medical College Hospital. According to the inclusion criteria, 79 patients were finally included in the following analysis. The LASSO regression and multivariate logistic regression analysis were performed to identify risk factors associated with CL and construct a predictive nomogram. Then, the ROC analysis, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were performed to assess its discrimination, accuracy, and efficacy. Due to the small sample size, we adopted the bootstrap resampling method with 500 repetitions for validation. Lastly, we plotted and analyzed the trend of postoperative drainage volume in CL patients.

Results

We revealed that venous resection (OR = 4.352, 95%CI 1.404–14.04, P = 0.011) was an independent risk factor for CL after TP. Prolonged operation time (OR = 1.473, 95%CI 1.015–2.237, P = 0.052) was also associated with an increased incidence of CL. We included these two factors in our prediction model. The area under the curve (AUC) was 0.752 (95%CI 0.622–0.874) after bootstrap. The calibration curve, DCA and CIC showed great accuracy and clinical benefit of our nomogram. In patients with CL, the mean drainage volume was significantly higher in venous resection group and grade B CL group.

Conclusion

Venous resection was an independent risk factor for chyle leak after TP. Patients undergoing vascular resection during TP should be alert for the occurrence of CL after surgery. We then constructed a nomogram consisted of venous resection and operation time to predict the odds of CL in patients undergoing TP.
Evolution and implications of SARS-CoV-2 variants in the post-pandemic era
Authors: Manirambona Emery , Okesanya Olalekan John , Olaleke Noah Olabode , Oso Tolutope Adebimpe , Lucero-Prisno Don Eliseo
Published: June 2024

SARS-CoV-2, the cause of the COVID-19 pandemic, has introduced a challenging era characterized by the persistent emergence of subvariants. Even after the World Health Organization announced the end of the pandemic, the virus continues to evolve, posing significant challenges to public health responses. This comprehensive review examines the multifaceted impacts of these subvariants, emphasizing their significance across diverse dimensions. SARS-CoV-2 has genetic variability, especially at the spike protein region, which has given rise to Variants of Concern, including Beta, Delta, Gamma, Alpha, and the highly mutable Omicron, which differently exhibit varying levels of immune evasion, disease severity, and transmissibility. Subvariants within the Omicron lineage, including BA.1, BA.2, BA.3, and others, further complicate the landscape with distinct genetic signatures and varying infectivity levels. The impacts extend to diagnostic techniques, treatment strategies, and vaccine effectiveness, underscoring the need for a comprehensive public health response emphasizing preventive measures, genomic surveillance, and vaccination campaigns. Sustaining these interventions is critical, necessitating long-term strategies considering socio-political factors, community involvement, continuous adaptation of healthcare approaches, robust monitoring, and sustainable public health interventions to effectively combat the virus's ever-changing landscape.
Effect of scapular posterior tilting exercise on scapular muscle activities in men and women with a rounded shoulder posture
Authors: Gu Qian , Pan Longlu , Yu Lijun , Jiang Qin
Published: June 2024

Round-shoulder posture (RSP) is a common postural condition, characterized by protraction, downward rotation, anterior tilting and internal rotation of the scapula. RSP can lead to shoulder dysfunction. Different methods have been proposed for rehabilitating and correcting the altered posture in RSP including stretching, strengthening exercises, and shoulder brace or taping. However, the findings are controversial and studies are ongoing to develop more effective method. The present study is aimed at investigating the effects of scapular posterior tilting (SPT) exercise in different support positions on scapular muscle activities in men and women with RSP. In a prospective observational clinical study, we assessed demographic, basic clinical parameters and study variables of the subjects with RSP (n = 20) (men/women = 9/11) attending Daegu University in Gyeongsan, South Korea. To do so, we compared electromyographic (EMG) activities of lower trapezius and serratus anterior muscles between men and women with RSP during SPT exercise on four different support surfaces to determine any difference in the EMG activities. The results revealed that women showed significant differences in EMG activities in the lower and left upper trapezius and serratus anterior muscles, while men showed significant differences in EMG activity only in the lower trapezius muscle during SPT exercise on four different surfaces (P < 0.05). The post-hoc analysis revealed significantly greater EMG activity values in the lower trapezius and serratus anterior muscles during SPT exercise on the upper body unstable surface and whole-body unstable surface (p < 0.05). Independent t-tests after the Bonferroni correction showed no significant differences in muscle activities between men and women on the four different surfaces (p > 0.0125).
Comparative effectiveness of cortical bone trajectory screws and pedicle screws in the treatment of adjacent segment degeneration after lumbar fusion surgery: a systematic review and meta-analysis
Authors: Shang Qisong , Luan Haopeng , Peng Cong , Song Xinghua
Published: June 2024

Purpose

To compare the efficacy and safety of cortical bone trajectory (CBT) screw and pedicle screw (PS) internal fixation in the treatment of adjacent segment degeneration (ASD) after lumbar fusion.

