Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Subcellular Machine Contributes to Basal Junction Remodeling in the Seminiferous Epithelium1

ABSTRACT Tubulobulbar complexes are cytoskeleton-related membrane structures that develop at sites of intercellular attachment in mammalian seminiferous epithelium. At apical junctions between Sertoli cells and spermatids, the structures internalize adhesion junctions and are a component of the sperm release mechanism. Here we explore the possibility that tubulobulbar complexes that form at the blood-testis barrier are subcellular machines that internalize basal junction complexes. Using electron microscopy, we confirmed that morphologically identifiable tight and gap junctions are present in basal tubulobulbar complexes in rats. In addition, immunological probes for claudin-11 (CLDN11), connexin-43 (GJA1), and nectin-2 (PVRL2) react with linear structures at the light level that we interpret as tubulobulbar complexes, and probes for early endosome antigen 1 (EEA1) and Rab5 (RAB5A) react in similar locations. Significantly, fluorescence patterns for actin and claudin-11 indicate that the amount of junction present is dramatically reduced over the time period that tubulobulbar complexes are known to be most prevalent during spermatogenesis. We also demonstrated, using electron microscopy and fluorescence microscopy, that tubulobulbar complexes develop at basal junctions in primary cultures of Sertoli cells and that like their in vivo counterparts, the structures contain junction proteins. We use this culture system together with transfection techniques to show that junction proteins from one transfected cell occur in structures that project into adjacent nontransfected cells as predicted by the junction internalization hypothesis. On the basis of our findings, we present a new model for basal junction remodeling as it relates to spermatocyte translocation in the seminiferous epithelium.
Implications of Political Patronage and Political Costs for Corporate Disclosure

We take advantage of China’s relationship-based institutional setting to investigate whether and how firms’ disclosure decision is affected by political patronage and associated political costs considerations. Using a sample of 65 firms involved in the Shanghai Pension corruption scandal of 2006, we find that relative to benchmark firms, the connected firms are associated with lower levels of disclosure prior to the scandal. However, they significantly increased their disclosures in the year immediately following the public exposure of the scandal. A content analysis indicates that the increased disclosures are value-relevant, and are not merely used as a public relations effort to subdue public outcry in the immediate aftermath of the scandal. Cross-sectional analyses further reveal that the increase in disclosure is positively associated with the extent of firm’s guanxi dependence and type/severity of involvement in the scandal. We conclude that the increased disclosures are in response to the heightened risk and potential costs of regulatory and public scrutiny in the wake of a major event involving high political and public sensitivity. The evidence is supportive of the political costs hypothesis, and has important managerial and policy implications.
Validation of international consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective

There is no standardized method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2× baseline tryptase+2 mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS). To validate consensus equation in a perioperative setting analyses of cases of suspected perioperative anaphylaxis during general anaesthesia (GA) were performed. Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria. Timed serial MCT measurements were mapped against the consensus equation and receiver operating characteristic (ROC) curves produced. A total of 82 patients (60 females, mean age 56.5 years±SD17.2) underwent investigation. Sixty (73%) patients fulfilled WAO criteria for anaphylaxis, and 22 patients did not. Aetiology included 59% IgE‐mediated anaphylaxis, 2% non‐IgE‐mediated anaphylaxis, 12% anaphylaxis of unknown cause and 27% deemed non‐anaphylaxis. IgE‐mediated anaphylaxis included the following: NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71 of 82 (87%) patients (60 anaphylaxis and 11 controls). The median interquartile range (IQR) time from reaction to peak MCT was 1.34 (0.82‐2.51) hours. Analyses confirmed that a rise in acute MCT greater than that defined by the equation had a sensitivity, specificity, positive predictive value (PPV) and negative (N) PV of 78%, 91%, 98% and 44%, respectively. The magnitude of increase in acute MCT above the threshold predicted by consensus equation was higher in the anaphylaxis group compared to controls (P=.0001). This equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.
How Do Independent Directors View Powerful CEOs? Evidence from a Quasi-Natural Experiment

