Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of trabectedin in germline BRCA1/2-mutated metastatic breast cancer: results of an international first-in-class phase II study.

BACKGROUND Breast cancer is a heterogeneous disease defined by both germline and somatic abnormalities. In preclinical models, tumors carrying homologous recombination defects are highly sensitive to trabectedin. This phase II trial evaluated the efficacy and safety of trabectedin in BRCA1/2 germline mutation carriers with pretreated metastatic breast cancer (MBC). PATIENTS AND METHODS Trabectedin 1.3 mg/m(2) as a 3-h i.v. infusion was administered every 3 weeks until progression or intolerance. The primary efficacy end point was the objective response rate (ORR) as per RECIST. Secondary efficacy end points comprised time-to-event end points, and changes in tumor volume and expression of tumor marker CA15.3. Safety was evaluated using the NCI-CTCAE. RESULTS Forty BRCA1/2 germline mutation carriers with MBC were included. Confirmed partial response (PR) occurred in 6 of 35 assessable patients [ORR = 17%; 95% confidence interval (CI) 7% to 34%] and lasted 1.4-6.8 months. Median PFS was 3.9 months (95% CI 1.6-5.5 months). Eight patients (21%) showed changes in tumor volume, and 14 (40%) a clinical benefit. Trabectedin-related adverse events were generally mild/moderate, the most common being fatigue, nausea, constipation and anorexia. Severe laboratory abnormalities (neutropenia, transaminase increases) were mostly transient and noncumulative, and were managed by dose adjustments. CONCLUSIONS With the caveat of the limited patient number, trabectedin monotherapy showed activity and was well tolerated in heavily pretreated MBC patients selected for germline BRCA mutation. These results prompt further evaluation of trabectedin alone or combined with other specific drugs in this indication. CLINICALTRIALSGOV NCT00580112.
Macrophage and adipocyte IGF1 maintain adipose tissue homeostasis during metabolic stresses

Insulin‐like growth factor‐1 (IGF1) regulates differentiation and growth of tissues and reduces stress and injury. IGF1 also in a tissue‐specific manner modulates the differentiation and lipid storage capacity of adipocytes in vitro, but its roles in adipose tissue development and response to stress are not known.
Automated Geocoding of Textual Documents: A Survey of Current Approaches

This survey article describes previous research addressing text‐based document geocoding, i.e. the task of predicting the geospatial coordinates of latitude and longitude, that best correspond to an entire document, based on its textual contents. We describe (1) early document geocoding systems that use heuristics over place names mentioned in the text (e.g. names of cities and states), (2) probabilistic language modeling approaches, where generative models are built for different regions in the world (usually considering a discretization based on a rectangular grid) from the words occurring in a set of georeferenced training documents, which are then used to predict per‐region probabilities for previously unseen test documents, (3) combinations of different models and heuristics, including clustering procedures, feature selection approaches, and/or language models built from different sources, and (4) recent approaches based on discriminative classification models.
Knowledge, attitudes and behaviour of Greek adults towards salt consumption: a Hellenic Food Authority project

Abstract Objective To investigate the knowledge, attitudes and behaviour of Greek adults towards salt as well as their differences with respect to gender, age and level of education. Design Cross-sectional, observational survey. Setting Voluntary participation to a telephone interview, using a seventeen-item questionnaire. Subjects Greek adults aged over 25 years (n 3609), nationally representative according to age, gender and geographical distribution of the Greek population, were interviewed. Results More women of all age groups compared with men reported adding salt during cooking (P < 0·001), while less reported adding salt on the plate (P < 0·001). Also, more women believed that salt added during cooking was the main source of salt in the diet (P < 0·001). Participants aged 25–34, 35–44 and 45–54 years old had better knowledge of the harmful effects of salt on health compared with the 55+ years age group (P = 0·002, P = 0·001, P < 0·001, respectively); respondents in the aforementioned age groups also knew that children should consume less salt than adults compared with 55+ years age group (P = 0·004, P < 0·001, P < 0·001, respectively). Respondents with secondary and higher educational status were more likely to avoid consumption of processed foods (P < 0·001) and to check the nutrition information on food packaging as compared with respondents having basic education status (P < 0·001). Conclusions Awareness needs to be raised regarding salt recommendations for adults and children, sources of sodium in the diet and adding less salt during cooking, as well as reading food labels. Future campaigns for salt reduction should consider gender, age and level of education differences regarding knowledge, attitudes and behaviour towards salt.
Routine Blood Parameters in Elite Soccer Players

