Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging drugs in endometriosis

Endometriosis is a common, estrogen-dependent, gynaecological disease, defined as the presence of endometrial-like tissue outside the uterus. Although several medications are used for treatment of the disease, they are associated with high recurrence rates, considerable side effects and limited duration of application. Due to these limitations and to the impact of endometriosis on the quality of life of affected women, their environment and the society, there is a great need for new drugs able to abolish endometriosis and its symptoms. Studies in recent years investigating the (patho)physiological mechanisms involved in disease aetiology have fostered the development of novel therapeutic concepts for endometriosis, by targeting the hypothalamic–pituitary–gonadal axis, by selective modulation of estrogenic and progestogenic pathways, by inhibiting angiogenesis or by interfering with inflammatory and immunological factors. This article presents a brief summary of the currently available medications and an overview regarding the development of some of the most interesting and/or most promising novel drug candidates for endometriosis.
The natural history of prostate carcinoma based on a Danish population treated with no intent to cure

Prostate carcinoma is one of the most commonly diagnosed cancers among Western males. In Denmark, the traditional therapeutic approach to prostate carcinoma regardless of tumor stage has been limited to palliative procedures. This conservative approach combined with a complete cancer and personal registration in Denmark provides an opportunity to describe the still debatable natural history of prostate carcinoma.
An acute care episode of a patient following bilateral total knee arthroplasty

More patients with bilateral joint problems are choosing to go through one surgery to replace both joints simultaneously rather than having two separate surgeries. The goals of physical therapy following the surgery are to decrease pain, maximize range of motion (ROM) and strength, improve ambulation, and improve overall function. Few studies have focused on the importance of the acute phase of rehabilitation and most concentrate instead on long-term outcomes and outpatient care. The patient was a 62-year-old male diagnosed with osteoarthritis of both knees. The day before the initial physical therapy evaluation, the patient underwent a bilateral total knee arthroplasty. By the end of his stay, active knee ROM increased to −6° to 88° on the right and −6° to 83° on the left. Passive ROM also increased to −5° to 90° on the right and −5° to 86° on the left. The patient was able to perform supine to sit transfers with supervision and sit to stand transfers with contact guard assistance and his ambulation progressed to walking 100 feet on level surfaces with a rolling walker and supervision. The positive gains of this patient suggest the potential value of high motivation combined with early aggressive physical therapy.
Ectodomain Lysines and Suramin Block of P2X1 Receptors

P2X1 receptors belong to a family of cation channels gated by extracellular ATP; they are found inter alia in smooth muscle, platelets, and immune cells. Suramin has been widely used as an antagonist at P2X receptors, and its analog 4,4′,4″,4‴-[carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino))] tetrakis-benzene-1,3-disulfonic acid (NF449) is selective for the P2X1 subtype. Human and mouse P2X1 receptors were expressed in human embryonic kidney cells, and membrane currents evoked by ATP were recorded. ATP (10 nm to 100 μm) was applied only once to each cell, to avoid the profound desensitization exhibited by P2X1 receptors. Suramin (10 μm) and NF449 (3–300 nm) effectively blocked the human receptor. Suramin had little effect on the mouse receptor. Suramin and NF449 are polysulfonates, with six and eight negative charges, respectively. We hypothesized that species differences might result from differences in positive residues presented by the large receptor ectodomain. Four lysines in the human sequence (Lys111, Lys127, Lys138, and Lys148) were changed individually and together to their counterparts in the mouse sequence. The substitution K138E, either alone or together with K111Q, K127Q, and K148N, reduced the sensitivity to block by both suramin and NF449. Conversely, when lysine was introduced into the mouse receptor, the sensitivity to block by suramin and NF449 was much increased for E138K, but not for Q111K, Q127K, or N148K. The results explain the marked species difference in antagonist sensitivity and identify an ectodomain lysine residue that plays a key role in the binding of both suramin and NF449 to P2X1 receptors.
Rotor loss estimation in permanent magnet machines with concentrated windings

The calculation of magnetic losses in the rotor of a three-phase motor with concentrated windings is presented in this paper. The finite-element code able to handle rotor motion and all the related phenomena (motional eddy currents and minor loops) is outlined. Solid and laminated rotors are considered, and losses are computed under no-load and load conditions. Finally, some experimental validations on a test prototype are given.
QT dispersion in patients with Churg-Strauss syndrome.

