bluuebunny/crossref_metadata_2025 huggingface dataset:
Marine prebiotics mediate decolonization of Pseudomonas aeruginosa from gut by inhibiting secreted virulence factor interactions with mucins and enriching Bacteroides population
Authors: Janapatla Rajendra Prasad , Dudek Anna , Chen Chyi-Liang , Chuang Chih-Hsien , Chien Kun-Yi , Feng Ye , Yeh Yuan-Ming , Wang Yi-Hsin , Chang Hsin-Ju , Lee Yuan-Chuan , Chiu Cheng-Hsun
Published: February 2023

Background

Pseudomonas aeruginosaintestinal carriage rates are significantly higher in immunosuppressed individuals and hospitalized patients who therefore have increased risk of infections and antibiotic-associated diarrhea. To combat intestinal dysbiosis and decolonizeP. aeruginosafrom gastrointestinal tract, we investigated the anti-adherence and gut microbiota modulation properties of marine prebiotic fucoidans.

Methods

Proteomic analysis of culture supernatant was performed by LC–MS/MS. Using lectin-based enzyme-linked immunosorbent assay, hemagglutinin domain interaction and inhibition with biomolecules were studied. We investigated the role of nutritional grade fucoidans in a mouse model and used 16S ribosomal RNA sequencing to examine fecal microbiota composition.

Results

Analysis of culture supernatant proteins indicated the secretion of two-partner secretion (TPS) family proteins, including TpsA1/CdiA2 and TpsA2/CdiA1. Lectin like activity at the N-terminal of TpsA due to a conserved hemagglutinin domain (Pfam identifier [ID] PF05860) mediates binding to mucins that carry multiple fucosylated glycans. Fucose-rich sulfated polysaccharides (fucoidans) and sulfated dextrans were found to be potent inhibitors of the recombinant N-terminal hemagglutinin domain of TpsA (TpsA-NT-HAD) binding to mucins. In a mouse model, antibiotic-induced dysbiosis was essential forP. aeruginosagastrointestinal colonization. After prophylactic oral fucoidans supplementation, a higher proportion (60%) of the mice were decolonized over time and resisted re-colonization, this was associated with remarkable expansion ofBacteroides(post-infection day-3 abundance, 29–50%) and consequential reductions in bloom ofEnterobacteriaceaeandEnterococcaceaepopulations. In the non-supplemented group,Parabacteroidesmediated recovery from dysbiosis but failed to decolonizeP. aeruginosa.

Conclusions

Supplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization ofP. aeruginosafrom gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficialBacteroidespopulation. We suggest the prophylactic use of nutritional grade fucoidans to decolonizeP. aeruginosafrom gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizingP. aeruginosa.
Vascular and pulmonary effects of ibuprofen on neonatal lung development
Authors: Chen Xueyu , Han Dongshan , Wang Xuan , Huang Xuemei , Huang Zilu , Liu Yijun , Zhong Junyan , Walther Frans J. , Yang Chuanzhong , Wagenaar Gerry T. M.
Published: February 2023

Background

Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD).

Methods

We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression.

Results

Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening.

Conclusions

In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.
A review on the role of long non-coding RNA and microRNA network in clear cell renal cell carcinoma and its tumor microenvironment
Authors: Zhang Qi , Ren Hao , Ge Luqi , Zhang Wen , Song Feifeng , Huang Ping
Published: February 2023

Renal cell carcinoma (RCC) is the second lethal urogenital malignancy with the increasing incidence and mortality in the world. Clear cell renal cell carcinoma (ccRCC) is one major subtype of RCC, which accounts for about 70 to 80% of all RCC cases. Although many innovative therapeutic options have emerged during the last few decades, the efficacy of these treatments for ccRCC patients is very limited. To date, the prognosis of patients with advanced or metastatic ccRCC is still poor. The 5-year survival rate of these patients remains less than 10%, which mainly attributes to the complexity and heterogeneity of the tumor microenvironment (TME). It has been demonstrated that long non-coding RNAs (lncRNAs) perform an indispensable role in the initiation and progression of various tumors. They mostly function as sponges for microRNAs (miRNAs) to regulate the expression of target genes, finally influence the growth, metastasis, apoptosis, drug resistance and TME of tumor cells. However, the role of lncRNA/miRNA/mRNA axis in the TME of ccRCC remains poorly understood. In this review, we summarized the biological function of lncRNA/miRNA/mRNA axis in the pathogenesis of ccRCC, then discussed how lncRNA/miRNA/mRNA axis regulate the TME, finally highlighted their potential application as novel biomarkers and therapeutic targets for ccRCC.
Characterizing mobility patterns of forest goers in southern Lao PDR using GPS loggers
Authors: Rerolle Francois , Dantzer Emily , Phimmakong Toula , Lover Andrew , Hongvanthong Bouasy , Phetsouvanh Rattanaxay , Marshall John , Sturrock Hugh , Bennett Adam
Published: February 2023

Background

In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programmes’ elimination efforts. A better understanding of forest-going populations’ mobility patterns and risk associated with specific types of forest-going trips is necessary for countries in the GMS to achieve their objective of eliminating malaria by 2030.

