Miracle-dz/UniFAR-FTUs huggingface dataset:
Revisiting Proinsulin Processing: Evidence That Human β-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2

Insulin is first produced in pancreatic β-cells as the precursor prohormone proinsulin. Defective proinsulin processing has been implicated in the pathogenesis of both type 1 and type 2 diabetes. Though there is substantial evidence that mouse β-cells process proinsulin using prohormone convertase 1/3 (PC1/3) and then prohormone convertase 2 (PC2), this finding has not been verified in human β-cells. Immunofluorescence with validated antibodies revealed that there was no detectable PC2 immunoreactivity in human β-cells and little PCSK2 mRNA by in situ hybridization. Similarly, rat β-cells were not immunoreactive for PC2. In all histological experiments, PC2 immunoreactivity in neighboring α-cells acted as a positive control. In donors with type 2 diabetes, β-cells had elevated PC2 immunoreactivity, suggesting that aberrant PC2 expression may contribute to impaired proinsulin processing in β-cells of patients with diabetes. To support histological findings using a biochemical approach, human islets were used for pulse-chase experiments. Despite inhibition of PC2 function by temperature blockade, brefeldin A, chloroquine, and multiple inhibitors that blocked production of mature glucagon from proglucagon, β-cells retained the ability to produce mature insulin. Conversely, suppression of PC1/3 blocked processing of proinsulin but not proglucagon. By demonstrating that healthy human β-cells process proinsulin by PC1/3 but not PC2, we suggest that there is a need to revise the long-standing theory of proinsulin processing.
An orally available hypoglycaemic peptide taken up by caveolae transcytosis displays improved hypoglycaemic effects and body weight control in db/db mice

Type 2 diabetes is one of the most severe chronic diseases and is an increasingly important public health problem worldwide. Several agonists of the glucagon‐like peptide‐1 (GLP‐1) receptor have been developed to treat Type 2 diabetes but most of them are administered by injection. This mode of administration seriously reduces patient compliance and increases the risk of infection. Here, we describe the actions of a novel, orally available, GLP‐1 receptor agonist ‐ oral hypoglycaemic peptide 2 (OHP2) ‐ derived from exendin‐4 by replacing amino acids. We have also investigated its pharmacokinetic profiles, therapeutic effects and absorption mechanism.
Pituitary Adenomas with Changing Phenotype: A Systematic Review

Abstract Purpose and Methods Phenotype transformation in pituitary adenomas (PA) is a little known and unexpected clinical phenomenon. We describe two illustrative cases and performed a systematic review of cases reported in literature. Results Case 1: A 24-year-old woman underwent surgery because of Cushing’s disease. A complete tumor resection and hypercortisolism resolution was achieved. Two years later, tumor recurred but clinical and hormonal hypercortisolism were absent. Case 2: A 77-year-old woman underwent surgery due to acromegaly. A complete tumor resection and GH excess remission was achieved. Four years later, tumor recurred but clinical and hormonal acromegaly was ruled out. Search of literature: From 20 patients (including our cases), 75% were female with median age 45 (19) years. Ten patients (50%) had initially functioning PA: 8 switched to NFPA (5 ACTH-secreting PA, 2 prolactinomas and 1 acromegaly) and 2 exchanged to acromegaly from TSH-secreting PA and microprolactinoma. One patient developed a pituitary carcinoma from ACTH-secreting PA. Ten patients (50%) initially had NFPA; 9 developed Cushing’s disease (4 silent corticotroph adenomas, 4 null cell PA and 1 managed conservatively). One patient with silent somatotroph PA changed to acromegaly. Treatments before transformation were surgery (80%), radiotherapy (40%), pharmacological (40%) and in 2 patients switching happened without any treatment. Median follow-up until transformation was 72 months (range 12–276). Conclusion PA can change from functioning to (NF) non-functioning (vice versa) and even exchange their hormonal expression. Clinicians should be aware and a careful lifelong follow-up is mandatory to detect it.
The Role of School Nurse Presence in Parent and Student Perceptions of Helpfulness, Safety, and Satisfaction With Type 1 Diabetes Care

