bluuebunny/crossref_metadata_2025 huggingface dataset:
High-intensity exercise prescription guided by heart rate variability in breast cancer patients: a study protocol for a randomized controlled trial
Authors: Lavín-Pérez Ana Myriam , Collado-Mateo Daniel , Hinojo González Carmen , de Juan Ferré Ana , Ruisánchez Villar Cristina , Mayo Xián , Jiménez Alfonso
Published: March 2023

Background

Breast cancer is a chronic disease with a large growth in its treatments, prognosis, improvements, side effects and rehabilitation therapies research. These advances have also highlighted the need to use physical exercise as a countermeasure to reduce the cardiotoxicity of pharmacological treatments, increase patients' strength and quality of life and improve body composition, physical condition and mental health. However, new investigations show the need for a closed exercise individualisation to produce higher physiological, physical and psychological benefits in remote exercise programs. To this end, the present study will use, in a novel way in this population, heart rate variability (HRV) as a measure for prescribing high-intensity training. Thus, the primary objective of this randomised clinical trial is to analyse the effects of a high-intensity exercise program daily guided by HRV, a preplanned moderate to high-intensity exercise intervention and a usual care group, in breast cancer patients after chemotherapy and radiotherapy treatments.

Methods

For this purpose, a 16-week intervention will be carried out with 90 breast cancer patients distributed in 3 groups (a control group, a moderate to high-intensity preplanned exercise group and a high-intensity exercise group guided by HRV). Both physical exercise interventions will be developed remotely and supervised including strength and cardiovascular exercises. Physiological variables, such as cardiotoxicity, biomarkers, lipid profile, glucose, heart rate and blood pressure; physical measures like cardiorespiratory capacity, strength, flexibility, agility, balance and body composition; and psychosocial variables, as health-related quality of life, fatigue, functionality, self-esteem, movement fear, physical exercise level, anxiety and depression will be measure before, after the intervention and 3 and 6 months follow up.

Discussion

Personalized high-intensity exercise could be a promising exercise intervention in contrast to moderate-intensity or usual care in breast cancer patients to reach higher clinical, physical and mental effects. In addition, the novelty of controlling HRV measures daily may reflect exercise effects and patients' adaptation in the preplanned exercise group and a new opportunity to adjust intensity. Moreover, findings may support the effectiveness and security of physical exercise remotely supervised, although with high-intensity exercise, to reach cardiotoxicity improvements and increase physical and psychosocial variables after breast cancer treatments.

Trial registrationClinicalTrials.gov nº NCT05040867 (https://clinicaltrials.gov/ct2/show/record/NCT05040867).
Can a 3 months treatment with oral Desogestrel prior to insertion of the etonogestrel-releasing contraceptive implant improve continuation rate at 1 year? A randomized trial
Authors: Lombardi Fäh Valeria , Catarino Rosa , Castillo Sarah , Badda Maria , Gezer-Dickschat Sibel , Thieringer Friederike , Tschudin Sibil , Viviano Manuela , Yaron Michal
Published: March 2023

Objective

To evaluate if daily oral 75 µg of Desogestrel (DSG) for 3 months prior to the insertion of etonogestrel-releasing contraceptive implant (ENG-IMPLANT) might help reduce its premature discontinuation.

Results

A total of 66 women were randomized in the ENG-IMPLANT group (26) and in the DSG + ENG-IMPLANT group (40), respectively, in the Geneva University Hospitals and Basel University Hospital, from August 15th, 2016 through September 30th, 2019. In the DSG + ENG-IMPLANT group, patients were given a 3 months’ supply of 75 µg of DSG before the insertion of the ENG-IMPLANT. All women were seen after 3 months for bleeding and satisfaction evaluation, and at 12 months post ENG-IMPLANT insertion. Higher levels of satisfaction at 12-months were found in the ENG-IMPLANT group compared to the DSG + ENG-IMPLANT group (8.5 ± 1.7 vs. 6.6 ± 2.9, p = 0.012). There were no statistically significant differences regarding tolerance (7.8 ± 2.5 vs 6.8 ± 2.6, p = 0.191) and contraceptive continuation (80% vs 72.4%, p = 0.544) between groups.

Conclusion

DSG prior to insertion of the ENG-IMPLANT did not improve its continuation rate neither its satisfaction at 1 year.

Trial registration NCT05174195. Retrospectively registered, the 30th December 2021
Purpose in life promotes resilience to age-related brain burden in middle-aged adults
Authors: Abellaneda-Pérez Kilian , Cattaneo Gabriele , Cabello-Toscano María , Solana-Sánchez Javier , Mulet-Pons Lídia , Vaqué-Alcázar Lídia , Perellón-Alfonso Ruben , Solé-Padullés Cristina , Bargalló Núria , Tormos Josep M. , Pascual-Leone Alvaro , Bartrés-Faz David
Published: March 2023

Background

Disease-modifying agents to counteract cognitive impairment in older age remain elusive. Hence, identifying modifiable factors promoting resilience, as the capacity of the brain to maintain cognition and function with aging and disease, is paramount. In Alzheimer’s disease (AD), education and occupation are typical cognitive reserve proxies. However, the importance of psychological factors is being increasingly recognized, as their operating biological mechanisms are elucidated. Purpose in life (PiL), one of the pillars of psychological well-being, has previously been found to reduce the deleterious effects of AD-related pathological changes on cognition. However, whether PiL operates as a resilience factor in middle-aged individuals and what are the underlying neural mechanisms remain unknown.

