Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of transplantation in Hodgkin lymphoma

Despite the success of frontline anthracycline-based chemotherapy for classical Hodgkin Lymphoma (cHL), approximately 15% of patients do not achieve an adequate response and require further therapy. For transplant-eligible patients, additional treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autoHCT) provides a durable response in 50% of patients. The most refractory patients, including those requiring multiple lines of therapy to achieve a response or those relapsing after an autoHCT, may achieve long-term survival with allogeneic hematopoietic stem cell transplant (alloHCT). Contemporary salvage regimens used as a bridge to transplant have expanded to include not only non-cross resistant chemotherapy, but also brentuximab vedotin (BV) and checkpoint inhibitors (CPI). As the management of relapsed/refractory (R/R) cHL evolves with the introduction of novel agents, so too does the role of transplantation. The paradigm of chemosensitivity as a predictor for autoHCT efficacy is being challenged by favorable post- autoHCT outcomes in heavily pre-treated CPI-exposed patients. Contemporary supportive care measures, validated comorbidity assessments, and an increased donor pool with haploidentical donors have broadened the application of transplantation to an increasingly older and diverse patient population. Despite the introduction of increasingly effective treatment options for R/R cHL, transplantation continues to play an important role in the management of these patients. In this review, we explore the impact of salvage therapy on autoHCT, conditioning regimens, maintenance therapy and the diminishing role of alloHCT for patients with cHL.
Effect of microstructure on the mechanical properties and corrosion resistance of a welded joint of 620-grade marine steel

The relationship between the microstructure and the mechanical and corrosion properties of a welded joint of 620-grade marine steel was studied using metallographic microscopy, scanning electron microscopy, an energy dispersive spectrometer, transmission electron microscopy, and microhardness and tensile tests. The results showed that the strength and hardness of the weld center area (WMmid) were higher than those of the inner and outer welding surface region (WMin and WMout) because the volume fraction of the martensite-austenite (MA) constituents (21.6%) was higher than that in WMin and WMout (18.0% and 14.3%, respectively). There were numerous MnO-Al2O3-SiO2-TiO2-type inclusions located at the bottom of dimples in the fracture surface; however, the MA constituents took precedence over this kind of inclusion in inducing pitting corrosion. In contrast, pitting corrosion can be initiated by Al2O3-MgO-CaO-CaS inclusions in the heat-affected zone (HAZ) and base metal (BM). The corrosion resistance of the welded joint was in the order of weld metal > HAZ > BM. The WMmid with smaller dendrite spacing and a larger size of MA constituents had better corrosion resistance compared with the WMin and WMout. The corrosion resistance of the HAZ decreased in the sequence of coarse grain HAZ, fine grain HAZ, and intercritical HAZ.
Extensive accumulation of misfolded protein aggregates during natural aging and senescence

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues. In this study, we analyzed whether proteins misfold, aggregate, and accumulate during normal aging in three different biological systems, namely senescent cells, Caenorhabditis elegans, and mouse tissues collected at different times from youth to old age. Our results show a significant accumulation of misfolded protein aggregates in aged samples as compared to young materials. Indeed, aged samples have between 1.3 and 2.5-fold (depending on the biological system) higher amount of insoluble proteins than young samples. These insoluble proteins exhibit the typical characteristics of disease-associated aggregates, including insolubility in detergents, protease resistance, and staining with amyloid-binding dye as well as accumulation in aggresomes. We identified the main proteins accumulating in the aging brain using proteomic studies. These results show that the aged brain contain large amounts of misfolded and likely non-functional species of many proteins, whose soluble versions participate in cellular pathways that play fundamental roles in preserving basic functions, such as protein quality control, synapsis, and metabolism. Our findings reveal a putative role for protein misfolding and aggregation in aging.
Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis

IC/BPS is a chronic inflammatory pelvic pain syndrome characterized by lower urinary tract symptoms including unpleasant sensation (pain, pressure, or discomfort) in the suprapubic or bladder area, as well as increased urinary frequency and urgency, and decreased bladder capacity. While its etiology remains unknown, increasing evidence suggests a role for changes in nerve growth factor (NGF) signaling. However, NGF signaling is complex and highly context dependent. NGF activates two receptors, TrkA and p75NTR, which activate distinct but overlapping signaling cascades. Dependent on their coexpression, p75NTR facilitates TrkA actions. Here, we show effects of CYP treatment and pharmacological inhibition of p75NTR (via LM11A-31) and TrkA (ARRY-954) on NGF signaling–related proteins: NGF, TrkA, phosphorylated (p)-TrkA, p75NTR, p-ERK1/2, and p-JNK. Cystitis conditions were associated with increased urothelial NGF expression and decreased TrkA and p75NTR expression as well as altering their co-expression ratio; phosphorylation of ERK1/2 and JNK were also altered. Both TrkA and p75NTR inhibition affected the activation of signaling pathways downstream of TrkA, supporting the hypothesis that NGF actions during cystitis are primarily TrkA-mediated. Our findings, in tandem with our recent companion paper demonstrating the effects of TrkA, TrkB, and p75NTR inhibition on bladder function in a mouse model of cystitis, highlight a variety of potent therapeutic targets and provide further insight into the involvement of NGF signaling in sustained conditions of bladder inflammation.
The relationship between father absence and hostility among Chinese depressed youths: A serial mediation model and the role of self-esteem and frustration tolerance

Background While the association between father absence and youth hostility has been well-documented among depressed youths, there is a lack of research on the potential mechanism underlying such an association. This study aimed to test a serial mediation model of self-esteem and frustration tolerance on the link between father absence and youth hostility. Methods A total of 137 Chinese youths with major depressive disorder were recruited from Wuhan Mental Health Center. They completed a survey including the Father Absence Questionnaire to measure father absence, the Chinese Hostility Inventory (CHI) to measure hostility, the Psychological Endurance Questionnaire to measure frustration tolerance, and the Self-esteem Scale (SES) to measure self-esteem. A series of multiple linear regression models were employed to assess the associations among father absence, self-esteem, frustration tolerance, and hostility. Results Although father absence was modestly associated with hostility (r = 0.30, p < 0.001), subsequent serial mediation analysis showed that father absence was not directly related to hostility (β = 0.06, p = 0.29) when self-esteem and frustration tolerance were included in the model. High levels of father absence had an adverse effect on levels of self-esteem, which decreased levels of frustration tolerance, and thus higher levels of hostility among depressed youths. The indirect effects of father absence on hostility through self-esteem, frustration tolerance, as well as through self-esteem and frustration tolerance serially accounted for 28%, 24%, and 24% of the total effect, respectively. Conclusion Our study tested a serial mediation model of self-esteem and frustration tolerance as mediators between father absence and hostility among depressed youths. The findings strengthened our understanding of the potential mechanism underlying the association between self-esteem and frustration tolerance, which may provide useful guidance for future intervention programs.
Scaling theory of the Hall effect in disordered electronic systems

Abstract : A scaling theory for the Hall effect in disordered electronic systems is developed. It is suggested that a universal scaling function for the Hall conductance exists, and the leading quantum correction to the classical value (d-2) of this function is calculated (d is the dimensionality). It is shown, by means of a scaling argument, that at the mobility edge the zero temperature Hall conductivity approached zero with an exponent t sub h = 2t, where t is the conductivity exponent. This relation between the exponents is supported by a microscopic calculation in 2 + epsilon dimensions, which yields t = 1, t sub h = 2.
Distinct sets of olfactory receptors highly expressed in different human tissues evaluated by meta-transcriptome analysis: Association of OR10A6 in skin with keratinization