Methods

Between March and November 2018, as part of a focal test and treat intervention (FTAT), 2,904 forest-goers were recruited in southern Lao PDR. A subset of forest-goers carried an “i-Got-U” GPS logger for roughly 2 months, configured to collect GPS coordinates every 15 to 30 min. The utilization distribution (UD) surface around each GPS trajectory was used to extract trips to the forest and forest-fringes. Trips with shared mobility characteristics in terms of duration, timing and forest penetration were identified by a hierarchical clustering algorithm. Then, clusters of trips with increased exposure to dominant malaria vectors in the region were further classified as high-risk. Finally, gradient boosting trees were used to assess which of the forest-goers’ socio-demographic and behavioural characteristics best predicted their likelihood to engage in such high-risk trips.

Results

A total of 122 forest-goers accepted carrying a GPS logger resulting in the collection of 803 trips to the forest or forest-fringes. Six clusters of trips emerged, helping to classify 385 (48%) trips with increased exposure to malaria vectors based on high forest penetration and whether the trip happened overnight. Age, outdoor sleeping structures and number of children were the best predictors of forest-goers’ probability of engaging in high-risk trips. The probability of engaging in high-risk trips was high (~ 33%) in all strata of the forest-going population.

Conclusion

This study characterized the heterogeneity within the mobility patterns of forest-goers and attempted to further segment their role in malaria transmission in southern Lao People’s Democratic Republic (PDR). National control programmes across the region can leverage these results to tailor their interventions and messaging to high-risk populations and accelerate malaria elimination.
The effects of COVID-19 on New York State’s Drug User Health Hubs and syringe service programs: a qualitative study
Authors: Ude Mercy , Behrends Czarina N. , Kelly Shea , Schackman Bruce R. , Clear Allan , Goldberg Rebecca , Gelberg Kitty , Kapadia Shashi N.
Published: February 2023

Background

Syringe service programs (SSPs) deliver critical harm reduction services to people who inject drugs (PWID). Some SSPs in New York State received enhanced funding to provide additional services to combat opioid overdose fatalities. These SSPs, known as Drug User Health Hubs, provide buprenorphine for the treatment of opioid use disorder and other health-related services in addition to their syringe services. While the COVID-19 pandemic posed widespread challenges to the delivery of health services nationwide, the effect of the pandemic on SSPs uniquely impacts PWID. This study examines the impact of COVID-19 on service delivery of Drug User Health Hubs and stand-alone SSPs in New York State.

Methods

Between July 2020 and September 2020, we performed eleven semi-structured virtual interviews with staff from three Health Hub SSPs and three stand-alone SSPs. The interviews explored the effect of the COVID-19 pandemic on SSPs and their clients as well as the changes implemented in response. Interviews were recorded and transcribed. We performed content analysis to identify emerging themes from the data.

Results

Due to the COVID-19 pandemic, some SSPs temporarily shut down while others limited their hours of operation. SSPs modified their service delivery to maintain syringe services and naloxone distribution over other services such as STI and HCV testing. They virtualized components of their services, including telemedicine for the provision of buprenorphine. While SSPs found virtualization to be important for maintaining their services, it negatively impacted the intimate nature of client interactions. Participants also described the impact of the pandemic on the well-being of PWID, including isolation, worsened mental health challenges, and increased drug overdoses.

Conclusions

In response to the COVID-19 pandemic, SSPs demonstrated innovation, adaptability, and togetherness. Despite the challenges posed by the pandemic, SSPs continued to be key players in maintaining access to sterile supplies, buprenorphine, and other services for PWID. In addition to adapting to COVID-19 restrictions, they also responded to the dynamic needs of their clients. Sustainable funding and recognition of the critical role of SSPs in supporting PWID can help to improve outcomes for PWID.
Enterococcus faecalis promotes the progression of colorectal cancer via its metabolite: biliverdin
Authors: Zhang Li , Liu Jing , Deng Mingxia , Chen Xiangliu , Jiang Lushun , Zhang Jiajie , Tao Lisheng , Yu Wei , Qiu Yunqing
Published: February 2023

Background

Enterococcus faecalis (Efa) has been shown to be a “driver bacteria” in the occurrence and development of colorectal cancer (CRC). This study aims to explore the effect of specific metabolites of Efa on CRC.

Methods

The pro-tumor effects of Efa were assessed in colonic epithelial cells. The tumor-stimulating molecule produced by Efa was identified using liquid chromatography mass spectrometry (LC-MS). The proliferative effect of metabolites on CRC cells in vitro was assayed as well. The concentration of vascular endothelial growth factor A (VEGFA) and interleukin-8 (IL-8) was determined using enzyme-linked immunosorbent assay (ELISA). Tubular formation assay of human umbilical vein endothelial cells (HUVEC) and cell migration assay were applied to study angiogenesis. Additionally, western blot analysis was used to investigate key regulatory proteins involved in the angiogenesis pathway. Tumor growth was assessed using mouse models with two CRC cells and human colon cancer organoid.