Methods

Data was obtained from 624 middle-aged adults (mean age 53.71 ± 6.9; 303 women) from the Barcelona Brain Health Initiative cohort. Individuals with lower (LP; N = 146) and higher (HP; N = 100) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status, a measure reflecting brain burden (white matter lesions; WMLs), and resting-state functional connectivity, examining system segregation (SyS) parameters using 14 common brain circuits.

Results

Neuropsychological status and WMLs burden did not differ between the PiL groups. However, in the LP group, greater WMLs entailed a negative impact on executive functions. Subjects in the HP group showed lower SyS of the dorsal default-mode network (dDMN), indicating lesser segregation of this network from other brain circuits. Specifically, HP individuals had greater inter-network connectivity between specific dDMN nodes, including the frontal cortex, the hippocampal formation, the midcingulate region, and the rest of the brain. Greater functional connectivity in some of these nodes positively correlated with cognitive performance.

Conclusion

Expanding previous findings on AD pathology and advanced age, the present results suggest that higher rates of PiL may promote resilience against brain changes already observable in middle age. Furthermore, having a purposeful life implies larger functional integration of the dDMN, which may potentially reflect greater brain reserve associated to better cognitive function.
Uncovering heterogeneous cognitive trajectories in mild cognitive impairment: a data-driven approach
Authors: Wang Xiwu , Ye Teng , Zhou Wenjun , Zhang Jie ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2023

Background

Given the complex and progressive nature of mild cognitive impairment (MCI), the ability to delineate and understand the heterogeneous cognitive trajectories is crucial for developing personalized medicine and informing trial design. The primary goals of this study were to examine whether different cognitive trajectories can be identified within subjects with MCI and, if present, to characterize each trajectory in relation to changes in all major Alzheimer’s disease (AD) biomarkers over time.

Methods

Individuals with a diagnosis of MCI at the first visit and ≥ 1 follow-up cognitive assessment were selected from the Alzheimer’s Disease Neuroimaging Initiative database (n= 936; age 73 ± 8; 40% female; 16 ± 3 years of education; 50% APOE4 carriers). Based on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) total scores from baseline up to 5 years follow-up, a non-parametrick-means longitudinal clustering method was performed to obtain clusters of individuals with similar patterns of cognitive decline. We further conducted a series of linear mixed-effects models to study the associations of cluster membership with longitudinal changes in other cognitive measures, neurodegeneration, and in vivo AD pathologies.

Results

Four distinct cognitive trajectories emerged. Cluster 1 consisted of 255 individuals (27%) with a nearly non-existent rate of change in the ADAS-Cog-13 over 5 years of follow-up and a healthy-looking biomarker profile. Individuals in the cluster 2 (n= 336, 35%) and 3 (n= 240, 26%) groups showed relatively mild and moderate cognitive decline trajectories, respectively. Cluster 4, comprising about 11% of our study sample (n= 105), exhibited an aggressive cognitive decline trajectory and was characterized by a pronouncedly abnormal biomarker profile.

Conclusions

Individuals with MCI show substantial heterogeneity in cognitive decline. Our findings may potentially contribute to improved trial design and patient stratification.
Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD
Authors: Xiao Yaqiong , Wen Teresa H. , Kupis Lauren , Eyler Lisa T. , Taluja Vani , Troxel Jaden , Goel Disha , Lombardo Michael V. , Pierce Karen , Courchesne Eric
Published: March 2023

Background

Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown.

Methods

We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3 ± 0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child’s social and language abilities were examined.

Results

While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal–visual region connectivity and communication ability (r(49) = 0.55, p < 0.001) and between temporal–precuneus connectivity and expressive language ability (r(49) = 0.58, p < 0.001).

Limitations

The distinct connectivity–behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range.

Conclusions

Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve.
Does clinical decision support system promote expert consensus for appropriate imaging referrals? Chest–abdominal–pelvis CT as a case study
Authors: Markus Talya , Saban Mor , Sosna Jacob , Assaf Jacob , Cohen Dotan , Vaknin Sharona , Luxenburg Osnat , Singer Clara , Shaham Dorith
Published: March 2023

Objectives

We assessed the appropriateness of chest–abdominal–pelvis (CAP) CT scan use in the Emergency Department (ED), based on expert physicians and the ESR iGuide, a clinical decision support system (CDSS).

Methods

A retrospective cross-study was conducted. We included 100 cases of CAP-CT scans ordered at the ED. Four experts rated the appropriateness of the cases on a 7-point scale, before and after using the decision support tool.

