Miracle-dz/UniFAR-FTUs huggingface dataset:
The Treatment Outcome of Smart Device–Based Tinnitus Retraining Therapy: Prospective Cohort Study

Background Tinnitus retraining therapy (TRT) is a standard treatment for tinnitus that consists of directive counseling and sound therapy. However, it is based on face-to-face education and a time-consuming protocol. Smart device–based TRT (smart-TRT) seems to have many advantages, but the efficacy of this new treatment has been questioned. Objective The aim of this study was to compare the efficacy between smart-TRT and conventional TRT (conv-TRT). Methods We recruited 84 patients with tinnitus. Results were compared between 42 patients who received smart-TRT and 42 control participants who received conv-TRT. An interactive smart pad application was used for directive counseling in the smart-TRT group. The smart pad application included detailed education on ear anatomy, the neurophysiological model of tinnitus, concept of habituation, and sound therapy. The smart-TRT was bidirectional: There were 17 multiple choice questions between each lesson as an interim check. The conv-TRT group underwent traditional person-to-person counseling. The primary outcome measure was the Tinnitus Handicap Inventory (THI), and the secondary outcome measure was assessed using a visual analogue scale (VAS). Results Both treatments had a significant treatment effect, which comparably improved during the first 2 months. The best improvements in THI were –23.3 (95% CI –33.1 to –13.4) points at 3 months and –16.8 (95% CI –30.8 to –2.8) points at 2 months in the smart-TRT group and conv-TRT group, respectively. The improvements on the VAS were also comparable: smart-TRT group: –1.2 to –3.3; conv-TRT: –0.7 to –1.7. Conclusions TRT based on smart devices can be an effective alternative for tinnitus patients. Considering the amount of time needed for person-to-person counseling, smart-TRT can be a cost-effective solution with similar treatment outcomes as conv-TRT.
Human factors in anaesthesia: a narrative review

Healthcare relies on high levels of human performance, as described by the ‘human as the hero’ concept. However, human performance varies and is recognised to fall in high‐pressure situations, meaning that it is not a reliable method of ensuring safety. Other safety‐critical industries embed human factors principles into all aspects of their organisations to improve safety and reduce reliance on exceptional human performance; there is potential to do the same in anaesthesia. Human factors is a broad‐based scientific discipline which aims to make it as easy as possible for workers to do things correctly. The human factors strategies most likely to be effective are those which ‘design out’ the chance of an error or adverse event occurring. When errors or adverse events do happen, barriers are in place to trap them and reduce the risk of progression to patient and/or worker harm. If errors or adverse events are not trapped by these barriers, mitigations are in place to minimise the consequences. Non‐technical skills form an important part of human factors barriers and mitigation strategies and include: situation awareness; decision‐making; task management; and team working. Human factors principles are not a substitute for proper investment and appropriate staffing levels. Although applying human factors science has the potential to save money in the long term, its proper implementation may require investment before reward can be reaped. This narrative review describes what is known about human factors in anaesthesia to date.
“The person in power told me to”—European PhD students’ perspectives on guest authorship and good authorship practice

Questionable authorship practices in scientific publishing are detrimental to research quality and management. The existing literature dealing with the prevalence, and perceptions, of such practices has focused on the medical sciences, and on experienced researchers. In contrast, this study investigated how younger researchers (PhD students) from across the faculties view fair authorship attribution, their experience with granting guest authorships to more powerful researchers and their reasons for doing so. Data for the study were collected in a survey of European PhD students. The final dataset included 1,336 participants from five European countries (Denmark, Hungary, Ireland, Portugal, and Switzerland) representing all major disciplines. Approximately three in ten reported that they had granted at least one guest authorship to “a person in power”. Half of these indicated that they had done so because they had been told to do so by the person in power. Participants from the medical, natural and technical sciences were much more likely to state that they had granted a guest authorship than those from other faculties. We identified four general views about what is sufficient for co-authorship. There were two dominant views. The first (inclusive view) considered a broad range of contributions to merit co-authorship. The second (strongly writing-oriented) emphasised that co-authors must have written a piece of the manuscript text. The inclusive view dominated in the natural, technical, and medical sciences. Participants from other faculties were more evenly distributed between the inclusive and writing oriented view. Those with an inclusive view were most likely to indicate that they have granted a guest authorship. According to the experiences of our participants, questionable authorship practices are prevalent among early-career researchers, and they appear to be reinforced through a combination of coercive power relations and dominant norms in some research cultures, particularly in the natural, technical, and medical sciences.
External fibre Fabry–Perot acoustic sensor based on a photonic-crystal mirror

