Miracle-dz/UniFAR-FTUs huggingface dataset:
Cetuximab and Radiotherapy in Laryngeal Preservation for Cancers of the Larynx and Hypopharynx: A Secondary Analysis of a Randomized Clinical Trial.

IMPORTANCE The appropriate use of surgery or radiotherapy-based approaches for organ preservation has been the subject of much debate. Unfortunately, there has been a lack of improvement in overall survival for patients with laryngeal carcinoma in the last 30 years. OBJECTIVE To assess the rates of laryngeal preservation and laryngectomy-free survival in patients receiving cetuximab and radiotherapy (CRT) and patients receiving radiotherapy alone. DESIGN, SETTING, AND PARTICIPANTS Patients were enrolled in a multicenter, open-label, stratified, randomized, phase 3 study from April 1, 1999, through March 31, 2002, from 73 centers in the United States and 14 other countries. A secondary subgroup analysis of patients with hypopharyngeal and laryngeal carcinoma was undertaken. Rates of laryngeal preservation and laryngectomy-free survival were estimated by the Kaplan-Meier method. The hazard ratios (HRs) were calculated using a Cox proportional hazards regression model. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer core questionnaire and head and neck module. MAIN OUTCOMES AND MEASURES Laryngeal preservation and laryngectomy-free survival. RESULTS Of the 424 patients included in the trial, 168 treated patients with cancer of the larynx or hypopharynx were included in this analysis (90 in the CRT group and 78 in the radiotherapy alone group). The median (range) age of the patients was 59 (40-80) years in the CRT group and 61 (35-81) years in the radiotherapy alone group. In the CRT group, 72 patients (80.0%) were male and 18 (20.0%) were female. In the radiotherapy alone group, 62 (79.5%) were male and 16 (20.5%) were female. The rates of laryngeal preservation at 2 years were 87.9% for CRT vs 85.7% for radiotherapy alone, with an HR of 0.57 (95% CI, 0.23-1.42; P = .22). Similarly, the HR for laryngectomy-free survival comparing CRT vs radiotherapy alone was 0.78 (95% CI, 0.54-1.11; P = .17). This study was not powered to assess organ preservation. Median overall survival was 27 (95% CI, 20-45) vs 21 (95% CI, 17-35) months for the CRT and radiotherapy alone groups, respectively, with an HR of 0.87 (95% CI, 0.60-1.27). No differences between treatments were reported regarding overall quality of life, need for a feeding tube, or speech. CONCLUSIONS AND RELEVANCE The results of a possible cetuximab-related laryngeal preservation benefit for patients with hypopharyngeal or laryngeal cancer are intriguing; these results need to be interpreted in the context of a retrospective subset analysis with limited sample size. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00004227.
Der Einfluss der Organisationsgestaltung produktbegleitender Dienstleistungen auf die Arbeitswelt der Dienstleistungsakteure

Im Mittelpunkt der Arbeit steht die empirische Analyse der organisatorischen Losungen kleiner und mittlerer Maschinenbauunternehmen (KMU), produktbegleitende Dienstleistungen zu integrieren. Dazu wird zunachst anhand einer schriftlichen Befragung in der Metall- und Elektroindustrie das Dienstleistungsangebot dieses Industriezweigs sowie die aufbauorganisatorische Einbettung der Dienstleistungen analysiert. In vertiefenden Fallstudien wird deutlich, dass ein Grosteil der Dienstleistungen "neben" der Arbeit fur die Maschinenproduktion, ganzheitlich und selbstorganisiert erbracht wird. Aus dem Zusammenspiel dieser, fur KMU typischen Arbeitsorganisation mit den dienstleistungsspezifischen Eigenschaften (schlechte Planbarkeit, Interaktion mit dem Kunden) entstehen entgrenzte, subjektivierte Arbeitsverhaltnisse. Die Chancen und Risiken dieser Entgrenzungs- und Subjektivierungsphanomene spielen damit nicht allein in der New Economy und der Grosindustrie, sondern auch bei den Dienstleistungsakteuren im Maschinenbau, eine zunehmende Rolle.
Intake of Minerals from Food Supplements in a German Population—A Nationwide Survey

