Miracle-dz/UniFAR-FTUs huggingface dataset:
PHOTOSENSORY TRANSDUCTION IN CILIATES. I. AN ANALYSIS OF LIGHT‐INDUCED ELECTRICAL AND MOTILE RESPONSES IN Stentor coeruleus

Abstract— Light‐induced membrane potantial changes and motile responses have been studied in Stentor cells with intracellular microelectrodes and video microscopy, respectively. Intracellulae microelectrode showed that step‐up increase in light induced an electrical membrane response which consisted of an initial membrane depolarization (photoreceptor potential) followed by an action potential and maintaining phase of depolarization (afterdepolarization). The amplitude of the receptor potetial is dependent on the intensity of light stimulus and the action potetials appears with a lag period (latency) after the onset of light stimuklus. The extent of the membrane established between the latency for te action poitential and the onset of ciliary reversal (stop responses). A time correlation was also observed between the duration of the membrane afterdepolarization and the duration of backward swimming. the action spectrum for the photoreceptor potential amplitude of Stentor resembled the action spectra for the latency of ciliary reversal and the photoresponsiveness, iondicating that the photomovement response and membrane potential changes are coupled through the same photosensor system. A hypothesis on the photosensory transduction chain in Stentor is discussed according to ehich the photoreceptors and the ciliary apparatus is mediated by the membrane potential canges.
Cellular and animal indispensable amino acid limitation responses and health promotion. Can the two be linked? A critical review

Cellular growth repression can mediate positive health outcomes by improving resistance while delaying the manifestation and decelerating the progression, of chronic diseases. Sensing systems that respond to amino acid limitation are, the general control non-derepressible kinase 2 (GCN2), the mammalian target of rapamycin (mTOR; namely mammalian target of rapamycin complex 1), the extracellular signal-regulated kinase (ERK)–mitogen-activated protein kinase pathway, the adenosine 5-mono-phosphate-activated protein kinase system. GCN2 particularly, under limiting essential amino acid conditions, activates the integrated stress response (ISR) causing selective up- /down-regulation of pro-survival/pro-apoptotic genes, respectively, rendering beneficial adaptation responses to amino acid limitation. This review attempts to bridge the link between molecular events and mechanisms observed at the cellular level with the potential health benefits possibly achieved at the whole organism level. The article describes mechanisms of essential amino acid sensing and provides a discussion on relevant research that suggests a potential role of essential amino acid sensing for promoting health.
Impaired Maraviroc and Raltegravir Clearance in a Human Immunodeficiency Virus–Infected Patient with End‐Stage Liver Disease and Renal Impairment: A Management Dilemma

Current product labels for maraviroc and raltegravir provide no dosing guidance for patients with end‐stage liver disease and worsening renal function. We describe a 41‐year‐old man with human immunodeficiency virus (HIV) infection and rapidly progressive liver failure and vanishing bile duct syndrome at presentation. Despite discontinuation of all potential offending drugs, the patient's liver function continued to deteriorate. To achieve and maintain HIV suppression while awaiting liver transplantation, a regimen consisting of maraviroc, raltegravir, and enfuvirtide was started. These agents were chosen because the patient was not exposed to them before the onset of liver failure. While receiving product label–recommended twice‐daily dosing of these drugs, he achieved and maintained HIV suppression. During a complicated and prolonged hospitalization, the patient also developed renal dysfunction. As hepatic metabolism is the primary route of clearance of maraviroc and raltegravir, we predicted that using approved doses of these drugs could result in significant drug accumulation. Since the safety profiles of supratherapeutic concentrations of these agents are not well defined, we chose to use therapeutic drug monitoring to guide further dosing. The reported concentrations showed severely impaired metabolic clearance of both drugs, with markedly prolonged elimination half‐lives of 189 hours for maraviroc and 61 hours for raltegravir. Previously reported half‐lives for maraviroc and raltegravir in HIV‐infected patients with normal hepatic and renal function are 14–18 hours and 9–12 hours, respectively. Based on these results, the dosing intervals were extended from twice/day to twice/week for maraviroc and every 48 hours for raltegravir. Unfortunately, the patient's clinical condition continued to deteriorate, and he eventually died of complications related to end‐stage liver disease. This case illustrates the difficulties in managing antiretroviral therapy in an HIV‐infected patient with combined severe liver and renal failure. Prolonged excessively high exposure to maraviroc and raltegravir is likely to result in some level of concentration‐dependent toxicity. Until more data are available, therapeutic drug monitoring remains the only evidence‐based approach to optimize dosage selection of these drugs in this patient population.
Measuring service quality in telematics service: development and validation of multidimensional TeleServQ scale

