Miracle-dz/UniFAR-FTUs huggingface dataset:
The evolving treatment landscape of chronic lymphocytic leukemia.

PURPOSE OF REVIEW This review provides guidance in the rapidly changing scenario of chronic lymphocytic leukemia (CLL) treatment. New studies as well as updates of other seminal ones have been recently presented and are likely to change the management of patients with CLL in everyday clinical practice. RECENT FINDINGS Kinase inhibitors (e.g. ibrutinib and idelalisib) have transformed the treatment paradigm in CLL in both front-line and relapsed/refractory patients. Longer follow-up data are now available supporting the safety of ibrutinib and the continuous administration required per current label. Novel studies show the superiority of the drug alone or in combination with monoclonal antibodies compared with standard chemoimmunotherapy. The combination of venetoclax and obinutuzumab (treatment-naïve, only in United States) or rituximab (relapsed/refractory) has granted approval from the regulatory authorities in United States and Europe, based on phase 3 randomized studies. These novel chemo-free combinations allow for fixed-duration treatment and undetectable minimal residual disease. Novel targeted strategies including second and third generation BTK and PI3K inhibitors are currently under investigation and promise to further improve the CLL treatment armamentarium. The chimeric-antigen receptor (CAR) T cells are coming to the stage with promising efficacy and new challenges. SUMMARY A bright chemo-free era for CLL patients is just around the corner. A deep knowledge of currently available evidences is key to tailor treatment choice and optimize long-term tolerability and disease control. Fixed-duration combinations are investigated to allow treatment holidays and avoid the emergence of resistant clones under the selective pressure of continuous treatment.
Immune-mediated polyarthritis

Basics OVERVIEW • “Erosive” refers to “wearing away” or “eating into”; “immune-mediated” refers to a condition caused by the response of the immune system; “polyarthritis” is the medical term for inflammation of several/many joints • “Erosive, immune-mediated polyarthritis” is an immune-mediated inflammatory disease of joints that results in wearing away (that is, erosion) of joint cartilage in several joints • Destruction of bone is evident on x-rays (radiographs) of affected joints
Prognostic value and association of Lauren classification with VEGF and VEGFR-2 expression in gastric cancer

Gastric cancer (GC) is one of the most common malignant tumors in the world. As anti-angiogenic therapy shows efficacy in the treatment of GC, but only works in certain patients, the identification of potential beneficiaries are urgently required in order to apply appropriate treatments. The Lauren classification demonstrates numerous differences in etiology, epidemiology and pathology; however, the association between Lauren classification and pro-angiogenic factors remains unclear. The present study aimed to investigate the clinicopathological factors associated with Lauren classification and the prognostic significance of Lauren classification and vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) expression in GC. Paraffin-embedded GC tissues and clinical information of 255 patients with GC were collected. The clinicopathological factors associated with Lauren classification were evaluated by Logistic regression analysis. Kaplan-Meier survival and Cox regression analyses were used to examine the prognostic significance of Lauren classification and of VEGF and VEGFR-2 expression in patients with GC. The results demonstrated that there was no association between Lauren classification and VEGF and VEGFR-2 expression. Furthermore, results from survival analysis demonstrated that Lauren classification (P=0.001) and Tumor-Node-Metastasis stage (stage II, P=0.002; stage III, P<0.001) were independent prognostic factors in GC. Following subgroup analysis based on Tumor-Node-Metastasis stage, Lauren classification was demonstrated to be an independent prognostic factor in patients with stage III GC (P=0.010) but not in patients with stage I or II GC. Furthermore, VEGFR-2 overexpression was an independent predictor of survival in intestinal-type GC (P=0.040) but not in diffuse-type GC. Taken together, these results indicate that Lauren classification may serve as an independent prognostic factor for patients with GC. In addition, although the expression of VEGF and VEGFR-2 was not associated with Lauren classification, VEGFR-2 overexpression may be considered as an independent prognostic factor in intestinal-type GC.
Comprehensive Analysis of a Competing Endogenous RNA Network Identifies Seven-lncRNA Signature as a Prognostic Biomarker for Melanoma

