Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropeptide Y–Induced Phase Shifts of PER2::LUC Rhythms Are Mediated by Long-Term Suppression of Neuronal Excitability in a Phase-Specific Manner

Endogenous circadian rhythms are entrained to the 24-h light/dark cycle by both light and nonphotic stimuli. During the day, nonphotic stimuli, such as novel wheel-induced exercise, produce large phase advances. Neuropeptide Y (NPY) release from the thalamus onto suprachiasmatic nucleus (SCN) neurons at least partially mediates this nonphotic signal. The authors examined the hypothesis that NPY-induced phase advances are accompanied by suppression of PER2 and are mediated by long-term depression of neuronal excitability in a phase-specific manner. First, it was found that NPY-induced phase advances in PER2::LUC SCN cultures are largest when NPY (2.35 µM) is given in the early part of the day (circadian time [CT] 0–6). In addition, PER2::LUC levels in NPY-treated (compared to vehicle-treated) samples were suppressed beginning 6–7 h after treatment. Similar NPY application to organotypic Per1::GFP SCN cultures resulted in long-term suppression of spike rate of green fluorescent protein–positive (GFP+) cells when slices were treated with NPY during the early or middle of the day (zeitgeber time [ZT] 2 or 6), but not during the late day (ZT 10). Furthermore, 1-h bath application of NPY to acute SCN brain slices decreased general neuronal activity measured through extracellular recordings. Finally, NPY-induced phase advances of PER2::LUC rhythms were blocked by latent depolarization with 34.5 mM K+ 3 h after NPY application. These results suggest that NPY-induced phase advances may be mediated by long-term depression of neuronal excitability. This model is consistent with findings in other brain regions that NPY-induced persistent hyperpolarization underlies mechanisms of energy homeostasis, anxiety-related behavior, and thalamocortical synchronous firing. (Author correspondence: klgamble@uab.edu)
Nonpharmacologic Approach to Fatigue in Patients With Cancer

AbstractCancer-related fatigue is a common yet underappreciated problem with a significant impact on functional ability and quality of life. Practice guidelines mandate that all cancer patients and survivors be screened for cancer-related fatigue (CRF) at regular intervals. Comorbidities that could contribute to fatigue should be treated, and patients with moderate to severe fatigue should undergo a comprehensive evaluation. Nonpharmacologic interventions are important tools to combat CRF and should be incorporated into routine practice. Physical activity, educational interventions, and cognitive-behavioral therapy have the most supportive data and can be recommended to patients with confidence. From a practical standpoint, general education on CRF is something that most care providers can readily offer patients as part of routine care. Other interventions that appear promising but are as yet lacking convincing evidence include mindfulness-based stress reduction, yoga, and acupuncture. Reiki, Qigong, hypnosis, and music therapy may be worthy of further investigation.
Azimuthal source localization using interaural coherence in a robotic dog: modeling and application

SUMMARY In nature, sounds from multiple sources, as well as reflections from the surfaces of the physical surroundings, arrive concurrently from different directions at the ears of a listener. Despite the fact that all of these waveforms sum at the eardrums, humans with normal hearing can effortlessly segregate interesting sounds from echoes and other sources of background noises. This paper presents a two-microphone technique for localization of sound sources to effectively guide robotic navigation. Its fundamental structure is adopted from a binaural signal-processing scheme employed in biological systems for the localization of sources using interaural time differences (ITDs). The two input signals are analyzed for coincidences along left/right-channel delay-line pairs. The coincidence time instants are presented as a function of the interaural coherence (IC). Specifically, we build a sphere head model for the selected robot and apply the mechanism of binaural cues selection observed in mammalian hearing system to mitigate the effects of sound echoes. The sound source is found by determining the azimuth at which the maximum of probability density function (PDF) of ITD cues occurs. This eliminates the localization artifacts found during tests. The experimental results of a systematic evaluation demonstrate the superior performance of the proposed method.
HIV transmission by organ and tissue transplantation

