bluuebunny/crossref_metadata_2025 huggingface dataset:
Harvester perceptions of climate vulnerability: Contributions to building climate resilient fisheries
Authors: Runnebaum Jocelyn M. , Nelson Laura K. , Harper Sarah J. , Bell Richard J. , Smith Geoffrey S. , Cullen Alison C. , Cutler Matthew J. , Levin Phillip S.
Published: January 2023

The uncertainty of future ocean conditions caused by climate change challenges the conventional fisheries management model that assumes resource extraction occurs in a steady-state environment. As managers respond to climate impacts and focus on long-term preparedness, an overarching goal is to minimize the vulnerability of fishing businesses and communities. However, during the adaptation process, challenges can arise when perceptions of climate change vulnerability differ among scientists, managers, and harvesters. A harvester’s perception of their risk to climate change influences their willingness to plan for and respond to change, yet these views are often overlooked in adaptation planning. To better understand this dynamic, we conducted a regional survey to evaluate the perceptions harvesters hold regarding the impacts of climate change on commercially fished species in the Northeastern United States and the resulting risks from those changes. The waters in this region of the Northwest Atlantic shelf are warming faster than the global average resulting in shifting distributions of species, altered seasonal migrations, and changes in productivity. Respondents’ perceptions aligned with an analysis conducted by scientists on the directionality of climate impacts for 12 out of 27 (44%) of the most commercially important species in the region. Additionally, an understanding of the variability in perceptions of climate change vulnerability emerged: 72% of respondents believe climate change is occurring, 53% believe climate change will harm them personally, and 28% have already seen a negative impact on their ability to catch fish. Respondents who believe that climate change is occurring had higher perceptions of vulnerability on average than those who do not believe it is occurring. Despite a sense of vulnerability to climate change, respondents did not rank it among the top three concerns (fisheries regulations, market access, and access to working waterfronts) for their fishing businesses. Investigating harvester’s perceptions is an opportunity to share their experiences and understand the diversity of perspectives regarding the impacts of climate change. Increasing the inclusion of social science indicators and diverse perspectives will increase climate resilience of fisheries management.
Morganella morganii septicemia and concurrent renal crassicaudiasis in a Cuvier’s beaked whale (Ziphius cavirostris) stranded in Italy
Authors: Romani-Cremaschi Umberto , Zoppi Simona , Mattioda Virginia , Audino Tania , Marsili Letizia , Varello Katia , Iulini Barbara , Marra Cristina , Zoccola Roberto , Battistini Roberta , Dondo Alessandro , Garibaldi Fulvio , Berio Enrica , Pautasso Alessandra , Rosso Massimiliano , Ascheri Davide , Casalone Cristina , Grattarola Carla , Giorda Federica
Published: January 2023

Information regarding bacterial diseases in Cuvier’s beaked whale (CBW, Ziphius cavirostris) is scattered and mostly incomplete. This report describes a case of septicemia byMorganella morganiiin a juvenile male CBW with concurrent renal crassicaudiasis. The animal stranded along the Ligurian coastline (Italy) and underwent a systematic post-mortem examination to determine the cause of death. Histopathology showed lesions consistent with a septicemic infection, severe meningoencephalitis, and renal crassicaudiasis. AnM. morganiialpha-hemolytic strain was isolated in pure culture from liver, lung, prescapular lymph node, spleen, hepatic and renal abscesses, and central nervous system (CNS). The antimicrobial susceptibility profile of the strain was evaluated with the minimum inhibitory concentrations (MICs) method and reduced susceptibility to Trimethoprim-Sulfamethoxazole is reported. Crassicauda sp. nematodes were retrieved from both kidneys. No other pathogens were detected by immunohistochemistry, serology, or biomolecular analyses. Toxicological investigations detected high concentrations of immunosuppressant pollutants in the blubber. The chronic parasitic infestation and the toxic effects of xenobiotics likely compromised the animal's health, predisposing it to an opportunistic bacterial infection. To our knowledge, this is the first description ofM. morganiisepticemia with CNS involvement in a wild cetacean.
Study on MEV90 of 0.5% ropivacaine for US-guided caudal epidural block in anorectal surgery
Authors: Zhang Pei , Chang Hong , Yang Taoran , Fu Yalong , He Xuemei , Li Jun , Yang Mingan , Wang Rurong , Li Xuehan
Published: January 2023

Background

Choosing the appropriate concentration and volume of anesthetics is critical for a successful nerve block. The current study aimed to determine the minimum effective volume (MEV) of 0.5% ropivacaine for US-guided CEB in 90% of patients (MEV90) undergoing anorectal surgery. The aims were to reduce the occurrence of complications associated with a sacral blockade in anorectal surgery, broaden the indications for surgical procedures and treatment, and improve patient satisfaction. This study presents the groundwork for the development of individualized anesthetic programs. We believe that the study would serve as a reference for the use of caudal epidural block (CEB) in lower abdominal surgery for intraoperative and postoperative analgesia.