Methods

This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023484937). We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Wei Pu Database by computer to collect controlled clinical studies on the efficacy and safety of cortical bone trajectory (CBT) screw and pedicle screw (PS) internal fixation in the treatment of adjacent segment degeneration (ASD) after lumbar fusion from database establishment to November 2023. Two researchers screened the literature, extracted data and evaluated the risk of bias of the included studies, recorded the authors, and sample size, and extracted the intraoperative blood loss, operation time, Oswestry disability index (ODI), Visual analogue scale (VAS), disc height (DH), hospital length stay and complications in each study. Meta-analysis was performed using Revman 5.4 software provided by Cochrane Library.

Results

A total of 6 cohort studies (CS) and 1 randomized controlled study with a total of 420 patients were included in this study, including 188 patients in the CBT group and 232 patients in the PS group. The CBT group had lower intraoperative blood loss than the PS group [mean difference (MD) = -129.38, 95% CI (-177.22, -81.55), P < 0.00001] and operation time was shorter than that of the PS group [MD = -1.42, 95% CI (-2.63, -0.20), P = 0.02]. Early postoperative back and leg pain improved more significantly in the CBT group [MD = -0.77, 95% CI (-1.35, -0.19), P = 0.01; MD = -0.24, 95% CI (-0.37, -0.10), P = 0.0005].

Conclusion

Compared with PS, CBT for adjacent segment degeneration after lumbar fusion has the advantages of less intraoperative blood loss, shorter operation time, and less back and leg pain in the early postoperative period.
The importance of mother-child interaction on smart device usage and behavior outcomes among toddlers: a longitudinal study
Authors: Chakranon Pairote , Huang Jian-Pei , Au Heng-Kien , Lin Chen-Li , Chen Yi-Yung , Mao Shih-Peng , Lin Wen-Yi , Zou Ming-Lun , Estinfort Wanda , Chen Yi-Hua
Published: June 2024

Background

In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers’ smart device usage and behavioral outcomes, are limited. Understanding the impact of parent–child interactions on this relationship is crucial for enhancing toddlers’ developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers’ behaviors, as well as the positive effects of mother–child interactions on this influence.

Methods

We used relevant data related to 277 children born between November 2016 and July 2020 and who were part of an ongoing prospective follow-up study conducted across five hospitals in Taipei City, Taiwan. We analyzed (1) data from maternal reports regarding children’s behavior by using the Child Behavior Checklist (for ages 11/2–5 years), (2) assessments of mother–child interactions by using the Brigance Parent–Child Interactions Scale, and (3) self-reported parental data covering the first 3 postpartum years. Statistical analyses involved group-based trajectory modeling and multiple linear regression.

Results

A considerable increase in screen time between the ages of 1 and 3 years was associated with less favorable behavioral outcomes at age 3. These outcomes included somatic complaints [adjusted beta coefficient (aβ) = 2.17, 95% confidence interval (CI) = 0.39–3.95, p-value = 0.01], withdrawal (aβ = 2.42, 95% CI = 0.15–4.69, p-value = 0.04), and aggressive behavior (aβ = 6.53, 95% CI = 0.25–12.81, p-value = 0.04). This association was particularly evident among children with lower levels of mother–child interaction. Nevertheless, positive mother–child interactions mitigated most of the adverse effects. Additionally, increased exposure to games and cartoons was associated with poorer behavioral outcomes in all children except for those experiencing positive mother–child interactions.

Conclusion

Early mother–child interactions play a crucial role in mitigating the risk of behavioral problems in toddlers who spend prolonged periods looking at screens and who are frequently exposed to game and cartoon content.
Cerebellar damage with inflammation upregulates oxytocin receptor expression in Bergmann Glia
Authors: Inutsuka Ayumu , Hattori Aisa , Yoshida Masahide , Takayanagi Yuki , Onaka Tatsushi
Published: June 2024

The cerebellum plays an important role in cognitive and social functioning. Childhood damage in the cerebellum increases the risk of autism spectrum disorder. Cerebellar inflammation induces social avoidance in mice. Oxytocin regulates social relationship and expression pattern of the oxytocin receptor in the brain is related to social behaviors. However, the expression patterns of the oxytocin receptor in the cerebellum remain controversial. Here, we report that the expression patterns of the oxytocin receptor in the cerebellum are highly variable among knock-in transgenic lines. We used Oxtr-Cre knock-in mice combined with a fluorescent reporter line and found that oxytocin receptor expression in Bergmann glia was more variable than that in Purkinje cells. We found that physical damage with inflammation induced the selective upregulation of the oxytocin receptor in Bergmann glia. Our findings indicate high variability in oxytocin receptor expression in the cerebellum and suggest that the oxytocin receptor can affect neural processing in pathological conditions, such as inflammation.
Copenhagen Mesenteric stent study (COMESS)—a randomized trial of stent versus covered stent treatment for chronic mesenteric ischemia
Authors: Brandtzäg Alexandra A. , Eiberg Jonas P. , Lönn Lars , Taudorf Mikkel , Resch Timothy A.
Published: June 2024

