Miracle-dz/UniFAR-FTUs huggingface dataset:
Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances

Simple Summary Immunotherapy has changed the landscape of treatment modalities available for many different types of malignancies. However, the factors that influence the success of immunotherapeutics have not been as clearly seen in advanced prostate cancer, likely due to immunosuppressive factors that exist within the prostate cancer tumor microenvironment. While there have been many immunotherapeutics used for prostate cancer, the majority have targeted a single immunosuppressive mechanism resulting in limited clinical efficacy. More recent research centered on elucidating the key mechanisms of immune resistance in the prostate tumor microenvironment has led to the discovery of a range of new treatment targets. With that in mind, many clinical trials have now set out to evaluate combination immunotherapeutic strategies in patients with advanced prostate cancer, in the hopes of circumventing the immunosuppressive mechanisms. Abstract The use of immunotherapy has become a critical treatment modality in many advanced cancers. However, immunotherapy in prostate cancer has not been met with similar success. Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to subvert the immune system, creating an immunosuppressive tumor microenvironment and leading to lower treatment efficacy in advanced prostate cancer. The lethality of metastatic castrate-resistant prostate cancer is driven by the lack of therapeutic regimens capable of generating durable responses. Multiple strategies are currently being tested to overcome immune resistance including combining various classes of treatment modalities. Several completed and ongoing trials have shown that combining vaccines or checkpoint inhibitors with hormonal therapy, radiotherapy, antibody–drug conjugates, chimeric antigen receptor T cell therapy, or chemotherapy may enhance immune responses and induce long-lasting clinical responses without significant toxicity. Here, we review the current state of immunotherapy for prostate cancer, as well as tumor-specific mechanisms underlying therapeutic resistance, with a comprehensive look at the current preclinical and clinical immunotherapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and impaired cellular immunity that have largely limited the utility of immunotherapy in advanced prostate cancer.
Kinesio Taping Relieves Pain and Improves Isokinetic Not Isometric Muscle Strength in Patients with Knee Osteoarthritis—A Systematic Review and Meta-Analysis

This study investigated the effects of kinesio taping (KT) or KT plus conventional therapy on pain, muscle strength, funrefction, and range of motion in patients with knee osteoarthritis (OA). Data sources: Databases included PubMed, Ovid Medline, CINAHL, Airiti Library, EMBASE, and WOS search engines. Search terms related to KT and knee OA were combined and searched. Articles that met the inclusion criteria and were graded with a Jadad score ≥3 were included in a meta-analysis to calculate the total effect. The exclusion criteria were non-English-language articles, non-original articles, non-full-text articles, no description of the intervention, or articles with a Jadad score ≤2. Eleven articles were included in the meta-analysis. KT treatment had a significant small total effect on pain reduction (p < 0.001; n = 1509; standardized mean difference (SMD) = −0.42; 95% CI = −0.65 to −0.18) and a significant moderate total effect on isokinetic muscle strength improvement (p = 0.001; n = 447; SMD = 0.72; 95% CI = 0.28 to 1.16). No significant total effects of KT on isometric muscle strength, time to complete functional tasks, or ROM improvement were found. KT or KT plus conventional therapy has a significant effect on pain relief and isokinetic but not isometric muscle strength improvement in patients with knee OA. KT can be an effective tool for treating knee OA pain and is especially valuable for aiding in isokinetic muscle strength. (PROSPERO register ID: CRD42021252313)
Exploration of the Cs Trapping Phenomenon by Combining Graphene Oxide with α-K6P2W18O62 as Nanocomposite