We demonstrate an acoustic sensor based on a Fabry–Perot interferometer formed by a single-mode fibre and an external silicon photonic-crystal mirror. Measurements in air indicate that this sensor has a relatively uniform frequency response up to at least 50 kHz, and detects pressures as low as 18 μPa Hz−1/2. This limit is four orders of magnitude lower than in similar types of acoustic fibre sensors. The sensor response agrees with mechanical calculations to within a few dB. We predict that this sensor has the potential to detect pressures as low as 600 nPa Hz−1/2, corresponding to the ambient thermal noise level in air at room temperature.
Functional role of GATA3 and CDX2 in lineage specification during bovine early embryonic development

In brief The lineage specification during early embryonic development in cattle remains largely elusive. The present study determines the effects of trophectoderm-associated factors GATA3 and CDX2 on lineage specification during bovine early embryonic development. Abstract Current understandings of the initiation of the trophectoderm (TE) program during mammalian embryonic development lack evidence of how TE-associated factors such as GATA3 and CDX2 participate in bovine lineage specification. In this study, we describe the effects of TE-associated factors on the expression of lineage specification marker genes such as SOX2, OCT4, NANOG, GATA6, and SOX17, by using cytosine base editor system. We successfully knockout GATA3 or CDX2 in bovine embryos with a robust efficiency. However, GATA3 or CDX2 deletion does not affect the developmental potential of embryos to reach the blastocyst stage. Interestingly, GATA3 deletion downregulates the NANOG expression in bovine blastocysts. Further analysis of the mosaic embryos shows that GATA3 is required for NANOG in the TE of bovine blastocysts. Single blastocyst RNA-seq analysis reveals that GATA3 deletion disrupts the transcriptome in bovine blastocysts. Altogether, we propose that GATA3 plays an important role in maintaining TE lineage program in bovine embryos and the functional role of GATA3 is species-specific.
Implementing human factors in anaesthesia: guidance for clinicians, departments and hospitals

Human factors is an evidence‐based scientific discipline used in safety critical industries to improve safety and worker well‐being. The implementation of human factors strategies in anaesthesia has the potential to reduce the reliance on exceptional personal and team performance to provide safe and high‐quality patient care. To encourage the adoption of human factors science in anaesthesia, the Difficult Airway Society and the Association of Anaesthetists established a Working Party, including anaesthetists and operating theatre team members with human factors expertise and/or interest, plus a human factors scientist, an industrial psychologist and an experimental psychologist/implementation scientist. A three‐stage Delphi process was used to formulate a set of 12 recommendations: these are described using a ‘hierarchy of controls’ model and classified into design, barriers, mitigations and education and training strategies. Although most anaesthetic knowledge of human factors concerns non‐technical skills, such as teamwork and communication, human factors is a broad‐based scientific discipline with many other additional aspects that are just as important. Indeed, the human factors strategies most likely to have the greatest impact are those related to the design of safe working environments, equipment and systems. While our recommendations are primarily provided for anaesthetists and the teams they work with, there are likely to be lessons for others working in healthcare beyond the speciality of anaesthesia.
LYSET/TMEM251- a novel key component of the mannose 6-phosphate pathway

