Miracle-dz/UniFAR-FTUs huggingface dataset:
The past, present, and future of basal insulins

Insulin production by the pancreas follows a basic pattern where basal levels of insulin are secreted during fasting periods, with prandial increases in insulin associated with food ingestion. The aim of insulin therapy in patients with diabetes is to match the endogenous pattern of insulin secretion as closely as possible without causing hypoglycaemia. There are several optimal pharmacokinetic and pharmacodynamic properties of long‐acting basal insulins that can help to achieve this aim, namely, as follows: activity that is flat and as free of peaks as possible, a duration of action of ≥24‐h, and as little day‐to‐day variation as possible. The long‐acting basal insulins are a fundamental therapy for patients with type 1 and type 2 diabetes, and those that are currently available have many benefits; however, the development of even longer‐acting insulins and improved insulin delivery techniques may lead to better glycemic control for patients in the future. Established long‐acting basal insulins available in the United States and Europe include insulin glargine 100 units/mL and insulin detemir, both of which exhibit similar glycemic control to that of the intermediate‐acting neutral protamine Hagedorn insulin, but with a reduction in hypoglycaemia. Newer insulin products available include new insulin glargine 300 units/mL (United States and Europe) and the ultra‐long‐acting insulin degludec (Europe) with basal insulin peglispro currently in development. These new insulins demonstrate different pharmacokinetic/pharmacodynamic profiles and longer durations of action (>24 h) compared with insulin glargine 100 units/mL, which may lead to potential benefits. The introduction of biosimilar insulins may also broaden access to insulins by reducing treatment costs. Copyright © 2015 John Wiley & Sons, Ltd.
Genome-wide analysis of lipoxygenase gene family in Arabidopsis and rice

The enzymes called lipoxygenases (LOXs) can dioxygenate unsaturated fatty acids, which leads to lipoperoxidation of biological membranes. This process causes synthesis of signaling molecules and also leads to changes in cellular metabolism. LOXs are known to be involved in apoptotic (programmed cell death) pathway, and biotic and abiotic stress responses in plants. Here, the members of LOX gene family in Arabidopsis and rice are identified. The Arabidopsis and rice genomes encode 6 and 14 LOX proteins, respectively, and interestingly, with more LOX genes in rice. The rice LOXs are validated based on protein alignment studies. This is the first report wherein LOXs are identified in rice which may allow better understanding the initiation, progression and effects of apoptosis, and responses to bitoic and abiotic stresses and signaling cascades in plants
Measuring the Job Satisfaction Level of the Academic Staff

This study was conducted for the aim to find the job satisfaction of academic staff in Abbottabad. Important factors that have an impact on job satisfaction level are pay, job security, relationship with coworkers and relationship with supervisor. A sample of 84 teachers is selected by simple random sampling technique. Data is collected from four colleges both public and private in Abbottabad region. Simple percentages indicated that academic staff of these four colleges is more satisfied with relationship with coworkers and supervisor than pay and job security.
Structured Reporting of Magnetic Resonance Enterography for Pediatric Crohn's Disease: Effect on Key Feature Reporting and Subjective Assessment of Disease by Referring Physicians.

PURPOSE To objectively compare the content of structured reports (SR) vs nonstructured reports (NSR) for magnetic resonance enterography (MRE) of pediatric patients with Crohn's disease, and to evaluate referring clinicians' subjective assessment of reports. METHODS This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included 25 pediatric subjects (15 male, 10 female; mean age = 14 years [range: 9-18 years]) with Crohn's disease imaged with MRE. Three radiologists independently interpreted all examinations using both NSR and SR, separated by 4 weeks. Reports were assessed for documentation of the presence or absence of 15 key reporting features. A total of 30 reports (15 NSR [5 per reader] and 15 SR [5 per reader]) were randomly selected for review by 3 referring physicians, who subjectively evaluated the reports independently. RESULTS NSR documented the presence or absence of 7.7 ± 2.5 key features, whereas SR documented 14.0 ± 0.8 features (P < 0.001). SR resulted in increased documentation of 12 of 15 features including stricture (P < 0.001), fistula (P < 0.001), fluid collection (P = 0.003), and perianal disease (P < 0.001). Referring physicians preferred SR regarding ease of information extraction, clarity of anatomy, and ability to identify disease phenotype (P < 0.01 for each). CONCLUSION The use of structured reporting in describing pediatric Crohn's disease, MRE resulted in significantly increased reporting of key features. Referring clinicians also demonstrated a subjective preference for SR.
Cytoarchitecture and cortical connections of the posterior cingulate and adjacent somatosensory fields in the rhesus monkey