A graphene oxide-based α-K6P2W18O62 (Dawson-type polyoxometalate) nanocomposite was formed by using two types of graphene oxide (GO) samples with different C/O compositions. Herein, based on the interaction of GO, polyoxometalates (POMs), and their nanocomposites with the Cs cation, quantitative data have been provided to explicate the morphology and Cs adsorption character. The morphology of the GO-POM nanocomposites was characterized by using TEM and SEM imaging. These results show that the POM particle successfully interacted above the surface of GO. The imaging also captured many small black spots on the surface of the nanocomposite after Cs adsorption. Furthermore, ICP-AES, the PXRD pattern, IR spectra, and Raman spectra all emphasized that the Cs adsorption occurred. The adsorption occurred by an aggregation process. Furthermore, the difference in the C/O ratio in each GO sample indicated that the ratio has significantly influenced the character of the GO-POM nanocomposite for the Cs adsorption. It was shown that the oxidized zone (sp2/sp3 hybrid carbon) of each nanocomposite sample was enlarged by forming the nanocomposite compared to the corresponding original GO sample. The Cs adsorption performance was also influenced after forming a composite. The present study also exhibited the fact that the sharp and intense diffractions in the PXRD were significantly reduced after the Cs adsorption. The result highlights that the interlayer distance was changed after Cs adsorption in all nanocomposite samples. This has a good correlation with the Raman spectra in which the second-order peaks changed after Cs adsorption.
Transcriptomic Analysis Reveals Differential Expression of Genes between Lung Capillary and Post Capillary Venules in Abdominal Sepsis

Lung endothelial cell dysfunction plays a central role in septic-induced lung injury. We hypothesized that endothelial cell subsets, capillary endothelial cells (capEC) and post capillary venules (PCV), might play different roles in regulating important pathophysiology in sepsis. In order to reveal global transcriptomic changes in endothelial cell subsets during sepsis, we induced sepsis in C57BL/6 mice by cecal ligation and puncture (CLP). We confirmed that CLP induced systemic and lung inflammation in our model. Endothelial cells (ECs) from lung capillary and PCV were isolated by cell sorting and transcriptomic changes were analyzed by bioinformatic tools. Our analysis revealed that lung capEC are transcriptionally different than PCV. Comparison of top differentially expressed genes (DEGs) of capEC and PCV revealed that capEC responses are different than PCV during sepsis. It was found that capEC are more enriched with genes related to regulation of coagulation, vascular permeability, wound healing and lipid metabolic processes after sepsis. In contrast, PCV are more enriched with genes related to chemotaxis, cell–cell adhesion by integrins, chemokine biosynthesis, regulation of actin filament process and neutrophil homeostasis after sepsis. In addition, we predicted some transcription factor targets that regulate a significant number of DEGs in sepsis. We proposed that targeting certain DEGs or transcriptional factors would be useful in protecting against sepsis-induced lung damage.
Comparison of the Effect of Pan-Retinal Photocoagulation and Intravitreal Conbercept Treatment on the Change of Retinal Vessel Density Monitored by Optical Coherence Tomography Angiography in Patients with Proliferative Diabetic Retinopathy

Background: This study compares the changes in retinal vessel density (VD) after pan-retinal photocoagulation (PRP) and intravitreal conbercept (IVC) treatment in proliferative diabetic retinopathy (PDR) eyes by optical coherence tomography angiography (OCTA). Methods: A total of 55 treatment-naïve PDR eyes were included in this retrospective study. Of these, 29 eyes were divided into a PRP group, and 26 eyes were divided into an IVC group based on the treatment they received. OCTA was performed to measure macular and papillary VD at each follow-up in both groups. Results: The macular VD for superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) and papillary VD for radial peripapillary capillary (RPC) between the two groups demonstrated no significant difference at baseline and month 12 (p > 0.05). The paired t-test results showed that the macular VD for SCP, DCP, CC and papillary VD for the RPC at month 12 did not differ to the baseline in each group (p > 0.05). Conclusions: During the 12-month follow-up, there was no significant change of macular and papillary VD between the PRP and IVC treatment in PDR eyes. Additionally, compared to the baseline, there were no significant changes of macular and papillary VD after either the PRP or IVC treatment. Considering the decrease in VD as DR progress, both treatment modalities can potentially prevent macular and papillary VD loss in PDR.
A Highly Reliable Convolutional Neural Network Based Soft Tissue Sarcoma Metastasis Detection from Chest X-ray Images: A Retrospective Cohort Study