Methods

This study used a biased coin design (BCD) up-and-down method (UDM). We divided the participants into two groups based on gender, and each group independently performed the biased coin design up-and-down method. We used 0.5% ropivacaine for the first patient in each group; however, the volume was 10 ml for men and 8 ml for women. Therefore, the dose of anesthetics given to each patient was determined by the response of the previous patient. If the block of the previous patient failed, the volume was increased by 2 ml in the following patient. Otherwise, the next subject had an 11% chance of receiving a volume of 2 ml less or an 89% chance of receiving no volume change. We defined a successful block as painless surgery with anal sphincter relaxation 15 min after the drug injection. Enrollment was completed after 45 successful caudal blocks for each group.

Results

Caudal epidural block was successfully performed on 50 men and 49 women. The MEV90 of ropivacaine for CEB was calculated to be 12.88 ml (95% CI: 10.8–14 ml) for men and 10.73 ml (95% CI: 9.67–12 ml) for women. Men had a MEV99 of 13.88 ml (95% CI: 12.97–14 ml), and women had a MEV99 of 11.87 ml (95% CI: 11.72–12 ml).

Conclusion

With operability and general applicability, it is possible to increase the success rate of CEB for anorectal surgery to 99% as well as decrease the incidence of anesthesia-related complications. CEB can meet the needs of patients for rapid postoperative rehabilitation, improve patient satisfaction, and lay a solid foundation for postoperative analgesia.
Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes
Authors: Allendes Francisca J. , Díaz Hugo S. , Ortiz Fernando C. , Marcus Noah J. , Quintanilla Rodrigo , Inestrosa Nibaldo C. , Del Rio Rodrigo
Published: January 2023

A significant percentage of COVID-19 survivors develop long-lasting cardiovascular sequelae linked to autonomic nervous system dysfunction, including fatigue, arrhythmias, and hypertension. This post-COVID-19 cardiovascular syndrome is one facet of “long-COVID,” generally defined as long-term health problems persisting/appearing after the typical recovery period of COVID-19. Despite the fact that this syndrome is not fully understood, it is urgent to develop strategies for diagnosing/managing long-COVID due to the immense potential for future disease burden. New diagnostic/therapeutic tools should provide health personnel with the ability to manage the consequences of long-COVID and preserve/improve patient quality of life. It has been shown that cardiovascular rehabilitation programs (CRPs) stimulate the parasympathetic nervous system, improve cardiorespiratory fitness (CRF), and reduce cardiovascular risk factors, hospitalization rates, and cognitive impairment in patients suffering from cardiovascular diseases. Given their efficacy in improving patient outcomes, CRPs may have salutary potential for the treatment of cardiovascular sequelae of long-COVID. Indeed, there are several public and private initiatives testing the potential of CRPs in treating fatigue and dysautonomia in long-COVID subjects. The application of these established rehabilitation techniques to COVID-19 cardiovascular syndrome represents a promising approach to improving functional capacity and quality of life. In this brief review, we will focus on the long-lasting cardiovascular and autonomic sequelae occurring after COVID-19 infection, as well as exploring the potential of classic and novel CRPs for managing COVID-19 cardiovascular syndrome. Finally, we expect this review will encourage health care professionals and private/public health organizations to evaluate/implement non-invasive techniques for the management of COVID-19 cardiovascular sequalae.
Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition
Authors: Dayanidhi Divya L. , Somarelli Jason A. , Mantyh John B. , Rupprecht Gabrielle , Roghani Roham Salman , Vincoff Sophia , Shin Iljin , Zhao Yiquan , Kim So Young , McCall Shannon , Hong Jiyong , Hsu David S.
Published: January 2023

Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In our prior work, we coupled high-throughput chemical screens with patient-derived models of cancer to identify new potential therapeutic targets for CRC. However, this pipeline is limited by (1) the use of cell lines that do not appropriately recapitulate the tumor microenvironment, and (2) the use of patient-derived xenografts (PDXs), which are time-consuming and costly for validation of drug efficacy. To overcome these limitations, we have turned to patient-derived organoids. Organoids are increasingly being accepted as a “standard” preclinical model that recapitulates tumor microenvironment cross-talk in a rapid, cost-effective platform. In the present work, we employed a library of natural products, intermediates, and drug-like compounds for which full synthesis has been demonstrated. Using this compound library, we performed a high-throughput screen on multiple low-passage cancer cell lines to identify potential treatments. The top candidate, psymberin, was further validated, with a focus on CRC cell lines and organoids. Mechanistic and genomics analyses pinpointed protein translation inhibition as a mechanism of action of psymberin. These findings suggest the potential of psymberin as a novel therapy for the treatment of CRC.
Comparison of pregnancy outcome after fresh embryo transfer between GnRH antagonist and GnRH agonist regimens in patients with thin endometrium
Authors: Zhao Depeng , Xie Rui , Li Xuemei
Published: January 2023

Objective

To compare the pregnancy outcome after fresh embryo transfer between GnRH antagonist and GnRH agonist regimens in patients with thin endometrium.

Methods

This retrospective study included all fresh embryo transfers following GnRH agonist or GnRH antagonist protocols in patients with thin endometrium from 2016 to 2021. The thin endometrium was defined as an endometrial thickness of 7.5 mm or less on the triggering day. Multivariant regression analysis was applied to assess the association of GnRH agonist or GnRH antagonist regimen with live birth following fresh embryo transfer in patients with thin endometrium.

