Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized, double-blind, placebo-controlled phase II study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy.

PURPOSE To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non-small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed. PATIENTS AND METHODS Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety. RESULTS TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = . 05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC. CONCLUSION TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.
Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study.

PURPOSE We investigated the long-term risk of second primary malignancy after chemotherapy for Hodgkin's lymphoma (HL) in a much larger cohort than any yet published, to our knowledge. PATIENTS AND METHODS We followed 5,798 patients with HL treated with chemotherapy in Britain from 1963 to 2001--of whom 3,432 also received radiotherapy--to assess second primary malignancy risks compared with general population-based expectations. RESULTS Second malignancies occurred in 459 cohort members. Relative risk (RR) of second cancer was raised after chemotherapy alone (RR, 2.0; 95% CI, 1.7 to 2.4) but was much lower than after combined modalities (RR, 3.9; 95% CI, 3.5 to 4.4). After chemotherapy alone, there were significantly raised risks of lung cancer, non-HL, and leukemia, each contributing approximately equal absolute excess risk. After combined modalities, there were raised risks of these and several other cancers. Second cancer risk peaked 5 to 9 years after chemotherapy alone, but it remained raised for 25 years and longer after combined modalities. Risk was raised after each common chemotherapy regimen except, based on limited numbers and follow-up, adriamycin, bleomycin, vinblastine, and dacarbazine. The age and time-course relations of lung cancer differed between chemotherapy alone and combined modalities. CONCLUSION Although chemotherapy alone leads to raised risk of second malignancy, this risk is lower and affects fewer anatomic sites than that after combined modalities, and it is slight if at all after 15 years follow-up. The mechanism of lung cancer etiology may differ between chemotherapy and radiotherapy.
Coma as a presenting symptom of primary HIV infection

Primary HIV infection (PHI) is symptomatic in 50–90% of patients. The diagnosis, however, is seldom made at first presentation. This is probably because of the multifaceted and unspecific manifestations, the omission to perform adequate diagnostic testing and the failure to assess risks for PHI. Meningoencephalitis has been described as a fairly common presenting condition in PHI, with nuchal rigidity, fatigue, photophobia and headache; therefore, PHI should be considered in the differential diagnosis of aseptic meningitis. We present the case of a man with acute coma and a presumptive diagnosis of viral encephalitis in whom serological testing showed HIV encephalitis during PHI.
Minimized Transient and Steady-State Cross Regulation in 55-nm CMOS Single-Inductor Dual-Output (SIDO) Step-Down DC-DC Converter

A single-inductor dual-output (SIDO) step-down DC-DC converter with continuous conduction mode (CCM) operation is proposed to achieve an area-efficient power management module. The low-voltage energy distribution controller (LV-EDC) can simultaneously guarantee good voltage regulation and low output voltage ripple. With the proposed dual-mode energy delivery methodology, cross regulation in steady-state output voltage ripple, which is rarely discussed, and cross regulation in load transient response are both effectively reduced. In addition, the energy mode transition operation helps obtain the appropriate energy operation mode using the energy delivery paths for dual outputs. Moreover, within the allowable output voltage ripple, the automatic energy bypass (AEB) mechanism can reduce the number of energy delivery paths, thereby ensuring voltage regulation and further enhancing efficiency. The test chip, fabricated in 55-nm CMOS, occupies 1.44 mm2 and achieves 91% peak efficiency, low output voltage ripple, and excellent load transient response for a high-efficiency system-on-a-chip (SoC) integration.
ROS1 rearrangements define a unique molecular class of lung cancers.

