Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting stress and mental wellbeing among doctoral researchers

Abstract Background Although mental health in higher education is increasingly recognised as a public health issue, postgraduate research students are often overlooked. Recent studies indicate a high prevalence of mental distress in this population. Aims This study assesses the experience of doctoral researchers and identifies factors influencing mental wellbeing and perceived stress. Methods A cross-sectional study examined how key demographic, individual and contextual factors related to stress and mental wellbeing in a sample of 431 doctoral researchers in the United Kingdom. Results Respondents gave positive reports about their supervisory relationship and identified feeling confidently prepared for their work. Family support, good general health, sleep and low levels of self-depreciation predicted stronger mental wellbeing and lower levels of stress. Students who were confident about their future career and felt well prepared for their studies were less stressed and those who were achievement orientated had better mental wellbeing. Conclusions Focused attention on exploring career options and building confidence may help reduce stress among doctoral researchers. Taking steps to tackle the imposter phenomenon may help further. These could include addressing fear of failure, improving confidence in research ability and clarifying the role of doctoral researchers within the wider academic community.
Very low-calorie ketogenic diet (VLCKD) in patients with psoriasis and obesity: an update for dermatologists and nutritionists

Abstract Psoriasis is a chronic skin immune-mediated disease with systemic pro-inflammatory activation; both genetic and lifestyles factors contribute to its pathogenesis and severity. In this context, nutrition plays a significant role, per se, in psoriasis’ pathogenesis. Obesity is another important risk factor for psoriasis, and weight reduction may improve psoriasis’ clinical severity. The excess body weight, particularly visceral fat mass, can affect both drug's pharmacokinetics and pharmacodynamics. Therefore, psoriasis and obesity share a certain degree of synergy, and the chronic inflammatory state represents the basis of this vicious cycle. Evidence reported that nutrition has different impact on the clinical severity of psoriasis, though some specific diets have been more investigated in clinical studies compared to others. Diets with systemic anti-inflammatory properties seem to have a higher effect on improving the clinical severity of psoriasis. Of interest, very-low-calorie ketogenic diet (VLCKD), through the production of ketone bodies, has been associated with both a significant reduction of body weight and inflammatory state. VLCKD leading to both weight loss and reduction of systemic inflammation may decrease the exacerbation of the clinical manifestations or even it may block the trigger of psoriatic disease. This dietary pattern could represent a potential first-line treatment in psoriatic patients with obesity. The review aims to summarize the current evidence regarding VLCKD and psoriasis with specific reference to antioxidant and anti-inflammatory effects of this dietary pattern.
Iris and Lens Trauma – Iris Reconstruction Iris-Linsen-Trauma – Irisrekonstruktion

Abstract Iris and lens injuries entail a large spectrum and occur in closed and open globe injuries. Depending on accompanying ocular trauma (e.g. corneal involvement) as well as on the extend of the injuries several different surgical options are available ranging from suturing techniques to special individualized implants. The aim of this article is to present and discuss current treatment options for lens and iris trauma in regards to typical cases. Zusammenfassung Iris- und Linsenverletzungen umfassen ein großes Spektrum und treten bei geschlossenen und offenen Bulbusverletzungen auf. Je nach weiteren Verletzungsmustern (bspw. Hornhautbeteiligung) und Ausmaß der Verletzungen gibt es eine Reihe von verschiedenen chirurgischen Optionen – von Nahttechniken bis hin zu speziellen, teils individualisierten Implantaten. In diesem Beitrag sollen die Möglichkeiten der chirurgischen Versorgung von Linsen- und Irisverletzungen anhand von typischen Kasuistiken dargestellt werden, um davon ausgehend den aktuellen Stand der Möglichkeiten der rekonstruktiven Versorgung der unterschiedlichen Verletzungsmuster darzustellen und zu erörtern.
Evolution and Cellular Resistance Mechanisms of the Immunity-Related GTPases