Introduction: Studies indicate that 17.9% - 60% of adults in Germany and Europe regularly use food supplements. Some reports suggest that their use might be responsible for excessive nutrient intake. The purpose of this survey was to examine the quantitative mineral intakes from food supplements: whether the tolerable upper intake levels (ULs) with supplements alone, or in combination with food was exceeded was checked. Methods: The survey was carried out by the Association for Consumer Research, Nurnberg, Germany. Anonymous data of 1070 supplement users (40.8% men, 59.2% women) aged 18 - 93 years were available. Three groups were examined based on dietary and supplemental mineral intakes: average, middle-high and high intake. Results: The mean number of supplements reported was 1.6 ± 1.1 products in men and 1.5 ± 0.9 products in women. The minerals most frequently consumed were magnesium, followed by calcium, zinc and selenium. The percentage of the supplement users with total intakes greater than the UL was minimal for all minerals. Supplement use in 143 cases increased the likelihood of intakes above the UL only for magnesium. Subjects particularly in the high intake group—as a worst case scenario—had intakes above the UL in the case of calcium (n = 23) and zinc (n = 34). The percentage of subjects taking several products was greater in subjects exceeding the UL than in those below (P < 0.001). Multiple use was seen significantly more often in men than in women (P < 0.01). Conclusions: In this survey, supplement use was generally not associated with excessive intake. Supplement use resulted in intakes above the UL in only a few cases relating to magnesium, calcium and zinc. This applies more often to elderly subjects and particularly to those who already have a high mineral intake from food in the model calculation.
1α,25‐dihydroxyvitamin D3 enhances fast‐myosin heavy chain expression in differentiated C2C12 myoblasts

We investigated the effect of VD3 (1α,25‐dihydroxyvitamin D3) on the proliferating, differentiating and differentiated phases of C2C12 myoblasts, a mouse skeletal muscle cell line. VD3 treatment in 10% FBS (fetal bovine serum) inhibited the proliferation and viability of the cells in a dose‐dependent manner. It also dose‐dependently increased the percentage of cells in the G0/G1 phase as shown by flow cytometry. In the differentiating phase, VD3 treatment inhibited the formation of myotubes and the expression of total myosin heavy chain at both the mRNA and protein levels. In the differentiated phase, treatment had no significant effect on the amount of total myosin heavy chain, as Western blot analysis with MF20 antibody [DSHB (Developmental Studies Hybridoma Bank)] showed. However, significantly greater expression of fast myosin heavy chain in 1 nM VD3 was found by Western blot analysis with MY‐32 (Sigma). Thus VD3 inhibited the proliferation of myoblasts during proliferating and differentiating phases, whereas it increased the expression of the fast myosin heavy chain isoform in the differentiated phase. The data indicate that an adequate concentration of VD3 might have an anabolic effect on differentiated skeletal muscle.
Targeted inhibition of glutaminase as a potential new approach for the treatment of NF1 associated soft tissue malignancies

Many cancer cells rely on glutamine as the source of carbon molecules to feed the biosynthetic pathways and are often addicted to glutaminolysis. Inhibitors of glutaminase activity have gained attention in the last few years due to their anti-proliferative effect and ability to induce apoptosis in some cancers. Although it is a promising therapeutic approach, its efficacy or the role played by glutamine in modulating cell proliferation in NF1 associated tumors has never been studied. We report for the first time, a strong correlation between the NF1 status of tumor cells and increased sensitivity to glutamine deprivation and glutaminase inhibition. Soft-tissue cell lines null for NF1 were highly dependent on glutamine for proliferation and showed decreased mTORC1 and Ras activity in response to glutaminase inhibition. Re-addition of glutamine or intermediary metabolite such as glutamate to the media restored mTORC1 and Ras activity. SiRNA mediated NF1 knockdown in wild-type NF1 cell line shows increased sensitivity to glutaminase inhibition. Conversely, NF1 overexpression in NF1 null cell lines results in reduced sensitivity to glutaminase inhibition, and restores mTORC1 signaling and Ras activity. These findings provide new insights into the role played by glutamine metabolism in NF1 associated tumors and strongly warrant further investigation as a potential therapy in the NF1 disease setting.
Different Testicular Gene Expression Patterns in the First Spermatogenic Cycle of Postnatal and Vitamin A-Deficient Rat Testis1

