Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-Cell Mononucleotide Microsatellite Analysis Reveals Differential Insertion-Deletion Dynamics in Mouse T Cells

Microsatellite sequences are particularly prone to slippage during DNA replication, forming insertion-deletion loops that, if left unrepaired, result in de novo mutations (expansions or contractions of the repeat array). Mismatch repair (MMR) is a critical DNA repair mechanism that corrects these insertion-deletion loops, thereby maintaining microsatellite stability. MMR deficiency gives rise to the molecular phenotype known as microsatellite instability (MSI). By sequencing MMR-proficient and -deficient (Mlh1 +/+ and Mlh1 −/− ) single-cell exomes from mouse T cells, we reveal here several previously unrecognized features of in vivo MSI. Specifically, mutational dynamics of insertions and deletions were different on multiple levels. Factors that associated with propensity of mononucleotide microsatellites to insertions versus deletions were: microsatellite length, nucleotide composition of the mononucleotide tract, gene length and transcriptional status, as well replication timing. Here, we show on a single-cell level that deletions — the predominant MSI type in MMR-deficient cells — are preferentially associated with longer A/T tracts, long or transcribed genes and later-replicating genes.
Prostate Cancer Stem Cells: Clinical Aspects and Targeted Therapies

Despite decades of research and successful improvements in diagnosis and therapy, prostate cancer (PC) remains a major challenge. In recent years, it has become clear that PC stem cells (PCSCs) are the driving force in tumorigenesis, relapse, metastasis, and therapeutic resistance of PC. In this minireview, we discuss the impact of PCSCs in the clinical practice. Moreover, new therapeutic approaches to combat PCSCs are presented with the aim to achieve an improved outcome for patients with PC.
Design, Synthesis, and Biological Evaluation of N-Acyl-Homoserine Lactone Analogs of Quorum Sensing in Pseudomonas aeruginosa

Quorum sensing plays a necessary role in the production of virulence factors and the formation of biofilm on Pseudomonas aeruginosa. Thus, the development of inhibition of quorum sensing is one of the most promising methods to control bacterial infection and antibiotic resistance. In this work, nine novel AHL analogs were designed, synthesized, and evaluated as potential quorum sensing inhibitors. The results depicted that structural modifications have significant effects on quorum sensing inhibition activity of AHL molecules. Without inhibiting the growth of P. aeruginosa, 2-(4-bromophenyl)-N-(2-oxotetrapyridinefuran-3-yl) butanamide (compound no.10) showed the excellent performance in inhibiting biofilm formation and virulence factor production among all the compounds through robustly suppressing the expression of QS related genes. In a molecular docking study, compound no.10 exhibited a higher affinity toward LasR than other AHL analogs. In addition, compound no.10 also exhibits the best inhibition effect on virulence production in the Caenorhabditis elegans infection model.
Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer

Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC.
Internet Survey Evaluation of Iliopsoas Injury in Dogs Participating in Agility Competitions

Objective To describe risk factors associated with demographics, training, and competition for iliopsoas injury in dogs participating in agility competitions, as well as describe owner reported treatment and return to sport following injury. Procedures An internet-based survey of agility handlers collected risk factor data for dogs participating in agility. Owners were asked questions about demographics, training, and competition as well as injury treatment and recovery if applicable. Associations between variables of interest and iliopsoas injury were estimated with logistic regression. The final risk factor model was built via modified backward selection, with all variables in the final model showing significant associations at p < 0.05. Results Of the 4,197 dogs in the sample, 327 (7.8%) reported iliopsoas injury. The final model identified six risk factors for iliopsoas injury. A higher risk of iliopsoas injury was observed for the Border Collie breed, dogs with handlers who are veterinary assistants, dogs competing on dirt, dogs competing on artificial turf 6+ times a year, and dogs that trained with the 2 × 2 method for weave poles. Dogs that were not acquired with agility in mind were observed to have a decreased risk of injury. Factors like number of competition days and jump height were not significantly associated with risk of iliopsoas injury. Owners sought veterinary care for 88% of dogs with iliopsoas injury, including specialty care for 63%. Treatment most often included rest, home rehabilitation, formal rehabilitation, and/or oral medications. Most dogs (80%) were able to return to sport within 6 months, while 20% were out for longer than 6 months, or retired. Conclusion and Clinical Relevance Iliopsoas injury can necessitate a significant amount of time off from training and competition, and even lead to retirement of dogs competing in agility. Some of the risk factors identified in this study can inherently not be modified (breed, intended use, and handler profession), but can be taken into consideration for injury prevention strategies. Competition and training risk factors that can be modified, such as weave training, may help to inform guidelines for best practices in management of the agility athlete.
Subtypes in Patients Taking Prescribed Opioid Analgesics and Their Characteristics: A Latent Class Analysis

