Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust early-learning: Hindering the memorization of noisy labels

The memorization effects of deep networks show that they will ﬁrst memorize training data with clean labels and then those with noisy labels. The early stopping method therefore can be exploited for learning with noisy labels. However, the side effect brought by noisy labels will inﬂuence the memorization of clean labels before early stopping. In this paper, motivated by the lottery ticket hypothesis which shows that only partial parameters are important for generalization, we ﬁnd that only partial parameters are important for ﬁtting clean labels and generalize well, which we term as critical parameters ; while the other parameters tend to ﬁt noisy labels and cannot generalize well, which we term as non-critical parameters . Based on this, we propose robust early-learning to reduce the side effect of noisy labels before early stopping and thus enhance the memorization of clean labels. Speciﬁcally, in each iteration, we divide all parameters into the critical and non-critical ones, and then perform different update rules for different types of parameters. Extensive experiments on benchmark-simulated and real-world label-noise datasets demonstrate the superiority of the proposed method over the state-of-the-art label-noise learning methods.
Personal Agency in Borderline Personality Disorder: The Impact of Adult Attachment Style

Background Personal agency- the degree to which one believes they have control over their life- is thought to influence how people understand their interpersonal relationships. Links between adult attachment and personal agency are theoretically relevant to the experience of borderline personality disorder (BPD) but this has yet to be empirically examined. The present research examines the impact of personal agency and adult attachment styles for individuals meeting criteria for BPD. Methods Participants consented to an online community study examining measures of locus of control (as an index of personal agency), BPD, and adult attachment. Participants meeting criteria for BPD (N = 96; mean age = 30.63; 70.5% female) were compared to age-matched healthy controls (N = 96; mean age = M = 31.99; 89.0% female). Results Individuals who met criteria for BPD displayed lower personal agency and higher fearful and preoccupied attachment styles in their close relationships, compared to Controls. Controls reported greater personal agency and were more securely attached in their relationships. Using multiple mediation modeling, the indirect effect of personal agency on BPD was significant for preoccupied, fearful, and secure attachment, but was non-significant for dismissive attachment. Lower personal agency was associated with insecure adult attachment styles. Conclusions Findings highlight the previously unexplored relationship between BPD and personal agency and indicate that adult attachment style plays a significant role. Low personal agency may increase challenges for individuals with symptoms of BPD by exacerbating relationship difficulties. People in treatment for BPD may benefit from focusing on both relationship insecurity and its impact on their perceived personal control.
Evaluation of Peripheral Immune Activation in Amyotrophic Lateral Sclerosis

Accumulating evidence has revealed that immunity plays an important role in amyotrophic lateral sclerosis (ALS) progression. However, the results regarding the serum levels of immunoglobulin and complement are inconsistent in patients with ALS. Although immune dysfunctions have also been reported in patients with other neurodegenerative diseases, few studies have explored whether immune dysfunction in ALS is similar to that in other neurodegenerative diseases. Therefore, we performed this study to address these gaps. In the present study, serum levels of immunoglobulin and complement were measured in 245 patients with ALS, 65 patients with multiple system atrophy (MSA), 60 patients with Parkinson's disease (PD), and 82 healthy controls (HCs). Multiple comparisons revealed that no significant differences existed between patients with ALS and other neurodegenerative diseases in immunoglobulin and complement levels. Meta-analysis based on data from our cohort and eight published articles was performed to evaluate the serum immunoglobulin and complement between patients with ALS and HCs. The pooled results showed that patients with ALS had higher C4 levels than HCs. In addition, we found that the IgG levels were lower in early-onset ALS patients than in late-onset ALS patients and HCs, and the correlations between age at onset of ALS and IgG or IgA levels were significant positive. In conclusion, our data supplement existing literature on understanding the role of peripheral immunity in ALS.
Regulatory Dendritic Cells Induced by Bendamustine Are Associated With Enhanced Flt3 Expression and Alloreactive T-Cell Death