PurposePublished reports in English of HIV infection in organ and tissue recipients were reviewed to examine (1) the effect of donor screening, allograft type, and allograft processing on risk of HIV transmission by transplantation; (2) the antibody response to HIV infection in organ recipients taking antirejection therapy; and (3) survival following transplantation for HIV-infected organ recipients. Data extractionDate of transplant, timing of HIV infection in relation to transplant, type of allograft, type of antirejection therapy, duration of follow-up, time to death, and time to antigen and antibody appearance were recorded for each of 32 reports. ResultsHIV transmission associated with transplantation of kidney (n=50), liver (n = 13), heart (n = 6), pancreas (n = 1), bone (n = 4), and skin (n = 1) has been reported. In all but 14 cases, transplantation occurred before routine donor screening for HIV antibody began. In addition, 24 cases of an organ transplant after the recipient became HIV-infected have been reported. Non-transmission of HIV from HIV-infected donors has also been reported in recipients of corneas (n = 9), bone (n = 26), other musculoskeletal tissue (n = 3), dura mater (n = 3), and kidneys (n = 2). Of 40 recipients with organ transplantation-associated infection who were tested for HIV antibody within 6 months of transplantation, 34 (85%) tested positive; only one recipient remained seronegative more than 6 months after transplantation. Estimated 1 – and 5-year survival following transplantation for 61 HIV-infected kidney recipients was 90 and 50%, respectively. ConclusionsWith current screening practices, HIV transmission by transplantation is rare. The transmission risk appears lower for recipients of processed or avascular tissues. The antibody response to HIV infection in organ recipients taking immunosuppressive therapy is similar to that reported in other infected people.
Actin Filaments Regulate Exocytosis at the Hair Cell Ribbon Synapse

Exocytosis at the inner hair cell ribbon synapse is achieved through the functional coupling between calcium channels and glutamate-filled synaptic vesicles. Using membrane capacitance measurements, we investigated whether the actin network regulates the exocytosis of synaptic vesicles at the mouse auditory hair cell. Our results suggest that actin network disruption increases exocytosis and that actin filaments may spatially organize a subfraction of synaptic vesicles with respect to the calcium channels. SIGNIFICANCE STATEMENT Inner hair cells (IHCs), the auditory sensory cells of the cochlea, release glutamate onto the afferent auditory nerve fibers to encode sound stimulation. To achieve this task, the IHC relies on the recruitment of glutamate-filled vesicles that can be located in close vicinity to the calcium channels or more remotely from them. The molecular determinants responsible for organizing these vesicle pools are not fully identified. Using pharmacological tools in combination with membrane capacitance measurements, we show that actin filament disruption increases exocytosis in IHCs and that actin filaments most likely position a fraction of vesicles away from the calcium channels.
Geographic distribution of restriction types of Mycobacterium bovis isolates from brush-tailed possums (Trichosurus vulpecula) in New Zealand

SUMMARY DNA restriction endonuclease analysis was used for intra-specific typing of Mycobacterium bovis isolates from 83 brush-tailed possums (Trichosurus vulpecula) obtained between 1982 and 1984 from the three major regions in New Zealand with endemic bovine tuberculosis. All the isolates were found to be genetically very similar. Differentiation of the isolates into 33 restriction types was achieved by using high-resolution electrophoresis and the combined results from separate digestions with the restriction enzymes Bst EII, Pvu II and Bcl I. The typing system was entirely reproducible. Isolates of the same type were usually found in adjacent localities and were always limited to one of the three major regions. In some cases, isolates of the same type were found in both 1982 and 1984. The phenotypic significance of the small genetic differences identified between different isolates is unknown. The typing system will be useful for monitoring the transmission of M. bovis to other species and the future spread of different M. bovis types through possum populations.
Triple Negative Breast Cancer versus Non-Triple Negative Breast Cancer Treated with Breast Conservation Surgery Followed by Radiotherapy: A Systematic Review and Meta-Analysis

Background: The aim of this study was to compare the efficacy of breast conservation surgery (BCS) followed by radiotherapy (RT) in triple negative breast cancer (TNBC) versus non-TNBC. Methods: We searched the MEDLINE and EMBASE databases from inception through March 31, 2014, using search terms related to TNBC, BCS, and RT. Studies comparing the efficacy of BCS followed by RT in TNBC versus non-TNBC were reviewed. Results: 5 studies including 2,922 non-TNBC and 510 TNBC cases were selected. The overall quality of included studies was deemed moderate to high. Compared with non-TNBC, the pooled relative risk of 5-year local relapse-free survival was 1.315 (95% confidence interval (CI) 0.967-1.789; p = 0.008) for TNBC, and that of 5-year overall survival, regional relapse-free survival, and distant metastasis-free survival was 1.929 (95% CI 1.392-2.674; p = 0.000), 3.052 (95% CI 1.629-5.715; p = 0.000), and 2.407 (95% CI 1.910-3.034; p = 0.000), respectively. Conclusion: The local control rate of TNBC treated with BCS plus RT is similar to that of non-TNBC.
Suicide in psychiatric patients: case-control study in Singapore.