PURPOSE Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. PATIENTS AND METHODS Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort. RESULTS Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and -negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. CONCLUSION ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.
A 0.8-mW 5-bit 250-MS/s Time-Interleaved Asynchronous Digital Slope ADC

Slope and digital-ramp converters are normally limited to very low sampling rates, since they require a digital counter at a highly oversampled clock rate. In this work, an asynchronous digital slope architecture is introduced that only requires a nonoversampled clock, thus enabling a much higher speed of operation. At the same time, the low complexity and the inherent accuracy of the slope-architecture enable very good power-efficiency without using complex calibration techniques. A two-channel time-interleaved 5-bit asynchronous digital slope ADC was implemented in a 90-nm CMOS technology and occupies 160 μm × 200 μm. The measured prototype achieves an ENOB of 4.6 bit, while operating at 250 MS/s and consuming 0.8 mW from a 1-V supply.
Sexually transmitted infections knowledge and its impact in the practice of risky sexual behaviours and HIV serostatus: results from rural Kilimanjaro, Tanzania

Objectives: To investigate the level of knowledge of different categories of sexually transmitted infections (STIs) and their impact on practice of risky sexual behaviours and HIV transmission in rural Kilimanjaro, Tanzania. Methods: A cross-sectional study, including all individuals aged 15–44 years living in Oria village, Kahe ward, was conducted between March and May 2005. All consenting individuals were interviewed and offered HIV testing. Results: The response rate was 73.0% (1528/2093). Overall, knowledge of STIs was 38.6%. Having a casual partner (59.4%) and multiple sexual partners (50.6%) were mentioned as the most potential sources of STI. Genital ulcers and vaginal discharge were the predominant symptoms noted whereas abstinence and condom use were the preferred preventive measures. Knowledge of STI complications, including HIV transmission, was very low (22.0%) in this community. The low knowledge of STI complications was significantly associated with recent (past 4 weeks) practice of multiple sexual partners (AOR 2.4, 95% CI 1.1 to 8.7), not using condoms with casual partners (AOR, 2.7, 95% CI 1.2 to 7.5) and HIV serostatus (AOR 3.4, 95% CI 1.8 to 14.5). Conclusions: Overall STI knowledge and its link to HIV transmission was alarmingly low in this community. Knowledge of STI complications may play an important role in inducing safer sexual behaviours and hence HIV prevention. Interventions addressing HIV/STI knowledge should put more emphasis on raising awareness of complications as this may play a major role in HIV/STI prevention.
The burden of asymptomatic sexually transmitted infections among men in Carletonville, South Africa: implications for syndromic management

Objectives: To determine the prevalence of sexually transmitted infections (STI) and HIV among men attending an outreach STI/HIV screening service in informal settlements in South Africa over a 3-month period. Methods: A mobile clinic van was utilised to offer men: (1) urine screening for gonorrhoea, trichomoniasis, chlamydial and Mycoplasma genitalium infections; (2) serological screening for syphilis and herpes simplex virus type 2 (HSV-2); (3) on-site HIV voluntary counselling and testing. Urethritis pathogens were detected by molecular methods. HIV serostatus was determined using rapid tests. Demographic, sexual behaviour and clinical data were recorded on a nurse-administered questionnaire. Statistical analysis utilised the χ2 test. Results: 309 men attended the service; 304 (98%) requested serological screening for syphilis and HSV-2, 301 (97%) underwent urine-based screening for urethritis pathogens and 269 (87%) had an HIV test. Over 90% of men were asymptomatic for STI. Gonorrhoea was more prevalent in the symptomatic group (p<0.001); there were no significant differences in the prevalence of other urethritis pathogens between the groups. The total number of infections with each urethritis pathogen was highest in the asymptomatic group with twice as much gonorrhoea, 25 times as much chlamydial infection, six times as much trichomoniasis and nine times as much M genitalium infection compared with the symptomatic group. The overall HIV prevalence among clinic attendees was 29.7%. Conclusions: The uptake of both STI and HIV testing was high among men attending the service. The relatively high burden of both STI and HIV among the male clinic attendees has implications for the transmission of HIV.
HIV testing and self-reported HIV status in South African men who have sex with men: results from a community-based survey