The growth factor Flt3 ligand (Flt3L) is central to dendritic cell (DC) homeostasis and development, controlling survival and expansion by binding to Flt3 receptor tyrosine kinase on the surface of DCs. In the context of hematopoietic cell transplantation, Flt3L has been found to suppress graft-versus-host disease (GvHD), specifically via host DCs. We previously reported that the pre-transplant conditioning regimen consisting of bendamustine (BEN) and total body irradiation (TBI) results in significantly reduced GvHD compared to cyclophosphamide (CY)+TBI. Pre-transplant BEN+TBI conditioning was also associated with greater Flt3 expression among host DCs and an accumulation of pre-cDC1s. Here, we demonstrate that exposure to BEN increases Flt3 expression on both murine bone marrow-derived DCs (BMDCs) and human monocyte-derived DCs (moDCs). BEN favors development of murine plasmacytoid DCs, pre-cDC1s, and cDC2s. While humans do not have an identifiable equivalent to murine pre-cDC1s, exposure to BEN resulted in decreased plasmacytoid DCs and increased cDC2s. BEN exposure and heightened Flt3 signaling are associated with a distinct regulatory phenotype, with increased PD-L1 expression and decreased ICOS-L expression. BMDCs exposed to BEN exhibit diminished pro-inflammatory cytokine response to LPS and induce robust proliferation of alloreactive T-cells. These proliferative alloreactive T-cells expressed greater levels of PD-1 and underwent increased programmed cell death as the concentration of BEN exposure increased. Alloreactive CD4+ T-cell death may be attributable to pre-cDC1s and provides a potential mechanism by which BEN+TBI conditioning limits GvHD and yields T-cells tolerant to host antigen.
T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses In Vivo

The cyclin-dependent kinase 6 (CDK6) regulates the transition through the G1-phase of the cell cycle, but also acts as a transcriptional regulator. As such CDK6 regulates cell survival or cytokine secretion together with STATs, AP-1 or NF-κB. In the hematopoietic system, CDK6 regulates T cell development and promotes leukemia and lymphoma. CDK4/6 kinase inhibitors are FDA approved for treatment of breast cancer patients and have been reported to enhance T cell-mediated anti-tumor immunity. The involvement of CDK6 in T cell functions remains enigmatic. We here investigated the role of CDK6 in CD8+ T cells, using previously generated CDK6 knockout (Cdk6 -/-) and kinase-dead mutant CDK6 (Cdk6 K43M) knock-in mice. RNA-seq analysis indicated a role of CDK6 in T cell metabolism and interferon (IFN) signaling. To investigate whether these CDK6 functions are T cell-intrinsic, we generated a T cell-specific CDK6 knockout mouse model (Cdk6 fl/fl CD4-Cre). T cell-intrinsic loss of CDK6 enhanced mitochondrial respiration in CD8+ T cells, but did not impact on cytotoxicity and production of the effector cytokines IFN-γ and TNF-α by CD8+ T cells in vitro. Loss of CDK6 in peripheral T cells did not affect tumor surveillance of MC38 tumors in vivo. Similarly, while we observed an impaired induction of early responses to type I IFN in CDK6-deficient CD8+ T cells, we failed to observe any differences in the response to LCMV infection upon T cell-intrinsic loss of CDK6 in vivo. This apparent contradiction might at least partially be explained by the reduced expression of Socs1, a negative regulator of IFN signaling, in CDK6-deficient CD8+ T cells. Therefore, our data are in line with a dual role of CDK6 in IFN signaling; while CDK6 promotes early IFN responses, it is also involved in the induction of a negative feedback loop. These data assign CDK6 a role in the fine-tuning of cytokine responses.
Treatment Adherence as Predictor of Outcome in Concentrated Exposure Treatment for Obsessive-Compulsive Disorder

