Miracle-dz/UniFAR-FTUs huggingface dataset:
Catamenial pneumothorax: Not only VATS diagnosis

Background Catamenial pneumothorax (CP) is a rare type of spontaneous, recurring pneumothorax occurring in women, from the day before menstruation until 72 hours after its beginning. Conservative treatment is generally associated with recurrence of CP. Video-assisted thoracic surgery (VATS) approach allows not only to obtain diagnosis but also to guide definitive treatment of causing lesions, such as ectopic endometrial implants or diaphragmatic defects and fenestrations. We report our experience in VATS management of CP to focus on its role in CP. Materials and methods In this retrospective observational study, we collected data from women referred to our center for CP, from January 2019 to April 2022. All patients underwent VATS approach, with muscle-sparing thoracotomy when diaphragmatic fenestrations were detected, to perform selective diaphragmatic plication and/or partial diaphragmatic resection. Results were analyzed in terms of pneumothorax recurrence after surgical treatment. All patients were referred to gynecologists for medical therapy. Results Eight women (median age 36 years, range: 21–45), all with right side CP, were included; three already had pelvic endometriosis and two had already undergone lung apicectomy at other institutions. VATS allowed us to detect diaphragmatic fenestrations in seven patients (87.5%) and apical bullae in five (62.5%). Apicectomy was performed in five cases (62.5%), selective diaphragmatic plication in two (25%), and partial diaphragmatic resection in five (62.5%). Chemical pleurodesis with talc was performed in all to minimize the risk of recurrence. Pathological diagnosis of endometriosis on the resected diaphragm was achieved in five patients (62.5%). No recurrence occurred, except for one woman who stopped medical treatment for endometriosis. Conclusions In the management of patients with CP, VATS should be recommended not only to obtain an explorative diagnosis of ectopic endometrial implants or diaphragmatic fenestrations but also to allow the most appropriate surgical treatment and obtain pathological specimens for confirmation and definitive diagnosis of thoracic endometriosis. Medical therapy to achieve ovarian rest is mandatory in the postoperative period and should not be discontinued.
In vitro evaluation of photon and carbon ion radiotherapy in combination with cisplatin in head and neck squamous cell carcinoma cell lines

Background Heavy ion radiotherapy, such as carbon ion radiotherapy (CIRT), has multiple advantages over conventional photon therapy. Cisplatin, as a classic anti-tumor drugs, has been tested and discovered as a photon radiosensitizer in several cell lines, including head and neck squamous cell carcinoma (HNSCC). Hence, the aim of our study is to evaluate whether cisplatin can sensitize CIRT towards HNSCC cell lines in vitro. Methods Human nasopharyngeal carcinoma cell line CNE-2, human tongue squamous carcinoma cell line TCA 8113 and human hypopharynx squamous carcinoma cell line FADU were all irradiated with photon beam of 2, 4, 6, 8 Gy (physical dose) and carbon ion beam of 1, 2, 3, 4 Gy (physical dose) and treated with cisplatin. Cell survival was assessed by clonogenic survival assay. Results CIRT showed significantly stronger cytotoxic effect than standard photon radiotherapy. The relative biological effectiveness (RBE) of carbon ion beam at 10% survival ( R B E 10 ) was calculated 3.07 for CNE-2, 2.33 for TCA 8113 and 2.36 for FADU. Chemoradiotherapy (both photon radiotherapy and CIRT) was more effective than radiotherapy alone. In vitro sensitizer enhancement ratios (SERs) of cisplatin in CNE-2, TCA 8113 and FA DU cell lines after photon irradiation were 1.33, 1.14 and 1.21, while after carbon ion irradiation were 1.02, 1.00 and 0.96, showed that cisplatin sensitized photon irradiation but showed no sensitization effect in carbon ion irradiation in all tested cell lines. Conclusions In conclusion, high linear energy transfer (LET) CIRT was more effective than photon irradiation to prevent the proliferation of HNSCC cell lines. Additional treatment with cisplatin could sensitize photon irradiation but showed no effect on carbon ion irradiation.
Inactivation of the lysine binding sites of human plasminogen (hPg) reveals novel structural requirements for the tight hPg conformation, M-protein binding, and rapid activation