Objective: To investigate the characteristics of South African men who have sex with men (MSM) who (1) have been tested for HIV and (2) are HIV positive. Methods: Data were collected from 1045 MSM in community surveys using questionnaires that were administered either face-to-face, by mail or on the internet. The mean age of the men was 29.9 years. The race distribution was 35.3% black, 17.0% coloured, 5.3% Indian and 41.1% white. Results: The proportion of MSM tested for HIV was 69.7%; having been tested was independently associated with being older, being more open about one’s homosexuality and being homosexually instead of bisexually attracted; black MSM, students and MSM living in KwaZulu-Natal were less likely to have been tested. Of the 728 MSM who had been tested, 14.1% (n = 103) reported to be HIV positive (9.9% of the total sample). Being HIV positive is independently associated with two factors: men who were positive were more likely to have a lower level of education and to know other people who had HIV/AIDS; race was not independently associated with HIV status among those who had been tested. Conclusions: The likelihood of having been tested for HIV seems to decrease with increasing social vulnerability. Racially, the distribution of HIV among MSM seems to differ from that of the general South African population, suggesting that while intertwined with the heterosexual epidemic there is also an epidemic among South African MSM with specific dynamics. These findings suggest that in-depth research is urgently needed to address the lack of understanding of HIV testing practices and HIV prevalence in South African MSM.
Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors.

PURPOSE This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), safety, preliminary activity, pharmacokinetics (PK), and pharmacodynamics of BKM120, a potent and highly specific oral pan-Class I PI3K inhibitor. PATIENTS AND METHODS Thirty-five patients with advanced solid tumors received daily BKM120 12.5 to 150 mg. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Assessments included archival tumor molecular status, response by Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography tracer uptake ([(18)F]fluorodeoxyglucose positron emission tomography [FDG-PET]), fasting plasma C-peptide, and phosphorylated ribosomal protein S6 (pS6) in skin biopsies. RESULTS Overall, treatment was well tolerated. Dose-limiting toxicities were grade 2 mood alteration (80 mg), grade 3 epigastralgia, grade 3 rash, grade 2 and grade 3 mood alteration (100 mg), and two grade 4 hyperglycemia (150 mg). The MTD was 100 mg/d. Frequent treatment-related adverse events included rash, hyperglycemia, diarrhea, anorexia, and mood alteration (37% each); nausea (31%); fatigue (26%); pruritus (23%); and mucositis (23%). BKM120 demonstrated rapid absorption, half-life of ∼40 hours, ∼three-fold steady-state accumulation, dose-proportional exposure, and moderate interpatient variability. One patient demonstrated a confirmed partial response (triple-negative breast cancer); seven patients (20%) were on study for ≥ 8 months. BKM120 demonstrated dose-dependent pharmacodynamic effects on [(18)F]FDG-PET, fasting C-peptide, fasting blood glucose, and pS6. No significant trends were seen to correlate tumor molecular alterations with clinical activity. CONCLUSION This study demonstrates feasibility and proof-of-concept of class I PI3K inhibition in patients with advanced cancers. BKM120, at the MTD of 100 mg/d, is safe and well tolerated, with a favorable PK profile, clear evidence of target inhibition, and preliminary antitumor activity.
Vandetanib Versus placebo in patients with advanced non-small-cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: a randomized, double-blind phase III trial (ZEPHYR).

PURPOSE Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor (EGFR), and RET signaling. This placebo-controlled trial assessed whether vandetanib conferred an overall survival benefit in patients with advanced non-small-cell lung cancer (NSCLC) after prior treatment with an EGFR tyrosine kinase inhibitor and one or two chemotherapy regimens. PATIENTS AND METHODS Eligible patients were randomly assigned 2:1 to receive vandetanib 300 mg/d or placebo until disease progression or unacceptable toxicity. The primary objective was to compare the outcomes between the two arms with respect to overall survival. RESULTS Overall, 924 patients received vandetanib (n = 617) or placebo (n = 307). No significant increase in overall survival was detected in the vandetanib cohort compared with placebo (hazard ratio = 0.95; 95.2% CI, 0.81 to 1.11; P = .527); median overall survival was 8.5 months versus 7.8 months for vandetanib and placebo patients, respectively. Statistically significant advantages favoring vandetanib were observed for progression-free survival (hazard ratio = 0.63; P < .001) and objective response rate (2.6% v 0.7%; P = .028). Postprogression therapy was balanced across the cohorts in both number and type. Adverse events were generally consistent with previous NSCLC studies of vandetanib 300 mg; common events occurring with a greater frequency in the vandetanib arm versus placebo included diarrhea (46% v 11%), rash (42% v 11%), and hypertension (26% v 3%). CONCLUSION The study did not demonstrate an overall survival benefit for vandetanib versus placebo. There was a higher incidence of some adverse events with vandetanib.
Development of a Standardized Telephone Interview Instrument