Abstract Often blood screening is repeatedly done in elite athletes although training and competition can affect its results and normal ranges for highly active individuals are widely unknown. This study was conducted to provide reference data in professional soccer players. 467 male soccer players of the 2 highest German leagues were observed over an entire season. Venous blood sampling was conducted 4 times in a standardized manner to determine complete blood count, AST, ALT, CK, creatinine, urea, uric acid, cholesterol, electrolytes, ferritin, CRP and TSH. There were significant changes during the season in hematocrit, creatinine, uric acid (decrease), CK, AST, urea, sodium, potassium, magnesium, and TSH (increase). Only the changes in hematocrit and CK were large enough to possibly interfere with clinical decisions in soccer players. Upper limits of the 95% confidence intervals exceeded population reference ranges slightly in AST, urea, creatinine, and potassium. The mean intraindividual coefficient of variation was below 10% in complete blood count (except leukocytes), creatinine, uric acid, total cholesterol, and all electrolytes. There seems to be a profound effect of elite soccer training and competition on hematocrit (plasma volume) and CK only. Spontaneous variability of most parameters is too small to justify repeated sampling only for routine screening. Trial Registration: NCT00946855 Effect of Elite Soccer Training on Routine Laboratory Parameters (SOCCERLAB), http://www.clinicaltrials. gov/ct2/show/NCT00946855? term=soccerlab&rank=1
The use of progesterone and other progestational agents to prevent spontaneous preterm labour and preterm birth

Background: Preterm birth is the major cause of perinatal mortality and morbidity in the developed world, making a huge impact on healthcare costs. There is accumulating evidence that the prophylactic use of progestagens is able to reduce significantly the incidence of low birth weight and preterm birth. Objectives: to emphasise the importance of preterm birth; to review the role of progesterone in inducing myometrial quiescence which prevent preterm labour and preterm birth; to review the published literature and planned future research on the use of progestagens for the prevention of preterm birth. Methods: A review of the published literature using accepted search engines. Results/conclusions: Progestagens have been demonstrated to reduce the incidence of low birth weight and preterm birth. Many questions remain unanswered, particularly the long-term safety concerns and also whether the use of progestagens results in improved neonatal and childhood outcomes.
Refractive error blindness in Yenagoa, Bayelsa state, Nigeria: a hospital based study

Background: Despite the priority attention giving to refractive error in vision 2020 programme, blindness due to uncorrected refractive error is relatively unexplored. The aim of this study is to determine the prevalence and causes of refractive error blindness in Yenagoa. Method: All consecutive patients presenting to our eye clinic that were diagnosed to have refractive error over a one year period was studied. They underwent a full ocular examination including anterior and posterior segment examination, objective and subjective refraction. Objective refraction was done using a Carl Zeiss 599R autorefractometer. Information obtained included their age, sex, occupation, presenting visual acuity, history of couching and that of cataract surgery without an implant. Statistical analysis was done manually using a scientific calculator. Results: 1168 patients was seen during the study period and 135 persons had refractive error. Of the number with refractive error, 63 were males while 72 were females (M:F=1:1.4). Their age ranged from 6 to 83 years with a mean of 35.7 years (SD±4.102). The prevalence of refractive error blindness was 0.68 %. High myopia accounted for 75% of the blindness while high hyperopia and aphakia accounted for 12.5% each respectively. The prevalence of low vision due to refractive error was 2.5%. Myopia was responsible for half of the cases of low vision while hyperopia and astigmatism accounted for 30% and 16% respectively. Aphakia was responsible for 3.3% of low vision seen. Conclusion: Uncorrected refractive error is potentially blinding with a prevalence of 0.68% in this population, myopia being responsible for majority of cases. Health education is needed to create awareness on the availability of refractive error services in this population in order to stem the tide of needless blindness. Keywords: Blindness, refractive error, Yenagoa, myopia, aphakia, hyperopia.
Fatal human metapneumovirus infection following allogeneic hematopoietic stem cell transplantation

Respiratory viruses are an important yet underestimated cause of infectious morbidity and mortality in immunocompromised children and adolescents. Here, we report the occurrence of fatal lower respiratory tract disease associated with human metapneumovirus (HMPV) infection in a 10‐year‐old girl with chronic graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation (HSCT) for secondary chronic myeloid leukemia. Symptoms occurred 8 months after HSCT while on immunosuppression with 0.2 mg/kg/day of prednisone, and presented as dry cough, bilateral pneumonitis, and progressive respiratory distress. Non‐invasive and invasive microbiological investigations revealed HMPV type B as the sole pathogen. Histopathological findings showed interstitial and intra‐alveolar pneumonitis with profound alveolar cell damage. The patient was treated with intravenous and oral ribavirin and polyvalent immunoglobulins, but ultimately died from respiratory failure. The case reflects the potentially fatal impact of infections by respiratory viruses in immunocompromised patients and the need for effective approaches to their prevention and treatment.
Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