OBJECTIVE Persons with psychiatric illness, especially depression and schizophrenia, are at relatively high risk of suicide, but there are few studies that look at the Asian population. The aim of the present study was to identify the risk period and risk factors for suicide in psychiatric patients in Singapore. The nature of psychiatric care that was provided, both inpatient and outpatient, was also explored. METHOD This is a case-control study of 123 patients who committed suicide from 2003 to 2004. Controls were 123 surviving patients who were individually matched for age, gender, principal diagnosis and calendar time. RESULTS The most common principal diagnoses among the suicide subjects were schizophrenia (46.3%) and depression (26.8%). Numerous factors were associated with significantly increased suicide risk. Stepwise conditional logistic regression showed that the following three independent factors best predicted suicide: history of attempted suicide using highly lethal means; coexisting significant physical illness; and delusions. Suicides occur mainly soon after discharge and after an outpatient consult. Subgroup analyses were done to distinguish between subjects who suicided early and late following discharge. CONCLUSIONS Suicidal risk remains high in Singaporean psychiatric patients soon after discharge. They share some common risk factors for suicide identified in Western studies but the lower prevalence of substance abuse and comorbidity in Singaporean suicide subjects was one notable difference. The phenomena of suicides soon after discharge and outpatient review suggest the need for proper identification and more intensive follow up during this period.
Do dispersive waves play a role in collisionless magnetic reconnection

Using fully kinetic simulations, we demonstrate that the properly normalized reconnection rate is fast ∼0.1 for guide fields up to 80× larger than the reconnecting field and is insensitive to both the system size and the ion to electron mass ratio. These results challenge conventional explanations of reconnection based on fast dispersive waves, which are completely absent for sufficiently strong guide fields. In this regime, the thickness of the diffusion layer is set predominantly by the electron inertial length with an inner sublayer that is controlled by finite gyro-radius effects. As the Alfven velocity becomes relativistic for very strong guide fields, the displacement current becomes important and strong deviations from charge neutrality occur, resulting in the build-up of intense electric fields which absorb a portion of the magnetic energy release. Over longer time scales, secondary magnetic islands are generated near the active x-line while an electron inertial scale Kelvin-Helmholtz instability is driven within the outflow. These secondary instabilities give rise to time variations in the reconnection rate but do not alter the average value.
The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.

CONTEXT Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene in familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone is involved in tumorigenesis. OBJECTIVE AIP sequence changes and expression were studied in FIPA and sporadic adenomas. The function of normal and mutated AIP molecules was studied on cell proliferation and protein-protein interaction. Cellular and ultrastructural AIP localization was determined in pituitary cells. PATIENTS Twenty-six FIPA kindreds and 85 sporadic pituitary adenoma patients were included in the study. RESULTS Nine families harbored AIP mutations. Overexpression of wild-type AIP in TIG3 and HEK293 human fibroblast and GH3 pituitary cell lines dramatically reduced cell proliferation, whereas mutant AIP lost this ability. All the mutations led to a disruption of the protein-protein interaction between AIP and phosphodiesterase-4A5. In normal pituitary, AIP colocalizes exclusively with GH and prolactin, and it is found in association with the secretory vesicle, as shown by double-immunofluorescence and electron microscopy staining. In sporadic pituitary adenomas, however, AIP is expressed in all tumor types. In addition, whereas AIP is expressed in the secretory vesicle in GH-secreting tumors, similar to normal GH-secreting cells, in lactotroph, corticotroph, and nonfunctioning adenomas, it is localized to the cytoplasm and not in the secretory vesicles. CONCLUSIONS Our functional evaluation of AIP mutations is consistent with a tumor-suppressor role for AIP and its involvement in familial acromegaly. The abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas indicate deranged regulation of this protein during tumorigenesis.
Genomic Characterization of an Endemic Mycobacterium tuberculosis Strain: Evolutionary and Epidemiologic Implications

ABSTRACT In a study of 302 Mycobacterium tuberculosis clinical isolates from the low-incidence Canadian-born population of Quebec, we characterized a large endemic strain family by using genomic deletions. The DS6Quebec deleted region (11.4 kb) defined a strain family of 143 isolates encompassing two subgroups: one characterized by pyrazinamide (PZA) susceptibility and the other marked by a PZA-monoresistant phenotype. A second deletion (8 bp) in the pncA gene was shared by all 76 isolates with the PZA resistance phenotype, whereas a third DRv0961 deletion (970 bp) defined a further subset of 15 isolates. From their deletion profiles, we derived a most parsimonious evolutionary scenario and compared multiple standard genotyping modalities (using IS6110 restriction fragment length polymorphism [RFLP], spoligotyping, and mycobacterial interspersed repetitive units [MIRU]) across the deletion-based subgroups. The use of a single genotyping modality yielded an unexpectedly high proportion of clustered isolates for a high IS6110 copy strain (27% by IS6110 RFLP, 61% by MIRU, and 77% by spoligotyping). By combining all three modalities, only 14% were genotypically clustered overall, a result more congruent with the epidemiologic profile of reactivation tuberculosis, as suggested by the older age (mean age, 60 years), rural setting, and low proportion of epidemiologic links. These results provide insight into the evolution of genotypes in endemic strains and the potential for false clustering in molecular epidemiologic studies.
Facial esthetics in a selected Saudi population.