Members of the immunity-related (p47) GTPases (IRGs) are essential, interferon-inducible resistance factors active against a broad spectrum of important intracellular bacterial and protozoal pathogens including Toxoplasma gondii. Despite the strong, partially overlapping but non-redundant susceptibility phenotypes of mice genetically deficient for individual members of the family, little is known about molecular mechanisms of function and regulation of the IRG resistance system. This study demonstrates that IRG GTPases function in a system of direct, nucleotide-dependent regulatory interactions between family members. Spontaneous GTP-dependent homo-oligomerisation of the GKS subfamily member Irga6 leads to the activation of GTPase function in vitro. In vivo, accumulation of activated, GTP-bound GKS proteins at the parasitophorous vacuolar membrane is associated with the IFN-induced, cell autonomous destruction of avirulent Toxoplasma gondii. In contrast, direct GDP-dependent interactions of the unusual GMS subfamily members with the GKS proteins Irga6 and Irgb6 via the G-domains prevent premature activation of the resistance system in absence of infection. Lack of GMS GTPases results in spontaneous activation and aggregation of Irga6 and Irgb6 on endomembranes and hinders association with the parasitophorous vacuolar membrane upon infection with T. gondii. The three GMS GTPases are both necessary and sufficient to regulate Irga6 and Irgb6. No other interferon-inducible proteins are required for the regulation of the resting localisation of Irga6 and Irgb6 in the IFN-induced cell or for their infection-induced assembly on the membrane of the parasitophorous vacuole. Nucleotide binding is essential for the translocation from the resting localisation to the vacuole. Virulent Toxoplasma efficiently inhibited the recruitment of IRG proteins to the parasitophorous vacuole. These findings provide the first link between the enzymatic properties of IRG proteins as GTPases and their function in pathogen resistance. The IRG resistance GTPases are an ancient family that underwent extensive expansion and diversification as well as contraction in the euchordates - a feature characteristic for multigene families associated with pathogen resistance due to host-pathogen coevolution. Despite its essential role in resistance to vacuolar pathogens in mice, the IRG resistance system as such is not conserved in higher primates. While all other groups of mammals possess multiple divergent IRG genes, humans and higher primates contain a largely reduced set of typically three genes. All of these genes lack IFN-inducible elements in their putative promoters and are either significantly truncated, drastically damaged in the nucleotide binding domain or show testis-specific expression paralleling sexual maturity. Consequently, mice and humans must deploy their immune resources against vacuolar pathogens in radically different ways.
Thermal decoherence of superradiance in lead halide perovskite nanocrystal superlattices.

Recent experiments by Rainò et al. have documented cooperative emission from CsPbBr3 nanocrystal superlattices, exhibiting the hallmarks of low temperature superradiance. In particular, the optical response is coherent and the radiative decay rate is increased by a factor of three, relative to that of individual nanocrystals. However, the increase is six orders of magnitude smaller than what is theoretically expected from the superradiance of large assemblies, consisting of 106 to 108 interacting nanocrystals. Here we develop a theoretical model of superradiance for such systems and show that thermal decoherence is largely responsible for the drastic reduction of the radiative decay rate in nanocrystal superlattices. Our theoretical approach explains the experimental results and provides insight into the design of small nanocrystal superlattices, able to show a four orders of magnitude enhancement in superradiant response. These quantitative predictions pave the path towards observing superradiance at higher temperatures.
The isolation and structure identification of four Lignan’s stereoisomers from Uncaria sinensis (Oliv. ) Havil.

The study of the chemical constituents from Uncaria sinensis (oliv.) Havil. has resulted in the isolation and identification of four stereosturcture of lignans, which were identified as: (2R,3R,4S)-lyoniresinol-3α-O-β-D-glucopyranoside (1); (2S,3S,4R)-lyoniresinol-3α-O-β-D-glucopyranoside (2); (2S,3R,4S)-lyoniresinol-3α-O-β-D-glucopyranoside (3); (2R,3S,4R)-lyoniresinol-3α-O-β-D-glucopyranoside (4). All these four compounds were obtained from theUncaria genus for the first time. The compounds were individually identified by one-dimensional (1D), two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectral analyses and comparisons with reported data, and their absolute stereosturcture were identified by the helicity rule of exciton coupled circular dichroism for the first time. The study also constitutes a method of the identification of absolute stereosturcture by the helicity rule of exciton coupled circular dichroism for the first time. Key words: Uncaria sinensis (oliv.) Havil. , Rubiaceae, natural products, lignans, the helicity rule.
Chloroplast gene markers detect diatom DNA in a drowned mice establishing drowning as a cause of death

Diatoms are unicellular microalgae with cell wall made up of rigid silica found in all open water bodies. They thus resist degradation and hence are important tool to diagnose cause of death in drowned bodies. The nitric acid digestion method practiced conventionally in forensic science laboratories has limitations due to manual error. Plant chloroplast genes found in diatoms such as ribulose‐1,5‐bisphosphate carboxylase oxygenase (rbcL‐3P) and rbcL, universal plastidic amplicon (UPA), and photosynthesis I P700 apoprotein chlorophyll Al (psaA), which play an important role in photosystems I and II of photosynthesis, are tested to diagnose drowning in experimental mice. It was seen that psaA‐2 showed amplification at 150 bp in all biological samples. The sequences of psaA‐2 gene marker showed 100% proximity to Thalassiosira weissflogii and rbcL‐3P showed 99% resemblance to Pseudo‐nitzschia multiseries. On the other hand, in postmortem drowned biological samples, the chloroplast‐based gene marker failed to show any amplification.
Feasibility of Using Strength Measures, Including Peak Inspiratory Flow, for Routine Monitoring in Case Management Patients Aged 65 and over

