bluuebunny/crossref_metadata_2025 huggingface dataset:
Xenoimplant of Collagen Matrix Scaffold in Liver Tissue as a Niche for Liver Cells
Authors: Martinez-Castillo Moises , León-Mancilla Benjamín , Ramírez-Rico Gerardo , Alfaro Ana , Pérez-Torres Armando , Díaz-Infante Daniela , García-Loya Jorge , Medina-Avila Zaira , Sanchez-Hernandez Jaime , Piña-Barba Cristina , Gutierrez-Reyes Gabriela
Published: April 2022

Hepatitis C virus-induced liver damage, chronic liver damage due to alcohol, and non-alcoholic liver disease-induced cellular alterations promote fibrosis, cirrhosis, and/or hepatocellular carcinoma. The recommended therapeutic option for advanced liver damage is liver transplantation. Extracellular matrix scaffolds have been evaluated as an alternative for tissue restoration. Studies on the biocompatibility and rejection of synthetic and natural scaffolds as an alternative to organ transplantation have been evaluated. Our group has recently described the xenoimplant of collagen matrix scaffold (CMS) in a rat model. However, no complete macroscopic and histological description of the liver parenchyma at the initial (day 3), intermediate (day 14), and advanced (day 21) stages has been obtained. In this study, we described and compared liver tissue from the CMS zone (CZ, CMS, and liver parenchyma), liver tissue from the normal zone (liver parenchyma close to the CMS), and basal tissue (resected tissue from the CMS implantation site). Our data strongly suggest that the collagen matrix xenoimplant is a good niche for hepatocytes, with no rejection, and does not affect liver function tests. The liver can regenerate after damage, but this capacity is inhibited in a chronic injury. At present, the use of CMS after liver damage has not been reported. This biomaterial could be a novel alternative in the field of regenerative medicine for liver diseases.
Development and Validation of a Two-Step Predictive Risk Stratification Model for Coronavirus Disease 2019 In-hospital Mortality: A Multicenter Retrospective Cohort Study
Authors: Li Yang , Kong Yanlei , Ebell Mark H. , Martinez Leonardo , Cai Xinyan , Lennon Robert P. , Tarn Derjung M. , Mainous Arch G. , Zgierska Aleksandra E. , Barrett Bruce , Tuan Wen-Jan , Maloy Kevin , Goyal Munish , Krist Alex H. , Gal Tamas S. , Sung Meng-Hsuan , Li Changwei , Jin Yier , Shen Ye
Published: April 2022

Objectives

An accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information.

Design

Multicenter retrospective observational cohort study.

Setting

Four health centers from Virginia Commonwealth University, Georgetown University, the University of Florida, and the University of California, Los Angeles.

Patients

Coronavirus Disease 2019-confirmed and hospitalized adult patients.

Measurements and Main Results

We included 1,673 participants from Virginia Commonwealth University (VCU) as the derivation cohort. Risk factors for in-hospital death were identified using a multivariable logistic model with variable selection procedures after repeated missing data imputation. A two-step risk score was developed to identify patients at lower, moderate, and higher mortality risk. The first step selected increasing age, more than one pre-existing comorbidities, heart rate >100 beats/min, respiratory rate ≥30 breaths/min, and SpO2 <93% into the predictive model. Besides age and SpO2, the second step used blood urea nitrogen, absolute neutrophil count, C-reactive protein, platelet count, and neutrophil-to-lymphocyte ratio as predictors. C-statistics reflected very good discrimination with internal validation at VCU (0.83, 95% CI 0.79–0.88) and external validation at the other three health systems (range, 0.79–0.85). A one-step model was also derived for comparison. Overall, the two-step risk score had better performance than the one-step score.

Conclusions

The two-step scoring system used widely available, point-of-care data for triage of COVID-19 patients and is a potentially time- and cost-saving tool in practice.
Strongyloidiasis in a Patient Diagnosed by Metagenomic Next-Generation Sequencing: A Case Report
Authors: Qu Junyan , Zong Zhiyong
Published: April 2022

Background

Strongylodiasis may be asymptomatic or cause mild gastrointestinal symptoms, and may be a fatal disseminated disease or Strongyloides hyperinfection syndrome. Non-specific clinical manifestations, such as pneumonia and gastroenteritis, pose a diagnostic dilemma.

Case Presentation

We report a case of a 67-year-old Chinese male who presented with abdominal pain, fever, headache, vomiting, constipation, and slight cough with sputum for nearly 2 months. He had been in good health and had no history of glucocorticoid use. He was diagnosed with enterococcal meningitis and intestinal obstruction at a local hospital and improved after treatment with vancomycin, but symptoms of headache and abdominal pain soon recurred. The metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid using Illumina X10 sequencer revealed seven sequence reads matching Strongyloides stercoralis. Strongyloidiasis was suspected. Microscopic examination of gastric fluid revealed the presence of S. stercoralis larvae, which was confirmed by PCR to amplify both S. stercoralis ribosomal DNA gene and mitochondrial cytochrome c oxidase subunit 1 gene and sequencing amplicons. Strongyloidiasis was diagnosed. Albendazole (400 mg, twice daily) was used, and the patient recovered gradually.

