bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractOsteogenesis 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

Abstract
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

AbstractThe 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

AbstractVortex 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

Abstract

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

AbstractAnaplastic 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

Abstract

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 &lt; .05). In the groups combined, non-HDL-C and glucose were positively related to VFMI (r = 0.337 and 0.313, respectively, P &lt; .05), and non-HDL-C and HOMA-IR were negatively related to physical activity (r = −0.411 and −0.368, respectively, P &lt; .05). HOMA-IR was positively related to VFMI in children with CP (r = 0.698, P &lt; .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 &lt; .05).

Conclusion
Children with CP demonstrate early signs of cardiometabolic disease, which are more closely related to increased visceral adiposity than decreased physical activity.