Olfactory receptors (ORs) are expressed in many tissues and have multiple functions. However, most studies have focused on individual ORs. Here, we aimed to conduct a comprehensive meta-transcriptome analysis of OR gene expression in human tissues by using open-source tools to search a large, publicly available genotype-tissue expression (GTEx) data set. Analysis of RNA-seq data from GTEx revealed that OR expression patterns were tissue-dependent, and we identified distinct sets of ORs that were highly expressed in 12 tissues, involving 97 ORs in total. Among them, OR5P2, OR5P3 and OR10A6 were associated with skin. We further examined the roles of these ORs in skin by performing weighted gene correlation network analysis (WGCNA) and c3net analysis. WGCNA suggested that the three ORs are involved in epidermal differentiation and water-impermeable barrier homeostasis, and OR10A6 showed the largest gene sub-network in the c3net network. Immunocytochemical examination of human skin keratinocytes revealed a sparse expression pattern of OR10A6, suggesting that it is not uniformly distributed among all keratinocytes. An OR10A6 agonist, 3-phenylpropyl propionate (3PPP), transiently increased intracellular Ca2+ concentration and increased cornified envelope (CE) production in cultured keratinocytes. Knock-down of OR10A6 diminished the effect of 3PPP. Overall, integration of meta-transcriptome analysis and functional analysis uncovered distinct expression patterns of ORs in various human tissues, providing basic data for future studies of the biological functions of highly expressed ORs in individual tissues. Our results further suggest that expression of OR10A6 in skin is related to epidermal differentiation, and OR10A6 may be a potential target for modulation of keratinization.
Soil bacterial community response to continuous cropping of cotton

Introduction Long-term continuous cropping may result in the outbreak and proliferation of soil-borne diseases, as well as reduction in annual crop production. Overcoming the obstacles of continuous cropping is critical for the long-term growth of modern agriculture. Soil microbes are essential for plant health, but the consequences of continuous cropping on soil microbiome are still poorly understood. Methods This study analyzed changes in soil bacterial community composition of Aksu (AKS) and Shihezi (SHZ) in Xinjiang Province during 1–20 years of continuous cropping by 16S amplicon sequencing. The results showed that the incidence of cotton Verticillium wilt rose with the number of cropping years. The bacterial alpha diversity in the AKS soil grew as the number of continuous cropping years increased, however it declined in the SHZ soil. Results The results of beta diversity analysis showed that there were significant differences in soil bacterial communities between different continuous cropping years and between different soils. The results of community composition changes at the level of main phyla and genus showed that the relative abundance of Actinobacteria, Bacteroidetes and Streptomyces decreased with the increase of continuous cropping years in the AKS and the SHZ soils. In addition, Actinobacteria, Propionibacteriales, and Nocardioidaceae were significantly enriched during the early stages of continuous cropping. Network analysis showed that long-term (≥8 years) continuous cropping interfered with the complexity of soil bacterial co-occurrence networks and reduced collaboration between OTUs. Discussion These findings suggested that continuous cropping and soil origin jointly affected the diversity and structural of bacterial communities, and the loss of Nocardioidaceae and Streptomyces in Actinobacteria might be one of the reasons of continuous cropping obstacles.
Induction of autophagy improves skin and hair conditions in dogs with underlying diseases

Background Autophagy was reported to play a crucial role in maintaining general and skin health. Methods The study used a synthesized autophagy inducer (AI) (Aquatide™ cospharm Inc.; Daejeon, Korea), for evaluating the effects of autophagy on skin and hair in dogs. Twenty-two dogs with poor skin and hair which were diagnosed with canine atopic dermatitis (CAD) or pituitary-dependent hyperadrenocorticism (PDH) were included. Clinical scores using Canine Atopic Dermatitis Extent and Severity Index-04 (CADESI-04), Pruritus Visual Analog Scale (PVAS) and skin barrier function using measurement of transepidermal water loss (TEWL) were evaluated and canine keratinocytes were also used in vitro investigation of pro-inflammatory cytokines after AI treatment. Results In the AI group, clinical scores and skin barrier function were improved at week 8 significantly compared to in the other groups. In particular, the AI significantly improved the hair surface damage at 8 weeks compared to the baseline. In vitro, the AI reduced pro-inflammatory cytokines by activating the 78-kDa glucose-regulated protein (GRP78). Conclusion AI improve skin barrier function and hair damage and reduce pro-inflammatory cytokines by inhibiting reactive oxygen species (ROS) production in dogs.
Rare events simulation for heavy-tailed distributions

