bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Metabolic Suitability Maps for the Thermophilic Invasive Hydroid Pennaria disticha Under Future Warming Mediterranean Sea Scenarios
Authors: Bosch-Belmar Mar , Piraino Stefano , Sarà Gianluca
Published: April 2022

Temperature is a fundamental variable for all biological processes. It influences the metabolism and tolerance limits of all living organisms, affecting species phenology and distribution patterns. It also facilitates the spread of non-indigenous species and the proliferation and expansion of native outbreak-forming species. Pennaria disticha is a colonial benthic cnidarian reported to be invasive in different Indian and Pacific coastal areas, as well as a harmful member of fouling communities found in Mediterranean marine aquaculture farms. Using the most basal functional trait (i.e., thermal tolerance), we explored the potential of P. disticha to colonize different habitats across the Mediterranean Sea in future warming scenarios. Respiration rate was measured as a proxy of P. disticha metabolism under 12 different experimental temperatures. The obtained thermal tolerance dataset was used to create a thermal performance curve (TPC). We then scaled modeled curve to occurrence probability to map species potential metabolic habitat suitability and phenological shifts within the Mediterranean Sea when subjected to different warming scenarios. Prediction maps for future climatic conditions showed a potential temporal and spatial expansion of P. disticha in the Western and Central Mediterranean. The present data increases our understanding of the ecological performance and potential distribution of an invasive and outbreak-forming species. This information will contribute to the development of early warning systems and to the design and implementation of risk assessment and management plans.
Variability and Intensity of the Sea Surface Temperature Front Associated With the Kuroshio Extension
Authors: Xi Jingyuan , Wang Yuntao , Feng Zhixuan , Liu Yang , Guo Xinyu
Published: April 2022

Seventeen years of satellite observational data are used to describe the variability in sea surface temperature (SST) fronts and associated features, e.g., frontal intensity and probability, in the northwestern Pacific Ocean. Compared with the SST gradient and frontal probability, the frontal intensity is less impacted by background noise in satellite observations and precisely represents the variability in frontal patterns. The seasonal variability in frontal intensity is prominent, and the corresponding seasonality varies spatially. Fronts are more common during winter in the northern region around the Oyashio Current but are most common during spring in the Kuroshio Current and to the south of the Kuroshio Extension. The meridional migration of fronts is associated with the seasonal movement of the North Pacific subtropical gyre. Though overall averaged frontal intensity along the Kuroshio Extension is most prominent in the northwestern Pacific Ocean, the associated variability in fronts is highly complex. The current study reveals that seasonality itself cannot capture the whole picture of frontal features because eddy-induced intraseasonal variability and basin-scale signal-induced interannual variability can modulate frontal dynamics. In particular, the monthly frontal intensity in regions where the seasonal cycle is not significant depends on the Pacific Decadal Oscillation and North Pacific Gyre Oscillation. Furthermore, the oscillation of the Kuroshio Extension and associated mesoscale eddies can impact its intraseasonal variability. The comprehensive analysis of frontal intensity in the Kuroshio Extension is helpful for delineating regional dynamics and has the potential to improve our understanding of controls on marine primary production.
Long-Term Harmful Algal Blooms and Nutrients Patterns Affected by Climate Change and Anthropogenic Pressures in the Zhanjiang Bay, China
Authors: Zhang Peng , Peng Conghui , Zhang Jibiao , Zhang Junxiao , Chen Jiyu , Zhao Hui
Published: April 2022

Climate change and anthropogenic pressures have significantly affected coastal environments. This study obtained historical data on harmful algal blooms (HABs) and nutrient patterns over a 30-year period to explore responses to long-term climate change and anthropogenic pressure indicators. Although the surrounding area has achieved great economic success over the past 30 years, the Zhanjiang Bay (ZJB) has been seriously affected by various pollutants and is threatened by increasing eutrophication and HABs due to climate change and anthropogenic pressures. In the ZJB, HABs rarely occurred before the 1980s but have occurred periodically and frequently since the 2000s. The largest HAB covered a cumulative area of 310 km2 in 2005. Most of the HABs occurred during spring. Additionally, the dominant phytoplankton species were Skeletonema costatum and Phaeocystis globosa, accounting for 37.50 and 43.75% of the HABs observed, respectively. Anthropogenic pressures have caused the nutrient regime to significantly increased in the ZJB over the past three decades (P < 0.05). Specifically, the concentration of dissolved inorganic nitrogen (DIN) increased threefold from the beginning of the 1990 to 2019 period, while the dissolved inorganic phosphorus (DIP) concentration increased 21-fold. Unsynchronized variation in nutrient patterns has led to changes in the composition of nutrients, and the ZJB ecosystem has shifted from a P-limited oligotrophic state before the 2000s to an N-limited eutrophic state. Anthropogenic pressure indicators showed a significant linear correlation with nutrients (P < 0.05), but climate change indicators did not play a direct role in the eutrophication problem in the ZJB during this period (P > 0.05). Therefore, integrated land-ocean environment management should be introduced to reduce land-based pollution sources, mitigate eutrophication, and curb the blooms of harmful algae in the ZJB.
Bacterial Community in Cold Surge-Caused Sea Ice Differs From Seawater in Mid-Latitude Region: A Case Study in Aoshan Bay, Southern Yellow Sea
Authors: Ren Hongwei , Liu Jihua , Li Gang , Hu Yubin
Published: April 2022

