Miracle-dz/UniFAR-FTUs huggingface dataset:
The Writers, Readers, and Erasers in Redox Regulation of GAPDH

Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.
The entropy loss on supercooling a liquid and anharmonic contributions

Interdependence of the configurational, vibrational, and anharmonic-force contributions to the entropy of a liquid during its supercooling is investigated, and the effect of the anharmonic-force contribution to the entropy at constant pressure and constant volume conditions is analyzed. For realistic values of the Gruneisen parameter and expansion coefficient of a liquid, this contribution is found to be 30–40% of the heat capacity, which is high enough to affect the relation between the viscosity and excess entropy. An analysis of the resolved contributions to entropy of liquid selenium, an N-type liquid, shows that its configurational entropy is not proportional to its excess entropy.
Effects of dental implant treatment on sleep quality in edentulous older people: A prospective cohort study

Background Edentulism and sleep disturbances are commonly seen among older people and cause serious negative effects on their daily lives. Edentulism can induce sleep problems by changing maxillo-mandibular anatomy and surrounding soft tissues. The effect of the treatment of complete edentulism on sleep disturbances is not sufficiently understood. The purpose of this cohort study is to detect how different treatment options affect sleep quality, daytime fatigue and sleep disorder breathing in totally edentulous elderly people. Material and Methods Ninety-six individulas (50 male and 46 female) participated in this prospective cohort study. The patients were non-randomly assigned to three groups, fixed implant-supported prostheses (FP), removable implant-supported prostheses (RP) and conventional total prostheses (CP). The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and the STOP-Bang questionnaire were calculated before (T0) and one year after (T1) their prosthetic rehabilitations. Results Although there was no statistically significant difference between groups in terms of mean PSQI (p=0.524), ESS (p=0.410) and STOP-Bang (p=0.697) scores at T0, there was a significant difference between groups in terms of mean PSQI (p=0.011), ESS (p=0.030) and STOP-Bang (p=0.024) scores at T1. The FP group, when compared to CP group was associated with significantly better scores in the PSQI (Δ = -3.399, 95% CI= -4.612 to -2.187), ESS (Δ = -1.663, 95% CI= -3.149 to -0.176) and STOP-Bang (Δ = -0.994, 95% CI= -1.592 to -0.397). Conclusions Within the limitations of this study FP was associated with a positive influence on sleep disturbances. Randomized controlled trials will be needed to provide reliable inference on this association. Key words:Dental implant, edentulism, older people, sleep disturbances.
A Systematic Review of Nutrition, Supplement, and Herbal-Based Adjunctive Therapies for Vitiligo.

Background: Vitiligo is an autoimmune skin condition that affects people globally anywhere, from <0.1% to more than 8% of individuals. The disease destroys skin melanocytes, resulting in a patchy depigmentation of the skin. About 50% of all patients develop the disease before their 20s. Methods: We systematically searched the literature and reviewed the evidence for the use of nutritional supplements and diet in the management of vitiligo. Embase and Medline were searched for diet, herbal, and nutrition-based clinical studies. Additional filters were applied that looked for controlled trial or randomized controlled trial and article or article in press or letter and English and clinical study. We selected clinical studies in humans that showed how diet or natural supplements can improve the symptoms of vitiligo in all of our searches. Results: There were 62 manuscripts that resulted from the PubMed search and 259 from the Embase search. A final of 26 studies were reviewed, and other supplemental case and case-control studies were used to introduce diet components that may influence either exacerbation or amelioration of vitiligo. Possible mechanisms of action are introduced for natural and supplemental interventions. Conclusion: Some of the supplements reviewed include Gingko biloba, oral Polypodium leucotomos, alpha lipoic acid, vitamins B12, D, and E, folic acid, phenylalanine, canthaxanthin, Nigella sativa oil, and other combined herbal bio-actives. Overall, the growing evidence is promising, but more studies are needed in this area to further explore the impact that supplements and diet can have on vitiligo management. The most promising therapies included oral phenylalanine as adjuvant therapy with UVA therapy, oral G. biloba as monotherapy, both of which can be used with other traditional therapies, and oral P. leucotomos with phototherapy or photochemotherapy.
One-electron reduction of di-imidosulphur compounds, S(NR)2, and some complexes of Group 6A metal carbonyl derivatives containing S(NR)2 ligands: studies of the radical products by electron spin resonance spectroscopy

