Miracle-dz/UniFAR-FTUs huggingface dataset:
Cetuximab is efficient and safe in patients with advanced cutaneous squamous cell carcinoma: a retrospective, multicentre study

There is no standard of care for unresectable cutaneous squamous cell carcinoma (cSCC). Chemotherapy, alone or combined with radiotherapy, is commonly used mostly as palliative treatment; moreover, its poor safety profile limits its use most of the time, especially in elderly patients. Thus, alternative options are needed. Targeted molecular inhibitors, such as the epidermal growth factor receptor inhibitor cetuximab, seem promising, but data are limited. We retrospectively evaluated clinical outcomes of cetuximab as a single agent in this indication. The primary endpoint was the Disease Control Rate (DCR) at 6 weeks according to RECIST criteria. Secondary endpoints included DCR at 12 weeks, objective response rate (ORR) at 6 and 12 weeks, progression-free-survival (PFS), overall survival (OS), and safety profile. Fifty-eight patients received cetuximab as monotherapy. The median age was 83.2 (range, 47.4 to 96.1). The majority of patients was chemotherapy naïve. The median follow-up was 11.7 months (95% CI: 9.6-30.1). The DCR at 6 and 12 weeks was 87% and 70%, respectively. The ORR was 53% and 42%, respectively, at 6 and 12 weeks. The median PFS and OS were 9.7 months (95% CI: 4.8-43.4) and 17.5 months (95% CI: 9.4-43.1), respectively. Fifty-one patients (88%) experienced toxicity, and 67 adverse events related to cetuximab occurred. Most of them (84%) were grade 1 to 2. Our study shows that cetuximab is safe and efficient for the treatment of patients, even elderly ones, with advanced cSCC. These results indicate that cetuximab is a promising agent to test in new combinations, especially with immune checkpoint inhibitors such as anti–PD-1 agents.
Brain atrophy and employment in multiple sclerosis patients: a 10-year follow-up study

Background Multiple sclerosis is often associated with unemployment. The contribution of grey matter atrophy to unemployment is unclear. Objectives To identify magnetic resonance imaging biomarkers of grey matter and clinical symptoms associated with unemployment in multiple sclerosis patients. Methods Demographic, clinical data and 1.5 T magnetic resonance imaging scans were collected in 81 patients at the time of inclusion and after 5 and 10 years. Global and tissue-specific volumes were calculated at each time point. Statistical analysis was performed using a mixed linear model. Results At baseline 31 (38%) of the patients were unemployed, at 5-year follow-up 44 (59%) and at 10-year follow-up 34 (81%) were unemployed. The unemployed patients had significantly lower subcortical deep grey matter volume (P < 0.001), specifically thalamus, pallidus, putamen and hippocampal volumes, and cortical volume (P = 0.011); and significantly greater T1 (P < 0.001)/T2 (P < 0.001) lesion volume than the employed patient group at baseline. Subcortical deep grey matter volumes, and to a lesser degree cortical volume, were significantly associated with unemployment throughout the follow-up. Conclusion We found significantly greater atrophy of subcortical deep grey matter and cortical volume at baseline and during follow-up in the unemployed patient group. Atrophy of subcortical deep grey matter showed a stronger association to unemployment than atrophy of cortical volume during the follow-up.
Allelic H3K27me3 to allelic DNA methylation switch maintains noncanonical imprinting in extraembryonic cells

Maternal H3K27me3–mediated imprinting switches to allelic DNA methylation to maintain imprinted expression in extraembryonic cells. Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation–dependent (canonical) imprinting is relatively stable during development, the recently found oocyte-derived H3K27me3-mediated noncanonical imprinting is mostly transient in early embryos, with some genes important for placental development maintaining imprinted expression in the extraembryonic lineage. How these noncanonical imprinted genes maintain their extraembryonic-specific imprinting is unknown. Here, we report that maintenance of noncanonical imprinting requires maternal allele–specific de novo DNA methylation [i.e., somatic differentially methylated regions (DMRs)] at implantation. The somatic DMRs are located at the gene promoters, with paternal allele–specific H3K4me3 established during preimplantation development. Genetic manipulation revealed that both maternal EED and zygotic DNMT3A/3B are required for establishing somatic DMRs and maintaining noncanonical imprinting. Thus, our study not only reveals the mechanism underlying noncanonical imprinting maintenance but also sheds light on how histone modifications in oocytes may shape somatic DMRs in postimplantation embryos.
Provision of Care to Preterm Infants at Resource Limited Health Facilities of Mopani District, South Africa

