Miracle-dz/UniFAR-FTUs huggingface dataset:
Current status and advances in esophageal drug delivery technology: influence of physiological, pathophysiological and pharmaceutical factors

Abstract Diseases affecting the esophagus are common. However, targeted drug delivery to the esophagus is challenging due to the anatomy and physiology of this organ. Current pharmacological treatment for esophageal diseases predominantly relies on the off-label use of drugs in various dosage forms, including those for systemic drug delivery (e.g. oral tablets, sublingual tablets, and injections) and topical drug delivery (e.g. metered dose inhaler, viscous solution or suspension, and endoscopic injection into the esophagus). In general, systemic therapy has shown the most efficacy but requires the use of high drug doses to achieve effective concentrations in the esophagus, which increases the risk of adverse effects and toxicity. Topical drug delivery has enormous potential in improving the way we treat patients with acute and chronic esophageal diseases, especially those requiring drugs that have low therapeutic index and/or significant adverse effects to non-targeted organs and tissues. This review will address the physiological, pathophysiological, and pharmaceutical considerations influencing topical drug delivery in the esophagus. The main conventional (e.g. liquid formulations, orodispersible tablets, lozenges, pastilles, troches, chewing gum) and innovative (e.g. stent-based, film-based, nanoparticulate-based) drug delivery approaches will be comprehensively discussed, along with the developments to improve their effectiveness for topical esophageal drug delivery. The translational challenges and future clinical advances of this research will also be discussed.
Transcatheter edge-to-edge mitral valve repair in patients with acute decompensated heart failure due to severe mitral regurgitation

Background Transcatheter edge-to-edge mitral valve repair (TEER) has been established as a therapy for severe symptomatic mitral regurgitation (MR) in stable patients, and it has recently emerged as a reasonable option for acutely ill patients. The aim of this study was to evaluate the safety and efficacy of TEER in hospitalized patients with acute decompensated heart failure (HF) and severe MR that was deemed to play a major role in their deterioration. Methods We included 31 patients who underwent emergent TEER for MR ≥ 3+ from 2012 to 2022 at Sheba Medical Center. Outcomes included procedural safety, procedural success, all-cause mortality, HF readmission, and functional improvement. Outcomes were evaluated at 3 months and at 1 year. Data were obtained retrospectively by chart review. Results Implantation of a TEER device was achieved in 97% of patients, and reduction in MR severity of at least two grades and final MR ≤ 2+ at discharge was achieved in 74%. No intra-procedural mortality or life-threatening complications were noted. Mortality at 30 days was 23%. No excess mortality occurred beyond 6 months, with a total mortality of 41%. At 1 year all survivors had MR ≤ 2+, all were free of HF hospitalizations, and 88% were at New York Heart Association class ≤ II. Conclusions Mitral valve TEER for patients with acute decompensated HF and significant MR is safe, feasible, and achieves substantial reduction in MR severity. Despite high early mortality, procedural success is associated with good long-term clinical outcomes for patients surviving longer than 6 months.
T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy

ABSTRACT Background Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20–30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. Objectives To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. Design and methods Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. Results Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. Conclusions Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.
Time‐series transcriptome analysis of peripheral blood mononuclear cells obtained from individuals who received the SARS‐CoV‐2 mRNA vaccine

Messenger ribonucleic acid (mRNA) vaccination against coronavirus disease 2019 (COVID‐19) is an effective prevention strategy, despite a limited understanding of the molecular mechanisms underlying the host immune system and individual heterogeneity of the variable effects of mRNA vaccination. We assessed the time‐series changes in the comprehensive gene expression profiles of 200 vaccinated healthcare workers by performing bulk transcriptome and bioinformatics analyses, including dimensionality reduction utilizing the uniform manifold approximation and projection (UMAP) technique. For these analyses, blood samples, including peripheral blood mononuclear cells (PBMCs), were collected from 214 vaccine recipients before vaccination (T1) and on Days 22 (T2, after second dose), 90, 180 (T3, before a booster dose), and 360 (T4, after a booster dose) after receiving the first dose of BNT162b2 vaccine (UMIN000043851). UMAP successfully visualized the main cluster of gene expression at each time point in PBMC samples (T1–T4). Through differentially expressed gene (DEG) analysis, we identified genes that showed fluctuating expression levels and gradual increases in expression levels from T1 to T4, as well as genes with increased expression levels at T4 alone. We also succeeded in dividing these cases into five types based on the changes in gene expression levels. High‐throughput and temporal bulk RNA‐based transcriptome analysis is a useful approach for inclusive, diverse, and cost‐effective large‐scale clinical studies.
Influence of menopausal status on physical function and performance: A cross-sectional study