This paper studies rare events simulation for the heavy-tailed case, where some of the underlying distributions fail to have the exponential moments required for the standard algorithms for the lighttailed case. Several counterexamples are given to indicate that in the heavy-tailed case, there are severe problems with the approach of developing limit results for the conditional distribution given the rare event; this is used as a basis for importance sampling. On the positive side, two algorithms having a relative error which is almost bounded are presented, one based upon order statistics and the other upon a different importance sampling idea.
Optimizing the mnemonic similarity task for efficient, widespread use

Introduction: The Mnemonic Similarity Task (MST) has become a popular test of memory and, in particular, of hippocampal function. It has been heavily used in research settings and is currently included as an alternate outcome measure on a number of clinical trials. However, as it typically requires ~15 min to administer and benefits substantially from an experienced test administrator to ensure the instructions are well-understood, its use in trials and in other settings is somewhat restricted. Several different variants of the MST are in common use that alter the task format (study-test vs. continuous) and the response prompt given to participants (old/similar/new vs. old/new). Methods: In eight online experiments, we sought to address three main goals: (1) To determine whether a robust version of the task could be created that could be conducted in half the traditional time; (2) To determine whether the test format or response prompt choice significantly impacted the MST’s results; and (3) To determine how robust the MST is to repeat testing. In Experiments 1–7, participants received both the traditional and alternate forms of the MST to determine how well the alternate version captured the traditional task’s performance. In Experiment 8, participants were given the MST four times over approximately 4 weeks. Results: In Experiments 1–7, we found that test format had no effect on the reliability of the MST, but that shifting to the two-choice response format significantly reduced its ability to reflect the traditional MST’s score. We also found that the full running time could be cut it half or less without appreciable reduction in reliability. We confirmed the efficacy of this reduced task in older adults as well. Here, and in Experiment 8, we found that while there often are no effects of repeat-testing, small effects are possible, but appear limited to the initial testing session. Discussion: The optimized version of the task developed here (oMST) is freely available for web-based experiment delivery and provides an accurate estimate of the same memory ability as the classic MST in less than half the time.
An Exploration of Sedentary Behavior, Physical Activity, and Quality of Life During the COVID-19 Outbreak

Objectives: Staying physically active is a cost-efficient strategy for disease prevention during a pandemic. The purposes of this study were to explore precautionary behaviors, psychological factors associated with physical activity and sedentary behavior, and impacts of active and sedentary lifestyles on the quality of life in the early stage of the coronavirus disease 2019 (COVID-19) outbreak. Methods: Participants were community-dwelling adults aged over 20 years who had not been infected with COVID-19 and who lived in the United States. A study with a cross-sectional design was conducted between July and October 2020. Quantitative data were collected by a self-reported questionnaire. Results: In total, 467 valid responses were obtained. Participants who engaged in an active lifestyle had significantly higher scores on all domains of quality of life compared to those who engaged in an inactive lifestyle. Participants with a non-sedentary lifestyle had significantly higher scores of psychological and social domains of quality of life than those with a sedentary lifestyle. Conclusion: Engaging in an active lifestyle and avoiding a sedentary lifestyle are recommended when facing future, unpredictable pandemics similar to COVID-19.
Efficacy and safety of riociguat replacing PDE-5is for patients with pulmonary arterial hypertension: A systematic review and meta-analysis

