Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian Control of Neuroendocrine Circuits Regulating Female Reproductive Function

Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary–gonadal (HPG) axis functioning. In mammals, the master circadian pacemaker in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus coordinates reproductively relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene) lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the gonadotropin-releasing hormone (GnRH) system in control of the preovulatory luteinizing hormone (LH) surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge.
Changes in Porteus Maze Scores of Brain-Operated Schizophrenics after an Eight-Year Interval

1. Eight years after the New York State Brain Research project, 27 operated and 23 non-operated hospitalized chronic schizophrenics, of an original population of 44 operated and 24 non-operated subjects, were reexamined with the Porteus Maze, the Wechsler-Bellevue I, revised Capps Homograph and Weigl Sorting Test. Analysis of the results of the Porteus Maze, which best represented the salient changes with all measures, showed systematic differences between initial and long-term post-operative effects. 2. In contrast to conclusions of a “drop and rise” pattern and “no permanent deficits” in intellectual functions by the original and two related Columbia-Greystone studies, scores eight years later showed statistically significant losses for operated groups in the Porteus Maze and seven other of the 14 individual measures. 3. Changes between initial and eight-year post-operative effects were related to four factors ( a ) length of the post-operative interval, ( b ) specific site of surgical intervention, ( c ) age of the subject at time of operation, and ( d ) nature of the measure, Of the four operated groups, only younger subjects with orbital topectomy failed to show successive post-operative losses. 4. The pattern of increasing decrements in psychological test scores is consonant with findings of increasing neurological degeneration reported in studies of cerebra of other subjects with psychosurgical lesions. The rate and amount of degeneration were found to be positively correlated with the factors of length of post-operative interval, site of surgical intervention (posterior lesions result in greater degeneration than anterior lesions) and age of the subject at the time of operation. This consonance suggests that changes in test scores may be the psychological analogue for neuro-anatomical changes due to later secondary degeneration. 5. Differences in long-term effects of excisions of lower (orbital) and upper (superior) portions in the forebrain contradict the theory of equipotentiality of areas in the “frontal lobes”. 6. Comparisons of early and later post-operative effects on older and younger subjects with orbital or superior topectomy clearly illustrate the complex and dynamic temporal nature of the effects of “brain-damage”. The effects of diaschisis or post-operative shock and the influence of the four factors cited in (3) above indicate that the reliability and validity of findings of any study are limited to its particular post-trauma time span. Results obtained shortly following brain insult are least reliable. The diverse and contradictory conclusions of many studies of apparently similar “brain damaged” populations may conceivably be reconciled when the above factors are taken into account.
On the APM power spectrum and the CMB anisotropy: evidence for a phase transition during inflation?

Adams et al. have noted that according to our current understanding of the unification of fundamental interactions, there should have been phase transitions associated with spontaneous symmetry breaking during the inflationary era. This may have resulted in the breaking of scale-invariance of the primordial density perturbation for brief periods. A possible such feature was identified in the power spectrum of galaxy clustering in the automated plate measurement (APM) survey at the scale k ∼ 0.1 h Mpc − 1 and it was shown that the secondary acoustic peaks in the power spectrum of the cosmic microwave background (CMB) anisotropy should consequently be suppressed. We demonstrate that this prediction is confirmed by the recent Boomerang and Maxima observations, which favour a step-like spectral feature in the range k ∼ (0.06–0.6) h Mpc − 1, independently of the similar previous indication from the APM data. Such a spectral break enables an excellent fit to both APM and CMB data with a baryon density consistent with the big bang nucleosynthesis (BBN) value. It also allows the possibility of a matter-dominated universe with zero cosmological constant, which we show can now account for even the evolution of the abundance of rich clusters.
Repetitive transcranial magnetic stimulation (rTMS) augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant obsessive-compulsive disorder (OCD): a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE Randomized controlled trials (RCTs) on repetitive transcranial magnetic stimulation (rTMS) as augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant obsessive-compulsive disorder (OCD) have yielded conflicting results. Therefore, this meta-analysis was conducted to assess the efficacy of this strategy for SSRI-resistant OCD. METHODS Scientific and medical databases, including international databases (PubMed, MEDLINE, EMBASE, CCTR, Web of Science, PsycINFO), two Chinese databases (CBM-disc, CNKI), and relevant websites dated up to July 2014, were searched for RCTs on this strategy for treating OCD. Mantel-Haenszel random-effects model was used. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, response rates and drop-out rates were evaluated. RESULTS Data were obtained from nine RCTs consisting of 290 subjects. Active rTMS was an effective augmentation strategy in treating SSRI-resistant OCD with a pooled WMD of 3.89 (95% CI = [1.27, 6.50]) for reducing Y-BOCS score and a pooled odds ratio (OR) of 2.65 (95% CI = [1.36, 5.17] for response rates. No significant differences in drop-out rates were found. No publication bias was detected. CONCLUSION The pooled examination demonstrated that this strategy seems to be efficacious and acceptable for treating SSRI-resistant OCD. As the number of RCTs included here was limited, further large-scale multi-center RCTs are required to validate our conclusions.
The effect of gender on aminoglycoside-associated nephrotoxicity .