The cytoarchitecture and connections of the caudal cingulate and medial somatosensory areas were investigated in the rhesus monkey. There is a stepwise laminar differentiation starting from retrosplenial area 30 towards the isocortical regions of the medial parietal cortex. This includes a gradational emphasis on supragranular laminar organization and general reduction of the infragranular neurons as one proceeds from area 30 toward the medial parietal regions, including areas 3, 1, 2, 5, 31, and the supplementary sensory area (SSA). This trend includes a progressive increase in layer IV neurons. Area 23c in the lower bank and transitional somatosensory area (TSA) in the upper bank of the cingulate sulcus appear as nodal points. From area 23c and TSA the architectonic progression can be traced in three directions: one culminates in areas 3a and 3b (core line), the second in areas 1, 2, and 5 (belt line), and the third in areas 31 and SSA (root line). These architectonic gradients are reflected in the connections of these regions. Thus, cingulate areas (30, 23a, and 23b) are connected with area 23c and TSA on the one hand and have widespread connections with parieto‐temporal, frontal, and parahippocampal (limbic) regions on the other. Area 23c has connections with areas 30, 23a and b, and TSA as well as with medial somatosensory areas 3, 1, 2, 5, and SSA. Area 23c also has connections with parietotemporal, frontal, and limbic areas similar to areas 30, 23a, and 23b. Area TSA, like area 23c, has connections with areas 3, 1, 2, 5, and SSA. However, it has only limited connections with the parietotemporal and frontal regions and none with the parahippocampal gyrus. Medial area 3 is mainly connected to medial and dorsal sensory areas 3, 1, 2, 5, and SSA and to areas 4 and 6 as well as to supplementary (M2 or area 6m), rostral cingulate (M3 or areas 24c and d), and caudal cingulate (M4 or areas 23c and d) motor cortices. Thus, in parallel with the architectonic gradient of laminar differentiation, there is also a progressive shift in the pattern of corticocortical connections. Cingulate areas have widespread connections with limbic, parietotemporal, and frontal association areas, whereas parietal area 3 has more restricted connections with adjacent somatosensory and motor cortices. TSA is primarily related to the somatosensory‐motor areas and has limited connections with the parietotemporal and frontal association cortices. J. Comp. Neurol. 469:37–69, 2004. © 2003 Wiley‐Liss, Inc.
Recombinant Infectious Bronchitis Coronavirus Beaudette with the Spike Protein Gene of the Pathogenic M41 Strain Remains Attenuated but Induces Protective Immunity

ABSTRACT We have replaced the ectodomain of the spike (S) protein of the Beaudette strain (Beau-R; apathogenic for Gallus domesticus chickens) of avian infectious bronchitis coronavirus (IBV) with that from the pathogenic M41 strain to produce recombinant IBV BeauR-M41(S). We have previously shown that this changed the tropism of the virus in vitro (R. Casais, B. Dove, D. Cavanagh, and P. Britton, J. Virol. 77:9084-9089, 2003). Herein we have assessed the pathogenicity and immunogenicity of BeauR-M41(S). There were no consistent differences in pathogenicity between the recombinant BeauR-M41(S) and its apathogenic parent Beau-R (based on snicking, nasal discharge, wheezing, watery eyes, rales, and ciliostasis in trachea), and both replicated poorly in trachea and nose compared to M41; the S protein from the pathogenic M41 had not altered the apathogenic nature of Beau-R. Both Beau-R and BeauR-M41(S) induced protection against challenge with M41 as assessed by absence of recovery of challenge virus and nasal exudate. With regard to snicking and ciliostasis, BeauR-M41(S) induced greater protection (seven out of nine chicks [77%]; assessed by ciliostasis) than Beau-R (one out of nine; 11%) but less than M41 (100%). The greater protection induced by BeauR-M41(S) against M41 may be related to the ectodomain of the spike protein of Beau-R differing from that of M41 by 4.1%; a small number of epitopes on the S protein may play a disproportionate role in the induction of immunity. The results are promising for the prospects of S-gene exchange for IBV vaccine development.
IS THE U.S. EXPERIENCING AN INCIPIENT EPIDEMIC OF HALLUCINOGEN USE?

