bluuebunny/crossref_metadata_2025 huggingface dataset:
CHI3L1 in the CSF is a potential biomarker for anti-leucine-rich glioma inactivated 1 encephalitis
Authors: Li Jinyi , Li Hongyan , Wang Yunhuan , Zhao Xiuhe , Wang Shengjun , Li Ling
Published: January 2023

Objective

Anti-leucine-rich glioma inactivated 1(LGI1) encephalitis is one rare autoimmune encephalitis which is accompanied by inflammatory responses. (Anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis is an autoimmune disease mediated by inflammatory responses.)This study aimed to investigate the Chitinase 3-like 1(CHI3L1) in anti-LGI1encephalitis patients and evaluate its association with modified Rankin Scale (mRS) score in anti-LGI1 encephalitis at admission and 6 months follow-up.(This study looked into the relationship between Chitinase 3-like 1 (CHI3L1) and the modified Ranking Scale (mRS) score in anti-LGI1 encephalitis patients at admission and 6 months later.)

Methods

Thirty-five patients with anti-LGI1 encephalitis and 22 patients with non-inflammatory neurological disease were enrolled in this study. (We enrolled 35 patients with anti-LGI1 encephalitis and 22 patients with non-inflammatory neurological disease.)Cerebrospinal fluid (CSF) and serum levels of CHI3L1 were measured by enzyme-linked immunosorbent assay. (We quantified CHI3L1 in the serum and cerebrospinal fluid (CSF) by performing an enzyme-linked immunosorbent assay.)Patients were evaluated for mRS score at admission and at 6 months follow-up.(We recorded the mRS score of the patients at admission and 6 months later.)

Results

CHI3L1 levels in CSF and serum were highly elevated in patients with anti-LGI1 encephalitis at admission compared those with the controls.(At admission, patients with anti-LGI1 encephalitis had elevated CHI3L1 levels in the CSF and serum.) Additionally, patients presenting with cognitive impairment had significantly higher CSF CHI3L1 levels and mRS scores than those without cognitive impairment symptoms. Patients presenting with only faciobrachial dystonic seizures at admission had lower CSF CHI3L1 levels than those with other symptoms. Finally, CSF CHI3L1 levels were positively correlated with CSF lactate levels.

Conclusion

CHI3L1 level in CSF is correlated with the severity and prognosis of anti-LGI1 encephalitis. (CSF CHI3L1 levels are correlated with the severity and prognosis of anti-LGI1 encephalitis.)
A novel model of urosepsis in rats developed by injection of Escherichia coli into the renal pelvis
Authors: Cao Yuanfei , Bai Can , Si Penghui , Yan Xin , Zhang Peng , Yisha Zuhaer , Lu Peixiang , Tuoheti Kuerban , Guo Linfa , Chen Zhao , Bai Xiaojie , Liu Tongzu
Published: January 2023

Despite extensive research, urosepsis remains a life-threatening, high-mortality disease. Currently, animal models of urosepsis widely accepted by investigators are very scarce. This study aimed to establish a standardized and reproducible model of urosepsis in rats. Forty adult Wistar rats were randomly divided into four groups according to the concentration of injected E. coli suspensions: Sham, Sep 3×, Sep 6×, and Sep 12×. Because the ureter is so thin and fragile, no conventional needle can be inserted into the ureter, which is probably why rats are rarely used to develop models of urosepsis. To solve this problem, the left ureter was ligated in the first procedure. After 24 hours, the left ureter above the ligation was significantly dilated, then saline or different concentrations of E. coli at 3 ml/kg were injected into the left renal pelvis using a 30G needle. The left ureter was subsequently ligated again at a distance of 1 cm from the renal hilum to maintain high pressure in the renal pelvis. Following injection of E. coli or saline for 24 h, three rats from each group were sacrificed and their organs (lung, liver, and right kidney) were collected. In contrast, the remaining seven rats continued to be observed for survival. At 10 days after E. coli injection, rats in the sep12× group had a higher mortality rate (100%) compared to the sep3× group (28.6%) or the sep6× group (71.4%). The significant changes in peripheral blood WBC count, serum IL-6 and TNF-α levels were also in the sep12× group. In addition, rats in the sepsis group showed multi-organ dysfunction, including damage to the lungs, liver, and kidneys. The establishment of a standardized rat model of urosepsis may be of great value for studying the pathophysiological of urosepsis.
Evaluating future climate change exposure of marine habitat in the South East Pacific based on metabolic constraints
Authors: Parouffe Alexandra , Garçon Véronique , Dewitte Boris , Paulmier Aurélien , Montes Ivonne , Parada Carolina , Mecho Ariadna , Veliz David
Published: January 2023

Introduction

On-going climate change is now recognized to yield physiological stresses on marine species, with potentially detrimental effects on ecosystems. Here, we evaluate the prospect of using climate velocities (CV) of the metabolic index (Φ) for assessing changes in habitat in the South East Pacific.

Methods

Our approach is based on a species with mean ecophysiotype (i.e. model species) and the use of a global Earth System Model simulation (CESM-LE) under RCP 8.5 scenario. The SEP is chosen as a case study as it hosts an Oxygen Minimum Zone and seamounts systems sustaining local communities through artisanal fisheries.