Background: Inadequate neonatal facilities in rural areas is one of the challenges affecting the management of preterm infants. In low income countries with limited resources, over 90% of preterm babies die within few days of life. Purpose: The purpose of this study was to describe the challenges encountered by midwives when providing care to preterm infants at resource limited health facilities in Limpopo Province, South Africa. Methods: Qualitative research approach, using exploratory and descriptive design was used. Non-probability purposive sampling was used to select twenty three midwives who had an experience of two or more years in maternity. Data was collected using unstructured individual interviews, which were voice recorded and transcribed and data analysed qualitatively through the open-coding method. Findings: Revealed one theme, preterm condition and expected care; with sub-themes namely; perceived causes of preterm complications and deaths, preterm babies experience several difficulties which need specialised care, the need for constant individualised care and monitoring of preterm infants by midwives, functional relevant equipment needed for care of preterm infants, a need for constant training for midwives regarding care of preterm infants, and importance for a proper structure to house preterm infants which will lead to quality care provision. Conclusion: Preterm babies need simple essential care such as warmth, feeding support, safe oxygen use and prevention of infection. Lack of adequate resources and limited skills from midwives could contribute to morbidity and mortality. Health facility managers need to create opportunities for basic and advanced preterm care to equip the skills of midwives by sending them to special trainings such as Limpopo Initiative Neonatal Care (LINC), Helping Baby Breath (HHB) and Neonatal Intensive Care Unit (NICU). Operational managers should be involved in the identification, procurement and supply of required equipment. Continuous health education should be provided on the mothers about kangaroo mother care (KMC) and measures to prevent infections in the neonatal unit.
Enhancement of service life of polymer electrolyte fuel cells through application of nanodispersed ionomer

We demonstrate the use of a supercritical fluid treatment for creating ionomer nanodispersions for fuel cell cathodes. In polymer electrolyte fuel cells (PEFCs), protons from the anode are transferred to the cathode through the ionomer membrane. By impregnating the ionomer into the electrodes, proton pathways are extended and high proton transfer efficiency can be achieved. Because the impregnated ionomer mechanically binds the catalysts within the electrode, the ionomer is also called a binder. To yield good electrochemical performance, the binder should be homogeneously dispersed in the electrode and maintain stable interfaces with other catalyst components and the membrane. However, conventional binder materials do not have good dispersion properties. In this study, a facile approach based on using a supercritical fluid is introduced to prepare a homogeneous nanoscale dispersion of the binder material in aqueous alcohol. The prepared binder exhibited high dispersion characteristics, crystallinity, and proton conductivity. High performance and durability were confirmed when the binder material was applied to a PEFC cathode electrode.
Histopathological analysis of sinonasal lesions associated with chronic rhinosinusitis and comparison with computed tomography diagnoses

Background &Objective: Chronic rhino sinusitis (CRS) is an inflammatory condition of the paranasal sinuses and the nasal passage lasting more than three months either with or without sinonasal polyps. This study aimed to report the common sinonasal lesions associated with CRS according to the histopathology results, to compare between clinical and histopathological diagnoses, and to compare between radiological and histopathological diagnoses of the sinonasal lesions. Methods: A retrospective study of the electronic records of 82 patients diagnosed with CRS with nasal polyps. All patients underwent endoscopic sinus surgery and histopathological examination of surgical biopsies. The collected data were analyzed using SPSS program. Coparison between clinical and histopathological diagnoses was done. This study was conducted at Alsafwa Consultative Medical center (ACMC) in Almukalla city, Hadhramout province in Republic of Yemen. Results: Out of 82 patients, the ages ranged from 4 to 90 years (mean: 34.48±17.74 years), and 54.88% were females. Inflammatory polyps were the most common lesion (31.4%), then allergic polyps (30.5%). Nasopharyngeal carcinoma (NPC) was reported in 9.8% of the lesions and all were unilateral. The results revealed strong compatibility between clinical and histopathological diagnoses (p<0.001, kappa= 0.215), and significant compatibility between radiological and histopathology diagnoses (p=0.007). Conclusion: Inflammatory and allergic polyps are the most common benign bilateral lesions associated with chronic rhinosinusitis, which can be correctly diagnosed clinically in most cases. Unilateral nasal polyps have high rates of malignancies and should be check carefully by endoscopy and histopathology. Computed tomography has some pitfalls in diagnosing of fungal sinusitis.
Unidirectional rotating molecular motors dynamically interact with adsorbed proteins to direct the fate of mesenchymal stem cells

