Miracle-dz/UniFAR-FTUs huggingface dataset:
Single‐cell transcriptome analysis reveals keratinocyte subpopulations contributing to psoriasis in corneum and granular layer

Abstract Background Psoriasis is a chronic, inflammatory skin disease that is common and relapses easily. While the importance of keratinocyte proliferation in psoriasis development is well‐documented, the specific functional subpopulations of epidermal keratinocytes associated with this disease remain enigmatic. Materials and Methods Therefore, in our analysis of single‐cell transcriptome data from both normal and psoriatic skin tissues, we observed significant increases in certain keratinocytes in the stratum corneum (KC) and stratum granulosum (KG) within psoriatic skin. Furthermore, we identified upregulated expression of specific secreted factors known to promote inflammatory responses. Additionally, we conducted a KEGG pathway enrichment analysis on these identified subsets. Results In the stratum corneum, the expression of FTL was upregulated in HIST1H1C+KC. S100P+KC displayed a significant increase in the expression of both S100P and S100A10, whereas PRR9+KC showed upregulated expression of DEFB4B, S100A8, and S100A12. SLURP1+KC was characterized by elevated expression levels of IL‐36G, SLURP1, and S100A12. Meanwhile, in the stratum granulosum, KRT1+KG highly expressed SLURP1, S100A7, S100A8, and S100A9, while DEFB4B expression was upregulated in PI3+KG. Our findings indicated that subsets within the stratum corneum primarily participate in pathways related to MAPK, NOD‐like receptors, HIF‐1, cell senescence, and other crucial processes. In contrast, subsets in the stratum granulosum were predominantly associated with pathways involving MAPK, NOD‐like receptors, HIF‐1, Hippo, mTOR, and IL‐17. Conclusion These findings not only uncover the keratinocyte subsets linked to psoriasis but also unveil the molecular mechanisms and related signaling pathways that drive psoriasis development. This knowledge opens new horizons for the development of innovative clinical treatment strategies for psoriasis.
Previously Uncharacterized Variants, OCF-E–OCF-J, of the Antifungal Occidiofungin Produced by Burkholderia contaminans MS14

The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized glycolipopeptide that has a unique mechanism of action, disrupting actin-mediated functions and inducing cellular apoptosis. Antifungal activity has been observed in vitro against various fungal species, including multidrug resistant Candida auris, and in vivo efficacy has been demonstrated in a murine vulvovaginal candidiasis model. Occidiofungin, a cyclic glycolipopeptide, is composed of eight amino acids and in previous studies, an asparagine residue was assigned at position 7 (ASN7). In this study, new structural variants of occidiofungin have been characterized which have aspartic acid (ASP7), glutamine (GLN7), or glutamic acid (GLU7) at position 7. The side chain of the ASP7 variant contains the only terminal carboxylic acid in the peptide and provides a useful site for selective chemical modifications. Analogues were synthesized at the ASP7 position and tested for antifungal activity. These analogues were shown to be more active as compared to the ASP7 variant against a panel of Candida species. The naturally occurring variants of occidiofungin with a side chain containing a carboxylic acid at the seventh amino acid position can be used to develop semisynthetic analogues with enhanced therapeutic properties.
A case report of cardia carcinoma: Underwent Heller myotomy for Achalasia

Background: One of the risk factors for esophageal adenocarcinoma is achalasia, an esophageal motility disorder that is typically treated surgically through laparotomy or laparoscopic surgery. The risk factors of gastric cardia cancer are also similar to esophageal adenocarcinoma due to the anatomical location of the gastric cardia close to the esophagus. There is currently no clinical evidence that achalching has a correlation with gastric cardia cancer. Case summary: We report the case of an 85-year-old female patient was admitted to our department with dysphagia for 6 months. She underwent a dissecting Heller myotomy for pancreatic achalasia in 2006, with occasional postoperative symptoms of reflux and heartburn. Outpatient upper gastrointestinal imaging was suggestive of cardia cancer, and gastroscopic pathological findings were suggestive of moderately-lowly-differentiated adenocarcinoma. The patient was admitted to the operating room on August 30, 2022 to undergo radical pancreatic cancer surgery plus abdominal adhesion release, and postoperative review of the upper gastrointestinal imaging showed a patent anastomosis with no spillage, filling of the residual stomach, and duodenal visualization. Conclusion: Postoperative patients with achalasia often have symptoms of reflux, which may be one of the factors for the development of pancreatic cancer in this patient, thus requiring clinicians to pay more attention to the use of antireflux procedures in the surgical treatment of pancreatic achalasia. And the choice of which modality to perform surgery in patients with previous surgical history is also one of the points to be discussed.
High resolution observations of free tropospheric humidity from METEOSAT over the Indian Ocean.