Simple Summary Soft tissue sarcomas are relatively rare malignant diseases. Part of the diagnosis and follow-up includes medical imaging of the thorax for detection of lung metastases. A Python script was created and trained using a set of lung X-rays and concordant CT scans from a high-volume German-speaking sarcoma center. It is capable of detecting malignant metastasis in the lung with a precision of 71.2%, specificity of 90.5%, sensitivity of 94% and accuracy of 91.2%. Furthermore, the program was able to detect even small nodules with a size <1 cm in conventional X-rays of the thorax. This algorithm was implemented into our daily clinical practice alongside with the radiologists’ findings. With this tool we aim to improve the quality of our service and reduce the expenditure of time. Abstract Introduction: soft tissue sarcomas are a subset of malignant tumors that are relatively rare and make up 1% of all malignant tumors in adulthood. Due to the rarity of these tumors, there are significant differences in quality in the diagnosis and treatment of these tumors. One paramount aspect is the diagnosis of hematogenous metastases in the lungs. Guidelines recommend routine lung imaging by means of X-rays. With the ever advancing AI-based diagnostic support, there has so far been no implementation for sarcomas. The aim of the study was to utilize AI to obtain analyzes regarding metastasis on lung X-rays in the most possible sensitive and specific manner in sarcoma patients. Methods: a Python script was created and trained using a set of lung X-rays with sarcoma metastases from a high-volume German-speaking sarcoma center. 26 patients with lung metastasis were included. For all patients chest X-ray with corresponding lung CT scans, and histological biopsies were available. The number of trainable images were expanded to 600. In order to evaluate the biological sensitivity and specificity, the script was tested on lung X-rays with a lung CT as control. Results: in this study we present a new type of convolutional neural network-based system with a precision of 71.2%, specificity of 90.5%, sensitivity of 94%, recall of 94% and accuracy of 91.2%. A good detection of even small findings was determined. Discussion: the created script establishes the option to check lung X-rays for metastases at a safe level, especially given this rare tumor entity.
Proton Pumping and Non-Pumping Terminal Respiratory Oxidases: Active Sites Intermediates of These Molecular Machines and Their Derivatives

Terminal respiratory oxidases are highly efficient molecular machines. These most important bioenergetic membrane enzymes transform the energy of chemical bonds released during the transfer of electrons along the respiratory chains of eukaryotes and prokaryotes from cytochromes or quinols to molecular oxygen into a transmembrane proton gradient. They participate in regulatory cascades and physiological anti-stress reactions in multicellular organisms. They also allow microorganisms to adapt to low-oxygen conditions, survive in chemically aggressive environments and acquire antibiotic resistance. To date, three-dimensional structures with atomic resolution of members of all major groups of terminal respiratory oxidases, heme-copper oxidases, and bd-type cytochromes, have been obtained. These groups of enzymes have different origins and a wide range of functional significance in cells. At the same time, all of them are united by a catalytic reaction of four-electron reduction in oxygen into water which proceeds without the formation and release of potentially dangerous ROS from active sites. The review analyzes recent structural and functional studies of oxygen reduction intermediates in the active sites of terminal respiratory oxidases, the features of catalytic cycles, and the properties of the active sites of these enzymes.
Understanding Fatal and Non-Fatal Drug Overdose Risk Factors: Overdose Risk Questionnaire Pilot Study—Validation

Background: Drug overdoses (fatal and non-fatal) are among the leading causes of death in population with substance use disorders. The aim of the current study was to identify risk factors for fatal and non-fatal drug overdose for predominantly opioid-dependent treatment–seeking population. Methods: Data were collected from 640 adult patients using a self-reported 25-item Overdose Risk (OdRi) questionnaire pertaining to drug use and identified related domains. The exploratory factor analysis (EFA) was primarily used to improve the interpretability of this questionnaire. Two sets of EFA were conducted; in the first set of analysis, all items were included, while in the second set, items related to the experience of overdose were removed. Logistic regression was used for the assessment of latent factors’ association with both fatal and non-fatal overdoses. Results: EFA suggested a three-factor solution accounting for 75 and 97% of the variance for items treated in the first and second sets of analysis, respectively. Factor 1 was common for both sets of EFA analysis, containing six items (Cronbach’s α = 0.70) focusing around “illicit drug use and lack of treatment. ” In the first set of analysis, Factors 2 (Cronbach’s α = 0.60) and 3 (Cronbach’s α = 0.34) were focusing around “mental health and emotional trauma” and “chronic drug use and frequent overdose” domains, respectively. The increase of Factor 2 was found to be a risk factor for fatal drug overdose (adjusted coefficient = 1.94, p = 0.038). In the second set of analysis, Factors 2 (Cronbach’s α = 0.65) and 3 (Cronbach’s α = 0.59) as well as Factor 1 were found to be risk factors for non-fatal drug overdose ever occurring. Only Factors 1 and 3 were positively associated with non-fatal overdose (one in a past year). Conclusion: The OdRi tool developed here could be helpful for clinical studies for the overdose risk assessment. However, integrating validated tools for mental health can probably help refining the accuracy of latent variables and the questionnaire’s consistency. Mental health and life stress appear as important predictors of both fatal and non-fatal overdoses.
Delayed Tibial Shaft Fracture Healing Associated with Smoking: A Systematic Review and Meta-Analysis of Observational Studies Conducted Worldwide

