Miracle-dz/UniFAR-FTUs huggingface dataset:
Sterilization of micronized indomethacin

Sterilization is a pivotal topic in the pharmaceutical industry, whereby the nomenclature of “sterile” refers to the absence of viable microorganisms. Since microorganisms can reproduce in the body and cause potentially fatal infections, it is critical to sterilize parenteral products to prevent this. In recent years, 70%–90% of potential drugs and 40% of marketed drugs have demonstrated a low solubility. Micronization is a widely spread approach to increase the dissolution rate. A subset of micronized products require sterilization, but published studies on the effects of sterilization on micronized products are currently lacking. The effect of sterilization on the micronized active pharmaceutical ingredient indomethacin was explored in this study. The sterilization methods in scope were one photon-based method using gamma irradiation and one gas-based method with nitrogen dioxide gas. Indomethacin was micronized using two micronization techniques, cryomilling and spray drying. Different conditions were used for cryomilling where the number of grinding balls in the ball mill and the degree of filling were varied. The solid state of all samples was evaluated after micronization, and only the effectively micronized samples were selected for sterilization with gamma rays and nitrogen dioxide. Gamma irradiation was performed with the active pharmaceutical ingredient stored at −80°C at a commonly used industry standard target dose of 25 kGy. Nitrogen dioxide sterilization took place at 21°C, a concentration of 10 mg/L, a relative humidity of 30% and using two NO2 pulses. Before and after sterilization, all samples were analyzed by high performance liquid chromatography with UV detection, whereby the assay of indomethacin was examined as well as the peak purity and the formation of impurities. In comparison to the non-micronized reference, both sterilization methods demonstrate a significant decrease of content of micronized samples and an increase of the impurity profile. The non-micronized sample showed no significant difference after sterilization. It could be observed that micronized indomethacin samples demonstrate more degradation and are subsequently more susceptible to degradation upon sterilization with gamma rays and nitrogen dioxide gas, driving towards the need for assessment of the micronization impact combined with sterilization approach.
Development of lacrimal gland organoids from iPSC derived multizonal ocular cells

Lacrimal gland plays a vital role in maintaining the health and function of the ocular surface. Dysfunction of the gland leads to disruption of ocular surface homeostasis and can lead to severe outcomes. Approaches evolving through regenerative medicine have recently gained importance to restore the function of the gland. Using human induced pluripotent stem cells (iPSCs), we generated functional in vitro lacrimal gland organoids by adopting the multi zonal ocular differentiation approach. We differentiated human iPSCs and confirmed commitment to neuro ectodermal lineage. Then we identified emergence of mesenchymal and epithelial lacrimal gland progenitor cells by the third week of differentiation. Differentiated progenitors underwent branching morphogenesis in the following weeks, typical of lacrimal gland development. We were able to confirm the presence of lacrimal gland specific acinar, ductal, and myoepithelial cells and structures during weeks 4–7. Further on, we demonstrated the role of miR-205 in regulation of the lacrimal gland organoid development by monitoring miR-205 and FGF10 mRNA levels throughout the differentiation process. In addition, we assessed the functionality of the organoids using the β-Hexosaminidase assay, confirming the secretory function of lacrimal organoids. Finally, metabolomics analysis revealed a shift from amino acid metabolism to lipid metabolism in differentiated organoids. These functional, tear proteins secreting human lacrimal gland organoids harbor a great potential for the improvement of existing treatment options of lacrimal gland dysfunction and can serve as a platform to study human lacrimal gland development and morphogenesis.
Clinical and immunological characteristics of TGM3 in pan-cancer: A potential prognostic biomarker

