Miracle-dz/UniFAR-FTUs huggingface dataset:
Diet-dependent Mucosal Colonization and Interleukin-1β Responses in Preterm Pigs Susceptible to Necrotizing Enterocolitis

Objectives: Intestinal colonization challenges the neonatal innate immune system, especially in newborns with an immature immune response lacking the supportive bioactive components from mother's milk. Accordingly, formula-fed preterm pigs frequently show bacterial overgrowth, mucosal atrophy, and gut lesions reflecting necrotizing enterocolitis (NEC) within the first days after birth. We hypothesized that NEC development is related to a diet-dependent bacterial adherence and a subsequent proinflammatory cytokine response in the gut mucosa immediately after introduction of enteral food. Materials and Methods: Premature piglets (92% gestation) received 2 to 3 days of total parenteral nutrition followed by 0, 8, or 17 hours of enteral formula or sow's colostrum feeding. Results: Following 8 hours, but not 17 hours, of colostrum feeding, a reduced number of intestinal samples with adherent bacteria (both Gram-negative and Gram-positive bacteria) was counted compared with 0 or 8 hours of formula feeding. Besides a more dense colonization, formula feeding leads to higher intestinal interleukin-1β (IL-1β) levels and more NEC-like lesions from 8 hours onward. The load of adherent bacteria was especially high in NEC lesions. Toll-like receptor 4 was detected in enteroendocrine, neuronal, and smooth muscle cells, potentially mediating the increase in IL-1β levels by Gram-negative bacteria. Conclusions: Formula feeding facilitates bacterial adherence and the development of a proinflammatory state of the intestine, which may be among the key factors that predispose formula-fed preterm neonates to NEC.
An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis

Background Voltage-gated potassium channel antibody-positive limbic encephalitis (VGKC+LE) frequently improves with immunotherapy, although the optimum regimen is unknown. The effectiveness of a combination immunomodulatory regimen was tested in consecutive VGKC+LE patients. Methods This was an open-label prospective study of nine VGKC+LE patients. All patients had plasma exchange (50 ml/kg), intravenous immunoglobulin (2 g/kg) and intravenous methylprednisolone (1 g×3), followed by maintenance oral prednisolone (1 mg/kg/day). Mycophenolate (2 g/day) was used in the first three patients. Assessments included serial clinical, cognitive, brain MRI and VGKC antibody testing. Results Within 1 week, seizures and hyponatraemia remitted in all affected patients. Cognitive function improved in all patients within 3 months. MRI appearances improved substantially within 9 months, with remission of inflammation in the majority of patients. All achieved immunological remission with normal VGKC antibody titres within 1–4 months. Major adverse events of therapy included one septicaemia and one thrombosis on plasma exchange and one death from sepsis after incidental bowel surgery. One patient remains in remission after 40 months of follow up, 26 months after being off all treatment. Conclusions Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.
Assessing Breast Cancer Awareness in Thai Women: Validation of the Breast Cancer Awareness Scale (B-CAS)

Background: Raising breast cancer awareness is a well-established first line strategy to reduce breast cancer mortality. A properly validated instrument is needed to gain a better understanding of breast cancer awareness. Objective: The objective of this study was to develop and validate an instrument to assess breast cancer awareness in Thai women. Methods: In this study, we develop and evaluate the validity of the Breast Cancer Awareness Scale (B-CAS). Construct validity was evaluated by using exploratory factor analysis and confirmatory factor analysis, and criterion validity was investigated using ROC curves to examine the associations between B-CAS subscales and breast self-examination. Internal consistency and test-retest reliability were also investigated. This validation process employed two independent samples of Thai women aged 20-64 years collected from communities in southern Thailand. Results: In total, 660 Thai women (mean age 41 years) participated in this study. Confirmatory factor analysis demonstrated the construct validity of B-CAS (CFI =0.91; NNFI=0.90; GFI=0.95; AGFI= 0.95; RMSEA=0.044, 95%CI 0.041 to 0.047; P< 0.05). Several of the B-CAS subscales demonstrated strong utility in discriminating between women who do and do not regularly conduct breast self-examination. B-CAS also demonstrated strong internal consistency (Cronbach’s α=0.86) and test-retest reliability. The final version of B-CAS contains 35 items across five domains: knowledge of risk factors, knowledge of signs and symptoms, attitude to breast cancer prevention, barriers of breast screening, and health behaviour related to breast cancer awareness. Conclusion: The breast cancer awareness scale (B-CAS) was shown to have good psychometric properties in Thai women, and is likely to prove useful in studying the epidemiology of breast cancer awareness in Thai women, and evaluating breast cancer prevention programs for raising awareness.
Treatment options in the management of necrotising fasciitis caused by Group A Streptococcus