Prior research shows that powerful CEOs can exacerbate the agency conflict, resulting in adverse corporate outcomes. Exploiting an exogenous shock introduced by the passage of the Sarbanes–Oxley Act, we explore whether board independence mitigates CEO power. Based on difference-in-difference estimation, our evidence shows that independent directors view powerful CEOs unfavorably. Board independence diminishes CEO power by more than a quarter. Based on a quasi-natural experiment, our research design is less vulnerable to the omitted-variable bias and reverse causality and therefore suggests that the effect of board independence on CEO power is likely causal.
Age at menopause, reproductive history, and venous thromboembolism risk among postmenopausal women: the Women’s Health Initiative hormone therapy clinical trials

ObjectiveThis study aims to investigate venous thromboembolism (VTE) risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause, as well as any interaction with randomized hormone therapy (HT) assignment, among postmenopausal women. MethodsUsing pooled data from the Women’s Health Initiative HT clinical trials including 27,035 postmenopausal women aged 50 to 79 years who had no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause by Cox proportional hazards models. Linear trends, quadratic relationships, and interactions of reproductive life characteristics with HT on VTE risk were systematically tested. ResultsDuring follow-up, 426 women reported a first VTE, including 294 non–procedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected, and there was not a significant association between VTE and age at menarche, age at menopause, parity, oophorectomy, or time since menopause. However, analyses restricted to non–procedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (P < 0.01). Compared with women aged 40 to 49 years at menopause, those who had early menopause (age <40 y) or late menopause (age >55 y) had a significantly increased VTE risk (hazard ratio [95% CI]: 1.8 [1.2-2.7] and 1.5 [1.0-2.4], respectively). ConclusionsReproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for non–procedure-related VTE.
Combined γ‐tocotrienol and Met inhibitor treatment suppresses mammary cancer cell proliferation, epithelial‐to‐mesenchymal transition and migration

Dysregulation of Met signalling is associated with malignant transformation. Combined treatment has been shown to reduce Met activation and mammary tumour cell proliferation. Experiments here, were conducted to determine mechanisms involved in mediating anti‐cancer effects of combined γ‐tocotrienol and SU11274 (Met inhibitor) treatment in various mammary cancer cell lines.
Lupeol targets liver tumor‐initiating cells through phosphatase and tensin homolog modulation

Liver tumor‐initiating cells (T‐ICs) are capable of self‐renewal and tumor initiation and are more chemoresistant to chemotherapeutic drugs. The current therapeutic strategies for targeting stem cell self‐renewal pathways therefore represent rational approaches for cancer prevention and treatment. In the present study, we found that Lup‐20(29)‐en‐3β‐ol (lupeol), a triterpene found in fruits and vegetables, inhibited the self‐renewal ability of liver T‐ICs present in both hepatocellular carcinoma (HCC) cell lines and clinical HCC samples, as reflected by hepatosphere formation. Furthermore, lupeol inhibited in vivo tumorigenicity in nude mice and down‐regulated CD133 expression, which was previously shown to be a T‐IC marker for HCC. In addition, lupeol sensitized HCC cells to chemotherapeutic agents through the phosphatase and tensin homolog (PTEN)–Akt–ABCG2 pathway. PTEN plays a crucial role in the self‐renewal and chemoresistance of liver T‐ICs; down‐regulation of PTEN by a lentiviral‐based approach reversed the effect of lupeol on liver T‐ICs. Using an in vivo chemoresistant HCC tumor model, lupeol dramatically decreased the tumor volumes of MHCC‐LM3 HCC cell line‐derived xenografts, and the effect was equivalent to that of combined cisplatin and doxorubicin treatment. Lupeol exerted a synergistic effect without any adverse effects on body weight when combined with chemotherapeutic drugs. Conclusion: Our results suggest that lupeol may be an effective dietary phytochemical that targets liver T‐ICs. (HEPATOLOGY 2011.)
Use of Robotic Pets in Providing Stimulation for Nursing Home Residents with Dementia

