bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Progression in Intraplaque Hemorrhage Volume in Patients With Carotid Atherosclerosis: A Serial Magnetic Resonance Imaging Study
Authors: Mingming Lu , Peng Peng , Lichen Zhang , Shaohua Liu , Fei Yuan , Hongtao Zhang , Shitong Liu , Yao He , Xihai Zhao , Jianming Cai
Published: July 2022

Background and Purpose

This study aimed to investigate the arterial disease risk factors for the progression of intraplaque hemorrhage (IPH) in patients with carotid atherosclerosis using serial high-resolution magnetic resonance (MR) imaging.

Methods

Consecutive symptomatic patients who had MRI evidence of intraplaque hemorrhage present in the ipsilateral carotid artery with respect to the side of the brain affected by stroke or TIA were recruited in the study. All the patients underwent follow-up MR imaging at least 6 months after baseline. The annual change in IPH and other carotid plaque morphology was calculated, and a tertile method was used to classify the plaques as progressed or not with respect to IPH volume using the software CASCADE. Logistic regression and receiver operating characteristic (ROC) curve were conducted to evaluate the risk factors for the progression of IPH.

Results

A total of thirty-four symptomatic patients (mean age: 67.1 years, standard deviation [SD]: 9.8 years, 27 men) were eligible for the final analysis, and contralateral plaques containing IPH were seen in 11 of these patients (making 45 plaques with IPH in total). During mean 16.6-month (SD: 11.0 months) follow-up, the overall annual change in IPH volume in 45 plaques with IPH was mean −10.9 mm3 (SD: 49.1 mm3). Carotid plaques were significantly more likely to be classified in progressed IPH group if the patient was taking antiplatelet agent at baseline (OR: 9.76; 95%CI: 1.05 to 90.56; p = 0.045), had a baseline history of current or past smoking (OR: 9.28; 95%CI: 1.26 to 68.31; p = 0.029), or had a larger baseline carotid plaque-containing vessel wall volume (OR: 1.36 per 10 mm3; 95%CI: 1.02 to 1.81; p = 0.032) after adjustments for confounding factors. ROC analysis indicated that the combination of these three risk factors in the final model produced good discriminatory value for the progressed IPH group (area under the curve: 0.887).

Conclusions

Taking an antiplatelet agent at baseline, a baseline history of current or past smoking and larger baseline carotid plaque-containing vessel wall volume were independently predictive of plaques being in the progressed IPH group. Our findings indicate that awareness and management of such risk factors may reduce the risk of intraplaque hemorrhage progression.
Feasibility and Safety of Flow Diversion in the Treatment of Intracranial Aneurysms via Transradial Approach: A Single-Arm Meta-Analysis
Authors: Liu Xiang , Luo Wenzhang , Wang Mingyan , Huang Changren , Bao Kunyang
Published: July 2022

Background

While studies have confirmed that flow diversion (FD) can treat intracranial aneurysms via transradial approach (TRA), it remains unclear whether their treatment ultimately impacts safety and feasibility. We aim to conduct a systematic review and meta-analysis assessing the safety and feasibility after FD treatment of intracranial aneurysms via TRA.

Methods

PubMed, EMBASE, and Web of Science were systematically reviewed. The primary outcomes were the success rate and the access-related complications of deploying FD via TRA. Meta-analysis was performed using a random or fixed effect model based on heterogeneity. And the publication bias was evaluated using a funnel plot. This study was registered with PROSPERO, number CRD42021244448.

Results

Data from 8 studies met inclusion criteria (250 non-duplicated patients). The success rate was 93% (95% confidence interval [CI] 0.86–0.98; I2 = 61.05%; p = 0.01). The access-related complications rate was 1% (95% CI 0–0.03; I2 = 0.00%; p < 0.01). The mainly access-related complications included radial artery spasm (85.7%) and radial artery occlusion (14.3%). The TRA convert to transfemoral approach (TFA) was 7% (95% CI 0.02–0.14; I2 = 61.05%; p = 0.01).

Conclusions

Although TFA is still the main access for FD in the treatment of intracranial aneurysms, the TRA also has a higher success rate and lower access-related complications rate. With the improvement of future experience and equipment, the TRA may become the main access for FD which has more advantages. Future studies should design prospective, multicenter randomized controlled studies for long-term follow-up.
Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus
Authors: Santoro Jonathan D. , Patel Lina , Kammeyer Ryan , Filipink Robyn A. , Gombolay Grace Y. , Cardinale Kathleen M. , Real de Asua Diego , Zaman Shahid , Santoro Stephanie L. , Marzouk Sammer M. , Khoshnood Mellad , Vogel Benjamin N. , Tanna Runi , Pagarkar Dania , Dhanani Sofia , Ortega Maria del Carmen , Partridge Rebecca , Stanley Maria A. , Sanders Jessica S. , Christy Alison , Sannar Elise M. , Brown Ruth , McCormick Andrew A. , Van Mater Heather , Franklin Cathy , Worley Gordon , Quinn Eileen A. , Capone George T. , Chicoine Brian , Skotko Brian G. , Rafii Michael S.
Published: July 2022

Objective

To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome.