Results and Discussion

Our results indicate that CVΦ pattern is mainly constrained by the oxygen distribution and that its sign is affected by contrasting oxygen trends (including a re-oxygenation in the upper OMZ) and warming. We further show that CVΦ is weakly dependent on physiological traits composing Φ, which conveys to this metrics some value for inferring the projected mean displacement and potential changes in viability of metabolic habitat in a region where physiological data are scarce. Based on sensitivity experiments to physiological traits and natural variability, we propose a general method for inferring broad areas of climate change exposure regardless of species-specific Φ. We show in particular that for the model used here, the upper OMZ region can be considered a “safe” area for the species with ecophysiotype close to that of 71 species used to derive the model species. Limitations of the approach and perspectives of this work are also discussed.
A comparative study on the three calculation methods for reproduction numbers of COVID-19
Authors: Abudunaibi Buasiyamu , Liu Weikang , Guo Zhinan , Zhao Zeyu , Rui Jia , Song Wentao , Wang Yao , Chen Qiuping , Frutos Roger , Su Chenghao , Chen Tianmu
Published: January 2023

Objective

This study uses four COVID-19 outbreaks as examples to calculate and compare merits and demerits, as well as applicational scenarios, of three methods for calculating reproduction numbers.

Method

The epidemiological characteristics of the COVID-19 outbreaks are described. Through the definition method, the next-generation matrix-based method, and the epidemic curve and serial interval (SI)-based method, corresponding reproduction numbers were obtained and compared.

Results

Reproduction numbers (Reff), obtained by the definition method of the four regions, are 1.20, 1.14, 1.66, and 1.12. Through the next generation matrix method, in region H Reff = 4.30, 0.44; region P Reff = 6.5, 1.39, 0; region X Reff = 6.82, 1.39, 0; and region Z Reff = 2.99, 0.65. Time-varying reproduction numbers (Rt), which are attained by SI of onset dates, are decreasing with time. Region H reached its highest Rt = 2.8 on July 29 and decreased to Rt < 1 after August 4; region P reached its highest Rt = 5.8 on September 9 and dropped to Rt < 1 by September 14; region X had a fluctuation in the Rt and Rt < 1 after September 22; Rt in region Z reached a maximum of 1.8 on September 15 and decreased continuously to Rt < 1 on September 19.

Conclusion

The reproduction number obtained by the definition method is optimal in the early stage of epidemics with a small number of cases that have clear transmission chains to predict the trend of epidemics accurately. The effective reproduction number Reff, calculated by the next generation matrix, could assess the scale of the epidemic and be used to evaluate the effectiveness of prevention and control measures used in epidemics with a large number of cases. Time-varying reproduction number Rt, obtained via epidemic curve and SI, can give a clear picture of the change in transmissibility over time, but the conditions of use are more rigorous, requiring a greater sample size and clear transmission chains to perform the calculation. The rational use of the three methods for reproduction numbers plays a role in the further study of the transmissibility of COVID-19.
Targeting envelope proteins of poxviruses to repurpose phytochemicals against monkeypox: An in silico investigation
Authors: Gulati Pallavi , Chadha Jatin , Harjai Kusum , Singh Sandeepa
Published: January 2023

The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking, molecular dynamic (MD) simulations, and MM/PBSA analysis were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity toward all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations and MM/PBSA calculations. Results from the iMODS server also complemented the findings from molecular docking and MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the envelope proteins of the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox.
Lorcaserin and phentermine exert anti-obesity effects with modulation of the gut microbiota
Authors: Song Eun-Ji , Shin Na Rae , Jeon Songhee , Nam Young-Do , Kim Hojun
Published: January 2023

Although drugs have been reported to modulate the gut microbiota, the effects of anti-obesity drugs on the gut microbiota remain unclear. Lorcaserin (LS) and phentermine (PT) are commonly used anti-obesity drugs. However, to our best knowledge, no studies have simultaneously assessed the effects of LS and PT on obesity and gut microbiota. This study aimed to explore the relationship between the anti-obesity effects of LS and PT and re-modulation of host gut microbiota. To test hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with LS and PT via oral gavage for 8 weeks. After sacrifice, body weight, fat accumulation, and serum biomarkers were measured, and the gut microbial composition was analyzed using 16 s rRNA amplicon sequencing. LS and PT were observed to modulate the gut microbial composition and restore gut microbial dysbiosis, as indicated by an increased Firmicutes/Bacteroidetes ratio. Significantly modulated genera by LS and PT treatment were strongly correlated with obesity-related markers. Additionally, LS and PT increased the mRNA level of G protein-coupled receptor 120 (GPR120) in the colon tissue. ASV3566, which corresponds to Eubacterium coprostanoligenes, was correlated with GPR120 and obesity-related markers such as glutamic pyruvic transaminase (GPT) and serum triglyceride (TG). In conclusion, LS and PT can modulate the gut microbiota dysbiosis and the gut microbiota plays a role in mediating the anti-obesity effect of drugs.
Protein adsorption by nanomechanical mass spectrometry: Beyond the real-time molecular weighting
Authors: Stachiv Ivo , Kuo Chih-Yun , Li Wei
Published: January 2023