Results

Co-incubation with the conditioned medium of Efa increased the proliferation of cultured CRC cells. Biliverdin (BV) was determined as the key metabolite produced by Efa using LC-MS screening. BV promoted colony formation and cell proliferation and inhibited cell cycle arrest of cultured CRC cells. BV significantly increased the expression level of IL-8 and VEGFA by regulating the PI3K/AKT/mTOR signaling pathway, leading to the acceleration of angiogenesis in CRC. The up-regulation of proliferation and angiogenesis by BV were also confirmed in mice.

Conclusion

In conclusion, BV, as the tumor-stimulating metabolite of Efa, generates proliferative and angiogenic effects on CRC, which is mainly mediated by the activation of PI3K/AKT/mTOR.
Horse-related injury patterns: a single center report
Authors: Hoffmann M. F. , Bernstorff M. , Kreitz N. , Roetman B. , Schildhauer T. A. , Wenning K. E.
Published: February 2023

Background

For ages, humankind and horses have been closely related to occupational and recreational activities. The dangers of engaging with horses have been previously reported. Among sporting activities, horse riding is well-known for its risks. Despite multiple recommendations to wear protective gear, horse-related activities still comprise the risk of severe injuries. This study aimed to examine: (1) if specific mechanisms are correlated to particular injury patterns and (2) if injury types are related to patient demographics.

Methods

From one level I trauma center, between July 2019 and July 2022 (3 years) all emergency reports and discharge letters were retrospectively reviewed by full-text search regarding horse-related injuries. Patient demographics, body mass index, trauma mechanism, injury types, and initiated treatment were extracted from medical records and analyzed.

Results

During the study period, 95 patients with 99 horse-related injuries were included. The overwhelming majority of the patients was female (93.7%). Age averaged 35.3 years (range 6 to 71). BMI was 23.6 kg/m2. Inpatient treatment was required in 60.6%. Length of hospital stay averaged 10 days. Surgical treatment was performed in 55 patients (55.6%). Open reduction and internal fixation was the most common procedure (74.5%). Trauma mechanism was fall from a horse followed by being hit by a horse (60.6% and 23.2%, respectively). Injured upper extremities counted up for 52.5% followed by spinal and pelvic injuries (23.2%). Spinal and pelvic injuries were related to fall from a horse (p < 0.001). Injuries to the lower extremities were predominantly caused by a kick of the horse when the rider was unmounted (p = 0.001) and negatively related to a fall from a horse (p = 0.002). Ten patients got their fingers tangled while holding the reins and suffered from injuries to the upper extremity (p < 0.001). Three of them required an amputation (30%).

Conclusion

Despite the fact that patients are young and healthy, horse related injuries must not be underestimated. In our study, almost two-thirds of the patients required inpatient treatment and 50% underwent surgery. We could show that patient age was related to injury severity according to the Abbreviated Injury Scale (AIS). Spinal and pelvic injuries were significantly related to a fall from a horse with a significantly greater trauma impact according to the AIS. Therefore, these severe entities need to be ruled out in such events. Accidents caused by holding the reins, may result in serious injuries to the hand with 30% requiring an amputation. Doctors need to be aware of possible horse-related injury patterns to reduce morbidity.
Treatments and whole exon sequencing of a case with multiple primary lung cancer
Authors: Bai Guangyu , Li Yuan , Ji Ying , Peng Yue , Yang Zhenlin , Zhao Liang
Published: February 2023

Introduction

The number of patients with synchronous multiple primary lung cancer (sMPLC) has increased recently. However, diagnosing and selecting the appropriate therapeutic strategy for this type of disease is not simple.

Case presentation

This report presented a case of sMPLC with lymph node metastasis. With no smoking and cancer history, this patient had seven nodules in the right lung and underwent single-portal video-assisted thoracoscopic surgery (VATS). In addition, she received four cycles of chemotherapy after the operation. Whole exon sequencing (WES) was performed in five resected tissue samples (four tumors and one lymph node). We conducted genomic profiling and clone evolution analysis of the five samples. Gene detection helped to confirm that the metastasis lymph node was transferred from one nodule. There was apparent heterogeneity of gene mutations among the five samples of the patient, with only one shared “neurofilament heavy polypeptide” (NEFH) mutation. A dominant substitution of C > T/G > A was found in all the samples. Pyclone model was used to calculate all tissues' cellular prevalence (CP) values, and NEFH mutations were thought to be the ancestral clones. During the follow-up period, residual lesions showed no apparent changes and limited response to chemotherapy.