Background

There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area.

Methods

The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome.

Results

During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on “other” studies) as were diagnostic criteria (96% agreement).

Conclusions

The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.
Adult Critical Care Electroencephalography Monitoring for Seizures: A Narrative Review
Authors: Sharma Sonali , Nunes Michelle , Alkhachroum Ayham
Published: July 2022

Electroencephalography (EEG) is an important and relatively inexpensive tool that allows intensivists to monitor cerebral activity of critically ill patients in real time. Seizure detection in patients with and without acute brain injury is the primary reason to obtain an EEG in the Intensive Care Unit (ICU). In response to the increased demand of EEG, advances in quantitative EEG (qEEG) created an approach to review large amounts of data instantly. Finally, rapid response EEG is now available to reduce the time to detect electrographic seizures in limited-resource settings. This review article provides a concise overview of the technical aspects of EEG monitoring for seizures, clinical indications for EEG, the various available modalities of EEG, common and challenging EEG patterns, and barriers to EEG monitoring in the ICU.
Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy
Authors: Roa Jorge A. , Abramova Marina , Fields Madeline , Vega-Talbott Maite La , Yoo Jiyeoun , Marcuse Lara , Wolf Steven , McGoldrick Patricia , Ghatan Saadi , Panov Fedor
Published: July 2022

Introduction

One-third of patients with epilepsy continue to have seizures despite antiepileptic medications. Some of these refractory patients may not be candidates for surgical resection primarily because the seizure onset zones (SOZs) involve both hemispheres or are located in eloquent areas. The NeuroPace Responsive Neurostimulation System (RNS) is a closed-loop device that uses programmable detection and stimulation to tailor therapy to a patient's individual neurophysiology. Here, we present our single-center experience with the use of RNS in thalamic nuclei to provide long-term seizure control in patients with refractory epilepsy.

Methods

We performed a prospective single-center study of consecutive refractory epilepsy patients who underwent RNS system implantation in the anterior (ANT) and centromedian (CM) thalamic nuclei from September 2015 to December 2020. Patients were followed postoperatively to evaluate seizure freedom and complications.

Results

Twenty-three patients underwent placement of 36 RNS thalamic leads (CM = 27 leads, ANT = 9 leads). Mean age at implant was 18.8 ± 11.2 years (range 7.8–62 years-old). Two patients (8.7%) developed infections: 1 improved with antibiotic treatments alone, and 1 required removal with eventual replacement of the system to recover the therapeutic benefit. Mean time from RNS implantation to last follow-up was 22.3 months. Based on overall reduction of seizure frequency, 2 patients (8.7%) had no- to <25% improvement, 6 patients (26.1%) had 25–49% improvement, 14 patients (60.9%) had 50–99% improvement, and 1 patient (4.3%) became seizure-free. All patients reported significant improvement in seizure duration and severity, and 17 patients (74%) reported improved post-ictal state. There was a trend for subjects with SOZs located in the temporal lobe to achieve better outcomes after thalamic RNS compared to those with extratemporal SOZs. Of note, seizure etiology was syndromic in 12 cases (52.2%), and 7 patients (30.4%) had undergone resection/disconnection surgery prior to thalamic RNS therapy.

Conclusion

Thalamic RNS achieved ≥50% seizure control in ~65% of patients. Infections were the most common complication. This therapeutic modality may be particularly useful for patients affected by aggressive epilepsy syndromes since a young age, those whose seizure foci are located in the mesial temporal lobe, and those who have failed prior surgical interventions.
Measuring the impact of suppression on visual acuity in children with amblyopia using a dichoptic visual acuity chart
Authors: Zhu Bixia , Liao Meng , Liu Longqian
Published: July 2022

Purpose

To develop a novel dichoptic visual acuity chart that measures the impact of interocular suppression on the visual acuity of each eye when two eyes are open.

Methods

Fifty-four subjects (19 anisometropic amblyopia, 20 treated amblyopia, and 15 normal children) participated in this study. The visual acuity that was tested under dichoptic-optotypes condition (i.e., presented optotypes to the untested eye) was compared with that under monocular condition (i.e., cover the untested eye with opaque patch). Visual acuity differences between these two conditions were compared among the three groups. The correlations between visual acuity differences and the depth of interocular suppression were then computed. Some participants performed the visual acuity test under dichoptic-luminance condition (i.e., presented mean luminance to the untested eye), and the test-retest reliability was established.

Results

A reduced visual acuity of the non-dominant eye was found in the dichoptic-optotypes condition for the amblyopia group (P < 0.001) and the treated group (P = 0.001); the difference in the treated group was less than that in the amblyopia group (P < 0.001) but more than that in the normal group (P = 0.026). A significant correlation was found between the visual acuity differences and the depth of suppression, which was tested with a binocular phase combination task (P = 0.005). No change was found in the dichoptic-luminance condition.