The extensive use of telematics system in the new generation of automobiles contributed to the rising trend of using automobiles as a channel to provide remote service. Yet the measurement of telematics service quality (TeleServQ) is not well established. This paper aims to identify the dimensions of TeleServQ. In-depth interviews are used to investigate the initial items in measuring telematics service. Conceptual framework of TeleServQ scale is proposed based on items sorting. Then the multidimensional scale is refined and validated with questionnaire survey. As a result, six dimensions including efficiency, system reliability, information quality, security, customisation and call centre service are identified. Some of the dimensions are consistent with the literature related to technology-based services, and others are specific in telematics context. Among six dimensions, efficiency and system reliability have the strongest relationship with customer satisfaction and loyalty intention. The scale demonstrates good psychometric properties based on the findings of reliability and validity tests. Finally, theoretical contributions and managerial implications about our TeleServQ scale are further discussed.
Factors Affecting Long-Term Treatment Results of Displaced Intraarticular Calcaneal Fractures: A Post Hoc Analysis of a Prospective, Randomized, Controlled Multicenter Trial

Objectives: To study the factors affecting long-term treatment results of displaced intraarticular calcaneal fractures (DIACFs). Design: A post hoc analysis. Settings: Tertiary care teaching hospitals. Patients: Eight to twelve years of results from a randomized controlled multicenter trial of operative versus nonoperative treatment (n = 56) were divided into 2 groups: the superior 50% results (n = 28) and the inferior 50% results (n = 28), regardless of the treatment given. The determinant of this division was a visual analog score for pain and function. Interventions: The operative treatment consists of open reduction and internal fixation, whereas the nonoperative treatment consists of nonweight bearing and early range of motion exercise. Main Outcome Measurements: A visual analog score for pain and function, the short-form 36 (SF-36) general health outcome questionnaire, the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scale, and Olerud-Molander score. We compared age, sex, fracture type (Sanders classification), treatment given, Böhler angle, residual articular surface step-off at healing, type of occupation, and injury insurance between the 2 groups. Results: Patients of the superior group had higher physical SF-36, AOFAS, and Olerud-Molander score than in the inferior group. Operative treatment, better Böhler angle and articular surface restoration, light labor/retirement, and absence of injury insurance were more common in the superior group. Age, sex, pretreatment Böhler angle, and fracture type were comparable in the superior and inferior groups. Conclusions: The decision making for definitive treatment of intraarticular calcaneal fractures is multifactorial with a spectrum of results and trends such as patient demographic features that should be considered in choosing the best treatment option. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Amelogenin- and Enamelysin (Mmp-20)-Deficient Mice Display Altered Birefringence in the Secretory-Stage Enamel Organic Extracellular Matrix