During past decades, enormous progress in understanding the mechanisms of the intermolecular interactions between the protein and surface at the single-molecule level has been achieved. These advances could only be possible by the ongoing development of highly sophisticated experimental methods such as atomic force microscopy, optical microscopy, surface plasmon resonance, ellipsometry, quartz crystal microbalance, conventional mass spectrometry, and, more recently, the nanomechanical systems. Here, we highlight the main findings of recent studies on the label-free single-molecule (protein) detection by nanomechanical systems including those focusing on the protein adsorption on various substrate surfaces. Since the nanomechanical techniques are capable of detecting and manipulating proteins even at the single-molecule level, therefore, they are expected to open a new way of studying the dynamics of protein functions. It is noteworthy that, in contrast to other experimental methods, where only given protein properties like molecular weight or protein stiffness can be determined, the nanomechanical systems enable a real-time measurement of the multiple protein properties (e.g., mass, stiffness, and/or generated surface stress), making them suitable for the study of protein adsorption mechanisms. Moreover, we also discuss the possible future trends in label-free detection and analysis of dynamics of protein complexes with these nanomechanical systems.
Evaluation of hemodialysis vascular access involving multidisciplinary integration: Perspective from Latin America and Peru
Authors: Castillo Velarde Edwin , Ruiz-Peñafiel José A. , Alfaro Ita Sheyla , Vachharajani Tushar J.
Published: January 2023

The perspective of vascular access care in patients with end-stage renal disease has migrated from nephrology-centered or vascular surgery-centered care to multidisciplinary-focused patient-centered care. This new perspective should not only be theoretical but also have practical utility. A non-multidisciplinary focus can contribute to the low prevalence of arteriovenous fistula (AVF) in the population. Latin America has multiple health systems and the coordination of vascular access is heterogeneous. In Peru, there is a high prevalence of central venous catheter use with its associated complications, such as stenosis, thrombosis, infection, and recurrent hospitalizations in the context of fragmented care. However, in the last few years, there has been an effort to integrate the communication between vascular surgery, interventional radiology, and nephrology to improve vascular access care. In this review, we analyze the availability of care, the intervention, and the future directions from the experience of both perspectives.
Dynamic motor practice improves movement accuracy, force control and leads to increased corticospinal excitability compared to isometric motor practice
Authors: Norup Malene , Bjørndal Jonas Rud , Nielsen August Lomholt , Wiegel Patrick , Lundbye-Jensen Jesper
Published: January 2023

The central nervous system has a remarkable ability to plan motor actions, to predict and monitor the sensory consequences during and following motor actions and integrate these into future actions. Numerous studies investigating human motor learning have employed tasks involving either force control during isometric contractions or position control during dynamic tasks. To our knowledge, it remains to be elucidated how motor practice with an emphasis on position control influences force control and vice versa. Furthermore, it remains unexplored whether these distinct types of motor practice are accompanied by differential effects on corticospinal excitability. In this study, we tested motor accuracy and effects of motor practice in a force or position control task allowing wrist flexions of the non-dominant hand in the absence of online visual feedback. For each trial, motor performance was quantified as errors (pixels) between the displayed target and the movement endpoint. In the main experiment, 46 young adults were randomized into three groups: position control motor practice (PC), force control motor practice (FC), and a resting control group (CON). Following assessment of baseline motor performance in the position and force control tasks, intervention groups performed motor practice with, augmented visual feedback on performance. Motor performance in both tasks was assessed following motor practice. In a supplementary experiment, measures of corticospinal excitability were obtained in twenty additional participants by application of transcranial magnetic stimulation to the primary motor cortex hot spot of the flexor carpi radialis muscle before and following either position or force control motor practice. Following motor practice, accuracy in the position task improved significantly more for PC compared to FC and CON. For the force control task, both the PC and FC group improved more compared to CON. The two types of motor practice thus led to distinct effects including positive between-task transfer accompanying dynamic motor practice The results of the supplementary study demonstrated an increase in corticospinal excitability following dynamic motor practice compared to isometric motor practice. In conclusion, dynamic motor practice improves movement accuracy, and force control and leads to increased corticospinal excitability compared to isometric motor practice.
Sensorimotor integration and motor learning during a novel force-matching task in young adults with attention-deficit/hyperactivity disorder
Authors: McCracken Heather S. , Murphy Bernadette A. , Ambalavanar Ushani , Glazebrook Cheryl M. , Yielder Paul C.
Published: January 2023

Introduction

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that exhibits unique neurological and behavioral characteristics. Those with ADHD often have noted impairments in motor performance and coordination, including during tasks that require force modulation. The present study provides insight into the role of altered neural processing and SMI in response to a motor learning paradigm requiring force modulation and proprioception, that previous literature has suggested to be altered in those with ADHD, which can also inform our understanding of the neurophysiology underlying sensorimotor integration (SMI) in the general population.