OBJECTIVE The purpose of this study is to analyze the soft tissue cephalometric norms of the Saudi population and to evaluate whether significant cephalometric soft tissue differences exist between Saudi and Caucasian population. METHODS Lateral cephalometric radiographs of 40 selected Saudis with esthetically pleasing faces (20 males and 20 females). The study was carried out in the College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia between 1999 - 2001. The age range between 20 and 30 years was analyzed using Burstone system of soft tissue analysis. The means, standard deviations and ranges of the measurements were compared between males and females, and both figures correlated with the results obtained for a Caucasian population. RESULTS Statistically, the facial convexity angle (glabella-subnasale-soft tissue pogonion) was found to be less convex for the Saudi group; the maxillary prognathism was more anterior, and the upper and lower lip positions were more anterior. CONCLUSION The results of the present study are significant, and showed that the normal Saudis have a slightly lesser obtuse nasolabial angle, and a more anteriorly positioned upper and lower lips. These results have a clinical implication in the diagnosis and treatment of adult Saudis with dentofacial deformities.
Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma.

BACKGROUND Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. OBJECTIVES This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. METHODS A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). RESULTS Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). CONCLUSIONS Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.
Casualties treated at the closest hospital in the Madrid, March 11, terrorist bombings

Background:At 07:39 am on March 11th, 2004, ten terrorist bomb explosions occurred almost simultaneously in four commuter trains in Madrid, Spain, killing instantly 177 people and injuring >2,000. There were 14 subsequent in-hospital deaths, bringing the definite death toll to 191 victims. This article describes the organization of the clinical management and patterns of injuries in casualties who were taken to the closest hospital, with emphasis on the critical patient population. Results:There were 312 patients taken to that center, and 91 were hospitalized, 89 of them (28.5%) for >24 hrs. Sixty-two patients only had superficial bruises or emotional shock, but the remaining 250 patients had more severe lesions. The data on 243 of the latter form the basis of this report. Tympanic perforation occurred in 41% of 243 victims with moderate-to-severe trauma, chest injuries in 40%, shrapnel wounds in 36%, fractures in 18%, first- or second-degree burns in 18%, eye lesions in 18%, head trauma in 12%, and abdominal injuries in 5%. Between 8:00 am and 5:00 pm, 34 surgical interventions were performed on 32 victims. Twenty-nine casualties (12% of the total or 32.5% of those hospitalized) were deemed in critical condition, and two of them died within minutes of arrival. The other 27 survived to be admitted to intensive care units, and three of them died, bringing the critical mortality rate to 17.2% (5/29). The mean Injury Severity Score and Acute Physiology and Chronic Health Evaluation II scores of critical patients were 34 and 23, respectively. Among these critical patients, soft-tissue and musculoskeletal injuries predominated in 85% of cases, ear blast injury was identified in 67%, and blast lung injury was present in 63% (17 cases). Fifty-two percent suffered head trauma. Conclusions:There was probably an overtriage to the closest hospital, and the time of the blasts proved crucial for the adequacy of the medical and surgical response. The number of blast lung injuries seen is probably the largest reported by a single institution, and the critical mortality rate was reasonably low.
Anthraquinone Photonucleases: A Surprising Role for Chloride in the Sequence‐Neutral Cleavage of DNA and the Footprinting of Minor Groove‐Bound Ligands

Irradiation of water‐soluble anthraquinone (AQ) reagents in the presence of chloride ions results in the spontaneous, sequence‐neutral cleavage of DNA. Mechanistic studies indicate that cleavage is initiated by chlorine atoms, produced by charge transfer interaction between chloride anion and AQ triplet states. High‐resolution gel electrophoresis suggests that cleavage arises from abstraction of a hydrogen atom from C‐4′ of deoxyribose units. The targeting of this hydrogen, which is located in the minor groove of duplex DNA, can be effectively blocked by netropsin and, to a lesser degree, berenil, leading to photofootprinting of these minor groove‐binding drugs.