Molecular motion of rotating motors delegates surface-adsorbed protein–stem cell interactions. Artificial rotary molecular motors convert energy into controlled motion and drive a system out of equilibrium with molecular precision. The molecular motion is harnessed to mediate the adsorbed protein layer and then ultimately to direct the fate of human bone marrow–derived mesenchymal stem cells (hBM-MSCs). When influenced by the rotary motion of light-driven molecular motors grafted on surfaces, the adsorbed protein layer primes hBM-MSCs to differentiate into osteoblasts, while without rotation, multipotency is better maintained. We have shown that the signaling effects of the molecular motion are mediated by the adsorbed cell-instructing protein layer, influencing the focal adhesion–cytoskeleton actin transduction pathway and regulating the protein and gene expression of hBM-MSCs. This unique molecular-based platform paves the way for implementation of dynamic interfaces for stem cell control and provides an opportunity for novel dynamic biomaterial engineering for clinical applications.
Systemic oncolytic adenovirus delivered in mesenchymal carrier cells modulate tumor infiltrating immune cells and tumor microenvironment in mice with neuroblastoma

Celyvir (autologous mesenchymal cells -MSCs- that carry an oncolytic adenovirus) is a new therapeutic strategy for metastatic tumors developed by our research group over the last decade. There are limitations for studying the immune effects of human oncolytic adenoviruses in murine models since these viruses do not replicate naturally in these animals. The use of xenografts in immunodeficient mice prevent assessing important clinical aspects of this therapy such as the antiadenoviral immune response or the possible intratumoral immune changes, both of tumor infiltrating leukocytes and of the microenvironment. In our strategy, the presence of MSCs in the medicinal product adds an extra level of complexity. We present here a murine model that overcomes many of these limitations. We found that carrier cells outcompeted intravenous administration of naked particles in delivering the oncolytic virus into the tumor masses. The protection that MSCs could provide to the oncolytic adenovirus did not preclude the development of an antiadenoviral immune response. However, the presence of circulating antiadenoviral antibodies did not prevent changes detected at the tumor masses: increased infiltration and changes in the quality of immune cells per unit of tumor volume, and a less protumoral and more inflammatory profile of the tumor microenvironment. We believe that the model described here will enable the study of crucial events related to the immune responses affecting both the medicinal product and the tumor.
Is there a difference in FDG PET findings of invasive ductal carcinoma of the breast with and without coexisting DCIS?