Trial experiments utilized robotic pets to facilitate self-reliance in nursing home residents. A remote-control robot modeled clear and meaningful behaviors to elderly residents. Special attention was paid to its effects on mental and social domains. Employing the robot as a gaze target and center of attention created a cue to initiate a communication channel between residents who normally show no interest in each other. The Sony AIBO robot in this study uses commercially available wireless equipment, and all its components are easily accessible to any medical or welfare institution interested in additional practice of these activities.
Research and development as an initiator of fixed capital investment

This paper investigates the causal relationship between firms’ R&D expenditures and their investments in fixed capital. It argues that a firm’s R&D expenditures lead to inventions that in turn trigger investments in fixed capital, as the manufacturing of newly invented goods or services requires the creation of additional production capacities. Using firm-level panel data ranging from 1990 to 2014, the paper applies a 2SLS approach to uncover the direction of causality between R&D expenditures and fixed capital investment. To obtain exogenous instruments, the paper exploits shocks to i) technological opportunities and ii) innovative sales of capital goods industries. The results reveal that firms’ R&D expenditures cause subsequent investments in fixed capital, while there is no evidence of the reverse effect. An increase in R&D expenditures of 1% leads to an increase in fixed capital investments between 0.4% and 0.6%. Therefore, increasing R&D expenditures may not only be valuable for long-term economic growth but also, via fixed capital investment, provide the economy with positive stimuli in times of prolonged stagnation.
Effect of animal density on endocrine development in gilts.

A study was conducted to determine the effect of social crowding on the development of endocrine organs involved in the reproductive process in growing and finishing gilts. One hundred four littermate gilts weighing approximately 30 kg were randomly assigned to treatment groups of either 8 or 16 pigs/pen. Gilts raised in pens of eight were allotted 1.06 m2 per pig from 30 to 65 kg and 1.25 m2 from 65 to 100 kg; whereas, one-half the area was provided for gilts raised in pens of 16. Littermate gilts raised in pens of 8 and 16 were slaughtered on the same day when the average weight of pigs reached 100 kg. At slaughter, the brain, adrenals, pituitary, uterus and ovaries were removed and weighted. The brain was lyophilyzed and reweighed to yield dry brain weight. Gilts raised in the low-density groups had heavier adrenal (P less than .01), pituitary (P less than .08), brain (P less than .11), dry-brain (P less than .02), uterine (P less than .09) and ovarian (P less than .07) tissues. Furthermore, significantly more gilts in the low-density, compared with the high-density groups, had ovulated at slaughter. In a second study, eight littermate gilts raised in pens of 8 or 16 and weighing approximately 100 kg were moved to individual pens and fitted with a jugular vein catheter. Following blood sample collection at 15-min intervals for 2 h, 200 IU of adrenocorticotropin (ACTH) were infused into the cannula. Blood samples were collected at 15-min intervals for an additional 2 h. There were no differences between basal or ACTH-stimulated concentrations of plasma cortisol between treatment groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Fibroblast growth factor messenger ribonucleic acid expression in a human astrocytoma cell line: regulation by serum and cell density.

A human astrocytoma cell line, U87-MG, synthesizes a growth factor which is structurally related to basic fibroblast growth factor (bFGF) by several criteria: 1) it binds to heparin-Sepharose and elutes at 2 M NaCl; 2) it cross-reacts with N-terminal specific anti-bFGF antibodies; 3) it is a potent mitogen for rabbit fetal chondrocytes. Northern blotting analysis of total RNA reveals that the cells express high levels of two bFGF mRNA transcripts of 7 and 3.7 kilobase in size. The levels of both transcripts rise rapidly (within 3 h) after addition of serum to serum-deprived cultures, reach a maximum within 6-12 h and remain elevated for at least 24 h. Basic FGF mRNA expression was low in confluent cultures but was increased after replating at sparse density. Transcript levels began to increase 4 h after plating, reaching a maximum (7-fold above confluent cells) within 24 h. The rise in bFGF mRNA levels was preceded by a rapid rise in c-myc expression which peaked 8 h after plating and then declined. The level of bFGF mRNA expression began to decline by 48 h, before any detectable increase in cell number, and returned to control levels when the cells reached confluence after 10 days. The level of transforming growth factor beta mRNA, which is also expressed in these cells, was not affected by cell density. The effects of density on bFGF mRNA levels were not duplicated by culturing low density cells in conditioned medium from confluent cultures or in medium containing 10 ng/ml bFGF. (ABSTRACT TRUNCATED AT 250 WORDS)
How Institutional Monitoring Creates Value: Evidence for the Free Cash Flow Hypothesis