Water vapor is a central element of the tropical climate through its interactions with longwave radiation as well as through its forcing onto convective activity. The scales of interest for water vapor span the Hadley circulation and its subsiding dry branches down to mesoscale features of around 50km. The satellite observations from METEOSAT-5 over the Indian Ocean in the 6.3 microns band are used to derive an estimate of the free tropospheric relative humidity at 5x5 km resolution in order to better document the various scale of the moisture field. The retrieval algorithm is similar to the operational algorithm run at EUMETSAT with slight modifications in the interpretation of the inverted signal. It relies on the use of local look up table and radiative transfer computations. The ancillary data needed for the algorithm are composed of the temperature profile taken from the ECMWF analysis. The final product is the weighting function weighted mean relative humidity over the free troposphere (FTH). The algorithm is fully presented and is validated thanks to an ensemble of radiosondes acquired during the INDOEX campaign. It is shown that the satellite derived FTH is in excellent agreement with the in-situ measurements with a bias of -2.7% and a standard deviation of 6%. The calibration of the captor is further investigated and shown to agree with radiosondes simulated brightness temperatures within 0.5K ruling out the idea of a calibration induced bias. The full resolution FTH imagery reveals the dryness of the intertropical troposphere with value often below 10% as well as the strong horizontal gradients associated with the FTH fields. Perspectives in the frame of the MEGHA-TROPIQUES mission are given.
Deduplication for Data Profiling using Open Source Platform

Many companies still do not know of the importance of data quality for the company’s improvement. Many companies in Indonesia, especially BUMN and Government companies have only single application with single database, which cause a problem related to duplication of data between columns, tables and applications when the application is integrated with other applications. This problem can be handled by doing the data preprocess, one of the data preprocess method is data profiling. Data profiling is the process of gathering information that can be determined by process or logic. The process of profiling data can be done with various tools both paid and open source tools, each has advantages both in performance and in data processing according to the desired case study. In this study, the main focus is on data analysis by conducting data profiling using deduplication method. The results of the profiling will be implemented in logical form in open source application and will do comparisons between open source applications. Keywords—data preprocess, data governance, levensthein distance
An ensemble learning method with GAN-based sampling and consistency check for anomaly detection of imbalanced data streams with concept drift

A challenge to many real-world data streams is imbalance with concept drift, which is one of the most critical tasks in anomaly detection. Learning nonstationary data streams for anomaly detection has been well studied in recent years. However, most of the researches assume that the class of data streams is relatively balanced. Only a few approaches tackle the joint issue of imbalance and concept drift. To overcome this joint issue, we propose an ensemble learning method with generative adversarial network-based sampling and consistency check (EGSCC) in this paper. First, we design a comprehensive anomaly detection framework that includes an oversampling module by generative adversarial network, an ensemble classifier, and a consistency check module. Next, we introduce double encoders into GAN to better capture the distribution characteristics of imbalanced data for oversampling. Then, we apply the stacking ensemble learning to deal with concept drift. Four base classifiers of SVM, KNN, DT and RF are used in the first layer, and LR is used as meta classifier in second layer. Last but not least, we take consistency check of the incremental instance and check set to determine whether it is anormal by statistical learning, instead of threshold-based method. And the validation set is dynamic updated according to the consistency check result. Finally, three artificial data sets obtained from Massive Online Analysis platform and two real data sets are used to verify the performance of the proposed method from four aspects: detection performance, parameter sensitivity, algorithm cost and anti-noise ability. Experimental results show that the proposed method has significant advantages in anomaly detection of imbalanced data streams with concept drift.
Ketamine for Primary Analgosedation in Critically Ill Surgery and Trauma Patients Requiring Mechanical Ventilation