Long non-coding RNAs (LncRNAs) can act as competing endogenous RNA (ceRNA) involving in tumor initiation and progression. Nevertheless, the prognostic roles of lncRNAs in lncRNA-related ceRNA network of melanoma remain elusive. In this study, RNA sequence profiles were downloaded from The Cancer Genome Atlas (TCGA) database, and there were 2020 differentially expressed messenger RNAs (DEmRNAs), 438 differentially expressed lncRNAs (DElncRNAs) and 65 differentially expressed microRNAs (DEmiRNAs) between primary and metastasis melanoma patients. A ceRNA regulatory network was constructed based on the DElncRNAs-DEmiRNAs and DEmiRNAs-DEmRNAs interactions, which contained 39 lncRNAs, 10 miRNAs, and 16 mRNAs. Furthermore, univariate and multivariate Cox regression analysis were carried out to establish a 7-lncRNA prognostic signature. Subsequently, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve and the Kaplan-Meier risk survival analysis revealed the significant performance of this signature. Finally, pathway enrichment analyses implied that lncRNA MIR205HG and MIAT were associated with multiple cancer-related pathways, especially epidermis development and immune response. The current study provides novel insights into the lncRNA-related ceRNA network and the potential of lncRNAs to be candidate prognostic biomarkers and therapeutic targets in melanoma.
Benign Breast Disease in Women.

BACKGROUND Most clinical breast changes in women are benign; in only 3% to 6% of cases are they due to breast cancer. How- ever, there is a lack of up-to-date, evidence-based treatment recommendations for the various benign differential diagnoses. METHODS Selective literature search of PubMed from 1985 to May 2019, including current national (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften [Association of Scientific Medical Societies in Germany]) and inter- national guidelines. RESULTS Mastalgia and fibrocystic changes are common (around 50% of all women over the age of 30). Fibroadenomas occur in 25% of women; they are the most common benign tumors of the breast and do not require treatment. With most benign breast changes the risk of dedifferentiation is very low. However, it is important in the differential diagnosis to distinguish between such benign changes and breast cancer or changes that carry a risk of malignancy. Complex cysts, for example, carry a risk of malig- nancy of 23% to 31%, papillary lesions 16% , and radial scars 7%. Where there is doubt, histological confirmation should be sought by means of percutaneous biopsy. CONCLUSION Benign breast changes can be definitively distinguished from malignant lesions through the selective use of avail- able diagnostic investigations and interdisciplinary collaboration. When lesions of uncertain malignant potential are found (B3 in the biopsy classification), complete excision is indicated. Prospective studies on the early diagnosis of breast cancer in lesions carrying a risk of malignancy are desirable.
Skin lesions caused by Orthopoxvirus in children

Introduction The global eradication of smallpox and abandonment of mandatory smallpox vaccination has led to an increased proportion of the population who are immunologically naïve to infections caused by Orthopoxviruses (OPV). Aim To present the different courses of OPV infection in children and to highlight the diagnostic difficulties in their differentiation from the other inflammatory processes. Material and methods We retrospectively evaluated the medical documentation of 5 children with OPV infection. Clinical diagnosis of OPV infection was based on evaluation of animal contact and skin symptoms, characterised by either a single ulcer or disseminated lesions. In all five cases, blood samples and skin swabs were collected from the lesion(s) to identify specific OPV DNA fragments (Vgf, b9R and D11L genes) using PCR. Results Two children presented with high fever, a single ulcer on the skin and local lymphadenopathy. The three other patients were in good general health and their skin lesions presented as a disseminated vesicular rash. Using the Vgf gene as the target for PCR, OPV infection was confirmed in material collected from skin lesions of all children and in blood samples of 4 children. The B9R and d11L genes tested positive in the skin material of 2 children and blood samples of 2 children. All analysed patients presented a history of ineffective antibiotic therapy. Conclusions In the case of unclear necrotising skin lesions in children, the primary diagnosis always includes bacterial dermatitis. However, if the patient has come into contact with animals, diagnosis of OPV infection should also be considered.
Physiological maturation stage of cervical vertebrate index in cleft lip/palate and non-cleft lip/palate patients