Institutional ownership of U.S. equities increased from 9.4% in 1980 to 42.9% in 2009. This paper analyzes the indirect role of institutional investors in monitoring firm managers and in the process of shareholder wealth maximization. Institutional monitoring reduces the agency problem of free cash flow. Controlling for reverse causality, we find that increased institutional ownership results in lower leverage and dividend payout that consequently lead to greater cash holdings and firm value. The results are consistent with the free cash flow hypothesis and provide an alternative explanation for why firms hold so much cash and why debt and dividends have decreased during the last thirty years.
Antibiotic Use Before Chemotherapy: A Risk Factor for Developing Neutropenic Colitis in Children With Leukemia

Background: It has been shown that the use of antimicrobials is a determinant that favors intestinal dysbiosis. The objective of this study is to establish the association between the previous use of antimicrobials and the development of neutropenic colitis (NC). Methods: A case-control study was carried out with subjects diagnosed with acute lymphoblastic leukemia from 2004 to July 2013. They were identified by cross-referencing the databases from the computing area and the records from the pediatric hematology section. Cases were children with neutropenia and fever, abdominal distension and pain, diarrhea or constipation, and ultrasonography or computed tomography showing an intestinal wall thickness of ≥4 mm. Controls were children with acute lymphoblastic leukemia with neutropenia and fever, with or without gastrointestinal symptomatology, but without images of NC. Results: Thirty-eight cases and 75 controls were included. The factors associated with the development of NC were severe neutropenia (odds ratio [OR], 12.4; 95% confidence interval [CI], 3-51; P=0.00001), the use of antimicrobials for >10 days, within the month previous to the appearance of NC (OR, 12.4; 95% CI, 3-51; P=0.00001), and use of doxorubicin (OR, 5.43, 95% CI, 2.1-13.8, P=0.00004). In particular, the risk of developing CN was 3.46 (95% CI, 0.88-14; P=0.04) when ceftriaxone was used. Conclusions: The use of antimicrobials during >10 days before the administration of chemotherapy is a risk factor for developing NC, along with other factors previously studied.
Relationship between chromatin condensation, DNA integrity and quality of ejaculated spermatozoa from infertile men

Normal chromatin condensation is important for sperm fertilising ability. However, routine semen analysis does not identify defects in sperm chromatin structure. This study aimed to investigate the condensation of chromatin and DNA integrity in spermatozoa of infertile men and deduce the relationship with sperm quality, as measured by conventional semen parameters. Semen analysis was carried out to assess sperm quality according to World Health Organization criteria. The remaining aliquot of each sample was processed for transmission electron microscopy, chromomycin A3 (CMA3) and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays. The ultrastructural analysis of spermatozoa from infertile men showed heterogeneity in sperm nuclear morphology. Some spermatozoa displayed a round nucleus with incomplete chromatin condensation. Immunoreactivity with antitransitional protein and antiprotamine antibodies indicated nuclear maturation defects in the spermatozoa of infertile men. Spearman’s correlation analysis indicated a positive correlation between the percentages of CMA3‐ and TUNEL‐positive spermatozoa. In addition, these two parameters were negatively correlated with sperm concentration, motility and normal morphology. This study demonstrated that men with morphologically normal spermatozoa of <30% have greater degree of protamine deficiency and DNA damage than men with morphologically normal spermatozoa of >30%. Evaluation of chromatin integrity appears to be a useful tool for assessing male fertility.
Collaborative Partnership for Culture Care: Enhancing Health Services for the Arab Community