Adolescents with type 1 diabetes (TID) and their parents depend on school nurses to keep students safe in school. Parent satisfaction with T1D care is impacted by school factors including school nurse presence. The purpose of this study was to determine the relationships among parental satisfaction with diabetes care in school, parental report of diabetes-related safety, adolescent report of school nurse helpfulness, and school nurse presence represented by school nurse to student ratios. The sample consisted of 89 parent–adolescent dyads. Adolescents 10–16 years old with T1D completed a questionnaire that included perceptions of school nurse helpfulness. Parents completed a questionnaire that included perceptions of T1D safety and satisfaction. Diabetes-related safety was positively correlated with parental satisfaction and school nurse helpfulness and inversely correlated with age and school nurse to student ratios. Findings validate the importance of school nurse presence to adolescents with T1D and their parents with implications for school nursing policy, practice, and research.
MAST1 modulates neuronal differentiation and cell cycle exit via P27 in neuroblastoma cells

Although 19p13.13 microdeletion syndrome has been consistently associated with intellectual disability, overgrowth, and macrocephaly, the underlying mechanisms remain unclear. MAST1, a member of the microtubule‐associated serine/threonine kinase family, has been suggested as a potential candidate gene responsible for neurologic abnormalities in 19p13.13 microdeletion syndrome, but its role in nervous system development remains to be elucidated. Here, we investigated how MAST1 contributes to neuronal development. We report that MAST1 is upregulated during neuronal differentiation of the human neuroblastoma cell line, SH‐SY5Y. Inhibition of MAST1 expression by RNA interference attenuated neuronal differentiation of SH‐SY5Y cells. Cell cycle analyses revealed that MAST1‐depleted cells did not undergo cell cycle arrest after RA treatment. Consistent with this observation, the number of EdU‐positive cells significantly increased in MAST1 knockdown cells. Intriguingly, levels of P27, a cyclin‐dependent kinase inhibitor, were also increased during neuronal differentiation, and MAST1 knockdown reduced the expression of P27. Moreover, reduced neuronal differentiation caused by MAST1 depletion was rescued partially by P27 overexpression in SH‐SY5Y cells. Collectively, these results suggest that MAST1 influences nervous system development by affecting neuronal differentiation through P27.
BCL-2 Proteins in Pathogenesis and Therapy of B-Cell Non-Hodgkin Lymphomas

The ability to inhibit mitochondrial apoptosis is a hallmark of B-cell non-Hodgkin lymphomas (B-NHL). Activation of mitochondrial apoptosis is tightly controlled by members of B-cell leukemia/lymphoma-2 (BCL-2) family proteins via protein-protein interactions. Altering the balance between anti-apoptotic and pro-apoptotic BCL-2 proteins leads to apoptosis evasion and extended survival of malignant cells. The pro-survival BCL-2 proteins: B-cell leukemia/lymphoma-2 (BCL-2/BCL2), myeloid cell leukemia-1 (MCL-1/MCL1) and B-cell lymphoma-extra large (BCL-XL/BCL2L1) are frequently (over)expressed in B-NHL, which plays a crucial role in lymphoma pathogenesis, disease progression, and drug resistance. The efforts to develop inhibitors of anti-apoptotic BCL-2 proteins have been underway for several decades and molecules targeting anti-apoptotic BCL-2 proteins are in various stages of clinical testing. Venetoclax is a highly specific BCL-2 inhibitor, which has been approved by the US Food and Drug Agency (FDA) for the treatment of patients with chronic lymphocytic leukemia (CLL) and is in advanced clinical testing in other types of B-NHL. In this review, we summarize the biology of BCL-2 proteins and the mechanisms of how these proteins are deregulated in distinct B-NHL subtypes. We describe the mechanism of action of BH3-mimetics and the status of their clinical development in B-NHL. Finally, we summarize the mechanisms of sensitivity/resistance to venetoclax.
Polysaccharide-Based Bioink Formulation for 3D Bioprinting of an In Vitro Model of the Human Dermis