Results

A total of 69 and 192 cases were, respectively, included in the GnRH antagonist or GnRH agonist group. The stimulation duration was significantly longer by the GnRH agonist protocol than the GnRH antagonist protocol (11.2 ± 2.1 vs. 9.1 ± 1.9 days, P = 0.002). The rates of clinical pregnancy or live birth were significantly lower in the GnRH antagonist group compared to the GnRH agonist group (26.1 vs. 47.9%, P = 0.027; 17.4 vs. 40.1%, P = 0.01, respectively). Multivariable regression analysis demonstrated that GnRH agonist regimen was related to higher live birth rate compared with GnRH agonist protocol [adjusted OR: 2.6, 95% confidence intervals (CI): 1.3–5.3]. No significant difference in miscarriage rate and the neonatal outcome was present between the two protocols.

Conclusion

Our findings suggest that GnRH agonist protocol results in a higher rate of live birth after fresh embryo transfer than GnRH antagonist protocol in patients with thin endometrium.
Influence of key histological characteristics on 18F-fluorodeoxyglucose /18F-choline positron emission tomography positivity in hepatocellular carcinoma: A machine learning study
Authors: Ghidaglia Jérôme , Laurent Vincent , Sebagh Mylène , Pascale Alina , Durand Emmanuel , Golse Nicolas , Besson Florent L.
Published: January 2023

Purpose

To determine the characteristics influence of key histological on 18F-fluorodeoxyglucose (18F-FDG) and 18F-choline positron emission tomography (PET) positivity in hepatocellular carcinoma (HCC).

Materials and methods

The 18F-FDG/18F-choline PET imaging findings of 103 histologically proven HCCs (from 62 patients, of which 47 underwent hepatectomy and 15 received liver transplantation) were retrospectively examined to assess the following key histological parameters: Grade, capsule, microvascular invasion (mVI), macrovascular invasion (MVI), and necrosis. Using a ratio of 70/30 for training and testing sets, respectively, a penalized classification model (Elastic Net) was trained using 100 repeated cross-validation procedures (10-fold cross-validation for hyperparameter optimization). The contribution of each histological parameter to the PET positivity was determined using the Shapley Additive Explanations method. Receiver operating characteristic curves with and without dimensionality reduction were finally estimated and compared.

Results

Among the five key histological characteristics of HCC (Grade, capsule, mVI, MVI, and necrosis), mVI and tumor Grade (I–III) showed the highest relevance and robustness in explaining HCC uptake of 18F-FDG and 18F-choline. MVI and necrosis status both showed high instability in outcome predictions. Tumor capsule had a minimal influence on the model predictions. On retaining only mVI and Grades I–III for the final analysis, the area under the receiver operating characteristic (ROC) curve values were maintained (0.68 vs. 0.63, 0.65 vs. 0.64, and 0.65 vs. 0.64 for 18F-FDG, 18F-choline, and their combination, respectively).

Conclusion

18F-FDG/18F-choline PET positivity appears driven by both the Grade and mVI components in HCC. Consideration of the tumor microenvironment will likely be necessary to improve our understanding of multitracer PET positivity.
Effect of different straw retention techniques on soil microbial community structure in wheat–maize rotation system
Authors: Zhang Shulin , Li Meng , Cui Xinyue , Pan Yuemin
Published: January 2023

Rotational straw return technique is considered an effective measure for improving soil quality and maintaining soil microorganisms. However, there are few reports on the influence of wheat–maize crop rotation and straw-returning tillage on crop soil microbial communities in China. This study aimed to investigate how wheat or maize straw-incorporation practices affect bacterial and fungal communities under wheat–maize rotational farming practices. To clarify the effects of straw incorporation on microbial composition, microbial communities from soils subjected to different treatments were identified using high-throughput sequencing. Our results showed that, before corn planting, wheat and maize straw returning reduced bacterial density and increased their diversity but had no effect on fungal diversity. However, before wheat planting, returning wheat and corn stalks to the field increased the diversity of soil bacteria and fungi, whereas returning corn stalks to the field reduced the diversity of fungi and other microorganisms. Straw return significantly increased the relative abundance of Ascomycota in the first season and decreased it in the second season; however, in the second season, wheat straw return increased the relative abundance of Bradyrhizobium, which can promote the soil microbial nitrogen cycle and provide nitrogen to the soil. Wheat and maize straw return increased the relative abundance of Chaetomium, whereas, individually, they decreased the relative abundance. In addition, we detected two fungal pathogens (Fusarium and Trichoderma) under the two planting patterns and found that the relative abundance of pathogenic Fusarium increased with wheat straw return (FW and SW). Trichoderma increased after treatment with maize straw return before wheat planting (S group). These results suggest that wheat straw return (FW and SW) and maize straw return might have a negative impact on the pathogenic risk. Therefore, further studies are needed to determine how to manage straw returns in agricultural production.
Comparative metabolomic analysis of exudates of microcystin-producing and microcystin-free Microcystis aeruginosa strains
Authors: Zhou Yuan , Xu Jun , MacIsaac Hugh J. , McKay Robert Michael , Xu Runbing , Pei Ying , Zi Yuanyan , Li Jiaojiao , Qian Yu , Chang Xuexiu
Published: January 2023