NHSDA and MTF survey data indicate “epidemic”-like growth in hallucinogen use from 1992–1996 and associated increases in cocaine, crack, heroin and amphetamine use. These trends might have resulted from a proliferation of raves and dance clubs in the U.S. as occurred in Europe and elsewhere, although in contrast to evidence regarding European experiences the American epidemic involves primarily teens as opposed to persons in their twenties and involves primarily use of LSD as opposed to MDMA. This analysis highlights the need for further research into the context, significance, and consequences of these recently popular American drug use practices.
Overview of History and Progress in BRCA1 Research: The First BRCA1 Decade

The BRCA1 protein presents a paradox to the scientists investigating its link to cancer. BRCA1 provides a function essential to all cell types, but its mutation is only associated with a subset of cancers including breast and ovarian cancers. The priorities of BRCA1 research are the identification of the function of BRCA1, which is required in all cells, and of the function specific to breast and ovarian cells that causes their cancerous transformation. BRCA1 has been shown to be required for multiple processes including transcription, chromatin remodeling, DNA damage repair, and the regulation of centrosome duplication. How BRCA1 regulates these processes is unclear: is the BRCA1 protein a direct participant in the biochemistry of each process, or is the BRCA1 protein regulating the gene expression of proteins that directly regulate all of these processes? The ubiquity of BRCA1 in multiple cellular processes is difficult to square with the specificity of tumors with which it is associated.
Thymus-Blood Protein Interactions Are Highly Effective in Negative Selection and Regulatory T Cell Induction1

Using hen egg-white lysozyme, the effect of blood proteins on CD4 thymic cells was examined. A small fraction of i.v. injected hen egg-white lysozyme rapidly entered the thymus into the medulla. There it was captured and presented by dendritic cells (DCs) to thymocytes from two TCR transgenic mice, one directed to a dominant peptide and a second to a poorly displayed peptide, both presented by MHC class II molecules I-Ak. Presentation by DC led to negative selection and induction of regulatory T cells, independent of epithelial cells. Presentation took place at very low levels, less than 100 peptide-MHC complexes per DC. Such low levels could induce negative selection, but even lower levels could induce regulatory T cells. The anatomy of the thymus-blood barrier, the highly efficient presentation by DC, together with the high sensitivity of thymic T cells to peptide-MHC complexes, results in blood protein Ags having a profound effect on thymic T cells.
Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states

We demonstrate that single interneurons can toggle the output neurons of the cerebellar cortex (the Purkinje cells) between their two states. The firing of Purkinje cells has previously been shown to alternate between an “up” state in which the cell fires spontaneous action potentials and a silent “down” state. We show here that small hyperpolarizing currents in Purkinje cells can bidirectionally toggle Purkinje cells between down and up states and that blockade of the hyperpolarization-activated cation channels (H channels) with the specific antagonist ZD7288 (10 μM) blocks the transitions from down to up states. Likewise, hyperpolarizing inhibitory postsnyaptic potentials (IPSPs) produced by small bursts of action potentials (10 action potentials at 50 Hz) in molecular-layer interneurons induce these bidirectional transitions in Purkinje cells. Furthermore, single interneurons in paired interneuron → Purkinje cell recordings, produce bidirectional switches between the two states of Purkinje cells. The ability of molecular-layer interneurons to toggle Purkinje cells occurs when Purkinje cells are recorded under whole-cell patch-clamp conditions as well as when action potentials are recorded in an extracellular loose cell-attached configuration. The mode switch demonstrated here indicates that a single presynaptic interneuron can have opposite effects on the output of a given Purkinje cell, which introduces a unique type of synaptic interaction that may play an important role in cerebellar signaling.
Use of confocal microscopy for quantification of plastic remnants on rough titanium after instrumentation and evaluation of efficacy of removal.