Objective(s): Studies have reported that invasive ductal carcinoma (IDC) with coexisting ductal carcinoma in situ (DCIS) show lower metastatic potential and recurrence and better overall survival than pure IDC. In this study, we assessed F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of patients with newly diagnosed IDC to determine if there is any difference in PET findings in IDC-DCIS and pure IDC cases. Methods: FDG PET/CT images of patients with newly diagnosed IDC of the breast who subsequently underwent breast surgery and had histopathology result in our records were further evaluated. Tumor grade, pathological staging, and presence of DCIS were noted from the histopathology results. Standardized uptake value (SUV) of the primary tumor (SUVmax and SULmax), other hypermetabolic foci in the breast, and ipsilateral normal breast were measured. Presence of axillary and distant metastases was noted. Results: Fifty seven (57) patients with IDC were included. Coexisting DCIS was present in 44 (IDC-DCIS) and not present in 13 (pure IDC) cases. Per histopathology, the primary tumor was unifocal in 33 IDC-DCIS (75%) and 12 pure IDC (92.3%) cases, and multifocal in 11 IDC-DCIS cases (25%), and 1 pure IDC case (7.7%). FDG uptake was multifocal in 20 IDC-DCIS cases (45.5%) and 1 pure IDC case (7.7%), and unifocal in 24 IDC-DCIS (54.5%), and 12 pure IDC (92.3%) cases. There was no significant difference in patient age, size of the primary tumor, SUVmax and SULmax of the primary tumor and SUVmax of the normal breast in IDC-DCIS and pure IDC cases (p>0.05). Pathology showed axillary metastasis in all 13 pure IDC (100%), and 27 IDC-DCIS (61.4%) cases. PET showed axillary uptake in 25 IDC-DCIS (56.8%), and 8 pure IDC (61.5%) cases, and abnormal/questionable distant uptake in 12 IDC-DCIS cases and 1 pure IDC case. Conclusion: In our preliminary findings, multifocal breast FDG uptake and multifocal tumor appear to be more common in IDC-DCIS than pure IDC. There is no significant difference in SUV and size of the primary tumor in IDC-DCIS and pure IDC cases. Axillary metastases appear to be more common in pure IDC than IDC-DCIS cases.
Quality of life of students of a private medical college

Objective: To determine the quality of life of students of a private medical college in Karachi in Pakistan. Methods: This cross sectional study was conducted among 217 medical students of Liaquat College of Medicine and Dentistry, Karachi from June 2017 to March 2018. Students were selected by a stratified sampling method and the World Health Organization Quality of Life BREF Instruments (WHO QOL-BREF) was used for the above-mentioned study. Statistical analysis was performed using SPSS (Statistical Package for Social Sciences) version 21 and Analysis of variance (ANOVA). Independent t-test was used as p <0.05 significant. Results: A total of 250 questionnaires were distributed among 2nd year, 3rd year, 4th year and final year students and the response rate was 86.8%. Among them 48.5% (n=105) students were male and 51.5% (n=112) students were female, while 9.2% (n=20) students were currently ill and the other 90.8% (n=197) were healthy. Conclusion: Medical education influences the quality of life (QOL) of students adversely. Social relationships and environmental domain were satisfactory in private medical institutes whereas physical and psychological progress was low due to academic load which requires improvement either by physical activities such as fitness classes or other extra-curricular activities.
Clinical And Economic Burden Of Eosinophilic COPD In A Large Retrospective US Cohort

Purpose We sought to describe clinical and economic outcomes for COPD patients by blood eosinophil (EOS) count. Methods This retrospective cohort study of COPD patients used data from the Practice Fusion electronic medical records (EMR) database linked to Symphony Health Solutions transactional pharmacy, medical, outpatient, and inpatient claims data to evaluate COPD-related and all-cause health care resource utilization and cost in the 12-month period following the date of each patient’s greatest recorded blood eosinophil count during the 27-month period from January 2014 to March 2016. A post-index moderate exacerbation was defined as an outpatient or emergency care visit for COPD and a prescription for oral corticosteroid and/or antibiotics within 10 days of the visit. Severe exacerbation was defined as an inpatient hospitalization with COPD as primary diagnosis. Results Of 48,090 EMR patients, 39,939 (83.1%) had a charge in the claims data both pre- and post-index (mean age 67.2 years, 58.3% female), 17,397 (43.6%) had EOS ≥220 cells/µL. Moderate and severe exacerbations were more frequent for patients with EOS≥220 cells/µL compared with those with EOS <220 cells/µL (moderate: 6.8% vs 6.1%, p<0.05; severe: 3.1% vs 2.5%, p<0.001). After adjustment for baseline clinical characteristics, each 100-unit increase in EOS count was associated with a significant 2.24% increase in total all-cause costs and 4.54% increase in total COPD-related costs (p<0.001 for both). COPD-related costs were significantly greater for patients with an EOS count of ≥220 cells/µL compared with those with EOS <220 cells/µL (p<0.001). These costs appear to have been driven by a greater percentage of patients in the ≥220 cells/µL cohort with COPD-related resource use including hospitalization, office visits, ambulatory procedures and pharmacy prescriptions. Conclusion COPD patients with EOS counts ≥220 cells/µL were more likely to have had moderate or severe exacerbations and greater cost of care than those with EOS <220 cells/µL.
Effects of Extracorporeal Magnetic Stimulation in Fecal Incontinence