Accelerated activation of the human plasminogen zymogen (hPg) to two-chain active plasmin (hPm) is achieved following conformational changes induced by ligand-binding at the lysine-binding sites (LBSs) in four of the five hPg kringle domains. In this manner, pattern D skin-trophic strains of Group A streptococci (GAS), through the expression of surface plasminogen-binding M-protein (PAM), immobilize surface hPg, thereby enabling rapid hPg activation by GAS-secreted streptokinase (SK). Consequently, GAS enhances virulence by digesting extracellular and tight cellular junctional barriers using hPm activity. Many studies have demonstrated the singular importance of the kringle-2 domain of hPg (K2hPg) to PAM-binding using hPg fragments. Recently, we showed, using full-length hPg, that K2hPg is critical for PAM binding. However, these studies did not eliminate any modulatory effects of the non-K2hPg LBS on this interaction. Moreover, we sought to establish the significance of the intramolecular interaction between Asp219 of the LBS of K2hPg and its serine protease domain binding partner, Lys708, to conformational changes in hPg. In the current study, selective inactivation of the LBS of K1hPg, K4hPg, and K5hPg revealed that the LBS of these kringle domains are dispensable for hPg binding to PAM. However, the attendant conformational change upon inactivation of K4hPg LBS increased the affinity of hPg for PAM by an order of magnitude. This finding suggests that the native hPg conformation encloses PAM-binding exosites or sterically hinders access to K2hPg. While simultaneous inactivation of the LBS of K1hPg, K4hPg, and K5hPg inhibited hPg/SK association alongside hPg activation, the replacement of Lys708 generated a slight conformational change that optimally accelerated hPg activation. Thus, we accentuate disparate functions of hPg LBS and conclude, using intact proteins, that K2hPg plays a central role in regulating hPg activation.
Statistical inferences and visualization based on a scale-space approach

SiZer (SIgnificant ZERo crossing of the derivatives) is a scale-space visualization tool for statistical inference that is originally developed by Chaudhuri and Marron (1999). It is an exploratory data analysis tool that uses local linear smoothing and convolutions with Gaussian kernel weights for inference and takes its views across a range of bandwidths. A number of authors also later go on to develop versions of this visualization tool that can account for two regression curves, instead of only one, and also dependent data. Motivated by these works, in this dissertation we will introduce a graphical method for the test of the equality of the mean of multiple time series based on SiZer. We will conduct a broad numerical study to demonstrate the sample performance of the proposed tool. In addition, we will investigate asymptotic properties of SiZer for the comparison of two time series. As an extension of this original one dimensional SiZer, Godtliebsen et al. (2004) propose a two dimensional SiZer. This creates a tool that gives analysts the ability to look at images at a number of different resolutions, or bandwidths. We will introduce an inferential tool, called Spatial SiZer, that takes into account the detection of trends within datasets that have spatially dependent error structure. Also, we will compare several multiple testing adjustment procedures by a simulation study. Finally, we will display the performance of Spatial SiZer through several numerical studies for simulated and real datasets. Index words: Comparison of multiple curves, Image analysis, Local linear smoothing, Multiple testing adjustment, Scale-space, SiZer, Time series, Weak convergence Statistical Inferences and Visualization Based on a Scale-Space Approach
Anti-schistosomal immunity to core xylose/fucose in N-glycans

Schistosomiasis is a globally prevalent, debilitating disease that is poorly controlled by chemotherapy and for which no vaccine exists. While partial resistance in people may develop over time with repeated infections and treatments, some animals, including the brown rat (Rattus norvegicus), are only semi-permissive and have natural protection. To understand the basis of this protection, we explored the nature of the immune response in the brown rat to infection by Schistosoma mansoni. Infection leads to production of IgG to Infection leads to production of IgG to parasite glycoproteins parasite glycoproteins with complex-type N-glycans that contain a non-mammalian-type modification by core α2-Xylose and core α3-Fucose (core Xyl/Fuc). These epitopes are expressed on the surfaces of schistosomula and adult worms. Importantly, IgG to these epitopes can kill schistosomula by a complement-dependent process in vitro. Additionally, sera from both infected rhesus monkey and infected brown rat were capable of killing schistosomula in a manner inhibited by glycopeptides containing core Xyl/Fuc. These results demonstrate that protective antibodies to schistosome infections in brown rats and rhesus monkeys include IgG responses to the core Xyl/Fuc epitopes in surface-expressed N-glycans, and raise the potential of novel glyco-based vaccines that might be developed to combat this disease.
Studying memory processes at different levels with simultaneous depth and surface EEG recordings