Conclusion

mNGS may be a useful tool for detecting uncommon infectious disease. The case would help clinicians to raise awareness of strongyloidiasis in non-endemic areas and reduce fatality.
Late-Onset Bartter Syndrome Type II Due to a Novel Compound Heterozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review
Authors: Tian Mi , Peng Hui , Bi Xin , Wang Yan-Qiu , Zhang Yong-Zhe , Wu Yan , Zhang Bei-Ru
Published: April 2022

Background

Bartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle’s loop. BS type II is typically considered as a disorder of infancy and seldom seen in adults.

Case Presentation

A 34-year-old woman was admitted with generalized body numbness and hand convulsions, without growth retardation. Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. She was misdiagnosed during the initial diagnosis process and was finally diagnosed with late-onset BS type II via genetic testing through next-generation sequencing combined with Sanger sequencing. A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene from her parents was identified and speculated to be a potential pathogenic gene variation.

Conclusion

We report a case of late-onset BS type II with a novel compound heterozygous mutation in KCNJ1. Both variants are novel and have never been reported. Our report will have a significant impact on the diagnosis of BS in other patients without typical clinical presentations and emphasizes the importance of genetic investigation.
Treatment of Placenta Increta With High-Intensity Focused Ultrasound Ablation and Leaving the Placenta in situ: A Multicenter Comparative Study
Authors: Guan Xiaoping , Huang Xiaoqin , Ye Min , Huang Guohua , Xiao Xiao , Chen Jinyun
Published: April 2022

Objective

To explore the feasibility of simple high-intensity focused ultrasound (HIFU) ablation for placenta increta.

Methods

Ninety-five patients after a vaginal delivery were enrolled in this retrospective cohort study, 53 patients were treated with simple HIFU ablation, and 42 patients were treated with HIFU followed by uterine curettage.

Results

All 95 patients were successfully treated with a single-session HIFU procedure, and in the control group, the necrotic placental tissue was removed with curettage. Vaginal hemorrhage did not occur in either group. The duration of bloody lochia was 25.9 ± 8.6 days in the sHIFU group and 24.2 ± 8.8 days in the control group (P > 0.05). The median serum human chorionic gonadotropin (HCG) level was 3,222 mIU/mL and 2,838 mIU/mL in the sHIFU and control groups, respectively, which decreased and returned to normal within 30 days, and the differences were not significantly on comparing the blood HCG level in the two groups at 7, 15, and 30 days after HIFU (all P > 0.05). Decreased menstrual volume occurred in 85.71% of patients in the control group, which was higher than that in the sHIFU group (23.08%) (χ2 = 6.839, P < 0.001). During 2–8 years of follow-up, six pregnancies occurred in the sHIFU group without any recurrence of placenta increta, three pregnancies occurred in the control group, and one patient developed a repeat placenta increta.

Conclusion

Simple HIFU treatment is safe and effective for postpartum placenta increta and leaving the placenta in situ. It is a promising option for patients who wish to preserve their fertility and conceive.
Co-occurrence of Lactobacillus Species During Fermentation of African Indigenous Foods: Impact on Food Safety and Shelf-Life Extension
Authors: Adesulu-Dahunsi Adekemi Titilayo , Dahunsi Samuel Olatunde , Ajayeoba Titilayo Adenike
Published: April 2022

The benefits derived from fermented foods and beverages have placed great value on their acceptability worldwide. Food fermentation technologies have been employed for thousands of years and are considered essential processes for the production and preservation of foods, with the critical roles played by the autochthonous fermenting food-grade microorganisms in ensuring food security and safety, increased shelf life, and enhanced livelihoods of many people in Africa, particularly the marginalized and vulnerable groups. Many indigenous fermented foods and beverages of Africa are of plant origin. In this review, the predominance, fermentative activities, and biopreservative role of Lactobacillus spp. during production of indigenous foods and beverages, the potential health benefit of probiotics, and the impact of these food-grade microorganisms on food safety and prolonged shelf life are discussed. During production of African indigenous foods (with emphasis on cereals and cassava-based food products), fermentation occurs in succession; the first group of microorganisms to colonize the fermenting substrates are lactic acid bacteria (LAB) with the diversity and dominance of Lactobacillus spp. The Lactobacillus spp. multiply rapidly in the fermentation matrix, by taking up nutrients from the surrounding environments, and cause rapid acidification in the fermenting system via the production of organic compounds that convert fermentable sugars into mainly lactic acid. Production of these compounds in food systems inhibits spoilage microorganisms, which has a direct effect on food quality and safety. The knowledge of microbial interaction and succession during food fermentation will assist the food industry in producing functional foods and beverages with improved nutritional profiling and technological attributes, as Lactobacillus strains isolated during fermentation of several African indigenous foods have demonstrated desirable characteristics that make them safe for use as probiotic microorganisms and even as a starter culture in small- and large-scale/industrial food production processes.
Oral SARS-CoV-2 Spike Protein Recombinant Yeast Candidate Prompts Specific Antibody and Gut Microbiota Reconstruction in Mice
Authors: Zhang Lilin , Yao Lan , Guo Yanyu , Li Xiaoyang , Ma Li , Sun Ruiqi , Han Xueqing , Liu Jing , Huang Jinhai
Published: April 2022