Cold surges result in a rapid drop in air temperature and freezing of seawater, which was likely to impact bacterial communities. We examined the differences in bacteria abundance and bacterial community composition in the sea ice and seawater during a cold surge along Aoshan Bay, southern Yellow Sea in January 2021. Results showed that the differences in bacteria abundance between sea ice and seawater likely resulted from the physical impact of ice formation. The parent water played a key role in bacterial community composition in the early phase of ice formation, in which bacterial community compositions at class level were similar, but the relative abundances were different between sea ice and seawater. The Gammaproteobacteria dominated in sea ice, and the relative abundances of Verrucomicrobiae were also significantly higher, possibly due to the high concentration of algal-derived DOM in coastal areas. The predicted functional profiles suggested the lower abundance of functional genes related to ATP-binding cassette transporters in sea ice than in seawater, which might be due to the bacteria not requiring varieties of functional genes of ATP-binding cassette transporters in restricted sea ice brine.
Designing and the Pilot Trial of Bivalve Molluscan Fishing Quotas on Maoming Coastal Waters of China, Northern South China Sea
Authors: Lyu Shaoliang , Deng Siman , Lin Kun , Zeng Jiawei , Wang Xuefeng
Published: April 2022

In the context of the declining fishery resources, some active management measures have been taken to strive for the sustainable development of fisheries. However, these input-oriented control management measures have not realized the expectation in alleviating the depressing depletion of fishery resources. The fishing quota (FQ) system, an output-oriented control management method, has been proved to be effective in curbing overfishing and conserving fishery resources. However, it has not been formally implemented in China until now. Thus, it is urgent to start the pilot trial on the implementation of the FQ system in China. We firstly formulated a framework for the FQ system on bivalve fisheries and then conducted an empirical analysis based on the field survey of bivalve mollusks in Maoming shallow waters, Guangdong, northern South China Sea. The species composition, dominant species, and density distribution of bivalves were analyzed. The swept-area method was used to assess the total allowable catch (TAC) of bivalves. Each step of the FQ system was discussed in depth. Results showed that a total of 45 bivalve species were identified. Meretrix planisulcata and Ruditapes philippinarum were the two dominant species. The spatial distribution of density varied largely. The estimated TAC value is 4.28 × 105 kg which can be allocated to fishermen under the regulations of the FQ system. Finally, the framework for the FQ system was improved in every step of the future procedure, including target species selection, TAC determination, quota allocation, catch report, and fishing supervision. The general framework of the FQ system in this study can also be referenced to other economically important fish or other marine organisms.
Machine Learning Applied to Identify Corrosive Environmental Conditions
Authors: Lee HsinYen , Gray Simon , Zhao Yifan , Castelluccio Gustavo M.
Published: April 2022

The reliability of turbine engines depends significantly on the environment experienced during flight. Air humidity, corrosive contaminant substances, and high operating temperatures are among the attributes that affect engine lifespans. The specifics of the environment that affect materials are not always known, and damage is often evaluated by time-consuming manual inspection. This study innovates by demonstrating that machine learning approaches can identify the environmental conditions that degrade jet engine metallic materials. We used the state-of-the-art pre-trained neural network models to assess images of damaged nickel-based superalloy samples to identify the environment temperature, the exposure time, and the deposited amounts of salt contaminants. These parameters are predicted by training the model with a database of approximately 3,600 sample images tested in laboratory conditions. A novel tree classification process results in excellent predictive power for classifying the type of environment experienced by nickel-based superalloys.
COVID-19 and Acute Kidney Injury: A Systematic Review
Authors: Sabaghian Tahereh , Kharazmi Amir Behnam , Ansari Ali , Omidi Fatemeh , Kazemi Seyyedeh Neda , Hajikhani Bahareh , Vaziri-Harami Roya , Tajbakhsh Ardeshir , Omidi Sajjad , Haddadi Sara , Shahidi Bonjar Amir Hashem , Nasiri Mohammad Javad , Mirsaeidi Mehdi
Published: April 2022

Introduction

Acute kidney injury (AKI) has been associated with an increased mortality rate among hospitalized patients with Coronavirus disease 2019 (COVID-19). The current review aimed to evaluate the symptoms, complications, and treatments performed to manage AKI in patients with COVID-19.

Methods

We searched PubMed/Medline, Web of Science, and Embase for the relevant scientific literature published up to February 1, 2022. The following keywords were used: “COVID-19”, “SARS-CoV-2”, and “Acute kidney injury”.

Results

Forty-four studies with a total number of 114 COVID-19 patients with AKI (Mean age: 53.6 years) were included in our systematic review. The most common comorbidities in patients with COVID-19 suffering from AKI were the history of diabetes, hypertension, and hyperlipidemia. Twelve out of the 44 included studies reported a history of chronic kidney disease (CKD) in this group of patients. Focal segmental glomerulosclerosis (FSGS) and acute tubular necrosis (ATN) were the most common pathological evidence. The average length of hospital stay was 19 days, and the average duration of need for mechanical ventilation was 3 days.