Invasive Group A Streptococcus (GAS) disease is a serious condition that has multiple manifestations. A particularly severe form of invasive GAS disease is necrotising fasciitis (NF). The case-fatality rate of GAS NF is ∼ 20%. Penicillin remains the antibiotic of choice when treating invasive GAS infections. Epidemiological studies have shown that clindamycin is effective in the treatment of deep infections that are caused by GAS. Clinicians should consider adding clindamycin to the β-lactam antibiotic regimen when NF or myositis is present. Intravenous immunoglobulin appears to be a promising adjunctive therapy in the management of GAS NF. Consultations with surgeons and infectious disease specialists are imperative.
Operating Charging Infrastructure in China to Achieve Sustainable Transportation: The Choice between Company-Owned and Franchised Structures

The rapid development of electric vehicles (EVs) is conducive to clean transportation, which is an important aspect of sustainable infrastructure. However, the introduction of EVs is constrained by the lagging development of EV chargers. To optimally promote the development of charging stations, we analyzed the differences in the optimal quality and quantity of EV chargers between company-owned and franchised enterprises by constructing a theoretical model, and the changes in the quality and quantity of EV chargers in different market environments are discussed. We found that the total number of franchised charging stations was larger in general, but that the quality of the franchised charging stations was worse compared with the company-owned stations. The supervision cost, operation cost, and the investment return affect the quality and quantity of EV chargers. Although franchised structures are more conducive in the initial stage to increasing the number of charging stations to meet the needs of EVs, company-owned structures perform better and will be needed to improve the quality of the EV chargers as the market becomes more saturated, necessitating a higher quality of EV chargers.
TIEG1 facilitates transforming growth factor‐β‐mediated apoptosis in the oligodendroglial cell line OLI‐neu

Transforming growth factor‐β (TGF‐β) plays an important role during the period of developmental cell death in the nervous system. Using the oligodendroglial precursor cell line OLI‐neu, we have previously established an in vitro system to analyze TGF‐β‐mediated cell death on the molecular level. We could show that the Krüppel‐like Zn‐finger transcription factor TIEG1 was up‐regulated after TGF‐β stimulation of OLI‐neu cells and mimicked TGF‐β effects in these cells; i.e., overexpression of TIEG1 in OLI‐neu cells induced apoptosis as shown by apoptosis ELISA, DNA fragmentation, and caspases‐3 activation. The apoptotic pathway seemed to be initiated by repressing the expression of the antiapoptotic protein Bcl‐XL. In contrast, the reporter activity of a SMAD consensus promoter was induced, whereas the promoter activity of the inhibitory SMAD7 was reduced, suggesting that SMAD‐dependent TGF‐β responses, such as TGF‐β‐induced apoptosis, are enhanced in the presence of TIEG1. © 2003 Wiley‐Liss, Inc.
Aldolase sequesters WASP and affects WASP/Arp2/3‐stimulated actin dynamics

In addition to its roles in sugar metabolism, fructose‐1,6‐bisphosphate aldolase (aldolase) has been implicated in cellular functions independent from these roles, termed “moonlighting functions. ” These moonlighting functions likely involve the known aldolase–actin interaction, as many proteins with which aldolase interacts are involved in actin‐dependent processes. Specifically, aldolase interacts both in vitro and in cells with Wiskott–Aldrich Syndrome Protein (WASP), a protein involved in controlling actin dynamics, yet the function of this interaction remains unknown. Here, the effect of aldolase on WASP‐dependent processes in vitro and in cells is investigated. Aldolase inhibits WASP/Arp2/3‐dependent actin polymerization in vitro. In cells, knockdown of aldolase results in a decreased rate of cell motility and cell spreading, two WASP‐dependent processes. Expression of exogenous aldolase rescues these defects. Whether these effects of aldolase on WASP‐dependent processes were due to aldolase catalysis or moonlighting functions is tested using aldolase variants defective in either catalytic or actin‐binding activity. While the actin‐binding deficient aldolase variant is unable to inhibit actin polymerization in vitro and is unable to rescue cell motility defects in cells, the catalytically inactive aldolase is able to perform these functions, providing evidence that aldolase moonlighting plays a role in WASP‐mediated processes. J. Cell. Biochem. 114: 1928–1939, 2013. © 2013 Wiley Periodicals, Inc.
Evaluating a Structural Model of Labor Supply and Welfare Participation: Evidence from State Welfare Reform Experiments