Abstract Spermatogenesis is a complicated process of germ cell differentiation, involving programmatic expression of diverse cell type- and developmental stage-specific genes. To date, the vitamin-A-deficiency (VAD) rats and postnatal rats are two models commonly used to study spermatogenesis. In the present study, we studied the expression of 1185 known genes in the vitamin-A-deficient and retinol-reinitiated spermatogenesis of rat testis using Clontech Atlas rat cDNA expression arrays. The mRNA expression patterns of post-vitamin-A (PVA) testis on Days 15 and 35 were compared with those of the spermatogenic arrested rat testis on Day 0. About 9% (110/1185) of the genes studied were highly expressed. When compared with VAD rat testis on Day 0, 20 and 31 genes were differentially expressed by a factor of twofold or greater on Days 15 and 35, respectively. Four genes (cytochrome P450 17, sulfated glycoprotein 2, protein kinase inhibitor, and cathepsin L) that play important roles in spermatogenesis were selected and their gene expression patterns were confirmed by semiquantitative reverse transcription-polymerase chain reaction. Comparison of the expression patterns of these genes between PVA-VAD and postnatal rat testis in developmentally matched stages revealed substantial differences during the early stages of spermatogenesis. This discrepancy could be caused by either the presence of arrested but mature somatic cells in the PVA-VAD testis that may contribute to a unique gene expression pattern in this model or the direct effect of retinol on spermatogenesis. Therefore, caution is needed in interpreting the gene expression data using the PVA-VAD and postnatal rat models in studying spermatogenesis in rat testes.
How Important is Secondary School Duration for Post-school Education Decisions? Evidence from a Natural Experiment

This paper investigates how post-school education decisions are affected by a one-year reduction of secondary school duration with an unchanged curriculum. Until recently, Germany had had a longstanding tradition of 13 years of schooling in preparation for university. During the last decade, however, most states abolished the 13th year. The implementation of the reform in 2003 in the state of Saxony-Anhalt provides a natural experiment for identification. Based on data from the double cohort of graduates, our estimates show significant effects of the reform. Affected female students in particular significantly delay university enrollment by one year, show a slightly lower participation in university education overall and are more likely to start a vocational education course. We can also reveal effect heterogeneity with respect to the fields of study. Due to the reform the probability of affected males studying mathematics or natural sciences is significantly reduced.
Squamous cell carcinoma of the vulva stage IA: long-term results.

OBJECTIVE The aim of this study was to evaluate the risk of metastases to lymph nodes and long-term results of radical and modified radical surgery in patients with a T1 squamous cell carcinoma of the vulva and </=1 mm of invasion. METHODS A retrospective review of 40 patients with T1 squamous cell carcinoma of the vulva and </=1 mm of invasion was performed. The clinical, pathologic, surgical, and follow-up data were abstracted from the patients' records. All slides were reviewed by two pathologists according to previously established guidelines. The overall mean follow-up was 7.6 years. RESULTS Vulvar recurrence developed in 2 patients (5-year rate, 5.9%). There were no groin recurrences among 10 patients undergoing groin lymphadenectomy. One of the 30 patients (10-year rate, 6.7%) without groin dissection developed groin metastases at 7.5 years, subsequent to an invasive vulvar recurrence. The 5- and 10-year cause-specific survivals were 100 and 94.7%, respectively. CONCLUSIONS T1 squamous cell carcinoma of the vulva with </=1 mm of invasion was associated with a low risk of vulvar recurrence and no groin node metastases. A low risk of subsequent groin node metastasis exists in patients developing an invasive vulvar recurrence. Long-term follow-up of these patients is recommended. Lesser forms of vulvar excision, such as wide local excision, were equally effective as radical vulvectomy for the prevention of vulvar recurrences. Patients treated by radical vulvar surgery experienced increased postoperative complications compared with patients treated by less radical surgery.
Improvement of coronary flow reserve after long-term therapy with enalapril.