Abstract Background Fecal incontinence (FI) is a common condition that has devastating consequences for patients’ QOL. In some patients, the conventional functional pelvic floor electrical stimulation has been effective but is an invasive and embarrassing treatment. The object of the study was to evaluate the feasibility of functional extracorporeal magnetic stimulation (FMS) in strengthening the pelvic floor muscles without an anal plug and the embarrassment of undressing. Materials and Methods Thirty patients (26 female and 4 males) with FI were enrolled. All patients were assessed during a specialized coloproctology evaluation followed by endoanal ultrasonography and anorectal manometry. All patients underwent an FMS treatment once weekly for 8 weeks. Patients’ outcome was assessed by the Cleveland Clinic Fecal Incontinence Score (CCFIS) and by the fecal incontinence QOL questionnaire (FIQL). Results After 8 weeks, the number of solid and liquid stool leakage per week was significantly reduced (p<0.05) with a significant improvement of the CCFIS and of the FIQL (p<0.05). Moreover, the authors recorded a missed recruitment of the agonist and antagonists’ defecation muscles. Conclusion FMS is a safe, non-invasive and painless treatment for FI. It could be recommended for selected patients with non-surgical FI to ensure a rapid clinical improvement.
Contralateral Lateral Femoral Condyle Allografts Provide an Acceptable Surface Match for Simulated Classic Osteochondritis Dissecans Lesions of the Medial Femoral Condyle

Background: Osteochondral allograft transplantation is an effective technique for repairing large lesions of the medial femoral condyle (MFC), but its use is limited by graft availability. Purpose/Hypothesis: The present study aimed to determine whether contralateral lateral femoral condyle (LFC) allografts can provide an acceptable surface match for posterolateral MFC lesions characteristic of classic osteochondritis dissecans (OCD). The hypothesis was that LFC and MFC allografts will provide similar surface contour matches in all 4 quadrants of the graft for posterolateral MFC lesions characteristic of OCD. Study Design: Controlled laboratory study. Methods: Ten fresh-frozen recipient human MFCs were each size-matched to 1 ipsilateral medial and 1 contralateral LFC donor (N = 30 condyles). After a nano–computed tomography (nano-CT) scan of the native recipient condyle, a 20-mm circular osteochondral “defect” was created 1 cm posterior and 1 cm medial to the roof of the intercondylar notch (n = 10). A size-matched, random-order donor MFC or LFC plug was then harvested, transplanted, and scanned with nano-CT. Nano-CT scans were then reconstructed, registered to the initial scan of the recipient MFC, and processed in MATLAB to determine the height deviation (d RMS) between the native and donor surfaces and percentage area unacceptably (>1 mm) proud (%A proud) and sunken (%A sunk). Circumferential step-off height (h RMS) and percentage circumference unacceptably (>1 mm) proud (%C proud) and sunken (%C sunk) were measured using DragonFly software. The process was then repeated for the other allograft plug. Results: Both MFC and LFC plugs showed acceptable step-off heights in all 4 quadrants (range, 0.53-0.94 mm). Neither allograft type nor location within the defect had a significant effect on step-off height (h RMS), surface deviation (d RMS), %A proud, or %A sunk. In general, plugs were more unacceptably sunken than proud (MFC, 13.4% vs 2.4%; LFC, 13.2% vs 8.1%), although no significant differences in %C sunk were seen between allograft types or locations within the defect. In LFC plugs, %C proud in the lateral quadrant (28.0% ± 26.1%) was significantly greater compared with all other quadrants (P = .0002). Conclusion: The present study demonstrates that 20-mm contralateral LFC allografts provide an acceptable surface match for posterolateral MFC lesions characteristic of OCD. Clinical Relevance: With comparable surface matching, MFC and LFC allografts can be expected to present similar stresses on the knee joint and achieve predictably positive clinical outcomes, thus improving donor availability and reducing surgical wait times for matches.