Background: Recent studies have identified that transglutaminases (TGMs) are involved in a widespread epigenetic modification in tumorigenesis. However, it remains unclear how transglutaminase 3 (TGM3) affects in pan-cancer. The present study aimed to explore the clinical and prognostic function of TGM3 in pan-cancer as well as to explore the relationship of TGM3 expression with clinical stage, survival rate, prognosis condition, immune infiltration and mutation indicators. Methods: The relevant data of tumors were obtained from The Cancer Genome Atlas (TCGA), TARGET, Cancer Cell Line Encyclopedia (CCLE) and Genotype-Tissue Expression (GTEx) databases. According to the Human Protein Atlas (HPA) and TIMER databases, we evaluated the protein expression levels of TGM3 in different organs and tissues as well as their association with immune cell infiltration and immunotherapeutic response in pan-cancers. Expression differences between normal and tumor tissues as well as survival and prognosis situation, clinical data characteristics, tumor mutational burden (TMB), microsatellite instability (MSI), and RNA methylation were also assessed. Oncogenic analyses were also evaluated by GSEA. Results: Compared to normal tissues, some tumor tissues had a lower expression level of TGM3, while other tumor tissues had a high expression level of TGM3. Further studies showed that high TGM3 expression had a certain risk impact on pan-cancer as high TGM3 expression levels were detrimental to the survival of several cancers, except for pancreatic cancer (PAAD). High expression level of TGM3 was also related to higher clinical stages in most cancers. The expression level of TGM3 was significantly negatively correlated with the expression of immune infiltration-related cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages and dendritic cells (DCs). Furthermore, in most cancer types, TGM3 was inversely correlated with TMB, MSI, and methylation, suggesting that TGM3 expression can be used to assess potential therapeutic response, especially immune-related targeted therapy. GSEA analysis elucidated the biological and molecular function of TGM3 in various cancer types. Taken together, these bioinformatic analyses identified TGM3 as an important biomarker for clinical tumor prognosis and evaluation of treatment efficacy. Conclusion: We comprehensively analyzed the clinical characteristics, tumor stages, immune infiltration, methylation level, gene mutation, functional enrichment analysis and immunotherapeutic value of TGM3 in pan-cancer, providing implications for the function of TGM3 and its role in clinical treatment.
A study on the factors influencing old age identity among the Chinese elderly

Background Old age identity is the self-perception of when old age begins, reflects public age values and acceptance of aging. Not all elderly people aged 60 and above identify with their old age status. The aging society in the traditional sense may not be “aging”. Therefore, redefining old age is crucial. Different from Western countries, China is a country with a long-standing culture of respect for the elderly and filial piety norms, and the influence of the cultural background on the old age identity is worthy of attention. Data and method Data were drawn from the 2014 China Longitudinal Aging Social Survey (CLASS). A total of 7400 participants answered questions about old age identity. Based on old age identity, we obtained two other types of indicators of perceived old age: elderly group identity and aging degree. For the continuous variable old age identity and aging degree, an OLS linear regression model was established. A binary logistic regression model was established for the binary variable elderly group identity. Result The average old age identity of Chinese people aged 60 and above is 70 years. Health status, psychological status, behavior, socioeconomic status, and some demographic characteristics significantly affect the old age identity of the Chinese elderly. Conclusion The traditional Chinese cultural background of respect for the elderly and the norms of filial piety have an impact on the old age identity of the Chinese elderly through family intergenerational support. The various forms of support provided by children to the elderly can help them achieve a positive age identity—enter old age later, raise the likelihood of identification with non-elderly groups, and reduce aging degree. The number of children of the elderly, the children's economic conditions and care support for grandchildren have negative effects. A positive old age identity can help the elderly improve their self-esteem.
Anterior cingulate cortex, but not amygdala, modulates the anxiogenesis induced by living with conspecifics subjected to chronic restraint stress in male mice

Cohabitation with a partner undergoing chronic restraint stress (CRE) induces anxiogenic-like behaviors through emotional contagion. We hypothesized that the anterior cingulate cortex (ACC) and the amygdala would be involved in the modulation of this emotional process. This study investigated the role of the ACC and amygdala in empathy-like behavior (e.g., anxiety-like responses) induced by living with a mouse subjected to CRE. Male Swiss mice were housed in pairs for 14 days and then allocated into two groups: cagemate stress (one animal of the pair was subjected to 14 days of restraint stress) and cagemate control (no animal experienced stress). Twenty-four hours after the last stress session, cagemates had their brains removed for recording FosB labeling in the ACC and amygdala (Exp.1). In experiments 2 and 3, 24 h after the last stress session, the cagemates received 0.1 μL of saline or cobalt chloride (CoCl2 1 mM) into the ACC or amygdala, and then exposed to the elevated plus-maze (EPM) for recording anxiety. Results showed a decrease of FosB labeling in the ACC without changing immunofluorescence in the amygdala of stress cagemate mice. Cohabitation with mice subjected to CRE provoked anxiogenic-like behaviors. Local inactivation of ACC (but not the amygdala) reversed the anxiogenic-like effects induced by cohabitation with a partner undergoing CRE. These results suggest the involvement of ACC, but not the amygdala, in anxiety induced by emotional contagion.
“Smart” drug delivery: A window to future of translational medicine

Chemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and enzyme degradation can be future of translational medicine. Therefore, SDDSs have the potential to be used as a viable cancer treatment alternative to traditional chemotherapy. This review focuses mostly on stimuli responsive drug delivery, inorganic nanocarriers (Carbon nanotubes, gold nanoparticles, Meso-porous silica nanoparticles, quantum dots etc.), organic nanocarriers (Dendrimers, liposomes, micelles), antibody-drug conjugates (ADC) and small molecule drug conjugates (SMDC) based SDDSs for targeted cancer therapy and strategies of targeted drug delivery systems in cancer cells. Graphical Abstract
Integrated manufacturing of direct 3D-printed clear aligners