To date, no clinical study shows an improvement in coronary flow reserve due to long-term antihypertensive therapy. in view of the contribution of the renin-angiotensin system to the process of hypertensive remodeling of the heart and coronary circulation, angiotensin-converting enzyme (ACE) inhibitors might act as cardioreparative drugs in arterial hypertension. Accordingly, our objective in this investigation was to examine under clinical conditions to what extent long-term antihypertensive treatment with an angiotensin-converting enzyme inhibitor improved the diminished coronary flow reserve in hypertensive patients with microvascular angina pectoris. For the purpose of comparison, we also treated a normotensive control group of 6 patients with hypertrophic nonobstructive cardiomyopathy. Fifteen hypertensive individuals (10 men, 5 women; age, 58 +/- 6 years) were treated with enalapril (10 to 20 mg/d; mean, 16.7 +/- 4.9 mg/d) for 11 to 13 months. At the end of the treatment period, systolic pressure decreased from 178 +/- 14 to 137 +/- 12 mm Hg and diastolic pressure from 102 +/- 11 to 86 +/- 4 mm Hg under ambulatory conditions. Left ventricular muscle mass index decreased by 8%, from 149 +/- 32 to 137 +/- 28 g/m2 (P < .05). Maximal coronary blood flow after dipyridamole was increased by 43%, from 181 +/- 69 to 258 +/- 116 mL/min per 100 g (P < .001), and minimal coronary vascular resistance was diminished by 29%, from 0.66 +/- 0.23 to 0.47 +/- 0.24 mm Hg x min x 100g x mL-1 (P < .001) after enalapril treatment. Consequently, the calculated coronary reserve increased from 2.2 +/- 0.6 to 3.3 +/- 1.2 (P < .001). After enalapril therapy, the functional class of angina pectoris according to the Canadian classification system had changed from 2.5 +/- 0.6 to 1.5 +/- 0.6 (P < .01). The maximal working capacity had increased from 23.775 +/- 3.970 to 26.255 +/- 4.598 J (mean +/- SE, P < .05). The maximal ST-segment depression at maximal work-load was reduced from 0.18 +/- 0.02 to 0.06 +/- 0.02 (mean +/- SE, (P < .01). In summary, long-term therapy with the angiotensin-converting enzyme inhibitor enalapril must be considered a cardioreparative treatment with respect to the coronary microcirculation in hypertensive heart disease.
Novel LTCC Distributed-Element Wideband Bandpass Filter Based on the Dual-Mode Stepped-Impedance Resonator

In this paper, a novel compact 3-D dual-mode stepped-impedance resonator (SIR) with centrally loaded stub is constructed for designing a wideband low-temperature cofired ceramic (LTCC) bandpass filter (BPF). By fully taking advantage of the LTCC technology, the dual-mode SIR, as a cell unit of the proposed filter, is reasonably folded in 3-D environment, and its properties are investigated using the transmission line theory. Accordingly, benefiting from the 3-D circuit layout, the proposed BPF designed by combining the SIR and dual-mode techniques can effectively overcome a vital and common drawback of large circuit size of the LTCC distributed-element filters. For demonstration, a fourth-order wideband BPF centered at 5 GHz is designed, fabricated, and measured. The circuit size of the designed BPF has a compact size of 3.875 × 4.8 × 1.4 mm3. The impact of the package on the coupling and routing scheme and frequency response/transmission zero has been analyzed and demonstrated. The simulated and measured results are presented and compared, showing a good agreement.
The protective effects of apocynin on kidney damage caused by renal ischemia/reperfusion.

PURPOSE This experimental study was designed to explore the protective effect of apocynin, the NADPH-oxidase inhibitor, on kidney damage induced by ischemia/reperfusion (I/R) in a rat model. METHODS Thirty-two rats were randomly divided into a control group and three I/R groups (1-hour ischemia followed by 23-hour reperfusion). Three I/R groups were treated by apocynin (20 mg/kg, i.p.) at two different time points (before ischemia and during ischemia). The histopathological findings, including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GPX), reduced glutathione (GSH), myeloperoxidase (MPO), blood urea nitrogen (BUN), and serum creatinine (Cr) levels, were determined. RESULTS Kidney tissue MDA and MPO, and serum BUN and Cr levels were found to be significantly higher in the I/R group, but there was no statistically significant difference in the levels of SOD, CAT, GPX, and GSH between the I/R and the control groups. Although apocynin significantly reduced MDA and MPO in group 3 and increased GPX in both treatment groups when compared to the I/R group, the elevated BUN and Cr levels were significantly reduced in treatment groups. Renal I/R injury also induced extensive tubular necrosis, glomerular damage, and apoptosis in the histological evaluation. Apocynin, especially when used during ischemia, ameliorated these histological damages in different amounts in treatment groups. CONCLUSION The beneficial effects of apocynin on renal I/R injury were evaluated for the first time.
Middle-aged female sexual dysfunction and multimorbidity: a population-based study