Conclusions

This report showed an essential role in genomic detection and selecting the appropriate treatment of sMPLC. Surgery remains the primary treatment strategy for this type of disease, and the occurrence and development of sMPLC need more in-depth research.
MitraClip as a therapeutic strategy for post-myocardial infarction mitral regurgitation
Authors: Huang Anwu , Chen Ying , Huang Yiwei , Ji Xiaojun , Jiang Wenbing
Published: February 2023

Mitral regurgitation is a serious complication of post-myocardial infarction, with increasing mortality. Surgery as the primary treatment carries a high risk. MitraClip is a new therapeutic to treat post-myocardial infarction mitral regurgitation. In this case, a 62-year-old male patient suffered from severe heart failure symptoms after emergency coronary intervention and extracorporeal membrane oxygenation support. Based on cardiac echocardiography, severe mitral regurgitation was monitored in this patient. After MitraClip treatment, the patient's condition was gradually improved and discharged successfully. This case highlights that MitraClip is a safe and effective strategy for post-myocardial infarction mitral regurgitation.
Common mouse models of tauopathy reflect early but not late human disease
Authors: Wenger Kathrin , Viode Arthur , Schlaffner Christoph N. , van Zalm Patrick , Cheng Long , Dellovade Tammy , Langlois Xavier , Bannon Anthony , Chang Rui , Connors Theresa R. , Oakley Derek , Renard Bernhard , Rappsilber Juri , Hyman Bradley , Steen Hanno , Steen Judith A.
Published: February 2023

Background

Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level.

Methods

We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation.

Results

Both mouse models accumulate insoluble Tau species during disease. The Tau aggregation is driven by progressive phosphorylation within the proline rich domain and the C-terminus of the protein. This is reflective of early disease stages of human AD and of the pathology of dementia patients carrying the P301L Tau mutation. However, Tau ubiquitination and acetylation, which are important to late-stage human AD are not represented in the mouse models.

Conclusion

AD mouse models that overexpress human Tau using risk mutations are a suitable tool for testing drug candidates that aim to intervene in the early formation of insoluble Tau species promoted by increased phosphorylation of Tau.
In vitro culture of the zoonotic nematode Anisakis pegreffii (Nematoda, Anisakidae)
Authors: Mladineo Ivona , Charouli Artemis , Jelić Filip , Chakroborty Anand , Hrabar Jerko
Published: February 2023

Background

Anisakiasis is a foodborne disease caused by the third-stage larvae (L3) of two species belonging to the genus Anisakis: Anisakis pegreffii and Anisakis simplex sensu stricto. Both species have been the subject of different -omics studies undertaken in the past decade, but a reliable in vitro culture protocol that would enable a more versatile approach to functional studies has never been devised. In nature, A. pegreffii shows a polyxenous life-cycle. It reproduces in toothed whales (final host) and disseminates embryonated eggs via cetacean faeces in the water column. In the environment, a first- (L1) and second-stage larva (L2) develops inside the egg, and subsequently hatched L2 is ingested by a planktonic crustacean or small fish (intermediate host). In the crustacean pseudocoelom, the larva moults to the third stage (L3) and grows until the host is eaten by a fish or cephalopod (paratenic host). Infective L3 migrates into the visceral cavity of its paratenic host and remains in the state of paratenesis until a final host preys on the former. Once in the final host’s gastric chambers, L3 attaches to mucosa, moults in the fourth stage (L4) and closes its life-cycle by becoming reproductively mature.

Methods

Testing two commercially available media (RPMI 1640, Schneider’s Drosophila) in combination with each of the six different heat-inactivated sera, namely foetal bovine, rabbit, chicken, donkey, porcine and human serum, we have obtained the first reliable, fast and simple in vitro cultivation protocol for A. pegreffii.

Results

Schneider’s Drosophila insect media supplemented with 10% chicken serum allowed high reproducibility and survival of adult A. pegreffii. The maturity was reached already at the beginning of the third week in culture. From collected eggs, hatched L2 were maintained in culture for 2 weeks. The protocol also enabled the description of undocumented morphological and ultrastructural features of the parasite developmental stages.

Conclusions

Closing of the A. pegreffii life-cycle from L3 to reproducing adults is an important step from many research perspectives (e.g., vaccine and drug–target research, transgenesis, pathogenesis), but further effort is necessary to optimise the efficient moulting of L2 to infective L3.

Graphical Abstract
Association of triglycerides to high-density lipoprotein cholesterol ratio to identify future prediabetes and type 2 diabetes mellitus: over one-decade follow-up in the Iranian population
Authors: Tohidi Maryam , Asgari Samaneh , Chary Abdolreza , Safiee Siavash , Azizi Fereidoun , Hadaegh Farzad
Published: February 2023

Background

To determine the association between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) for identifying subjects at risk of incident prediabetes and type 2 diabetes mellitus (T2DM).

Methods

In 5064 subjects (men = 2247) aged ≥ 20 years, using Cox proportional hazards regression analyses, the associations of TG/HDL-C with incident prediabetes and T2DM were examined among normoglycemic men and women. Furthermore, the association of this lipid ratio with incident T2DM was also assessed among prediabetic subjects (n = 1414). The multivariable analyses were adjusted for age, body mass index, waist-to-height ratio, wrist circumference, systolic blood pressure, family history of T2DM, education level, history of cardiovascular diseases, and fasting plasma glucose (FPG).