OBJECTIVES: Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting. DESIGN: Retrospective cohort study. SETTING: Academic medical center in Minnesota. PATIENTS: Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours. INTERVENTIONS: None. MEASUREMENTS: Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected. MAIN RESULTS: Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1–4.5) and ICU length of stay of 4.9 days (3–8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1–0.3) and 30 hours (15.1–51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33–96%), while 64% (37–91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients. CONCLUSIONS: Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy.
The protective influence of family support on anxiety, depressive symptoms, and suicidal ideation among elderly Chinese nursing home residents: A study of serial mediation

In light of the aging demographic in China, heightened attention is warranted for the mental well-being of elderly individuals. Nevertheless, the prevalence of suicidal ideation among older residents in Chinese nursing homes and the nuanced impact of family support on this phenomenon, mediated by anxiety and depressive symptoms, remain unclear. A cohort of 506 Chinese elderly adults participated in the study. Psychosocial traits were assessed using the Perceived Social Support from Family scale (PSS-Fa) for family support, the 7-item Generalized Anxiety Disorder scale (GAD-7) for anxiety symptoms, the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms, and suicidal ideation. A structural equation model (SEM) was employed to execute a serial mediation model. The analysis of 506 elderly adults revealed that 8.1% reported varying levels of suicidal ideation within Chinese nursing homes. The pathway from family support to anxiety symptoms (standardized beta = −0.025, P = .241), family support to depressive symptoms (standardized beta = −0.072, P < .05), and family support to suicidal ideation (standardized beta = −0.082, P < .05) were explored. Additionally, pathways from anxiety symptoms to suicidal ideation (standardized beta = 0.364, P < .001), anxiety symptoms to depressive symptoms (standardized beta = 0.647, P < .001), and depressive symptoms to suicidal ideation (standardized beta = 0.369, P < .001) were examined. This study elucidated the underlying mechanisms connecting family support to suicidal ideation, with depressive symptoms partially mediating this association. Additionally, our discoveries shed light on the partial mediation of anxiety symptoms by depressive factors when it came to the realm of suicidal ideation.
The impact of digital economy on environmental pollution: Evidence from 267 cities in China

Environmental pollution has become a pressing global issue, severely threatening human health and ecosystems. As an emerging driver of economic development in countries worldwide, the digital economy (DE) has the potential to enhance resource utilization efficiency and promote the development of clean technologies, thereby reducing environmental pollution. Based on the panel data of 267 cities in China from 2012 to 2021, the spatial econometric model is used to test the impact of DE on environmental pollution. The mediating effect model is used to explore the transmission mechanism of DE affecting environmental pollution. The panel threshold model is used to examine the threshold effect of marketization. The results are as follows: (1) DE can significantly reduce environmental pollution. The conclusion is still valid after conducting robustness tests such as selecting historical data as instrumental variables and the “Broadband China” pilot as a quasi-natural experiment. (2) From the perspective of transmission mechanism, DE can reduce environmental pollution through green technology innovation and industrial structure upgrading. (3) From the perspective of spatial spillover effect, DE can reduce the environmental pollution level of surrounding cities. (4) From the perspective of threshold effect, DE has obvious market-oriented single threshold effect on environmental pollution. When the marketization level crosses the threshold of 11.6611, the emission reduction effect of DE is significant. (5) From the perspective of heterogeneity, DE has a heterogeneous impact on environmental pollution in cities with different geographic locations, resource endowments and administrative level. Regarding geographical heterogeneity, DE can effectively reduce environmental pollution in eastern and central regions, but has no significant impact on environmental pollution in western regions. Regarding the heterogeneity of resource endowment, compared to non-resource-based cities, resource-based cities suffer more from the negative effects of DE on their environment. Regarding the heterogeneity of administrative levels, compared with non-central cities, the DE of central cities has a greater emission reduction effect. Based on empirical results, this paper proposes strategic recommendations in areas such as enhancing the application of DE in emission reduction, upgrading industrial structures, promoting green technology innovation, and improving the level of marketization. This study not only enriches the research of DE and environmental pollution, but also provides a reference for the formulation of environmental pollution control policies.
Efficacy and safety of 40 mg osimertinib administered every other day for non‐small cell lung cancer harboring an epidermal growth factor receptor mutation: A single‐center retrospective cohort study