Objective To compare the physical function and performance in pre-, peri-, and postmenopausal women. Study design A cross sectional study using convenience sampling method was conducted in 210 women categorized into premenopausal, perimenopausal, and postmenopausal. Main outcome measures Flexibility, muscle strength, muscle endurance, cardiovascular endurance, static balance, dynamic balance, and gait speed. Results The mean age of the premenopausal, perimenopausal, and postmenopausal women was 46.55 ± 1.77, 49.54 ± 3.38 and 54.85 ± 3.77 years respectively. There is significant difference observed between premenopausal, perimenopausal, and postmenopausal women in muscle strength, upper limb endurance, lower limb endurance, static balance, dynamic balance, gait speed, and cardiovascular endurance (p < .05) using Kruskal Wallis test. There is no significant difference observed between the groups for flexibility (p > .05). Conclusion It was observed that physical function and performance was impaired in postmenopausal women when compared to pre- and perimenopausal women. Hence, these components should be included during assessment which will provide a holistic and multimodal approach toward the understanding, planning and management of postmenopausal women in community settings.
Nanosecond Repetitively Pulsed Plasmas in Preheated Air at Atmospheric Pressure - The Diffuse Regime

Many applications for atmospheric-pressure air plasmas require non-thermal largevolume low-power plasmas with high chemical reactivity at low gas temperature. The Nanosecond Repetitively Pulsed (NRP) method can generate such non-thermal plasmas for power budgets lower than those of traditional generation methods by several orders of magnitude. A diffuse non-thermal plasma regime in air at atmospheric pressure from 3001000 K has been generated using the NRP method. This diffuse plasma develops through an initial cathode-directed streamer, followed by a return wave of potential redistribution. Furthermore, at a given gas temperature, there is a minimum gap distance required for the existence of the diffuse regime. The sequence of events observed in the formation of the diffuse plasma lead us to conclude that it is an “imminent” glow discharge. The applied electric field is maintained long enough (~10 ns) to initiate a streamer that interacts with the cathode to produce a return wave. However, the field is switched off before the development of significant ion-electron emission, which requires tens of nanoseconds. This limits the formation of the cathode fall, thus avoiding the imminent creation of a glow discharge. The non-uniform electric field generated by the pin-pin geometry can explain the minimum gap distance requirement. Using an approximate analytic expression for the Laplacian field, it can be shown that the gap distance primarily affects the field in the middle of the gap, whereas the radius of curvature of the electrodes primarily affects the field near the tips of the electrodes. Thus, the discharge gap can be divided into high-field regions near the electrodes where strong ionization occurs and a low-field weakly ionizing region between the electrodes, which can inhibit the spread of ionization instability and prevent the diffuse-tofilamentary regime transition. As the gas temperature is decreased, the field in strongly ionizing regions must be increased to maintain sufficient ionization, but the gap distance must be simultaneously increased for the weakly ionizing region to remain a buffer against the spread of the ionization instability.
Parental awareness of the implications of myopia and strategies to control its progression: A survey‐based study

Myopia has emerged as a significant public health concern. Effective methods have now been developed to delay its onset and progression. However, this information may not be reaching parents, and they are key players in terms of implementing the necessary preventive measures. This study investigated parental awareness of myopia, its implications and the strategies available for controlling it.
Local Plasma Parameter Measurements by Nearwall Probes Inside the SPT Accelerating Channel Under Thruster Operation with Kr

Last years there were restarted studies of the SPT performance and operation with different gases in several Russian institutes including RIAME MAI in order to find more cheap than Xe propellant for SPT. These studies have shown that operating with Kr and Kr/Xe mixtures with low fraction of Xe it is possible to obtain thrust efficiency of SPT over 50% under increased by 1,5-2 times discharge powers (relative to Xe case) and increased specific impulses. Such level of output parameters could be acceptable for some missions. Therefore it is interesting to study the SPT operation on these gases more detaily. In particular it is interesting to realize comparative study of the local plasma parameter distributions inside the accelerating channel under thruster operation with Kr and Xe. Such measurements were made inside the accelerating channel of the SPT-100 scale thruster by nearwall probes. Obtained results show that plasma potential and ion current density distributions are similar for Xe and Kr cases under close discharge currents (that is under increased mass flow rates in the Xe case). Under close mass flow rates the accelerating layer in a Kr case is more wide and shifted inside channel. The electron temperature distribution in a Kr case is more wide and has lower maximum than in Xe case. These results could be used for the analysis of particularities of the SPT operation with different gases.
Construction of ternary matrices with small coherence for compressed sensing