Background

Current management of mesenteric ischemia is primarily endovascular stent treatment. Typical CMI symptoms are postprandial abdominal pain, food fear, weight loss, and diarrhea. Revascularization is often necessary, as mesenteric ischemia may progress to bowel necrosis and death if left untreated. This study aims to compare the outcome using bare metal stent (BMS) or covered stent (CS) in the endovascular treatment of chronic and acute on chronic mesenteric ischemia.

Methods

This is an investigator-driven, prospective, randomized, single-blinded, and single-center, national cohort study at the Copenhagen University Hospital, Denmark. A total of 98 patients with chronic mesenteric ischemia (CMI) and acute-on-chronic mesenteric ischemia (AoCMI) will be randomized to treatment with either BeSmooth BMS (Bentley Innomed GmbH) or BeGraft CS (Bentley Innomed GmbH). Randomization occurs intraoperatively after lesion crossing.

Discussion

There is currently no published data from prospective controlled trials regarding the preferred type of stent used for the treatment of chronic and acute-on-chronic mesenteric ischemia. This trial will evaluate the short- and long-term outcome of BMS versus CS when treating CMI and AoCMI, as well as the benefit of a more intense postoperative surveillance program.

Trial registration

ClinicalTrials.gov NCT05244629. Registered on February 8, 2022.
QbD green analytical procedure for the quantification of tolvaptan by utilizing stability indicating UHPLC method
Authors: Hashmi Shadab Anwar , Alegete Pallavi
Published: June 2024

For the first time a new QbD-assisted green stability indicating ultra-high-performance liquid chromatography (UHPLC) method was developed and validated for quantifying Tolvaptan. The method is simple, quick, cost-effective, and stable, and it was used to formulate a quality target product profile (QTPP) with strategically defined critical analytical attributes (CAAs) to meet specific criteria. Chromatographic separation was undertaken using a 10 cm long column of ACE excel super C18 with an interior diameter of 2.1 mm and particle size of 1.7 µm. The analysis was performed under controlled conditions at 25 ℃ with the mobile phase flowing at a rate of 0.2 mL/min and detection occurring at 220 nm. Injected 3 µL of standard by using an isocratic mobile phase system consisting of acetonitrile and water in a 95:5 v/v ratio. The diluents, prepared by mixing acetonitrile with water at a 90:10 volumetric ratio, were utilized. The analyte’s retention time was determined to be 1.63 min. The developed method provided reliable results with accuracy exceeding 99% and a correlation coefficient exceeding 0.999 ranged between 10 and 150 µg/mL across the range for LOQ—150% levels. Notably, during forced degradation testing, Tolvaptan exhibited susceptibility to acidic hydrolysis. The method effectively separated degradation products during stress testing, demonstrating its stability-indicating status. Environmental sustainability assessment of the developed method was conducted through the investigation of various indicators of Complex GAPI, Analytical Eco scale and Analytical GREEness and it was concluded the optimized method aligns with environmentally friendly practices.
Comparison of resistance training vs static stretching on flexibility and maximal strength in healthy physically active adults, a randomized controlled trial
Authors: Rosenfeldt Morten , Stien Nicolay , Behm David G. , Saeterbakken Atle Hole , Andersen Vidar
Published: June 2024

Background

The aim of the present study was to compare the effects of resistance training through full range of motion and static stretching (SS) of the hip and lower back extensors on flexibility and strength in healthy, physically active, adults.

Methods

Eighteen participants (age: 24.2 ± 3.0 years, body mass: 71.3 ± 8.9 kg, height: 172.8 ± 7.5 cm) were randomly assigned to either a Resistance Training (RT) (n = 6), SS (n = 6), or control (CON) group (n = 6). The sit & reach (S&R) flexibility test and maximum isometric straight legged deadlift (ISLDL) at 95% and 50% range of motion (ROM) were tested pre- and post-intervention with significance set atp < 0.05. Both groups conducted four to eight sets per session. Within each set, the RT group performed eight repetitions each lasting four seconds, while the SS group stretched continuously for 32 s. The rest periods between each set were 60–90 s. Consequently training volume and rest times were matched between the groups.