Background: The treatment of choice for obsessive-compulsive disorder (OCD) is exposure and response prevention (EX/RP). Previous studies have demonstrated that treatment adherence predicts treatment outcome for patients with OCD, but there is little knowledge on its role in concentrated exposure treatment for OCD. Method: In the present study, 42 patients received EX/RP treatment using the Bergen 4-day format. Adherence was measured with the Exposure and Response Prevention Adherence Scale (PEAS, rated both by patients and therapists) after the second and third day. Treatment outcome (symptoms of OCD, depression, anxiety, work- and social functioning, and well-being) was assessed at 3-month follow-up. Results: At follow-up, 71.4% were in remission. High adherence was reported (mean score of 6 on a 1–7 scale). The combination of patient- and therapist rated adherence was significantly associated with treatment outcome whilst controlling for age, sex, and pre-treatment scores. Patients with higher degree of adherence reported less symptoms, higher functioning, and more well-being at follow-up. Conclusions: The results of the present study indicated that adherence in concentrated exposure treatment is significantly associated with a wide range of treatment outcomes for OCD.
Strength Training Intensity and Volume Affect Performance of Young Kayakers/Canoeists

Purpose The aim of this study was to compare the effects of moderate intensity, low volume (MILV) vs. low intensity, high volume (LIHV) strength training on sport-specific performance, measures of muscular fitness, and skeletal muscle mass in young kayakers and canoeists. Methods Semi-elite young kayakers and canoeists (N = 40, 13 ± 0.8 years, 11 girls) performed either MILV (70–80% 1-RM, 6–12 repetitions per set) or LIHV (30–40% 1-RM, 60–120 repetitions per set) strength training for one season. Linear mixed-effects models were used to compare effects of training condition on changes over time in 250 and 2,000 m time trials, handgrip strength, underhand shot throw, average bench pull power over 2 min, and skeletal muscle mass. Both between- and within-subject designs were used for analysis. An alpha of 0.05 was used to determine statistical significance. Results Between- and within-subject analyses showed that monthly changes were greater in LIHV vs. MILV for the 2,000 m time trial (between: 9.16 s, SE = 2.70, p < 0.01; within: 2,000 m: 13.90 s, SE = 5.02, p = 0.01) and bench pull average power (between: 0.021 W⋅kg–1, SE = 0.008, p = 0.02; within: 0.010 W⋅kg–1, SE = 0.009, p > 0.05). Training conditions did not affect other outcomes. Conclusion Young sprint kayakers and canoeists benefit from LIHV more than MILV strength training in terms of 2,000 m performance and muscular endurance (i.e., 2 min bench pull power).
Irradiation-Modulated Murine Brain Microenvironment Enhances GL261-Tumor Growth and Inhibits Anti-PD-L1 Immunotherapy

Purpose Clinical evidence suggests radiation induces changes in the brain microenvironment that affect subsequent response to treatment. This study investigates the effect of previous radiation, delivered six weeks prior to orthotopic tumor implantation, on subsequent tumor growth and therapeutic response to anti-PD-L1 therapy in an intracranial mouse model, termed the Radiation Induced Immunosuppressive Microenvironment (RI2M) model. Method and Materials C57Bl/6 mice received focal (hemispheric) single-fraction, 30-Gy radiation using the Leksell GammaKnife® Perfexion™, a dose that does not produce frank/gross radiation necrosis. Non-irradiated GL261 glioblastoma tumor cells were implanted six weeks later into the irradiated hemisphere. Lesion volume was measured longitudinally by in vivo MRI. In a separate experiment, tumors were implanted into either previously irradiated (30 Gy) or non-irradiated mouse brain, mice were treated with anti-PD-L1 antibody, and Kaplan-Meier survival curves were constructed. Mouse brains were assessed by conventional hematoxylin and eosin (H&E) staining, IBA-1 staining, which detects activated microglia and macrophages, and fluorescence-activated cell sorting (FACS) analysis. Results Tumors in previously irradiated brain display aggressive, invasive growth, characterized by viable tumor and large regions of hemorrhage and necrosis. Mice challenged intracranially with GL261 six weeks after prior intracranial irradiation are unresponsive to anti-PD-L1 therapy. K-M curves demonstrate a statistically significant difference in survival for tumor-bearing mice treated with anti-PD-L1 antibody between RI2M vs. non-irradiated mice. The most prominent immunologic change in the post-irradiated brain parenchyma is an increased frequency of activated microglia. Conclusions The RI2M model focuses on the persisting (weeks-to-months) impact of radiation applied to normal, control-state brain on the growth characteristics and immunotherapy response of subsequently implanted tumor. GL261 tumors growing in the RI2M grew markedly more aggressively, with tumor cells admixed with regions of hemorrhage and necrosis, and showed a dramatic loss of response to anti-PD-L1 therapy compared to tumors in non-irradiated brain. IHC and FACS analyses demonstrate increased frequency of activated microglia, which correlates with loss of sensitivity to checkpoint immunotherapy. Given that standard-of-care for primary brain tumor following resection includes concurrent radiation and chemotherapy, these striking observations strongly motivate detailed assessment of the late effects of the RI2M on tumor growth and therapeutic efficacy.
Exocrine Pancreatic Maturation in Pre-term and Term Piglets Supplemented With Bovine Colostrum