Recently, the binary matrix with binary correlations between columns has attracted attention for its sparse structure and competitive performance. However, such kind of matrix tends to suffer an increasing coherence, i.e. the maximum absolute correlation between columns, as the compression ratio decreases. It is shown here that the binary matrix mentioned above allows to be duplicated in columns, while not degrading the coherence, if bipolar signs are introduced. The resulting ternary matrix is thus expected to present smaller coherence than the aforementioned binary matrix of same size.
Culturing human pluripotent stem cells for regenerative medicine

ABSTRACT Introduction The development of human pluripotent stem cell (hPSC) culture protocols has led to the establishment of directed differentiation induction methods, resulting in their application in regenerative medicine. Cell therapy products derived from hPSCs have been transplanted into patients, and promising results have been observed in some ongoing clinical trials. Area covered This review provides an overview of the challenges associated with the culture of hPSCs for clinical applications and the development of culture technologies designed to address these challenges. We also review future cell culture strategies for large-scale manufacturing to enhance patient access. Expert opinion Despite the great potential of hPSCs, difficulties such as safety, quality control, and cost management continue to pose obstacles to their product development and clinical translation. A substantial contribution of these issues lies in the cell culture process. Therefore, selecting the appropriate ancillary materials (AMs) and integrating effective culture methods in standard operating procedures (SOPs) from the early stages of clinical development are essential for success. Moreover, incorporating an automated scaling process is imperative to ensure the commercial feasibility of hPSC-based products. Human pluripotent stem cells (hPSCs) show great potential as a valuable resource for regenerative medicine. However, three significant obstacles must be overcome: safety, quality, and costs. Thankfully, recent progress in hPSC culture techniques has effectively tackled these challenges, opening up exciting possibilities for realizing hPSC-based regenerative medicine.
Intravenous anakinra for the treatment of haemophagocytic lymphohistiocytosis/macrophage activation syndrome: A systematic review

Haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) has a potentially high mortality rate. Anakinra, an interleukin‐1 receptor antagonist, is now recommended early in HLH/MAS, with intravenous (IV) use proposed in critically unwell patients. This systematic review establishes the literature relating to IV anakinra in secondary HLH/MAS (sHLH/MAS).
Collaborative depression care sensitive to the needs of underserved patients with cancer: Feasibility, acceptability and outcomes

Abstract Purpose A single-arm trial evaluated the feasibility, acceptability, and outcomes of COPE-D, a collaborative care intervention for underserved cancer patients with depression. Methods Bilingual (Spanish and English) care managers provided counseling and/or medication management in consultation with physicians. Outcomes were treatment improvement (≥ 5-point reduction in PHQ-9), treatment response (≥ 50% reduction in PHQ-9), suicidal ideation resolution, and changes in depression (PHQ-9), anxiety (GAD-2), sleep disturbance (PSQI), global mental and physical health (PROMIS), social isolation (PROMIS), and qualitative feedback. Results 193 patients consented to participate. 165 initiated and 141 completed treatment, with 65% and 56% achieving treatment improvement and response, respectively. Outcomes did not differ by ethnicity (31% Hispanic), cancer stage (71% stages III-IV), income, or education. Suicidal ideation, depression, anxiety, sleep disturbance, and social isolation also improved. Qualitative feedback was largely positive. Conclusion COPE-D improved depression and quality of life among underserved patients, with acceptable retention rates.
Balanced Cohen-Macaulay complexes

A balanced complex of type (a,,., am) is a finite pure sim- plicial complex A together with an ordered partition (Vx.Vm) of the vertices of A such that card( V¡ r\ F) = a¡ for every maximal face F of A. If b = (ó,, . . , bm), then define /b(A) to be the number of F G A satisfying card( Vt, n F) = b¡. The formal properties of the numbers /b(A) are investigated in analogy to the /-vector of an arbitrary simplicial complex. For a special class of balanced complexes known as balanced Cohen-Macaulay complexes, simple techniques from commutative algebra lead to very strong conditions on the numbers/b(A). For a certain complex A(/") coming from a poset P, our results are intimately related to properties of the Möbius function of P.
Chronotype, Social Jetlag, and Nicotine Use