Reduction of the di-imidosulphur compounds, S(NR)2(R = But, Ph, 4-MeC6H4, or 4-O2NC6H4), in 1,2-dimethoxyethane solution with a potassium mirror in vacuo gives fairly stable solutions of the corresponding anion radicals [S(NR)2]– which have been studied by e.s. r. spectroscopy. The frozen-solution e.s. r spectrum of K[S(NBut)2] has also been recorded. Isotropic coupling constants A(14N), A(1H) and, for R = But, A(33S) have been deduced and analysed in terms of the electronic structures of the radicals using empirical electron-density relationships. Some CNDO/2 and INDO calculations have been made and the experimental and calculated electron-spin densities compared. Variable-temperature e.s. r. measurements have given no indication of the presence of distinct geometric isomers of the anions in solution. The model calculations suggest that the E/E conformation is most stable and that interconversion to give the E/Z or Z/Z forms is unlikely. The experimental evidence in all cases indicates the two nitrogen atoms to the magnetically equivalent. Alkali-metal isotropic coupling constants A(MI) for the species MI[S(NBut)2](MI=7Li, 23Na, or 39K) have been estimated and indicate that the metal–anion interaction increases in the order K < Na < Li.Potassium-metal reduction of [M(Co)4{S(NBut)2}](M = Cr, Mo, or W) produces the corresponding anions with well defined isotropic e.s. r spectra. Values for A(14N) and A(M)(M =95/97Mo or 183W) have been deduced and the spectra analysed. The results suggest that the unpaired electron is located mainly in the S(NBut)2 ligand. CNDO/2 calculations for the chromium anion are consistent with this observation. Attempts to produce [M(CO)4{S(NPh)2}]– have been unsuccessful except for M = Cr, when an unstable species is formed. A tentative analysis of the e.s. r spectrum of this radical anion is presented.
The Potential of Proteolytic Chimeras as Pharmacological Tools and Therapeutic Agents

The induction of protein degradation in a highly selective and efficient way by means of druggable molecules is known as targeted protein degradation (TPD). TPD emerged in the literature as a revolutionary idea: a heterobifunctional chimera with the capacity of creating an interaction between a protein of interest (POI) and a E3 ubiquitin ligase will induce a process of events in the POI, including ubiquitination, targeting to the proteasome, proteolysis and functional silencing, acting as a sort of degradative knockdown. With this programmed protein degradation, toxic and disease-causing proteins could be depleted from cells with potentially effective low drug doses. The proof-of-principle validation of this hypothesis in many studies has made the TPD strategy become a new attractive paradigm for the development of therapies for the treatment of multiple unmet diseases. Indeed, since the initial protacs (Proteolysis targeting chimeras) were posited in the 2000s, the TPD field has expanded extraordinarily, developing innovative chemistry and exploiting multiple degradation approaches. In this article, we review the breakthroughs and recent novel concepts in this highly active discipline.
Ticking the "Family Meeting" Box-Unlikely to Be Enough.

At the preround Senior Intensive Care Team meeting, I ask for any specific concerns and issues to be brought to my attention before starting. “Dr. Boyd, the patient in bed 17 is doing very badly, and the family don’t seem to be fully understanding. Can you make sure you talk to them please? ” asks the senior nurse of the day. He is supported by wry nods from the residents; it has obviously been a difficult night. Often the most challenging part of my job, as a senior intensivist, is the communication with relatives and friends about the patient’s condition, and as I get more senior, I only seem to give information about a poor prognosis; others have got in before me delivering the good news. On this occasion, the relatives are frightened and unsure, but have been expecting bad news, and the who is who pictures on the wall have helped them identify who I am. We discuss the case, and at the end, they thank me and all the ICU staff for our care. I am pleased with the job I have done here, although when I leave, the family are in tears, grieving already. This is likely to be the last I see of the family and I do not know what will become of them. We focus our follow-ups, patient diaries, and ward reviews on our patients, rarely the relatives of the bereaved. Did I actually do a good job communicating, did I really help? After all, this is what the relatives will remember us by. For a number of years, family discussions around the time of imminent death on the ICU have been recommended, initially from Consensus opinion (1, 2) and then supported by research work showing that the discussion can be useful (3) and needs to be undertaken well by allowing, for instance, sufficient time for the family to speak (4). The purpose of the family discussion will have a different focus depending on the clinical condition of the patient, the likelihood of death or debilitating survival, the possibility of organ donation, and the cultural and legal landscape in which the ICU physicians practice. More recently, guidelines using formal research evaluation have provided recommendations for family-centered care when a relative is critically ill in the ICU (5). However, these recommendations are methodologically weak, highlighting the need for future research to identify the most effective interventions to improve this important aspect in the totality of ICU care. In this issue of Critical Care Medicine, Tang et al (6) readdress this important topic and consider how the organization of end-of-life care undertaken in the ICU can effect anxiety and depression symptoms in family members up to 6 months after the death. They ask whether anxiety and depression assessed at 1, 3, and 6 months can be improved by interventions made within the ICU prior to the bereavement. They found that anxiety and depressive symptoms, perhaps unsurprisingly, occurred in, respectively, 22% and 42% of family members Owen Boyd, MBChB, BSc, MD, FRCA, FRCP, FFICM Ticking the “Family Meeting” Box—Unlikely to Be Enough*
The lncRNA Toolkit: Databases and In Silico Tools for lncRNA Analysis