Cyanobacterial harmful algal blooms (cHABs) dominated by Microcystis aeruginosa threaten the ecological integrity and beneficial uses of lakes globally. In addition to producing hepatotoxic microcystins (MC), M. aeruginosa exudates (MaE) contain various compounds with demonstrated toxicity to aquatic biota. Previously, we found that the ecotoxicity of MaE differed between MC-producing and MC-free strains at exponential (E-phase) and stationary (S-phase) growth phases. However, the components in these exudates and their specific harmful effects were unclear. In this study, we performed untargeted metabolomics based on liquid chromatography-mass spectrometry to reveal the constituents in MaE of a MC-producing and a MC-free strain at both E-phase and S-phase. A total of 409 metabolites were identified and quantified based on their relative abundance. These compounds included lipids, organoheterocyclic compounds, organic acid, benzenoids and organic oxygen compounds. Multivariate analysis revealed that strains and growth phases significantly influenced the metabolite profile. The MC-producing strain had greater total metabolites abundance than the MC-free strain at S-phase, whereas the MC-free strain released higher concentrations of benzenoids, lipids, organic oxygen, organic nitrogen and organoheterocyclic compounds than the MC-producing strain at E-phase. Total metabolites had higher abundance in S-phase than in E- phase in both strains. Analysis of differential metabolites (DMs) and pathways suggest that lipids metabolism and biosynthesis of secondary metabolites were more tightly coupled to growth phases than to strains. Abundance of some toxic lipids and benzenoids DMs were significantly higher in the MC-free strain than the MC-producing one. This study builds on the understanding of MaE chemicals and their biotoxicity, and adds to evidence that non-MC-producing strains of cyanobacteria may also pose a threat to ecosystem health.
Quorum sensing and QsvR tightly control the transcription of vpa0607 encoding an active RNase II-type protein in Vibrio parahaemolyticus
Authors: Zhang Yiquan , Xue Xingfan , Sun Fengjun , Li Xue , Zhang Miaomiao , Wu Qimin , Zhang Tingting , Luo Xi , Lu Renfei
Published: January 2023

Vibrio parahaemolyticus, a Gram-negative, halophilic bacterium, is a leading cause of acute gastroenteritis in humans. AphA and OpaR are the master quorum sensing (QS) regulators operating at low cell density (LCD) and high cell density (HCD), respectively. QsvR is an AraC-type protein that integrates into the QS system to control gene expression by directly controlling the transcription of aphA and opaR. However, the regulation of QsvR itself remains unclear to date. In this study, we show that vpa0607 and qsvR are transcribed as an operon, vpa0607-qsvR. AphA indirectly activates the transcription of vpa0607 at LCD, whereas OpaR and QsvR directly repress vpa0607 transcription at HCD, leading to the highest expression levels of vpa0607 occurs at LCD. Moreover, VPA0607 acts as an active RNase II-type protein in V. parahaemolyticus and feedback inhibits the expression of QsvR at the post-transcriptional level. Taken together, this work deepens our understanding of the regulation of QsvR and enriches the integration mechanisms of QsvR with the QS system in V. parahaemolyticus.
Preclinical evaluation of tolvaptan and salsalate combination therapy in a Pkd1-mouse model
Authors: Song Xuewen , Leonhard Wouter N. , Kanhai Anish A. , Steinberg Gregory R. , Pei York , Peters Dorien J. M.
Published: January 2023

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder and an important cause of end stage renal disease (ESRD). Tolvaptan (a V2R antagonist) is the first disease modifier drug for treatment of ADPKD, but also causes severe polyuria. AMPK activators have been shown to attenuate cystic kidney disease.

Methods: In this study, we tested the efficacy of the combined administration of salsalate (a direct AMPK activator) and tolvaptan using clinically relevant doses in an adult-onset conditional Pkd1 knock-out (KO) mouse model.

Results: Compared to untreated Pkd1 mutant mice, the therapeutic effects of salsalate were similar to that of tolvaptan. The combined treatment tended to be more effective than individual drugs used alone, and was associated with improved kidney survival (p < 0.0001) and reduced kidney weight to body weight ratio (p < 0.0001), cystic index (p < 0.001) and blood urea levels (p < 0.001) compared to untreated animals, although the difference between combination and single treatments was not statistically significant. Gene expression profiling and protein expression and phosphorylation analyses support the mild beneficial effects of co-treatment, and showed that tolvaptan and salsalate cooperatively attenuated kidney injury, cell proliferation, cell cycle progression, inflammation and fibrosis, and improving mitochondrial health, and cellular antioxidant response.

