Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial and Temporal Distributions of Short-, Medium-, and Long-Chain Chlorinated Paraffins in Sediment Cores from nine Lakes in China.

The spatial and temporal distributions of short-, medium-, and long- chain chlorinated paraffins (SCCPs, MCCPs, and LCCPs) were studied in sediment cores and surface sediment from nine lakes in China. The highest total CP concentrations in surface sediment were found in the plateau lakes of southwest China, followed by lakes in the northeast, east, and remote northwest. The concentrations of three CP groups in cores showed an increasing trend from the 1970s to 2014, with the most rapid increase occurring from the late 2000s to 2014, consistent with the statistics on historical production of CPs in China. The three CP groups showed site-specific profiles in sediments from the nine lakes, and their percentages changed with sedimentary years. In sediment samples with dated year after 1980, MCCPs were dominant in sediment from Lakes Sihailongwan maar, Taihu, Erhai and Chenghai, and LCCPs were predominant compounds in other five lakes. The proportions of LCCPs rapidly increased after 1980, reflecting the increasing production and usage of LCCPs in China. The total burdens of ∑SCCPs, ∑MCCPs, and ∑LCCPs in sediment prior to 2006 were estimated to be 0.26-5100, 0.29-21000, and 0.07-4300 kg, respectively, which were 1.4-440-fold higher than those of ∑PBDEs.
Polyurethane tissue adhesives for annulus fibrosus repair: Mechanical restoration and cytotoxicity

The microdiscectomy used for the treatment of intervertebral disc disorders leaves an open incision in the annulus fibrosus that must be sealed to avoid re-herniation and other subsequent degenerations. In this study, we developed an injectable and in situ polymerizable polyurethane adhesive as a long-term post-surgical annulus fibrosus repair strategy. It was investigated the chemical structure of the urethane-based adhesive and its physico-chemical, viscoelastic, kinetic, and in vitro cytotoxic properties. The adhesive formulated from the polycarbonate diol with the highest molar mass was the one that exhibited a compressive behavior closest to the intervertebral disc outer region, and therefore, the most suitable for restoration. This adhesive showed 18-day stability under moisture and required a preparation time of 10 h at 60°C before use. The material also adhered covalently to gelatin (without catalyst or initiator) and positively impacted cell proliferation after its polymerization, which are essential requirements for clinical translation. These findings confirmed the ability of the polyurethane adhesive to act as an annulus fibrosus sealant, although further improvements in its formulation are necessary.
CAR T cells for brain tumors: Lessons learned and road ahead

Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the potential to improve outcomes for patients with brain tumors. Chimeric antigen receptors (CAR) T cells, a promising immunotherapeutic modality, utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The remarkable clinical response rates of CD19‐targeted CAR T cells and early clinical experiences in glioblastoma demonstrating safety and evidence for disease modifying activity support the potential of further advancements ultimately providing clinical benefit for patients. The brain, however, is an immune specialized organ presenting unique and specific challenges to immune‐based therapies. Remaining barriers to be overcome for achieving effective CAR T cell therapy in the central nervous system (CNS) include tumor antigenic heterogeneity, an immune‐suppressive microenvironment, unique properties of the CNS that limit T cell entry, and risks of immune‐based toxicities in this highly sensitive organ. This review will summarize preclinical and clinical data for CAR T cell immunotherapy in glioblastoma and other malignant brain tumors, including present obstacles to advancement.
In Vivo Intrathecal Tracer Dispersion in Cynomolgus Monkey Validates Wide Biodistribution Along Neuraxis

Objective: It is commonly believed that in intrathecal (IT) drug delivery, agent distribution is confined to a narrow region close to the injection site, thereby undermining the efficacy of the method. Methods: To test the claim, multimodal in vivo imaging was used to experimentally observe the effects of IT infusion in cynomolgus monkey, looking at cerebrospinal fluid flow, anatomy, and dispersion of a radiolabeled tracer. Results: At high infusion rates, the tracer reached the cervical region after only 2 h, demonstrating rapid and wide distribution. The same in vivo nonhuman primate imaging data also provided evidence in support of a computational fluid dynamic model for the prediction of drug distribution following IT injection. Tracer dispersion was predicted in two specimens matching the distribution acquired with positron emission tomography (PET). For the third specimen, tracer dispersion simulations were conducted as a blind study: predictions were made before in vivo biodistribution data was known. In all cases, the computational fluid dynamics (CFD) predictions of drug dispersion after IT administration showed close spatio-temporal agreement with tracer biodistribution in vivo. Conclusion: Validation by in vivo nonhuman primate data confirms our ability to predict the biodistribution of intrathecally administered agents in subject-specific models of the central nervous system from first principles. Significance: The experiments reinstate IT delivery as a viable administration method when targeting molecules to the whole spine or the brain. The proposed computational methodology enables rational design of novel therapies for neurological diseases that require reliable, efficient, and safe delivery of therapeutic agents to specific target sites in the central nervous system.
Perceptual-Aware Sketch Simplification Based on Integrated VGG Layers