Conclusions

The current systematic review shows that AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, prolonged duration of hospitalization, and poor prognosis. Given the extent of the adverse impact of AKI, early detection of comorbidities and renal complications is essential to improve the outcomes of COVID-19 patients.
Gypenosides Prevent and Dissolve Cholesterol Gallstones by Modulating the Homeostasis of Cholesterol and Bile Acids
Authors: Zhuang Qian , Cheng Jinnian , Xia Jie , Ning Min , Wu Shan , Shen Shuang , Shi Yan , Huang Dan , Dong Zhixia , Wan Xinjian
Published: April 2022

Gypenosides (GPs), obtained from Gynostemma pentaphyllum (Thunb.) Makino, have been traditionally prescribed to treat metabolic disorders in Asians. This study assessed whether GPs could prevent lithogenic diet (LD)-induced cholesterol gallstone (CG) formation and enhance CG dissolution in mice. Gallstone-susceptible C57BL/6J mice were fed an LD or normal chow, with or without GPs. Bile acids (BAs) in gallbladder bile were analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed hepatic genes were identified by RNA sequencing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. GPs were found to prevent LD-induced CG formation and to dissolve pre-existing LD-induced CGs. GPs reduced total cholesterol levels and increased BA levels in bile, as well as reducing the BA Hydrophobicity Index, ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs, and Cholesterol Saturation Index in gallbladder bile. GO and KEGG pathway enrichment analyses indicated that GPs-induced genes were involved in BA biosynthesis and cholesterol metabolism. GPs increased the hepatic expression of genes encoding the cytochrome P450 (Cyp) enzymes Cyp7a1, Cyp7b1, and Cyp8b1, while decreasing the hepatic expression of genes encoding the adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8. GPs may be a promising strategy for preventing and dissolving CGs.
Comparison of Visual Outcomes Between Toric Intraocular Lenses and Clear Corneal Incisions to Correct Astigmatism in Image–Guided Cataract Surgery
Authors: Ding Ning , Song Xudong , Wang Xiaozhen , Wei Wenbin
Published: April 2022

Purpose

To compare the astigmatism correction effects of toric intraocular lenses (IOL) and clear corneal incisions during image-guided cataract surgery.

Methods

All patients with regular corneal astigmatism of 0.75–1.5 D underwent cataract surgery and astigmatism correction using the Callisto eye image-guided system. One group had implantation of an AcrySof toric IOL. Another group had implantation of aspheric IOL with 3.0 mm single clear corneal incision (SCCI) on the steep axis. Uncorrected and best-corrected spectacle visual acuity, refraction, and toric IOL axis were evaluated at 1, 4, and 12 weeks postoperatively.

Results

Sixty-eight eyes of 68 patients were included. The mean residual refractive cylinder was 0.34 ± 0.40 D in the toric group and 0.64 ± 0.57 D in the SCCI group. There were no significant differences in residual refractive cylinder, spherical equivalent, uncorrected distance visual acuity (UDVA), and best-corrected spectacle visual acuity (BCSVA) between groups. The percentage of the residual cylinder within ± 0.50 D was 75 and 56% for toric and SCCI cases, respectively (p > 0.1). The mean surgical induced astigmatism vector was 0.61 ± 0.29 D in the SCCI group and 1.04 ± 0.38 D in the toric group. The mean magnitude of error was negative (−0.54 ± 0.48 D) and the correction index was <1.0 (p < 0.05) in SCCI group. At 3 months, all toric IOL alignment errors were within 5 degrees from the intended axis.

Conclusions

Both toric IOL and SCCI can correct low and medium astigmatism effectively with the help of a precise image-guided system.
Correlation Between Clinical Factors and Pregnancy Outcome Following Repeat Cerclage: A Retrospective Analysis of a Chinese Population
Authors: Cai Benshuo , Xia Yajun , Na Xinni
Published: April 2022

Background

The role of repeat cerclage (RC) among patients with prolapsed membranes remains controversial. We aimed to investigate the effectiveness of RC and assess the correlation between clinical factors and pregnancy outcome following RC.

Methods

The clinical data of patients who underwent RC for prolapsed membranes after prior cerclage were retrospectively investigated. The clinical characteristics of patients were compared between singleton and twin pregnancies. The clinical characteristics of singleton pregnancies were compared between the gestational age (GA) at delivery <28 weeks' and ≥28 weeks' groups. Receiver operating characteristic (ROC) curve analysis was performed to determine predictive factors. Singleton patients were divided into two groups according to GA at RC as follows: GA <22.3 weeks and GA ≥22.3 weeks. Pregnancy outcomes were compared between groups.

Results

The mean GA at delivery of singleton pregnancies was significantly higher than that of twin pregnancies. The mean latency between RC and delivery of singleton pregnancies was significantly longer than their twin counterparts. There were significant differences in the pregnancy outcomes between the GA <22.3 weeks group and GA ≥22.3 weeks group. Kaplan–Meier survival curves showed a lower incidence of neonatal death in the GA ≥22.3 weeks group compared with that in the GA <22.3 weeks group.

Conclusions

RC may be an effective method to prolong the duration of pregnancy among patients with singleton pregnancy. However, the selection of RC for patients with twin pregnancies remains controversial. GA at RC appears to be fair for predicting pregnancy outcomes following RC.
The Use and Potential of Biomedical Detection Dogs During a Disease Outbreak
Authors: Maughan Michele N. , Best Eric M. , Gadberry Jenna Dianne , Sharpes Caitlin E. , Evans Kelley L. , Chue Calvin C. , Nolan Patrick Lawrence , Buckley Patricia E.
Published: April 2022

Biomedical detection dogs offer incredible advantages during disease outbreaks that are presently unmatched by current technologies, however, dogs still face hurdles of implementation due to lack of inter-governmental cooperation and acceptance by the public health community. Here, we refine the definition of a biomedical detection dog, discuss the potential applications, capabilities, and limitations of biomedical detection dogs in disease outbreak scenarios, and the safety measures that must be considered before and during deployment. Finally, we provide recommendations on how to address and overcome the barriers to acceptance of biomedical detection dogs through a dedicated research and development investment in olfactory sciences.
Environment and Co-occurring Native Mussel Species, but Not Host Genetics, Impact the Microbiome of a Freshwater Invasive Species (Corbicula fluminea)
Authors: Chiarello Marlène , Bucholz Jamie R. , McCauley Mark , Vaughn Stephanie N. , Hopper Garrett W. , Sánchez González Irene , Atkinson Carla L. , Lozier Jeffrey D. , Jackson Colin R.
Published: April 2022

