Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates. Patients were treated with pralatrexate (10 to 25 mg/m2) and romidepsin (12 to 14 mg/m2) on 1 of 3 schedules: every week × 3 every 28 days, every week × 2 every 21 days, and every other week every 28 days. Treatment continued until progression, withdrawal of consent, or medical necessity. Twenty-nine patients were enrolled and evaluable for toxicity. Coadministration of pralatrexate and romidepsin was safe, well tolerated, with 3 DLTs across all schedules (grade 3 oral mucositis × 2; grade 4 sepsis × 1). The recommended phase 2 dose was defined as pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every other week. Twenty-three patients were evaluable for response. The overall response rate was 57% (13/23) across all patients and 71% (10/14) in PTCL. The phase 1 study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase 2 study in PTCL will determine the efficacy of the combination. This trial was registered at www.clinicaltrials. gov as #NCT01947140.
Fatal misuse of humidifier disinfectants in Korea: importance of screening risk assessment and implications for management of chemicals in consumer products.

In Korea, humidifier disinfectants have been putin the water tanks of humidifiers for the prevention of germs,mold, and/or algae. According to the authorities, as of August31, 2011, 28 adults, including 13 pregnant women, have beenhospitalized because of this unidentified lung disease similar toacute interstitial pneumonia. Among them, four patients passedaway because of the rapid development of pulmonary fibrosisafter long exposure to the disinfectants over several months.
Prevention of post‐dural puncture headache (PDPH) in parturients. Contributions from experimental research

of 72 + 72 was required. Being part of a PhD thesis, however, including 144 patients was not realistic in the available time frame. So, we intended to conduct a two-centre study and include 80 patients, well aware of the risk of a type 1 error, as mentioned in the discussion. Unfortunately, one of the centres was not able to include patients as planned. Including patients from more than one centre is advantageous in underlining the effect of an intervention. This, however, requires a representative number of cases from each centre. In this specific study, the number of patients, included in the second centre, was not representative. We chose to exclude these patients from analysis, primarily due to questionable quality of data; secondly due to obvious differences in local traditions, regarding anaesthetic and surgical treatment, as well as discharge criteria. Including these patients in analysis would, in our opinion, potentially add more bias than accuracy to the results. Data of the remaining 40 patients, however, were of high quality with limited missing data. Thus, to evaluate the effect of fluid-related complications (non-primary endpoint) we decided to use multiple regression with stepwise elimination in the analysis. Furthermore, the effect of non-matching demographic and intraoperative data was tested in this model. Fitting of the model was performed in collaboration with a professional biostatistician. We agree with Dr. Jammer that conclusions from this study must be drawn with caution. As stated in the title we believe that there may be ‘room for improvement’ in haemodynamic optimisation of patients for lower limb revascularisation. This specific group of patients is at a high risk of having impaired compensatory mechanisms for meeting increased oxygen demands, inflicted by anaesthesia and surgery. Thus, measuring flowrelated haemodynamic parameters and optimising circulation according to well-validated algorithms may very well contribute to improving outcome. We look forward to seeing larger randomised controlled trials investigating this particular subject in the future.
Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience.

We previously reported durable responses and manageable safety of ibrutinib from a 3-year follow-up of treatment-naïve (TN) older patients (≥65 years of age) and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We now report on long-term efficacy and safety with median follow-up of 5 years in this patient population with TN (N = 31) and R/R (N = 101) CLL/SLL. With the current 5-year follow-up, ibrutinib continues to yield a high overall response rate of 89%, with complete response rates increasing over time to 29% in TN patients and 10% in R/R patients. The median progression-free survival (PFS) was not reached in TN patients. The 5-year PFS rate was 92% in TN patients and 44% in R/R patients. Median PFS in R/R patients was 51 months; in those with del(11q), del(17p), and unmutated IGHV, it was 51, 26, and 43 months, respectively, demonstrating long-term efficacy of ibrutinib in some high-risk subgroups. Survival outcomes were less robust for R/R patients with del(17p) and those who received more prior therapies. The onset of grade ≥3 cytopenias, such as neutropenia and thrombocytopenia, decreased over time. Treatment--limiting adverse events were more frequent during the first year compared with subsequent periods. These results demonstrate sustained efficacy and acceptable tolerability of ibrutinib over an extended time, providing the longest experience for Bruton tyrosine kinase inhibitor treatment in patients with CLL/SLL. These trials were registered at www.clinicaltrials. gov as #NCT01105247 and #NCT01109069.
Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation.