PURPOSE Many experts have proposed the treatment of titanium surfaces with plastic or nonmetal tips to prevent damage to implant surfaces by metal instruments during professional cleaning. It is also known that any material that is softer than titanium may leave remnants of itself on the treated surface. The aim of this study was to quantify the surface area covered by plastic remnants after instrumentation with various plastic instruments and to evaluate the efficacy of the removal of these remnants by confocal microscopy. MATERIALS AND METHODS Twenty-seven rough-surfaced titanium disks were used for quantification of plastic remnants. Nine disks each were cleaned with (1) a plastic tip on ultrasonic scaler A, (2) a carbon tip on ultrasonic scaler B, or (3) a plastic curette. Three disks from each group were cleaned with a three-way syringe for 10 seconds, and three other disks were cleaned with 0.2% chlorhexidine-soaked cotton pellets. Images were obtained at random areas on each disk with a confocal microscope, and a digital image analysis program was used to quantify the area with autofluorescence. RESULTS Approximately 10% to 20% of the surface was covered with plastic remnants of the instrument, irrespective of the instrument used. These remnants were not removed with a three-way syringe or chlorhexidine-soaked cotton pellets. CONCLUSION Plastic remnants remained after instrumentation, regardless of the instrument used. Moreover, the study highlighted the difficulty of removing all remnants with water spray or a chlorhexidine-soaked cotton pellet. This study suggests that confocal microscopy is a reproducible method for quantification that may be applied for future comparisons of methods to remove plastic residue. Further research is warranted to evaluate the biologic effects of plastic remnants.
Personality Factors in the Explanation of Sex Differences in Pain Catastrophizing and Response to Experimental Pain

Objective:To examine the effects of personality and pain catastrophizing upon pain tolerance and pain ratings and to examine the impact of an experimental pain induction on subsequent ratings of catastrophizing. Method:Two hundred nineteen college students participated in a cold pressor task. Sex-differentiating personality constructs were measured by the Extended Personal Attributes Questionnaire. The Pain Catastrophizing Scale was given before and after the cold pressor task. Results:A path-analytic model fit the data well and permitted tests of explanatory relationships. Mediational analyses demonstrated that sex differences in catastrophizing were explained by the Personal Attributes Questionnaire Masculinity–Femininity and Verbal Passive-Aggressiveness scales. Pain tolerance and pain ratings differed significantly between men and women, but Masculinity–Femininity partially mediated those sex–pain relationships. Additionally, higher pain ratings and lower pain tolerance were independently associated with increased catastrophizing after the cold pressor task. Conclusions:The results suggest that sex differences in catastrophizing and pain responsivity are partially accounted for by the dispositional tendency to describe oneself as emotionally vulnerable. The findings also suggest that pain catastrophizing may be situational as well as dispositional.
Long-term outcome and prognostic factors of surgically treated thymic carcinoma: results of 306 cases from a Japanese Nationwide Database Study.

OBJECTIVES Thymic carcinoma is a rare thymic malignancy. The purpose of this study was to evaluate the prognostic impact of clinicopathological variables and perioperative therapy for surgically treated thymic carcinoma using a nationwide database. METHODS Of 2835 patients with surgically treated thymic epithelial tumours collected from 32 Japanese institutions, a total of 306 patients with thymic carcinomas, excluding neuroendocrine tumours, were enrolled in this retrospective study. Multivariable Cox regression analyses were performed for overall (OS) and recurrence-free survival (RFS) after R0 resection. RESULTS Of 306 patients, 228 (75%) patients presented with Masaoka stage III-IV. Squamous cell carcinoma was the most common histological type (n = 216, 71%). R0 resection was performed in 181 (61%) patients, R1 in 46 (16%), R2 sub-total (≥80% tumour resection) in 43 (14%) and R2 non-resection in 27 (9%). The 5-year OS rate was 61%. Prognostic factors for OS were Masaoka stage and resection status. R0 resection was associated with most improved OS; however, both R1 and R2 sub-total resection resulted in superior OS compared with R2 non-resection [hazard ratio (95% confidence interval) for R0, R1 and R2 sub-total, 0.27 (0.15-0.48), 0.40 (0.22-0.74) and 0.38 (0.20-0.72), respectively]. Histological type and perioperative therapy did not affect OS, whereas tumour size and postoperative radiotherapy were associated with improved RFS after R0 resection. CONCLUSIONS R0 resection is essential for prolonged OS for surgically treated thymic carcinoma, but maximal debulking surgery might be beneficial and worth evaluating for advanced disease deemed difficult for R0 resection. The benefit of postoperative radiotherapy after R0 resection should also be evaluated prospectively.
[Child maltreatment in binge eating disorder: a systematic literature review].