BACKGROUND Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. METHODS A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. RESULTS A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. CONCLUSION The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.
Efficacy and safety of biweekly i.v. administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small-cell and non-small-cell lung cancer: a multi-tumour, multi-institutional phase II

BACKGROUND This multi-centre phase II trial assessed the activity, safety (CTCAE 3.0) and pharmacokinetics (PK) of the pan-Aurora kinase inhibitor danusertib hydrochloride (PHA-739358) in breast (BC), ovarian (OC), pancreatic (PC), colorectal (CRC), small-cell (SCLC) and non-small-cell lung (NSCLC) cancers. METHODS Consenting adult patients with good performance and organ function with advanced/metastatic tumours who had failed systemic therapy were treated in independent, disease-specific cohorts with danusertib 500 mg/m(2) given as 24-h i.v. infusion every 14 days with until progression or unacceptable toxicity. A two-stage design was applied. Primary end point was the progression-free rate (PFR) at 4 months (RECIST1.1). RESULTS A total of 223 patients were enrolled with 219 actively treated. The median relative dose intensity of danusertib was similar for all tumour types (84.6%-99.6%). The median number of biweekly treatment cycles ranged from 3 to 4/patient (maximum 5-40 cycles/entity) and the median treatment duration varied between 7.6 and 10.0 weeks per histotype. Danusertib did not meet pre-specified protocol criteria for clinically relevant activity in any of the treated cancers. The PFR at 4 months was 18.4% in BC, 12.1% in OC, 10.0% in PC, 10.4% in NSCLC (all histotypes), 16.1% in squamous NSCLC and 0% in SCLC and CRC. Some radiological and/or biochemical indication of antitumor activity was seen in BC, OC, PC and NSCLC, including two confirmed partial responses. The most frequent drug-related non-laboratory adverse events (AEs) were fatigue/asthenia, nausea, diarrhoea, anorexia, vomiting, alopecia, constipation and pyrexia. Common laboratory AEs included haematological toxicity, hypalbuminaemia and increases in liver enzymes. Treatment was discontinued due to AEs in only 5.5% of patients. Plasma concentrations of danusertib were in line with results from earlier studies. CONCLUSION Single-agent danusertib did show only marginal anti-tumour activity in common solid tumours after failure of prior systemic therapies. The safety and PK profile was consistent with previous experience. CLINICAL TRIAL NUMBER 2006-003772-35.
Neuroplasticity in action post-stroke: Challenges for physiotherapists

Abstract Knowledge regarding neuroplasticity post-stroke is increasingly expanding. In spite of this, only a few physiotherapy interventions have been able to demonstrate effectiveness in achieving recovery of lost sensorimotor control. The aims of this review article are to highlight and discuss challenges for physiotherapists working with patients post-stroke, to question some current assessment methods and treatment approaches, and to pose critical questions indicating a possible new direction for physiotherapists in stroke rehabilitation. Differentiation between recovery and compensation post-stroke is increasingly being emphasized. Implementation of this goal in the clinic is insufficient, with a lack of assessment tools with potential to discriminate between the concepts. Large-scale reviews are performed without considering whether functional gains are achieved through “more effective” compensatory strategies or through recovery. Cortical plasticity in neurorehabilitation research and voluntary control in contemporary treatment methods are in focus. Challenges for physiotherapists in stroke rehabilitation consist of rethinking, including looking upon the body under the influence of gravity, focusing on implicit factors that impact movement control and developing new assessment tools. The introduction of a new assessment and treatment concept aiming at expanding the boundaries of center of mass movements towards the paretic side is proposed. In conclusion, we need to assume our responsibilities and step forward as the experts in movement science that we have the potential to be.
Treatment of BK virus‐associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single‐center experience

BK virus (BKV)‐associated hemorrhagic cystitis (BKV‐HC) is a severe complication after hematopoietic stem cell transplantation (HSCT). Cidofovir (CDV) has emerged as an effective agent for the treatment of BKV nephropathy, but its use for BKV‐HC in pediatric HSCT recipients has not yet been established as a standard therapy.
Reply to “Maintenance immunosuppression and the risk of herpes zoster after kidney transplantation”