ABSTRACT Degradation of macromolecules delivered to lysosomes by processes such as autophagy or endocytosis is crucial for cellular function. Lysosomes require more than 60 soluble hydrolases in order to catabolize such macromolecules. These soluble hydrolases are tagged with mannose6-phosphate (M6P) moieties in sequential reactions by the Golgi-resident GlcNAc-1-phosphotransferase complex and NAGPA/UCE/uncovering enzyme (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), which allows their delivery to endosomal/lysosomal compartments through trafficking mediated by cation-dependent and -independent mannose 6-phosphate receptors (MPRs). We and others recently identified TMEM251 as a novel regulator of the M6P pathway via independent genome-wide genetic screening strategies. We renamed TMEM251 to LYSET (lysosomal enzyme trafficking factor) to establish nomenclature reflective to this gene’s function. LYSET is a Golgi-localized transmembrane protein important for the retention of the GlcNAc-1-phosphotransferase complex in the Golgi-apparatus. The current understanding of LYSET’s importance regarding human biology is 3-fold: 1) highly pathogenic viruses that depend on lysosomal hydrolase activity require LYSET for infection. 2) The presence of LYSET is critical for cancer cell proliferation in nutrient-deprived environments in which extracellular proteins must be catabolized. 3) Inherited pathogenic alleles of LYSET can cause a severe inherited disease which resembles GlcNAc-1-phosphotransferase deficiency (i.e., mucolipidosis type II). Abbreviations: GlcNAc-1-PT: GlcNAc-1-phosphotransferase; KO: knockout; LSD: lysosomal storage disorder; LYSET: lysosomal enzyme trafficking factor; M6P: mannose 6-phosphate; MPRs: mannose-6-phosphate receptors, cation-dependent or -independent; MBTPS1/site-1 protease: membrane bound transcription factor peptidase, site 1; MLII: mucolipidosis type II; WT: wild-type
Tissue-preferential recruitment of electron transfer chains for cytochrome P450-catalyzed phenolic biosynthesis

Cytochrome P450 system consists of P450 monooxygenase and redox pattern(s). While the importance of monooxygenases in plant metabolism is well documented, the metabolic roles of the related redox components have been largely overlooked. Here, we show that distinct electron transfer chains are recruited in phenylpropanoid-monolignol P450 systems to support the synthesis and distribution of different classes of phenolics in different plant tissues. While Arabidopsis cinnamate 4-hydroxylase adopts conventional NADPH-cytochrome P450 oxidoreductase (CPR) electron transfer chain for its para-hydroxylation reaction, ferulate 5-hydroxylase uses both NADPH-CPR-cytochrome b5 (CB5) and NADH–cytochrome b5 reductase–CB5 chains to support benzene ring 5-hydroxylation, in which the former route is primarily recruited in the stem for syringyl lignin synthesis, while the latter dominates in the syntheses of 5-hydroxylated phenolics in seeds and seed coat suberin. Our study unveils an additional layer of complexity and versatility of P450 system that the plants evolved for diversifying phenolic repertoires.
Exploration of immunotherapy in advanced pulmonary lymphoepithelioma‐like carcinoma

Pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a rare and histologically distinctive subtype of nonsmall cell lung cancer (NSCLC). High expression of programmed death ligand 1 (PD‐L1) and scarcity of druggable driver mutations raise the potential of immunotherapy for advanced PELEC. However, evidence on the clinical impact of immune‐checkpoint inhibitors (ICIs) remained limited and unconvincing. The present study retrospectively enrolled advanced PLELC patients who received ICIs either as up‐front or salvage therapy in SYSUCC between March 15, 2017 and March 15, 2022. The comparative efficacy of chemoimmunotherapy vs chemotherapy in the first‐line setting and chemoimmunotherapy vs ICIs monotherapy in the ≥2 line setting was investigated. A total of 96 patients were finally enrolled; 49 PLELC patients received immunotherapy plus platinum‐based chemotherapy, while 45 patients received platinum‐based chemotherapy as first‐line treatment. Patients with chemoimmunotherapy significantly obtain more survival benefits than those receiving chemotherapy (median progression‐free survival [PFS]: 15.6 vs 8.6 months, P = .0015). Additionally, patients with chemoimmunotherapy obtained more PFS benefits than those with ICIs monotherapy in the ≥2 line of therapy (median PFS: 21.7 months vs 7.8 months, P = .094). A significant correlation was observed between prognostic nutritional index (PNI) and favorable treatment outcomes in patients receiving first‐line chemoimmunotherapy (median PFS: 17.8 months vs 7.6 months, P < .0001). Likewise, patients in the monocyte‐to‐lymphocyte ratio (MLR)‐high group had significantly shorter PFS than the MLR‐low group (median PFS: 11.2 months vs not reached, P = .0009). Our study elucidated the superior efficacy of ICIs therapy, especially chemoimmunotherapy in advanced PLELC, which may provide new insight into the role of immunotherapy in advanced PLELC.
Somatic Variants and Exon-Level Copy Number Changes in Five Hyperplastic Oral Leukoplakias