Results

Before using the ESR iGuide the overall mean rating of the experts was 5.2 ± 1.066, and it increased slightly after using the system (5.85 ± 0.911 (p < 0.01)). Using a threshold of 5 (on a 7-level scale), the experts considered only 63% of the tests appropriate before using the ESR iGuide. The number increased to 89% after consultation with the system. The degree of overall agreement among the experts was 0.388 before ESR iGuide consultation and 0.572 after consultation. According to the ESR iGuide, for 85% of the cases, CAP CT was not a recommended option (score 0). Abdominal–Pelvis CT was "usually appropriate" for 65 out of the 85 (76%) cases (score 7–9). 9% of the cases did not require CT as first exam modality.

Conclusions

According to both the experts and the ESR iGuide, inappropriate testing was prevalent, in terms of both frequency of the scans and also inappropriately chosen body regions. These findings raise the need for unified workflows that might be achieved using a CDSS. Further studies are needed to investigate the CDSS contribution to the informed decision-making and increased uniformity among different expert physicians when ordering the appropriate test.
Improving detection of impacted animal bones on lateral neck radiograph using a deep learning artificial intelligence algorithm
Authors: Chen Yueh-Sheng , Luo Sheng-Dean , Lee Chi-Hsun , Lin Jian-Feng , Lin Te-Yen , Ko Sheung-Fat , Yu Chiun-Chieh , Chiang Pi-Ling , Wang Cheng-Kang , Chiu I.-Min , Huang Yii-Ting , Tai Yi-Fan , Chiang Po-Teng , Lin Wei-Che
Published: March 2023

Objective

We aimed to develop a deep learning artificial intelligence (AI) algorithm to detect impacted animal bones on lateral neck radiographs and to assess its effectiveness for improving the interpretation of lateral neck radiographs.

Methods

Lateral neck radiographs were retrospectively collected for patients with animal bone impaction between January 2010 and March 2020. Radiographs were then separated into training, validation, and testing sets. A total of 1733 lateral neck radiographs were used to develop the deep learning algorithm. The testing set was assessed for the stand-alone deep learning AI algorithm and for human readers (radiologists, radiology residents, emergency physicians, ENT physicians) with and without the aid of the AI algorithm. Another radiograph cohort, collected from April 1, 2020, to June 30, 2020, was analyzed to simulate clinical application by comparing the deep learning AI algorithm with radiologists’ reports.

Results

In the testing set, the sensitivity, specificity, and accuracy of the AI model were 96%, 90%, and 93% respectively. Among the human readers, all physicians of different subspecialties achieved a higher accuracy with AI-assisted reading than without. In the simulation set, among the 20 cases positive for animal bones, the AI model accurately identified 3 more cases than the radiologists’ reports.

Conclusion

Our deep learning AI model demonstrated a higher sensitivity for detection of animal bone impaction on lateral neck radiographs without an increased false positive rate. The application of this model in a clinical setting may effectively reduce time to diagnosis, accelerate workflow, and decrease the use of CT.
Correlation of androgen receptor with ultrasound, clinicopathological features and clinical outcomes in breast cancer
Authors: Zhang Xudong , Cui Hao , Hu Nana , Han Peng , Fan Wei , Wang Panting , Zuo Xiaoxuan , Zhao Dantong , Huang He , Li Shuo , Kong Hanqing , Peng Fuhui , Tian Jiawei , Zhang Lei
Published: March 2023

Background

This study aimed to explore whether there is an association between androgen receptor (AR) expression and ultrasound, clinicopathological features and prognosis of breast cancer.

Methods

A total of 141 breast cancer patients were included in this retrospective study. AR expression was analyzed by immunohistochemistry. The images of B-mode, color Doppler and strain elastography from 104 patients were collected continuously, and the corresponding ultrasound characteristics were obtained. The differences in ultrasound and clinicopathological features in different AR status were analyzed. Progression-free survival (PFS) of patients was obtained through up to 90 months of follow-up; then, the effect of AR on PFS was analyzed. Subsequently, a nomogram was constructed to predict the AR status. The predictive accuracy was calculated using C-index.

Results

The positive expression of AR (AR +) was associated with lower histological grade (p = 0.034) and lower Ki-67 level (p = 0.029). Triple-negative breast cancer (TNBC) had the lowest probability of AR + (p < 0.001). The AR + group mostly showed unsmooth margin (p < 0.001), posterior acoustic shadowing (p = 0.002) and higher elasticity score (p = 0.022) on ultrasound. The echo pattern of most tumors with AR + was heterogeneous (p = 0.024) in Luminal A subtype. AR + could be a sign of a better prognosis in overall breast cancer (p < 0.001), as well as in human epidermal growth factor receptor 2 (HER2) overexpression and Luminal B subtypes (p = 0.001 and 0.025). The nomogram showed relatively reliable performance with a C-index of 0.799.