Methods

Adults with ADHD (n = 15) and neurotypical controls (n = 15) performed a novel force-matching task, where participants used their right-thumb to match a trace template that varied from 2–12% of their Abductor Pollicis Brevis maximum voluntary contraction. This motor task was completed in pre, acquisition, and post blocks. Participants also completed a retention test 24 h later. Median nerve somatosensory-evoked potentials (SEPs) were collected pre and post motor acquisition. SEPs were stimulated at two frequencies, 2.47 Hz and 4.98 Hz, and 1,000 sweeps were recorded using 64-electrode electroencephalography (EEG) at 2,048 Hz. SEP amplitude changes were normalized to each participant’s baseline values for that peak.

Results

Both groups improved at post measures (ADHD: 0.85 ± 0.09; Controls: 0.85 ± 0.10), with improvements maintained at retention (ADHD: 0.82 ± 0.11; Controls: 0.82 ± 0.11). The ADHD group had a decreased N18 post-acquisition (0.87 ± 0.48), while the control N18 increased (1.91 ± 1.43). The N30 increased in both groups, with a small increase in the ADHD group (1.03 ± 0.21) and a more pronounced increase in controls (1.15 ± 0.27).

Discussion

Unique neural differences between groups were found after the acquisition of a novel force-matching motor paradigm, particularly relating to the N18 peak. The N18 differences suggest that those with ADHD have reduced olivary-cerebellar-M1 inhibition when learning a novel motor task dependent on force-modulation, potentially due to difficulties integrating the afferent feedback necessary to perform the task. The results of this work provide evidence that young adults with ADHD have altered proprioceptive processing when learning a novel motor task when compared to neurotypical controls.
Lactoferrin: A glycoprotein that plays an active role in human health
Authors: Cao Xiang , Ren Yang , Lu Qinyue , Wang Kun , Wu Yanni , Wang YuHao , Zhang Yihui , Cui Xiang-shun , Yang Zhangping , Chen Zhi
Published: January 2023

Lactoferrin (Lf), existing widely in human and mammalian milk, is a multifunctional glycoprotein with many functions, such as immune regulation, anti-inflammation, antibacterial, antiviral, and antioxidant. These extensive functions largely attribute to its ability to chelate iron and interfere with the cellular receptors of pathogenic microorganisms and their hosts. Moreover, it is non-toxic and has good compatibility with other supplements. Thus, Lf has been widely used in food nutrition, drug carriers, biotechnology, and feed development. Although Lf has been continuously explored and studied, a more comprehensive and systematic compendium is still required. This review presents the recent advances in the structure and physicochemical properties of Lf as well as clinical studies on human diseases, with the aim of providing a reference for further research of Lf and the development of its related functional products.
Maternal prebiotic supplementation impacts colitis development in offspring mice
Authors: Lê Amélie , Selle Amandine , Aubert Philippe , Durand Tony , Brosseau Carole , Bordron Philippe , Delage Erwan , Chaffron Samuel , Petitfils Camille , Cenac Nicolas , Neunlist Michel , Bodinier Marie , Rolli-Derkinderen Malvyne
Published: January 2023

Background and aims

Maternal diet plays a key role in preventing or contributing to the development of chronic diseases, such as obesity, allergy, and brain disorders. Supplementation of maternal diet with prebiotics has been shown to reduce the risk of food allergies and affect the intestinal permeability in offspring later in life. However, its role in modulating the development of other intestinal disorders, such as colitis, remains unknown. Therefore, we investigated the effects of prebiotic supplementation in pregnant mice on the occurrence of colitis in their offspring.

Materials and methods

Offspring from mothers, who were administered prebiotic galacto-oligosaccharides and inulin during gestation or fed a control diet, were subjected to three cycles of dextran sulphate sodium (DSS) treatment to induce chronic colitis, and their intestinal function and disease activity were evaluated. Colonic remodelling, gut microbiota composition, and lipidomic and transcriptomic profiles were also assessed.

Results

DSS-treated offspring from prebiotic-fed mothers presented a higher disease score, increased weight loss, and increased faecal humidity than those from standard diet-fed mothers. DSS-treated offspring from prebiotic-fed mothers also showed increased number of colonic mucosal lymphocytes and macrophages than the control group, associated with the increased colonic concentrations of resolvin D5, protectin DX, and 14-hydroxydocosahexaenoic acid, and modulation of colonic gene expression. In addition, maternal prebiotic supplementation induced an overabundance of eight bacterial families and a decrease in the butyrate caecal concentration in DSS-treated offspring.

Conclusion

Maternal prebiotic exposure modified the microbiota composition and function, lipid content, and transcriptome of the colon of the offspring. These modifications did not protect against colitis, but rather sensitised the mice to colitis development.
Assessing and testing anomaly detection for finding prostate cancer in spatially registered multi-parametric MRI
Authors: Mayer Rulon , Turkbey Baris , Choyke Peter , Simone Charles B.
Published: January 2023

Background

Evaluating and displaying prostate cancer through non-invasive imagery such as Multi-Parametric MRI (MP-MRI) bolsters management of patients. Recent research quantitatively applied supervised target algorithms using vectoral tumor signatures to spatially registered T1, T2, Diffusion, and Dynamic Contrast Enhancement images. This is the first study to apply the Reed-Xiaoli (RX) multi-spectral anomaly detector (unsupervised target detector) to prostate cancer, which searches for voxels that depart from the background normal tissue, and detects aberrant voxels, presumably tumors.