The Asian clam Corbicula fluminea (Family: Cyneridae) has aggressively invaded freshwater habitats worldwide, resulting in dramatic ecological changes and declines of native bivalves such as freshwater mussels (Family: Unionidae), one of the most imperiled faunal groups. Despite increases in our knowledge of invasive C. fluminea biology, little is known of how intrinsic and extrinsic factors, including co-occurring native species, influence its microbiome. We investigated the gut bacterial microbiome across genetically differentiated populations of C. fluminea in the Tennessee and Mobile River Basins in the Southeastern United States and compared them to those of six co-occurring species of native freshwater mussels. The gut microbiome of C. fluminea was diverse, differed with environmental conditions and varied spatially among rivers, but was unrelated to host genetic variation. Microbial source tracking suggested that the gut microbiome of C. fluminea may be influenced by the presence of co-occurring native mussels. Inferred functions from 16S rRNA gene data using PICRUST2 predicted a high prevalence and diversity of degradation functions in the C. fluminea microbiome, especially the degradation of carbohydrates and aromatic compounds. Such modularity and functional diversity of the microbiome of C. fluminea may be an asset, allowing to acclimate to an extensive range of nutritional sources in invaded habitats, which could play a vital role in its invasive success.
Bacteriophage-Mediated Control of Biofilm: A Promising New Dawn for the Future
Authors: Chang Cheng , Yu Xinbo , Guo Wennan , Guo Chaoyi , Guo Xiaokui , Li Qingtian , Zhu Yongzhang
Published: April 2022

Biofilms are complex microbial microcolonies consisting of planktonic and dormant bacteria bound to a surface. The bacterial cells within the biofilm are embedded within the extracellular polymeric substance (EPS) consisting mainly of exopolysaccharides, secreted proteins, lipids, and extracellular DNA. This structural matrix poses a major challenge against common treatment options due to its extensive antibiotic-resistant properties. Because biofilms are so recalcitrant to antibiotics, they pose a unique challenge to patients in a nosocomial setting, mainly linked to lower respiratory, urinary tract, and surgical wound infections as well as the medical devices used during treatment. Another unique property of biofilm is its ability to adhere to both biological and man-made surfaces, allowing growth on human tissues and organs, hospital tools, and medical devices, etc. Based on prior understanding of bacteriophage structure, mechanisms, and its effects on bacteria eradication, leading research has been conducted on the effects of phages and its individual proteins on biofilm and its role in overall biofilm removal while also revealing the obstacles this form of treatment currently have. The expansion in the phage host-species range is one that urges for improvement and is the focus for future studies. This review aims to demonstrate the advantages and challenges of bacteriophage and its components on biofilm removal, as well as potential usage of phage cocktail, combination therapy, and genetically modified phages in a clinical setting.
Comparing the Efficacy and Safety of Cell Transplantation for Spinal Cord Injury: A Systematic Review and Bayesian Network Meta-Analysis
Authors: Xu Xiongjie , Liang Zeyan , Lin Yike , Rao Jian , Lin Fabin , Yang Zhelun , Wang Rui , Chen Chunmei
Published: April 2022

Objective

To compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).

Design

A systematic review and Bayesian network meta-analysis.

Data Sources

Medline, Embase, and the Cochrane Central Register of Controlled Trials.

Study Selection

We included randomized controlled trials, case–control studies, and case series related to cell transplantation for SCI patients, that included at least 1 of the following outcome measures: American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS grade), ASIA motor score, ASIA sensory score, the Functional Independence Measure score (FIM), International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), or adverse events. Follow-up data were analyzed at 6 and 12 months.

Results

Forty-four eligible trials, involving 1,266 patients, investigated 6 treatments: olfactory ensheathing cells (OECs), neural stem cells/ neural progenitor cells (NSCs), mesenchymal stem cells (MSCs), Schwann cells, macrophages, and combinations of cells (MSCs plus Schwann cells). Macrophages improved the AIS grade at 12 months (mean 0.42, 95% credible interval: 0–0.91, low certainty) and FIM score at 12 months (42.83, 36.33–49.18, very low certainty). MSCs improved the AIS grade at 6 months (0.42, 0.15–0.73, moderate certainty), the motor score at 6 months (4.43, 0.91–7.78, moderate certainty), light touch at 6 (10.01, 5.81–13.88, moderate certainty) and 12 months (11.48, 6.31–16.64, moderate certainty), pinprick score at 6 (14.54, 9.76–19.46, moderate certainty) and 12 months (12.48, 7.09–18.12, moderate certainty), and the IANR-SCIFRS at 6 (3.96, 0.62–6.97, moderate certainty) and 12 months (5.54, 2.45–8.42, moderate certainty). OECs improved the FIM score at 6 months (9.35, 1.71–17.00, moderate certainty). No intervention improved the motor score significantly at 12 months. The certainty of other interventions was low or very low. Overall, the number of adverse events associated with transplanted cells was low.