The purpose of this study was to discover perceptions, experiences, and patterns of health care behavior among Arab Americans in an urban Midwestern area of the United States and then to discover perceptions and experiences of health care providers related to culturally competent care. The goal of the study was to generate findings that would provide the basis for implementing system-wide changes to include culturally competent care. A qualitative focus group methodology was used to discover the care patterns and perceptions of Arab Americans and the local health care providers. The nurse researchers conducted 10 focus groups. Six themes were identified, including the unique caring behaviors of Arab families, the complexity of the health care system to Arab Americans, communication gaps, the diversity of perceptions of cultural competency, obstacles to accessibility of care, and workforce diversity issues.
Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy.

BACKGROUND Cinacalcet is a new effective treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients (HP), but the alterations of parathyroid gland (PTG) hyperplasia determined by cinacalcet and vitamin D have not been extensively investigated in humans. METHODS We performed histological analyses of 94 PTGs removed from 25 HP who underwent parathyroidectomy (PTx) because of SHPT refractory to therapy with vitamin D alone (group A=13 HP and 46 PTGs) or associated with cinacalcet (group B=12 HP and 48 PTGs). The number, weight, the macroscopic cystic/hemorrhagic changes, and type of hyperplasia of PTG (nodular=NH, diffuse=DH) were assessed. In randomly selected HP of group A (4 HP and 14 PTGs) and group B (4 HP and 15 PTGs), the labeling index of cells positive to Ki-67 and TUNEL and the semiquantitative score of immunohistochemistry staining of vitamin D receptor, calcium-sensing receptor, and vascular endothelial growth factor-α (VEGF-α) were measured in the entire PTGs and in the areas with DH or NH. RESULTS The number and weight of single and total PTG of each HP were similar in the two groups as well as the number of PTG with macroscopic cystic/hemorrhagic areas. TUNEL, Ki-67, and VEGF-α scores were higher in NH than in DH areas. CONCLUSION This observational study of a highly selected population of HP, submitted to PTx because SHPT refractory to therapy, shows that the macroscopic, microscopic, and immunochemistry characteristics of PTG in HP who received or did not receive cinacalcet before PTx did not differ significantly.
Further Assessment of 17α-Ethinyl Estradiol as an Inhibitor of Different Human Cytochrome P450 Forms in Vitro

17α-Ethinyl estradiol (EE) was systematically evaluated as a reversible and time-dependent inhibitor of 11 human drug-metabolizing cytochromes P450 (P450s) (CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and CYP3A5) in vitro. When ranked, the lowest IC50 (concentration of inhibitor required to decrease activity by 50%) values were obtained with recombinant CYP1A1 (rCYP1A1) [IC50(total) = IC50(free) = 2.7 μM] and CYP2C19 activity in human liver microsomes (HLM) [IC50(total) = 4.4 μM; IC50(free) = 2.8 μM]. For rCYP1A1, formal inhibition studies revealed that EE was a competitive inhibitor [Ki(free) = 1.4 μM]. All the other IC50 values were greater than 8.0 μM, and the weakest inhibition was observed with CYP1A2 activity in HLM (IC50(free) > 39 μM). In agreement, the IC50 characterizing the inhibition of melatonin (MEL) 6-hydroxylation in human intestine microsomes (CYP1A1-catalyzed) was lower than that of HLM (0.91 versus >40 μM). Because EE is known to affect the pharmacokinetics of CYP2C19 probe drugs, this result raises the possibility that the concentration of EE during first pass may exceed 1000 nM, sufficient to affect CYP1A1 and CYP2C19, with less impact on CYP3A4 and other P450s. The results implicate intestinal CYP1A1, and possibly CYP2C19, as the loci of EE drug interactions with highly extracted drugs like MEL. Overall, it is very difficult to rationalize drug interactions involving EE based on direct inhibition of CYP2B6 (e.g., selegiline) and hepatic CYP1A2 (e.g., MEL, tizanidine, caffeine, and theophylline).