Introduction: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach treatment goals. As a novel soluble guanylate cyclase agonist, riociguat acts on the same pathway as PDE-5is but functions via different mechanisms. Whether riociguat is more effective and safer than PDE-5is is ambiguous. We aimed to evaluate the efficacy and safety of switching from PDE-5is to riociguat among these patients. Methods: Original published articles were retrieved from PubMed/Medline, Embase, Web of Science, Open Grey and Google Scholar. Studies that assessed the World Health Organization functional class (WHO-FC), 6-min walking distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac index (CI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected. Adverse events after switching were evaluated. Results: Ten published studies were included. Compared to PDE-5is, riociguat significantly increased the 6MWD by 26.45 m weighted mean difference (WMD) = 26.45 m, 95% confidence intervals (CIs): 9.70–43.2 m, p = 0.002) and improved mPAP (WMD = −3.53, 95% CIs: −5.62–1.44 mmHg, p = 0.0009), PVR (WMD = −130.24 dyn·s·cm−5, 95% CI −187.43–73.05, p < 0.0001), CIs (WMD = 0.36 L/min·cm−2, 95% CIs: 0.25–0.47, p < 0.00001) and WHO-FC (OR = 0.11, 95% CIs: 0.08–0.16, p < 0.0001) but not NT-proBNP. In addition, we did not observe the most common side effects during the replacement of riociguat for PDE-5is. Conclusions: PAH patients benefit from PDE-5is compared to riociguat, including in hemodynamic parameters, 6MWD, WHO-FC and biomarkers.
Group A streptococci induce stronger M protein-fibronectin interaction when specific human antibodies are bound

Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that is known to manipulate the immune system through various mechanisms. GAS’ M protein constitutes a primary target of the immune system due to its spatial configuration and dominance on the bacterial surface. Antibody responses targeting the M protein have been shown to favor the conserved C region. Such antibodies (Abs) circumvent antigenic escape and efficiently bind to various M types. The ability of GAS to bind to fibronectin (Fn), a high molecular weight glycoprotein of the extracellular matrix, has long been known to be essential for the pathogen’s evolutionary success and fitness. However, some strains lack the ability to efficiently bind Fn. Instead, they have been found to additionally bind Fn via the A-B domains of their M proteins. Here, we show that human Abs can induce increased Fn-binding affinity in M proteins, likely by enhancing the weak A-B domain binding. We found that this enhanced Fn binding leads to a reduction in Ab-mediated phagocytosis, indicating that this constitutes a GAS immune escape mechanism. We could show that the Fc domain of Abs is necessary to trigger this phenomenon and that Ab flexibility may also play a key role. We, moreover, saw that our Abs could enhance Fn binding in 3 out of 5 emm type strains tested, belonging to different clades, making it likely that this is a more generalizable phenomenon. Together our results suggest a novel synergistic interplay of GAS and host proteins which ultimately benefits the bacterium.
Detection of sarcopenia using deep learning-based artificial intelligence body part measure system (AIBMS)

Background: Sarcopenia is an aging syndrome that increases the risks of various adverse outcomes, including falls, fractures, physical disability, and death. Sarcopenia can be diagnosed through medical images-based body part analysis, which requires laborious and time-consuming outlining of irregular contours of abdominal body parts. Therefore, it is critical to develop an efficient computational method for automatically segmenting body parts and predicting diseases. Methods: In this study, we designed an Artificial Intelligence Body Part Measure System (AIBMS) based on deep learning to automate body parts segmentation from abdominal CT scans and quantification of body part areas and volumes. The system was developed using three network models, including SEG-NET, U-NET, and Attention U-NET, and trained on abdominal CT plain scan data. Results: This segmentation model was evaluated using multi-device developmental and independent test datasets and demonstrated a high level of accuracy with over 0.9 DSC score in segment body parts. Based on the characteristics of the three network models, we gave recommendations for the appropriate model selection in various clinical scenarios. We constructed a sarcopenia classification model based on cutoff values (Auto SMI model), which demonstrated high accuracy in predicting sarcopenia with an AUC of 0.874. We used Youden index to optimize the Auto SMI model and found a better threshold of 40.69. Conclusion: We developed an AI system to segment body parts in abdominal CT images and constructed a model based on cutoff value to achieve the prediction of sarcopenia with high accuracy.