Dental enamel is the most mineralized tissue of vertebrate organisms. Enamel biosynthesis is initiated by the secretion, processing, and self-assembly of a complex mixture of proteins. The formation of an ordered enamel organic extracellular matrix (ECM) seems be a crucial step for the proper formation of mineral phase. Polarizing microscopy demonstrates that the ordered supramolecular structure of the secretory-stage enamel organic ECM is strongly birefringent. In the present work we analyzed the birefringence of secretory-stage enamel organic ECM in amelogenin (Amelx)- and enamelysin (Mmp20)-deficient mice. Female Amelx+/− animals showed significant reduction in optical retardation values when compared with the Amelx+/+ subgroup (p = 0.0029). The secretory-stage enamel organic ECM of the Amelx−/− subgroup did not exhibit birefringence. The secretory-stage enamel organic ECM of Mmp20−/− mice showed a significant decrease in optical retardation as compared with Mmp20+/+ and Mmp20+/− mice (p = 0.0000). Mmp20+/− and Mmp20+/+ mice exhibited similar birefringence (p = 1.0000). The results presented here support growing evidence for the idea that the birefringence of secretory-stage enamel organic ECM is influenced by the ordered supramolecular organization of its components.
Identity, identification and medical education: why should we care?

Context Medical education is as much about the development of a professional identity as it is about knowledge learning. Professional identities are contested and accepted through the synergistic internal–external process of identification that is constituted in and through language and artefacts within specific institutional sites. The ways in which medical students develop their professional identity and subsequently conceptualise their multiple identities has important implications for their own well‐being, as well as for the relationships they form with fellow workers and patients.
Multiple Oral Candida Infections in Patients with Sjögren’s Syndrome — Prevalence and Clinical and Drug Susceptibility Profiles

Objective. To determine the prevalence of oral candidiasis and multiple oral Candida infections in patients with primary Sjögren’s syndrome (SS), and the clinical and drug susceptibility profile. Methods. Thirty patients with primary SS were enrolled in our study. The diagnosis of oral candidiasis was based on the clinical manifestation, and confirmed by a concentrated rinse culture. Candida spp. assessment was accomplished using standard methods: Sabouraud dextrose agar with 50 mg/l chloramphenicol and CHROMagar were used for the rapid screening of clinical species, followed by the API 20C system for further species identification. In vitro antifungal drug susceptibility of Candida isolates was determined by the minimal inhibitory concentrations. Results. In our study, 87% (26/30) of subjects had oral candidiasis, in which 42% (11/26) had multiple Candida spp. infection. Although C. albicans remains the predominant isolate, other rare species such as C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei were present, alone or in combination. Chronic atrophic candidiasis is the most common clinical type of oral candidiasis in patients with SS. The susceptibilities of the 44 Candida isolates to 7 antifungal agents varied dramatically. The resistance to azoles was remarkable, and the phenomenon of cross-resistance between itraconazole and fluconazole was observed. Conclusion. Patients with primary SS carry a high risk of oral candidiasis and a high frequency of multiple Candida infections. The azole resistance patterns of Candida spp. support the necessity for drug susceptibility testing as a routine procedure for patients with oral Candida infections.
Molecular Epidemiology of Respiratory Syncytial Virus Infections among Children with Acute Respiratory Symptoms in a Community over Three Seasons

ABSTRACT To study the molecular epidemiology of respiratory syncytial virus (RSV) in a community, children with acute respiratory symptoms at a pediatric outpatient clinic in Niigata, Japan, were analyzed over three seasons from November 2001 to July 2004. Of 499 nasopharyngeal aspirate specimens, 185 (37.1%) were RSV positive, and only 8 (4.5%) of 177 patients were shown by the reverse transcription (RT)-PCR method to be reinfected. RSV infection occurred beginning in the early winter, and the rates declined in the spring. The predominant subgroup changed from A to B and returned to A over the three seasons. Phylogenetic analysis also revealed that multiple genotypes cocirculated each year, with genotype GA5 of subgroup A predominating in the 2001-2002 and the 2003-2004 seasons. A new genotype of subgroup B (named BA, according to the nomenclature for viruses) with a 60-nucleotide insertion in the second variable region of the attachment glycoportein protein was predominant as an emerging strain in the 2002-2003 season, but this was not associated with new epidemiological or clinical features, unlike the cases of disease caused by other genotypes in the other seasons. In conclusion, our molecular analysis of RSV confirms that multiple genotypes cocirculate each year and that the genotype predominating may shift with the season. Support for determination of the genotype by RT-PCR as an effective tool for characterization of RSV circulation patterns in the community is provided.
KPT‐330 inhibitor of CRM1 (XPO1)‐mediated nuclear export has selective anti‐leukaemic activity in preclinical models of T‐cell acute lymphoblastic leukaemia and acute myeloid leukaemia