AIMS The kidney disease improving global outcomes (KDIGO) clinical practice guidelines for acute kidney injury (AKI) has endorsed the widely held belief that female gender is a risk factor for aminoglycoside-associated nephrotoxicity (AAN). In contrast, female gender is protective in animal models. In light of this dichotomy, we sought to explore this relationship in greater detail. METHODS We performed a meta-analysis of studies published between 1978 and 2015 which examined aminoglycoside nephrotoxicity and provided gender-specific data. RESULTS 24 studies were identified that provided univariate gender-specific data. The incidence of AAN did not differ between the sexes (odds ratio (OR) for females vs. males 1.00 (0.81, 1.22), p = 0.97, n = 5,980). Twelve studies utilized logistic regression analysis with gender as a covariate. Meta-analysis of the 5 studies that utilized multivariate analysis and reported gender-specific OR found no effect of gender on the risk of AAN (OR 0.99 (0.58, 1.69), p = 0.96, n = 2,994). Similarly, gender was not an independent risk factor for AAN in the remaining 7 studies that utilized multivariate analysis with gender as a covariate but failed to report gender-specific OR (n = 1,636). DISCUSSION Our meta-analysis contradicts the generally held consensus that female gender is an independent risk factor for the development of AAN. Our findings may have much wider implications insofar as AAN cannot be used as an example to support the conclusion of the KDIGO Clinical Practice Guidelines that female gender is an independent risk factor for AKI.
LRP1 Functions as an Atheroprotective Integrator of TGFβ and PDGF Signals in the Vascular Wall: Implications for Marfan Syndrome

Background The multifunctional receptor LRP1 controls expression, activity and trafficking of the PDGF receptor-β in vascular smooth muscle cells (VSMC). LRP1 is also a receptor for TGFβ1 and is required for TGFβ mediated inhibition of cell proliferation. Methods and Principal Findings We show that loss of LRP1 in VSMC (smLRP−) in vivo results in a Marfan-like syndrome with nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers, tortuous aorta, and increased expression of the TGFβ target genes thrombospondin-1 (TSP1) and PDGFRβ in the vascular wall. Treatment of smLRP1− animals with the PPARγ agonist rosiglitazone abolished nuclear pSmad accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth muscle proliferation, fibrosis and atherosclerosis independent of plasma cholesterol levels. Conclusions and Significance Our findings are consistent with an activation of TGFβ signals in the LRP1-deficient vascular wall. LRP1 may function as an integrator of proliferative and anti-proliferative signals that control physiological mechanisms common to the pathogenesis of Marfan syndrome and atherosclerosis, and this is essential for maintaining vascular wall integrity.
Evaluation of frozen semen by a crosomal integrity and sperm concentration - two vital quality parameters of male fertility in bovines.

Acrosomal integrity and sperm concentration are two important parameters to assess the quality of frozen semen doses which in terms validates the fertilizing capacity and conception rate. The present study was undertaken to evaluate acrosomal integrity by Giemsa's stain and sperm concentration of FSS using improved neubauer chamber in Exotic pure Jersey, Crossbred Jersey, Indigenous Gir cattle and Indigenous Murrah buffalo prior to the field use. The overall values of Giemsa's stain were observed as 73.74±0.31, 18.65±0.33 and 7.79±0.25 percent for Intact Acrosome, Partially Damaged Acrosome and Fully Damaged Acrosome, respectively. Overall values of sperm concentration were 21.98±0.28 million per straw. The study indicated that there was no significant difference (P<0.05) among the breeds and the values mostly correlates with the guideline of Minimum Standard Protocol for Production of bovine semen, 2012 of Govt. of India.
Automatically Detecting Pain in Video Through Facial Action Units