OBJECTIVE This review is to provide a first overview about prevalences and associations of forms of child maltreatment in binge eating disorder (BED). METHODS Systematic literature search in PubMed and Web of Science in December 2013. Terms considered were "binge eating disorder" AND "child* maltreatment", "child* abuse", "child* sexual abuse", "child* emotional abuse", "child* physical abuse", "child* emotional neglect" as well as "child* physical neglect". Inclusion criteria were studies published between 1990 and 2013, publications in English or German, adult patients, studies that considered patients with full DSM criteria for BED, and studies that reported prevalences of forms of child maltreatment. RESULTS Eight studies out of 366 met criteria. Child maltreatment rates in BED were more than two times higher than in representative samples, but they were similar to psychiatric comparisons. Up to 83 % of patients with BED reported at least one form of child maltreatment. There were associations to psychiatric comorbidity, but not to gender, obesity and specific features of the eating behaviour. CONCLUSION Child maltreatment is very prevalent among BED. Its contribution to the development and the maintenance of BED is not understood yet.
Development and plasticity of interstitial cells of Cajal

Interstitial cells of Cajal (ICC) are the pacemakers in gastrointestinal (GI) muscles, and these cells also mediate or transduce inputs from the enteric nervous system. Different classes of ICC are involved in pacemaking and neurotransmission. ICC express specific ionic conductances that make them unique in their ability to generate and propagate slow waves in GI muscles or transduce neural inputs. Much of what we know about the function of ICC comes from developmental studies that were made possible by the discoveries that ICC express c‐kit and proper development of ICC depends upon signalling via the Kit receptor pathway. Manipulating Kit signalling with reagents to block the receptor or downstream signalling pathways or by using mutant mice in which Kit or its ligand, stem cell factor, are defective has allowed novel studies into the specific functions of the different classes of ICC in several regions of the GI tract. Kit is also a surface antigen that can be used to conveniently label ICC in GI muscles. Immunohistochemical studies using Kit antibodies have expanded our knowledge about the ICC phenotype, the structure of ICC networks, the interactions of ICC with other cells in the gut wall, and the loss of ICC in some clinical disorders. Preparations made devoid of ICC have also allowed analysis of the consequences of losing specific classes of ICC on GI motility. This review describes recent advances in our knowledge about the development and plasticity of ICC and how developmental studies have contributed to our understanding of the functions of ICC. We have reviewed the clinical literature and discussed how loss or defects in ICC affect GI motor function.
Design and analysis of a terahertz bandpass filter

In this paper, a terahertz waveguide filter using micromechanical milling process is designed and fabricated. The filter is designed at 255 GHz with a 3dB bandwidth of 30 GHz. The measured results show that the return loss is better than 15 dB and the insertion loss is about 3.9 dB at center frequency, good agreement between the measured and simulated results is achieved. In addition, the main loss of the terahertz passive components fabricated by micromechanical milling process is also analyzed. A 25mm waveguide is also fabricated and the unit length loss of the waveguide is about 0.16 dB/mm at 400 GHz.
Warm Partner Contact Is Related to Lower Cardiovascular Reactivity

Abstract The authors investigated the relationship between brief warm social and physical contact among cohabitating couples and blood pressure (BP) reactivity to stress in a sample of healthy adults (66 African American, 117 Caucasian; 74 women, 109 men). Prior to stress, the warm contact group underwent a 10-minute period of handholding while viewing a romantic video, followed by a 20-second hug with their partner, while the no contact group rested quietly for 10 minutes and 20 seconds. In response to a public speaking task, individuals receiving prestress partner contact demonstrated lower systolic BP, diastolic BP, and heart rate increases compared with the no contact group. The effects of warm contact were comparable for men and women and were greater for African Americans compared with Caucasians. These findings suggest that affectionate relationships with a supportive partner may contribute to lower reactivity to stressful life events and may partially mediate the benefit of marital support on better cardiovascular health.