Methods

MP-MRI (T1, T2, diffusion, dynamic contrast-enhanced images, or seven components) were prospectively collected from 26 patients and then resized, translated, and stitched to form spatially registered multi-parametric cubes. The covariance matrix (CM) and mean μ were computed from background normal tissue. For RX, noise was reduced for the CM by filtering out principal components (PC), regularization, and elliptical envelope minimization. The RX images were compared to images derived from the threshold Adaptive Cosine Estimator (ACE) and quantitative color analysis. Receiver Operator Characteristic (ROC) curves were used for RX and reference images. To quantitatively assess algorithm performance, the Area Under the Curve (AUC) and the Youden Index (YI) points for the ROC curves were computed.

Results

The patient average for the AUC and [YI] from ROC curves for RX from filtering 3 and 4 PC was 0.734[0.706] and 0.727[0.703], respectively, relative to the ACE images. The AUC[YI] for RX from modified Regularization was 0.638[0.639], Regularization 0.716[0.690], elliptical envelope minimization 0.544[0.597], and unprocessed CM 0.581[0.608] using the ACE images as Reference Image. The AUC[YI] for RX from filtering 3 and 4 PC was 0.742[0.711] and 0.740[0.708], respectively, relative to the quantitative color images. The AUC[YI] for RX from modified Regularization was 0.643[0.648], Regularization 0.722[0.695], elliptical envelope minimization 0.508[0.605], and unprocessed CM 0.569[0.615] using the color images as Reference Image. All standard errors were less than 0.020.

Conclusions

This first study of spatially registered MP-MRI applied anomaly detection using RX, an unsupervised target detection algorithm for prostate cancer. For RX, filtering out PC and applying Regularization achieved higher AUC and YI using ACE and color images as references than unprocessed CM, modified Regularization, and elliptical envelope minimization.
Treatment of hepatic venous system hemorrhage and carbon dioxide gas embolization during laparoscopic hepatectomy via hepatic vein approach
Authors: Qu Zhen , Wu Ke-jia , Feng Jia-wei , Shi Ding-sen , Chen Yu-xiang , Sun Dong-lin , Duan Yun-Fei , Chen Jing , He Xiao-zhou
Published: January 2023

With the improvement of laparoscopic surgery, the feasibility and safety of laparoscopic hepatectomy have been affirmed, but intraoperative hepatic venous system hemorrhage and carbon dioxide gas embolism are the difficulties in laparoscopic hepatectomy. The incidence of preoperative hemorrhage and carbon dioxide gas embolism could be reduced through preoperative imaging evaluation, reasonable liver blood flow blocking method, appropriate liver-breaking device, controlled low-center venous pressure technology, and fine-precision precision operation. In the case of blood vessel rupture bleeding in the liver vein system, after controlling and reducing bleeding, confirm the type and severity of vascular damage in the liver and venous system, take appropriate measures to stop the bleeding quickly and effectively, and, if necessary, transfer the abdominal treatment in time. In addition, to strengthen the understanding, prevention and emergency treatment of severe CO2 gas embolism in laparoscopic hepatectomy is also the key to the success of surgery. This study aims to investigate the methods to deal with hepatic venous system hemorrhage and carbon dioxide gas embolization based on author’s institutional experience and relevant literature. We retrospectively analyzed the data of 60 patients who received laparoscopic anatomical hepatectomy of hepatic vein approach for HCC. For patients with intraoperative complications, corresponding treatments were given to cope with different complications. After the operation, combined with clinical experience and literature, we summarized and discussed the good treatment methods in the face of such situations so that minimize the harm to patients as much as possible.
Case report: Metastatic metaplastic breast cancer with choriocarinomatous features: Targeting the choriocarcinoma component for cure
Authors: Mehta Krisha K. , Nouvini Rosa , Liu Jingxuan , Wang Yi , Stopeck Alison
Published: January 2023

Breast cancer with choriocarcinomatous features (BCCF) is a rare and aggressive breast cancer. BCCF carries a poor prognosis and there is unfortunately scant literature to guide treatment beyond surgical resection with most patients receiving standard regimens for breast cancer. In our case, we present a 42-year-old female with an initial hCG of 2,324 and two suspicious lesions of the right breast. On biopsy, each lesion had distinct histopathology with the larger lesion diagnosed as BCCF and the smaller lesion being an invasive ER/PR positive ductal carcinoma. The diagnosis of BCCF rather than metastatic choriocarcinoma was confirmed using DNA typing. Salvage chemotherapy targeting choriocarcinoma resulted in marked clinical and biomarker success including normalization of the hCG. After recurrent brain metastases were diagnosed, high dose chemotherapy with methotrexate was administered resulting in long term remission.
Case report: Primary Ewing sarcoma of the ureter, an exceptional finding of unique manifestation of disease
Authors: Valeri Marina , Dore Leocadia , Rudini Noemi , Cieri Miriam , Elefante Grazia Maria , Saita Alberto , Bertuzzi Alexia , Colombo Piergiuseppe
Published: January 2023