In a clinical setting, pain is reported either through patient self-report or via an observer. Such measures are problematic as they are: 1) subjective, and 2) give no specific timing information. Coding pain as a series of facial action units (AUs) can avoid these issues as it can be used to gain an objective measure of pain on a frame-by-frame basis. Using video data from patients with shoulder injuries, in this paper, we describe an active appearance model (AAM)-based system that can automatically detect the frames in video in which a patient is in pain. This pain data set highlights the many challenges associated with spontaneous emotion detection, particularly that of expression and head movement due to the patient's reaction to pain. In this paper, we show that the AAM can deal with these movements and can achieve significant improvements in both the AU and pain detection performance compared to the current-state-of-the-art approaches which utilize similarity-normalized appearance features only.
Abruptio Placentae at The University of Nigeria Teaching Hospital, Enugu: A 3‐Year Study

EDITORIAL COMMENT: This paper will remind readers about the clinical problems of abruptio placentae that accounts for about 20% of perinatal deaths and can threaten maternal life, usually by haemorrhage associated with blood coagulation failure. In the author's hospital in Nigeria which serves a population of 4 million, the incidence of abruption was 0.4% (81 of 81,215 confinements). This low incidence is partly accounted for by the strict clinical criteria for diagnosis (abdominal pain 85%, tenderness 88%) which in turn explained the high incidence of blood transfusion (93%) and high perinatal mortality rate (58%). These results are similar to those reported from the Maternity Hospital, University of Cape Town, 1986, where the incidence of abruption was 0.6% (149 of 25,402) and the perinatal mortality rate 55%. The incidence reported from the National Maternity Hospital, Dublin, 1986, was 0.3% (22 of 7,823) with a perinatal mortality rate of 59%, although blood transfusion was required in only 23% of patients. The prize for perinatal mortality associated with placenta! abruption must belong to Hong Kong — in the Queen Mary and Tsan Yuk Hospitals, 1983, the incidence of abruptio placentae was 0.3% and the associated perinatal mortality rate was 5%. It would seem that not only do the Chinese have low incidences of prematurity, fetal malformations and multiple pregnancy, but also fewer cases of severe abruption. At the Mercy Maternity hospital, Melbourne, there is a much higher incidence of abruption but here the diagnostic criterion is evidence of an old retroplacental clot at delivery — the incidence in this hospital, 1984–1986, was 2.2% (337 of 15,658) with a perinatal mortality rate of 15% and a blood transfusion rate of 17%. In the Melbourne series disseminated intravascular coagulopathy occurred in 1% of patients with abruption whereas in the author's series the incidence was 11%. The author concludes that good antenatal and intrapartum care minimizes the maternal and fetal hazards of placenta! abruption; he also gives the good advice that coagulation failure must be ruled out before embarking on Caesarean section in these patients.
Antibodies to the kinesin motor domain and CENP-E inhibit microtubule depolymerization-dependent motion of chromosomes in vitro

Chromosomes can move with the ends of depolymerizing microtubules (MTs) in vitro, even in the absence of nucleotide triphosphates (Coue, M., V. A. Lombillo, and J. R. McIntosh. 1991. J. Cell Biol. 112:1165-1175.) Here, we describe an immunological investigation of the proteins important for this form of motility. Affinity-purified polyclonal antibodies to kinesin exert a severe inhibitory effect on depolymerization-dependent chromosome motion. These antibodies predominantly recognize a polypeptide of M(r) approximately 250 kD on immunoblots of CHO chromosomes and stain kinetochores as well as some vesicles that are in the chromosome preparation. Antibodies to CENP-E, a kinetochore-associated kinesin-like protein, also recognize a 250-kD electrophoretic component, but they stain only the kinetochroe region of isolated chromosomes. Polyclonal antibodies that recognize specific domains of the CENP-E polypeptide affect MT disassembly-dependent chromosome motion in different ways; antibodies to the head or tail portions slow motility threefold, while those raised against the neck region stop motion completely. Analogous antibodies that block conventional, ATP-dependent motility of cytoplasmic dynein (Vaisberg, G., M. P. Koonce, and J. R. McIntosh. 1993. J. Cell Biol. 123:849-858) have no effect on disassembly-dependent chromosome motion, even though they bind to kinetochores. These observations suggest that CENP-E helps couple chromosomes to depolymerizing MTs. A similar coupling activity may allow spindle MTs to remain kinetochore-bound while their lengths change during both prometaphase and anaphase A.
Predicting Suicide Ideation for Substance Users: The Role of Self-Esteem, Abstinence, and Attendance at 12-Step Meetings