Conclusions

Patients with SCI who receive transplantation of macrophages, MSCs, NSCs, or OECs may have improved disease prognosis. MSCs are the primary recommendations. Further exploration of the mechanism of cell transplantation in the treatment of SCI, transplantation time window, transplantation methods, and monitoring of the number of transplanted cells and cell survival is needed.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD 42021282043.
Comparison of Resting-State Functional MRI Methods for Characterizing Brain Dynamics
Authors: Maltbie Eric , Yousefi Behnaz , Zhang Xiaodi , Kashyap Amrit , Keilholz Shella
Published: April 2022

Resting-state functional MRI (fMRI) exhibits time-varying patterns of functional connectivity. Several different analysis approaches have been developed for examining these resting-state dynamics including sliding window connectivity (SWC), phase synchrony (PS), co-activation pattern (CAP), and quasi-periodic patterns (QPP). Each of these approaches can be used to generate patterns of activity or inter-areal coordination which vary across time. The individual frames can then be clustered to produce temporal groupings commonly referred to as “brain states.” Several recent publications have investigated brain state alterations in clinical populations, typically using a single method for quantifying frame-wise functional connectivity. This study directly compares the results of k-means clustering in conjunction with three of these resting-state dynamics methods (SWC, CAP, and PS) and quantifies the brain state dynamics across several metrics using high resolution data from the human connectome project. Additionally, these three dynamics methods are compared by examining how the brain state characterizations vary during the repeated sequences of brain states identified by a fourth dynamic analysis method, QPP. The results indicate that the SWC, PS, and CAP methods differ in the clusters and trajectories they produce. A clear illustration of these differences is given by how each one results in a very different clustering profile for the 24s sequences explicitly identified by the QPP algorithm. PS clustering is sensitive to QPPs with the mid-point of most QPP sequences grouped into the same single cluster. CAPs are also highly sensitive to QPPs, separating each phase of the QPP sequences into different sets of clusters. SWC (60s window) is less sensitive to QPPs. While the QPPs are slightly more likely to occur during specific SWC clusters, the SWC clustering does not vary during the 24s QPP sequences, the goal of this work is to improve both the practical and theoretical understanding of different resting-state dynamics methods, thereby enabling investigators to better conceptualize and implement these tools for characterizing functional brain networks.
A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the CCM1 Gene: A Case Report and Review of the Literature
Authors: Liu Wenyu , Liu Ming , Lu Di , Wang Jiwei , Cao Zexin , Liu Xuchen , Feng Zichao , Huang Bin , Wang Xinyu
Published: April 2022

Background

Familial cerebral cavernous malformation (FCCM) is a vascular malformation disease closely linked to three identified genes:KRIT1/CCM1, MGC4607/CCM2andPDCD10/CCM3. Over the past decade, a few cases of cerebral cavernous malformation (CCM) caused by different gene mutations have been reported in Chinese families. Herein, we introduce a Chinese family affected by FCCM due to a kind ofKRIT1/CCM1frameshift mutation. At the same time, a literature review was conducted to identify case reports of familial cerebral cavernous malformation.

Case presentation

The proband in the family in question demonstrated a series of clinical symptoms and features, including headache and bleeding. The proband was hospitalized for headache twice and, both times was examined under suspicion of CCM and received surgical treatment. Magnetic resonance imaging results showed that the proband had multiple intracranial vascular lesions, including on the brain, brainstem, and cerebellum. Genetic test results showed that the classicKRIT1gene in the proband had a pathogenic mutation. The family members of the proband also showed typical cerebral cavernous malformation when considering clinical manifestations, magnetic resonance imaging findings and genetic test results.

Conclusions

We report a case of Chinese FCCM and its associated symptoms withCCM1-deletion mutations in China. Our findings deepen our understanding of CCM mutations and related phenotypes, the investigation results of this clinical experiment further show that the gene mutation form we reported plays an important role in human FCCM, and this trial investigation is beneficial for genetic counseling for CCM patients.
Delayed Post-Hypoxic Leukoencephalopathy Following Nitrite Poisoning: A Case Report and Review of the Literature
Authors: Chen Yankun , Liu Qiumei , Wang Jian , Li Hui , Zhang Yousheng , Sun Lingling , Liu Jianli
Published: April 2022

Background

Delayed post-hypoxic leukoencephalopathy (DPHL) is a demyelinating syndrome that occurs days to weeks after the brain has recovered from a coma. It is caused by the period of hypoxia and is characterized by mental disorders, extrapyramidal system symptoms, and motor changes. Common causes include cardiogenic shock, severe anemia, massive blood loss, and poisoning. Poisoning, mostly resulting from intoxication with carbon monoxide and several narcotic drugs, has been reported to be a cause of DPHL. There are only a few reports of DPHL due to nitrite poisoning in literature. We report DPHL in a patient following nitrite poisoning and a review of the literature in this context.

Case Presentation

A 64-year-old man presented with dizziness and nausea without vomiting. He later went into a coma after consuming a spare rib soup. After blood gas analysis, we suspected nitrite poisoning combined with metabolic acidosis, hypoxemia, and electrolyte imbalance. He gradually showed neurologic recovery to premorbid baseline after intravenous administration of methylene blue (40 mg) and symptomatic treatment. Two months later, the patient's cerebral magnetic resonance imaging (MRI) showed signs that are compatible with injury, with the patient in late stages of mental decline.