Conclusion: These data suggest that salsalate-tolvaptan combination, if confirmed in clinical testing, might represent a promising therapeutic strategy in the treatment of ADPKD.
Evaluating depression- and anxiety-like behaviors in non-human primates
Authors: Ausderau Karla K. , Colman Ricki J. , Kabakov Sabrina , Schultz-Darken Nancy , Emborg Marina E.
Published: January 2023

Depression and anxiety are some of the most prevalent and debilitating mental health conditions in humans. They can present on their own or as co-morbidities with other disorders. Like humans, non-human primates (NHPs) can develop depression- and anxiety-like signs. Here, we first define human depression and anxiety, examine equivalent species-specific behaviors in NHPs, and consider models and current methods to identify and evaluate these behaviors. We also discuss knowledge gaps, as well as the importance of evaluating the co-occurrence of depression- and anxiety-like behaviors in animal models of human disease. Lastly, we consider ethical challenges in depression and anxiety research on NHPs in order to ultimately advance the understanding and the personalized treatment of these disorders.
Revealing the contribution of astrocytes to glutamatergic neuronal transmission
Authors: Cuellar-Santoyo Ares Orlando , Ruiz-Rodríguez Victor Manuel , Mares-Barbosa Teresa Belem , Patrón-Soberano Araceli , Howe Andrew G. , Portales-Pérez Diana Patricia , Miquelajáuregui Graf Amaya , Estrada-Sánchez Ana María
Published: January 2023

Research on glutamatergic neurotransmission has focused mainly on the function of presynaptic and postsynaptic neurons, leaving astrocytes with a secondary role only to ensure successful neurotransmission. However, recent evidence indicates that astrocytes contribute actively and even regulate neuronal transmission at different levels. This review establishes a framework by comparing glutamatergic components between neurons and astrocytes to examine how astrocytes modulate or otherwise influence neuronal transmission. We have included the most recent findings about the role of astrocytes in neurotransmission, allowing us to understand the complex network of neuron-astrocyte interactions. However, despite the knowledge of synaptic modulation by astrocytes, their contribution to specific physiological and pathological conditions remains to be elucidated. A full understanding of the astrocyte’s role in neuronal processing could open fruitful new frontiers in the development of therapeutic applications.
Prediction of motor function in patients with traumatic brain injury using genetic algorithms modified back propagation neural network: a data-based study
Authors: Dang Hui , Su Wenlong , Tang Zhiqing , Yue Shouwei , Zhang Hao
Published: January 2023

Objective

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. In this study, the characteristics of the patients, who were admitted to the China Rehabilitation Research Center, were elucidated in the TBI database, and a prediction model based on the Fugl-Meyer assessment scale (FMA) was established using this database.

Methods

A retrospective analysis of 463 TBI patients, who were hospitalized from June 2016 to June 2020, was performed. The data of the patients used for this study included the age and gender of the patients, course of TBI, complications, and concurrent dysfunctions, which were assessed using FMA and other measures. The information was collected at the time of admission to the hospital and 1 month after hospitalization. After 1 month, a prediction model, based on the correlation analyses and a 1-layer genetic algorithms modified back propagation (GA-BP) neural network with 175 patients, was established to predict the FMA. The correlations between the predicted and actual values of 58 patients (prediction set) were described.

Results

Most of the TBI patients, included in this study, had severe conditions (70%). The main causes of the TBI were car accidents (56.59%), while the most common complication and dysfunctions were hydrocephalus (46.44%) and cognitive and motor dysfunction (65.23 and 63.50%), respectively. A total of 233 patients were used in the prediction model, studying the 11 prognostic factors, such as gender, course of the disease, epilepsy, and hydrocephalus. The correlation between the predicted and the actual value of 58 patients was R2 = 0.95.

Conclusion

The genetic algorithms modified back propagation neural network can predict motor function in patients with traumatic brain injury, which can be used as a reference for risk and prognosis assessment and guide clinical decision-making.
The impact of hemodiafiltration on cognitive function in patients with end-stage renal disease
Authors: Wang Xiaoyan , Chen Xiaohui , Tang Yuting , Zhang Liuping , Wang Yue , Hou Zhenghua , Jang Wenhao , Yuan Yonggui
Published: January 2023

Background

Patients with end-stage renal disease are more likely to suffer cognitive impairment. Cognitive impairment may lead to long-term severe adverse consequences.

Purpose

To explore the impact of different blood purification therapy on cerebral blood flow and cognitive functions in end-stage renal disease.

Materials and methods

This prospective study evaluated patients with end-stage renal disease undergoing blood purification from January to March 2021. Matched healthy controls were also included. Participants performed neurocognitive measurements, including a mini-mental state examination, logical memory test-20-minutes delayed, verbal fluency test, digit span test, clock drawing test, and stroop color and word test C. In addition, we tested plasma amyloid-β protein levels, serum Fe and hemoglobin levels in blood samples. Cerebral blood flow was measured using pulsed pseudocontinuous arterial spin labeling. We analyzed and compared the correlation between cognitive function, biomarkers, and cerebral blood flow between patients and healthy subjects, as well as between patients with different treatments.