Conclusion

The amblyopic eye and the previous amblyopic eye seem to suffer from a reduced visual acuity when two eyes are open due to suppression. This was successfully captured by our novel and reliable dichoptic-optotypes visual acuity chart.
Glutamatergic Synapse Dysfunction in Drosophila Neuromuscular Junctions Can Be Rescued by Proteostasis Modulation
Authors: Chakravorty Anushka , Sharma Ankit , Sheeba Vasu , Manjithaya Ravi
Published: July 2022

Glutamate is the major excitatory neurotransmitter in the nervous system, and the Drosophila glutamatergic neuromuscular junctions (NMJs) offer a tractable platform to understand excitatory synapse biology both in health and disease. Synaptopathies are neurodegenerative diseases that are associated with synaptic dysfunction and often display compromised proteostasis. One such rare, progressive neurodegenerative condition, Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph Disease (MJD), is characterized by cerebellar ataxia, Parkinsonism, and degeneration of motor neuron synapses. While the polyQ repeat mutant protein ataxin-3 is implicated in MJD, it is unclear how it leads to impaired synaptic function. In this study, we indicated that a Drosophila model of MJD recapitulates characteristics of neurodegenerative disorders marked by motor neuron dysfunction. Expression of 78 polyQ repeats of mutant ataxin-3 protein in Drosophila motor neurons resulted in behavioral defects, such as impaired locomotion in both larval and adult stages. Furthermore, defects in eclosion and lifespan were observed in adult flies. Detailed characterization of larval glutamatergic neuromuscular junctions (NMJs) revealed defects in morphological features along with compromised NMJ functioning. Autophagy, one of the key proteostasis pathways, is known to be impaired in the case of several synaptopathies. Our study reveals that overexpression of the autophagy-related protein Atg8a rescued behavioral defects. Thus, we present a model for glutamatergic synapse dysfunction that recapitulates synaptic and behavioral deficits and show that it is an amenable system for carrying out genetic and chemical biology screens to identify potential therapeutic targets for synaptopathies.
Effect of oral administration of GABA on thermoregulation in athletes during exercise in cold environments: A preliminary study
Authors: Wang Hongli , Cheng Lin , Han Yanbai
Published: July 2022

Background

γ-aminobutyric acid (GABA), a common ingredient in sports supplements and other health products, regulates body temperature in the preoptic area and anterior hypothalamus (PO/AH). To date, no study has examined the effect of GABA on thermoregulation during exercise in humans in a cold temperature environment (11 ± 0.3°C, 45% ± 2% relative humidity).

Methods

We performed a randomized, double-blind study. Ten trained male athletes consumed either a drink (3 ml/kg weight) containing GABA (1,000 mg, trial G) or an equivalent amount of placebo drink (trial C) before exercise. They rested for 20 min and then cycled at 60% of maximum output power for 40 min, pedaling at 60 rpm, and recovered for 20 min. Core temperature (Tc), skin temperature (upper arm, chest, thigh, calf), and heart rate (HR) were monitored at rest (T0), exercise begins (T20), 20 min of exercise (T40), the exercise ends (T60), and at recovery (T80).

Results

Compared to T0, Tc decreased significantly at T20 and increased significantly at T40, T60 and T80 (p < 0.01). From 35–80 min, the Tc was higher in trial G (peaked at 37.96 ± 0.25°C) than in trial C (37.89 ± 0.37°C), but it failed to reach significant difference (p > 0.05); Tsk continued to increase during exercise and was significantly higher than T0 at T40 (p < 0.05), T60 and T80 (p < 0.01). There was no significant difference in Tsk between the two trials (p > 0.05).

Conclusion

Our findings provide initial evidence that oral administration of GABA does not affect thermoregulation and has no adverse effects on the body as an ergogenic exercise supplement during exercise in cold environments.
Effect of Particle Size on Physicochemical Properties and in vitro Hypoglycemic Ability of Insoluble Dietary Fiber From Corn Bran
Authors: Jiang Caixia , Wang Rui , Liu Xiaolan , Wang Juntong , Zheng Xiqun , Zuo Feng
Published: July 2022

This study was designed for determining the effect of particle size on the functional properties of corn bran insoluble dietary fiber (IDF). Results showed that some physicochemical properties were improved with the decrease in particle size. The structure of the IDF was observed by the scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The surface was found wrinkled and sparse, the particle size was smaller, the crystallinity of IDF had increased slightly, and more -OH and C-O groups were exposed. Moreover, the corn bran IDF with a smaller particle size had a better hypoglycemic effect in vitro, and the inhibitory activity of α-glucosidase and α-amylase were also increased significantly with the decrease in particle size (p < 0.05). When the IDF was 300 mesh, the inhibitory rate of α-glucosidase was 61.34 ± 1.12%, and the inhibitory rate of α-amylase was 17.58 ± 0.33%. It had increased by 25.54 and 106.83%, respectively compared to the control treatment (CK) group. In addition, correlation analysis found that the particle size was highly negatively correlated with some functional properties of IDF (p < 0.05), and the content of cellulose was positively correlated with the functional properties of IDF except WHC (p < 0.05). To sum up, reducing particle size was suitable for the development of high value-added IDF products. This study also revealed the potential value of corn bran IDF and provided a new idea for the diversified application of IDF.
Risk Prediction Model for Synchronous Oligometastatic Non-Small Cell Lung Cancer: Thoracic Radiotherapy May Not Prolong Survival in High-Risk patients
Authors: Meng Chunliu , Wang Fang , Tian Jia , Wei Jia , Li Xue , Ren Kai , Xu Liming , Zhao Lujun , Wang Ping
Published: July 2022

Background and Purpose

On the basis of the promising clinical study results, thoracic radiotherapy (TRT)1 has become an integral part of treatment of synchronous oligometastatic non–small cell lung cancer (SOM-NSCLC). However, some of them experienced rapid disease progression after TRT and showed no significant survival benefit. How to screen out such patients is a more concerned problem at present. In this study, we developed a risk-prediction model by screening hematological and clinical data of patients with SOM-NSCLC and identified patients who would not benefit from TRT.