A recent study showed that patients with coronavirus disease 2019 (COVID-19) have gastrointestinal symptoms and intestinal flora dysbiosis. Yeast probiotics shape the gut microbiome and improve immune homeostasis. In this study, an oral candidate of yeast-derived spike protein receptor-binding domain (RBD) and fusion peptide displayed on the surface of the yeast cell wall was generated. The toxicity and immune efficacy of oral administration were further performed in Institute of Cancer Research (ICR) mice. No significant difference in body weights, viscera index, and other side effects were detected in the oral-treated group. The detectable RBD-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more complex microbiota were detected from oral administration mice compared with those of the control group. Interestingly, the recombinant yeast was identified in female fetal of the high-dose group. These results revealed that the displaying yeast could fulfill the agent-driven immunoregulation and gut microbiome reconstitution. The findings will shed light on new dimensions against SARS-CoV-2 infection with the synergistic oral agents as promising non-invasive immunization and restoring gut flora.
Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma
Authors: Xiao Yiwei , Cao Junning , Zhang Ze , Zeng Chaoting , Ou Guomin , Shi Jihang , Liu Zhixiu , Li Yi , Deng Juan , Xu Yinzhe , Zhang Wenwen , Li Jie , Li Tong , Zhuang Hui , Lu Shichun , Xiang Kuanhui
Published: April 2022

Background

The existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients.

Methods

We collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis.

Results

We found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44.

Conclusion

HBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.
Multiple Regions Drive Hepatitis Delta Virus Proliferation and Are Therapeutic Targets
Authors: Zi Jun , Gao Xiuzhu , Du Juan , Xu Hongqin , Niu Junqi , Chi Xiumei
Published: April 2022

Hepatitis Delta Virus (HDV) is the smallest mammalian single-stranded RNA virus. It requires host cells and hepatitis B virus (HBV) to complete its unique life cycle. The present review summarizes the specific regions on hepatitis D antigen (HDAg) and hepatitis B surface antigen (HBsAg) that drive HDV to utilize host cell machinery system to produce three types of RNA and two forms of HDAg, and hijack HBsAg for its secretion and de novo entry. Previously, interferon-α was the only recommended therapy for HDV infection. In recent years, some new therapies targeting these regions, such as Bulevirtide, Lonafarnib, Nucleic acid polymers have appeared, with better curative effects and fewer adverse reactions.
Distribution Characteristics of Soil Viruses Under Different Precipitation Gradients on the Qinghai-Tibet Plateau
Authors: Cao Miao-Miao , Liu Si-Yi , Bi Li , Chen Shu-Jun , Wu Hua-Yong , Ge Yuan , Han Bing , Zhang Li-Mei , He Ji-Zheng , Han Li-Li
Published: April 2022

Viruses are extremely abundant in the soil environment and have potential roles in impacting on microbial population, evolution, and nutrient biogeochemical cycles. However, how environment and climate changes affect soil viruses is still poorly understood. Here, a metagenomic approach was used to investigate the distribution, diversity, and potential biogeochemical impacts of DNA viruses in 12 grassland soils under three precipitation gradients on the Qinghai-Tibet Plateau, which is one of the most sensitive areas to climate change. A total of 557 viral operational taxonomic units were obtained, spanning 152 viral families from the 30 metagenomes. Both virus-like particles (VLPs) and microbial abundance increased with average annual precipitation. A significant positive correlation of VLP counts was observed with soil water content, total carbon, total nitrogen, soil organic matter, and total phosphorus. Among these biological and abiotic factors, SWC mainly contributed to the variability in VLP abundance. The order Caudovirales (70.1% of the identified viral order) was the predominant viral type in soils from the Qinghai-Tibet Plateau, with the Siphoviridae family being the most abundant. Remarkably, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes represented by glycoside hydrolases were identified, indicating that soil viruses may play a potential role in the carbon cycle on the Qinghai-Tibet Plateau. There were more diverse hosts and abundant CAZyme genes in soil with moderate precipitation. Our study provides a strong evidence that changes in precipitation impact not only viral abundance and virus–host interactions in soil but also the viral functional potential, especially carbon cycling.
Gut Bacterial Composition and Functional Potential of Tibetan Pigs Under Semi-Grazing
Authors: Niu Hui , Feng Xi-Ze , Shi Chun-Wei , Zhang Di , Chen Hong-Liang , Huang Hai-Bin , Jiang Yan-Long , Wang Jian-Zhong , Cao Xin , Wang Nan , Zeng Yan , Yang Gui-Lian , Yang Wen-Tao , Wang Chun-Feng
Published: April 2022