Cleft lip and palate is one of the most common congenital anomalies. Cleft lip and palate patients encounter growth problems in lip and palate area, although their overall growth and development remains unknown. Cervical vertebral maturation are indicators of physiological maturation used in interceptive treatment and orthognathic surgery. The present study aims to determine physiological maturation stage of cervical vertebrae maturation index in cleft andnon-cleft patients. Lateral cephalogram of 26 cleft patients and 27 non-cleft patients with a range of chronological age from 8-16 years old were involved. The cervical vertebrae maturation were analyzed in six stages of cervical vertebrae maturation method of Hassel and Farman. Data were analyzed using t-test (p≤ 0.05). The result shows that physiologicalmaturation stage of cervical vertebrae maturation index in cleft and non-cleft patients has no significant difference in stage acceleration (p= 0.38), stage transition (p= 0.41) and deceleration (p= 0.39). Likewise, there is no significant difference in physiological maturation stage of cervical vertebrae maturation index between cleft and non-cleft patients.
Incidence of portal vein thrombosis after splenectomy and its influence on transjugular intrahepatic portosystemic shunt stent patency

BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) is widely accepted as an alternative to surgery for management of complications of portal hypertension. TIPS has been used to treat portal vein thrombosis (PVT) in many centers since the 1990s. Although TIPS has good therapeutic effects on the formation of PVT, the effect of PVT on TIPS stenting has rarely been reported. Patients with splenectomy and pericardial devascu-larization have a high incidence of PVT, which can markedly affect TIPS stent patency and increase the risk of recurrent symptoms associated with shunt stenosis or occlusion. AIM To investigate the incidence of PVT after splenectomy and its influence on the patency rate of TIPS in patients with cirrhosis and portal hypertension. METHODS Four hundred and eighty-six patients with portal hypertension for refractory ascites and/or variceal bleeding who required TIPS placement between January 2010 and January 2016 were included in this retrospective analysis. Patients without prior splenectomy were defined as group A (n = 289) and those with prior splenectomy as group B (n = 197). The incidence of PVT before TIPS was compared between the two groups. After TIPS placement, primary patency rate was compared using Kaplan–Meier analysis at 3, 6, 9 and 12 mo, and 2 and 3 years. The clinical outcomes were analyzed. RESULTS Before TIPS procedure, the incidence of PVT in group A was lower than in group B (P = 0.003), and TIPS technical success rate in group A was higher than in group B (P = 0.016). The primary patency rate in group A tended to be higher than in group B at 3, 6, 9 and 12 mo, 2 years and 3 years (P = 0.006, P = 0.011, P = 0.023, P = 0.032, P = 0.037 and P = 0.028, respectively). Recurrence of bleeding and ascites rate in group A was lower than in group B at 3 mo (P ≤ 0.001 and P = 0.001), 6 mo (P = 0.003 and P = 0.005), 9 mo (P = 0.005 and P = 0.012), 12 mo (P = 0.008 and P = 0.024), 2 years (P = 0.011 and P = 0.018) and 3 years (P = 0.016 and P = 0.017), respectively. During 3-years follow-up, the 1-, 2- and 3-year survival rate in group A were higher than in group B (P = 0.008, P = 0.021, P = 0.018, respectively), but there was no difference of the incidence of hepatic encephalopathy (P = 0.527). CONCLUSION Patients with prior splenectomy have a high incidence of PVT, which potentially increases the risk of recurrent symptoms associated with shunt stenosis or occlusion.
Changing attitudes to mathematics in primary school teachers in England

ABSTRACT Concern about attitudes to mathematics and mathematics education is not unique to England. Studies across the world, including the USA, Canada and Australia, indicate similar concerns. This research aimed to identify the factors that impacted on the formation of teachers’ attitudes to mathematics in primary schools in England and to discover how these have been shaped and/or changed during an in-service professional development programme, The Mathematics Specialist Teacher Programme (MaST). We thus take a unique position in attempting to develop a possible model for reducing teacher mathematics anxiety, and its consequences in classrooms. Findings were analysed using key typologies of professional learning and and revealreveal that teachers who undertook the programme made strong, explicit links between previous experiences of being taught mathematics, their own feelings of mathematics confidence and competence, and levels of mathematics anxiety. High-level collaboration with colleagues and expert facilitators were evident as significant factors in overcoming this anxiety.
Identification and performance evaluation of housekeeping genes for microRNA expression normalization by reverse transcription-quantitative PCR using liquid-based cervical cytology samples