Materials and Methods

We investigated patients with SOM-NSCLC between 2011 and 2019. A formula named Risk-Total was constructed using factors screened by LASSO-Cox regression analysis. Stabilized inverse probability treatment weight analysis was used to match the clinical characteristics between TRT and non-TRT groups. The primary endpoint was overall survival (OS).

Results

We finally included 283 patients divided into two groups: 188 cases for the training cohort and 95 for the validation cohort. Ten prognostic factors included in the Risk-Total formula were age, N stage, T stage, adrenal metastasis, liver metastasis, sensitive mutation status, local treatment status to metastatic sites, systemic inflammatory index, CEA, and Cyfra211. Patients were divided into low- and high-risk groups based on risk scores, and TRT was found to have improved the OS of low-risk patients (46.4 vs. 31.7 months, P = 0.083; 34.1 vs. 25.9 months, P = 0.078) but not that of high-risk patients (14.9 vs. 11.7 months, P = 0.663; 19.4 vs. 18.6 months, P = 0.811) in the training and validation sets, respectively.

Conclusion

We developed a prediction model to help identify patients with SOM-NSCLC who would not benefit from TRT, and TRT could not improve the survival of high-risk patients.
Incidence of late-onset hemorrhagic cystitis and its effect on PFS in acute leukemia patients after haplo-PBSCT: The 5-year single-center data
Authors: Yuan Hailong , Chen Gang , Xu Jianli , Yang Ruixue , Muhashi Maria , Aizezi Gulibadanmu , Jiang Ming
Published: July 2022

We conducted a single-center 5-year retrospective study on the occurrence of hemorrhagic cystitis (HC) and its effect on survival after haploid high-dose peripheral blood stem cell transplantation (haplo-PBSCT) in patients with acute leukemia. We retrospectively analyzed 153 patients with acute leukemia who were treated with non-in vitro T-cell depleted haplo-PBSCT and myeloablative conditioning regimen. All patients were followed up for more than 180 days after transplantation. HC occurrence and its effect on long-term progression free survival (PFS) were retrospectively analyzed. Totally, 64 out of 153 patients had late onset HC (LOHC). No early onset HC occurred. The median onset time was 38.5 (17-163) days after transplantation. The cumulative incidence of LOHC was 41.8%. The cumulative incidence of LOHC in patients under 27 years old (50.0%) and in ALL patients (54.1%) was significantly higher than that in patients over 27 years old (34.5%) and in AML patients (36.9%), respectively. The cumulative incidence of mild LOHC was 44.2% and that of severe LOHC was 28.6%. However, urine copies of BK virus were not related to LOHC duration. There was no significant difference in 3-year expected PFS between AML and ALL patients with and without LOHC, or between LOHC duration more than and less than 38.5 days (P>0.05). Conclusively, LOHC incidence is higher in patients under 27 years old and in ALL patients. LOHC occurrence is related to urine BK virus copy, but not blood BK virus load. LOHC duration and severity has no significant effect on PFS.
Effects of polymorphisms in the MTHFR gene on 5-FU hematological toxicity and efficacy in Thai colorectal cancer patients
Authors: Atasilp Chalirmporn , Lenavat Rinradee , Vanwong Natchaya , Chansriwong Phichai , Sirachainan Ekaphop , Reungwetwattana Thanyanan , Jinda Pimonpan , Aiempradit Somthawin , Sirilerttrakul Suwannee , Chamnanphon Monpat , Puangpetch Apichaya , Sankuntaw Nipaporn , Satapornpong Patompong , Sukasem Chonlaphat
Published: July 2022

Background

The two common methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677G>A and 1298A>C may have been affecting 5-FU toxicity in cancer patients for decades. Drug efficacy has also been shown by previous studies to be affected. In this study, we investigated the effects of these polymorphisms on 5-FU hematological toxicity and treatment efficacy, to provide enhanced pharmacological treatment for cancer patients.

Methods

This is a retrospective study involving 52 Thai colorectal cancer patients who were treated with 5-FU based therapy, using TaqMAN real-time PCR to genotype the MTHFR polymorphisms (677G>A and 1298A>C). The toxicity and response rate were assessed using standardized measures.