Conclusion

Our research demonstrated that AR expression was closely related to ultrasound, clinicopathological features and prognosis of breast cancer.
Characterization of high-grade prostate cancer at multiparametric MRI: assessment of PI-RADS version 2.1 and version 2 descriptors across 21 readers with varying experience (MULTI study)
Authors: Di Franco Florian , Souchon Rémi , Crouzet Sébastien , Colombel Marc , Ruffion Alain , Klich Amna , Almeras Mathilde , Milot Laurent , Rabilloud Muriel , Rouvière Olivier ,   on behalf of the MULTI Study Group, Debeer Sabine , Dubreuil-Chambardel Marine , Bravetti Stéphanie , Cadot Stéphane , Cayot Bénédicte , Jouve de Guibert Paul-Hugo , Moldovan Paul Cezar , Pagnoux Gaele , Pernet Clément , Perrier Louis , Stacoffe Nicolas , Transin Sarah , Abihanna Michel , Ronze Sébastien , Ben Cheikh Alexandre , Bratan Flavie , Rosset Rémy , Cadiot Domitille , Iv Leangsing , Champagnac Jean , Girouin Nicolas , Lopez Olivier , Soto Thammavong Athivada
Published: March 2023

Objective

To assess PI-RADSv2.1 and PI-RADSv2 descriptors across readers with varying experience.

Methods

Twenty-one radiologists (7 experienced (≥ 5 years) seniors, 7 less experienced seniors and 7 juniors) assessed 240 ‘predefined’ lesions from 159 pre-biopsy multiparametric prostate MRIs. They specified their location (peripheral, transition or central zone) and size, and scored them using PI-RADSv2.1 and PI-RADSv2 descriptors. They also described and scored ‘additional’ lesions if needed. Per-lesion analysis assessed the ‘predefined’ lesions, using targeted biopsy as reference; per-lobe analysis included ‘predefined’ and ‘additional’ lesions, using combined systematic and targeted biopsy as reference. Areas under the curve (AUCs) quantified the performance in diagnosing clinically significant cancer (csPCa; ISUP ≥ 2 cancer). Kappa coefficients (κ) or concordance correlation coefficients (CCC) assessed inter-reader agreement.

Results

At per-lesion analysis, inter-reader agreement on location and size was moderate-to-good (κ = 0.60–0.73) and excellent (CCC ≥ 0.80), respectively. Agreement on PI-RADSv2.1 scoring was moderate (κ = 0.43–0.47) for seniors and fair (κ = 0.39) for juniors. Using PI-RADSv2.1, juniors obtained a significantly lower AUC (0.74; 95% confidence interval [95%CI]: 0.70–0.79) than experienced seniors (0.80; 95%CI 0.76–0.84;p = 0.008) but not than less experienced seniors (0.74; 95%CI 0.70–0.78;p = 0.75). As compared to PI-RADSv2, PI-RADSv2.1 downgraded 17 lesions/reader (interquartile range [IQR]: 6–29), of which 2 (IQR: 1–3) were csPCa; it upgraded 4 lesions/reader (IQR: 2–7), of which 1 (IQR: 0–2) was csPCa. Per-lobe analysis, which included 60 (IQR: 25–73) ‘additional’ lesions/reader, yielded similar results.

Conclusions

Experience significantly impacted lesion characterization using PI-RADSv2.1 descriptors. As compared to PI-RADSv2, PI-RADSv2.1 tended to downgrade non-csPCa lesions, but this effect was small and variable across readers.
Efficient structured reporting in radiology using an intelligent dialogue system based on speech recognition and natural language processing
Authors: Jorg Tobias , Kämpgen Benedikt , Feiler Dennis , Müller Lukas , Düber Christoph , Mildenberger Peter , Jungmann Florian
Published: March 2023

Background

Structured reporting (SR) is recommended in radiology, due to its advantages over free-text reporting (FTR). However, SR use is hindered by insufficient integration of speech recognition, which is well accepted among radiologists and commonly used for unstructured FTR. SR templates must be laboriously completed using a mouse and keyboard, which may explain why SR use remains limited in clinical routine, despite its advantages. Artificial intelligence and related fields, like natural language processing (NLP), offer enormous possibilities to facilitate the imaging workflow. Here, we aimed to use the potential of NLP to combine the advantages of SR and speech recognition.

Results

We developed a reporting tool that uses NLP to automatically convert dictated free text into a structured report. The tool comprises a task-oriented dialogue system, which assists the radiologist by sending visual feedback if relevant findings are missed. The system was developed on top of several NLP components and speech recognition. It extracts structured content from dictated free text and uses it to complete an SR template in RadLex terms, which is displayed in its user interface. The tool was evaluated for reporting of urolithiasis CTs, as a use case. It was tested using fictitious text samples about urolithiasis, and 50 original reports of CTs from patients with urolithiasis. The NLP recognition worked well for both, with an F1 score of 0.98 (precision: 0.99; recall: 0.96) for the test with fictitious samples and an F1 score of 0.90 (precision: 0.96; recall: 0.83) for the test with original reports.