Background Owing to their pharmacological properties the use of opioid analgesics carries a risk of abuse and dependence, which are associated with a wide range of personal, social, and medical problems. Data-based approaches for identifying distinct patient subtypes at risk for prescription opioid use disorder in Germany are lacking. Objective This study aimed to identify distinct subgroups of patients using prescribed opioid analgesics at risk for prescription opioid use disorder. Methods Latent class analysis was applied to pooled data from the 2015 and 2021 Epidemiological Survey of Substance Abuse. Participants were aged 18–64 years and self-reported the use of prescribed opioid analgesics in the last year (n = 503). Seven class-defining variables based on behavioral, mental, and physical health characteristics commonly associated with problematic opioid use were used to identify participant subtypes. Statistical tests were performed to examine differences between the participant subtypes on sociodemographic variables and prescription opioid use disorder. Results Three classes were extracted, which were labeled as poor mental health group (43.0%, n = 203), polysubstance group (10.4%, n = 50), and relatively healthy group (46.6%, n = 250). Individuals within the poor mental health group (23.2%, n = 43) and the polysubstance group (31.1%, n = 13) showed a higher prevalence of prescription opioid use disorder compared to those of the relatively healthy group. Conclusion The results add further evidence to the knowledge that patients using prescribed opioid analgesics are not a homogeneous group of individuals whose needs lie in pain management alone. Rather, it becomes clear that these patients differ in their individual risk of a prescription opioid use disorder, and therefore identification of specific risks plays an important role in early prevention.
Local-To-Global Hypotheses for Robust Robot Localization

Many robust state-of-the-art localization methods rely on pose-space sample sets that are evaluated against individual sensor measurements. While these methods can work effectively, they often provide limited mechanisms to control the amount of hypotheses based on their similarity. Furthermore, they do not explicitly use associations to create or remove these hypotheses. We propose a global localization strategy that allows a mobile robot to localize using explicit symbolic associations with annotated geometric features. The feature measurements are first combined locally to form a consistent local feature map that is accurate in the vicinity of the robot. Based on this local map, an association tree is maintained that pairs local map features with global map features. The leaves of the tree represent distinct hypotheses on the data associations that allow for globally unmapped features appearing in the local map. We propose a registration step to check if an association hypothesis is supported. Our implementation considers a robot equipped with a 2D LiDAR and we compare the proposed method to a particle filter. We show that maintaining a smaller set of data association hypotheses results in better performance and explainability of the robot’s assumptions, as well as allowing more control over hypothesis bookkeeping. We provide experimental evaluations with a physical robot in a real environment using an annotated geometric building model that contains only the static part of the indoor scene. The result shows that our method outperforms a particle filter implementation in most cases by using fewer hypotheses with more descriptive power.
NUTRIENTS ASSESSMENT OF ANAEROBIC PALM OIL MILL EFFELUENT (AnPOME) AS AN ALTERNATIVE MEDIA FOR MICROALGAE CULTURE

The main aim of the present study is to investigate the availability of macronutrient andmicronutrient in AnPOME. All collected samples were analyzed using HACH method. Theresults reveal that the C/N and N/P ratio of the AnPOME is six times more than the theoreticalvalue. Concentration of micronutrients also shown higher concentration range compared tothat of the Bold Basal Medium (BBM). However, the concentration of phosphorus inAnPOME six times lower than nitrogen indicates that phosphorus limitation in AnPOME.Hence, this finding suggested the best microalgae to be grown in AnPOME is mixotrophic orheterotrophic mode. Overall, reuse of AnPOME replacing synthetic growth is highlyrecommended considering that enough composition of macronutrient and micronutrient inAnPOME and inexpensive alternative to synthetic media.Keywords: microalgae; Anaerobic Palm Oil Mill Effluent (AnPOME); BBM; macronutrient;micronutrient.
Psychological Wellbeing and Employability of Retrenched Workforce During COVID-19: A Qualitative Study Exploring the Mitigations for Post Pandemic Recovery Phase

The ongoing COVID-19 pandemic has triggered several employment-related issues, followed by different response strategies. With retrenchment measures being a common response strategy during economic downturns, many individuals have been faced with unemployment. This study aimed to explore the effect of the COVID-19 pandemic related retrenchment on the psychological wellbeing of the Malaysian workforce, using a qualitative research approach and based on the Latent-deprivation Model. A purposive sample of 30 retrenched participants was interviewed via telephone during Malaysia's Movement Control Order (MCO). Thematic analysis was subsequently conducted to identify key themes in the data set. Six themes emerged from the thematic analysis: (1) Retrenchment leading to the deterioration of psychological wellbeing; (2) Unemployment, financial strain and economic uncertainty; (3) Emotions related to the COVID-19 virus; (4) Coping with lifestyle change; (5) Recommendations to improve the psychological wellbeing and mental health of the retrenched workforce, and (6) Career and financial support at the recovery phase. The present study provides valuable insight into the wellbeing of retrenched workforce who are forced to cope with both unemployment and a global pandemic, and workforce perspectives regarding types of support needed during the recovery phase.
How Staying Negative Is Good for the (Adult) Brain: Maintaining Chloride Homeostasis and the GABA-Shift in Neurological Disorders