Oral leukoplakia (OL), an oral potentially malignant disorder, begins with a hyperplastic/hyperkeratotic stage at which no genome-scale somatic single nucleotide variant profiles have been described so far. We performed exome sequencing of five cases at this stage with no evidence of dysplasia to identify genetic alterations (exon-level copy number alterations, indels, and single nucleotide variants), their association with transcript levels, and relationship with oral cancer susceptibility. Pathway enrichment analysis of genes associated with tobacco chewing and age-related mutation signatures, transcripts with variants predicted to be functionally damaging and those with significantly altered levels all indicated the involvement of focal adhesion, ECM-receptor interactions, regulation of cytoskeleton, and DNA repair. Two novel mutations identified in FAT1 tumor suppressor gene were associated with decreased transcript levels. In addition, 16 expressed cancer driver genes contained functionally damaging variants. Many of the affected genes were also reported in dysplastic OL lesions. The presence of variants in cancer driver genes and those shared with oral dysplasias possibly provides a basis for further progression and increased susceptibility to oral cancer.
Overflow metabolism at the thermodynamic limit of life: How carboxydotrophic acetogens mitigate carbon monoxide toxicity

Carboxydotrophic metabolism is gaining interest due to its applications in gas fermentation technology, enabling the conversion of carbon monoxide to fuels and commodities. Acetogenic carboxydotrophs play a central role in current gas fermentation processes. In contrast to other energy‐rich microbial substrates, CO is highly toxic, which makes it a challenging substrate to utilize. Instantaneous scavenging of CO upon entering the cell is required to mitigate its toxicity. Experiments conducted with Clostridium autoethanogenum at different biomass‐specific growth rates show that elevated ethanol production occurs at increasing growth rates. The increased allocation of electrons towards ethanol at higher growth rates strongly suggests that C. autoethanogenum employs a form of overflow metabolism to cope with high dissolved CO concentrations. We argue that this overflow branch enables acetogens to efficiently use CO at highly variable substrate influxes by increasing the conversion rate almost instantaneously when required to remove toxic substrate and promote growth. In this perspective, we will address the case study of C. autoethanogenum grown solely on CO and syngas mixtures to assess how it employs acetate reduction to ethanol as a form of overflow metabolism.
Snowboard Landings from Different Heights: Electroencephalography Activity in Motor Preparation and Lower Limb Electromyography Changes

The neural strategies for movements of the lower extremities for landings from different landing heights in trained half-pipe snowboarders are not well known. We observed changes in brain activity as measured by electroencephalography (EEG) and lower limb muscle activity as measured by electromyography (EMG) in trained and untrained half-pipe snowboarders landing from different heights (30 and 60 cm). There were 12 trained male half-pipe snowboarders (HS) and 12 untrained participants (UP). We recorded EEG signals during motor preparation prior to dropping and EMG signals from right lateral rectus femoris (RF), tibialis anterior (TA), and gastrocnemius lateralis (GL) muscles during landings. Generally, theta power in the frontal cortex significantly increased in the preparation period compared to the resting state, while the alpha 1 and alpha 2 power values in central and parietal cortical areas decreased as dropping heights increased. Additionally, the HS group displayed greater magnitudes of change in power values in three frequency bands compared to the UP group. The HS group (relative to UP group) also showed higher normalized EMG amplitudes for RF and GL during contact, especially at 60 cm. The HS group (relative to the UP group) presented lower antagonist EMG activity and a higher GL/TA ratio at the 60 cm dropping height. Long-term specialized training might lead to greater neural modulation of predictive sensorimotor control and specific neuromuscular activation patterns during landing.
Steps toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. IX. Ultraviolet Observations of Fairall 9