Results

Neutropenia was significantly more likely to be experienced (P=0.049, OR=7.286, 95% CI=0.697-76.181) by patients with the MTHFR 677G>A polymorphism, in the same way as leukopenia (P =0.036, OR=3.333, 95%CI=2.183-5.090) and thrombocytopenia (P<0.001, OR=3.917, 95%CI=2.404-6.382). The MTHFR 1298A>C polymorphism had no statistical association with hematological toxicity in 5-FU treatment. The response rate to 5-FU was not significantly affected by these two polymorphisms.

Conclusion

The MTHFR polymorphism 677G>A is a significant risk factor for developing leukopenia, neutropenia and thrombocytopenia as toxic effects of 5-FU therapy in cancer patients. Therefore, patients receiving 5-FU-based therapy should be aware of their polymorphisms as one risk factor for experiencing severe toxicity.
Role of exosomal microRNAs in cancer therapy and drug resistance mechanisms: focus on hepatocellular carcinoma
Authors: Zelli Veronica , Compagnoni Chiara , Capelli Roberta , Corrente Alessandra , Di Vito Nolfi Mauro , Zazzeroni Francesca , Alesse Edoardo , Tessitore Alessandra
Published: July 2022

Extracellular vesicles (EVs), defined as intercellular messengers that carry their cargos between cells, are involved in several physiological and pathological processes. These small membranous vesicles are released by most cells and contain biological molecules, including nucleic acids, proteins and lipids, which can modulate signaling pathways of nearby or distant recipient cells. Exosomes, one the most characterized classes of EVs, include, among others, microRNAs (miRNAs), small non-coding RNAs able to regulate the expression of several genes at post-transcriptional level. In cancer, exosomal miRNAs have been shown to influence tumor behavior and reshape tumor microenvironment. Furthermore, their possible involvement in drug resistance mechanisms has become evident in recent years. Hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for 75-85% of all liver tumors. Although the improvement in HCC treatment approaches, low therapeutic efficacy in patients with intermediate-advanced HCC is mainly related to the development of tumor metastases, high risk of recurrence and drug resistance. Exosomes have been shown to be involved in pathogenesis and progression of HCC, as well as in drug resistance, by regulating processes such as cell proliferation, epithelial-mesenchymal transition and immune response. Herein, we summarize the current knowledge about the involvement of exosomal miRNAs in HCC therapy, highlighting their role as modulators of therapeutic response, particularly chemotherapy and immunotherapy, as well as possible therapeutic tools.
Clinical Implications of Nadir Serum Prostate-Specific Antigen Levels After Transurethral Enucleation of the Prostate
Authors: Cheng Yung-Ting , Hong Jian-Hua , Lu Yu-Chuan , Chang Yi-Kai , Hung Shih-Chun , Feng Kuo-Kang , Liu Shih-Ping , Chow Po-Ming , Chang Hong-Chiang , Chen Chung-Hsin , Pu Yeong-Shiau
Published: July 2022

Objective

Prostate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer.

Materials and Methods

We retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis.

Results

In total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate.

Conclusions

The post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.
Incremental validity of acceptance over coping in predicting adjustment to endometriosis
Authors: Bernini Olivia , Tumminaro Giovanni , Compare Lisa , Belviso Cristina , Conforti Valentina , Berrocal Montiel Carmen
Published: July 2022

Psychological acceptance has emerged as an important construct to explain low psychological distress in different clinical samples. However, the incremental validity of psychological acceptance to explain adjustment to medical conditions over other related and well-established constructs, such as coping, is relatively unclear. This study explored whether psychological acceptance significantly contributes to explain adjustment above and beyond coping in females with endometriosis. A total of 169 females (Mage = 34.95 years; SDage = 6.07 years) with endometriosis and pain symptoms completed the Acceptance and Action Questionnaire-II, the Brief-COPE, the Hospital Anxiety and Depression Scale, the Psychological Wellbeing Scale, and the Endometriosis Health Profile-5. We conducted Hierarchical Regression Analyses to determine the contribution of psychological acceptance to explaining adjustment. The results showed that the contribution of psychological acceptance ranged from 11 to 20% when controlling for coping, while coping explained from 1 to 8% when the model was reversed. The findings suggest that psychological acceptance is a more useful construct than coping for predicting PD and other psychological outcomes in females with endometriosis.
An Inducible Nitric Oxide Synthase Dimerization Inhibitor Prevents the Progression of Osteoarthritis
Authors: Xian Bo Shang , Yan Jie Wang , De Chao Cai , Sai Ma , Zhe Wang , Ya Kun Zhu , Hui Hui Guo , Chen Wang , Xiao Ma , Zhong Yao Hu , Hao Ran Yu , Ji Sen Zhang , Wen Dan Cheng
Published: July 2022

Objective: Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS). The aim of this study was to design and synthesize an iNOS dimerization inhibitor and evaluate its effects on chondrocyte inflammation and articular cartilage injury in OA via in vitro and in vivo experiments.

Design: The title compound 22o was designed, synthesized, and screened based on a previous study. The effects of different concentrations (5, 10, and 20 μM) of compound 22o on chondrocyte inflammatory response and ECM anabolism or catabolism were evaluated by Western blot and real-time quantitative reverse transcription-polymerase chain reaction using the rat chondrocyte model of IL-1β-induced OA. Furthermore, different doses (40 and 80 mg/kg) of compound 22o were administered by gavage to a rat OA model induced by anterior cruciate ligament transection (ACLT), and their protective effects on the articular cartilage were evaluated by histopathology and immunohistochemistry.