Conclusion

Nitrite poisoning can cause DPHL. There is a period of intermittent recovery between the time of poisoning and the development of DPHL, but the specific pathogenesis and treatment are still unclear.
Post-Treatment Plasma D-Dimer Levels Are Associated With Short-Term Outcomes in Patients With Cancer-Associated Stroke
Authors: Nakajima Sho , Kawano Hiroyuki , Yamashiro Kazuo , Tanaka Ryota , Kameda Tomoaki , Kurita Naohide , Hira Kenichiro , Miyamoto Nobukazu , Ueno Yuji , Watanabe Masao , Hirano Teruyuki , Fujimoto Shigeru , Urabe Takao , Hattori Nobutaka
Published: April 2022

Background and Objective

Hypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment and short-term outcomes in patients with cancer-associated stroke.

Methods

This retrospective, observational, multicenter study analyzed consecutive patients with cancer-associated ischemic stroke. Hypercoagulability was assessed by plasma D-dimer levels before and after stroke treatment. Short-term outcomes were assessed in terms of poor outcomes (a modified Rankin Scale score >3), cumulative rates of recurrent ischemic stroke, and mortality at 30 days after admission.

Results

Of 282 patients, 135 (47.9%) showed poor outcomes. Recurrent ischemic stroke was observed in 28 patients (9.9%), and the cumulative mortality rate was 12.4%. Multivariate analysis showed that post-treatment plasma D-dimer levels ≥10 μg/ml were independently associated with both poor outcomes (adjusted odds ratio [OR], 9.61; 95% confidence interval [CI], 3.60–25.70; P < 0.001) and mortality (adjusted OR, 9.38; 95% CI, 3.32–26.44; P < 0.001). Pre-treatment plasma D-dimer levels ≥10 μg/ml were not associated with these outcomes. Patients who received heparin had higher pre-treatment plasma D-dimer levels than those treated with other anticoagulants. Heparin produced a significant reduction in D-dimer levels from pre- to post-treatment without increasing the incidence of hemorrhagic events.

Conclusion

A high plasma D-dimer level after stroke treatment was associated with poor short-term outcomes in patients with cancer-associated stroke. Using anticoagulants to reduce D-dimer levels may improve short-term outcomes in these patients.
cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal
Authors: Shahoha Meishar , Cohen Ronni , Ben-Simon Yoav , Ashery Uri
Published: April 2022

Cyclic adenosine monophosphate (cAMP) is a crucial second messenger involved in both pre- and postsynaptic plasticity in many neuronal types across species. In the hippocampal mossy fiber (MF) synapse, cAMP mediates presynaptic long-term potentiation and depression. The main cAMP-dependent signaling pathway linked to MF synaptic plasticity acts via the activation of the protein kinase A (PKA) molecular cascade. Accordingly, various downstream putative synaptic PKA target proteins have been linked to cAMP-dependent MF synaptic plasticity, such as synapsin, rabphilin, synaptotagmin-12, RIM1a, tomosyn, and P/Q-type calcium channels. Regulating the expression of some of these proteins alters synaptic release probability and calcium channel clustering, resulting in short- and long-term changes to synaptic efficacy. However, despite decades of research, the exact molecular mechanisms by which cAMP and PKA exert their influences in MF terminals remain largely unknown. Here, we review current knowledge of different cAMP catalysts and potential downstream PKA-dependent molecular cascades, in addition to non-canonical cAMP-dependent but PKA-independent cascades, which might serve as alternative, compensatory or competing pathways to the canonical PKA cascade. Since several other central synapses share a similar form of presynaptic plasticity with the MF, a better description of the molecular mechanisms governing MF plasticity could be key to understanding the relationship between the transcriptional and computational levels across brain regions.
The Association Between Total Protein Intake and All-Cause Mortality in Middle Aged and Older Korean Adults With Chronic Kidney Disease
Authors: Kwon Yu-Jin , Lee Hye Sun , Park Go Eun , Kim Hyung-Mi , Lee Jung Joo , Kim Woo Jeong , Lee Ji-Won
Published: April 2022

Background and Aims

Over the past decades, the optimum protein intake for patients with chronic kidney disease (CKD) has been an important, controversial issue. Dietary protein restriction has been commonly recommended for patients with CKD for preserving kidney function. However, evidence of the associations between long-term protein intake and mortality is not consistent in patients with CKD. Therefore, we aimed to examine the associations between total protein intake and all-cause mortality in Korean adults with CKD.

Methods

From three sub-cohorts of the Korean Genome and Epidemiology Study (KoGES) starting from 2001, total 3,892 participants with eGFR < 60 mL/min/1.73 m2 (CKD stage 3–5) were included in this study. Dietary data were collected using food-frequency questionnaires at baseline. Deaths were followed from 2001 to 2019. Cox proportional hazards regression model was used to evaluate the association between protein intake and all-cause mortality.

Results

During a median follow-up (min-max) of 11.1 years (0.3–15.1), 602 deaths due to all causes of mortality were documented. After adjustment for covariates, higher total protein intake was not associated with all-cause mortality [highest vs. lowest quintile of total protein intake (g/kg/day) and proportion (%) (Q5 vs. Q1), HR = 1.14 (0.75–1.72), and HR = 0.87 (0.67–1.13)] in CKD stage 3–5 patients.