Conclusion

Due to its unique ability to integrate speech into SR, this novel tool could represent a major contribution to the future of reporting.
Development and clinical utility analysis of a prostate zonal segmentation model on T2-weighted imaging: a multicenter study
Authors: Xu Lili , Zhang Gumuyang , Zhang Daming , Zhang Jiahui , Zhang Xiaoxiao , Bai Xin , Chen Li , Peng Qianyu , Jin Ru , Mao Li , Li Xiuli , Jin Zhengyu , Sun Hao
Published: March 2023

Objectives

To automatically segment prostate central gland (CG) and peripheral zone (PZ) on T2-weighted imaging using deep learning and assess the model’s clinical utility by comparing it with a radiologist annotation and analyzing relevant influencing factors, especially the prostate zonal volume.

Methods

A 3D U-Net-based model was trained with 223 patients from one institution and tested using one internal testing group (n = 93) and two external testing datasets, including one public dataset (ETDpub, n = 141) and one private dataset from two centers (ETDpri, n = 59). The Dice similarity coefficients (DSCs), 95th Hausdorff distance (95HD), and average boundary distance (ABD) were calculated to evaluate the model’s performance and further compared with a junior radiologist’s performance in ETDpub. To investigate factors influencing the model performance, patients’ clinical characteristics, prostate morphology, and image parameters in ETDpri were collected and analyzed using beta regression.

Results

The DSCs in the internal testing group, ETDpub, and ETDpri were 0.909, 0.889, and 0.869 for CG, and 0.844, 0.755, and 0.764 for PZ, respectively. The mean 95HD and ABD were less than 7.0 and 1.3 for both zones. The U-Net model outperformed the junior radiologist, having a higher DSC (0.769 vs. 0.706) and higher intraclass correlation coefficient for volume estimation in PZ (0.836 vs. 0.668). CG volume and Magnetic Resonance (MR) vendor were significant influencing factors for CG and PZ segmentation.

Conclusions

The 3D U-Net model showed good performance for CG and PZ auto-segmentation in all the testing groups and outperformed the junior radiologist for PZ segmentation. The model performance was susceptible to prostate morphology and MR scanner parameters.
Retroperitoneal lymphangioma as the final diagnosis of a middle-aged woman with abdominal pain: a case report
Authors: Asadzadeh Aghdaei Hamid , Rabbani Amirhassan , Sadeghi Amir , Rezvani Hamid , Sherkat Ghazal , Salarieh Naghmeh , Ketabi Moghadam Pardis
Published: March 2023

Background

Lymphangiomas are lesions attributed to congenital malformations of the lymphatic system, or acquired chronic obstruction of the lymphatic network due to trauma, radiation, surgical manipulation, inflammation, or infection. Overall, lymaphangiomas are rare, and particularly, retroperitoneal lymphangiomas are far more uncommon per reported cases.

Case presentation

A 49-year-old Iranian woman presented with a progressive abdominal pain since approximately 1 month before admission. She was found to have a retroperitoneal lymphangioma after a precise radiological and surgical workup.

Conclusion

Retroperitoneal lymphangiomas are rare lesions, sometimes indistinguishable from malignant lesions originating from pancreas and adjacent organs. Complete surgical removal and histologic evaluation of the lesion is the gold standard of treatment and diagnosis.
Cubital tunnel syndrome of the ulnar nerve caused by an epineural ganglion cyst: a case report and review of the literature
Authors: Gashi Y. N. , Naiem Mohamed Eltayeb Abdelrahman
Published: March 2023

Background

The ulnar nerve has a long and complex anatomical course, originating from the brachial neural plexus in the neck with nerve trunk formation at the posterior neck triangle, and on to the axilla. This intricate anatomical pathway renders the nerve susceptible to compression, direct injury, and traction throughout its course. Compression of the ulnar nerve is the second most common compression neuropathy of the median nerve adjacent to the wrist joint, after carpal tunnel syndrome.

Case presentation

A 45-year-old Sudanese housewife complained of progressive right forearm and hand muscle wasting, pain, and neuropathic symptoms. She was diagnosed with right-sided cubital tunnel syndrome. The diagnosis was derived intraoperatively from a nerve conduction study suggesting the level of conduction block and recommending decompression. Magnetic resonance imaging was not done preoperatively due to financial limitations. An epineural ganglion (15 × 20 mm2) compressing and flattening the ulnar nerve was diagnosed intraoperatively. Surgical decompression of the ulnar nerve and removal of the epineural ganglion achieved a remarkable postoperative result and pleasing outcome.

Conclusion

Surgical management is the cornerstone of treatment for compressive neuropathy and ranges from simple nerve decompression to complex neurolysis procedures and nerve transposition to adjust the anatomical course of the nerve.
Abdominal nonfunctional paraganglioma in which succinate dehydrogenase subunit B (SDHB) immunostaining was performed: a case report
Authors: Tanaka Takazo , Joraku Akira , Ishibashi Sayuri , Endo Keisuke , Emura Masahiro , Kikuchi Yusuke , Shikama Akito , Kimura Noriko , Shimazui Toru
Published: March 2023

Background

Abdominal nonfunctional paraganglioma is rare. Malignant potential of paraganglioma is assessed by Grading of Adrenal Pheochromocytoma and Paraganglioma score and genetic testing, but genetic testing is not common. We present a case of abdominal nonfunctional paraganglioma whose malignant potential was assessed by grading of adrenal pheochromocytoma and paraganglioma score and succinate dehydrogenase subunit B staining alternative to genetic testing.