Results

During a median follow-up of 11.2 years, 2140 new cases of prediabetes (men = 1070) and 360 incident T2DM (men = 152) were identified among normoglycemic individuals. In the prediabetic population, 574 new cases of T2DM (men = 252) were developed. Among the whole population, compared to the first quartile (reference), higher quartiles of TG/HDL-C were significantly associated with higher risks of incident prediabetes and T2DM among normoglycemic individuals and incident T2DM in the prediabetic population (all P for trend < 0.001). The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for the fourth quartiles were 1.37(1.20–1.58), 1.92(1.34–2.75), and 1.57(1.22–2.01), respectively. The sex-stratified analyses demonstrated similar significant associations in both sexes; however, TG/HDL-C lost its association with incident T2DM among prediabetic men. Among the normoglycemic population, 1 unit increase in TG/HDL-C was significantly associated with incident prediabetes and T2DM [1.02(1.00–1.03) and 1.06(1.03–1.08), respectively]. The corresponding value for incident T2DM in prediabetic individuals was 1.01(1.00–1.03). In a subgroup population having insulin data (n = 2897), the associations between TG/HDL-C and incident prediabetes and T2DM among normoglycemic individuals generally persisted even after replacing FPG with an index of insulin resistance (IR), i.e., homeostasis model assessment of IR (HOMA-IR) in the adjusted model.

Conclusions

In conclusion, in the normoglycemic population, the increasing value of TG/HDL-C was unfavorably associated with incident prediabetes and T2DM, especially among women. Similarly, TG/HDL-C was associated with incident T2DM in prediabetic individuals. Generally, we found that the correlation between TG/HDL-C and different states of dysglycemia is independent of HOMA-IR.
Mesenchymal stem cells in the treatment of osteogenesis imperfecta
Authors: Lang Erica , Semon Julie A.
Published: February 2023

Osteogenesis imperfecta (OI) is a disease caused by mutations in different genes resulting in mild, severe, or lethal forms. With no cure, researchers have investigated the use of cell therapy to correct the underlying molecular defects of OI. Mesenchymal stem cells (MSCs) are of particular interest because of their differentiation capacity, immunomodulatory effects, and their ability to migrate to sites of damage. MSCs can be isolated from different sources, expanded in culture, and have been shown to be safe in numerous clinical applications. This review summarizes the preclinical and clinical studies of MSCs in the treatment of OI. Altogether, the culmination of these studies show that MSCs from different sources: 1) are safe to use in the clinic, 2) migrate to fracture sites and growth sites in bone, 3) engraft in low levels, 4) improve clinical outcome but have a transient effect, 5) have a therapeutic effect most likely due to paracrine mechanisms, and 6) have a reduced therapeutic potential when isolated from patients with OI.
Predictive value of soluble CD59 for poor 28-day neurological prognosis and all-cause mortality in patients after cardiopulmonary resuscitation: a prospective observatory study
Authors: Wang Ling , Li Rui-Fang , Guan Xiao-Lan , Liang Shuang-Shuang , Gong Ping
Published: February 2023

Background

sCD59, as a soluble form of CD59, is observed in multiple types of body fluids and correlated with the cell damage after ischemia/reperfusion injury. This study aims to observe the dynamic changes of serum sCD59 in patients after restoration of spontaneous circulation (ROSC) and explore the association of serum sCD59 with neurological prognosis and all-cause mortality in patients after ROSC.

Methods

A total of 68 patients after ROSC were prospectively recruited and divided into survivors (n = 23) and non-survivors (n = 45) groups on the basis of 28-day survival. Twenty healthy volunteers were enrolled as controls. Serum sCD59 and other serum complement components, including sC5b-9, C5a, C3a, C3b, C1q, MBL, Bb, and pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), neurological damage biomarkers neuron-specific enolase (NSE) and soluble protein 100β (S100β) were measured by enzyme linked immunosorbent assay on day 1, 3, and 7 after ROSC. Neurologic outcome was assessed using cerebral performance category scores, with poor neurologic outcome defined as 3–5 points.

Results

In the first week after ROSC, serum levels of sCD59, sC5b-9, C5a, C3a, C3b, C1q, MBL, Bb, TNF-α, IL-6, NSE and S100β were significantly elevated in patients after ROSC compared to healthy volunteers, with a significant elevation in the non-survivors compared to survivors except serum C1q and MBL. Serum sCD59 levels were positively correlated with serum sC5b-9, TNF-α, IL-6, NSE, S100β, SOFA score and APACHE II score. Moreover, serum sCD59 on day 1, 3, and 7 after ROSC could be used for predicting poor 28-day neurological prognosis and all-cause mortality. Serum sCD59 on day 3 had highest AUCs for predicting poor 28-day neurological prognosis [0.862 (95% CI 0.678–0.960)] and 28-day all-cause mortality [0.891 (95% CI 0.769–0.962)]. In multivariate logistic regression analysis, the serum level of sCD59D1 was independently associated with poor 28-day neurological prognosis and all-cause mortality.