Tibial fractures represent a great burden of disease globally, being the most common long-bone fracture; smoking is a known risk factor for delayed skeletal healing and post-fracture complications. This systematic review and meta-analysis aims to analyse the effect of smoking on healing of tibial shaft fractures. PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched from inception to March 2021, with no limitation on language, to find relevant research. All observational studies that assessed the association between cigarette smoking and tibial shaft fracture healing in adults (≥18 years) were included. The quality of studies was evaluated using the Newcastle Ottawa Quality Assessment Scale. A random effects model was used to conduct meta-analysis. Tobacco smoking was associated with an increased rate of non-union and delayed union as well as an increase in time to union in fractures of the tibial shaft. Among the 12 included studies, eight reported an increased rate of non-union, three reported delayed union, and five reported an increase in time to union. However, the results were statistically significant in only three studies for non-union, one for delayed union, and two studies for increased time to union. This review confirms the detrimental impact of smoking on tibial shaft fracture healing and highlights the importance of patient education regarding smoking cessation.
Biochemical Analysis of Leukocytes after In Vitro and In Vivo Activation with Bacterial and Fungal Pathogens Using Raman Spectroscopy

Biochemical information from activated leukocytes provide valuable diagnostic information. In this study, Raman spectroscopy was applied as a label-free analytical technique to characterize the activation pattern of leukocyte subpopulations in an in vitro infection model. Neutrophils, monocytes, and lymphocytes were isolated from healthy volunteers and stimulated with heat-inactivated clinical isolates of Candida albicans, Staphylococcus aureus, and Klebsiella pneumoniae. Binary classification models could identify the presence of infection for monocytes and lymphocytes, classify the type of infection as bacterial or fungal for neutrophils, monocytes, and lymphocytes and distinguish the cause of infection as Gram-negative or Gram-positive bacteria in the monocyte subpopulation. Changes in single-cell Raman spectra, upon leukocyte stimulation, can be explained with biochemical changes due to the leukocyte’s specific reaction to each type of pathogen. Raman spectra of leukocytes from the in vitro infection model were compared with spectra from leukocytes of patients with infection (DRKS-ID: DRKS00006265) with the same pathogen groups, and a good agreement was revealed. Our study elucidates the potential of Raman spectroscopy-based single-cell analysis for the differentiation of circulating leukocyte subtypes and identification of the infection by probing the molecular phenotype of those cells.
Practical Utility of Diagnostic Clinical Breast Examination in the Diagnosis of Breast Cancer