Results

The RT and SS groups achieved significant, large magnitude improvements in the S&R test compared to the CON group (p < 0.01 g = 2.53 andp = 0.01, g = 2.44), but no differences were observed between the RT and SS groups (p = 1.00). Furthermore, the RT group demonstrated a larger improvement in 50% and 95% ROM ISLDL compared to SS (p < 0.01, g = 2.69–3.36) and CON (p < 0.01, g = 2.44–2.57).

Conclusion

Resistance training through a full ROM was equally effective as SS for improving S&R flexibility, but improved hip- and lower back extensor strength more than SS and the CON. The authors recommend using large ROM resistance training to improve hip and lower back extensor flexibility and muscle strength.

Trial registration

ISRCTN88839251, registered 24. April 2024, Retrospectively registered.
Comparison of plasma soluble and extracellular vesicles-associated biomarkers in Alzheimer’s disease patients and cognitively normal individuals
Authors: Boyer Emilien , Deltenre Louise , Dourte Marion , Colmant Lise , Paître Esther , Sleegers Kristel , Suelves Nuria , Hanseeuw Bernard , Kienlen-Campard Pascal
Published: June 2024

Background

Amyloid-β (Aβ) and tau are brain hallmarks of Alzheimer’s disease (AD), also present in blood as soluble biomarkers or encapsulated in extracellular vesicles (EVs). Our goal was to assess how soluble plasma biomarkers of AD pathology correlate with the number and content of EVs.

Methods

Single-molecule enzyme-linked assays were used to quantify Aβ42/40 and tau in plasma samples and neurally-derived EVs (NDEVs) from a cohort of APOE ε4– (n = 168) and APOE ε4+ (n = 68) cognitively normal individuals and AD patients (n = 55). The ratio of CD56 (Neuronal cell-adhesion molecule) to CD81 signal measured by ELISA-DELFIA was used for the relative quantification of NDEVs in plasma samples.

Results

The soluble plasma Aβ42/40 ratio is decreased in AD patients compared to cognitively normal individuals. The amount and content (Aβ40, Aβ42, tau) of plasma NDEVs were similar between groups. Plasma NDEVs quantity remain consistent with aging and between AD and CN individuals. However, the quantity of soluble biomarkers was negatively correlated to NDEVs number in cognitively normal individuals, while in AD patients, this correlation is lost, suggesting a shift in the mechanism underpinning the production and the release of these biomarkers in pathological conditions.

Conclusion

Soluble plasma Aβ42/40 ratio is the most robust biomarker to discriminate between AD patients and CN individuals, as it normalizes for the number of NDEVs. Analysis of NDEVs and their content pointed toward peculiar mechanisms of Aβ release in AD. Further research on independent cohorts can confirm our findings and assess whether plasma Aβ and tau need correction by NDEVs for better AD risk identification in CN populations.
Generation and transcriptomic characterization of MIR137 knockout miniature pig model for neurodevelopmental disorders
Authors: Xu Shengyun , Wang Jiaoxiang , Mao Kexin , Jiao Deling , Li Zhu , Zhao Heng , Sun Yifei , Feng Jin , Lai Yuanhao , Peng Ruiqi , Fu Yu , Gan Ruoyi , Chen Shuhan , Zhao Hong-Ye , Wei Hong-Jiang , Cheng Ying
Published: June 2024

Background

Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans.

Results

In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137–/–) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137–/– miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137–/– miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD.

Conclusions

Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137–/– miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.
A RSBU-LSTM network for radio frequency fingerprint identification relying on multiple features
Authors: Ling Haoran , Zhu Fengchao , Yao Minli
Published: June 2024

Radio frequency fingerprint identification (RFFI) can distinguish highly similar wireless communication devices to protect physical layer security and improve the security of wireless networks effectively, which has been widely used for spectrum management and physical layer secure communication. However, most RFFI methods show a degradation of performance under low signal-to-noise ratio (SNR) environments. In this paper, we propose a RSBU-LSTM network relying on multiple features to improve the identification accuracy with low SNR. Firstly, we use multiple features of in-phase (I), quadrature (Q), and phase as inputs. Then, we use multiple Residual Shrinkage Building Units (RSBUs) to extract the correlation features within the cycle of signals and preserve as many features as possible in low SNR environments. Finally, we use the long short-term memory (LSTM) to extract the relevant features of the signals of non-adjacent cycles. The experimental results show that the proposed network can effectively complete RFFI in low SNR environments and show better performance than other models used for comparison.
Therapeutic potential of extracellular vesicles from diverse sources in cancer treatment
Authors: Lin Haihong , Zhou Jun , Ding Tao , Zhu Yifan , Wang Lijuan , Zhong Tianyu , Wang Xiaoling
Published: June 2024