Deep learning has been recently demonstrated as an effective tool for raster-based sketch simplification. Nevertheless, it remains challenging to simplify extremely rough sketches. We found that a simplification network trained with a simple loss, such as pixel loss or discriminator loss, may fail to retain the semantically meaningful details when simplifying a very sketchy and complicated drawing. In this paper, we show that, with a well-designed multi-layer perceptual loss, we are able to obtain aesthetic and neat simplification results preserving semantically important global structures as well as fine details without blurriness and excessive emphasis on local structures. To do so, we design a multi-layer discriminator by fusing all VGG feature layers to differentiate sketches and clean lines. The weights used in layer fusing are automatically learned via an intelligent adjustment mechanism. Furthermore, to evaluate our method, we compare our method to state-of-the-art methods through multiple experiments, including visual comparison and intensive user study.
Relationship between electromyographic activity of knee joint muscles with vertical and posterior ground reaction forces in anterior cruciate ligament reconstructed patients during a single leg vertical drop landing task

ABSTRACT The objective of the present study is to examine the relation between activity patterns of knee joint muscles with vertical and posterior ground reaction forces (VGRF and PGRF, respectively) in patients after anterior cruciate ligament reconstruction (ACLR). Twenty males post-ACLR participated in this cross-sectional study. The association between muscle activity with VGRF and PGRF was assessed during a single leg vertical drop-landing task. There were strong negative associations between preparatory VL, VM and MG activity and PGRF (P< 0.05). Strong positive associations were found between reactive VM and LH activity with PGRF (P< 0.05). Preparatory co-activation of VM: MH had significant negative associations with VGRF (P< 0.05) and reactive co-activation of VL:LH had a significant positive relation with PGRF(P< 0.05). Greater preparatory activity and co-activation of knee muscles were associated with lower peak PGRF and VGRF, whereas greater reactive activity and co-activation of knee muscles was associated with greater peak PGRF and VGRF. According to our findings, both activity and co-activation of knee muscles during the preparatory phase were associated with reduced PGRF and VGRF, respectively in ACLR patients; thus, incorporating exercises in order to increase preparatory activity and co-activation of knee joint muscles into rehabilitation programs in ACLR patients seems necessary.
Differential focus on probability and losses between young and older adults in risky decision-making

ABSTRACT We examined young and older adults’ use of descriptive information about risk (i.e., probability and expected value) in financial decision-making. In Experiment 1, participants chose between lotteries in pairs of bets that offered either two risky gains or one risky gain and one sure gain. Whereas they showed a strong and indiscriminate preference for high-probability gambles in risky-risky pairs, they selected sure options at high rates and risky options at low rates in risky-sure pairs, with slightly stronger effects in older relative to young adults due to age differences in ability. Experiment 2 involved the same task but in terms of losses. Participants, especially older adults, preferred low-probability gambles not accounted for by age differences in ability. Results suggest minimal consideration of expected value and a strong focus on probabilities in decision-making. They also suggest that cognitive ability and chronic goals differentially influence age effects depending on risk context.
Scanpath similarity measure reveals not only a decreased social preference, but also an increased nonsocial preference in individuals with autism

We compared scanpath similarity in response to repeated presentations of social and nonsocial images representing natural scenes in a sample of 30 participants with autism spectrum disorder and 32 matched typically developing individuals. We used scanpath similarity (calculated using ScanMatch) as a novel measure of attentional bias or preference, which constrains eye-movement patterns by directing attention to specific visual or semantic features of the image. We found that, compared with the control group, scanpath similarity of participants with autism was significantly higher in response to nonsocial images, and significantly lower in response to social images. Moreover, scanpaths of participants with autism were more similar to scanpaths of other participants with autism in response to nonsocial images, and less similar in response to social images. Finally, we also found that in response to nonsocial images, scanpath similarity of participants with autism did not decline with stimulus repetition to the same extent as in the control group, which suggests more perseverative attention in the autism spectrum disorder group. These results show a preferential fixation on certain elements of social stimuli in typically developing individuals compared with individuals with autism, and on certain elements of nonsocial stimuli in the autism spectrum disorder group, compared with the typically developing group.
Group sequential adaptive designs in series of time-to-event randomised trials in rare diseases: A simulation study