Gut bacterial community plays a key role in maintaining host health. The Tibetan pig (Sus scrofa), an ancient breed in China, has been known for its high adaptability to harsh environments and for its meat quality. To understand the underlying mechanisms facilitating to shape these unique features, in this study, 16S rRNA sequencing using pigs feces and subsequent bacterial functional prediction were performed. Also, the gut bacteria of two other breeds of pigs, Barkshire and Landrace, were examined for comparison. It was revealed that the structure of bacterial community in Tibetan pigs appeared to be more complex; the relative abundances of dominant bacterial families varied inversely with those of the other pigs, and the proportion of Firmicutes in Tibetan pigs was lower, but Bacteroides, Fibrobacterota, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae were higher. Bacterial functional prediction revealed that the dominant flora in the Tibetan pigs was more correlated with functions regulating the hosts’ immune and inflammatory responses, such as NOD-like_receptor_signaling_pathway and vitamin metabolism. In addition, in Tibetan pigs, the taxonomic relationships in the gut bacteria on day 350 were closer than those on earlier stages. Furthermore, gender played a role in the composition and function of bacterial inhabitants in the gut; for boars, they were more correlated to drug resistance and xenobiotics metabolism of the host compared to the sows. In sum, our preliminary study on the gut bacterial composition of the Tibetan pigs provided an insight into the underlying host–microorganism interactions, emphasizing the role of intestinal bacteria in the context of modulating the host’s immune system and host development.
The Ton Motor
Authors: Ratliff Anna C. , Buchanan Susan K. , Celia Herve
Published: April 2022

The Ton complex is a molecular motor at the inner membrane of Gram-negative bacteria that uses a proton gradient to apply forces on outer membrane (OM) proteins to permit active transport of nutrients into the periplasmic space. Recently, the structure of the ExbB–ExbD subcomplex was determined in several bacterial species, but the complete structure and stoichiometry of TonB have yet to be determined. The C-terminal end of TonB is known to cross the periplasm and interact with TonB-dependent outer membrane transport proteins with high affinity. Yet despite having significant knowledge of these transport proteins, it is not clear how the Ton motor opens a pathway across the outer membrane for nutrient import. Additionally, the mechanism by which energy is harnessed from the inner membrane subcomplex and transduced to the outer membrane via TonB is not well understood. In this review, we will discuss the gaps in the knowledge about the complete structure of the Ton motor complex and the relationship between ion flow used to generate mechanical work at the outer membrane and the nutrient transport process.
Spatiotemporal Variation of Microbial Communities in the Ultra-Oligotrophic Eastern Mediterranean Sea
Authors: Haber Markus , Roth Rosenberg Dalit , Lalzar Maya , Burgsdorf Ilia , Saurav Kumar , Lionheart Regina , Lehahn Yoav , Aharonovich Dikla , Gómez-Consarnau Laura , Sher Daniel , Krom Michael D. , Steindler Laura
Published: April 2022

Marine microbial communities vary seasonally and spatially, but these two factors are rarely addressed together. In this study, the temporal and spatial patterns of the bacterial and archaeal community were studied along a coast-to-offshore transect in the Eastern Mediterranean Sea (EMS) over six cruises, in three seasons of 2 consecutive years. Amplicon sequencing of 16S rRNA genes and transcripts was performed to determine presence and activity, respectively. The ultra-oligotrophic status of the Southeastern Mediterranean Sea was reflected in the microbial community composition dominated by oligotrophic bacterial groups such as SAR11, even at the most coastal station sampled, throughout the year. Seasons significantly affected the microbial communities, explaining more than half of the observed variability. However, the same few taxa dominated the community over the 2-year sampling period, varying only in their degree of dominance. While there was no overall effect of station location on the microbial community, the most coastal site (16 km offshore) differed significantly in community structure and activity from the three further offshore stations in early winter and summer. Our data on the microbial community compositions and their seasonality support previous notions that the EMS behaves like an oceanic gyre.
Antimicrobial Coating Efficacy for Prevention of Pseudomonas aeruginosa Biofilm Growth on ISS Water System Materials
Authors: Mettler Madelyn K. , Parker Ceth W. , Venkateswaran Kasthuri , Peyton Brent M.
Published: April 2022

Biofilms can lead to biofouling, microbially induced corrosion, physical impediment and eventual loss in function of water systems, and other engineered systems. The remoteness and closed environment of the International Space Station (ISS) make it vulnerable to unchecked biofilm growth; thus, biofilm mitigation strategies are crucial for current ISS operation and future long duration and deep-space crewed missions. In this study, a space flown bacterial strain of Pseudomonas aeruginosa (PA14) was used as a model organism for its ability to form biofilms. Additionally, a novel antimicrobial coating’s ability to reduce biofilm accumulation on stainless steel, Teflon, titanium, and Inconel (all used in the ISS water treatment and handling systems) was analyzed. Coated materials demonstrated reductions of P. aeruginosa biofilm across all materials when tested in a continuous flow system with tryptic soy broth medium. However, the coating lost efficacy in potato dextrose broth medium. These findings were corroborated via scanning electron microscopy. This study illustrates the fundamental importance of using multiple approaches to test antibiofilm strategies, as well as the specificity in which conditions such strategies can be implemented.
Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
Authors: Vicente-Garcés Clara , Esperanza-Cebollada Elena , Montesdeoca Sara , Torrebadell Montserrat , Rives Susana , Dapena José Luis , Català Albert , Conde Nuria , Camós Mireia , Vega-García Nerea
Published: April 2022