This study tested if a three-way interaction between gender, abstinence, and self-esteem could predict the occurrence of suicidal thoughts in a sample of drug users who are one year post-treatment. It was expected that those who resolved their drug and alcohol problems and had higher self-esteem would have a lower risk of suicide ideation than those who had resolved their drug and alcohol problems (e.g. were abstinent) and had lower self-esteem, and that this effect would be stronger for women than men. Using a 3-step hierarchical logistic regression, results indicated a significant 2-way interaction between self-esteem and abstinence in the predicted direction, and no effect for gender. However, it was also found that those who had lower levels of self-esteem, regardless of abstinence or continued use, had virtually identical odds of suicidal ideation. Further, increased frequency of attendance at AA/NA meetings also predicted a higher risk of suicide ideation. This suggests that careful assessment of depression symptoms or suicidal ideation for drug users seeking assistance be completed before automatically urging attendance at 12-step meetings. Implications for clinical work with clients are presented.
Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats

Using adult rats, the characteristic transporting system for lactoferrin (LF) from intestinal lumen into the blood circulation was investigated. The rats were randomly divided into two groups, a non‐collected thoracic lymph (NC) group and a collected thoracic lymph (LC) group. Peripheral blood and thoracic lymph were collected from a jugular vein and a thoracic lymph duct, respectively, under anaesthesia. Bovine LF (bLF) was infused into the duodenal lumen by needle over a 1‐min period at a dose of 1 g kg−1. The transported bLF in the plasma and lymph was assayed quantitatively by double‐antibody enzyme‐linked immunosorbent assay (ELISA). Morphological investigation was also carried out in the intestine, lymph node, and liver. Following intraduodenal administration of bLF, the transported bLF in the NC group was detected in the plasma, and reached a peak value at 2 h. Furthermore, the bLF concentration in the thoracic duct lymph fluid in the LC group increased significantly, and peaked 2 h after the administration. In addition, bLF was not detected in the plasma of the LC group. Immunohistochemical analysis clearly showed anti‐bLF positive particles in the epithelial cells of the apical villi. The striated border and baso‐lateral membrane were also bLF positive. These results suggest that intraduodenally infused bLF is transported into the blood circulation via the lymphatic pathway, not via portal circulation in adult rats.
Credit RiskA Survey

This paper presents a review of the developments in the area of credit risk. Starting in 1974, Merton developed a pricing method for a bond facing default risk, which was mainly settled in the framework of Black and Scholes (1973). Certain attempts have been made to relax the assumptions, giving rise to a class of models called structural models. A second class, called hazard rate models, was first addressed in Pye (1974) and more recently reached attention with the works of, e.g., Lando (1994). There are extensions in different directions, e.g., models which incorporate ratings, models for a portfolio of bonds or market models. The so called commercial models are readily implemented models which are widely accepted in practice. Finally we describe certain credit derivatives. 1. Structural Models The first class of models tries to measure the credit risk of a corporate bond by relating the firm value of the issuing company to its liabilities. If the firm value at maturity T is below a certain level, the company is not able to pay back the full amount of money, so that a default event occurs. 1.1. Merton (1974). In his landmark paper Merton (1974) applied the framework of Black and Scholes (1973) to the pricing of a corporate bond. A corporate bond promises the repayment F at maturity T . Since the issuing company might not be able to pay the full amount of money back, the payoff is subject to default risk. Let Vt denote the firm’s value at time t. If, at time T , the firm’s value VT is below F , the company is not able to make the promised repayment so that a default event occurs. In Merton’s model it is assumed that there are no bankruptcy costs and that the bond holder receives the remaining VT , thus facing a financial loss. If we consider the payoff of the corporate bond in this model, we see that it is equal to F in the case of no default (VT ≥ F ) and VT otherwise, i.e., 1{VT >F}F + 1{VT≤F}VT = F − (F − VT ). 1991 Mathematics Subject Classification. 2000 AMS Classification. Primary: 60-02, 91B28, 91B26, Secondary: 60H30, 60J75.
Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

Background Severe and persistent mental illnesses in children and adolescents, such as early- onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP. Methods PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined. Results Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare. Conclusions The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.