Cancer, a prevalent and complex disease, presents a significant challenge to the medical community. It is characterized by irregular cell differentiation, excessive proliferation, uncontrolled growth, invasion of nearby tissues, and spread to distant organs. Its progression involves a complex interplay of several elements and processes. Extracellular vesicles (EVs) serve as critical intermediaries in intercellular communication, transporting critical molecules such as lipids, RNA, membrane, and cytoplasmic proteins between cells. They significantly contribute to the progression, development, and dissemination of primary tumors by facilitating the exchange of information and transmitting signals that regulate tumor growth and metastasis. However, EVs do not have a singular impact on cancer; instead, they play a multifaceted dual role. Under specific circumstances, they can impede tumor growth and influence cancer by delivering oncogenic factors or triggering an immune response. Furthermore, EVs from different sources demonstrate distinct advantages in inhibiting cancer. This research examines the biological characteristics of EVs and their involvement in cancer development to establish a theoretical foundation for better understanding the connection between EVs and cancer. Here, we discuss the potential of EVs from various sources in cancer therapy, as well as the current status and future prospects of engineered EVs in developing more effective cancer treatments.
Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial
Authors: Dumitrascu Oana M. , Doustar Jonah , Fuchs Dieu-Trang , Koronyo Yosef , Sherman Dale S. , Miller Michelle Shizu , Johnson Kenneth O. , Carare Roxana O. , Verdooner Steven R. , Lyden Patrick D. , Schneider Julie A. , Black Keith L. , Koronyo-Hamaoui Maya
Published: June 2024

The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer’s disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.
Functional performance of a novel compression top for female throwing athletes
Authors: Michaelson Dawn , Gascon Sarah , Teel Karla P.
Published: June 2024

This study forged an interdisciplinary design partnership between an apparel designer, biomechanical kinesiologist, and a professional female athlete to design and test a novel new upper body performance garment for improved fit, mobility, comfort, donning/doffing and throwing performance in female professional athletes. Researchers collaborated to address garment functionality and performance during the multi-phase prototyping design process. The final designed performance top was tested against a control for satisfaction differences with fit, mobility, comfort, donning, and doffing, along with throwing performance utilizing a mixed methods questionnaire and motion capture equipment. Open-ended questions were analyzed with content analysis, while quantitative measures utilized ANOVA and independent t-tests. Results indicated the designed performance top had higher fit satisfaction and more optimal positioning during the overhead throw when compared to the control garment, with no difference in comfort or mobility, and the designed top had lower donning and doffing satisfaction. The designed performance top illustrates the need for further research in increasing satisfaction in donning and doffing with bust/bra satisfaction in performance garments and future research to better understand the psychological sensory cues in posture cueing garments.
Contrast enhanced digital mammography as a predictor of breast cancer in patient with pathological nipple discharge
Authors: Khalaf Lamiaa M. R. , El-Sharkawy Mostafa A. M. , Zedan Mohamed , Rezk Khaled , Mosaed Marwa , Kamel Hosam M.
Published: June 2024

Background

Pathological nipple discharge (PND) commonly caused by benign diseases, but occasionally it signifies a major medical concern. Ultrasonography, in addition to mammography, is regarded as the standard imaging modality in the diagnosis of PND but their sensitivity in some cases are low, subsequently we used a contrast enhanced mammography (CEDM) as supplementary diagnostic modality in patients with PND. The purpose of our study was to investigate the diagnostic efficacy of CEDM in evaluating PND patients, added values of incorporating the CEDM in the diagnostic workup of patients with PND and to demonstrate its diagnostic significance as a predictor of malignancy in these patients as there have been few studies that have addressed the role of CEDM in the evaluation of PND.

Results

Forty seven patients with PND were enrolled in this prospective study and underwent CEDM. The CEDM had high specificity (83.2%) compared to the combined sonomammography (SM) (59.3%), as there was a decrease in the number of false positive cases detected by the CEDM (6 cases) compared to the combined SM (11 cases). Combined (SM) had a moderate degree of agreement (55%, P = 0.01) with the final diagnosis, whereas CEDM had a strong degree of agreement (75%, P < 0.001). Additionally, the combined SM reported 76.6% accuracy with an area under the curve of 0.8, whereas the CEDM had 87.2% accuracy with an area under the curve of 0.89.

Conclusions

CEDM had higher specificity, positive predictive value, and accuracy than SM in PND patients, along with its stronger agreement with the final pathology results, subsequently reduce the rate of false positive cases and the rate of recall back, making it a highly accurate malignancy predictor in those patients and can be an invaluable diagnostic imaging tool for identifying associated malignancies.
Tubercular abdominal cocoon: a rare cause of subacute small bowel obstruction
Authors: Girdhar Sachin , Naik Alisha , Uniyal Maneesh
Published: June 2024

Background

Encapsulating peritoneal sclerosis (EPS) or abdominal cocoon is a very rare cause of subacute intestinal obstruction. We hereby report an elderly male presenting with recent-onset subacute intestinal obstruction with characteristic imaging findings of this entity in a background of abdominal tuberculosis on computed tomography (CT) scan that enabled timely diagnosis and appropriate clinical management. The report aims to highlight the typical radiological findings of this rare entity that may otherwise go undetected on imaging investigations, thereby causing a delay in diagnosis with adverse clinical outcomes.