Conclusions

The elevated serum level of sCD59 was positively correlated with disease severity after ROSC. Moreover, serum sCD59 could have good predictive values for the poor 28-day neurological prognosis and all-cause mortality in patients after ROSC.
Cancelable biometric schemes for Euclidean metric and Cosine metric
Authors: Jiang Yubing , Shen Peisong , Zeng Li , Zhu Xiaojie , Jiang Di , Chen Chi
Published: February 2023

The handy biometric data is a double-edged sword, paving the way of the prosperity of biometric authentication systems but bringing the personal privacy concern. To alleviate the concern, various biometric template protection schemes are proposed to protect the biometric template from information leakage. The preponderance of existing proposals is based on Hamming metric, which ignores the fact that predominantly deployed biometric recognition systems (e.g. face, voice, gait) generate real-valued templates, more applicable to Euclidean metric and Cosine metric. Moreover, since the emergence of similarity-based attacks, those schemes are not secure under a stolen-token setting. In this paper, we propose a succinct biometric template protection scheme to address such a challenge. The proposed scheme is designed for Euclidean metric and Cosine metric instead of Hamming distance. Mainly, the succinct biometric template protection scheme consists of distance-preserving, one-way, and obfuscation modules. To be specific, we adopt location sensitive hash function to realize the distance-preserving and one-way properties simultaneously and use the modulo operation to implement many-to-one mapping. We also thoroughly analyze the proposed scheme in three aspects: irreversibility, unlinkability and revocability. Moreover, comprehensive experiments are conducted on publicly known face databases. All the results show the effectiveness of the proposed scheme.
Effect of vortex generator spanwise height distribution pattern on aerodynamic characteristics of a straight wing
Authors: Hao Lishu , Hu Bao , Gao Yongwei , Wei Binbin
Published: February 2023

Vortex generator (VG) is a passive flow control technology, which can effectively inhibit flow separation. Recently, significant research efforts have been devoted to the study on the application of VG in airfoil, wing/blade and aircraft flow separation inhibition. However, the research on the variable height distribution of VG along the wingspan still lacks. This study focuses on the experimental investigation of the influence of variable height distribution of ramp VG on aerodynamic characteristics. First, VG was designed, such that it was composed of two parts, one fixed region and one deformed region, which allowed for height modification. The height of VGs along the wingspan presented equal-height, triangular and trapezoidal distribution, forming a total of 15 VG layouts. Then, the connection mode of the model, the change of angle of attack and the collection and processing of aerodynamic data were introduced. Finally, a wind tunnel experiment was performed to investigate the influence of height distribution of VG on aerodynamic characteristics of wing. The experimental results show that: (1) the height distribution of the three types of VGs could inhibit the stall flow and improve the aerodynamic performance of the wing; (2) “Triangular translation 3” and “Trapezoidal translation 2” were the best layouts, both of which could increase the maximum lift coefficient, delay stall, and significantly increase the lift-to-drag ratio at high angle of attack; (3) the influence of VG height and position factors on wing stall characteristics was analyzed by using the rough set theory, and the key position information of VG arrangement was provided. This study indicates that the variable height distribution is obviously better than the equal height distribution, which can provide ideas and references for the active control of variable height distribution of VGs.
A Clinical-Genetic Risk Score for Predicting Cancer-Associated Venous Thromboembolism: A Development and Validation Study Involving Two Independent Prospective Cohorts
Authors: Muñoz Andrés , Ay Cihan , Grilz Ella , López Sonia , Font Carme , Pachón Vanesa , Castellón Victoria , Martínez-Marín Virginia , Salgado Mercedes , Martínez Eva , Calzas Julia , Ortega Laura , Rupérez Ana , Salas Eduardo , Pabinger Ingrid , Soria Jose Manuel
Published: February 2023

PURPOSE

Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis.

METHODS

The new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population.

RESULTS

Nine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m2 were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001).

CONCLUSION

The ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.
Fluid Restriction Reduces Delayed Hyponatremia and Hospital Readmissions After Transsphenoidal Surgery
Authors: Cooper Odelia , Lis Rita , Bonert Vivien , Labadzhyan Artak , Liu Ning-Ai , Ben-Shlomo Anat , Ljubimov Vladimir , Krutikova Viktoria , Mamelak Adam N
Published: February 2023

Context

Postoperative hyponatremia leads to prolonged hospital length of stay and readmission within 30 days.

Objective

To assess 3 strategies for reducing rates of postoperative hyponatremia and analyze risk factors for hyponatremia.

Design

Two retrospective analyses and 1 prospective study.

Setting

Tertiary referral hospital.

Patients

Patients undergoing transsphenoidal surgery for pituitary adenomas and other sellar and parasellar pathologies.

Intervention(s)

Phase 1: no intervention. Phase 2: postoperative day (POD) 7 sodium testing and patient education. Phase 3: fluid restriction to 1 L/day on discharge in addition to phase 2 interventions.

Main outcome measures

Rates of early and delayed hyponatremia and readmissions. Secondary outcomes were risk factors for hyponatremia and readmission costs.

Results

In phase 1, 296 patients underwent transsphenoidal surgery. Twenty percent developed early and 28% delayed hyponatremia. Thirty-eight percent underwent POD 7 sodium testing. Readmission rates were 15% overall and 4.3% for hyponatremia. In phase 2 (n = 316), 22% developed early and 25% delayed hyponatremia. Eighty-nine percent complied with POD 7 sodium testing. Readmissions were unchanged although severity of hyponatremia was reduced by 60%. In phase 3 (n = 110), delayed hyponatremia was reduced 2-fold [12.7%, relative risk (RR) = 0.52] and readmissions 3-fold [4.6%, RR = 0.30 (0.12–0.73)]; readmissions for hyponatremia were markedly reduced. Hyponatremia readmission increased costs by 30%.