Objectives:The aim of the study was to evaluate the association between multimorbidity and sexual dysfunction in women aged 45 to 60 years in a cross-sectional population-based study in a specific Brazilian city. It was also to evaluate the main factors associated with sexual dysfunction in the group with multimorbidity. Methods:Cross-sectional population-based study conducted with 736 women (household survey), representative of a population of 257,434 women, to obtain data on multimorbidity and sexual dysfunction, as part of a broader study on women's health. The instrument used to evaluate sexual dysfunction was the Short Personal Experiences Questionnaire. Associations were determined between multimorbidity and sexual dysfunction and sexual dysfunction and demographic, behavioral, and medical characteristics. Results:53% of the women reported multimorbidity and 49.6% of them reported sexual dysfunction. Multiple regression analysis showed no association between sexual dysfunction and multimorbidity. Sexual dysfunction in the whole sample (with and without multimorbidity) was associated with sexual activity in the last month (prevalence ratio [PR] = 0.27, 95% CI 0.22-0.33, P < 0.001), having physical activity greater than or equal to 2 times a week (PR = 0.70, 95% CI 0.58-0.84, P < 0.001), menopause rating symptoms greater than 8 (PR = 1.25, 95% CI 1.09-1.43, P = 0.002), perimenopausal or postmenopausal status (PR = 1.57, 95% CI 1.13-2.17, P = 0.007), alcohol use greater than or equal to 1 drink/week (PR = 0.81, 95% CI 0.67-0.97, P = 0.025), and anxiety (PR = 1.15, 95% CI 1.01-1.31, P = 0.039). In the group with multimorbidity, the main factors associated with sexual dysfunction were sexual activity in the last month (PR = 0.31, 95% CI 0.25-0.39, P < 0.001), anxiety (PR = 1.33, 95% CI 1.15-1.53, P < 0.001), and physical activity (PR = 0.70, 95% CI 0.56-0.87, P = 0.002). Conclusions:There was no evidence that multimorbidity was associated with sexual dysfunction in this sample of middle-aged women. The main factors associated with sexual dysfunction in women with multimorbidity in this sample were lack of sexual activity in the last month, physical inactivity, and anxiety. This highlights the importance of sexual activity, psychological health, and physical activity for a satisfactory sexual life in the case of women with multimorbidity.
Pressure volume curve and alveolar recruitment/de-recruitment. A morphometric model of the respiratory cycle.

HYPOTHESIS The changes in pulmonary volume taking place during respiration are accompanied by the opening and closing of the alveoli, with the number of alveoli open, at the same transpulmonary pressure (TPP) differing, depending on whether the lung is insufflated or deflated. MATERIAL AND METHODS Seventy 344 Fischer rats divided into five groups. Group 1 lungs were fixed by instilling 10% formalin through the trachea to a pressure of 25 cm H2O. The lungs of the next four groups were air-filled and fixed via the pulmonary artery: group 2 lungs were fixed in inflation at 10 cm H2O TPP; group 3 lungs were fixed in inflation at 20 cm. H2O TPP; the lungs of groups 4 and 5 were fixed in deflation and, therefore, were inflated with air up to 27 cm. H2O to drop to 20 cm in group 4 and to 10 cm in group 5. The lungs were processed for light microscopy, carrying out a morphometric study. The results were statistically processed. RESULTS The lungs insufflated with liquid fixative at 25 cm of TPP reached higher values in the variables Pulmonary Volume, Internal Alveolar Surface (IAS) and Number of Alveoli, being statistically significant (p < 0.05) in comparison with the other four groups. In the lungs fixed in deflation, the pulmonary volume, IAS and number of alveoli were greater than in those fixed in inflation. The lungs fixed to 20 cm in deflation displayed significant statistical differences compared with those fixed to 20 cm in inflation. The IAS and number of alveoli gave good rates in relation with the pulmonary volume (r > or = 0.65). Three variables were used to measure the size of the alveoli, alveolar cord, alveolar surface and Lm, but none showed significant modifications. CONCLUSION This study supports the hypothesis that changes in lung volume are related to the increase/decrease in the number of alveoli that are open/closed and not to the modification in the size of the alveoli. Alveolar recruitment is the microscopic expression of pulmonary hysteresis, since the number of alveoli open in deflation is greater than the number open during inflation.