Excitatory-inhibitory (E-I) imbalance has been shown to contribute to the pathogenesis of a wide range of neurodevelopmental disorders including autism spectrum disorders, epilepsy, and schizophrenia. GABA neurotransmission, the principal inhibitory signal in the mature brain, is critically coupled to proper regulation of chloride homeostasis. During brain maturation, changes in the transport of chloride ions across neuronal cell membranes act to gradually change the majority of GABA signaling from excitatory to inhibitory for neuronal activation, and dysregulation of this GABA-shift likely contributes to multiple neurodevelopmental abnormalities that are associated with circuit dysfunction. Whilst traditionally viewed as a phenomenon which occurs during brain development, recent evidence suggests that this GABA-shift may also be involved in neuropsychiatric disorders due to the “dematuration” of affected neurons. In this review, we will discuss the cell signaling and regulatory mechanisms underlying the GABA-shift phenomenon in the context of the latest findings in the field, in particular the role of chloride cotransporters NKCC1 and KCC2, and furthermore how these regulatory processes are altered in neurodevelopmental and neuropsychiatric disorders. We will also explore the interactions between GABAergic interneurons and other cell types in the developing brain that may influence the GABA-shift. Finally, with a greater understanding of how the GABA-shift is altered in pathological conditions, we will briefly outline recent progress on targeting NKCC1 and KCC2 as a therapeutic strategy against neurodevelopmental and neuropsychiatric disorders associated with improper chloride homeostasis and GABA-shift abnormalities.
The Dynamic Role of FOXP3+ Tregs and Their Potential Therapeutic Applications During SARS-CoV-2 Infection

Coronavirus disease 2019 (COVID-19) has been raging all around the world since the beginning of 2020, and leads to acute respiratory distress syndrome (ARDS) with strong cytokine storm which contributes to widespread tissue damage and even death in severe patients. Over-activated immune response becomes one of the characteristics of severe COVID-19 patients. Regulatory T cells (Treg) play an essential role in maintaining the immune homeostasis, which restrain excessive inflammation response. So FOXP3+ Tregs might participate in the suppression of inflammation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides suppressive function, tissue resident Tregs are also responsible for tissue repair. In this review, we mainly summarize the latest research focusing on the change of FOXP3+ Tregs in the COVID-19 patients, discuss the relationship between disease severity and number change of Tregs and speculate the potential role of FOXP3+ Tregs during SARS-CoV-2 infection. Furthermore, we introduce some potential Treg-based therapies to improve patients’ outcomes, which include small molecular drugs, antibody drugs, CAR-Treg and cytokine treatment. We hope to reduce tissue damage of severe COVID-19 patients and offer better prognosis through Treg-based therapy.
COVID-19 Lockdown and Lifestyle Changes in Saudi Adults With Types 1 and 2 Diabetes

Objective We aimed to evaluate and compare the impact of COVID-19 lockdown on lifestyle changes and other common related effects of the lockdown in Saudi adults with diabetes mellitus (DM), both type 1 (T1D) and type 2 diabetes (T2D). Methods 265 T1D and 285 T2D individuals were included in this cross-sectional survey during lockdown using an online questionnaire and compared with 297 participants without DM. Variables included demographics, treatment changes, use of supplements, change in sleeping habits and physical activity, dietary changes, social and mental health, and education and awareness during COVID-19 lockdown. Results The COVID-19 lockdown was associated with more treatment doses in people with T1D but not in those with T2D (p = 0.003). More participants with T1D and T2D than the control group reported that they felt symptoms of depression during lockdown (ORs of 1.83, p = 0.008 and 2.2, p = 0.001, respectively) and that lockdown affected them psychologically (ORs of 1.64, p = 0.019 and 1.85, p = 0.005, respectively). More participants with T1D than controls reported that their physical activity decreased during lockdown (OR of 2.70, p = 0.024). Furthermore, significantly lesser participants in both DM groups than controls agreed that the health education regarding COVID-19 covered everything (ORs of 0.41, p < 0.001 and 0.56, p < 0.001, respectively for T1D and T2D groups). Regarding dietary habits, the DM groups reported more changes in either the number of daily meals, meal content, or mealtimes than the control group. Conclusions COVID-19 lockdown-associated lifestyle changes were more prevalent in individuals with T1D and T2D compared to control. Findings may assist public health authorities in outlining their responses in pandemics and promote healthy lifestyle adaptations in this high-risk cohort to limit adverse effects in future lockdowns.
China's Financial System and Economy: A Review