Screening for cervical cancer by cytology has been effective in reducing the worldwide incidence and mortality rates of this disease. However, a number of studies have demonstrated that the sensitivity of conventional cervical cytology may be too low for detection of cervical intraepithelial neoplasias (CIN). Therefore, it is important to incorporate more sensitive molecular diagnostic tests that could substantially improve the detection rates and accuracy for identifying CIN lesions. MicroRNAs (miRNAs) are a class of small non-coding RNAs with the potential to provide robust non-invasive cancer biomarkers for detecting CIN lesions in liquid-based cervical cytology (LBC) samples. At present, there is no consensus on which are the best housekeeping genes for miRNA normalization in LBC. The present study aimed to identify housekeeping genes with consistent and reproducible performance for normalization of reverse transcription-quantitative PCR (RT-qPCR) expression analysis of miRNA using LBC samples. The present study firstly selected six potential candidate housekeeping genes based on a systematic literature evaluation. Subsequently, the expression levels of microRNAs U6, RNU-44, RNU-47, RNU-48, RNU-49 and hsa-miR-16 were measured in 40 LBC samples using RT-qPCR. The stability of each potential housekeeping gene was assessed using the NormFinder algorithm. The results revealed that U6 and RNU-49 were the most stable genes among all candidates requiring fewer amplification cycles and smaller variation across the sample set. However, RNU-44, RNU-47, RNU-48 and hsa-miR-16 stability exceeded the recommended housekeeping value suitable for normalization. The findings revealed that U6 may be a reliable housekeeping gene for normalization of miRNA RT-qPCR expression analysis using LBC samples.
An Investigation into the Significance and Effect of Bowel and Bladder Dysfunction on Personal Burden for People Who Have Parkinson’s Disease

This research centres on the experiences of people with Parkinson's disease (PD) and how they perceive two autonomic non-motor symptoms, bowel and bladder dysfunction, both highly associated with PD. Many studies have addressed urinary and faecal incontinence among general populations; however, few have focused on populations of people with PD. Further, no evidence of the personal burden that is associated with the presence of these autonomic dysfunctions has been reported. The position of this thesis is that the burden experienced by people with PD who also suffer from bowel and bladder dysfunction significantly affects their ability to fully participate in a social life and that the current clinical management used to treat either of these two symptoms fails to alleviate their burdensomeness. Using a novel mix of qualitative and quantitative research methods it was possible to identify the type, presence and legitimacy of the symptoms experienced by participants; how they searched for and used available clinical resources; and whether their search for additional personal resources alleviated or cause additional burdens and disruptions to their life quality. The study comprised 67 people with PD who were experiencing a bowel or bladder dysfunction or a combination of both. They completed a series of quantitative surveys and answered semi-structured interview questions focused on the symptoms and their current management. Quantitative data were subjected to a range of descriptive and inferential statistical analyses and, to bring participants' perceptions to the forefront, qualitative data were converted into participant-generated quantitative burden scales that were used to statistically compare and contrast all other quantitative data sets, in gauging the severity and importance of the participants’ experiences. This process ensured the participants’ voices remained central though out the study.
Circulating syndecan-1 as a novel biomarker relates to lung function, systemic inflammation, and exacerbation in COPD