Development of next-generation sequencing (NGS) has provided useful genetic information to redefine diagnostic, prognostic, and therapeutic strategies for the management of acute leukemia (AL). However, the application in the clinical setting is still challenging. Our aim was to validate the AmpliSeq™ for Illumina® Childhood Cancer Panel, a pediatric pan-cancer targeted NGS panel that includes the most common genes associated with childhood cancer, and assess its utility in the daily routine of AL diagnostics. In terms of sequencing metrics, the assay reached all the expected values. We obtained a mean read depth greater than 1000×. The panel demonstrated a high sensitivity for DNA (98.5% for variants with 5% variant allele frequency (VAF)) and RNA (94.4%), 100% of specificity and reproducibility for DNA and 89% of reproducibility for RNA. Regarding clinical utility, 49% of mutations and 97% of the fusions identified were demonstrated to have clinical impact. Forty-one percent of mutations refined diagnosis, while 49% of them were considered targetable. Regarding RNA, fusion genes were more clinically impactful in terms of refining diagnostic (97%). Overall, the panel found clinically relevant results in the 43% of patients tested in this cohort. To sum up, we validated a reliable and reproducible method to refine pediatric AL diagnosis, prognosis, and treatment, and demonstrated the feasibility of incorporating a targeted NGS panel into pediatric hematology practice.
Interactive Training of the Emergency Medical Services Improved Prehospital Stroke Recognition and Transport Time
Authors: Sveikata Lukas , Melaika Kazimieras , Wiśniewski Adam , Vilionskis Aleksandras , Petrikonis Kȩstutis , Stankevičius Edgaras , Jurjans Kristaps , Ekkert Aleksandra , Jatužis Dalius , Masiliūnas Rytis
Published: April 2022

Background and Purpose

Acute stroke treatment outcomes are predicated on reperfusion timeliness which can be improved by better prehospital stroke identification. We aimed to assess the effect of interactive emergency medical services (EMS) training on stroke recognition and prehospital care performance in a very high-risk cardiovascular risk population in Lithuania.

Methods

We conducted a single-center interrupted time-series study between March 1, 2019 and March 15, 2020. Two-hour small-group interactive stroke training sessions were organized for 166 paramedics serving our stroke network. We evaluated positive predictive value (PPV) and sensitivity for stroke including transient ischemic attack identification, onset-to-door time, and hospital-based outcomes during 6-months prior and 3.5 months after the training. The study outcomes were compared between EMS providers in urban and suburban areas.

Results

In total, 677 suspected stroke cases and 239 stroke chameleons (median age 75 years, 54.8% women) were transported by EMS. After the training, we observed improved PPV for stroke recognition (79.8% vs. 71.8%, p = 0.017) and a trend of decreased in-hospital mortality (7.8% vs. 12.3, p = 0.070). Multivariable logistic regression models adjusted for age, gender, EMS location, and stroke subtype showed an association between EMS stroke training and improved odds of stroke identification (adjusted odds ratio [aOR] 1.6 [1.1–2.3]) and onset-to-door ≤ 90 min (aOR 1.6 [1.1–2.5]). The improvement of PPV was observed in urban EMS (84.9% vs. 71.2%, p = 0.003), but not in the suburban group (75.0% vs. 72.6%, p = 0.621).

Conclusions

The interactive EMS training was associated with a robust improvement of stroke recognition, onset to hospital transport time, and a trend of decreased in-hospital mortality. Adapted training strategies may be needed for EMS providers in suburban areas. Future studies should evaluate the long-term effects of the EMS training and identify optimal retraining intervals.
Effects of a 6-Min Treadmill Walking Test on Dual-Task Gait Performance and Prefrontal Hemodynamics in People With Multiple Sclerosis
Authors: Broscheid Kim-Charline , Behrens Martin , Dettmers Christian , Jöbges Michael , Schega Lutz
Published: April 2022

Fatigue is one of the most limiting symptoms in people with multiple sclerosis (pwMS) and can be subdivided into trait and state fatigue. Activity-induced state fatigue describes the temporary decline in motor and/or cognitive performance (motor and cognitive performance fatigability, respectively) and/or the increase in the perception of fatigue (perceived fatigability) in response to motor or cognitive tasks. To the best of our knowledge, the effects of a 6-min walk test (6MWT), which was often used to assess motor performance fatigability in pwMS, on motor-cognitive dual-task performance (i.e., walking + arithmetic task) and prefrontal cortex (PFC) hemodynamics are not well-known. This is of importance, since daily activities are often performed as multitasks and a worse dual-task walking performance is associated with an increased risk of falling. Consequently, we investigated the effect of a fast 6MWT (comfort velocity + 15%) performed on a treadmill on motor-cognitive performance fatigability (spatio-temporal gait parameters/accuracy during the arithmetic task) and perceived fatigability measures (rating of perceived exhaustion; RPE) as well as PFC hemodynamics recorded during dual-task walking in pwMS and healthy controls (HCs). Twenty pwMS (48.3 ± 9.0 years; 13 females/7 males; expanded disability status scale 2.7 ± 1.0, first diagnosis 13.8 ± 8.8 years) and 24 HC with similar age and sex (48.6 ± 7.9 years; 17 females/7 males) were included. Only cognitive performance fatigability (increased error rate) during dual-task walking was found after the fast 6MWT on the treadmill in pwMS. However, the changes in gait parameters did not indicate motor performance fatigability, although both the groups reported perceived fatigability (increased RPE) after the fast 6MWT. Moreover, no change in the PFC activation was detected in both groups. Our results suggest that the intensity and/or duration of the fast 6MWT was not sufficient to induce motor performance fatigability in pwMS. These factors should be addressed by future studies on this topic, which should also consider further parameters, e.g., muscular oxygenation and/or myoelectrical activity, to verify that exercise intensity and/or duration was appropriate to induce motor performance fatigability in pwMS.