Long non-coding RNAs (lncRNAs) are a rapidly expanding field of research, with many new transcripts identified each year. However, only a small subset of lncRNAs has been characterized functionally thus far. To aid investigating the mechanisms of action by which new lncRNAs act, bioinformatic tools and databases are invaluable. Here, we review a selection of computational tools and databases for the in silico analysis of lncRNAs, including tissue-specific expression, protein coding potential, subcellular localization, structural conformation, and interaction partners. The assembled lncRNA toolkit is aimed primarily at experimental researchers as a useful starting point to guide wet-lab experiments, mainly containing multi-functional, user-friendly interfaces. With more and more new lncRNA analysis tools available, it will be essential to provide continuous updates and maintain the availability of key software in the future.
Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors (Eur. J. Org. Chem. 21/2010)

The cover picture shows the key steps of a convergent and versatile synthesis of Syringolin A (SylA) and other syrbactins. SylA is a small-molecule virulence factor produced by some plant pathogenic Pseudomonas syringae pv. syringae strains during infection. It leads to irreversible inhibition of the plant's 20S proteasome (lower right corner depicts the binding mode of SylA to one of the active-site centres of the proteasome), resulting in the so-called brown-spot disease. The synthetic preparation of SylA and its analogues opens up further possibilities for biological investigation into the mode of action of SylA in plant–pathogen interactions. Details are discussed in the article by M. Kaiser et al. on p. 3991 ff.
Molecular Anchors for Self-Assembled Monolayers on ZnO: A Direct Comparison of the Thiol and Phosphonic Acid Moieties

Two of the most promising schemes for attaching organic molecules to metal oxides are based on the chemistry of the thiol and phosphonic acid moieties. We have made a direct comparison of the efficacy of these two molecular anchors on zinc oxide by comparing the chemical and physical properties of n-hexane derivatives of both. The surface properties of polycrystalline ZnO thin films and ZnO(0001)-O crystals modified with 1-hexanethiol and 1-hexanephosphonic acid were examined with a novel quartz crystal microbalance (QCM)-based flow cell reactor, angle-resolved and temperature-dependent photoelectron spectroscopy, and contact angle measurements. A means of using ammonium chloride as a probe of molecule-ZnO interactions is introduced and used to ascertain the relative quality of self-assembled monolayers (SAMs) based on thiols and phosphonic acids. QCM data shows that a phosphonic acid-anchored alkyl chain only six carbons long can provide significant corrosion protection for ZnO against Bronsted acids, r.
Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches

Simple Summary When we ingest a meal, our intestine secretes hormones that are released into the bloodstream. Amongst these hormones are the incretins hormones which stimulate the release of insulin from the pancreas which is essential for the regulation of in particular postprandial glucose concentrations. In patients with type 2 diabetes, the effect of the incretins is diminished. This is thought to contribute importantly to the pathophysiology of the disease. However, in pharmacological amounts, the incretins may still influence insulin secretion and metabolism. Much research has therefore been devoted to the development of incretin-based therapies for type 2 diabetes. These therapies include compounds that strongly resemble the incretins, hereby stimulating their effects as well as inhibitors of the enzymatic degradation of the hormones, thereby increasing the concentration of incretins in the blood. Both therapeutic approaches have been implemented successfully, but research is still ongoing aimed at the development of further optimized therapies. Abstract Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.
Determination of the Forming Limit for a ZIRLO™ Sheet with High Anisotropy