Case presentation

A 39-year-old Japanese man had a right retroperitoneal tumor without symptoms. Uptake in the tumor was shown by 123I-meta-iodobenzylguanidine scintigraphy. There were no metastases. The results of biochemical workups including blood hormones and urinary metanephrines were normal. We performed retroperitoneoscopic surgery. The tumor was positive for chromogranin A staining but negative for tyrosine hydroxylase. On the basis of the preoperative biochemical workups and pathology results, we diagnosed the tumor as nonfunctional paraganglioma. The Grading of Adrenal Pheochromocytoma and Paraganglioma score classified the tumor as moderately differentiated. Furthermore, negative succinate dehydrogenase subunit B staining suggested the patient has the SDHx (SDHA, SDHB, SDHC and SDHD) mutation.

Conclusion

Abdominal nonfunctional PGLs are associated with SDHB mutation, and SDHB staining should be performed as a screening.
Presumed veterinary niclosamide-induced retinal toxicity in a human: a case report
Authors: Bazvand Fatemeh , Riazi-Esfahani Hamid , Salari Farhad
Published: March 2023

Background

To report the first case of bull’s eye maculopathy associated with veterinary niclosamide.

Case presentation

A 27-year-old Iranian female presented with a history of reduced vision and photopsia since 3 years, after accidental ingestion of four boluses of veterinary niclosamide. Fundus examination showed atrophy in parafoveal retinal pigmentary epithelium, appearing as bilateral bull’s-eye maculopathy. Optical coherence tomography revealed disruption of the parafoveal ellipsoid zone and outer retinal thinning, appearing as a flying saucer sign. Electroretinography displayed decreased scotopic and photopic amplitudes with normal waveform in both eyes. The causality score was 4, showing “possible” retinopathy due to niclosamide according to Naranjo’s causality assessment algorithm. Based on clinical and ancillary findings, a diagnosis of niclosamide-induced maculopathy was made.

Conclusion

Veterinary niclosamide is an anthelmintic drug that in higher doses could be detrimental to the human retina. Awareness about its side effects and appropriate drug labeling could prevent accidental toxicity.
Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
Authors: Yan Yaping , Li Kaixiu , Jiang Jiang , Jiang Lihong , Ma Xiang , Ai Fang , Qiu Shuai , Si Wei
Published: March 2023

Background

The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated.

Methods

The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group.

Results

A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis.

Conclusions

We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis.
Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine
Authors: Aguirre-Vázquez Alain , Castorena-Torres Fabiola , Silva-Ramírez Beatriz , Peñuelas-Urquides Katia , Camacho-Moll María Elena , Salazar-Olivo Luis A. , Velasco Iván , Bermúdez de León Mario
Published: March 2023

Background

The generation of induced pluripotent stem cells has opened the field of study for stem cell research, disease modeling and drug development. However, the epigenetic signatures present in somatic cells make cell reprogramming still an inefficient process. This epigenetic memory constitutes an obstacle in cellular reprogramming. Here, we report the effect of hydralazine (HYD) and valproic acid (VPA), two small molecules with proven epigenetic activity, on the expression of pluripotency genes in adult (aHF) and neonatal (nbHF) human fibroblasts.

Methods

aHF and nbHF were treated with HYD and/or VPA, and viability and gene expression assays for OCT4, NANOG, c-MYC, KLF4, DNMT1, TET3, ARID1A and ARID2 by quantitative PCR were performed. aHF and nbHF were transfected with episomal plasmid bearing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and exposed to HYD and VPA to determine the reprogramming efficiency. Methylation sensitive restriction enzyme (MSRE) qPCR assays were performed on OCT4 and NANOG promoter regions. Immunofluorescence assays were carried out for pluripotency genes on iPSC derived from aHF and nbHF.

Results

HYD upregulated the expression of OCT4 (2.5-fold) and NANOG (fourfold) genes but not c-Myc or KLF4 in aHF and had no significant effect on the expression of all these genes in nbHF. VPA upregulated the expression of NANOG (twofold) in aHF and c-MYC in nbHF, while it downregulated the expression of NANOG in nbHF. The combination of HYD and VPA canceled the OCT4 and NANOG overexpression induced by HYD in aHF, while it reinforced the effects of VPA on c-Myc expression in nbHF. The HYD-induced overexpression of OCT4 and NANOG in aHDF was not dependent on demethylation of gene promoters, and no changes in the reprogramming efficiency were observed in both cell populations despite the downregulation of epigenetic genes DNMT1, ARID1A, and ARID2 in nbHF.