Conclusions

Restricting fluid to 1 L/day on discharge decreases rates of delayed hyponatremia and readmissions by 50%. Standardized patient education and POD 7 sodium testing decreases severity of hyponatremia but does not impact readmission rates. These protocols should be considered standard practice for patients undergoing transsphenoidal surgery.
LINC00886 Negatively Regulates Malignancy in Anaplastic Thyroid Cancer
Authors: Ma Ben , Luo Yi , Xu Weibo , Han Litao , Liu Wanlin , Liao Tian , Yang Yichen , Wang Yu
Published: February 2023

Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. This study aimed to identify specific long noncoding RNAs (lncRNAs) associated with ATC, and further investigated their biological functions and molecular mechanism underlying regulation of malignancy in ATC. We searched for lncRNAs associated with dedifferentiation and screened out specific lncRNAs significantly deregulated in ATC by using transcriptome data of dedifferentiation cancers from Fudan University Shanghai Cancer Center (FUSCC) and the Gene Expression Omnibus (GEO) database. The above lncRNAs were analyzed to identify a potential biomarker in thyroid cancer patients from the FUSCC, GEO, and The Cancer Genome Atlas, which was then investigated for its functional roles and molecular mechanism in ATC in vitro. The clinicopathological association analyses revealed that LINC00886 expression was significantly correlated with dedifferentiation and suppressed in ATC. In vitro, LINC00886 was confirmed to negatively regulate cell proliferation, and cell migration and invasion of ATC. LINC00886 physically interacted with protein kinase R (PKR) and affected its stability through the ubiquitin/proteasome-dependent degradation pathway in the ATC cell. Decreased PKR caused by downregulation of LINC00886 enhanced the activity of eukaryotic initiation factor 2α (eIF2α) via reducing phosphorylation of eIF2α and thus promoted protein synthesis to maintain ATC malignancy. Our findings identify LINC00886 as a novel biomarker of thyroid cancer and suggest that LINC00886/PKR/eIF2α signaling is a potential therapeutic target in ATC.
Cardiometabolic Risk and Its Relationship With Visceral Adiposity in Children With Cerebral Palsy
Authors: Batson Trevor , Lee Junsoo , Kindler Joseph M , Pollock Norman K , Barbe Mary F , Modlesky Christopher M
Published: February 2023

Context

Adults with cerebral palsy (CP) display a higher prevalence of cardiometabolic disease compared with the general population. Studies examining cardiometabolic disease risk in children with CP are limited.

Objective

The purpose of this study was to determine if children with CP exhibit higher cardiometabolic risk than typically developing children, and to examine its relationship with visceral adiposity and physical activity.

Methods

Thirty ambulatory children with CP and 30 age-, sex-, and race-matched typically developing control children were tested for blood lipids, glucose, and the homeostatic model assessment of insulin resistance (HOMA-IR). Visceral fat was assessed using dual-energy x-ray absorptiometry. Physical activity was assessed using accelerometer-based monitors.

Results

Children with CP had higher total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (non-HDL-C), glucose, prevalence of dyslipidemia, prevalence of prediabetes, and visceral fat mass index (VFMI) and lower physical activity than controls (all P < .05). In the groups combined, non-HDL-C and glucose were positively related to VFMI (r = 0.337 and 0.313, respectively, P < .05), and non-HDL-C and HOMA-IR were negatively related to physical activity (r = −0.411 and −0.368, respectively, P < .05). HOMA-IR was positively related to VFMI in children with CP (r = 0.698, P < .05), but not in controls. Glucose was not related to physical activity in children with CP, but it was negatively related in controls (r = −0.454, P < .05).

Conclusion

Children with CP demonstrate early signs of cardiometabolic disease, which are more closely related to increased visceral adiposity than decreased physical activity.
Mechanically Ventilated Patients With Coronavirus Disease 2019 Had a Higher Chance of In-Hospital Death If Treated With High-Flow Nasal Cannula Oxygen Before Intubation
Authors: Nurok Michael , Friedman Oren , Driver Matthew , Sun Nancy , Kumaresan Abirami , Chen Peter , Cheng Susan , Talmor Daniel S. , Ebinger Joseph
Published: February 2023

BACKGROUND:

The impact of high-flow nasal cannula (HFNC) on outcomes of patients with respiratory failure from coronavirus disease 2019 (COVID-19) is unknown. We sought to assess whether exposure to HFNC before intubation was associated with successful extubation and in-hospital mortality compared to patients receiving intubation only.

METHODS:

This single-center retrospective study examined patients with COVID-19-related respiratory failure from March 2020 to March 2021 who required HFNC, intubation, or both. Data were abstracted from the electronic health record. Use and duration of HFNC and intubation were examined‚ as well as demographics and clinical characteristics. We assessed the association between HFNC before intubation (versus without) and chance of successful extubation and in-hospital death using Cox proportional hazards models adjusting for age, sex, race/ethnicity, obesity, hypertension, diabetes, prior chronic obstructive pulmonary disease or asthma, HCO3, CO2, oxygen-saturation-to-inspired-oxygen (S:F) ratio, pulse, respiratory rate, temperature, and length of stay before intervention.