Peak inspiratory flow (PIF) is a portable, relatively new method for measuring respiratory function and indirect muscle strength; the feasibility of its routine clinical measurement is unknown. To investigate the acceptability, reliability and short-term stability of PIF, alongside the established measures of peak expiratory flow (PEF) and grip strength in community dwelling case management patients. Patients were tested in a sitting position, initially on two occasions, one week apart; seven patients having repeated measures taken on a further four occasions over a seven-week period. The best of three attempts for all measures were recorded. Reliability was tested using intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimal detectable change (MDC) and Bland–Altman analysis. Eight patients aged 69–91 years (mean age 81.5 ± 7.7 years; 5 males) participated. For between-day reliability using the first two time points, one week apart the ICCs (3,1) were 0.97, 0.98 and 0.99 for PIF, PEF and grip strength respectively; using all five time points resulted in ICCs of 0.92, 0.99 and 0.99 respectively. Bland–Altman plots also illustrated a good level of agreement across days. Feedback on the acceptability of the measures was gathered from patients. PIF, PEF and grip strength showed excellent reliability and acceptability. Whilst excellent reliability was observed over the seven-week period, the occurrence of clinically significant symptoms and adverse events in the presence of unchanging PIF, PEF and grip strength, suggests that the measures may not be suitable to identify patients with multiple health conditions entering a period of acute decline.
Bilateral Subthalamic Nucleus Deep Brain Stimulation under General Anesthesia: Literature Review and Single Center Experience

Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson’s disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative macrostimulation under local anesthesia (LA). However, many patients cannot tolerate the long operation time under LA without medication. In addition, it cannot be even be performed on PD patients with poor physical and neurological condition. Recently, it has been reported that STN DBS under general anesthesia (GA) can be successfully performed due to the feasible MER under GA, as well as the technical advancement in direct targeting and intraoperative imaging. The authors reviewed the previously published literature on STN DBS under GA using intraoperative imaging and MER, focused on discussing the technique, clinical outcome, and the complication, as well as introducing our single-center experience. Based on the reports of previously published studies and ours, GA did not interfere with the MER signal from STN. STN DBS under GA without intraoperative stimulation shows similar or better clinical outcome without any additional complication compared to STN DBS under LA. Long-term follow-up with a large number of the patients would be necessary to validate the safety and efficacy of STN DBS under GA.
Evidence for a stereoselective mechanism for bitopic activity by extended-length antagonists of the D3 dopamine receptor.

The D3 dopamine receptor (D3R) has been suggested as a drug target for the treatment of a number of neuropsychiatric disorders, including substance use disorders (SUD). Many D3R-selective antagonists are bivalent in nature in that they engage two distinct sites on the receptor - a primary pharmacophore binds to the orthosteric site, where dopamine binds, whereas a secondary pharmacophore interacts with a unique secondary binding pocket (SBP). When engagement of the secondary pocket exerts allosteric activity, the compound is said to be bitopic. We recently reported the synthesis and characterization of two bitopic antagonists of the D3R, (±)-VK04-87 and (±)-VK05-95, which incorporated a racemic trans-cyclopropylmethyl linking chain. To gain a better understanding of the role of chirality in determining the pharmacology of such compounds, we resolved the enantiomers of (±)-VK04-87. We found that the (+)-isomer displays higher affinity for the D3R and exhibits greater selectivity versus the D2R than the (-)-isomer. Strikingly, using functional assays, we found that (+)-VK04-87 inhibits the D3R in a noncompetitive manner, while (-)-VK04-87 behaves as a purely competitive antagonist, indicating that the apparent allosteric activity of the racemate is due to the (+)-isomer. Molecular dynamic simulations of (+)-VK04-87 and (-)-VK04-87 binding to the D3R suggest that the (+)-isomer is able to interact with the SBP of the receptor whereas the (-)-isomer bends away from this pocket, thus potentially explaining their differing pharmacology. These results emphasize the importance of the linker, and its isomeric conformations, within extended-length molecules for their positioning and engagement within GPCR binding pockets.
Clinical Significance of Carbapenem-Tolerant Pseudomonas aeruginosa Isolated in the Respiratory Tract