BACKGROUND Churg-Strauss syndrome (CSS) is a rare, systemic necrotising small and middle-sized vessel vasculitis, accompanied by blood eosinophilia, eosinophil infiltration of various tissues and bronchial asthma. Cardiac injury caused by myocardial eosinophilic infiltration and/or vasculitis in CSS seems to be very common. Active inflammatory process accompanied by myocardial fibrosis has been described in this population even despite disease remission. Nevertheless, little is known about the possible myocardial repolarisation abnormalities in CSS which may lead to life-threatening ventricular arrhythmias. AIM To evaluate myocardial repolarisation in CSS patients at the time of initial diagnosis and during the last disease remission. METHODS In 20 CSS patients (8 male, 12 female) QT dispersion (QTd) and QTc dispersion (QTcd) calculated from heart rate corrected QT (QTc) from the surface 12-lead electrocardiograms were measured at the time of initial diagnosis and during the last disease remission. As a control group, 20 sex- and age-matched healthy volunteers were studied. Transthoracic echocardiography was performed in all CSS patients at remission and in the control group. RESULTS QTcd was higher in CSS (n = 20) than in healthy controls (n = 20) in each period of time: at the time of initial diagnosis (45.4 ± 14.2 vs 26.1 ± 6.5, p < 0.0001) and at the remission (38.6 ± 13.4 vs 26.1 ± 6.5, p = 0.002). At the time of initial diagnosis in CSS patients with heart involvement (n = 13), when compared to patients without heart involvement, (n = 7), both QTcd (52.2 ± 12.1 vs 34.7 ± 10.7, p = 0.007) and QTd (37.7 ± 12.7 vs 24 ± 11.4, p = 0.008) were higher, and this difference remained significant at remission only for QTcd (46.7 ± 13.2 vs 33.1 ± 10.8, p = 0.03). No significant correlation was observed between QTcd/QTd and disease activity (measured using the Birmingham Vasculitis Activity Score - BVAS), eosinophil blood count, presence of ANCA, nor the duration of the disease. CONCLUSIONS The most pronounced increased QTcd was detected in the CSS patients with cardiac involvement at the time of initial diagnosis and remained higher at remission in all CSS patients when compared to healthy controls. Nevertheless, in the CSS patients, QTcd remains within the normal ranges, which may explain the relatively small number of ventricular arrhythmias in these patients.
Expression of endogenous nuclear bradykinin B2 receptors mediating signaling in immediate early gene activation

Bradykinin (BK) represents a pro‐inflammatory mediator that partakes in many inflammatory diseases. The mechanism of action of BK is thought to be primarily mediated by specific cell surface membrane B2 receptors (B2Rs). Some evidence has suggested, however, the existence of an intracellular/nuclear B2R population. Whether these receptors are functional and contribute to BK signaling remains to be determined. In this study, by mean of Western blotting, 3D‐confocal microscopy, receptor autoradiography and radioligand binding analysis, we showed that plasma membrane and highly purified nuclei from isolated rat hepatocytes contain specific B2R that bind BK. The results depicting B2R nuclear expression in isolated nuclear organelles were reproduced in situ on hepatic sections by immunogold labeling and transmission electron microscopy. Functional tests on single nuclei, by means of confocal microscopy and the calcium‐sensitive probe fluo‐4AM, showed that BK induces concentration‐dependent transitory mobilization of nucleoplasmic calcium; these responses were blocked by B2R antagonist HOE 140, not by the B1R antagonist R954 and, were also found in wild‐type C57/Bl6 mice, but not in B2R‐KO mice. In isolated nuclei, BK elicited activation/phosphorylation of Akt, acetylation of histone H3 and ensuing pro‐inflammatory iNOS gene induction as determined by Western blot and RT‐PCR. ChIP assay confirmed binding of acetylated‐histone H3 complexes, but not B2R, to promoter region of iNOS gene suggesting that B2R‐mediated gene expression is bridged with accessory downstream effectors. This study discloses a previously undescribed mechanism in BK‐induced transcriptional events, via intracrine B2R‐mediated signaling, occurring in rat autologous hepatic cells. J. Cell. Physiol. 216: 234–244, 2008. © 2008 Wiley‐Liss, Inc.
Knowledge of Osteoporosis Among Men in the Primary Care Setting