Clinical Trial Register

DRKS00021057.
Infant Distress in a Food Delay Task Changes With Development and Predicts Amount Consumed
Authors: Stein Sara F. , Riley Hurley O. , Kaciroti Niko , Rosenblum Katherine L. , Sturza Julie M. , Gearhardt Ashley N. , Grogan-Kaylor Andrew C. , Lumeng Julie C. , Miller Alison L.
Published: April 2022

Objective

Eating behavior regulation emerges during early development and involves general self-regulation (emotional, behavioral), appetite regulation (homeostatic metabolic need) and appetite self-regulation (including both Bottom-Up Food Approach and Bottom-Up Food Avoidance and top-down purposeful self-control of eating). Limited research has investigated developmental trajectories of the regulation of eating behavior before the preschool years. The current study used a novel food delay task to assess infant distress as an early emerging marker of eating behavior regulation constructs across early infancy and examine associations with amount of milk consumed.

Method

Mother-infant dyads (n = 179) completed the Ability to Delay Gratification for Food in Infants Task (ATDG-FIT) at 2 weeks, 8 weeks, and 16 weeks of age. The ATDG-FIT required infants to wait before being fed while their bottle was present, but not accessible (3-min Pre-Feeding Delay). After this, the infant was fed for 1 min, then the feeding was paused for 30 s (Mid-Feeding Delay). Infant distress was coded during each feeding delay period and the amount of milk consumed was measured.

Results

The mean proportion of distress during the Pre-Feeding Delay period decreased from 8 to 16 weeks of age (F(2,230) = 15.02, p < 0.001), whereas the mean proportion of distress during the Mid-Feeding Delay increased from 2 to 8 weeks of age (F(2,230) = 27.04, p < 0.001). There was a positive interaction between distress during Mid-Feeding Delay and infant age predicting the amount consumed in the protocol (ß = 0.30, p = 0.022), suggesting that the association between distress during this part of the task and amount consumed strengthens as infants get older.

Conclusion

The ATDG-FIT may be an effective method to assess emerging eating behavior regulation constructs during early infancy.
Digital Solutions to Diagnose and Manage Postbariatric Hypoglycemia
Authors: Schönenberger Katja A. , Cossu Luca , Prendin Francesco , Cappon Giacomo , Wu Jing , Fuchs Klaus L. , Mayer Simon , Herzig David , Facchinetti Andrea , Bally Lia
Published: April 2022

Postbariatric hypoglycemia (PBH) is an increasingly recognized late metabolic complication of bariatric surgery, characterized by low blood glucose levels 1–3 h after a meal, particularly if the meal contains rapid-acting carbohydrates. PBH can often be effectively managed through appropriate nutritional measures, which remain the cornerstone treatment today. However, their implementation in daily life continues to challenge both patients and health care providers. Emerging digital technologies may allow for more informed and improved decision-making through better access to relevant data to manage glucose levels in PBH. Examples include applications for automated food analysis from meal images, digital receipts of purchased food items or integrated platforms allowing the connection of continuously measured glucose with food and other health-related data. The resulting multi-dimensional data can be processed with artificial intelligence systems to develop prediction algorithms and decision support systems with the aim of improving glucose control, safety, and quality of life of PBH patients. Digital innovations, however, face trade-offs between user burden vs. amount and quality of data. Further challenges to their development are regulatory non-compliance regarding data ownership of the platforms acquiring the required data, as well as user privacy concerns and compliance with regulatory requirements. Through navigating these trade-offs, digital solutions could significantly contribute to improving the management of PBH.
Characterization, Antioxidant Activities, and Pancreatic Lipase Inhibitory Effect of Extract From the Edible Insect Polyrhachis vicina
Authors: Zhang Zongqi , Chen Sicong , Wei Xunfan , Xiao Jinhua , Huang Dawei
Published: April 2022

Oxidative stress and obesity are critical risk factors for metabolic syndrome. The consumption of functional food ingredients can a viable strategy to alleviate oxidative stress and obesity. In this study, the hydro-ethanolic extract of the edible insect Polyrhachis vicina was prepared and its bioactive components were characterized. The total polyphenol contents, total flavonoid contents, antioxidant and pancreatic lipase (PL) inhibitory activities of the extract were determined in vitro. In total, 60 bioactive components were tentatively identified in the P. vicina extract. Polyphenols and fatty acids were further quantified using LC-MS and GC-MS, respectively. P. vicina extract possessed excellent antioxidant and PL inhibition activities. Salicylic acid, gallic acid, liquiritigenin, and naringenin, which were the major polyphenols in the P. vicina extract, interacted with PL through hydrogen bonding, hydrophilic or hydrophobic and pi-cation interactions. Thus, P. vicina extract can be used as a nutraceutical to alleviate oxidative stress-induced disease and manage obesity.
Sustainable Upcycling of Fisheries and Aquaculture Wastes Using Fish-Derived Cold-Adapted Proteases
Authors: Khiari Zied
Published: April 2022