Limitations in wound management have prompted scientists to introduce bioprinting techniques for creating constructs that can address clinical problems. The bioprinting approach is renowned for its ability to spatially control the three-dimensional (3D) placement of cells, molecules, and biomaterials. These features provide new possibilities to enhance homology to native skin and improve functional outcomes. However, for the clinical value, the development of hydrogel bioink with refined printability and bioactive properties is needed. In this study, we combined the outstanding viscoelastic behavior of nanofibrillated cellulose (NFC) with the fast cross-linking ability of alginate (ALG), carboxymethyl cellulose (CMC), and encapsulated human-derived skin fibroblasts (hSF) to create a bioink for the 3D bioprinting of a dermis layer. The shear thinning behavior of hSF-laden bioink enables construction of 3D scaffolds with high cell density and homogeneous cell distribution. The obtained results demonstrated that hSF-laden bioink supports cellular activity of hSF (up to 29 days) while offering proper printability in a biologically relevant 3D environment, making it a promising tool for skin tissue engineering and drug testing applications.
Bypass protein technology and the impact of feeding bypass protein to dairy animals in tropics: A review

Under tropical conditions, even the medium producing dairy animals can be fed bypass protein, to increase their productivity, in terms of growth and milk production. The availability of naturally occurring bypass protein is very less, hence the highly degradable proteins like groundnut-, mustard-, sunflower-, safflower-cakes and soybean-meal could be given protection, either through heat treatment (roasting) as in soybean-meal, or given formaldehyde treatment, for the other cakes. Through the research studies conducted at NDRI, Karnal, all the apprehensions about the safety of formaldehyde treatment have been removed. There is an additional advantage of treating mustard-cake with formaldehyde, as it not only protects protein in rumen, but also protects the glucosinolates from its conversion to `thiocynate in rumen. In India, the technology of feeding bypass protein to dairy animals has been accepted by some farmers, and bypass protein Feed is now being manufactured exclusively by some commercial feed factories, including NDDB, Anand.
One new α,β-unsaturated 7-ketone sterol from the mangrove-derived fungus Phomopsis sp.MGF222

Abstract A new α,β-unsaturated 7-ketone sterol, 5β,6β-epoxy-3β, 15α-dihydroxy-(22E,24R)-ergosta-8(14),22-dien-7-one (1), along with five known sterone derivatives, 5β,6β-epoxy-3β,7α-dihydroxy-(22E,24R)-ergosta-8(14),22-dien-15-one (2), 5β,6β-epoxy-3β,7α,9α-trihydroxy-(22E,24R)-ergosta-8(14),22-dien-15-one (3), 3β,9α,15α-trihydroxy-(22E,24R)-10(5→4)-abeo-ergosta-6,8(14),22-trien-5-one (4), 3,15-dihydroxyl-(22E,24R)-ergosta-5,8(14),22-trien-7-one (5) and (22E,24R)-ergosta-4,6,8(14),22-tetraen-3,15-dione (6) were isolated from the mangrove-derived fungus Phomopsis sp. MGF222. Their structures were established on the basis of extensive spectroscopic data and comparison with the data of literature. Compound 2 showed weak antibacterial activity against Micrococcus tenuis with the MIC value of 28.2 (±0.52) μM. Compound 5 exhibited moderate antibacterial activity against Staphylococcus aureus with the MIC value of 14.6 (±0.47) μM. Graphical Abstract
Depression and Resting Masticatory Muscle Activity

Background: The aim of this study was to determine the influence of moderate depression determined based on Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMDs) Axis II on the bioelectrical resting activity of temporal muscles and masseter muscles. Methods: The research participants were 68 healthy adult women. Of these, 46 people h (mean age: 22 ± 1 year) who had no temporomandibular disorders were selected for the research. They were divided based on results from RDC/TMDs (Axis II: scale’s measurement) into the study group with a moderate level of depression (23 people), rest of participants without symptoms of depression were classified to control group (23 people). The resting activity of temporal muscles and masseter muscles was examined by using BioEMGIII electromyograph. Two statistical analyses were used: Shapiro–Wilk test and Mann–Whitney U test. Results: Despite higher mean tensions of temporal muscles and masseter muscles in the group with depression, results findings were not statistically significant (p > 0.05). Conclusions: Moderate depression determined based on the RDC/TMDs II axis questionnaire is not related to the resting activity of selected masticatory muscles. Further research should be continued on a larger group of respondents in order to establish the relationship between psychological factors and bioelectrical parameters of the masticatory muscles.
Effects of Workstation Type on Mental Stress: FNIRS Study