The inception of the laboratory work for a removable tooth moving appliance construction by sectioning the teeth from the malocclusion model to align them with wax and achieve minor dental correction has evolved into a state of digital planning and appliance manufacturing for a wide spectrum of malocclusion. The disruptive technology of directly printing clear aligners has drawn the clinician and researcher's interest in the orthodontic fraternity contemporarily. This workflow enables to the development of an in-house aligner system with complete control over desired aligner thickness, extent, and attachments; also technically resource-efficient with greater accuracy by excluding all the intermediate steps involved in the thermoforming method of manufacturing. This promising exploratory subject demands to be well-received with further research-based improvements. This article intends to summarize the digital orthodontic workflow and the literature evidence.
Volumetric modulated arc therapy based total marrow and lymphoid irradiation: Workflow and clinical experience

Background The aim of this study is to report historical treatment planning experience at our institution for patients receiving total marrow and lymphatic irradiation (TMLI) using volumetric modulated arc therapy (VMAT) as part of the conditioning regimen prior to hematopoietic stem cell transplant. Methods We identified a total of fifteen patients with VMAT TMLI, ten with a prescription dose of 20 Gy (targeting the skeletal bones, lymph nodes, spleen, and spinal canal, with 12 Gy to the brain and liver) and five with a prescription dose of 12-16 Gy (targeting the skeletal bones, lymph nodes, spleen, and spinal canal). Representative dosimetric parameters including total treatment time, mean and median dose, D80, and D10 (dose covering 80% and 10% of the structure volume, respectively) for targets and normal organs were extracted and compared to historical patients treated with helical tomotherapy. Results The median treatment time for the first and subsequent fractions was 1.5 and 1.1 hours, respectively. All the target volumes had a mean dose greater than the prescribed dose except the ribs, which had an average mean dose of 19.5 Gy. The skeletal bones had an average mean dose of 21.1 Gy. The brain and liver have average mean doses of 14.8 and 14.1 Gy, respectively. The mean lung dose had an average of 7.6 ± 0.6 Gy for the 20-Gy cohort. Relative to the prescription dose of 20 Gy, the average mean dose for the normal organ volumes ranged from 16.5% to 72.0%, and the average median dose for the normal organs ranged from 16.5% to 71.0%. Dosimetry for patients treated to 12-16 Gy fell within expected ranges based on historical helical tomotherapy plans. Conclusions Dosimetric data in the VMAT TMLI plans at our institution are summarized for 20 Gy and 12-16 Gy cohorts. Dose distributions and treatment times are overall similar to plans generated with helical tomotherapy. TMLI may be delivered effectively using a VMAT technique, even at escalated doses.
ALMOST 2-FULLY NORMAL, PAIRWISE PARACOMPACT AND COMPLETE DEVELOPABLE BISPACES

Dedicated to Professor Sergio Salbany on the occasion of his 60th birthday. Abstract We introduce and study the notion of an almost 2-fully normal bispace. In particular, we prove that a bispace is quasi-pseudometrizable if and only if it is almost 2-fully normal and pairwise developable. We obtain conditions under which an almost 2-fully normal bispace is subquasi-metrizable and show that the fine quasi-uniformity of any subquasi-metrizable topological space is bicomplete. We prove that every pairwise paracompact bispace (in the sense of Romaguera and Marin, 1988) is almost 2-fully normal and that the finest quasi-uniformity of any 2-Hausdorff pairwise paracompact bispace is bicomplete. We also characterize pairwise paracompactness in terms of a property of σ-Lebesgue type of the finest quasi-uniformity. Finally, we use Salbany's compactification of pairwise Tychonoff bispaces to characterize those bispaces that admit a bicomplete pair development and deduce that an interesting example of R. Fox of a non-quasi-metrizable pairwise stratifiable pairwise developable bispace admits a bicomplete pair development.
Cross-species transmission, evolution and zoonotic potential of coronaviruses

Coronaviruses (CoVs) continuously evolve, crossing species barriers and spreading across host ranges. Over the last two decades, several CoVs (HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2) have emerged in animals and mammals, causing significant economic and human life losses. Due to CoV cross-species transmission and the evolution of novel viruses, it is critical to identify their natural reservoiurs and the circumstances under which their transmission occurs. In this review, we use genetic and ecological data to disentangle the evolution of various CoVs in wildlife, humans, and domestic mammals. We thoroughly investigate several host species and outline the epidemiology of CoVs toward specific hosts. We also discuss the cross-species transmission of CoVs at the interface of wildlife, animals, and humans. Clarifying the epidemiology and diversity of species reservoirs will significantly impact our ability to respond to the future emergence of CoVs in humans and domestic animals.
A brief review and clinical evidences of teriparatide therapy for atypical femoral fractures associated with long-term bisphosphonate treatment