Pre-term infants have an immature digestive system predisposing to short- and long-term complications including feeding intolerance, maldigestion and necrotizing enterocolitis (NEC). Optimal feeding strategies are required to promote maturation of the gut including the exocrine pancreas. Little is known about age- and diet-related development of pancreatic exocrine enzymes following pre-term birth. Currently, bovine colostrum supplementation is investigated in clinical trials on pre-term infants. Using pigs as models for infants, we hypothesized that pancreatic enzyme content is (1) immature following pre-term birth, (2) stimulated by early colostrum supplementation, and (3) stimulated by later colostrum fortification. Thus, using piglets as models for infants, we measured trypsin, amylase, lipase and total protein in pancreatic tissue collected from piglets delivered by cesarean section either pre-term (90% gestation) or close to term. Experiment 1:Pre-term and term pigs were compared at birth and 11 days. Experiment 2: Pre-term and term pigs were either enterally supplemented with bovine colostrum or fed total parenteral nutrition for 5 days, followed by exclusive milk feeding until day 26. Experiment 3: Pre-term pigs were fed bovine's milk with or without colostrum fortification until 19 days. The results showed that pancreatic trypsin, amylase and total protein contents were reduced in pre-term vs. term pigs. Trypsin mainly increased with advancing post-conceptional age (2-fold), while amylase was affected predominantly by advancing post-natal age, and mostly in pre-term pigs from birth to 11 or 26 days. Colostrum feeding in both term and pre-term piglets decreased trypsin and increased amylase contents. Lipase activity decreased with advancing gestational age at birth and post-natal age, with no consistent responses to colostrum feeding, with lipase activities decreasing relative to total pancreatic protein content. In summary, key pancreatic enzymes, amylase and trypsin, are immature following pre-term birth, potentially contributing to reduced digestive capacity in pre-term neonates. Rapid post-natal increases occurs within few weeks of pre-term birth, partly stimulated by enteral colostrum intake, reflecting a marked adaptation capacity. Alternatively, lipase is less affected by pre-/post-natal age and feeding. Thus, there is a highly enzyme-specific and asymmetric perinatal development of the exocrine pancreas.
Physiological and Proteomic Responses to Drought in Leaves of Amygdalus mira (Koehne) Yü et Lu