Case presentation

A 57-year-old male patient presented to the hospital with complaints of diffuse abdominal pain with obstipation and recurrent episodes of vomiting since last three days. Clinical evaluation also revealed an ill-defined lump in right lower abdomen. An urgent contrast-enhanced CT scan after oral contrast administration was performed that revealed dilated, clumped up small bowel loops in a ‘whorl-like’ pattern in right iliac fossa region. These obstructed loops were encased by a thick peritoneal membrane giving a ‘cocoon-like’ appearance. Also appreciated were scattered punctate calcific foci in jejunal walls and adjacent peritoneum along with mild ascites. On the basis of typical imaging findings, provisional diagnosis of tubercular cocoon abdomen was given that was later confirmed by laboratory investigations and diagnostic laparoscopy.

Conclusion

Encapsulating peritoneal sclerosis or cocoon abdomen is an extremely rare cause of subacute intestinal obstruction. Further, cocoon abdomen in a background of abdominal tuberculosis is even rarer. However, this case report highlights the characteristic imaging findings for broader audience that enabled prompt diagnosis and appropriate clinical management in this case, achieving optimal clinical outcome.
Awareness of radiation hazards and knowledge of radioprotective measures among radiologists and non-radiology staff: a cross-sectional survey
Authors: Fataftah Jehad , Tayyem Raed , Al-Dwairy Salem , Al Manasra Abdel Rahman , Ibrahim Aqleh , Al Ryalat Randa , Alwreikat Mallak , Al-Shraah Hebatuallah , Alharbi Razan , Alharbi Banan
Published: June 2024

Background

Ionizing radiation has become increasingly utilized in medical practice. Consequently, healthcare workers must be aware of radiation hazards and apply the necessary countermeasures to reduce occupational exposure. This study assessed the awareness of radiation hazards and knowledge of radiation protection measures among radiologists and non-radiologists. These findings may improve the application of various safety measures during medical interventions involving radiation.

Methods

We conducted a cross-sectional questionnaire-based study among 200 medical personnel, including consultant surgeons, physicians, radiologists, nurses, and radiographers, across five hospitals in Jordan between November 2022 and February 2023. The questionnaire collected data on demographic characteristics, awareness of radiation hazards, and knowledge of radioprotective techniques.

Results

Overall, the knowledge of radiation protection and awareness of radiation hazards among the participants were poor (51.55% and 37.17%, respectively). No significant difference was detected between the medical disciplines in terms of the level of knowledge of radiation protection; however, radiographers were significantly more aware of radiation hazards.

Conclusions

According to our findings, medical personnel generally have poor awareness of radiation hazards and radiation protection protocols. However, this understanding can be enhanced through periodic in-service training and regular monitoring of occupational radiation exposure by health professionals.
Multi-omics analyses and molecular subtypes to provide potential therapeutic implications in fumarate hydratase-deficient renal cell carcinoma.
Authors: Zhang Xingming , Zhao Junjie , Yin Xiaoxue , Liang Jiayu , Wang Yongquan , Zheng Linmao , Tan Ping , Zhu Sha , Chen Junru , Zhao Jinge , Rupp Niels J , Sheng Xinan , Wei Qiang , Li Xiang , Yao Jin , Liu Zhenhua , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: June 2024

4522

Background: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare yet highly lethal kidney cancer. To deepen our understanding of FH-deficient RCC, we conducted a comprehensive integrated genomic study. Methods: A total of 126 treatment naïve FH-deficient RCC tissue samples were extracted from our multi-center database. Whole-exome, RNA-seq, and DNA-methylation sequencing were performed. All cases were confirmed with both FH/2SC immunohistochemical staining and FH alterations analysis. Results: Through whole-exome sequencing, we found FH alteration patterns were associated with both tumor behavior and patient survival outcomes. Tumors harboring FH truncating alteration (including nonsense, frameshift and splice site mutations) and mutations near hinge regions (such as p.S419L), were predominantly associated with more aggressive tumor behavior and poorer prognosis. We further developed a CpG sites-specific methylation signature for precise identification of FH-deficient RCC. More importantly, transcriptomic analysis unveiled three distinctive molecular subtypes characterized by enrichment of immune/Angiogenic/Stromal (C1), WNT/Notch/MAPK (C2), and proliferation/stemness (C3) pathways, respectively. Tumors in C1 derived the most substantial survival benefit from a combination of immune checkpoint blockade (ICB) and anti-angiogenic therapy. Tumors in C2 displayed moderate response to this therapeutic approach. In contrast, tumors in C3 exhibited an unfavorable response to anti-angiogenic monotherapy and its combination with ICB. Conclusions: These findings contribute to a profound understanding of the aggressive nature of FH-deficient RCC, offering insights into potential precision medicine approaches for disease management.
FGFR3-mutated urothelial carcinoma of bladder and upper tract including ureter and renal pelvis: A comparative genomic profiling study.
Authors: Basin Michael , Sager Rebecca A , Pavlick Dean , Necchi Andrea , Spiess Philippe E. , Li Roger , Kamat Ashish M. , Grivas Petros , Cheng Liang , Lin Douglas I. , Ross Jeffrey S. , Bratslavsky Gennady , Jacob Joseph M , Gupta Shilpa , Agarwal Neeraj , Basnet Alina
Published: June 2024