In rare diseases, fully powered large trials may not be doable in a reasonable time frame even with international collaborations. In a previous work, we proposed an approach based on a series of smaller parallel group two-arm randomised controlled trials (RCT) performed over a long research horizon. Within the series of trials, the treatment selected after each trial becomes the control treatment of the next one. We concluded that running more trials with smaller sample sizes and relaxed α-levels leads in the long term and under reasonable assumptions to larger survival benefits with a moderate increase of risk as compared to traditional designs based on larger but fewer trials designed to meet stringent evidence criteria. We now extend this quantitative framework with more ‘flexible’ designs including interim analyses for futility and/or efficacy, and three-arm adaptive designs with treatment selection at interim. In the simulation study, we considered different disease severities, accrual rates, and hypotheses of how treatments improve over time. For each design, we estimated the long-term survival benefit as the relative difference in hazard rates between the end and the start of the research horizon, and the risk defined as the probability of selecting at the end of the research horizon a treatment inferior to the initial control. We assessed the impact of the α-level and the choice of the stopping rule on the operating characteristics. We also compared the performance of series based on two- vs. three-arm trials. We show that relaxing α-levels within the limit of 0.1 is associated with larger survival gains and moderate increase of risk which remains within acceptable ranges. Including an interim analysis with a futility rule is associated with an additional survival gain and a better risk control as compared to series with no interim analysis, when the α-level is below or equal to 0.1, whereas the benefit of including an interim analysis is rather small for higher α-levels. Including an interim analysis for efficacy yields almost no additional gain. Series based on three-arm trials are associated with a systematic improvement in terms of survival gain and risk control as compared to series of two-arm trials.
Verbal fluency in Mexican Spanish-speaking subjects with high educational level: Ranking of letters and semantic categories

ABSTRACT Introduction: Verbal fluency tasks are useful tools in clinical practice and research studies across languages and contexts, but specific data obtained using Spanish phonological tasks and semantic tasks with different levels of difficulty are lacking. The present study aimed to determine the difficulty level of a phonological tasks and semantic tasks among Spanish-speakers. Method: Both tasks were ordered across five difficulty levels based on the frequency of use in Mexican Spanish (phonological) and the number of elements given by a group of participants (semantic). One hundred healthy Mexican Spanish-speaking participants (aged 24–63 years; 55 females) were presented with five phonological and five semantic categories. The participants also underwent a neuropsychological test and sociodemographic interview. The number of words correctly produced in each category within one minute was calculated. An ANOVA and a Kruskal-Wallis analysis were conducted in order to know if there were different levels of difficulty in the tasks. Additionally, correlation analyzes were performed to test the effect of the sociodemographic and cognitive variables on the participants’ responses. Results: According to the analyzes, there were different levels of difficulty in the categories; P was the easiest and O was the most difficult category in the phonological tasks, and body parts and precious stones were the easiest and most difficult, respectively, in the semantic tasks. Age had a negative correlation with four-legged animals and a positive correlation with O; Positive correlations were also found between education and professions, vegetables, and alcoholic beverages; and between IQ and D, N, musical instruments, sports, vegetables, and trees. Conclusions: Both tasks offer categories with different level of difficulty based on the performance of a highly educated Mexican population. These data may be useful for clinical and research purposes.
On the Likelihood of Surrogates Conforming to the Substituted Judgment Standard When Making End-of-Life Decisions for Their Partner

A considerable proportion of end-of-life decisions are made by the patient’s next-of-kin, who can be asked to follow the substituted judgment standard and decide based on the patient’s wishes. The question of whether these surrogate decision makers are actually able to do so has become an important issue. In this study, we examined how the likelihood of surrogates conforming to the substituted judgment standard varies with individual differences in mortality acceptance and confidence in their decision making. We recruited 153 participants in romantic relationships between 18 and 80 years old from the general population. We asked them to make hypothetical end-of-life decisions for themselves and on behalf of their partner, as well as predict what their partner would do, and complete a series of questionnaires. Participants predicted that their partner would make similar decisions to their own but were more likely to accept a life-saving treatment that could result in reduced quality of life on their partner’s behalf than for themselves. Decisions made by older adults were more likely to conform to the substituted judgment standard, which is encouraging given that they are more likely to be confronted with these decisions in real life, although this was not due to differences in mortality acceptance. Older adults were also more likely to have had previous discussions with their partner and thereby know that person’s wishes and feel confident that they made the right decision, but these factors did not affect their likelihood of conforming to the substituted judgment standard. This shows that encouraging discussions about end of life among families would ease the decision process, but more work is needed to ensure that surrogates can adhere to the substituted judgment standard.
Patient Satisfaction in Spine Surgery: A Systematic Review of the Literature