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has also been described in adults with highly aggressive behavior. ES belongs to the small round blue cell tumor family and presents the distinctive translocation of FET-ETS family genes (85% with EWSR1), generating gene fusions. Extraskeletal ES mainly occurs in soft tissues; the urogenital tract is rarely affected, and ureteral localization is an exceptional event with only 4 cases described in the literature. Here we report the first Italian case of primary ES of the ureter, a 24-year-old young man with lower back pain and a narrowed left ureteral lumen on CT scan. ES of the urogenital tract is an almost unique condition with a nonspecific clinical presentation and a challenging diagnosis for pathologists. We encourage awareness of these exceptional events in the differential diagnosis of ureteral lesions in young patients.
Effectiveness and safety of anti-PD-1 monotherapy or combination therapy in Chinese advanced gastric cancer: A real-world study
Authors: Li Tao , Liu Tingting , Zhao Lei , Liu Lu , Zheng Xuan , Wang Jinliang , Zhang Fan , Hu Yi
Published: January 2023

Purpose

Gastric cancer (GC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths worldwide, especially in eastern Asia and China. Anti-PD-1 immune checkpoint inhibitors, Pembrolizumab and Nivolumab, have been approved for the treatment of locally advanced or metastatic gastric or gastroesophageal junction cancer (GC/GEJC). Our study evaluated the effectiveness and safety of anti-PD-1-based treatment (monotherapy or combination therapy) in Chinese patients with advanced or metastatic GC/GEJCs in a real-world setting.

Methods

A retrospective cohort study was conducted, and 54 patients from May 31, 2015, to May 31, 2021, were included in our analysis, including 19 patients treated with anti-PD-1 monotherapy and 35 patients treated with anti-PD-1 combination therapy. Demographic and clinical information were evaluated. Clinical response, survival outcomes, and safety profile were measured and analyzed.

Results

Overall, the median overall survival (mOS) was 11.10 months (95% CI, 7.05–15.15), and the median progression-free survival (mPFS) was 3.93 months (95% CI, 2.47–5.39). Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and increased clinical response were observed in the combination group compared with the monotherapy group, although statistical significance was not reached. In subgroups with live metastases or elevated baseline neutrophil-to-lymphocyte ratio (NLR) levels, combination therapy outperformed anti-PD-1 alone in survival outcomes. Patients treated with anti-PD-1 monotherapy (n = 5, 26.3%) had fewer treatment-related adverse events (TRAEs) than those in the combination group (n = 22, 62.9%). There were also fewer patients with TRAEs of grades 3–5 with monotherapy (n = 2, 10.5%) than with combination therapy (n = 7, 20.0%). Pneumonitis in three patients was the only potential immune-related adverse event reported.

Conclusions

Anti-PD-1-based monotherapy and combination therapy showed favorable survival outcomes and manageable safety profiles in advanced or metastatic GC/GEJCs. In clinical treatment, immunotherapy should be an indispensable choice in the treatment strategy for GC/GEJC. Patients with a heavy tumor burden and more metastatic sites might benefit more from combination therapy. Elderly patients and patients with more treatment lines or high Eastern Cooperative Oncology Group (ECOG) performance scores might be more suitable for immune monotherapy, and some clinical benefits have been observed.
Re-irradiation of recurrent vertebral metastasis after two previous spinal cord irradiation: A case report
Authors: Bentahila Rita , Kinj Rémy , Huck Constance , El Houat Yasmine , Mampuya Ange , Tuleasca Constantin , Ozsahin Mahmut , Bourhis Jean , Schiappacasse Luis
Published: January 2023

Background

Management of a recurrent vertebral metastasis in a situation of previously irradiated spinal cord is a challenging clinical dilemma.

Case presentation

We report a first case of second retreatment of a spinal metastasis initially irradiated with standard radiotherapy and stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression at the same level. After a third course of irradiation with SBRT, a complete response was achieved. After 8 months of follow-up, the patients remain free of local recurrence.

Conclusion

A third course of vertebral irradiation for a recurrent vertebral metastasis failing to two previous irradiations, in this particular case, have shown the feasibility and efficacy of the technique as a salvage treatment option. This approach could be used in a selected group of patient if an adequate dose is delivered to the target while observing critical tissue tolerance limits.
Case Report: Serial changes of ocular complications related to immune checkpoint inhibitors pembrolizumab and nivolumab
Authors: Cho Wan-Hua , Chiang Wei-Yu
Published: January 2023

Background

To demonstrate the rare ocular side effects in a patient receiving pembrolizumab and nivolumab for metastatic ovarian cancer.

Case presentation

A 37-year-old woman with recurrent metastatic ovarian cancer presented with blurred vision and photophobia after receiving pembrolizumab. Ocular findings were bilateral anterior chamber reactions, iris cysts, and macular flecks. Optical coherence tomography (OCT) indicated retinal pigment epithelium (RPE) and ellipsoid-band disruption. Her symptoms subsided with topical steroids but fundal appearance persisted despite cessation of immunotherapies. Similar episodes attacked again with multiple exudative subretinal fluid (SRF) developed after she received pembrolizumab and nivolumab. Steroids could cease anterior chamber reactions while SRF only subsided after discontinuation of immunotherapy. Extensive RPE and ellipsoid-band disruption remained without vision improvements.