This study explored the anti‐leukaemic efficacy of novel irreversible inhibitors of the major nuclear export receptor, chromosome region maintenance 1 (CRM1, also termed XPO1). We found that these novel CRM1 antagonists, termed SINE (Selective Inhibitors of Nuclear Export), induced rapid apoptosis at low nanomolar concentrations in a panel of 14 human T‐cell acute lymphoblastic leukaemia (T‐ALL) cell lines representing different molecular subtypes of the disease. To assess in vivo anti‐leukaemia cell activity, we engrafted immunodeficient mice intravenously with the human T‐ALL MOLT‐4 cells, which harbour activating mutations of NOTCH1 and NRAS as well as loss of function of the CDKN2A, PTEN and TP53 tumour suppressors and express a high level of oncogenic transcription factor TAL1. Importantly, we examined the in vivo anti‐leukaemic efficacy of the clinical SINE compound KPT‐330 against T‐ALL and acute myeloid leukaemia (AML) cells. These studies demonstrated striking in vivo activity of KPT‐330 against T‐ALL and AML cells, with little toxicity to normal murine haematopoietic cells. Taken together, our results show that SINE CRM1 antagonists represent promising ‘first‐in‐class’ drugs with a novel mechanism of action and wide therapeutic index, and imply that drugs of this class show promise for the targeted therapy of T‐ALL and AML.
Perspective-Taking and Depth of Theory-of-Mind Reasoning in Sequential-Move Games

Theory-of-mind (ToM) involves modeling an individual's mental states to plan one's action and to anticipate others' actions through recursive reasoning that may be myopic (with limited recursion) or predictive (with full recursion). ToM recursion was examined using a series of two-player, sequential-move matrix games with a maximum of three steps. Participants were assigned the role of Player I, controlling the initial and the last step, or of Player II, controlling the second step. Appropriate for the assigned role, participants either anticipated or planned Player II's strategy at the second step, and then determined Player I's optimal strategy at the first step. Participants more readily used predictive reasoning as Player II (i.e., planning one's own move) than as Player I (i.e., anticipating an opponent's move), although they did not differ when translating reasoning outcome about the second step to optimal action in the first step. Perspective-taking influenced likelihood of predictive reasoning, but it did not affect the rate at which participants acquired it during the experimental block. We conclude that the depth of ToM recursion (related to perspective-taking mechanisms) and rational application of belief-desire to action (instrumental rationality) constitute separate cognitive processes in ToM reasoning.
Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART II: Multidisciplinary management

Biliary tract cancers (gallbladder cancer, intra‐ and extra‐hepatic cholangiocarcinoma and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases. J. Surg. Oncol. 2012; 106:339–345. © 2012 Wiley Periodicals, Inc.
The incidence of deep venous thrombosis in Chinese medical Intensive Care Unit patients.