TO THE EDITOR: The approval of the hypomethylating agents (HMAs) azacitidine and decitabine for therapy of myelodysplastic syndromes (MDS) has been celebrated by the MDS community as a major milestone in improving the clinical outcomes of patients. [1][1],[2][2] Although both drugs lead to
Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review

Post‐operative pain affects millions of patients worldwide and the post‐operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non‐opioid analgesics: paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta‐analyses of analgesic efficacy and/or adverse effects of perioperative non‐opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post‐operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single‐dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non‐opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
Positive Illusions: Creative Self-Deception and the Healthy Mind

The very name of this book and its subtitle, "Creative Self-Deception," start a fountain of thoughts going in all directions. Is it useful to deny reality; is it helpful; and, in sickness, or in health? We all have areas of denial, and its import is whether they are vital areas, and whether we can live or function better by denying in seeking to cope with reality. The book is full of generalizations. In some instances there are attempts to validate through citing research, but often the references are unclear and at times run counter to the thesis they are cited to prove. For example, an instance is given of a person seeing a lion on the savannah and thinking either "The lions are back, it must be spring" or "The lions are back—I must run or be killed. " Thinking it is spring is a "positive illusion," but there is no
Bone mineral density in pediatric transplant recipients1

Background. Reduced bone mass and fragility fractures are known complications after transplantation in adults. Far less is known about the skeletal effects of transplantation in children and adolescents. Methods. This cross-sectional study examined the skeletal status of children (ages 9–18 years) who were at least 1 year post-cardiac (n=13), post-renal (n=8), or post-bone marrow (BMT; n=15) transplantation. Bone mass at total hip, femoral neck, spine (L2-4), and whole body (WB) was determined by dual energy x-ray absorptiometry and compared with age, sex, and ethnic-specific reference data. Standard deviations (z-scores) were calculated for both areal bone mineral density (BMD) and estimated volumetric bone density (bone mineral apparent density [BMAD]). Results. Cardiac transplant patients had significantly lower BMD z-scores compared with the reference population at all skeletal sites. BMT recipients had significantly reduced BMD z-scores at total hip, spine, and WB. Kidney transplant patients had a significantly reduced WB BMD z-score only. Spine BMAD z-scores remained significantly reduced in cardiac and BMT subjects. Three of 36 patients had radiographic evidence of spinal fracture after transplantation. No correlation between steroid dosage and any measure of bone mass was observed. Conclusions. Cardiac and BMT recipients had reduced BMD at multiple skeletal sites, and renal transplant recipients had reduced WB BMD for age. Deficits in spine bone density persisted after correcting for small bone size using BMAD. Low bone density and the occurrence of vertebral fractures indicate that cardiac, renal, and bone marrow transplantation in children is associated with reduced bone health.
A general method for sensor linearization based on neural networks

We propose a general method for linearizing the response of an arbitrary sensor. The procedure consists of a simple artificial neural network that compensates the nonlinear characteristic of the sensor. The neural network (a multilayer perceptron) is trained with input-output data: the (nonlinear) output of the sensor is used as input data, and the difference between sensor outputs and the desired linear responses are the target values. In this paper, an NTC sensor is used as application example of the procedure, and several practical results are provided. As this method is particularly suitable for embedded systems based on simple, low-resolution microcontrollers, its implementation on this kind of system is studied and analyzed.
A randomized clinical trial of the effects of ultra‐low‐dose naloxone infusion on postoperative opioid requirements and recovery

Tolerance to remifentanil during sevoflurane anesthesia may increase postoperative analgesic requirements. Low‐dose naloxone not only has been shown to block the development of acute opioid tolerance but also to ameliorate undesired opioid‐induced side effects. We hypothesized that naloxone prevents the acute opioid tolerance produced by a large dose of remifentanil, and reduces the incidence of opioid‐induced side effects.
Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease

Objective & design Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that refers to progressive histological changes ranging from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). We evaluated the status of cytosine methylation (5mC) of liver mitochondrial DNA (mtDNA) in selected regions of the mtDNA genome, such as D-loop control region, and mitochondrially encoded NADH dehydrogenase 6 (MT-ND6) and cytochrome C oxidase I (MT-CO1), to contrast the hypothesis that epigenetic modifications play a role in the phenotypic switching from SS to NASH. Methods We studied liver biopsies obtained from patients with NAFLD in a case-control design; 45 patients and 18 near-normal liver-histology subjects. Results MT-ND6 methylation was higher in the liver of NASH than SS patients (p<0.04) and MT-ND6 methylated DNA/unmethylated DNA ratio was significantly associated with NAFLD activity score (p<0.02). Liver MT-ND6 mRNA expression was significantly decreased in NASH patients (0.26±0.30) versus SS (0.74±0.48), p<0.003, and the protein level was also diminished. The status of liver MT-ND6 methylation in NASH group was inversely correlated with the level of regular physical activity (R=-0.54, p<0.02). Hepatic methylation levels of D-Loop and MT-CO1 were not associated with the disease severity. DNA (cytosine-5) methyltransferase 1 was significantly upregulated in NASH patients (p<0.002). Ultrastructural evaluation showed that NASH is associated with mitochondrial defects and peroxisome proliferation. Conclusion Hepatic methylation and transcriptional activity of the MT-ND6 are associated with the histological severity of NAFLD. Epigenetic changes of mtDNA are potentially reversible by interventional programs, as physical activity could modulate the methylation status of MT-ND6.
The main pathway to musculoskeletal disability

The epidemiology of disability uses epidemiological methods to describe the disability process and to identify factors that improve or delay its course. A conceptual model for the way chronic health problems affect functional ability is examined with an emphasis on endurance and muscle strength and examples from a Danish cohort study. Disability is difficulty in doing complex activities because of a long‐term physical or mental condition. In Glostrup only 10% and 18% of 75‐year‐old men and women, respectively, were dependent on personal help to perform mobility functions such as moving or walking outdoors, but 66% of the men and 71% of the women became tired during some or all of these activities. Functional limitations are restrictions in doing basic physical and mental activities. Up to 50% of 75‐year‐olds with loss of the ability to step a height of 40 cm or‐walk at least 1.4 m/s may have difficulties in city traffic. Impairment refers to dysfunctions in specific body systems. Muscle strength is reduced in the elderly by 10% per decade. The 75‐year‐olds who performed mobility functions without tiredness had 50% higher muscle strength values in several muscle groups and 15% higher VO2max. The pathological conditions most commonly associated with functional disability in old age are in the locomotor and cardiovascular organ systems. The influence of living conditions and individual lifestyle on functional ability is mainly indirect through the influence of those factors on chronic morbidity. Smoking and low physical activity are, however, direct risk factors. At all levels of tie disability process, it is possible by regular physical activity and exercise to prevent further consequences of disease. Focused intervention strategies are needed during the total life course. In 75‐year‐olds, light physical activity 4 h per week is sufficient. Exercise in impaired but only moderately disabled people is perhaps the most cost‐effective effort against the burden of disability facing society with the increasing life‐span.
Platelet-derived TLT-1 is a prognostic indicator in ALI/ARDS and prevents tissue damage in the lungs in a mouse model.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) affect >200 000 individuals yearly with a 40% mortality rate. Although platelets are implicated in the progression of ALI/ARDS, their exact role remains undefined. Triggering receptor expressed in myeloid cells (TREM)-like transcript 1 (TLT-1) is found on platelets, binds fibrinogen, and mediates clot formation. We hypothesized that platelets use TLT-1 to manage the progression of ALI/ARDS. Here we retrospectively measure plasma levels of soluble TLT-1 (sTLT-1) from the ARDS Network clinical trial and show that patients whose sTLT-1 levels were >1200 pg/mL had nearly twice the mortality risk as those with <1200 pg/mL (P < .001). After correcting for confounding factors such as creatinine levels, Acute Physiology And Chronic Health Evaluation III scores, age, platelet counts, and ventilation volume, sTLT-1 remains significant, suggesting that sTLT-1 is an independent prognostic factor (P < .0001). These data point to a role for TLT-1 during the progression of ALI/ARDS. We use a murine lipopolysaccharide-induced ALI model and demonstrate increased alveolar bleeding, aberrant neutrophil transmigration and accumulation associated with decreased fibrinogen deposition, and increased pulmonary tissue damage in the absence of TLT-1. The loss of TLT-1 resulted in an increased proportion of platelet-neutrophil conjugates (43.73 ± 24.75% vs 8.92 ± 2.4% in wild-type mice), which correlated with increased neutrophil death. Infusion of sTLT-1 restores normal fibrinogen deposition and reduces pulmonary hemorrhage by 40% (P ≤ .001) and tissue damage by 25% (P ≤ .001) in vivo. Our findings suggest that TLT-1 uses fibrinogen to govern the transition between inflammation and hemostasis and facilitate controlled leukocyte transmigration during the progression of ARDS.
The Connection of U.S. Best Practices to Outcomes for Vietnamese American Women Abused by Intimate Partners