Conclusions

Our data provide evidence that HYD regulates the expression of OCT4 and NANOG pluripotency genes as well as ARID1A and ARID2 genes, two members of the SWI/SNF chromatin remodeling complex family, in normal human dermal fibroblasts.
Intrathecal CAR-NK cells infusion for isolated CNS relapse after allogeneic stem cell transplantation: case report
Authors: Yuan Jing , Wang Fuxu , Ren Hanyun
Published: March 2023

A 24-year-old man with central nervous system (CNS) involvement of T-cell lineage acute lymphoblastic leukemia received sibling allogeneic stem cell transplantation (allo-SCT). He developed isolated CNS relapse early post-SCT, while high-dose systemic chemotherapy, intrathecal (IT) triple infusion and IT donor lymphocytes infusion (DLI) all demonstrated effectiveness. We performed IT umbilical cord blood-derived CAR-NK (target CD7) cells infusion, which was not previously reported. After infusion, detection of cytokines revealed that interferon-γ, interleukin-6 and interleukin-8 increased in CSF. He developed high fever, headache, nausea, vomiting and a spinal cord transection with incontinence in a short time, whereas the ptosis and blurred vision improved completely. The bone marrow remained encouragingly complete remission and complete donor chimerism over 9 months after IT CAR-NK cells infusion. In conclusion, IT CAR-NK cells infusion is a potentially feasible and effective option for patients with CNS relapse, with limited neurological toxicity.
Human umbilical cord mesenchymal stem cells conditioned medium exerts anti-tumor effects on KGN cells in a cell density-dependent manner through activation of the Hippo pathway
Authors: Wan Wenjing , Miao Yuyang , Niu Yuwei , Zhu Kunyuan , Ma Yingwan , Pan Menghao , Ma Baohua , Wei Qiang
Published: March 2023

Background

The conditioned medium from human umbilical cord mesenchymal stem cells (UCMSCs-CM) provides a new cell-free therapy for tumors due to its unique secretome. However, there are many contradictory reports about the effect of UCMSCs-CM on tumor cells. The loss of contact inhibition is a common characteristic of tumor cells. A relationship between the effect of UCMSCs-CM on tumor cells and contact inhibition in tumor cells is rarely concerned. Whether the effect of UCMSCs-CM on tumor cells is affected by cell density? Here, we explored the effect of UCMSCs-CM on granulosa tumor cell line (KGN) cells at low or high density.

Methods

Growth curve and CCK8 assay were used to assess cell proliferation and viability. Scratch wound and matrigel invasion assay were implicated to detect cell motility of KGN cells. UCMSCs-CM effects on cell cycle, apoptosis and pathway-related proteins were investigated by flow cytometry, TUNEL assay, western blot and immunofluorescence analysis respectively.

Results

In growth curve analysis, before KGN cells proliferated into confluence, UCMSCs-CM had no effect on cell proliferation. However, once the cells proliferate to contact each other, UCMSCs-CM significantly inhibited proliferation. Meanwhile, when KGN cells were implanted at high density, UCMSCs-CM could induce cell cycle arrest at G1 phase, inhibit cell migration, invasion and promote apoptosis. While it had no similar effect on KGN cells implanted at low density. In mechanism, the UCMSCs-CM treatment activated the Hippo pathway when KGN cells were implanted at high density. Consistently, the MST1/2 inhibitor, XMU-MP-1, inhibited the activation of the Hippo pathway induced by UCMSCs-CM treatment and accordingly declined the anti-tumor effect of UCMSCs-CM on KGN cells.

Conclusions

The effect of UCMSCs-CM on tumor cells is affected by cell density. UCMSCs-CM exerted anti-tumor effect on KGN cells by activating Hippo pathway to restore contact inhibition. Our results suggest that UCMSCs-CM is a promising therapeutic candidate for GCT treatment.
Residual periodontal ligament in the extraction socket promotes the dentin regeneration potential of DPSCs in the rabbit jaw
Authors: Luo Bin , Luo Yu , He Lin , Cao Yangyang , Jiang Qingsong
Published: March 2023

Background

Because of the low regeneration efficiency and unclear underlying molecular mechanism, tooth regeneration applications are limited. In this study, we explored the influence of residual periodontal ligament on the dentin regeneration potential of dental pulp stem cells (DPSCs) in the jaw.

Methods

To establish a tooth regeneration model, the incisors of New Zealand white rabbits were extracted while preserving residual periodontal ligament, followed by the implantation of DPSCs. After 3 months, micro-computed tomography (micro-CT), stereomicroscopy and scanning electron microscopy (SEM) were used to observe the volume, morphology and microstructure of regenerated tissue. Histological staining and immunostaining analyses were used to observe the morphological characteristics and expression of the dentin-specific proteins DMP1 and DSPP. To explore the mechanism, DPSCs and periodontal ligament stem cells (PDLSCs) were cocultured in vitro, and RNA was collected from the DPSCs for RNA-seq and bioinformatic analysis.