Conclusion

Dietary protein intake was not associated with mortality from all causes in patients with CKD. Further research is needed to establish optimal protein intake levels and examine the impact of the dietary source of protein on various health outcomes and mortality in CKD.
The Reduction of Salt in Different Cheese Categories: Recent Advances and Future Challenges
Authors: Tidona Flavio , Zago Miriam , Carminati Domenico , Giraffa Giorgio
Published: April 2022

Public awareness about excessive sodium intake and nutrition claims related to salt content entail the need for food industries to carefully reconsider the composition and processing of high sodium foods. Although in some products the reformulation with alternative ingredients is commonly practiced, in cheese the reduction of salt is still a challenging task, as sodium chloride exerts multiple and fundamental functions. Salt favors the drainage of the residual whey, enhances the taste and the aroma profile, regulates the texture, the final pH, the water activity, and affects the microbial growth. Ultimately, salt content modulates the activity of starter and non-starter lactic acid bacteria (NSLAB) during cheese manufacturing and ripening, influencing the shelf-life. Any modification of the salting procedure, either by reducing the level of sodium chloride content or by replacing it with other salting agents, may affect the delicate equilibrium within the above-mentioned parameters, leading to changes in cheese quality. The decrease of Na content may be differently approached according to cheese type and technology (e.g., soft, semi-hard, hard, and mold-ripened cheeses). Accordingly, targeted strategies could be put in place to maintain the overall quality and safety of different cheeses categories.
Mediterranean Diet Combined With a Low-Carbohydrate Dietary Pattern in the Treatment of Overweight Polycystic Ovary Syndrome Patients
Authors: Mei Shanshan , Ding Jie , Wang Kaili , Ni Zhexin , Yu Jin
Published: April 2022

Objectives

To determine the therapeutic effect of a Mediterranean diet (MED) combined with a low-carbohydrate (LC) dietary model in overweight polycystic ovary syndrome (PCOS) patients.

Methods

In this 12-week randomized controlled clinical trial, 72 overweight patients with PCOS were randomly assigned to one of two energy-restricted dietary models: the MED/LC diet or the Low fat (LF) diet. After the intervention, the number of the two groups returned to normal menstruation was counted. Body weight, body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), serum fasting insulin(FINS), fasting plasma glucose(FPG), insulin resistance index (HOMA-IR), quantitative insulin sensitivity index (QUIKI), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were compared between 2 groups before and after intervention.

Results

MED/LC group had more significant reduction trend in weight (−6.10 ± 1.52 kg vs −4.79 ± 0.97 kg, P < 0.05), BMI (−2.12 ± 0.57 kg/m2 vs −1.78 ± 0.36 kg/m2, P < 0.05), WC (−6.12 ± 5.95 cm vs −3.90 ± 1.58 cm, P < 0.05), WHR (−0.06 ± 0.02 vs −0.03 ± 0.02, P < 0.05), BF% (−2.97% ± 1.78% vs −1.19% ± 0.91%, P < 0.05), TT (−0.20 ± 0.24 ng/mL vs 0.08 ± 0.11 ng/Ml, P < 0.001), LH (−5.28 ± 3.31 mIU/mL vs −3.39 ± 3.64 mIU/mL, P < 0.05), and LH/FSH (−1.18 ± 0.75 vs -0.66 ± 1.05, P < 0.05) compared with the LF group. In addition, FPG (0.05 ± 0.38 mmol/mL vs -0.50 ± 1.01 mmol/mL, P < 0.001), FINS (−4.88 ± 6.11 μU/mL vs −8.53 ± 5.61 μU/mL, P < 0.01), HOMA-IR index (−1.11 ± 1.51 vs −2.23 ± 0.25, P < 0.05), and QUIKI index (0.014 ± 0.016 vs 0.028 ± 0.019, P < 0.05) decreased significantly in the MED/LC group compared with the LF group. Comparing the changes in lipid parameters between the two groups (LF vs MED/LC), significant differences in TG (−0.33 ± 0.32 mmol vs −0.76 ± 0.97 mmol, P < 0.05), TC (−0.40 ± 1.00 mmol vs −1.45 ± 2.00 mmol, P < 0.05), and LDL-C (−0.41 ± 1.05 mmol vs −0.73 ± 0.76 mmol, P < 0.05) were observed.

Conclusion

The results of this study suggest that the MED/LC diet model is a good treatment for overweight PCOS patients, significantly restoring their menstrual cycle, improving their anthropometric parameters and correcting their disturbed endocrine levels, and its overall effectiveness is significantly better than the LF diet model. Therefore, this study recommends that the MED/LC diet model can be used in the clinical treatment of patients with overweight PCOS.
Recent Advances in Medical Therapy for Urological Cancers
Authors: Yuasa Takeshi , Urasaki Tetsuya , Oki Ryosuke
Published: April 2022

The mainstay of medical treatment has been tyrosine kinase inhibitors (TKIs) for renal cell cancer (RCC), cytotoxic chemotherapy for urothelial cancer (UC), and androgen deprivation therapy for prostate cancer. These therapeutic modalities still play important roles in these malignancies. However, immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 or CTLA-4 are being rapidly introduced for the treatment of metastatic urological cancers, just as they have been for other malignancies. Currently, the paradigm of medical treatment for patients with metastatic urological cancer is dramatically changing. Accordingly, we need to organize and summarize the new therapeutic tools, which include immune checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and antibody-drug conjugates (ADCs). This review provides an overview of agents and regimens that have just launched or will be launched in the near future in Japan. Based on the promising anti-tumor efficacy and manageable safety profiles being demonstrated in clinical trials, these new agents and therapies are expected to be rapidly introduced in Japanese clinical practice. Additionally, the newly designed ADC, enfortumab vedotin, which comprises a fully human monoclonal antibody conjugated to an anti-cancerous agent via a protease-cleavable linker, has just been launched in Japan. In order to provide the optimal treatment for our patients, we need to completely understand these new therapeutic tools.
BRAF Inhibitor Resistance Confers Increased Sensitivity to Mitotic Inhibitors
Authors: Misek Sean A. , Foda Bardees M. , Dexheimer Thomas S. , Akram Maisah , Conrad Susan E. , Schmidt Jens C. , Neubig Richard R. , Gallo Kathleen A.
Published: April 2022