RESULTS:

A total of n = 440 patients were identified, of whom 311 (70.7%) received HFNC before intubation, and 129 (29.3%) were intubated without prior use of HFNC. Patients who received HFNC before intubation had a higher chance of in-hospital death (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.06–4.05). No difference was found in the chance of successful extubation between the 2 groups (0.70, 0.41–1.20).

CONCLUSIONS:

Among patients with respiratory failure from COVID-19 requiring mechanical ventilation, patients receiving HFNC before intubation had a higher chance of in-hospital death. Decisions on initial respiratory support modality should weigh the risks of intubation with potential increased mortality associated with HFNC.
Perioperative Red Blood Cell Transfusion Is Associated With Adverse Cardiovascular Outcomes in Heart Valve Surgery
Authors: Kim Hee Jung , Kim Ji Eon , Lee Ji Yoon , Lee Seung Hyung , Jung Jae Seung , Son Ho Sung
Published: February 2023

BACKGROUND:

We examined the relationship between blood transfusion and long-term adverse events to evaluate the clinical impact of red blood cell (RBC) transfusion on patients undergoing cardiac valve surgery.

METHODS:

From the National Health Insurance Service database, individuals undergoing heart valve surgery were verified, including aortic valve (AV), mitral valve (MV), tricuspid valve (TV), and complex valves (more than 2 valve surgeries). The interested outcomes were incidence of death, ischemic stroke, hemorrhagic stroke, and admission for myocardial infarction during follow-up. Associations between perioperative RBC transfusion and long-term cardiovascular events were analyzed with Cox-proportional hazard model.

RESULTS:

Perioperative RBC transfusion (±2 days from the day of surgery) was categorized into 0, 1, 2, and >3 units based on the number of packs transfused. From 2003 to 2019, the data of 58,299 individuals were retrieved (51.6% were male and 58% were aged above 60 years). The median follow-up duration was 5.53 years. Of the total cohort, 86.5% received at least 1 transfusion. In multivariable analysis, adverse cardiovascular event risk proportionally increased with transfusion in a dose-dependent manner. The adjusted hazard ratios and 95% confidence intervals of outcomes after the transfusion of 1, 2, and ≥3 units compared to those with no transfusion were as follows: death, 1.53 (1.41–1.66), 1.97 (1.81–2.14), and 3.03 (2.79–3.29); ischemic stroke, 1.27 (1.16–1.39), 1.31 (1.19–1.44), and 1.51 (1.38–1.66); hemorrhagic stroke, 1.38 (1.16–1.66), 1.71 (1.43–2.05), and 2.31 (1.94–2.76); and myocardial infarction 1.35 (1.13–1.62), 1.60 (1.33–1.91), and 1.99 (1.66–2.38), respectively (all P < .01).

CONCLUSIONS:

In the analysis of the national cohort, perioperative RBC transfusion during heart valve surgery was associated with adverse cardiovascular outcomes correlated with the volume of RBC transfusion.
Direct Comparison of Peak Bulk Flow Rate of Programmable Intermittent Epidural Bolus and Manual Epidural Bolus Using a Closed-End Multiorifice Catheter: An Experimental Study
Authors: Younger Joshua D. , Faryami Ahmad , Prasad Monica , Viar Daniel , Menkara Adam , Tang Amy , Harris Carolyn A.
Published: February 2023

BACKGROUND:

The programmable intermittent epidural bolus (PIEB) has been popularized as the optimal delivery technique for labor analgesia. Suggested advantages of this method are less local anesthetic consumption, improved maternal satisfaction, potentially shorter duration of labor, and decreased workload requirements for the anesthesia providers. However, a manual bolus is still routinely used for breakthrough pain when the PIEB is underperforming.

METHODS:

We conducted a laboratory-based study to quantify the flow through a multiorifice epidural catheter using the PIEB setting on an epidural pump compared to the manual epidural bolus. Four syringe volumes, 3, 5, 10, and 20 mL, were selected for this experiment. The flow in a manual bolus was also studied with and without the presence of an epidural catheter filter. A generalized estimating equation analysis was done to compare data between the groups.

RESULTS:

Regardless of the syringe size, there was a several-fold increase in flow when a manual bolus was used compared to a pump-administered dose, with the highest difference in the peak flow rate observed in 3-mL boluses with up to a 12-fold difference, while the difference was, at most, 7-fold in 5-mL and 10-mL boluses. Manual boluses without a filter achieve a mean peak flow rate higher than manual boluses with a filter.

CONCLUSIONS:

Our study found that manual boluses produced a higher flow rate compared to the CADD-Solis epidural pump (Smiths Medical). This study also found that the placement of a particulate filter reduces the flow rates generated while bolusing. Bulk flow rate is directly correlated with induced pressure and solution spread. Because higher bolus pressure has been shown to provide a more efficient distribution of local anesthetic and more efficient pain relief, these results may have impactful clinical significance and will pave the way for future studies.