An 8 month monitoring campaign on the Seyfert 1 galaxy Fairall 9 has been conducted with the International Ultraviolet Explorer in an attempt to obtain reliable estimates of continuum-continuum and continuum-emission-line delays for a high-luminosity active galactic nucleus (AGN). While the results of this campaign are more ambiguous than those of previous monitoring campaigns on lower luminosity sources, we find general agreement with the earlier results: (1) there is no measurable lag between ultraviolet continuum bands, and (2) the measured emission-line time lags are very short. It is especially notable that the Lyα + N V emission-line lag is about 1 order of magnitude smaller than determined from a previous campaign by Clavel, Wamsteker, & Glass (1989) when Fairall 9 was in a more luminous state. In other well-monitored sources, specifically NGC 5548 and NGC 3783, the highest ionization lines are found to respond to continuum variations more rapidly than the lower ionization lines, which suggests a radially ionization-stratified broad-line region. In this case, the results are less certain, since none of the emission-line lags are very well determined. The best-determined emission line lag is Lyα + N V, for which we find that the centroid of the continuum-emission-line cross-correlation function is τcent ≈ 14-20 days. We measure a lag τcent ≲ 4 days for He II λ1640; this result is consistent with the ionization-stratification pattern seen in lower luminosity sources, but the relatively large uncertainties in the emission-line lags measured here cannot rule out similar lags for Lyα + N V and He II λ1640 at a high level of significance. We are unable to determine a reliable lag for C IV λ1550, but we note that the profiles of the variable parts of Lyα and C IV λ1550 are not the same, which does not support the hypothesis that the strongest variations in these two lines arise in the same region.
On the Bayesian estimation of the weighted Lindley distribution

The weighted distributions provide a comprehensive understanding by adding flexibility in the existing standard distributions. In this article, we considered the weighted Lindley distribution which belongs to the class of the weighted distributions and investigated various its properties. Although, our main focus is the Bayesian analysis however, stochastic ordering, the Bonferroni and the Lorenz curves, various entropies and order statistics derivations are obtained first time for the said distribution. Different types of loss functions are considered; the Bayes estimators and their respective posterior risks are computed and compared. The different reliability characteristics including hazard function, stress and strength analysis, and mean residual life function are also analysed. The Lindley approximation and the importance sampling are described for estimation of parameters. A simulation study is designed to inspect the effect of sample size on the estimated parameters. A real-life application is also presented for the illustration purpose.
Breaching the family walls: Modelling the impact of prolonged visa insecurity on asylum-seeking children

Objective: Children in asylum-seeking families are increasingly subject to deterrent host nation policies that undermine security in the post-migration context, however, little is known on the mental health consequences of such policy. This study examined the impact of prolonged visa insecurity on child mental health, by comparing two cohorts of refugee children entering Australia between 2010 and 2013, distinguished by visa security. Methods: The insecure visa sample comprised children from Tamil asylum-seeking families, while the secure visa sample was drawn from refugee families participating in the multi-ethnic ‘Building a New Life in Australia’ cohort study. Children in each sample were assessed for current mental health problems and trauma exposure. Mothers were assessed for trauma exposure, post-migration family stressors and post-traumatic stress disorder (PTSD). The effects of prolonged visa insecurity on child mental health via family-and child-level variables were modelled using multi-level path analysis. Results: Data comprised 361 children, aged 10–18, and 242 mothers across three levels of visa insecurity: permanent protection (n = 293), temporary protection (n = 40) and bridging visa (n = 28). Modelling showed that (1) visa insecurity was associated with poorer child mental health, (2) the association was mediated sequentially by post-migration family stressors and maternal PTSD and (3) the association was moderated by maternal PTSD. Conclusion: Our findings suggest that when government policy persistently undermines post-migration security, the capacity of families to protect children from accrued stressors is lowered, leaving a significantly higher proportion of children developing along trajectories of risk rather than resilience.