Although survey research methods have been accepted in the scientific community, applications of telephone interview methods in occupational therapy research and program evaluation studies remain limited. The benefits of telephone interview methods include high response rates, ability to ask exploratory questions, cost-effectiveness, and ability to branch questions to subsets of a study population. Through the process of standardizing research instruments and administration procedures, the reliability of data collected by telephone can be increased substantially. The evaluation of an interview instrument is a critical aspect of study design. Details of an evaluation study and strategies to enhance the process of assessing interview instruments are provided.
Cervical adenocarcinoma in a patient with Lynch syndrome, Muir-Torre variant.

Introduction Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer syndrome, is the most common form of hereditary colorectal cancer. Patients with Lynch syndrome are at high risk of developing colorectal cancer at an early age (mean, age 45 years), in addition to extracolonic cancers. The most common extracolonic cancer in Lynch syndrome is endometrial carcinoma. Other extracolonic cancers seen in Lynch syndrome include carcinoma of the ovary, stomach, small bowel, pancreas, hepatobiliary, brain, and upper genitourinary tract. Patients with Lynch syndrome may also have skin tumors, which is consistent with the Muir-Torre variant of Lynch syndrome. We report the case of a 39-year-old woman with Lynch syndrome who was found to have endocervical adenocarcinoma and later developed carcinoma of the skin, making her disease a Muir-Torre variant of Lynch syndrome. To our knowledge, there has been only one other case report of cervical carcinoma in a patient with Lynch syndrome.
New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes.

PURPOSE To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population. PATIENTS AND METHODS We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed. RESULTS There was a strong correlation between the extent of reduction of amyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L), partial response (dFLC decrease > 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation. CONCLUSION This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials.
Is adjuvant chemotherapy useful for women with luminal a breast cancer?

Alan S. Coates, International Breast Cancer Study Group and University of Sydney, Sydney, New South Wales, Australia Marco Colleoni, International Breast Cancer Study Group and European Institute of Oncology, Milan, Italy Aron Goldhirsch, International Breast Cancer Study Group and European Institute of Oncology, Milan, Italy; and Swiss Center for Breast Health, St Anna Clinic, Lugano, Switzerland
Gastrointestinal stromal tumors (gists): Definition, clinical, histological, immunohistochemical and molecular genetic features and predictors of malignant potential and differential diagnosis

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the gastrointestinal (GI) tract GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The cellular origin, differentiation, nomenclature and prognosis of GISTs are controversial. Because GISTs, like the interstitial cells of Cajal, the GI pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the Cajal cells has recently been suggested. GISTs are also known for their wide variability in clinical behavior and for the difficulty to determine their malignant condition The most reproducible predictors of malignancy are mitotic count >1-5 per10 high-powered fields (HPF), size >5 cm, tumor necrosis, infiltration and metastasis to other sites. However, some tumors with mitotic activity <1/10 HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm. Recently, mutations in c-kit gene (exon 11) preferentially occur in malignant GISTs and may be a clinically useful adjunct marker in evaluation of GISTs. In conclusion, the strong CD117 expression mostly defines primary GI mesenchymal tumors as GIST. Specific identification of GIST may become clinically important if therapies targeting the c-kit tyrosine kinase activation become available.