Objectives We aimed to investigate the effectiveness of physician-performed diagnostic clinical breast examination (DCBE) for the diagnosis of breast cancer in clinical practice and to determine the rates of breast cancer diagnosed with DCBE compared to the results of breast ultrasonography (US), mammography (MG), and histopathology. Methods In the retrospective cohort study, the files of female patients diagnosed with breast cancer and admitted to the general surgery outpatient clinics of a university hospital over a 10-year period (2011-2021) were examined. Patients with complete DCBE findings in their files were identified and analyzed (n = 1,091). The examinations of the patients were performed by general surgery specialists with 5-22 years of experience and by radiologists with 4-15 years of experience. Results The mean age of breast cancer diagnosis of the patients was 55.1 ± 13.5 years. While the sensitivity of DCBE was found to be 88.9%, MG sensitivity was 89.8% and breast US sensitivity was 95.1%. Cancer was detected by MG, breast US, and DCBE in 47.9% (n = 523), by breast US and DCBE in 38.9% (n = 424), by MG and breast US in 5.6% (n = 61), by DCBE alone in 3.6% (n = 39), by MG and DCBE in 2.4% (n = 26), and by breast US alone in 1.6% (n = 18). Early-stage breast cancer (p = 0.00) consisted of 73.2% (n = 383) of cancers detected with DCBE, breast US and MG, 74.6% (n = 316) of cancers detected with DCBE and breast US, 93.4% of cancers detected with breast US and MG (n = 57), 92.3% (n = 24) of cancers detected with DCBE and MG, 94.4% (n = 17) of cancers detected with breast US alone, and 69.2% of cancers detected with DCBE alone (n = 27). Conclusions CBE still maintains its importance in societies where screening participation and awareness of breast cancer are low. A breast cancer diagnosis is often done after a complaint of a palpable mass in the breast, and only then are more advanced-stage breast cancers are seen. CBE is among the important diagnostic methods preventing breast cancer from being overlooked, especially in places where health resources are limited.
Novel monkey mAbs induced by a therapeutic vaccine targeting the hepatitis B surface antigen effectively suppress hepatitis B virus in mice

ABSTRACT Background We have previously obtained a mouse anti-hepatitis B surface antigen (HBsAg) antibody E6F6 with long-lasting serum HBsAg clearance effects. The E6F6 epitope-based protein CR-T3-SEQ13 (HBsAg aa 113-135) vaccination therapy in cynomolgus monkeys induced long-term polyclonal antibodies-mediated clearance of HBsAg in the HBV transgenic (HBV-Tg) mice. Methods We isolated monoclonal antibodies from CR-T3-SEQ13 vaccinated cynomolgus monkeys, compared their therapeutic effects with E6F6, identified their epitopes on HBsAg, determined the pharmacokinetics and studied their physical property. Results A panel of anti-HBsAg mAbs was generated through memory B cell stimulatory culture. Two lead monkey-human chimeric antibodies, C1-23 and C3-23, effectively suppressed HBsAg and HBV DNA in HBV-Tg mice. The humanized antibodies and humanized-mouse reverse chimeric antibodies of two antibodies exhibited comparable HBsAg clearance and viral suppression efficacy as those versions of E6F6 in HBV-Tg mice. Humanized antibody hu1-23 exhibited more efficacy HBsAg-suppressing effects than huE6F6-1 and hu3-23 in HBV-Tg mice at dose levels of 10 and 20 mg/kg. Evaluation of the binding sites indicates that the epitope recognized by hu1-23 is located in HBsAg aa 118-125 and 121-125 for hu3-23. Physical property study revealed that hu1-23 and hu3-23 are stable enough for further development as a drug candidate. Conclusions Our data suggest that the CR-T3-SEQ13 protein is a promising HBV therapeutic vaccine candidate, and hu1-23 and hu3-23 are therapeutic candidates for the treatment of chronic hepatitis b. Moreover, the generation of antibodies from the epitope-based vaccinated subjects may be an alternative approach for novel antibody drug discovery.
Effects of a 10-Week Combined Coordination and Agility Training Program on Young Male Soccer Players

The current literature has shown how working on coordination and agility produces effects on specific aspects in team sports. The purpose of this study was to examine the effects of a ten-week coordination training program applied to soccer on different tests that evaluate speed (30 m speed test), agility (Illinois Agility Test (IAT)) and lower body strength (countermovement jump (CMJ)). Forty U16 male soccer players from two nonprofessional teams (twenty in the control group (CG) (aged = 14.70 ± 0.47, body weight = 60.15 ± 8.07 kg, height = 1.71 ± 0.06 m) and twenty in the experimental group (EG) (aged = 14.50 ± 0.51, body weight = 58.08 ± 9.78 kg, height = 1.69 ± 0.06 m)) performed a combined coordination and agility program during 10 min every training day (3 days a week) for 10 weeks. The results of this study showed that coordination training produced adaptations in the power (CMJ of EG (p = 0.001)) and agility capacities (IAT of EG (p = 0.002)) of young soccer players, but not on speed performance at longer distances (CG, p = 0.20 and EG, p = 0.09). Despite the benefits of the training program, a combination of training methods that includes power, agility, speed, and strength can enhance such improvements.