Objectives: Osteoporosis has been often viewed as a disease affecting women; however, men are at risk for osteoporosis, and the mortality after hip fracture in men older than 75 years of age is significantly higher than in women. We aimed to assess knowledge of osteoporosis and its risk factors in men. Methods: A questionnaire assessing knowledge of osteoporosis was presented to 136 male patients randomly in Internal Medicine and Family Practice clinics at Saint Joseph Hospital. Results: A total of 136 men agreed to fill in the questionnaire. Only 130 patients who completed the entire questionnaire were included in the data analysis. Twenty-three percent of men surveyed had never heard about osteoporosis. Thirty-nine percent were unaware that osteoporosis is directly responsible for disabling hip fractures. Sixty-seven percent did not know that a potential outcome of hip fracture is death. Only 38% recognized that smoking is a risk factor, 20% knew that excessive caffeine intake can put them at risk, and 35% realized that excessive alcohol intake is a risk factor. Only 21% could correctly identify the calcium-rich foods among the choices. There was a positive relationship (P < 0.05) between receiving an official discussion with a physician regarding osteoporosis and the actual score on the "knowledge of osteoporosis" questionnaire. Conclusion: A significant percentage of men are unaware of the complications and risk factors for osteoporosis. Receiving educational information about osteoporosis from a physician should be considered at an early stage, especially for those patients with modifiable risk factors.
Interrelation between inflammation, thrombosis, and neuroprotection in cerebral ischemia

Abstract Stroke by mechanism of thrombotic cerebral ischemia is one of the leading causes of death and/or disability worldwide. Current research is under consensus that there are sex-based differences in both the prevalence and presentation of stroke and thrombosis. Here we discuss the interrelation between thrombosis and inflammation and call attention to points in the cerebral ischemic cascade where estrogen may be involved in neuroprotection. Cerebral ischemia triggers a series of events including inflammation, which is deeply interrelated with thrombosis; inflammation not only produces local thrombosis, but thrombosis can also amplify inflammation especially through the synergism of leukocyte and platelet activity. Research involving experimental animal models of cerebral ischemia has shown that sex hormones, especially estrogen, offer a degree of neuroprotection. Mechanisms of this neuroprotection may be linked to certain anti-inflammatory properties of estrogen, as well as estrogen’s regulation of thrombosis through the lowering of coagulation factors, among others. It is also understood that sex hormones alter the function and morphology of platelets and fibrin networks, and changes in platelet and fibrin network morphology offer one of the earliest confirmations of inflammation. Sex hormone levels, inflammatory processes, and thrombotic mechanisms are profoundly interconnected in predicting the outcome of cerebral ischemia.
Corticosteroid‐induced scleroderma renal crisis