OBJECTIVE To evaluate the incidence of deep venous thrombosis in critically ill, Intensive Care Unit patients of Chinese ethnicity. DESIGN Prospective, observational study. SETTING Intensive Care Unit in a Hong Kong teaching hospital. PATIENTS Consecutive adult Chinese medical patients not receiving pharmacological or mechanical prophylaxis for deep venous thrombosis. MAIN OUTCOME MEASURES Compression and duplex Doppler ultrasound examinations of the lower limbs within 24 hours of admission and twice weekly thereafter during their Intensive Care Unit stay. After discharge, a 1-week follow-up investigation was also performed. Demographic data and risk factors for deep venous thrombosis were prospectively recorded. RESULTS Over a 9-month study period, 80 patients were investigated. Deep venous thrombosis was detected by ultrasound examination in 15 (19%) of the patients (95% confidence interval, 14-23%). Nine of 15 had isolated below-knee deep venous thrombosis, and of these, five had bilateral involvement. Characteristics of patients with or without deep venous thrombosis were similar. Of the 15 patients who had a positive ultrasound examination, only four (27%) had clinical signs of deep venous thrombosis. Of the 65 patients without a positive ultrasound examination, only two (3%) had positive clinical signs (P=0.01). This yielded a moderate positive likelihood ratio of 9 (95% confidence interval, 2-43) and a small negative likelihood ratio of 0.76 (95% confidence interval, 0.56-1.03). There were no cases of pulmonary embolism. Hospital mortality in those with and without deep venous thrombosis was 33% and 28%, respectively. CONCLUSIONS In the absence of prophylaxis, the incidence of deep venous thrombosis in Chinese medical Intensive Care Unit patients is lower than that reported in similar Caucasian patients, but higher than expected. As clinical features are not able to reliably exclude the presence of deep venous thrombosis, early routine prophylaxis for deep venous thrombosis in Chinese medical Intensive Care Unit patients should be considered.
Prodromal depression in pancreatic cancer: Retrospective evaluation on ten patients

Abstract Objective: Since the description by Yaskin in 1931, it has been observed that pancreatic cancer and depression are two clinical entities that share a high affinity. This observation relies on the higher incidence of depressive syndromes associated with pancreatic cancer than in any other type of digestive tumor, and on the possible occurrence of depressive symptoms several months before the diagnosis of cancer. We present here a series of cases whose screening returned positive for depression-related diagnoses in the months prior to revelation of the cancer. Method: We employed a structured psychiatric interview based on DSM–IV criteria (SCID–I). The diagnoses considered were major depressive episode, minor depressive episode, and subsyndromal depression. All subjects were free of psychiatric history. Results: Some 15 patients were initially included: 10 presented compatible criteria for a past depressive episode, 2 presented a major depressive episode, 4 met the diagnosis of minor depression, and 4 evidenced subsyndromal depression over the one-year period prior to cancer diagnosis. Significance of results: This series of cases is consistent with previous work on the subject that suggested an increased vulnerability to depressive events in the premorbid phase of pancreatic cancer. If the possibility of depressive syndromes constituting the early stages of neoplastic disease is a common idea, it is still impossible to determine the natural history of these two disorders and therefore their causal linkage.
The influence of cryotherapy on reduction of swelling, pain and trismus after third-molar extraction: a preliminary study.

BACKGROUND Swelling, pain and trismus are undesirable consequences of impacted mandibular third-molar extraction. The authors conducted a study to evaluate the effectiveness of cryotherapy, the therapeutic use of cold, in reducing undesirable consequences after surgery. METHODS Fourteen patients aged 20 to 28 years comprised the sample. The authors extracted two impacted mandibular third molars at different times from each patient. Immediately after surgery, the patient underwent cryotherapy on one side for 30 minutes every one and one-half hours for 48 hours when he or she was awake. The patient did not receive cryotherapy on the other side. The authors performed clinical examinations to measure trismus and swelling before surgery, immediately after surgery and 24 and 48 hours after surgery. RESULTS The authors compared both sides for differences in swelling, pain and trismus in each patient. The results showed significant statistical differences in two of the five points that were used to measure the swelling (Wilcoxon nonparametric signed rank test of linear distances between the angle of the mandible to the pogonion and to the tragus). They found statistical differences between the two sides in relation to the pain; however, they found no significant differences in relation to trismus. CONCLUSIONS Cryotherapy was effective in reducing swelling and pain in this sample. Despite playing no role in the reduction of trismus, cryotherapy was effective in reducing swelling and pain in this sample, and the authors still recommend it be used. CLINICAL IMPLICATIONS Cryotherapy is helpful after third-molar extraction. Further studies need to be conducted that use larger samples of patients and other types of therapy, such as low-level laser therapy.