4588

Background: Activating DNA sequence genomic alterations (GA) in the FGFR3 gene are known oncodrivers and relevant precision targets for patients with urothelial carcinoma. THOR-1 trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs chemotherapy (taxane or vinflunine) in patients with advanced urothelial carcinoma of the bladder (UCB) or upper tract urothelial carcinoma (UTUC). PROOF-302 trial showed higher frequency of FGFR3 GA in UTUC (30%) vs UCB (13%). We sought to explore differences in frequency of FGFR3 alterations and the genomic landscapes of FGFR3-altered UCB, ureteral urothelial carcinoma (UUC) and renal pelvic urothelial carcinoma (RPUC). Methods: 10,798 UCB and 2,392 UTUC (871 UUC and 1521 RPUC) underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of GA and measure MSI status, TMB level, genomic ancestry, genomic signature, germline mutations and HRD score. PD-L1 was determined by IHC Dako 22C3 using the TPS system. Results were compared using the Fisher Exact method with the Benjamini-Hochberg adjustment. Results: FGFR3mut+ status was significantly higher in RPUC (27.8%), followed by UUC (22.0%), and UCB (18.1%) (P<.0001) (Table). Patients with UCB were more often male compared to patients with UTUC. Median age, EUR ancestry, and GA/tumor were similar. “Targetable” GA in ERBB2 (P=.03), PIK3CA(P=.05), KDM6A (P=.0009) were more frequent in FGFR3mut+ UCB vs FGFR3mut+ UTUC. Targetable GA in PTEN, TSC1 and MTAP currently associated with drugs tested in trials were similar in UBC and UTUC. The KEGG ERBB and VEGF signaling pathways were more frequently identified in UCB (P=.036) and the MMR pathway more frequently identified in UTUC (P=.014). The HRD signature was similar in the groups. MSI-high status was significantly higher in UTUC vs UCB, but there was no significant difference in TMB or PD-L1 expression levels. Conclusions: Although histologically similar, the genomic landscape of FGFR3mut+ RPUC and UUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation, inherent selection biases, and the retrospective nature of this work. Findings may impact clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents. CGP may also inform resistance mechanisms and putative biomarkers of response. [Table: see text]
Outcomes in high-risk subgroups after fixed-duration ibrutinib + venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Up to 5.5 years of follow-up in the phase 2 CAPTIVATE study.
Authors: Wierda William G. , Jacobs Ryan , Barr Paul M. , Allan John N. , Siddiqi Tanya , Tedeschi Alessandra , Kipps Thomas J. , O'Brien Susan Mary , Badoux Xavier C. , Visentin Andrea , Lasica Masa , Carney Dennis , Elinder Camburn Anna , De La Serna Torroba Javier , Szafer-Glusman Edith , Zhou Cathy , Szoke Anita , Dean James P. , Ghia Paolo , Tam Constantine S.
Published: June 2024