TO THE EDITOR: A 63-year-old woman presented with polyuria, polydipsia, lethargy and vomiting. Two weeks previously, she had been diagnosed as having diffuse scleroderma with possible interstitial lung disease, and had started taking 50 mg prednisolone daily. Her past history included diabetes, hypertension, hypercholesterolaemia and β-thalassemia trait, and her other medications were metformin, glibenclamide, quinapril and amlodipine. Examination revealed blood pressure 150/60 mmHg, a loud second heart sound with no murmurs, and late inspiratory crepitations at lung bases. Her serum creatinine concentration was 270 mol/L (compared with 100 mol/L two weeks previously) and serum glucose concentration was 26.5 mmol/L. Treatment by the admitting doctor included insulin, rehydration, and cessation of prednisolone (given hyperglycaemia) and quinapril (secondary to acute renal impairment). She developed a fever and cough, with bilateral pneumonia, which was treated with intravenous ceftriaxone. Despite normotension, concern regarding scleroderma renal crisis (SRC) was raised. On Day 12 of admission, when renal failure had developed to the dialysisdependent level (serum creatinine level, 690 mol/L), quinapril was recommenced for its proposed renoprotective effect and haemodialysis was initiated. Microangiopathic haemolytic anaemia (haemoglobin, 7.2 g/L) was diagnosed, with fragmented red blood cells (Box). Several months later, she continues on haemodialysis three times a week. Renal biopsy was not performed given the clinical picture of diffuse scleroderma and recent corticosteroid use with rapid development of renal failure — consistent with SRC. SRC is defined as rapidly progressive renal failure and/or new onset of malignant hypertension during the course of scleroderma, occurring in 15%–20% of patients with the diffuse variety.1 Risk factors include male sex, black race, and early diffuse scleroderma with rapidly progressive skin thickening.2 Precipitation of SRC by corticosteroid use, especially in normotensive patients, is well described, particularly with high-dose (>15 mg/day) treatment.2 Early diagnosis is critical because treatment may preserve renal function. Outcomes have improved with use of angiotensin-converting enzyme (ACE) inhibitors, which are thought to improve renal function by controlling the high renin levels seen in patients with SRC. About 61% of patients have a good outcome, with no or temporary dialysis.3 Predictors of poor outcome, despite ACE inhibitor use, include older age, male sex, higher initial serum creatinine level, and scleroderma myocardial disease. Eleven per cent of SRC patients remain normotensive and have significantly reduced 12-month survival rates. This may relate to delay in diagnosis of SRC. The use of high dose corticosteroids in patients with early diffuse scleroderma should be strongly discouraged, and intensive monitoring for SRC is recommended if low dose corticosteroids are required.
Yersinia enterocolitica Promotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

ABSTRACT Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogen Yersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulent Y. enterocolitica leads to vigorous intestinal and systemic adaptive immunity. Y. enterocolitica infection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4+ T cells produced Yersinia-specific gamma interferon (IFN-γ) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed to Y. enterocolitica were associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-γ and CD4+ cells, but not B cells, are critical for protection of neonates during primary Y. enterocolitica infection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4+ cells from wild-type, IFN-γ-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4+ T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-γ, IL-17A, or IL-17F. Overall, these studies support the idea that Y. enterocolitica promotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.
Factors influencing the use of mobile financial services: The extended technology acceptance model

Mobile service innovation has become a critical issue in the financial sectors. Currently, many banks in Taiwan have developed various mobile services for their customers. However, mobile services in financial sectors are different from Internet services because of the mobility. First, mobile services enable mobile extensions of existing electronic services and new services that are valuable to users on the move. Second, most people have their own, personal mobile devices in the hands, but they may not have the computers with them anytime. Although consumers' technology acceptance has been examined in the context of e-commerce, mobile financial services are gained scant attention. Thus, this study aims to explore the factors influencing the use of mobile financial services (MFS). We conducted a qualitative research in depth, and investigated a renowned bank in Taiwan which developed various MFS for customers. The findings reveal that mobility and personal habit are two important antecedents influencing the use of MFS. Mobility positively affects perceived ease-of-use and perceived usefulness, which in turn influence the use of MFS. Furthermore, personal habit positively affects the use of MFS.
Emergence of mmpT5 Variants during Bedaquiline Treatment of Mycobacterium intracellulare Lung Disease