This paper assesses the ability of a structural labor supply model to predict the impacts of a welfare policy change by studying two state welfare reform experiments conducted in Minnesota (MN) and Vermont (VT) during the mid-1990s. I estimate and evaluate a static discrete choice model of labor supply and welfare participation that incorporates heterogeneity in preferences, fixed costs of work, and disutility associated with welfare take-up. Although this type of labor supply models has been commonly estimated and applied to welfare and tax policy simulations, there have been very few attempts to verify the predictive ability of the existing models. I use the experimental impacts of the welfare policy change in each state as a benchmark for the structural model’s predictions. This approach is similar in spirit to LaLonde (1986). The utility parameters of the model are estimated using data from the MN control group. First, based on the parameter estimates, I make predictions regarding labor supply, welfare participation, and government costs under the treatment group program in MN and compare them with the observed effects of the MN experiment. Next, I apply the parameter estimates to the VT control group and compare the predicted and observed impacts of the policy change in VT. The results show that the model fits the estimation sample very well, but is unable to replicate the observed treatment effects on labor supply and welfare participation outcomes of the two experiments. Consequently, the effect on net government costs is under-predicted by 31 to 93 percent in MN. The prediction biases are even larger for the VT sample.
A Duty to Kill? A Duty to Die? Rethinking the Euthanasia Controversy of 1906

This essay seeks to chronicle the controversy surrounding euthanasia that came to a head in the United States around 1906, and to situate that debate in a meaningful historical context. An extensive examination of newspaper coverage of the legislative proposals to legalize the practice in Ohio and Iowa reveals that (1) the discourse occurred in a context in which both supporters and opponents of euthanasia generally agreed that the practice already occurred with frequency; (2) the discussion was heavily influenced by a simultaneous controversy surrounding eugenics; and (3) most of the opponents of legalization relied upon practical rather than religious or moral arguments to further their cause.
T-bet Is Required for the Rapid Clearance of Attenuated Rabies Virus from Central Nervous System Tissue

Much of our understanding of CNS immunity has been gained from models involving pathological inflammation. Attenuated rabies viruses (RABV) are unique tools to study CNS immunity in the absence of conventional inflammatory mechanisms, as they spread from the site of inoculation to the CNS transaxonally, thereby bypassing the blood–brain barrier (BBB), and are cleared without neutrophil or monocyte infiltration. To better understand the role of CD4 T cell subsets in the clearance of the virus from CNS tissues, we examined the development of antiviral immunity in wild-type (WT) and T-bet knockout mice (T-bet−/−), which lack Th1 cells. Early control of RABV replication in the CNS tissues of WT mice is associated with the production of IFN-γ, with antiviral effects likely mediated through the enhanced expression of type I IFNs. Of interest, IFN-α and -γ are overexpressed in the infected T-bet−/− by comparison with WT CNS tissues, and the initial control of RABV infection is similar. Ultimately, attenuated RABV are cleared from the CNS tissues of WT mice by Ab locally produced by the activities of infiltrating T and B cells. Although T and B cell infiltration into the CNS of infected T-bet−/− mice is comparable, their activities are not, the consequence being delayed, low-level Ab production and prolonged RABV replication. More importantly, neither T-bet−/− mice immunized with an attenuated virus, nor WT mice with Th2 RABV-specific immunity induced by immunization with inactivated virus, are protected in the long term against challenge with a pathogenic RABV.
Time synchronization for OFDM systems in very dispersive channels