Conclusions

We report a rare case of uveitis and retinopathy after immunotherapies with sequent pembrolizumab and nivolumab. A serial change of the maculopathy is demonstrated. Possible ocular toxicities during the treatment course should be considered, and the benefits of continuing the immunotherapy must be weighed against the risks.
Cross-cultural adaptation and validation of the PedsQL™ stem cell transplant module in China: A methodological and cross-sectional study
Authors: Wei Yuting , Zhang Heng , Qian Xiaowen , Xue Yao , Rong Liucheng , Wang Yaping , Jiang Wenjin , Lin Rufeng , Lu Shifeng , Zhai Xiaowen , Fang Yongjun
Published: January 2023

Background

Hematopoietic stem cell transplantation (HSCT), as a mature technology, has significantly improved the survival rate of children. However, there lack efficient scales to assess the quality of life (QoL) of children with HSCT in China, which has important implications in the care of this population. This study aimed to translate the original English Pediatric Quality of Life Inventory™ (PedsQL™) Stem Cell Transplant Module into a Chinese mandarin version, and evaluate its reliability.

Methods

Children of ages 2–18 years who had received HSCT at Children's Hospital of Nanjing Medical University and Children's Hospital of Fudan University were recruited. Children or their parents were asked to fill the PedsQL™ 4.0 Generic Core Scales, PedsQL™ Stem Cell Transplant Module, and PedsQL™ Family Information Form. Feasibility was evaluated by completion rate and the percentage of missing items, reliability by the internal consistency and test-retest reliability, and validity by factor analysis and correlation analysis between the scores of total scale and each dimension.

Results

A total of 120 children (mean age 6.37, SD = 3.674) and some parents were included. A low percentage of items were missed in returned reports. Cronbach's alpha coefficient reached 0.70 in the majority of dimensions of both child self-report and parent proxy-report. Test-retest reliability was 0.685 in parents' forms and 0.765 in child's forms. Eight factors were extracted, with a cumulative contribution rate of 74.54%. The correlation between PedsQL™ 4.0 and Transplant Module was 0.748 for children self-report and 0.808 for parent proxy-report.

Conclusions

This study provides evidence that the Chinese mandarin version of the PedsQL™ Stem Cell Transplant is feasible, reliable and valid in evaluating the QoL of Chinese children after HSCT.
Chemical synthesis of a reported p47phox/p22phox inhibitor and characterization of its instability and irreproducible activity
Authors: Zang Jie , Cambet Yves , Jaquet Vincent , Bach Anders
Published: January 2023

The nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) multi-subunit complex is a highly abundant and central source of reactive oxygen species. NOX2 is a key enzyme of the innate immune system involved in antibacterial response, but excessive NOX2 activity is involved in oxidative stress and inflammation in many diseases. Inhibition of NOX2 has great potential as a therapeutic strategy. An intriguing pharmacological approach for inhibiting NOX2 is to target the p47phox subunit and thereby block the protein-protein interaction with p22phox, whereby assembling and activation of NOX2 is prevented. However, the shallow binding pocket of p47phox makes it difficult to develop drug-like p47phox/p22phox inhibitors. Recently, the small molecule LMH001 was reported to inhibit the p47phox/p22phox interaction, reduce endothelial NOX2 activity, and protect mice from angiotensin II-induced vascular oxidative stress. These noteworthy results could have significant impact on the field of NOX2 pharmacology, as specific and efficient inhibitors are scarce. Here, we synthesized and tested LMH001 to have it available as a positive control. We established a robust synthetic route for providing LMH001, but subsequently we experienced that LMH001 is chemically unstable in aqueous buffer. In addition, neither LMH001 nor its breakdown products were able to inhibit the p47phox/p22phox interaction in a non-cellular fluorescence polarization assay. However, LHM001 was a weak inhibitor of NOX2 in a functional cell assay, but with same low potency as one of its breakdown products. These findings question the activity and suggested mechanism of LMH001 and constitute important information for other researchers interested in chemical probes for studying NOX2 biology.
Bone marrow mesenchymal stromal cell-derived small extracellular vesicles: A novel therapeutic agent in ischemic heart diseases
Authors: Chang Wenguang , Li Peifeng
Published: January 2023

Myocardial injury is a major pathological factor that causes death in patients with heart diseases. In recent years, mesenchymal stromal cells (MSCs) have been generally used in treating many diseases in animal models and clinical trials. mesenchymal stromal cells have the ability to differentiate into osteocytes, adipocytes and chondrocytes. Thus, these cells are considered suitable for cardiac injury repair. However, mechanistic studies have shown that the secretomes of mesenchymal stromal cells, mainly small extracellular vesicles (sEVs), have better therapeutic effects than mesenchymal stromal cells themselves. In addition, small extracellular vesicles have easier quality control characteristics and better safety profiles. Therefore, mesenchymal stromal cell-small extracellular vesicles are emerging as novel therapeutic agents for damaged myocardial treatment. To date, many clinical trials and preclinical experimental results have demonstrated the beneficial effects of bone marrow-derived mesenchymal stromal cells (BMMSCs) and bone marrow-derived mesenchymal stromal cells-small extracellular vesicles on ischemic heart disease. However, the validation of therapeutic efficacy and the use of tissue engineering methods require an exacting scientific rigor and robustness. This review summarizes the current knowledge of bone marrow-derived mesenchymal stromal cells- or bone marrow-derived mesenchymal stromal cells-small extracellular vesicle-based therapy for cardiac injury and discusses critical scientific issues in the development of these therapeutic strategies.
A simplified model for acoustic focalization in environments with seabed uncertainties
Authors: Qu Ke , Ou Zhenyi , Huang Xin , Liu Liwen
Published: January 2023