China's financial system has been integral to its spectacular economic growth over the past 40 years. We review the recent literature on China's financial system and its connections to the Chinese economy based on the categories of Aggregate Financing to the Real Economy (AFRE), a broad measure of the nation's yearly flow of liquidity accounting for unique features of China's financial system. While early work on China's financial system emphasizes the state-owned enterprise reform, the recent literature explores other more market-based financing channels—including shadow banking—that grew rapidly after 2010 and have become important components of AFRE. These new financing channels not only are intertwined with each other, but also, and more importantly, are often ultimately tied back to the dominant banking sector in China. Understanding the mechanisms behind these channels and their intrinsic connections is crucial to alleviate capital allocation distortion and mitigate potential systemic financial risk in China. Expected final online publication date for the Annual Review of Economics, Volume 15 is August 2023. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Histological changes and neural elements in the subacromial bursa on patients with rotator cuff tear: Pilot study

Objective: This study aimed to investigate the neural elements of the subacromial bursa (SAB) in rotator cuff tears. Materials and methods: Twenty patients with rotator cuff tears were recruited, and their visual analog scale (VAS) score, duration of symptoms, and range of motion (ROM), including flexion, external rotation, and internal rotation were evaluated. Tear size was measured using magnetic resonance imaging (MRI). The SAB specimens obtained during arthroscopic rotator cuff repair were studied using routine hematoxylin and eosin staining and immunohistochemistry (S-100 protein and PGP 9.5 protein). The SAB specimen for the control group was obtained from 2 fresh cadavers and 2 patients with acute humeral shaft fracture. The Mann-Whitney U test was applied to assess the difference between histological findings of the rotator cuff tear group and control group. The correlation between the histological findings and clinical features was evaluated using the Spearman correlation coefficient. Results: The mean duration of symptom was 10.2 ± 6.4 months. The preoperative average VAS score was 2.9 ± 1.2. The degrees of preoperative ROM in forward flexion and external and internal rotations were 143.8 ± 19.5, 49.5 ± 23.1, and –4.3 ± 4.2, respectively. The tear was 2.0 ± 0.9 cm. For histological findings, the number of neural elements per low power field in the rotator cuff tear group was significantly less than the control group in both immunohistochemical stainings (S-100: 0.5 ± 0.7 vs 2.8 ± 0.5, p < .01; PGP 9.5: 0.4 ± 0.7 vs 3.5 ± 0.6, p < .01). During the correlation analysis, the number of neural elements in the PGP 9.5 staining was negatively correlated with the ROM in forward flexion and external rotation. Conclusion: This study revealed that chronic rotator cuff tears may induce degeneration of neural elements in SAB.
Susceptibilities of pus cultures in diabetic foot patients: an observational study

Objectives: The aim of our study is to evaluate the organisms growing into the pus cultures of diabetic foot patients and to further document their sensitivity and resistance toward antibiotics. Methods: This study was conducted among admitted patients in the department of Medicine and Orthopedics, of a tertiary care hospital, including patients with known diabetes mellitus for the last 5 years, with a foot ulcer of any grade and a positive culture for bacterial growth. Cultures showing fungal growth were excluded. Results: There were 139 participants in our study with a mean age of 55.27 years, and mean HbA1c levels of 9.51%, 101 (72.66%) patients were males and 38 (27.33%) females. According to the Wagner classification; there were 48 (34.53%) patients in grade 2, 27 (19.42%) patients in grade 3, 54 (38.84%) patients in grade 4, and 10 (7.19%) patients in grade 5. The most frequently isolated bacteria were Staphylococcus aureus (43.16%), methicillin-resistant staphylococcal aureus (5.03%), Enterococcus species (5.75%), Streptococcus species (7.91%), Pseudomonas aeruginosa (20.14%), Escherichia coli (24.46%), Klebsiella pneumonia 7 (5.03%), Proteus vulgaris 6 (4.31%), Proteus mirabilis 3 (2.15%), Enterobacter species 7 (5.03%), Morganella morganii 2 (1.43%), and Acinetobacter 7 (5.03%). Amikacin was the most susceptible antibiotic to the majority of the microorganisms, followed by gentamicin, piperacillin/tazobactam, vancomycin chloramphenicol, and clindamycin. Among the resistant antibiotics, penicillins and cephalosporins were the notable ones. Conclusions: This study will decipher the bacteriological profiles among patients of diabetic foot ulcers according to their susceptibility and might be helpful to provide effective treatment.