7009

Background: The phase 2 CAPTIVATE study evaluated first-line ibrutinib (Ibr) + venetoclax (Ven) for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). Ibr±Ven retreatment was allowed in patients (pts) who had progressive disease (PD). Here, we report outcomes for pts with high-risk genomic features from the FD cohort and retreatment outcomes in pts from the FD cohort and MRD cohort placebo arm. Methods: Pts aged ≤70 y with previously untreated CLL/SLL without restriction on genomic risk factors received 3 cycles of Ibr, then 12 cycles of Ibr+Ven (Ibr, 420 mg/d orally; Ven, 5-wk ramp up to 400 mg/d orally). On-study retreatment included single-agent Ibr (FD cohort or MRD cohort placebo arm); pts with PD >2 y after end of treatment (EOT) could be retreated with FD Ibr+Ven (FD cohort). Results: In the FD cohort (n=159) with a median follow-up of 61.2 mo (range, 0.8–66.3), 5-y PFS and OS rates (95% CI) were 67% (59–74) and 96% (91–98), respectively. 5-y PFS rates were higher in pts with undetectable MRD at 3 mo after EOT in peripheral blood (83%) or bone marrow (84%) vs those without (48% and 50%, respectively). 5-y PFS rates (95% CI) in pts with genomic risk factors were: del(17p)/mutated TP53 41% (21–59), complex karyotype 57% (37–72), del(11q) 64% (30–85), and unmutated IGHV 68% (50–80) (Table). In total, 18 second malignancies occurred in 13 pts (10 events in 8 pts during FD Ibr+Ven, 6 events in 4 pts after EOT and before retreatment, and 2 events in 2 pts during retreatment). Of 202 pts who completed Ibr+Ven (FD cohort, n=159; MRD cohort placebo arm, n=43), 63 have had PD to date; PD occurred >2 y after EOT in 43/63 pts (68%). 32/63 (51%) pts initiated retreatment with Ibr (n=25) or Ibr+Ven (n=7). With a median time on Ibr retreatment of 21.9 mo (range, 0.03–50.4), ORR was 86% in 22 evaluable pts (best response: 1 CR; 1 nodular PR; 17 PR; 2 SD; 1 PD [Richter transformation]). With a median time on Ibr+Ven retreatment of 13.8 mo (range, 3.7–15.1), ORR was 71% in 7 evaluable pts (best response: 1 CR; 4 PR; 1 PR with lymphocytosis; 1 SD). Conclusions: With up to 5.5 y of follow-up, FD Ibr+Ven continues to provide clinically meaningful PFS in pts with high-risk genomic features, as well as in the overall population. Ibr-based retreatment provides promising responses in pts needing subsequent therapy after the all-oral FD regimen of Ibr+Ven. Clinical trial information: NCT02910583 . [Table: see text]
Real-world outcomes of lisocabtagene maraleucel (liso-cel) in patients (pt) with Richter transformation (RT) from the Center for International Blood and Marrow Transplant Research (CIBMTR).
Authors: Winter Allison Marie , Bharadwaj Sushma , Herrera Alex Francisco , Iragavarapu Chaitanya , Mirza Sayeef , Palomba Maria Lia , Patel Sagar S. , Gharibo Mecide Meric , Bernasconi David , Krimmel Tracy , Liu Fei Fei , Roy Debasmita , Pasquini Marcelo C.
Published: June 2024

7010

Background: Pts with RT have poor prognosis and no standard treatment options with median OS of 3–12 mo (Eyre TA. Hematology Am Soc Hematol Educ Program 2023), indicating an unmet need. We report the largest cohort of real-world pts with RT treated with commercial liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product. Methods: This analysis included US pts with RT from the CIBMTR who received commercial liso-cel between 02/2021 and 02/2023. Primary outcomes included ORR, CR rate, duration of response (DOR), PFS, OS, and safety (including cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS] based on Lee 2018 criteria, and prolonged cytopenia defined as grade [gr] 4 thrombocytopenia and/or neutropenia persistent at 30 d after infusion). Results: At data cutoff (08/04/2023), 30 pts with RT were included. Demographics and baseline characteristics at liso-cel infusion are shown in the Table; additional data regarding the pts’ indolent disease and treatment history will be provided in the presentation. Median time from leukapheresis to liso-cel infusion was 35 d (range, 28–63). At median follow-up of 12.3 mo, ORR was 76% among evaluable pts (n = 29) with 66% in CR. Median time to first response was 1.1 mo (range, 0–3.1). Median DOR was not reached (NR); 12-mo DOR rate was 77% (95% CI, 49.5–91). Median PFS (n = 29) and median OS (n = 30) were NR; estimated 12-mo PFS was 54% (95% CI, 33–72) and 12-mo OS was 67% (95% CI, 44–83). Overall, 70% of pts had CRS (gr 3, 0; gr 4, 3%; gr 5, 3% [this pt also had hemophagocytic lymphohistiocytosis]); most common CRS treatments were corticosteroids and tocilizumab (23%) and tocilizumab (20%). ICANS was seen in 47% of pts (gr 3, 17%; gr 4, 10%; gr 5, 0) and most commonly treated with corticosteroids (23%), antiepileptics and corticosteroids (7%), and antiepileptics (7%). Prolonged cytopenia occurred in 17% of pts. One pt had a second primary malignancy (gastrointestinal). Eight (27%) pts died, including 7 because of progression. Conclusions: Pts with RT have poor prognosis with a high unmet need. Here, we show that liso-cel provided meaningful clinical benefit with low incidences of gr ≥ 3 CRS and ICANS observed. The high CR rate is promising in this difficult-to-treat population, and longer follow-up in a larger cohort is needed. [Table: see text]