Introduction Patients with COPD often show increased systemic inflammation which is associated with lower functional status, greater exacerbation risk, and worse clinical outcomes. Syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs), have been found to involve in inflammatory processes in many chronic inflammatory diseases. The aim of this preliminary clinical study was to investigate the possible association between two SDCs, SDC-1 and SDC-4, with lung function, systemic inflammation, and risk of exacerbations in COPD patients. Method Serum SDC-1 and SDC-4 levels were measured in 101 COPD patients and 57 health controls. Correlations between SDCs and other parameters were analyzed using Spearsman’s rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status. Results Although both serum SDC-1 and SDC-4 showed a downward trend in COPD patients, only SDC-1 levels were correlated positively with the ratio of FEV1/FVC and parameters of small airway obstruction. Besides, SDC-1 but not SDC-4, was negatively correlated with C-reactive protein (CRP) in COPD patients and downregulated in frequent exacerbators (FEs) of COPD. Using a cutoff value of 2.08 ng/mL, the sensitivity and specificity of SDC-1 to differentiate FE were 44% and 93.4%, respectively. Conclusion In conclusion, circulating SDC-1 may be a novel inflammatory biomarker associated with lung function and systemic inflammation in patients with COPD, which could also be useful to identify the risk of COPD exacerbation. Further studies should be performed to clarify the influences of SDC-1 on the pathogenesis and outcomes of COPD.
HUBUNGAN TEKNIK MENERAN DENGAN KEJADIAN RUPTURE PERINEUM

Mechanical menerant is an influence on the incidence of perineal rupture in normal delivery that causes postpartum hemorrhage. Postpartum hemorrhage is the main cause of 40% of maternal deaths in Indonesia in 2010. The results of the initial survey in Midwefery Hause Practice”N” that the incidence of perineal rupture is caused by incorrect technique menerant. This study aims to determine the relationship menerant techniques with perineum rupture incidence in normal birth mothers in BPM. N Padang Panjang 2015.This type of research is analytic survey. This research is implemented from April to May in BPM. N. Data collection techniques are the primary data collected by observation with checklis sheet. Respondents in this study were all normal birth mothers in Midwifery House Practice is counted from April to May 2015 using the technique of taking samples obtained accidental sampling and sample 32 with chis-squre test.Most respondents are correct technique who experienced rupture menerant 2 (6.3%), which does not mengalalami rupture 7 (21, 9%). While the mother can not menerant who experienced rupture 23 people (71.9%). Results showed that there is a correlation with the incidence of rupture menerant techniques perineum in primigravida and multigravida (p = 0.000). Conclusion of this research is that there is a relationship meneran technique with perineum rupture incidence in normal birth mothers in midwifery haose Practice“N” Padang Panjang in 2015. if menerant mother is not correct then the resulting incidence of rupture perineum. Suggestions for Helper lead time of delivery menerant correct technique teaches that there are no eyents perineum.
Albumin to fibrinogen ratio and fibrinogen to pre-albumin ratio are economical, simple and promising prognostic factors for solid malignancy.

The exploration of cancer prognostic factor has received increasing attention in recent years. Traditional indicators such as tumor-node-metastasis system, histological subtype and carcinoembryonic antigen (CEA) have been recognized as prognostic indicators. However, invasiveness and high cost of these factors restrict the widespread use in clinic, particularly in economically underdeveloped basic health units. Therefore, economic, simple and effective biomarkers are warranted to manage and improve prognosis of cancer individuals.
The impact of multiple rounds of indoor residual spraying on malaria incidence and haemoglobin levels in a high transmission setting.

BACKGROUND Indoor residual spraying is widely used as a vector control measure although there are conflicting findings of its effectiveness in reducing malaria incidence. The objective of this study was to estimate the effect of multiple indoor residual spraying (IRS) rounds on malaria incidence and haemoglobin levels in a cohort of children in rural southeastern Uganda. METHODS The study was based upon a dynamic cohort of children aged 0.5-10 years enrolled from August 2011 to June 2017 in Nagongera subcounty. Confirmed malaria infections and haemoglobin levels were recorded over time for each participant. Following each of four rounds of IRS, malaria incidence, haemoglobin levels, and parasite density evaluated and compared to pre-IRS levels. Analyses were carried out at the participant level while accounting for repeated measures and clustering by household. RESULTS Incidence rate ratios comparing post-IRS to pre-IRS incidence rates for age groups 0-3, 3-5, and 5-11 were 0.108 (95% CI 0.078, 0.149), 0.173 (95% CI 0.136, 0.222), and 0.226 (0.187, 0.274), respectively. The mean haemoglobin levels significantly increased from 11.01 (pre-IRS) to 12.18 g/dL (post-IRS). CONCLUSIONS Our study supports the policy recommendation of IRS usage in a stable and perennial transmission area to rapidly reduce malaria transmission.