Results: Compound 22o showed effective iNOS inhibitory activity by inhibiting the dimerization of iNOS. It inhibited the IL-1β-induced expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase 3 (MMP3) in the chondrocytes, decreased NO production, and significantly increased the expression levels of the ECM anabolic markers, aggrecan (ACAN), and collagen type II (COL2A1). Gavage with compound 22o was found to be effective in the rat OA model induced by ACLT, wherein it regulated the anabolism and catabolism and exerted a protective effect on the articular cartilage.

Conclusions: Compound 22o inhibited the inflammatory response and catabolism of the chondrocytes and reduced articular cartilage injury in the rat OA model, indicating its potential as a disease-modifying OA drug.
High-Dose Rifampicin Mediated Systemic Alterations of Cytokines, Chemokines, Growth Factors, Microbial Translocation Markers, and Acute-Phase Proteins in Pulmonary Tuberculosis
Authors: Kathamuthu Gokul Raj , Bhavani Perumal Kannabiran , Singh Manjula , Saini Jitendra Kumar , Aggarwal Ashutosh , Ansari Mohammed Soheb S. , Garg Rajiv , Babu Subash
Published: July 2022

High-dose rifampicin (HDR) is now undergoing clinical trials to improve the efficacy of anti-tuberculosis treatment (ATT). However, the influence of HDR in the modulation of different cytokines, chemokines/growth factors, microbial translocation markers (MTMs), and acute-phase proteins (APPs) in pulmonary tuberculosis (PTB) is not well known. PTB individuals were separated into three different arms (R10, R25, and R35) based on their rifampicin dosage. We examined the circulating levels of Type 1, Type 2, pro-inflammatory/regulatory cytokines, chemokines/growth factors, MTMs, and APPs at baseline and after completion of the second month of ATT by ELISA. The baseline levels of cytokines, chemokines/growth factors, MTMs, and APPs did not (except IL-5, IL-6, IL-17A, MCP-1, MIP-1β, GCSF, SAA, ⍺2 MG, Hp) significantly differ between the study individuals. However, at the second month, the plasma levels of Type 1 (TNFα and IFNγ), Type 2 (IL-4, IL-5, and IL-13), pro-inflammatory/regulatory cytokines (IL-6, IL-17A, IL-10, and GMCSF), and APPs were significantly decreased in R35 regimen- compared to R25 and/or R10 regimen-treated PTB individuals. In contrast, the plasma levels of IL-2, IL-8, MCP-1, MIP-1β, GSF, and MTMs were significantly increased in the R35 regimen compared to R25 and/or R10 regimen-treated PTB individuals. Overall, our data reveal that HDR could potentially be beneficial for host immunity by altering different immune and inflammatory markers.
Synergistic effect of VEGF and SDF-1α in endothelial progenitor cells and vascular smooth muscle cells
Authors: Yang Haiyan , He Cancan , Bi Yang , Zhu Xu , Deng Dan , Ran Tingting , Ji Xiaojuan
Published: July 2022

Vascular endothelial growth factor (VEGF) is a potent agonist of angiogenesis that induces proliferation and differentiation of endothelial progenitor cells (EPCs) after vascular injury. Previous studies have suggested that stromal cell-derived factor 1-alpha (SDF-1α) and VEGF have a synergistic effect on vascular stenosis. The aim of the present study was to investigate whether VEGF and SDF-1α act synergistically in EPCs and vascular smooth muscle cells (VSMCs). In this study, EPCs were isolated from rat bone marrow and their morphology and function were studied. Subsequently, VEGF was delivered into EPCs using an adenoviral vector. Tube formation, migration, proliferation, and apoptosis of VEGF-overexpressing EPCs was analyzed. Then, EPCs were co-cultured with VSMCs in the presence or absence of SDF-1α, the migration, proliferation, apoptosis, and differentiation capacity of EPCs and VSMCs were analyzed respectively. The isolated EPCs showed typical morphological features, phagocytic capacity, and expressed surface proteins. While stable expression of VEGF remarkably enhanced tube formation, migration, and proliferation capacity of EPCs, apoptosis was decreased. Moreover, the proliferation, migration, and differentiation capacity of EPCs in the co-cultured model was enhanced in the presence of SDF-1α, and apoptosis was decreased. However, these effects were reversed in VSMCs. Therefore, our results showed that VEGF and SDF-1α synergistically increased the migration, differentiation, and proliferation capabilities of EPCs, but not VSMCs. This study suggests a promising strategy to prevent vascular stenosis.
Renoprotective potentials of small molecule natural products targeting mitochondrial dysfunction
Authors: Rahman Md. Ataur , Akter Sumaya , Dorotea Debra , Mazumder Arpita , Uddin Md. Naim , Hannan Md. Abdul , Hossen Muhammad Jahangir , Ahmed Md. Selim , Kim Woojin , Kim Bonglee , Uddin Md Jamal
Published: July 2022

Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), have become critical clinical, socioeconomic, and public health concerns worldwide. The kidney requires a lot of energy, and mitochondria act as the central organelle for the proper functioning of the kidney. Mitochondrial dysfunction has been associated with the pathogenesis of AKI and CKD. Natural products and their structural analogs have been sought as an alternative therapeutic strategy despite the challenges in drug discovery. Many studies have shown that small-molecule natural products can improve renal function and ameliorate kidney disease progression. This review summarizes the nephroprotective effects of small-molecule natural products, such as berberine, betulinic acid, celastrol, curcumin, salidroside, polydatin, and resveratrol. Treatment with small-molecule natural products was shown to attenuate renal oxidative stress and mitochondrial DNA (mtDNA) damage and restore mitochondrial biogenesis and dynamics in the kidneys against various injury stimuli. Therefore, small-molecule natural products should be recognized as multi-target therapeutics and promising drugs to prevent kidney diseases, particularly those with mitochondrial dysfunction.
Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling
Authors: Porta Exequiel O. J. , Isern Jaime A. , Kalesh Karunakaran , Steel Patrick G.
Published: July 2022

Leishmaniasis are a group of diseases caused by parasitic protozoa of the genus Leishmania. Current treatments are limited by difficult administration, high cost, poor efficacy, toxicity, and growing resistance. New agents, with new mechanisms of action, are urgently needed to treat the disease. Although extensively studied in other organisms, serine proteases (SPs) have not been widely explored as antileishmanial drug targets. Herein, we report for the first time an activity-based protein profiling (ABPP) strategy to investigate new therapeutic targets within the SPs of the Leishmania parasites. Active-site directed fluorophosphonate probes (rhodamine and biotin-conjugated) were used for the detection and identification of active Leishmania serine hydrolases (SHs). Significant differences were observed in the SHs expression levels throughout the Leishmania life cycle and between different Leishmania species. Using iTRAQ-labelling-based quantitative proteomic mass spectrometry, we identified two targetable SPs in Leishmania mexicana: carboxypeptidase LmxM.18.0450 and prolyl oligopeptidase LmxM.36.6750. Druggability was ascertained by selective inhibition using the commercial serine protease inhibitors chymostatin, lactacystin and ZPP, which represent templates for future anti-leishmanial drug discovery programs. Collectively, the use of ABPP method complements existing genetic methods for target identification and validation in Leishmania.
RAB39B as a Chemosensitivity-Related Biomarker for Diffuse Large B-Cell Lymphoma
Authors: Xu Cong , Liang Ting , Liu Jing , Fu Yunfeng
Published: July 2022

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma with an increased tendency to relapse or refractoriness. RAB39B, a member of the Ras-oncogene superfamily, is associated with a variety of tumors. Nevertheless, the role of RAB39B in DLBCL is still unknown. This study aimed to identify the role of RAB39B in DLBCL using integrated bioinformatics analysis.

Methods: RAB39B expression data were examined using TIMER, UCSC, and GEO databases. The LinkedOmics database was used to study the genes and signaling pathways related to RAB39B expression. A Protein–protein interaction network was performed in STRING. TIMER was used to analyze the correlation between RAB39B and infiltrating immune cells. The correlation between RAB39B and m6A-related genes in DLBCL was analyzed using TCGA data. The RAB39B ceRNA network was constructed based on starBase and miRNet2.0 databases. Drug sensitivity information was obtained from the GSCA database.

Results: RAB39B was highly expressed in multiple tumors including DLBCL. The protein–protein interaction network showed enrichment of autophagy and RAS family proteins. Functional enrichment analysis of RAB39B co-expression genes revealed that RAB39B was closely related to DNA replication, protein synthesis, cytokine–cytokine receptor interaction, JAK-STAT signaling pathway, NF-kappa B signaling pathway, and autophagy. Immune infiltrate analysis showed that the amount of RAB39B was negatively correlated with iDC, Tem, and CD8 T-cell infiltration. CD4+ T cell and DC were negatively correlated with CNV of RAB39B. DLBCL cohort analysis found that RAB39B expression was related to 14 m6A modifier genes, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, ZC3H13, METTL14, METTL3, RBM15, RBM15B, VIRMA, FTO, and ALKBH5. We constructed 14 possible ceRNA networks of RAB39B in DLBCL. The RAB39B expression was associated with decreased sensitivity of chemotherapy drugs such as dexamethasone, doxorubicin, etoposide, vincristine, and cytarabine and poor overall survival in DLBCL. In vitro experiments showed that RAB39B was associated with proliferation, apoptosis, and drug sensitivity of DLBCL cells.