Late chronotype, which often leads to higher social jetlag (SJL), is strongly associated with the prevalence of smoking. Any circadian disruption, strain, or misalignment, results in people not being able to live according to their biological time as is described by SJL, which we will therefore use as umbrella term. We hypothesized two scenarios potentially explaining the association between smoking and SJL: (A) If smoking delays the clock, circadian phase should advance upon quitting. (B) If people smoke more to compensate the consequences of SJL, circadian phase should not change upon quitting. To distinguish between these two hypotheses, we accompanied participants of a smoking cessation program (not involving nicotine replacement products) across the cessation intervention (3 weeks prior and 6 weeks after) by monitoring their circadian behavior, sleep quality, and daytime sleepiness via questionnaires and actimetry. Our results show no effects of cessation on SJL, chronotype, sleep quality, or daytime sleepiness, thereby favoring scenario (B). Thus, smoking may be a consequence of rather than a cause for SJL. Daytime sleepiness was a significant predictor for the outcome in our model but did not improve with cessation.
Complex Regulation of Gamma-Hemolysin Expression Impacts Staphylococcus aureus Virulence

S. aureus virulence in pneumonia results in its ability to produce several virulence factors, including the leucocidin PVL. Here, we demonstrate that HlgCB, another leucocidin, which targets the same receptors as PVL, highly contributes to S. aureus virulence in pvl-negative strains. ABSTRACT Staphylococcus aureus gamma-hemolysin CB (HlgCB) is a core-genome-encoded pore-forming toxin that targets the C5a receptor, similar to the phage-encoded Panton-Valentine leucocidin (PVL). Absolute quantification by mass spectrometry of HlgCB in 39 community-acquired pneumonia (CAP) isolates showed considerable variations in the HlgC and HlgB yields between isolates. Moreover, although HlgC and HlgB are encoded on a single operon, their levels were dissociated in 10% of the clinical strains studied. To decipher the molecular basis for the variation in hlgCB expression and protein production among strains, different regulation levels were analyzed in representative clinical isolates and reference strains. Both the HlgCB level and the HlgC/HlgB ratio were found to depend on hlgC promoter activity and mRNA processing and translation. Strikingly, only one single nucleotide polymorphism (SNP) in the 5′ untranslated region (UTR) of hlgCB mRNA strongly impaired hlgC translation in the USA300 strain, leading to a strong decrease in the level of HlgC but not in HlgB. Finally, we found that high levels of HlgCB synthesis led to mortality in a rabbit model of pneumonia, correlated with the implication of the role of HlgCB in severe S. aureus CAP. Taken together, this work illustrates the complexity of virulence factor expression in clinical strains and demonstrates a butterfly effect where subtle genomic variations have a major impact on phenotype and virulence. IMPORTANCE S. aureus virulence in pneumonia results in its ability to produce several virulence factors, including the leucocidin PVL. Here, we demonstrate that HlgCB, another leucocidin, which targets the same receptors as PVL, highly contributes to S. aureus virulence in pvl-negative strains. In addition, considerable variations in HlgCB quantities are observed among clinical isolates from patients with CAP. Biomolecular analyses have revealed that a few SNPs in the promoter sequences and only one SNP in the 5′ UTR of hlgCB mRNA induce the differential expression of hlgCB, drastically impacting hlgC mRNA translation. This work illustrates the subtlety of regulatory mechanisms in bacteria, especially the sometimes major effects on phenotypes of single nucleotide variation in noncoding regions.
Oral isotretinoin in the treatment of juvenile acne and psychiatric adverse effects – a systematic review

Abstract Purpose Acne vulgaris is a very prevalent dermatological condition, especially among adolescents and young adults up to 25 years old, classifying it as juvenile acne. One of the most effective treatments for severe acne is isotretinoin, a derivative of retinoic acid. Despite its high efficacy, this drug has been linked to several side effects including psychiatric adverse alterations, such as anxiety, depression and even suicide. With this systematic review we aim to determine if it is possible to establish a causal relation between oral isotretinoin in the treatment of juvenile acne and the appearance of psychiatric adverse effects. Materials and methods We searched two distinct databases, PubMed and Web of Science, and considered the work published between January 2000 and November 2021. Results Out of the 599 identified articles, we included 19 studies in this systematic review. Globally, the results we found do not support an association between the use of isotretinoin for acne treatment and mental side effects and the safety of this drug appears to be assured. However, the individual characteristics of each adolescent and their environment should be considered; the personal and family history of mental disorders are pointed out as red flags we should look out for when treating these patients. Conclusion Despite this being a highly debated topic, especially among the dermatology community, more studies with larger populations and randomised controlled trials are necessary to increase the strength of the evidence presented.