Objective The purpose of this study is to examine the effect of the workstation type on the severity of mental stress by means of measuring prefrontal cortex (PFC) activation using functional near-infrared spectroscopy. Background Workstation type is known to influence worker’s health and performance. Despite the practical implications of ergonomic workstations, limited information is available regarding their impact on brain activity and executive functions. Method Ten healthy participants performed a Montreal imaging stress task (MIST) in ergonomic and nonergonomic workstations to investigate their effects on the severity of the induced mental stress. Results Cortical hemodynamic changes in the PFC were observed during the MIST in both the ergonomic and nonergonomic workstations. However, the ergonomic workstation exhibited improved MIST performance, which was positively correlated with the cortical activation on the right ventrolateral and the left dorsolateral PFC, as well as a marked decrease in salivary alpha‐amylase activity compared with that of the nonergonomic workstation. Further analysis using the NASA Task Load Index revealed a higher weighted workload score in the nonergonomic workstation than that in the ergonomic workstation. Conclusion The findings suggest that ergonomic workstations could significantly improve cognitive functioning and human capabilities at work compared to a nonergonomic workstation. Application Such a study could provide critical information on workstation design and development of mental stress that can be overlooked during traditional workstation design and mental stress assessments.
The unforeseen during biotechnological therapy for moderate‐to‐severe psoriasis: How to manage pregnancy and breastfeeding, infections from Mycobacterium tuberculosis, hepatitis B virus, hepatitis C virus, and HIV, surgery, vaccinations, diagnosis of malignancy, and dose tapering

The use of biotechnological therapies for moderate‐to‐severe psoriasis is ever‐expanding and it is becoming increasingly more frequent to encounter different unforeseen events during their use, such as fertile patients becoming pregnant and breastfeeding, development of infections due to personal habits like tuberculosis, hepatitis B virus, hepatitis C virus, or HIV, scheduling of surgical procedures, need of vaccinations, development of malignancy, and evaluation of dose tapering. As any clinician may experience at least one of these unexpected events, it should be good practice to know how to manage them. Thus, a practical analysis has been proposed in this study.
Plant Secondary Metabolites in the Battle of Drugs and Drug-Resistant Bacteria: New Heroes or Worse Clones of Antibiotics?

Infectious diseases that are caused by bacteria are an important cause of mortality and morbidity in all regions of the world. Bacterial drug resistance has grown in the last decades, but the rate of discovery of new antibiotics has steadily decreased. Therefore, the search for new effective antibacterial agents has become a top priority. The plant kingdom seems to be a deep well for searching for novel antimicrobial agents. This is due to the many attractive features of plants: they are readily available and cheap, extracts or compounds from plant sources often demonstrate high-level activity against pathogens, and they rarely have severe side effects. The huge variety of plant-derived compounds provides very diverse chemical structures that may supply both the novel mechanisms of antimicrobial action and provide us with new targets within the bacterial cell. In addition, the rapid development of modern biotechnologies opens up the way for obtaining bioactive compounds in environmentally friendly and low-toxic conditions. In this short review, we ask the question: do antibacterial agents derived from plants have a chance to become a panacea against infectious diseases in the “post-antibiotics era”.
Detection of Friction-Modulated Textures is Limited by Vibrotactile Sensitivity

Modulation of the frictional force of a fingertip sliding over a surface-haptic device can produce compelling sensations of texture and relief. The virtual sensation is particularly apparent and feel as fixed in space if the stimulus is rigorously correlated with the displacement of the finger. While frictional textures tactually resemble their real counterparts, some exploratory conditions under which the sharpness of the texture declines exist. We postulate that this decline in sharpness is caused by the perceptual limitation of the attempt to interpret the variation in friction as an out-of-plane sinusoidal topography. To investigate these questions, we measured the detection thresholds of sinusoidal friction-modulated gratings for a wide range of spatial periods explored at two different speeds. We compared the results with the detection thresholds, reported in the literature, of real gratings and vibrotactile stimuli. We found that the detection of spatial friction-modulated textures does not follow the same trend as that of real textures but is more similar to the vibrotactile rendering, which is strongly influenced by the exploratory speed. This article provides a better understanding of the perception of friction-modulated textures and provides insight into how to design impactful stimuli on surface-haptic devices.
A GaN HEMT Amplifier Design for Phased Array Radars and 5G New Radios