A grounded theory approach and sensitizing concepts were used to study U.S. best practices for addressing intimate partner violence against 55 Vietnamese American women interviewed at the beginning and end of a twelve‐month period. Advocacy agency, police, and court contact were associated with women's decisions to leave abusive relationships. Also associated were Vietnamese‐speaking professionals and referrals between helping sources. Women's observation of the deterrent effect of the law and of justice‐system involvement explained the stopping of abuse in several but not all cases. Women who stayed in abusive situations received social work help from Vietnamese‐speaking staff who understood their cultures, and those with emotional abuse tended to receive no assistance. All women initially had high levels of feeling controlled, frightened, and depressed. The greatest improvements were for women whose abuse stopped or who left. Best practices (coordinated community responses, culturally competent services) appeared to be effective, but nationally they are not uniformly available to many cultural and linguistic groups.
Musculoskeletal Ultrasound in Sports Medicine

Diagnostic musculoskeletal ultrasound is the use of sound waves to evaluate soft tissues and bony structures in the body. Ultrasound has been used extensively as a therapeutic modality for decades. However, its diagnostic application did not arise until the introduction of high-frequency transducers in the 1980s, which allowed for more detailed anatomic imaging necessary to evaluate the musculoskeletal system. Musculoskeletal ultrasound provides several advantages over other imaging techniques including plain radiography, computer tomography (CT), and magnetic resonance imaging (MRI). Ultrasound is able to provide a fast, portable, and relatively inexpensive way for high-resolution imaging of soft tissue. There is no radiation, minimal metal or hardware artifact interference, and no known contraindications. Images are produced in real-time, which allows for interactive and dynamic examinations of anatomic structures. Precise localization of symptomatic structures by sonopalpation, localizing the maximally tender structures with the ultrasound probe, can allow for focused examination. Provocative testing can be performed under ultrasound visualization to evaluate pathologies such as dislocating tendons or nerves. Ultrasound can also easily be used to guide procedures like aspirations or injections. However, there are several disadvantages to musculoskeletal ultrasound as well. The most significant limitations relate to the field of view and scope of penetration. Since only a limited area is visualized with ultrasound, pain that is poorly localized may be better evaluated with other imaging modalities like plain radiographs, CT, or MRI. Ultrasound also has lower resolution at greater body depth and incomplete penetration into bone. This makes it difficult to fully assess intraarticular regions, areas deep to the bone, deep body regions, and anatomy of obese patients. The use of musculoskeletal ultrasound is further limited by the skill of the examiner and the great variety in technical specifications of ultrasound machines available. Musculoskeletal ultrasound, when used appropriately, can be an important tool in the arsenal of the musculoskeletal and sports medicine clinician. This article provides an overview of the fundamentals of clinical musculoskeletal ultrasound imaging.
Evaluation of renal allograft function by Doppler spectrum analysis A preliminary study

Abstract. A decreased renal function is rather common after renal transplantation. The causes of this decreased function are diverse and difficult to differentiate. Yet, duplex examination, and especially quantitative Doppler spectrum analysis of the blood velocities in the renal artery, may be an effective method for differentiating between some of these causes. Forty‐five renal transplant recipients were included in this preliminary study. Doppler spectra were recorded from the renal artery to the allograft. Parameters were derived from every Doppler spectrum in order to characterize each spectrum. Renal allograft function was evaluated on the basis of a number of clinical parameters. A significant correlation was found between the clinical parameters and the Doppler spectrum parameters indicative for changes in the peripheral resistance. Patients with a normal renal allograft function showed Doppler spectra with a high diastolic flow, typical of a vascular bed with a low peripheral resistance. Patients with a decreased renal allograft function caused by a stenosis in the renal artery could be distinguished by a low peak velocity and a low pulsatility index. A decreased allograft function caused by allograft rejection or cyclosporin nephrotoxicity also led to characteristic arterial flow disturbances. In these cases, the peripheral resistance was increased, and this was primarily reflected in a decrease in the diastolic blood velocity. We conclude that quantitative analysis of the blood velocities in the renal artery by Doppler spectrum analysis seems to be a useful, noninvasive diagnostic tool that discriminates between some of the causes of a decreased renal allograft function.