Abstract Osimertinib is a first‐line or adjuvant therapy for non‐small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation. However, owing to the adverse events associated with treatment, certain patients cannot maintain a daily regimen of 80 or 40 mg. In this study, we examined the efficacy of 40 mg of osimertinib administered every other day. In this single‐center, retrospective study, we evaluated patients with NSCLC harboring an EGFR mutation in whom treatment was initiated with 40 mg osimertinib every other day at our institution between May 2016 and June 2023. The major outcome was the duration of administering 40 mg osimertinib every other day. Six patients with NSCLC were evaluated. The median duration of 40 mg osimertinib intake every other day was 12.6 months. Four of the six patients weighed below 50 kg, and four experienced weight loss. Additionally, four of the six patients had severe renal impairment upon receiving 40 mg osimertinib every other day. Thus, our findings suggest the efficacy of administering 40 mg osimertinib every other day in patients with low bodyweight, weight loss, or severe renal impairment.
A Case of Spindle Cell Squamous Cell Carcinoma Manifesting in the Mandible Following Resection of Buccal Mucosal Squamous Cell Carcinoma

Spindle cell squamous cell carcinoma (SCSCC) represents a distinctive subtype of squamous cell carcinoma, characterized by a marked malignancy and sarcomatoid transformations predominantly comprising spindle-shaped cells. In this context, we executed a surgical resection of a buccal mucosal squamous cell carcinoma, encompassing the mandibular periosteum, for a case where buccal mucosal cancer had pervaded the mandibular gingival mucosa. Notably, in a period of one year and four months subsequent to this procedure, a spindle cell squamous cell carcinoma emerged as an intraosseous carcinoma, originating from the periosteum resection. This report delineates the occurrence of this rare pathology. The subject of this case is an 83-year-old female. She underwent a resection of a buccal mucosal squamous cell carcinoma, including the mandibular gingival periosteum, for cancer on the right buccal mucosa. The histopathological evaluation post-surgery confirmed the diagnosis of squamous cell carcinoma with clear margins. A computed tomography (CT) scan, conducted one year and four months postoperatively, disclosed a contrast-enhanced tumorous growth in the mandible. Owing to the considerable restriction in opening caused by scarring and the attendant challenges in biopsy acquisition, an expedited intraoperative diagnosis was rendered. This preliminary assessment indicated a spindle cell sarcoma, leading to a hemimandibular resection. The final histopathological diagnosis was spindle cell squamous cell carcinoma. Twelve months have elapsed since the surgical intervention, with no evidence of recurrence or metastasis observed to date.
Heat shock protein 90: biological functions, diseases, and therapeutic targets

Abstract Heat shock protein 90 (Hsp90) is a predominant member among Heat shock proteins (HSPs), playing a central role in cellular protection and maintenance by aiding in the folding, stabilization, and modification of diverse protein substrates. It collaborates with various co‐chaperones to manage ATPase‐driven conformational changes in its dimer during client protein processing. Hsp90 is critical in cellular function, supporting the proper operation of numerous proteins, many of which are linked to diseases such as cancer, Alzheimer's, neurodegenerative conditions, and infectious diseases. Recognizing the significance of these client proteins across diverse diseases, there is a growing interest in targeting Hsp90 and its co‐chaperones for potential therapeutic strategies. This review described biological background of HSPs and the structural characteristics of HSP90. Additionally, it discusses the regulatory role of heat shock factor‐1 (HSF‐1) in modulating HSP90 and sheds light on the dynamic chaperone cycle of HSP90. Furthermore, the review discusses the specific contributions of HSP90 in various disease contexts, especially in cancer. It also summarizes HSP90 inhibitors for cancer treatment, offering a thoughtful analysis of their strengths and limitations. These advancements in research expand our understanding of HSP90 and open up new avenues for considering HSP90 as a promising target for therapeutic intervention in a range of diseases.