Power amplifiers applied in modern active electronically scanned array (AESA) radars and 5G radios should have similar features, especially in terms of phase distortion, which dramatically affects the spectral regrowth and, moreover, they are difficult to be compensated by predistortion algorithms. This paper presents a GaN-based power amplifier design with a reduced level of transmittance distortions, varying in time, without significantly worsening other key features such as output power, efficiency and gain. The test amplifier with GaN-on-Si high electron mobility transistors (HEMT) NPT2018 from MACOM provides more than 17 W of output power at the 62% PAE over a 1.0 GHz to 1.1 GHz frequency range. By applying a proposed design approach, it was possible to decrease phase changes on test pulses from 0.5° to 0.2° and amplitude variation from 0.8 dB to 0.2 dB during the pulse width of 40 µs and 40% duty cycle.
Estimation of Dietary Amino Acid Intake and Independent Correlates of Skeletal Muscle Mass Index among Korean Adults

The aim of this study was to develop a database to identify dietary amino acid intake levels, and to determine whether any amino acid groups were independently correlated with skeletal muscle mass index (SMI). We used data from the Korea National Health and Nutrition Examination Survey 2008–2011, and a total of 3292 participants aged 50–64 years were included in the analysis. Dietary data were obtained using the 24 h recall method. Data regarding dietary amino acid intake was assessed using the computer-aided nutritional analysis program 4.0 published by the Korean Nutrition Society. Multivariate linear regression analysis was used to identify independent correlates of SMI. The major food group that contributed the highest essential amino acid intake was grain and grain products (histidine 25.5%, isoleucine 43.9%, leucine 44.2%, methionine 31.0%, phenylalanine 44.8%, tryptophan 26.4%, and valine 50.8%). Higher SMI was independently associated with sex (men), lower age and body mass index, higher levels of physical activity, and a higher intake of energy and branched-chain amino acids. These results are expected to be used as a basis for developing dietary amino acid intake guidelines for Koreans.
Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Inherited retinal degeneration (RD) leads to the impairment or loss of vision in millions of individuals worldwide, most frequently due to the loss of photoreceptor (PR) cells. Animal models, particularly the laboratory mouse, have been used to understand the pathogenic mechanisms that underlie PR cell loss and to explore therapies that may prevent, delay, or reverse RD. Here, we reviewed entries in the Mouse Genome Informatics and PubMed databases to compile a comprehensive list of monogenic mouse models in which PR cell loss is demonstrated. The progression of PR cell loss with postnatal age was documented in mutant alleles of genes grouped by biological function. As anticipated, a wide range in the onset and rate of cell loss was observed among the reported models. The analysis underscored relationships between RD genes and ciliary function, transcription-coupled DNA damage repair, and cellular chloride homeostasis. Comparing the mouse gene list to human RD genes identified in the RetNet database revealed that mouse models are available for 40% of the known human diseases, suggesting opportunities for future research. This work may provide insight into the molecular players and pathways through which PR degenerative disease occurs and may be useful for planning translational studies.
Daily proactive problem-solving and next day stress appraisals: the moderating role of behavioral activation

ABSTRACT Background and objectives: Drawing upon transactional theory, this study examined the interactive effects of daily problem-prevention behaviors and an aspect of personality relevant to stress responses (i.e., behavioral activation) on next-day stress appraisals of problem-solving demands. Design and methods: Data were collected from 188 employees across a range of industries using an initial survey to collect information on personality, followed by twice-daily surveys over five consecutive work days to measure daily problem-prevention, stress appraisals and problem-solving demands. Results: Multilevel analyses revealed that behavioral activation system (BAS) affected stress appraisals in unique ways. As hypothesized, BAS had a positive direct effect on challenge appraisal. It also moderated the effects of problem-prevention on next-day hindrance appraisals, such that the relationship was more strongly positive for individuals with low levels of BAS. Conclusions: The results demonstrate the BAS has implications not just for promoting positive challenge appraisals, but also for alleviating detrimental effects on stress appraisal. Overall, the findings emphasize the value of exploring the interactive effects of day- and person-level factors on stress appraisals, thereby offering a platform for future research.