Various environmental stresses strongly influence plant development. Among these stresses is drought, which is a serious threat that can reduce agricultural productivity and obstruct plant growth. Although the mechanism of plants in response to drought has been studied extensively, the adaptive strategies of Amygdalus mira (Koehne) Yü et Lu grown in drought and rewatered habitats remain undefined. Amygdalus mira from the Tibetan Plateau has outstanding nutritional and medicinal values and can thrive in extreme drought. In this study, the physiological and proteomic responses in leaves of A. mira were investigated during drought and recovery period. The changes in plant growth, photosynthesis, enzymes, and non-enzymatic antioxidant under drought and rewatering were also analyzed in leaves. Compared with controls, A. mira showed stronger adaptive and resistant characteristics to drought. In addition, the proteomic technique was also used to study drought tolerance mechanisms in A. mira leaves. Differentially expressed proteins were identified using mass spectrometry. Accordingly, 103 proteins involved in 10 functional categories: cytoskeleton dynamics, energy metabolism, carbohydrate metabolism, photosynthesis, transcription and translation, transport, stress and defense, molecular chaperones, other materials metabolism, and unknown function were identified. These results showed that an increase of stress-defense-related proteins in leaves after drought treatment contributed to coping with drought. Importantly, A. mira developed an adaptive mechanism to scavenge reactive oxygen species (ROS), including enhancing antioxidant enzyme activities and non-enzymatic antioxidant contents, reducing energy, and adjusting the efficiency of gas exchanges. These results may help to understand the acclimation of A. mira to drought.
Effects of Active Upper Limb Orthoses Using Brain–Machine Interfaces for Rehabilitation of Patients With Neurological Disorders: Protocol for a Systematic Review and Meta-Analysis

Introduction: The field of brain–machine interfaces (BMI) for upper limb (UL) orthoses is growing exponentially due to improvements in motor performance, quality of life, and functionality of people with neurological diseases. Considering this, we planned a systematic review to investigate the effects of BMI-controlled UL orthoses for rehabilitation of patients with neurological disorders. Methods: This systematic review and meta-analysis protocol was elaborated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P 2015) and Cochrane Handbook for Systematic Reviews of Interventions. A search will be conducted on Pubmed, IEEE Xplore Digital Library, Medline, and Web of Science databases without language and year restrictions, and Patents Scope, Patentlens, and Google Patents websites in English, Spanish, French, German, and Portuguese between 2011 and 2021. Two independent reviewers will include randomized controlled trials and quasi-experimental studies using BMI-controlled active UL orthoses to improve human movement. Studies must contain participants aged >18 years, diagnosed with neurological disorders, and with impaired UL movement. Three independent reviewers will conduct the same procedure for patents. Evidence quality and risk of bias will be evaluated following the Cochrane collaboration by two review authors. Meta-analysis will be conducted in case of homogeneity between groups. Otherwise, a narrative synthesis will be performed. Data will be inserted into a table containing physical description, UL orthoses control system, and effect of BMI-controlled orthoses. Discussion: BMI-controlled orthoses can assist individuals in several routine activities and provide functional independence and sense of overcoming limitations imposed by the underlying disease. These benefits will also be associated with orthoses descriptions, safety, portability, adverse events, and tools used to assess UL motor performance in patients with neurological disorders. PROSPERO Registration Number: CRD42020182195.
Enhanced Protocatechuic Acid Production From Glucose Using Pseudomonas putida 3-Dehydroshikimate Dehydratase Expressed in a Phenylalanine-Overproducing Mutant of Escherichia coli

Protocatechuic acid (PCA) is a strong antioxidant and is also a potential platform for polymer building blocks like vanillic acid, vanillin, muconic acid, and adipic acid. This report presents a study on PCA production from glucose via the shikimate pathway precursor 3-dehydroshikimate by heterologous expression of a gene encoding 3-dehydroshikimate dehydratase in Escherichia coli. The phenylalanine overproducing E. coli strain, engineered to relieve the allosteric inhibition of 3-deoxy-7-phosphoheptulonate synthase by the aromatic amino acids, was shown to give a higher yield of PCA than the unmodified strain under aerobic conditions. Highest PCA yield of 18 mol% per mol glucose and concentration of 4.2 g/L was obtained at a productivity of 0.079 g/L/h during cultivation in fed-batch mode using a feed of glucose and ammonium salt. Acetate was formed as a major side-product indicating a shift to catabolic metabolism as a result of feedback inhibition of the enzymes including 3-dehydroshikimate dehydratase by PCA when reaching a critical concentration. Indirect measurement of proton motive force by flow cytometry revealed no membrane damage of the cells by PCA, which was thus ruled out as a cause for affecting PCA formation.