The fisheries and aquaculture industries are some of the major economic sectors in the world. However, these industries generate significant amounts of wastes that need to be properly managed to avoid serious health and environmental issues. Recent advances in marine waste valorization indicate that fish waste biomass represents an abundant source of high-value biomolecules including enzymes, functional proteins, bioactive peptides, and omega-3 rich oils. Enzyme-assisted processes, for the recovery of these value-added biomolecules, have gained interest over chemical-based processes due to their cost-effectiveness as well as their green and eco-friendly aspects. Currently, the majority of commercially available proteases that are used to recover value-added compounds from fisheries and aquaculture wastes are mesophilic and/or thermophilic that require significant energy input and can lead to unfavorable reactions (i.e., oxidation). Cold-adapted proteases extracted from cold-water fish species, on the other hand, are active at low temperatures but unstable at higher temperatures which makes them interesting from both environmental and economic points of view by upcycling fish waste as well as by offering substantial energy savings. This review provides a general overview of cold-adapted proteolytic enzymes from cold-water fish species and highlights the opportunities they offer in the valorization of fisheries and aquaculture wastes.
Efficacy and Biomarker Exploration of Sintilimab Combined With Chemotherapy in the Treatment of Advanced Penile Squamous Cell Carcinoma—A Report of Two Cases
Authors: Mei Xinkuan , Zhao Yanyan , Zhang Yiruo , Liao Jinhua , Jiang Chen , Qian Hesheng , Du Yingying
Published: April 2022

Penile squamous cell carcinoma is a rare malignant tumor of the male reproductive system. We report two cases of advanced penile squamous cell carcinoma with persistent partial response/complete response after sintilimab combined with chemotherapy and analyze the relevant tumor biomarkers.
Radiomics for the Preoperative Evaluation of Microvascular Invasion in Hepatocellular Carcinoma: A Meta-Analysis
Authors: Li Liujun , Wu Chaoqun , Huang Yongquan , Chen Jiaxin , Ye Dalin , Su Zhongzhen
Published: April 2022

Background

Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). To perform a meta-analysis to investigate the diagnostic performance of radiomics for the preoperative evaluation of MVI in HCC and the effect of potential factors.

Materials and Methods

A systematic literature search was performed in PubMed, Embase, and the Cochrane Library for studies focusing on the preoperative evaluation of MVI in HCC with radiomics methods. Data extraction and quality assessment of the retrieved studies were performed. Statistical analysis included data pooling, heterogeneity testing and forest plot construction. Meta-regression and subgroup analyses were performed to reveal the effect of potential explanatory factors [design, combination of clinical factors, imaging modality, number of participants, and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) applicability risk] on the diagnostic performance.

Results

Twenty-two studies with 4,129 patients focusing on radiomics for the preoperative prediction of MVI in HCC were included. The pooled sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were 84% (95% CI: 81, 87), 83% (95% CI: 78, 87) and 0.90 (95% CI: 0.87, 0.92). Substantial heterogeneity was observed among the studies (I²=94%, 95% CI: 88, 99). Meta-regression showed that all investigative covariates contributed to the heterogeneity in the sensitivity analysis (P < 0.05). Combined clinical factors, MRI, CT and number of participants contributed to the heterogeneity in the specificity analysis (P < 0.05). Subgroup analysis showed that the pooled sensitivity, specificity and AUC estimates were similar among studies with CT or MRI.

Conclusion

Radiomics is a promising noninvasive method that has high preoperative diagnostic performance for MVI status. Radiomics based on CT and MRI had a comparable predictive performance for MVI in HCC. Prospective, large-scale and multicenter studies with radiomics methods will improve the diagnostic power for MVI in the future.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259363, identifier CRD42021259363.
Preoperative Metabolic Syndrome and HDL-C Level Predict the Prognosis of Patients Following Radical Cystectomy: A Propensity Score Matching Study
Authors: Liu Zenan , Bi Hai , He Wei , Zhu Xuehua , He Jide , Lu Min , Lu Jian
Published: April 2022

Objective

To investigate the prognostic significance of metabolic syndrome (MetS) and its components in patients with bladder cancer (BCa) treated with radical cystectomy (RC).

Methods

A total of 335 BCa patients who underwent RC between 2004 and 2019 at Peking University Third Hospital (PUTH) were analyzed retrospectively. The Kaplan-Meier method with the log-rank test was performed to assess overall survival (OS) and progression-free survival (PFS). Univariate and multivariate Cox proportional hazard models were conducted to identify the prognostic factors of OS and PFS before and after propensity score matching (PSM).