To the Editor We thank Dr. Arasaratnam (1) for the interest in our publication on the increased incidence of herpes zoster (HZ) in the setting of cytomegalovirus (CMV) preemptive therapy after kidney transplantation (KT). HZ is caused by reactivation of the varicella zoster virus (VZV), a phenomenon that is dependent on the balance between VZV and the host’s immune status. Indeed, elderly and immunocompromised patients show a higher incidence of HZ (2–4). The incidence of HZ in KT patients is reported to be 11% (5), and induction with anti-thymocyte immunoglobulin and specific agents, such as mycophenolate mofetil and sirolimus, are thought to increase the risk of HZ (3). Thus, Arasaratnam’s point that stronger immunosuppression might increase the incidence of HZ in patients receiving CMV preemptive therapy is reasonable (1, 3). As Arasaratnam points out, the follow-up period for patients receiving CMV pre-emptive prophylaxis was shorter than that for patients receiving universal prophylaxis for <3 months (15 6 months vs. 23 8 months; P < 0.001) or for those receiving universal prophylaxis for >3 months (15 6 months vs. 29 5 months; P = 0.046) (6). This means that each group might have received different preand posttransplantation management protocols (e.g., immune induction and maintenance immunosuppression), because patients receiving CMV preemptive therapy were more recently transplanted. Thus, we carefully reviewed the induction and immunosuppressive regimens. The differences we found were that more patients on CMV preemptive therapy received rituximab and basiliximab as induction agents, but higher development of HZ was found in patients receiving CMV preemptive therapy, even in subgroup analysis adjusting for these confounding factors (6). The intensity of the immunosuppressive regimen was stronger during the early period post transplantation because the patient’s immune system is strongly suppressed by induction therapy, and higher doses of immunosuppressants are maintained for the first 3 months post KT. For example, the cyclosporine doses are adjusted to maintain whole blood cyclosporine trough levels of 200–300 ng/mL for the first 3 months post KT. The doses are subsequently tapered to yield trough levels between 50 and 150 ng/mL. The target whole blood trough concentrations of tacrolimus are 8– 10 lg/L for the first 3 months, and 3–7 lg/L thereafter. Thus, it is natural that most infectious complications developed during the early period post KT (7).
Prevalence and association of female weight status and dietary habits with sociodemographic factors: a cross-sectional study in Saudi Arabia

Abstract Objective Research about the prevalence of underweight and overweight/obesity in the Saudi Arabian female population is limited. The aim of the present study was to examine the dietary habits and the prevalence of underweight and overweight/obesity and associated factors among female university students. Design A cross-sectional study. Setting A university centre for female students in south-western Saudi Arabia. Subjects The study involved 663 randomly selected female university students who self-reported their physical activities, nutritional habits and socio-economic factors. Multiple linear and logistic regression analyses were used to identify factors associated with the students’ BMI, dietary variables, underweight and overweight/obesity. Results The majority of the university females were normal weight (56·9 %), but a high prevalence of underweight (19·2 %) and overweight/obesity (23·8 %) occurred. Social factors significantly associated with BMI were the presence of obese parents and siblings as well as physical activity levels, marital status, number of sisters, father’s level of education and more frequent intake of French fries/potato chips (>3 times/week). Several variables were found to correlate with dietary habits, underweight and overweight/obesity. Of special interest is the association between the number of siblings and the participants’ BMI and dietary intake in both negative and positive ways. Conclusions The findings of this research have implications for health promotion and prevention of malnutrition among college-aged females. Health-care providers and policy makers need to involve the whole family when promoting females’ physical activity. The study serves as an evidence-based background for planning and implementation of interventions targeting improvement of highly educated populations’ nutritional habits.
UL54 foscarnet mutation in an hematopoietic stem cell transplant recipient with cytomegalovirus disease

We present a case of foscarnet (FOS) resistance arising from a UL54 mutation after a short duration of FOS exposure, which has not been previously described in a stem cell transplant recipient, to our knowledge. We discuss the use of FOS to treat other viral infections and the implications this may have for the development of resistance mutations and treatment of cytomegalovirus disease.
Efficacy and safety of hepatitis A vaccination in kidney transplant recipients

In recent years, symptomatic hepatitis A virus (HAV) infection has been reported with increasing frequency in Korea. Therefore, HAV vaccination should be considered in kidney transplant recipients (KTRs). The study investigated the efficacy and safety of HAV vaccination in KTRs under modern triple immunosuppressive agents.