Investigating cognitive brain functions using non-invasive electrophysiology can be challenging due to the particularities of the task-related EEG activity, the depth of the activated brain areas, and the extent of the networks involved. Stereoelectroencephalographic (SEEG) investigations in patients with drug-resistant epilepsy offer an extraordinary opportunity to validate information derived from non-invasive recordings at macro-scales. The SEEG approach can provide brain activity with high spatial specificity during tasks that target specific cognitive processes (e.g., memory). Full validation is possible only when performing simultaneous scalp SEEG recordings, which allows recording signals in the exact same brain state. This is the approach we have taken in 12 subjects performing a visual memory task that requires the recognition of previously viewed objects. The intracranial signals on 965 contact pairs have been compared to 391 simultaneously recorded scalp signals at a regional and whole-brain level, using multivariate pattern analysis. The results show that the task conditions are best captured by intracranial sensors, despite the limited spatial coverage of SEEG electrodes, compared to the whole-brain non-invasive recordings. Applying beamformer source reconstruction or independent component analysis does not result in an improvement of the multivariate task decoding performance using surface sensor data. By analyzing a joint scalp and SEEG dataset, we investigated whether the two types of signals carry complementary information that might improve the machine-learning classifier performance. This joint analysis revealed that the results are driven by the modality exhibiting best individual performance, namely SEEG.
Case Report: Coexistence of bullous pemphigoid and psoriasis: Therapeutic challenge and IL17A-targeted parallel treatment strategy

Autoimmune blistering diseases of the skin have all been reported in patients with psoriasis, bullous pemphigoid (BP) being the most frequently observed. The pathophysiologic triggers for BP in psoriatic patients are unclear. Recent observational studies have suggested that chronic psoriatic inflammation may cause pathological changes to the basement membrane zone, thus inducing autoimmunity against BP antigens through cross reactivity and “epitope spreading. ” The coexistence of BP and psoriasis poses challenging therapeutic dilemmas related to the incompatibility of their standard treatments. Considering the probable common immunologic mechanisms in the pathogenesis of these inflammatory skin disorders, a suitable treatment regimen should be applied for their parallel control. We report three patients, who developed BP in the course of preceding long-lasting psoriasis. Secukinumab was administered as first-line treatment with promising therapeutic effect for both skin disorders and long-term disease control in two of the cases. In the third case, parallel disease control was initially achieved with methotrexate. A few years later, secukinumab was used for the treatment of a relapse of both dermatoses but worsening of BP was observed and methotrexate was reintroduced. Our experience on the therapeutic potential of secukinumab in BP is supported by the data in the literature. Recently, it was demonstrated that the proinflammatory cytokine IL17A has a functional role in the process of skin inflammation in BP, similarly to psoriasis. IL17A inhibition has emerged as a promising therapeutic strategy in patients with extensive or refractory BP but paradoxical development of BP after secukinumab treatment for psoriasis has also been described. This controversy emphasizes the need for further investigation into the development of optimal treatment strategies and recommendations.
Patient-derived xenografts or organoids in the discovery of traditional and self-assembled drug for tumor immunotherapy

In addition to the rapid development of immune checkpoint inhibitors, there has also been a surge in the development of self-assembly immunotherapy drugs. Based on the immune target, traditional tumor immunotherapy drugs are classified into five categories, namely immune checkpoint inhibitors, direct immune modulators, adoptive cell therapy, oncolytic viruses, and cancer vaccines. Additionally, the emergence of self-assembled drugs with improved precision and environmental sensitivity offers a promising innovation approach to tumor immunotherapy. Despite rapid advances in tumor immunotherapy drug development, all candidate drugs require preclinical evaluation for safety and efficacy, and conventional evaluations are primarily conducted using two-dimensional cell lines and animal models, an approach that may be unsuitable for immunotherapy drugs. The patient-derived xenograft and organoids models, however, maintain the heterogeneity and immunity of the pathological tumor heterogeneity.
Endoscopic diagnosis and treatment in gastric cancer: Current evidence and new perspectives

Gastric cancer is the fifth most common cause of cancer related deaths worldwide. Despite advancement in endoscopic techniques, the majority of the cases are diagnosed at late stage, when the curative treatment options are very limited. The early gastric cancer (EGC) on the other side is potentially curable, and in selected cases endoscopic resection techniques offer similar survival rates then surgical resection. The detection of EGC is endoscopically challenging and requires high quality examination. Recent data show that close to 10% of the gastric cancer cases had a previous negative endoscopy. This highlights the urgent need to improve the quality of the endoscopy services, what can be achieved by increasing the awareness of gastroenterologists and continuously monitoring the key performance indicators of upper gastrointestinal endoscopy. Newer endoscopic imaging techniques are also becoming commonly available to aid the detection of gastric premalignant lesions and EGC. High-definition endoscopy with image enhancement techniques is preferred over white light endoscopy to recognize these lesions, and they are also useful to determine the invasion depth of EGC. The endoscopic optical characterization of lesions is necessary for the selection of proper resection method and decide whether endoscopic resection techniques can be considered. Artificial intelligence systems aid the detection of EGC and can help to determine the depth of invasion. Endoscopic mucosal resection and endoscopic submucosal dissection requires centralized care and tertiary referral centers with appropriate expertise to ensure proper patient selection, high success rate and low adverse event rate. Appropriately scheduled endoscopic surveillance of high-risk patients, premalignant lesions and after resection of EGC is also important in the early detection and successful treatment of gastric cancer.
Effects of awake prone position vs. usual care on acute hypoxemic respiratory failure in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials

Background Previous studies have shown that an awake prone position may be beneficial for the treatment of acute respiratory distress syndrome (ARDS) or acute hypoxic respiratory failure (AHRF) in patients with COVID-19, but the results are not consistent, especially in terms of oxygenation outcomes and intubation rate. This systematic review and meta-analysis assessed the effects of the awake prone position on AHRF in patients with COVID-19 with all randomized controlled trials (RCTs). Methods An extensive search of online databases, including MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials from 1 December 2019 to 30 October 2022, with no language restrictions was performed. This systematic review and meta-analysis are based on the PRISMA statement. We only included RCTs and used the Cochrane risk assessment tool for quality assessment. Results Fourteen RCTs fulfilled the selection criteria, and 3,290 patients were included. A meta-analysis found that patients in the awake prone position group had more significant improvement in the SpO2/FiO2 ratio [mean difference (MD): 29.76; 95% confidence interval (CI): 1.39–48.13; P = 0.001] compared with the usual care. The prone position also reduced the need for intubation [odd ratio (OR): 0.72; 95% CI: 0.61 to 0.84; P < 0.0001; I2 = 0%]. There was no significant difference in mortality, hospital length of stay, incidence of intensive care unit (ICU) admission, and adverse events between the two groups. Conclusion The awake prone position was a promising intervention method, which is beneficial to improve the oxygenation of patients with ARDS or AHRF caused by COVID-19 and reduce the need for intubation. However, the awake prone position showed no obvious advantage in mortality, hospital length of stay, incidence of ICU admission, and adverse events. Systematic review registration International Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42022367885.
Analysis of cognitive function and its related factors after treatment in Meniere’s disease

A growing body of research recently suggested the association between vestibular dysfunction and cognitive impairment. Meniere’s disease (MD), a common clinical vestibular disorder, is usually accompanied by hearing loss and emotional stress, both of which may mediate the relationship between vestibule dysfunction and cognition. It is currently unknown whether the cognitive decline in MD patients could improve through treatment and how it relates to multiple clinical characteristics, particularly the severity of vertigo. Therefore, in the present study, the MD patients were followed up for 3, 6, and 12 months after treatment, and the cognitive functions, vertigo symptoms, and related physical, functional, and emotional effects of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and Dizziness Handicap Inventory (DHI), aiming to explore the change in cognition before and after therapy and the correlation with various clinical features. It was found that cognitive decline in MD patients compared to healthy controls before therapy. Importantly, this cognitive impairment could improve after effective therapy, which was related to the severity of vertigo, especially in functional and physical impacts. Our results support the view that vestibular dysfunction is a potentially modifiable risk factor for cognitive decline.
Dyslipidemia and serum cystatin C levels as biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus

Background Diabetic nephropathy is a leading cause of end-stage renal disease. The diagnostic markers of nephropathy, including the presence of albuminuria and/or a reduced estimated glomerular filtration rate, are not clinically ideal, and most of them are raised after a significant reduction in renal function. Therefore, it is crucial to seek more sensitive and non-invasive biomarkers for the diagnosis of diabetic nephropathy. Objective of the study This study aimed to investigate the serum cystatin C levels and dyslipidemia for the detection of diabetic nephropathy in patients with type 2 diabetes mellitus. Methodology A hospital-based comparative cross-sectional study was conducted from December 2021 to August 2022 in Tikur, Anbessa specialized teaching hospital with a sample size of 140 patients with type2 diabetes mellitus. Socio-demographic data was collected using a structured questionnaire, and 5 mL of blood was collected from each participant following overnight fasting for biochemical analyses. Results In type 2 diabetes patients with nephropathy, we found significant lipoprotein abnormalities and an increase in serum cystatin C (P < 0.001) compared to those without nephropathy. Serum cystatin C, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein, very low-density lipoprotein, high density lipoprotein, and duration of diabetes were identified as being significantly associated with diabetic nephropathy (P < 0.05) in multivariable logistic regression analysis. The mean values of total cholesterol levels, triglyceride levels, and high-density lipoprotein cholesterol levels were also found to be significantly higher (P < 0.05) in females as compared to male type-2 diabetic patients. The fasting blood glucose levels and lipid profiles of the participants were found to be significantly associated with serum cystatin C levels. Conclusion The present study found significant serum cystatin C and lipoprotein abnormalities in T2DM patients with diabetic nephropathy when compared with those without diabetic nephropathy, and these lipoprotein abnormalities were significantly associated with serum cystatin C levels.