Patient satisfaction reflects the patients’ perception of the outcome of care and is being considered for use in future reimbursement schemes. No consensus exists regarding the best instrument to measure patient satisfaction in the field of spine surgery. This systematic review aimed to determine how patient satisfaction for spine surgery has been measured previously and whether a disease-specific, comprehensive instrument to measure patient satisfaction has been established; we also aimed to define the dimensions of care that determine patient satisfaction in spine surgery. A systematic search of three online databases, unpublished sources, and citations was undertaken to identify 156 empirical studies that reported on patient satisfaction in the field of spine surgery. Manuscripts were reviewed in terms of the patient satisfaction instrument used, and the instruments were categorized as per content and method axes. Taxonomy of patient satisfaction with spine surgery identified the major characteristics of providers and medical care that influenced patient satisfaction and acted as a structure to categorically define the dimensions of patient satisfaction in spine surgery. The reviewed studies predominantly used global (108/156) rather than multidimensional (46/156), instruments. Most studies (96.2%) reported satisfaction with outcome rather than with care, and only 18.5% of the studies (29/156) utilized a disease-specific instrument. The following seven dimensions of patient status, outcome, and care experience that affected patient satisfaction were identified: pain, function, patient expectations/preference, specific patient health characteristics, caregiver interpersonal manner, efficacy/clinical outcomes, and postoperative care/therapy. Currently, no disease-specific instrument that includes all dimensions of patient satisfaction in spine surgery has been developed. Such a patient satisfaction instrument should be designed, tested for reliability and validity, and widely implemented.
Effects of autophagy on macrophage adhesion and migration in diabetic nephropathy

Abstract Objective: Macrophage infiltration in kidney is a major pathological feature of diabetic nephropathy (DN), which has been demonstrated associate with macrophages autophagy homeostasis. However, the relationships between autophagy and the infiltration response related of macrophages adhesion and migration are unknown. This study aims to investigate the impact of macrophages adhesion and migration by modulating autophagy. Methods: In vivo, rats were randomly distributed into control (NC) and DN groups. The pathological changes in renal tissue were assessed, and expression of CD68, LC3, P62 were analyzed. In vitro, RAW264.7 cells were divided into NC and high glucose (HG) groups. The capacity of macrophages adhesion migration and the expression of autophagy markers were observed with and without autophagy modulators (rapamycin, 3-methyladenine, chloroquine, and bafilomycin A1 for RAPA, 3-MA, CQ, BAFA). The macrophages autophagosome and the process of degradation and fusion of autophagosome-lysosome were observed by electron microscopy. Results: In vivo, renal injury is aggravated in diabetic rat compared with NC group. The autophagy level is inhibited in renal tissues of DN group with the increasing expression of CD68 and P62, while expression level of LC3 decreased (p < .05). In vitro, HG and 3-MA reduce the numbers of autophagosome of macrophages to inhibit autophagy level with decrease expression of LC3 and Beclin-1, but increase expression of P62, which promote the adhesion and migration capacity of macrophages (p < .05). Moreover, CQ and BAFA suppress autophagy level by inhibiting the process of autophagosome-lysosome degradation and fusion of macrophages, as well as the expression of LC3 and Beclin-1. We notice an increase expression of P62 by CQ and BAFA stimulation (p < .05). CQ and BAFA further facilitate the adhesion and migration capacity of macrophages. However, RAPA increases the numbers of macrophages autophagosome that inhibited by HG, resulting in a recovery of autophagy level with increase expression of LC3 and Beclin-1, whereas a reduction expression of P62, which lead to inhibition of adhesion and migration of macrophages induced by HG (p < .05) Conclusions: High glucose efficiently reduced the level of macrophage autophagy, following macrophages adhesion and migration enhanced when autophagy is suppressed. Activation of autophagosome improve the level of autophagy, but leading to a reduction of the macrophages adhesion and migration. While, inhibiting the process of degradation and fusion of autophagosome-lysosome suppress the level of autophagy and promote the macrophages adhesion and migration. These results indicate that high glucose may play an important role in macrophages adhesion and migration through modulating autophagy activities in diabetic nephropathy.
Sinonasal quality‐of‐life outcomes after endoscopic endonasal skull base surgery

There are substantial gaps in our understanding of the influence of the endoscopic endonasal approach (EEA) for endoscopic skull base surgery on sinonasal‐specific quality of life (QOL) as well as the instruments available for assessment. Our primary objective in this study was to characterize postoperative changes in sinonasal QOL, specifically using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22), with a secondary objective of delineating weaknesses in our current understanding of patient symptomatology after EEA for skull base surgery.