We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBCAD)/minimal inhibitory concentration for adherent bacteria (MICAD) ≥ 32 (n = 9) group and low-tolerance MBCAD/MICAD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections.
Physical health monitoring in dementia and associations with ethnicity: a descriptive study using electronic health records

Background Good physical health monitoring can increase quality of life for people with dementia, but the monitoring may vary and ethnic inequalities may exist. Aim To investigate UK primary care routine physical health monitoring for people with dementia by: (a) ethnic groups, and (b) comorbidity status. Design & setting A retrospective cohort study was undertaken using electronic primary care records in the UK. Method Physical health monitoring was compared in people with dementia from white, black, and Asian ethnic groups and compared those with ≥1 comorbidity versus no comorbidity, from 1 April 2015 to 31 March 2016. Using the Dementia : Good Care Planning framework and expert consensus, good care was defined as receiving, within 1 year: a dementia review; a blood pressure (BP) check (at least one); a GP consultation (at least one); a weight and/or body mass index (BMI) recording (at least one); and an influenza vaccination. Results Of 20 821 people with dementia, 68% received a dementia review, 80% at least one BP recording, 97% at least one GP contact, 48% a weight and/or BMI recording, and 81% an influenza vaccination in 1 year. Compared with white people, black people were 23% less likely and Asian people 16% less likely to have weight recorded (adjusted incidence rate ratio [IRR] = 0.77, 95% confidence interval [CI] = 0.60 to 0.98/0.84, 0.71 to 1.00). People without comorbidities were less likely to have weight recorded (adjusted IRR = 0.74, 95% CI = 0.69 to 0.79) and BP monitored (adjusted IRR = 0.71, 95% CI = 0.68 to 0.75). Conclusion Ethnic group was not associated with differences in physical health monitoring, other than weight monitoring. Comorbidity status was associated with weight and BP monitoring. Physical health monitoring in dementia, in particular nutrition, requires improvement.
Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.
Vowel and consonant length in four Alemannic dialects and their influence on the respective varieties of Swiss Standard German

Dass die Alemannischen Dialekte (ALM) die Vokalqualitat des Schweizerhochdeutschen (SHD) pragt, wurde bereits mehrmals untersucht. Hingegen liegen noch keine systematischen Studien uber die dialektale Pragung der Vokal- und Konsonantenquantitat im SHD vor. Diese Studie erforscht deshalb bei vier Dialekten, wie sich ALM auf die Lange der Vokale (V) und Konsonanten (K) in den jeweiligen SHD-Varietaten auswirkt. Segmentdaueranalysen zweisilbigerWorter mit kurzen/langen V/K zeigten, dass (1) die vier Dialekte im Prinzip das gleiche V/K-Quantitatssystem aufweisen (trotz z.T. unterschiedlicher Verteilung der Vokalquantitaten bei bestimmten Wortern) und dass dieses System auch im SHD angewendet wird. (2) Statistisch signifikante Dauerunterschiede in den regionalen SHD-Varietaten wurden nur bei Wortern gefunden, bei denen ein phonologischer Quantitatsunterschied zwischen den ALM- und SHD-Aquivalenten vorliegt. Diese Unterschiede sind jedoch nicht dialektspezifisch, sondern konnen bei allen Dialekten mit diesen Quantitatsunterschieden vorkommen.
Isobaric quantitative protein interaction reporter technology for comparative interactome studies.

Chemical cross-linking with mass spectrometry (XL-MS) has emerged as a useful tool for the large scale study of protein structures and interactions from complex biological samples including intact cells and tissues. Quantitative XL-MS (qXL-MS) provides unique information on protein conformational and interaction changes resulting from perturbations such as drug treatment and disease state. Previous qXL-MS studies relied on incorporation of stable isotopes into the cross-linker (primarily deuterium) or metabolic labeling with SILAC. Here, we introduce isobaric quantitative Protein Interaction Reporter (iqPIR) technology which utilizes stable isotopes selectively incorporated into the cross-linker design, allowing for isobaric cross-linked peptide pairs originat-ing from different samples to display distinct quantitative isotope signatures in tandem mass spectra. This enables improved quan-titation of cross-linked peptide levels from proteome-wide samples due to the reduced complexity of tandem mass spectra relative to MS1 spectra. In addition, because of the isotope incorporation in the reporter and the residual components of the cross-linker that remain on released peptides, each fragmentation spectrum can offer multiple independent opportunities and therefore, im-proved confidence for quantitative assessment of cross-linker pair level. Finally, in addition to providing information on solvent accessibility of lysine sites, dead end iqPIR cross-linked products can provide protein abundance and/or lysine site modification level information all from a single in vivo cross-linking experiment.