Results

A total of 44 patients with end-stage renal disease (mean age, 57.39 years ± 8.63) and 46 healthy controls (mean age, 56.15 years ± 6.40) were recruited. Patients receive hemodialysis three times a week, and 27 of them have been replaced hemodialysis for hemodiafiltration twice a month. The cognitive function of patients was worse than healthy controls (P < 0.05). The patients showed higher plasma concentrations of amyloid-β40, amyloid-β42, Tau, and pTau181 than healthy controls (P < 0.05). The group receiving both hemodialysis and hemodiafiltration had higher cerebral blood flow signal values in the left caudate nucleus (chuster-level P < 0.05, voxel-level P < 0.001). They also exhibited better verbal fluency function than the hemodialysis-only group (P < 0.05).

Conclusion

Patients with the end-stage renal disease showed widespread cognitive declines. Cerebral blood flow generally decreased in the cerebral cortex and increased in subcortical regions. The hemodiafiltration may protect verbal function by increasing cerebral blood flow in the left caudate.
Memantine as a neuroprotective agent in ischemic stroke: Preclinical and clinical analysis
Authors: Pichardo-Rojas Diego , Pichardo-Rojas Pavel Salvador , Cornejo-Bravo José Manuel , Serrano-Medina Aracely
Published: January 2023

The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients’ NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients’ post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke.
Construction and sustained release of konjac glucomannan/naringin composite gel spheres
Authors: Dao Liping , Chen Siyang , Sun Xiangyun , Pang Wenyuan , Zhang Hengzhe , Liao Jun , Yan Jiqiang , Pang Jie
Published: January 2023

Objective

To improve the bioavailability of active substances and reduce the toxic and side effects on the human body, natural biological macromolecules are used to load active substances and control their release speed in different environments of the human body. In this study, mesoporous silica (MSN) was combined with konjac glucomannan (KGM) and sodium alginate (AC) to prepare pH-sensitive konjac glucomannan/sodium alginate–mesoporous silica loaded naringin gel spheres (KS/MSN). On this basis, the structure, morphology, and release properties of the composite gel spheres were characterized. The results showed that the cumulative release rates of both simulated gastric fluid (SGF) and Simulated colonic fluid (SCF) were lower than that of simulated small intestinal fluid (SIF), which indicated that the prepared composite gel spheres were pH-sensitive to SIF and obtained the best release rate of about 70% under SIF environment.

Methods

The pH-sensitive konjac glucomannan/sodium alginate composite gel spheres (KGM/SA) were prepared by combining inorganic nano-materials mesoporous silica (MSN) with natural macromolecular polysaccharides konjac glucomannan (KGM) and sodium alginate (SA) and characterized.

Results

The results showed that there was a process of ionic crosslinking and entanglement between konjac glucomannan (KGM) and sodium alginate (SA). Naringin (NG) and mesoporous silica (MSN) were successfully compounded and had good compatibility. The gel microstructure diagram showed that the addition of MSN improved the gel properties of KGM, and KGM and SA gel spheres (KGM/SA) had good compatibility with mesoporous silica/naringenin nanoparticles (NG/MSN). The study of the simulated digestive environment of the gastrointestinal release medium showed that Konjac glucomannan/sodium alginate-mesoporous silica loaded naringin gel spheres (KS/NM) composite gel spheres had the best slow-release effect and the highest final-release completion degree in SIF. The release of NG from KS/NM composite gel spheres showed a slow upward trend. The results showed that KS/NM composite gel spheres were pH-sensitive.

Conclusion

The KS/NM composite gel spheres showed obvious pH sensitivity to the release of NG, and the gel spheres had a good sustained release effect on NG.
Association between daily eating frequency and mortality in people with diabetes: Findings from NHANES 1999–2014
Authors: Xie Jing , Wang Zhenwei , Zhang Xin , Wang Junjie , Feng Wei , Hu Yifang , Liu Naifeng , Liu Yun
Published: January 2023

Background

Previous studies have shown that increasing the frequency of eating is beneficial in terms of cardiovascular metabolic risk factors; however, limited evidence is available for the association between daily eating frequency and mortality, especially in people with diabetes. Therefore, we aimed to explore the association between eating frequency and long-term mortality in populations with diabetes.

Methods

We selected 4,924 individuals suffering from diabetes (mean age: 57.77 years; 51.3% men) from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2014. Daily eating frequency was used as the exposure factor in this study. We extracted the mortality data from the National Death Index records and matched them with the population of NHANES. All participants were followed up from the date of getting enrolled in NHANES to 31 December 2015. Multivariate Cox proportional hazards regression, Kaplan–Meier survival curves, and restricted cubic spline were used to assess the associations between eating frequency and all-cause and cause-specific mortality among people with diabetes.

Results

During 34,950 person–years of follow-up, 1,121 deaths were documented, including 272 cardiovascular disease (CVD)-related deaths and 156 cancer-related deaths. After adjusting for confounding factors, the daily eating frequency was linearly inversely associated with all-cause and CVD-related mortality, and the HR (95% CIs) for per one-time increment of eating frequency was 0.88 (0.80–0.98) and 0.77 (0.63–0.93), respectively. Sensitivity analyses showed that the main results and statistical significance were still stable.