Single agent and combination therapy with BRAFV600E/K and MEK inhibitors have remarkable efficacy against melanoma tumors with activating BRAF mutations, but in most cases BRAF inhibitor (BRAFi) resistance eventually develops. One resistance mechanism is reactivation of the ERK pathway. However, only about half of BRAFi resistance is due to ERK reactivation. The purpose of this study is to uncover pharmacological vulnerabilities of BRAFi-resistant melanoma cells, with the goal of identifying new therapeutic options for patients whose tumors have developed resistance to BRAFi/MEKi therapy. We screened a well-annotated compound library against a panel of isogenic pairs of parental and BRAFi-resistant melanoma cell lines to identify classes of compounds that selectively target BRAFi-resistant cells over their BRAFi-sensitive counterparts. Two distinct patterns of increased sensitivity to classes of pharmacological inhibitors emerged. In two cell line pairs, BRAFi resistance conferred increased sensitivity to compounds that share the property of cell cycle arrest at M-phase, including inhibitors of aurora kinase (AURK), polo-like kinase (PLK), tubulin, and kinesin. Live cell microscopy, used to track mitosis in real time, revealed that parental but not BRAFi-resistant melanoma cells were able to exit from compound-induced mitotic arrest through mitotic slippage, thus escaping death. Consistent with the key role of Cyclin B1 levels in regulating mitosis at the spindle checkpoint in arrested cells, we found lower Cyclin B1 levels in parental compared with BRAFi-resistant melanoma cells, suggesting that inability to down-regulate Cyclin B1 expression levels may explain the increased vulnerability of resistant cells to mitotic inhibitors. Another BRAFi-resistant cell line showed increased sensitivity to Chk1/2 inhibitors, which was associated with an accumulation of DNA damage, resulting in mitotic failure. This study demonstrates that BRAFi-resistance, in at least a subset of melanoma cells, confers vulnerability to pharmacological disruption of mitosis and suggests a targeted synthetic lethal approach for overcoming resistance to BRAF/MEK-directed therapies.
Genomic and Molecular Signatures of Successful Patient-Derived Xenografts for Oral Cavity Squamous Cell Carcinoma
Authors: Yen Wei-Chen , Chang Ian Yi-Feng , Chang Kai‐Ping , Ouyang Chun‐Nan , Liu Chiao-Rou , Tsai Ting-Lin , Zhang Yi-Cheng , Wang Chun-I , Wang Ya-Hui , Yu Alice L. , Liu Hsuan , Wu Chih-Ching , Chang Yu-Sun , Yu Jau-Song , Yang Chia-Yu
Published: April 2022

Background

Oral cavity squamous cell carcinoma (OSCC) is an aggressive malignant tumor with high recurrence and poor prognosis in the advanced stage. Patient-derived xenografts (PDXs) serve as powerful preclinical platforms for drug testing and precision medicine for cancer therapy. We assess which molecular signatures affect tumor engraftment ability and tumor growth rate in OSCC PDXs.

Methods

Treatment-naïve OSCC primary tumors were collected for PDX models establishment. Comprehensive genomic analysis, including whole-exome sequencing and RNA-seq, was performed on case-matched tumors and PDXs. Regulatory genes/pathways were analyzed to clarify which molecular signatures affect tumor engraftment ability and the tumor growth rate in OSCC PDXs.

Results

Perineural invasion was found as an important pathological feature related to engraftment ability. Tumor microenvironment with enriched hypoxia, PI3K-Akt, and epithelial–mesenchymal transition pathways and decreased inflammatory responses had high engraftment ability and tumor growth rates in OSCC PDXs. High matrix metalloproteinase-1 (MMP1) expression was found that have a great graft advantage in xenografts and is associated with pooled disease-free survival in cancer patients.

Conclusion

This study provides a panel with detailed genomic characteristics of OSCC PDXs, enabling preclinical studies on personalized therapy options for oral cancer. MMP1 could serve as a biomarker for predicting successful xenografts in OSCC patients.
Enhanced Recovery After Surgery Protocol Optimizes Results and Cost of Laparoscopic Radical Nephrectomy
Authors: Chen Siming , He Zhiwen , Yao Shijie , Xiong Kangping , Shi Jiageng , Wang Gang , Qian Kaiyu , Wang Xinghuan
Published: April 2022

Purpose

To assess the impact of enhanced recovery after surgery (ERAS) protocols in laparoscopic radical nephrectomy (LRN).

Methods

The clinical data of 89 patients underwent LRN in Zhongnan Hospital of Wuhan University from February 2019 to September 2021 were collected (40 in the ERAS group and 49 in the pre-ERAS group). The clinical characteristics, prognosis, and length of hospital stay (LOS) were compared between the two groups using t test, Mann-Whitney test, and chi-square test.

Results

Total LOS and postoperative LOS were significantly shorter in ERAS group than in pre-ERAS group [15.0 (13.5-19.5) vs. 12.0 (10.0-14.0), P < 0.001; 8.0 (7.0-10.0) vs. 7.0 (5.0-8.8), P = 0.001]. Compared with the pre-ERAS group, the hospitalization expenses of the ERAS group were also lower (P = 0.023). In addition, the incidence of postoperative complications in the ERAS group also decreased (P = 0.054).

Conclusions

ERAS protocol in LRN could help accelerate the recovery of patients and is worthy of clinical promotion.