In this study, the experimental two-dimensional forming limit diagram (FLD) data for a ZIRLO™ sheet, which is used in nuclear fuel rod support grids, were converted and presented as a triaxiality failure diagram (TFD). Most previous studies assumed ZIRLO™ to be isotropic when calculating the effective stress and strain. However, for highly anisotropic materials, the anisotropy should be considered for calculations of effective stress and strain; hence, in this study, they were calculated by introducing the normal anisotropy coefficient. To obtain this parameter of the ZIRLO™ specimens, tensile tests were performed on specimens with 0°, 45°, and 90° angles with respect to the rolling direction. It was observed that the average normal anisotropy coefficient measured during the tests was 4.94, which is very high. The von Mises isotropic and Hill 48 anisotropic yield criterion were applied to the FLD data that were experimentally determined using a limit dome height test and were converted into effective stress and effective strain. When the FLD is converted to TFD, the curve will increase in the top-right direction if the r-value is greater than 1, and this become more severe as the r-value increases. The TFD, which was converted considering the anisotropy, is almost the same to the TFD obtained using the digital image correlation method in the tensile tests of four specimens with different stress states. If anisotropy is not considered, then the formability is normally underestimated. However, a highly accurate TFD can be obtained with the method proposed in this study.
Update on Chemotherapeutic Approaches and Management of Bevacizumab Usage for Glioblastoma

Glioblastoma, the most common primary brain tumor in adults, has one of the most dismal prognoses in cancer. In 2009, bevacizumab was approved for recurrent glioblastoma in the USA. To evaluate the clinical impact of bevacizumab as a first-line drug for glioblastoma, two randomized clinical trials, AVAglio and RTOG 0825, were performed. Bevacizumab was found to improve progression-free survival (PFS) and was reported to be beneficial for maintaining patient performance status as an initial treatment. These outcomes led to bevacizumab approval in Japan in 2013 as an insurance-covered first-line drug for glioblastoma concurrently with its second-line application. However, prolongation of overall survival was not evinced in these clinical trials; hence, the clinical benefit of bevacizumab for newly diagnosed glioblastomas remains controversial. A recent meta-analysis of randomized controlled trials of bevacizumab combined with temozolomide in recurrent glioblastoma also showed an effect only on PFS, and the benefit of bevacizumab even for recurrent glioblastoma is controversial. Here, we discuss the clinical impact of bevacizumab for glioblastoma treatment by reviewing previous clinical trials and real-world evidence by focusing on Japanese experiences. Moreover, the efficacy and safety of bevacizumab are summarized, and we provide suggestions for updating the approaches and management of bevacizumab.
Neonatal teeth: Importance of histological findings in management update.

BACKGROUND Presence of teeth in a newborn represents a rare finding and a disturbance of biological chronology of teeth. The aim of this paper is to report two cases with neonatal teeth histologically examined. CASE REPORT In this paper two cases of patients with neonatal teeth are reported and histological examinations of three extracted teeth are described. We report an exceptional finding in one of the neonatal teeth microscopically examined: a massive inflammatory infiltration in the pulp tissue similar to that in pulpitis. RESULTS The management of natal and neonatal teeth usually includes the extraction in case of ulceration on the tongue or severe tooth mobility to prevent accidental inhalation or feeding disturbances. The presence of an inflammatory infiltration of pulp tissue in one of teeth histologically examined suggests to review the indications for extraction considered to date. CONCLUSION The management of natal and neonatal teeth should consider the presence of an inflammatory infiltration of pulp tissue. An anamnestic interview is advisable in ordert to deeply investigate about possible behaviours of the child due to pain or discomfort.
Construction and validation of educational technology to prevent complications in intestinal ostomies / periestomy skin.

OBJECTIVE To build and validate an educational booklet for preventing complications in intestinal ostomy and peristomy skin. METHODS Methodological study developed in: 1. Survey of the clinical profile of patients; 2. Integrative review; 3. Construction of technology; 4. Validation of educational material. The Delphi technique was used, with 18 judges with expertise in the field of stomatherapy. For data treatment, the Collective Subject Discourse (CSD), descriptive analysis, Kappa Index (K), binomial test and Content Validity Index (CVI) were used. RESULTS The agreement rate between judges was higher than 0.61, for K p> 0.05, a proportion of 80% for the binomial test and 80% for the CVI. The booklet showed an excellent index for K, binomial test and global content validity, becoming validated. FINAL CONSIDERATIONS The booklet was validated in appearance and content, being an instrument that can favor communication between professionals and people with ostomies.