Conclusion

Higher eating frequency was independently related to lower all-cause and CVD-related mortality in people with diabetes, which can be used as a potential strategy for daily-diet management among populations suffering from diabetes.
Enhancer RNA-based modeling of adverse events and objective responses of cancer immunotherapy reveals associated key enhancers and target genes
Authors: Guo Mengbiao , Lu Zhiya , Xiong Yuanyan
Published: January 2023

Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 or CTLA-4 are emerging and effective immunotherapy strategies. However, ICI-treated patients present heterogeneous responses and adverse events, thus demanding effective ways to assess benefit over risk before treatment. Here, by integrating pan-cancer clinical and molecular data, we tried to predict immune-related adverse events (irAEs, risk) and objective response rates (ORRs, benefit) based on enhancer RNAs (eRNAs) expression among patients receiving anti-PD-1/PD-L1 therapies. We built two tri-variate (eRNAs) regression models, one (with ENSR00000326714, ENSR00000148786, and ENSR00000005553) explaining 71% variance (R=0.84) of irAEs and the other (with ENSR00000164478, ENSR00000035913, and ENSR00000167231) explaining 79% (R=0.89) of ORRs. Interestingly, target genes of irAE-related enhancers, including upstream regulators of MYC, were involved in metabolism, inflammation, and immune activation, while ORR-related enhancers target PAK2 and DLG1 which participate in T cell activation. More importantly, we found that ENSR00000148786 probably enhanced TMEM43/LUMA expression mainly in B cells to induce irAEs in ICI-treated patients. Our study provides references for the identification of immunotherapy-related biomarkers and potential therapeutic targets during immunotherapy.
Non-phosphorylatable mutants of Ser184 lead to incomplete activation of Bax
Authors: Simonyan Lilit , Gonin Mathilde , Hanks James , Friedlein Jordan , Dutrec Kevin , Arokium Hubert , Rouchidane Eyitayo Akandé , Doudy Toukounou Megann , Chaignepain Stéphane , Manon Stéphen , Dejean Laurent
Published: January 2023

The S184 residue of Bax is the target of several protein kinases regulating cell fate, including AKT. It is well-established that, in cellulo, the substitution of S184 by a non-phosphorylatable residue stimulates both the mitochondrial localization of Bax, cytochrome c release, and apoptosis. However, in in vitro experiments, substituted mutants did not exhibit any increase in their binding capacity to isolated mitochondria or liposomes. Despite exhibiting a significant increase of the 6A7 epitope exposure, substituted mutants remain limited in their ability to form large oligomers, suggesting that they high capacity to promote apoptosis in cells was more related to a high content than to an increased ability to form large pores in the outer mitochondrial membranes.
The Uridine diphosphate (UDP)-glycosyltransferases (UGTs) superfamily: the role in tumor cell metabolism
Authors: Liu Wenyu , Li Jing , Zhao Rui , Lu Yao , Huang Panpan
Published: January 2023

UDP-glycosyltransferases (UGTs), important enzymes in biotransformation, control the levels and distribution of numerous endogenous signaling molecules and the metabolism of a wide range of endogenous and exogenous chemicals. The UGT superfamily in mammals consists of the UGT1, UGT2, UGT3, and UGT8 families. UGTs are rate-limiting enzymes in the glucuronate pathway, and in tumors, they are either overexpressed or underexpressed. Alterations in their metabolism can affect gluconeogenesis and lipid metabolism pathways, leading to alterations in tumor cell metabolism, which affect cancer development and prognosis. Glucuronidation is the most common mammalian conjugation pathway. Most of its reactions are mainly catalyzed by UGT1A, UGT2A and UGT2B. The body excretes UGT-bound small lipophilic molecules through the bile, urine, or feces. UGTs conjugate a variety of tiny lipophilic molecules to sugars, such as galactose, xylose, acetylglucosamine, glucuronic acid, and glucose, thereby inactivating and making water-soluble substrates, such as carcinogens, medicines, steroids, lipids, fatty acids, and bile acids. This review summarizes the roles of members of the four UGT enzyme families in tumor function, metabolism, and multiple regulatory mechanisms, and its Inhibitors and inducers. The function of UGTs in lipid metabolism, drug metabolism, and hormone metabolism in tumor cells are among the most important topics covered.
Emerging patterns and trends in global cancer burden attributable to metabolic factors, based on the Global Burden of Disease Study 2019
Authors: Zhang Yan , Ding Yuwei , Zhu Ning , Mi Mi , Lu Yier , Zheng Jia , Weng Shanshan , Yuan Ying
Published: January 2023

Background

The exponential growth of the cancer burden attributable to metabolic factors deserves global attention. We investigated the trends of cancer mortality attributable to metabolic factors in 204 countries and regions between 1990 and 2019.

Methods

We extracted data from the Global Burden of Disease Study (GBD) 2019 and assessed the mortality, age-standardized death rate (ASDR), and population attributable fractions (PAFs) of cancers attributable to metabolic factors. Average annual percentage changes (AAPCs) were calculated to assess the changes in the ASDR. The cancer mortality burden was evaluated according to geographic location, SDI quintiles, age, sex, and changes over time.