ABSTRACT Bedaquiline (BDQ), a diarylquinoline antibiotic that targets ATP synthase, is effective for the treatment of Mycobacterium tuberculosis infections that no longer respond to conventional drugs. While investigating the off-label use of BDQ as salvage therapy, seven of 13 patients with Mycobacterium intracellulare lung disease had an initial microbiological response and then relapsed. Whole-genome comparison of pretreatment and relapse isolates of M. intracellulare uncovered mutations in a previously uncharacterized locus, mmpT5. Preliminary analysis suggested similarities between mmpT5 and the mmpR5 locus, which is associated with low-level BDQ resistance in M. tuberculosis. Both genes encode transcriptional regulators and are adjacent to orthologs of the mmpS5-mmpL5 drug efflux operon. However, MmpT5 belongs to the TetR superfamily, whereas MmpR5 is a MarR family protein. Targeted sequencing uncovered nonsynonymous mmpT5 mutations in isolates from all seven relapse cases, including two pretreatment isolates. In contrast, only two relapse patient isolates had nonsynonymous changes in ATP synthase subunit c (atpE), the primary target of BDQ. Susceptibility testing indicated that mmpT5 mutations are associated with modest 2- to 8-fold increases in MICs for BDQ and clofazimine, whereas one atpE mutant exhibited a 50-fold increase in MIC for BDQ. Bedaquiline shows potential for the treatment of M. intracellulare lung disease, but optimization of treatment regimens is required to prevent the emergence of mmpT5 variants and microbiological relapse.
An introduction to oil market volatility analysis

Modelling and forecasting crude oil price volatility is crucial in many financial and investment applications. The main purpose of this paper is to review and assess the current state of oil market volatility knowledge. It highlights the properties and characteristics of the oil price volatility that models seek to capture, and discuss the different modelling approaches to oil price volatility. Asymmetric response to price change, persistence and mean reversion, structural breaks, and possible market spillover of volatility are discussed. To complement the discussion, West Texas Intermediate futures price data are used to illustrate these properties using non-parametric and conditional modelling methods. The generalised autoregressive conditional heteroskedasticity-type models usually applied in the oil price volatility literature are also explored. We additionally examine the exogenous factors that may influence volatility in the oil markets.
Is Intracellular Ice Formation the Cause of Death of Mouse Sperm Frozen at High Cooling Rates?1

Abstract Mouse spermatozoa in 18% raffinose and 3.8% Oxyrase in 0.25× PBS exhibit high motilities when frozen to −70°C at 20–130°C/min and then rapidly warmed. However, survival is <10% when they are frozen at 260 or 530°C/min, presumably because, at those high rates, intracellular water cannot leave rapidly enough to prevent extensive supercooling and this supercooling leads to nucleation and freezing in situ (intracellular ice formation [IIF]). The probability of IIF as a function of cooling rate can be computed by coupled differential equations that describe the extent of the loss of cell water during freezing and from knowledge of the temperature at which the supercooled protoplasm of the cell can nucleate. Calculation of the kinetics of dehydration requires values for the hydraulic conductivity (Lp) of the cell and for its activation energy (Ea). Using literature values for these parameters in mouse sperm, we calculated curves of water volume versus temperature for four cooling rates between 250 and 2000°C/min. The intracellular nucleation temperature was inferred to be −20°C or above based on the greatly reduced motilities of sperm that underwent rapid cooling to a minimum temperature of between −20 and −70°C. Combining that information regarding nucleation temperature with the computed dehydration curves leads to the conclusion that intracellular freezing should occur only in cells that are cooled at 2000°C/min and not in cells that are cooled at 250–1000°C/min. The calculated rate of 2000°C/min for IIF is approximately eightfold higher than the experimentally inferred value of 260°C/min. Possible reasons for the discrepancy are discussed.