Introduction: Parameter mismatch poses a challenge to source localization in cases involving environments with seabed uncertainties. By including environmental parameters in the search space, focalization can be used to estimate the location of the source using environmental information that is limited a priori. Methods: To reduce the number of parameters, a simplified seabed model is proposed here for such focalization. Only two geoacoustic parameters—the amplitude F and phase cF of reflection—are used to describe the seabed. Focalization is generally tested using genetic algorithms for the colored noise case (COLNOISE) benchmark problem. Results: The proposed simplified model can obtain the location of the source more easily than a layered model. Due to its advantage in terms of parameter sensitivity and inter-coupling, the simplified model can ensure the robustness of the results of inversion. The proposed method was tested on a broadband signal in the Asian Seas International Acoustics Experiment (ASIAEX2001), where both the location and the geoacoustic parameters were easily inverted. Discussion: The simplified model provides a sufficiently high acoustic resolution for focalization, and its reduction of the geoacoustic parameters helpes solve the problem of inversion.
The impact of heat therapy on neuromuscular function and muscle atrophy in diabetic rats
Authors: AlSabagh Abdullah T. , Rao Muddanna S. , Renno Waleed M.
Published: January 2023

Introduction: Diabetes Mellitus (DM) is the most common metabolic disease worldwide and is associated with many systemic complications. Muscle atrophy is one of the significant complications in DM patients, making routine tasks laborious as atrophy continues. It is known that heat stress stimulates heat shock proteins and other proteins that maintain muscle mass; however, it is not thoroughly studied in diabetic conditions. This study addressed whether heat therapy can attenuate muscle atrophy in STZ-induced diabetic rats and explored its mechanism of action on specific muscle proteins.

Methods: Male Sprague Dawley rats were randomly divided into short-term (3 weeks) and long-term (6 weeks) experiments. In each experiment rats were divided into control, heat therapy, diabetic and diabetic + heat therapy groups. Rats in heat therapy groups were exposed to heat therapy for 30 min daily for three or six weeks in a temperature-controlled (42°C) chamber.

Results: The attenuation of neuromuscular functions assessed by Rotarod, Kondziella’s inverted screen, and extensor postural thrust tests showed that diabetic rats exposed to heat therapy performed significantly better than diabetic controls. Muscle cross sectional area data established that heat therapy reduced muscle atrophy by 34.3% within 3 weeks and 44.1% within 6 weeks in the diabetic groups. Further, heat therapy significantly decreased muscle atrophy markers (CD68, KLF, and MAFbx) and significantly elevated muscle hypertrophy markers (AKT, mTOR, and HSP70).

Conclusions: This study shows the relevance and clinical significance of utilizing heat therapy as a viable treatment to attenuate muscle atrophy in diabetic patients.
Multi-locus genome-wide association studies reveal genomic regions and putative candidate genes associated with leaf spot diseases in African groundnut (Arachis hypogaea L.) germplasm
Authors: Oteng-Frimpong Richard , Karikari Benjamin , Sie Emmanuel Kofi , Kassim Yussif Baba , Puozaa Doris Kanvenaa , Rasheed Masawudu Abdul , Fonceka Daniel , Okello David Kallule , Balota Maria , Burow Mark , Ozias-Akins Peggy
Published: January 2023

Early leaf spot (ELS) and late leaf spot (LLS) diseases are the two most destructive groundnut diseases in Ghana resulting in ≤ 70% yield losses which is controlled largely by chemical method. To develop leaf spot resistant varieties, the present study was undertaken to identify single nucleotide polymorphism (SNP) markers and putative candidate genes underlying both ELS and LLS. In this study, six multi-locus models of genome-wide association study were conducted with the best linear unbiased predictor obtained from 294 African groundnut germplasm screened for ELS and LLS as well as image-based indices of leaf spot diseases severity in 2020 and 2021 and 8,772 high-quality SNPs from a 48 K SNP array Axiom platform. Ninety-seven SNPs associated with ELS, LLS and five image-based indices across the chromosomes in the 2 two sub-genomes. From these, twenty-nine unique SNPs were detected by at least two models for one or more traits across 16 chromosomes with explained phenotypic variation ranging from 0.01 - 62.76%, with exception of chromosome (Chr) 08 (Chr08), Chr10, Chr11, and Chr19. Seventeen potential candidate genes were predicted at ± 300 kbp of the stable/prominent SNP positions (12 and 5, down- and upstream, respectively). The results from this study provide a basis for understanding the genetic architecture of ELS and LLS diseases in African groundnut germplasm, and the associated SNPs and predicted candidate genes would be valuable for breeding leaf spot diseases resistant varieties upon further validation.