Results

Enrolled patients were allocated into two groups according to the presence or absence of MetS (n=84 MetS vs n=251 non-MetS), and 82 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In the Kaplan-Meier analysis, MetS was associated with better OS (P=0.031) than the group without MetS. In addition, a body mass index (BMI) ≥ 25 was associated with better OS (P=0.011) and PFS (P=0.031), while low high-density lipoprotein cholesterol (HDL-C) was associated with worse OS (P=0.033) and PFS (P=0.010). In all patients, multivariate Cox analysis showed that hemoglobin, pathologic tumor stage and lymph node status were identified as independent prognostic factors for both OS and PFS, while age, MetS and HDL-C were independent prognostic factors only for OS. Reproducible results of multivariate analysis can still be observed in propensity matched patients. The results of further subgroup analysis revealed that the association of MetS with increased OS (P=0.043) and BMI ≥25 with increased OS (P=0.015) and PFS (P=0.029) was observed in non-muscle invasive bladder cancer (NMIBC) patients.

Conclusions

MetS was independently associated with better OS in BCa patients after RC, and HDL-C was the only component of MetS that was independently associated with worse OS. MetS and HDL-C may become reliable prognostic biomarkers of OS in BCa patients after RC to provide individualized prognostication and assist in the formulation of clinical treatment strategies.
Mechanism of Phellodendron and Anemarrhena Drug Pair on the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics
Authors: Ruan Xiaofeng , Li Wenyuan , Du Peng , Wang Yao
Published: April 2022

Background

This study aims to explore the key targets and signaling pathways of the traditional Chinese medicine Phellodendron and Anemarrhena drug pair (PADP) for the treatment of liver cancer.

Methods

Firstly, bioinformatics technology was used to analyze GSE62232 gene chip to obtain the differential genes of liver cancer. A network pharmacology technology was used to find the active components of PADP and their targets. Secondly, the differential genes were imported into STRING database to draw a PPI network, and network topology structure map combined with Cytoscape software. And the R language was used to identify differential gene targets and pathways through GO and KEGG pathway enrichment analysis. In addition, AutoDock Vina was used for molecular docking of core targets and core compounds. Moreover, GEPIA online analysis tool was used to perform survival analysis of the core target genes. Finally, RT-PCR was used to verify the changes of key target genes. CCK−8 assay was performed to detect cell proliferation. Flow cytometry was performed to detect the cell cycle and apoptotic. Transwell invasion assay was performed to detect cell invasion.

Results

Firstly, a total of 21,654 genes were obtained. After screening, 1019 differential genes were obtained, including 614 down-regulated genes and 405 up-regulated genes. Furthermore, after screening by ADME standards, 52 active ingredients were obtained, of which 37 were Phellodendron and 15 were Anemarrhena. And a total of 36 differential genes have been identified, including 13 up-regulated genes and 23 down-regulated genes. Moreover, through enrichment analysis, we found that PADP may treat liver cancer through multiple channels and multiple pathways including the p53 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway and so on. Secondly, the molecular docking results showed that there was certain affinity between the core compounds and core target genes. In addition, GEPIA online analysis showed that ESR1, AR, CCNB1, CDK1, AKR1C3 and CCNA2 might become potential target genes for the survival and prognosis of PADP for the treatment of liver cancer. Finally, it was found that PADP could up regulate genes ESR1 and AR, down regulate genes CCNB1, CDK1, AKR1C3, and CCNA2. PADP could promote the apoptosis of liver cancer cells, shorten the cell cycle, and inhibit the proliferation and invasion of liver cancer cells.

Conclusion

PADP may treat liver cancer through multiple targets, multiple channels, and multiple pathways, thereby suppressing cancer cells and improving the living quality of patients.
FGF19 Is Coamplified With CCND1 to Promote Proliferation in Lung Squamous Cell Carcinoma and Their Combined Inhibition Shows Improved Efficacy
Authors: Zhang Yanshuang , Wu Tingyu , Li Fan , Cheng Yirui , Han Qing , Lu Xin , Lu Shun , Xia Weiliang
Published: April 2022

Lung squamous cell carcinoma (LUSC) remains as a major cause of cancer-associated mortality with few therapeutic options. Continued research on new driver genes is particularly important. FGF19, a fibroblast growth factor, is frequently observed as amplified in human LUSC, which is also associated with multiple genomic gains and losses. However, the importance of these associated changes is largely unknown. In this study, we aimed to clarify a novel mechanism that link neighboring oncogene co-amplification in the development of LUSC. We found that FGF19 was co-amplified and co-expressed with its neighboring gene CCND1 in a subset of LUSC patients and associated with poor prognosis. Moreover, FGF19 combined with CCND1 promoted the cell cycle progression of LUSC cells. Mechanistically, FGF19 also enhanced CCND1 expression by activating FGFR4-ERK1/2 signaling and strengthening CCND1-induced phosphorylation and inactivation of retinoblastoma (RB). In a murine model of lung orthotopic cancer, knockdown of CCND1 was found to prolong survival by attenuating FGF19-induced cell proliferation. Furthermore, the combination treatment of the FGFR4 inhibitor BLU9931 and the CDK4/6 inhibitor palbociclib potentiated the growth inhibition and arrested cells in G1 phase. In vivo, co-targeting FGFR4 and CDK4/6 also showed marked inhibition of tumor growth than single agent treatment. These findings further elucidate the oncogenic role of FGF19 in LUSC and provide insights into how the co-amplification of neighboring genes synergistically function to promote cancer growth, and combined inhibition against both FGF19 and CCND1 is more effective.