Conclusion: RAB39B is abnormally elevated and related to drug resistance and poor OS in DLBCL, which may be due to its involvement in immune infiltration, m6A modification, and regulation by multiple non-coding RNAs. RAB39B may be used as an effective biomarker for the diagnosis and treatment of DLBCL.
Native Lizards Living in Brazilian Cities: Effects of Developmental Environments on Thermal Sensitivity and Morpho-Functional Associations of Locomotion
Authors: Rossigalli-Costa Nathalia , Kohlsdorf Tiana
Published: July 2022

Environmental conditions often affect developmental processes and consequently influence the range of phenotypic variation expressed at population level. Expansion of urban sites poses new challenges for native species, as urbanization usually affects the intensity of solar exposure and shade availability, determining the thermal regimes organisms are exposed to. In this study, we evaluate the effects of different developmental conditions in a Tropidurus lizard commonly found in Brazilian urban sites. After incubating embryos of Tropidurus catalanensis in two different thermal regimes (Developmental Environments [DE]: cold 24°C and warm 30°C), we measured morphological traits in the neonates and quantified locomotor performance in horizontal and vertical surfaces at three temperatures [Test Temperatures (TT) = 24°C, 30°C and 36°C]. Results indicate effects of developmental temperatures on morphological features, expressing functional implications that might be decisive for the viability of T. catalanensis in urbanized areas. Lizards ran similarly on horizontal and vertical surfaces, and isolated analyses did not identify significant effects of DE or TT on the sprint speeds measured. Absolute Vmax (i.e., the maximum sprint speed reached among all TTs) positively correlated with body size (SVL), and neonates from the warm DE (30°C) were larger than those from the cold DE (24°C). Morpho-functional associations of absolute Vmax also involved pelvic girdle width and forelimb, hindlimb, trunk, and tail lengths. Emerging discussions aim to understand how animals cope with abrupt environmental shifts, a likely common challenge in urbanized sites. Our findings add a new dimension to the topic, providing evidence that temperature, an environmental parameter often affected by urbanization, influences the thermal sensitivity of locomotion and the morphological profile of T. catalanensis neonates. Thermal sensitivity of specific developmental processes may influence the ability of these lizards to remain in habitats that change fast, as those suffering rapid urbanization due to city growth.
Effects of autotoxicity and allelopathy on seed germination and seedling growth in Medicago truncatula
Authors: Wang Chang , Liu Zhe , Wang Zicheng , Pang Wenhui , Zhang Long , Wen Zhaozhu , Zhao Yiran , Sun Juan , Wang Zeng-Yu , Yang Chao
Published: July 2022

Autotoxicity is a form of intraspecific allelopathy, in which a plant species inhibits the establishment or growth of the same species through the release of toxic chemical compounds into the environment. The phenomenon of autotoxicity in crops is best traced in alfalfa (Medicago sativa). A close relative of alfalfa, M. truncatula, has been developed into an excellent model species for leguminous plants. However, it is not known whether M. truncatula has autotoxicity. In this study, M. truncatula root exudates showed a negative impact on the growth of M. truncatula seedlings, indicating autotoxicity. Detailed analyses with plant extracts from M. truncatula and alfalfa revealed varying degrees of suppression effects in the two species. The extracts negatively affected seed germination potential, germination rate, radicle length, hypocotyl length, synthetic allelopathic effect index, plant height, root growth, fresh weight, dry weight, net photosynthetic rate, transpiration rate, and stomatal conductance in both M. truncatula and alfalfa. The results demonstrated that autotoxicity and allelopathic effects exist in M. truncatula. This opens up a new way to use M. truncatula as a model species to carry out in-depth studies of autotoxicity and allelopathy to elucidate biochemical pathways of allelochemicals and molecular networks controlling biosynthesis of the chemicals.
Looking for peptides from rice starch processing by-product: Bioreactor production, anti-tyrosinase and anti-inflammatory activity, and in silico putative taste assessment
Authors: Ferri Maura , Tedeschi Tullia , Prandi Barbara , Michelini Elisa , Calabretta Maria Maddalena , Babini Elena , Graen-Heedfeld Jürgen , Bretz Karlheinz , Raddadi Noura , Gianotti Andrea , Lamborghini Matteo , Tassoni Annalisa
Published: July 2022

One of the major challenges for the modern society, is the development of a sustainable economy also aiming at the valorization of agro-industrial by-products in conjunction with at a significant reduction of generated residues from farm to retail. In this context, the present study demonstrates a biotechnological approach to yield bioactive peptides from a protein fraction obtained as a by-product of the rice starch production. Enzymatic hydrolysis, with the commercial proteases Alcalase and Protamex, were optimized in bioreactor up to 2 L of volume. The two best digestates, selected with respect to peptide release and extract antioxidant capacity, were further fractionated (cut-offs of 10, 5, and 1 kDa) via cross-flow filtration. Amino acid composition indicated that most of the fractions showed positive nutritional characteristics, but a putative bitter taste. A fraction obtained with Alcalase enzyme (retentate 8 kDa) exerted anti-inflammatory potential, while the smaller molecular weight fractions (retentate 1–5 kDa and permeate < 1 kDa) were more active in tyrosinase inhibition. The latter were further sub-fractionated by size-exclusion chromatography. From the 15 most anti-tyrosinase sub-fractions, 365 peptide sequences were identified via liquid chromatography coupled with high resolution mass spectrometry. The present data support the possible exploitation of bioactive peptide from rice starch by-product as ingredients into food, nutraceutical, pharmaceutical, and cosmetic formulations.