Results

Cancer attributable to metabolic factors contributed 865,440 (95% UI, 447,970-140,590) deaths in 2019, a 167.45% increase over 1990. In the past 30 years, the increase in the number of deaths and ASDR in lower SDI regions have been significantly higher than in higher SDI regions (from high to low SDIs: the changes in death numbers were 108.72%, 135.7%, 288.26%, 375.34%, and 288.26%, and the AAPCs were 0.42%, 0.58%, 1.51%, 2.36%, and 1.96%). Equatorial Guinea (AAPC= 5.71%), Cabo Verde (AAPC=4.54%), and Lesotho (AAPC=4.42%) had the largest increase in ASDR. Large differences were observed in the ASDRs by sex across different SDIs, and the male-to-female ratios of ASDR were 1.42, 1.50, 1.32, 0.93, and 0.86 in 2019. The core population of death in higher SDI regions is the age group of 70 years and above, and the lower SDI regions are concentrated in the age group of 50-69 years. The proportion of premature deaths in lower SDI regions is significantly higher than that in higher SDI regions (from high to low SDIs: 2%, 4%, 7%, 7%, and 9%). Gastrointestinal cancers were the core burden, accounting for 50.11% of cancer deaths attributable to metabolic factors, among which the top three cancers were tracheal, bronchus, and lung cancer, followed by colon and rectum cancer and breast cancer.

Conclusions

The cancer mortality burden attributable to metabolic factors is shifting from higher SDI regions to lower SDI regions. Sex differences show regional heterogeneity, with men having a significantly higher burden than women in higher SDI regions but the opposite is observed in lower SDI regions. Lower SDI regions have a heavier premature death burden. Gastrointestinal cancers are the core of the burden of cancer attributable to metabolic factors.
Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment
Authors: Schoeppe Robert , Babl Nathalie , Decking Sonja-Maria , Schönhammer Gabriele , Siegmund Andreas , Bruss Christina , Dettmer Katja , Oefner Peter J. , Frick Linus , Weigert Anna , Jantsch Jonathan , Herr Wolfgang , Rehli Michael , Renner Kathrin , Kreutz Marina
Published: January 2023

Introduction

Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function.

Methods

Different types of myeloid cells were cultured in the absence or presence of glutamine and/or with L-methionine-S-sulfoximine (MSO), an irreversible glutamine synthetase (GS) inhibitor. GS expression was analyzed on mRNA and protein level. GS activity and the conversion of glutamate to glutamine by myeloid cells was followed by 13C tracing analyses.

Results

The absence of extracellular glutamine only slightly affected postmitotic human monocyte to dendritic cell (DC) differentiation, function and survival. Similar results were obtained for monocyte-derived macrophages. In contrast, proliferation of the monocytic leukemia cell line THP-1 was significantly suppressed. While macrophages exhibited high constitutive GS expression, glutamine deprivation induced GS in DC and THP-1. Accordingly, proliferation of THP-1 was rescued by addition of the GS substrate glutamate and 13C tracing analyses revealed conversion of glutamate to glutamine. Supplementation with the GS inhibitor MSO reduced the survival of DC and macrophages and counteracted the proliferation rescue of THP-1 by glutamate.

Discussion

Our results show that GS supports myeloid cell survival in a glutamine poor environment. Notably, in addition to suppressing proliferation and survival of tumor cells, the blockade of GS also targets immune cells such as DCs and macrophages.
Huashi baidu granule in the treatment of pediatric patients with mild coronavirus disease 2019: A single-center, open-label, parallel-group randomized controlled clinical trial
Authors: Chen Jiande , Tang Qiuyu , Zhang Baoqin , Yuan Shuhua , Chen Jia , Shen Shiyu , Wang Dong , Lin Jilei , Dong Hongliang , Yin Yong , Gao Jian
Published: January 2023

Background: Since late February 2022, a wave of coronavirus disease 2019 (COVID-19) mainly caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China. Traditional Chinese medicine treatment is recommended for pediatric patients; however, the safety and efficacy remain to be confirmed. We conducted a single-center, open-label, parallel-group randomized controlled trial to assess the efficacy and safety of a Chinese herb compound, Huashi Baidu granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19.

Methods: 108 recruited children (aged 3–18 years) with laboratory-confirmed mild COVID-19 were randomly allocated 2:1 to receive oral HSBDG for five consecutive days (intervention group) and to receive compound pholcodine oral solution for five consecutive days (control group). The negative conversion time of SARS-CoV-2 nucleic acid and symptom scores were recorded.

Results: The median negative conversion time of SARS-CoV-2 nucleic acid was significantly shorter in the intervention group than in the control group (median days [interquartile range (IQR)]: 3 [3–5] vs. 5 [3–6]; p = 0.047). The median total symptom score on day 3 was significantly lower in the intervention group than in the control group (median total symptom score [IQR]: 1 [0–2] vs. 2 [0–3]; p = 0.036). There was no significant differences in the frequency of antibiotic use and side effects between the two groups.

Conclusion: HSBDG is a safe, effective oral Chinese herbal compound granule, which shows a good performance within the Omicron wave among pediatric patients.