Orthogonal Frequency Division Multiplexing (OFDM) systems guarantee transmissions free from intersymbol interference (ISI) and interchannel interference (ICI) over frequency selective channels, provided that the channel delay spread is less than the duration of the cyclic-prefix (or the zero-padding guard interval). However, it is realistic to consider practical implementation scenarios in which the channel delay spread exceeds this limit so that both ISI and ICI do arise. We show that in such cases, the objective of symbol synchronization should be to maximize the ratio of the total useful received power over all subcarriers to the total power of ISI and ICI for the given channel realization, and that this aim can be achieved through a proper choice of the symbol timing. We also present a practical low-complexity synchronization scheme for this case and show that its performance tops the results obtained by the best existing correlation-based timing estimators. Furthermore, we determine upper bounds on the achievable signal-to-interference ratio based on the ideal assumptions of either perfect channel state information or at least knowledge of the channel statistical description, and show that they are very closely approached by the proposed method.
Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma.

BACKGROUND Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. PURPOSE The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. METHODS Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. RESULTS A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. CONCLUSIONS Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. IMPLICATIONS The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders.
Privacy and Information Disclosure by Consumers

I study the question of what information consumers should disclose to firms. A consumer discloses information to a multi-product firm, which learns about his preferences, sets prices, and makes product recommendations. While the consumer benefits from disclosure as it enables the firm to make accurate recommendations, the firm may use the information to price discriminate. I show three main results. First, the firm prefers to commit not to price discriminate, which encourages the consumer to provide information that is useful for product recommendations. This explains why price discrimination by online sellers seems to be uncommon, which, empirically, has been puzzling. Second, nondiscriminatory pricing hurts the consumer, who would be better off by precommitting to withhold some information. This provides a rationale for privacy regulations that limit the amount of personal data that firms can possess. Third, equilibrium is often inefficient even if the consumer can potentially disclose any information about his preferences. ∗Stanford University, Department of Economics, Email: shota2@stanford.edu. I am grateful to Paul Milgrom, Gabriel Carroll, Matthew Gentzkow, and Ilya Segal for their unfailing support and guidance. I would like to thank Mohammad Akbarpour, Luca Braghieri, Isaias Chaves, Weixin Chen, Piotr Dworczak, Takako Fujiwara-Greve, Pedro Gardete, Michihiro Kandori, Fuhito Kojima, Shengwu Li, Sitian Liu, Giorgio Martini, Guido Martirena, Shunya Noda, Takuo Sugaya, and participants in Paul Milgrom’s group meeting, Stanford Theory Lunch, and Stanford Market Design Seminar. I am grateful for the financial support from the Yoshida Scholarship Foundation and the Stanford Graduate Fellowship.
Peroxisome Subpopulations of the Rat Liver: Isolation by Immune Free Flow Electrophoresis

Peroxisomes (POs) are a heterogenous population of cell organelles which, in mammals, are most abundant in liver and kidney. Although they are usually isolated by differential and density gradient centrifugation, isolation is hampered by their high fragility, sensitivity to mechanical stress, and their sedimentation characteristics, which are close to those of other major organelles, particularly microsomes. Consequently, until now only the so-called “heavy” POs with a buoyant density of 1.22-1.24 g/cm3 have been highly purified from rat liver, whereas the other subpopulations also present in that tissue have escaped adequate characterization. The purification of these subpopulations has become an essential task in view of the functional significance of POs in humans, and the putative importance of peroxisomal subpopulations in the biogenesis of this organelle. Here we used an alternative novel approach to density gradient centrifugation, called immune free flow electrophoresis (IFFE). IFFE combines the advantages of electrophoretic separation with the high selectivity of an immune reaction. It makes use of the fact that the electrophoretic mobility of a subcellular particle complexed to an antibody against the cytoplasmic domain of one of its integral membrane proteins is greatly diminished, provided that the pH of the electrophoresis buffer is adjusted to pH ∼8.0, the pI of IgG molecules. Because of this reduced electrophoretic mobility, IgG-coupled particles can be separated in an electric field from those that are noncoupled and hence more mobile. The IFFE technique has been recently applied for isolation of regular POs (ρ = 1.22-1.24 g/cm3) from a light mitochondrial fraction of rat liver. We succeeded in isolating different subpopulations of POs by applying IFFE to heavy, light, and postmitochondrial fractions separated by differential centrifugation of a rat liver homogenate. The PO subfractions obtained differed in their composition of matrix and membrane proteins, as revealed by immunoblotting. This indicates that they indeed represent distinct subpopulations of rat hepatic POs.