The risk of bisphosphonate (BP)-associated atypical femur fracture (AFF) has markedly increased over recent decades due to suppression of bone turnover, accumulation of structural micro-damage and reduction of bone remodeling consequent to long-term BP treatment. These medications further delay bone union and result in challenging clinical management. Teriparatide (TPTD), a synthetic human parathyroid hormone, exhibits unique anabolic effects and can increase bone remodeling and improve bone microarchitecture, further promoting fracture healing and reducing the rate of bone non-union. In this study, we briefly define AFF as well as the effects of BPs on AFFs, detailed the role of TPTD in AFF management and the latest clinical therapeutic findings. We have confirmed that TPTD positively promotes the healing of AFFs by reducing the time to bone union and likelihood of non-union. Thus, teriparatide therapy could be considered as an alternative treatment for AFFs, however, further research is required for the establishment of effective clinical guidelines of TPTD use in the management of AFF.
Numerical analysis of the internal flow and pressure pulsation characteristics of a submersible tubular electric pump device

In order to clarify the non-constant flow characteristics of the impeller and bulb body of the submersible tubular electric pump device, the entire flow rate conduit of the pump device is numerically calculated using the numerical simulation method, focusing on the analysis of the non-constant flow field characteristics of the guide vane body and bulb body and the time–frequency variation law of the pressure pulsation, and the results of the physical model testing confirm the validity of the numerical simulation. The findings demonstrate that the impeller of a submersible tubular electric pump is mostly responsible for the impeller’s inlet pressure pulsation, and the number of impeller blades to the number of peaks and valleys is consistent. Under the high flow rate condition of 1.2 Q d, the pressure fluctuation in the impeller inlet, between the impeller and the guide vane is small, and the main frequency is located at three times the rotational frequency, and the pressure pulsation at the outlet of the guide vane body has no obvious pattern and small amplitude. As the flow rate increases, the peak value of pressure pulsation at each monitoring point in the characteristic section of the pump device gradually decreases. The pressure pulsation peak value varies widely, ranging from 0.058 to 0.15, at each monitoring location of the impeller inlet. The peak value of pressure pulsation at each monitoring point of the impeller outlet fluctuates less due to the change of flow rate. The size and scale of the omega vortex structure in the guide vane body at different moments of the same cycle is small, and the number of vortex structures from the guide vane body inlet to the outlet direction shows a gradual increase in the trend; with a rise in flow rate, there is a tendency for the velocity and deflection angle of the guide vane body outlet and bulb body outlet surface to decrease.
Chinese medicine for residual symptoms of COVID-19 recovered patients (long COVID)—A double-blind, randomized, and placebo-controlled clinical trial protocol

Introduction Coronavirus disease 2019 (COVID-19) is the current global pandemic of which residual symptoms exhibited by post-acute, rehabilitating patients include fatigue, dyspnoea, and insomnia. Chinese medicine (CM) has been widely used in China to treat different stages of COVID-19. While there are a significant number of clinical studies suggesting its efficacy and safety in its use during acute stage, there are very few randomized controlled trials focusing on the rehabilitation stage. Liujunzhi Decoction and Shashen Maidong Decoction are frequently recommended by official clinical guidelines in China to treat COVID-19 patients in rehabilitation stage. This double-blind, randomized, placebo controlled study aims to evaluate the efficacy and safety of the combination of the two formulae [named “COVID-19 Rehab Formula (CRF)”] in treating COVID-19 residual symptoms (long COVID). Methods Eligible subjects will be randomly divided into treatment group and control group in 1:1 ratio. Treatment group will receive CRF along with certain pre-defined CM according to symptoms for 8 weeks, while control group will receive equivalent packs of placebo for 8 weeks. Data in terms of Fatigue Severity Score (FSS), self-reported COVID-19 long term symptom assessment, the modified British Medical Research Council (mMRC) Dyspnoea Scale, EuroQol Five-Dimension Five-Level (EQ-5D-5L) Questionnaire, pulmonary function test and adverse events will be collected and analyzed by SPSS 24. Blood test on liver and renal functions will also be conducted as safety measures. Conclusion This study will evaluate the efficacy and safety of CRF in the treatment COVID-19 residual symptoms in a scientifically rigorous design. Clinical trial registration [ClinicalTrials.gov], identifier [NCT04924881].