Results

The results of micro-CT and stereomicroscopy showed that the number of sites with regeneration and the volume of regenerated tissue in the DPSCs/PDL group (6/8, 1.07 ± 0.93 cm3) were larger than those in the DPSCs group (3/8, 0.23 ± 0.41 cm3). The results of SEM showed that the regenerated dentin-like tissue in the DPSCs and DPSCs/PDL groups contained dentin tubules. Haematoxylin and eosin staining and immunohistochemical staining indicated that compared with the DPSCs group, the DPSCs/PDL group showed more regular regenerated tissue and higher expression levels of the dentin-specific proteins DMP1 and DSPP (DMP1: P = 0.02, DSPP: P = 0.01). RNA-seq showed that the coculture of DPSCs with PDLSCs resulted in the DPSCs differentially expressing 427 mRNAs (285 upregulated and 142 downregulated), 41 lncRNAs (26 upregulated and 15 downregulated), 411 circRNAs (224 upregulated and 187 downregulated), and 19 miRNAs (13 upregulated and 5 downregulated). Bioinformatic analysis revealed related Gene Ontology function and signalling pathways, including extracellular matrix (ECM), tumour necrosis factor (TNF) signalling and chemokine signalling pathways.

Conclusions

Residual periodontal ligament in the extraction socket promotes the dentin regeneration potential of DPSCs in the jaw. RNA-seq and bioinformatic analysis revealed that ECM, TNF signalling and chemokine signalling pathways may represent the key factors and signalling pathways.
Interpreting vibrational circular dichroism spectra: the Cai•factor for absolute configuration with confidence
Authors: Lam Jonathan , Lewis Richard J. , Goodman Jonathan M.
Published: March 2023

Vibrational circular dichroism (VCD) spectroscopy can generate the data required for the assignment of absolute configuration, but the spectra are hard to interpret. We have recorded VCD data for thirty pairs of small organic compounds and we use this database to validate a method for the automated analysis of VCD spectra and the assignment of absolute configuration: the Cai•factor (Configuration: absolute information). The analysis of the data demonstrates that the procedure is a reliable and time-efficient method for determination of absolute configuration, which gives both the assignment and a measure of confidence in the outcome, even when the spectra are imperfect. The majority of molecules tested have a high confidence score and all of these have the correct assignment.
Chemical rules for optimization of chemical mutagenicity via matched molecular pairs analysis and machine learning methods
Authors: Lou Chaofeng , Yang Hongbin , Deng Hua , Huang Mengting , Li Weihua , Liu Guixia , Lee Philip W. , Tang Yun
Published: March 2023

Chemical mutagenicity is a serious issue that needs to be addressed in early drug discovery. Over a long period of time, medicinal chemists have manually summarized a series of empirical rules for the optimization of chemical mutagenicity. However, given the rising amount of data, it is getting more difficult for medicinal chemists to identify more comprehensive chemical rules behind the biochemical data. Herein, we integrated a large Ames mutagenicity data set with 8576 compounds to derive mutagenicity transformation rules for reversing Ames mutagenicity via matched molecular pairs analysis. A well-trained consensus model with a reasonable applicability domain was constructed, which showed favorable performance in the external validation set with an accuracy of 0.815. The model was used to assess the generalizability and validity of these mutagenicity transformation rules. The results demonstrated that these rules were of great value and could provide inspiration for the structural modifications of compounds with potential mutagenic effects. We also found that the local chemical environment of the attachment points of rules was critical for successful transformation. To facilitate the use of these mutagenicity transformation rules, we integrated them into ADMETopt2 (http://lmmd.ecust.edu.cn/admetsar2/admetopt2/), a free web server for optimization of chemical ADMET properties. The above-mentioned approach would be extended to the optimization of other toxicity endpoints.

Graphical Abstract
Comprehensive genome analysis of Burkholderia contaminans SK875, a quorum-sensing strain isolated from the swine
Authors: Kim Eiseul , Jung Hae-In , Park Si Hong , Kim Hae-Yeong , Kim Soo-Ki
Published: March 2023

The Burkholderia cepacia complex (BCC) is a Gram-negative bacterial, including Burkholderia contaminans species. Although the plain Burkholderia is pervasive from taxonomic and genetic perspectives, a common characteristic is that they may use the quorum-sensing (QS) system. In our previous study, we generated the complete genome sequence of Burkholderia contaminans SK875 isolated from the respiratory tract. To our knowledge, this is the first study to report functional genomic features of B. contaminans SK875 for understanding the pathogenic characteristics. In addition, comparative genomic analysis for five B. contaminans genomes was performed to provide comprehensive information on the disease potential of B. contaminans species. Analysis of average nucleotide identity (ANI) showed that the genome has high similarity (> 96%) with other B. contaminans strains. Five B. contaminans genomes yielded a pangenome of 8832 coding genes, a core genome of 5452 genes, the accessory genome of 2128 genes, and a unique genome of 1252 genes. The 186 genes were specific to B. contaminans SK875, including toxin higB-2, oxygen-dependent choline dehydrogenase, and hypothetical proteins. Genotypic analysis of the antimicrobial resistance of B. contaminans SK875 verified resistance to tetracycline, fluoroquinolone, and aminoglycoside. Compared with the virulence factor database, we identified 79 promising virulence genes such as adhesion system, invasions, antiphagocytic, and secretion systems. Moreover, 45 genes of 57 QS-related genes that were identified in B. contaminans SK875 indicated high sequence homology with other B. contaminans strains. Our results will help to gain insight into virulence, antibiotic resistance, and quorum sensing for B. contaminans species.