nils-herrmann/clean_scirepeval huggingface dataset:
Thiol protein defect in sodium-lithium countertransport in subset of essential hypertension.

There is probably a heterogeneous etiology for essential hypertension (EHT), and abnormal erythrocyte sodium-lithium countertransport (Na/Li CT) is common in a subgroup of patients with a strong family history of hypertension and cardiovascular disease (EHT-FH patients). The aim of this study was to test the hypothesis that altering a membrane thiol protein could mimic the abnormal Na/Li CT observed in the patients and that a more refined understanding of the mechanism of abnormal Na/Li CT would facilitate a clearer identification of a subgroup of patients with a homogeneous biochemical abnormality. Na/Li CT kinetics were determined in untreated erythrocytes and after thiol group alkylation with N-ethylmaleimide (NEM). Compared with normal control erythrocytes, untreated erythrocytes from EHT-FH patients had a low K(m) of Na/Li CT, with a high ratio of maximum velocity to K(m). This kinetic pattern was reproduced in normal erythrocytes by treatment with NEM in sodium-free medium. The same treatment in EHT-FH erythrocytes caused a markedly abnormal effect with an increase in maximum velocity, indicating an increase in transporter turnover in contrast to the increase in sodium affinity seen in normal control erythrocytes. Frequency distributions of these kinetic changes showed a subgroup of approximately 75% of EHT-FH patients with abnormal kinetic changes with NEM. Therefore, the key Na/Li CT thiol group that is very reactive to NEM and causes the abnormal Na/Li CT in a subgroup of hypertensive patients may be a useful intermediate phenotype for a disease group within the syndrome of EHT. The single flux assay of Na/Li CT at 140 mmol/L sodium poorly discriminates this group. Identification of the thiol protein involved may lead to a molecular explanation of the altered membrane function in this subgroup of patients.
An assessment of the HIV/TB knowledge and skills of home-based carers working in the North West province in South Africa: a cross-sectional study

Home-based carers (HBCs) play a critical role in ensuring the success of the primary health care re-engineering strategy in South Africa. Their role includes ensuring improved access to and delivery of primary health care at the household level, and better co-ordination and improved linkages between community and health facilities for HIV/TB services. The objective of this study was to assess the knowledge, skills, challenges and training needs of HBCs involved in HIV/TB care in one sub-district in the North-West province of South Africa.



We conducted a descriptive, cross-sectional study in which 157 HBCs were interviewed to assess their knowledge and skills regarding HIV and TB. Data were collected using a pre-tested semi-structured questionnaire. Quantitative and qualitative data were analysed using SPSS statistical software and thematic analysis respectively.



One hundred and forty-four (92%) of the interviewees were female and 13 (8%) were male. The median age of the participants was 35 years (interquartile range (IQR): 22-27). The median score for knowledge of both HIV and TB questions was 66% (IQR: 57-75). In general, HIV knowledge scores were higher than TB knowledge scores (73% versus 66%). A significant association was found between knowledge scores and formal training (p < 0.05), and knowledge scores and highest educational levels (p < 0.05). Irrespective of knowledge, HBCs reported providing a variety of services to support HIV/TB services in the communities in which they worked. HBCs also reported facing various challenges in their jobs related to stigma and the social contexts in which they work.



The study showed that the overall knowledge of HBCs was limited, given the skills required and the services they provide. Given the increasing role of HBCs in various health initiatives, targeted interventions are required to support and improve their competencies and service provision.
A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir.

To investigate the pharmacodynamic profile and duration of action for five subcutaneous doses of insulin detemir (0.1, 0.2, 0.4, 0.8, and 1.6 units/kg; 1 unit = 24 nmol) and one subcutaneous dose of NPH insulin (0.3 IU/kg; 1 IU = 6 nmol).



This single-center, randomized, double-blind, six-period, crossover study was carried out as a 24-h isoglycemic clamp (7.2 mmol/l) in 12 type 1 diabetic patients.



Duration of action for insulin detemir was dose dependent and varied from 5.7, to 12.1, to 19.9, to 22.7, to 23.2 h for 0.1, 0.2, 0.4, 0.8, and 1.6 units/kg, respectively. Interpolation of the dose-response relationships for AUC(GIR) (area under the glucose infusion rate curve) revealed that a detemir dose of 0.29 units/kg would provide the same effect as 0.3 IU/kg NPH but has a longer duration of action (16.9 vs. 12.7 h, respectively). Lower between-subject variability was observed for insulin detemir on duration of action (0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, P < 0.05) and GIR(max) (maximal glucose infusion rate) (0.2 and 0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, both P < 0.05). Assessment of endogenous glucose production (EGP) and peripheral glucose uptake (PGU) resulted in an AOC(EGP) (area over the EGP curve) of 636 mg/kg (95% CI 279-879) vs. 584 (323-846) and an AUC(PGU) (area under the PGU curve) of 173 (47-316) vs. 328 (39-617) for 0.29 units/kg detemir vs. 0.3 IU/kg NPH, respectively.



This study shows that insulin detemir provides a flat and protracted pharmacodynamic profile.
Elective countershock in unanesthetized patients with use of an esophageal electrode.

CONSIDERABLE attention has recently been shown in dispensing with general anesthesia during countershock.1-4 This problem has also interested us and the present report deals with our attempt at solving it by using an esophageal electrode. Only a fraction of the energy administered to the patient during countershock by the usual, surface electrode technic is usefully consumed within the heart. The remainder is dissipated elsewhere, in driving current not only to and from the heart, but through pathways that circumvent it entirely. The distribution of electrical energy among these fractions is determined by the location of the electrodes on the chest and by the spatial configuration of the varyingly resistive tissues of the thorax. When electrodes are applied directly to the heart, depolarization is achieved with about 5 watt-seconds of energy5; in clinical external countershock, even with optimal electrode placement and a good subject, energies of 50 watt-seconds or more are almost always necessary. Thus, the greater part by far of the administered energy is expended in extracardiac tissues where, since it does not participate in depolarizing the heart, it is wasted. Clinical external countershock is, then, at best an operation of appreciably low efficiency. The relevance of these considerations to the problem of avoiding the need for anesthesia 124 is that it is precisely that fraction which is dissipated outside the heart which gives rise to the discomfort of countershock: it is current flow in tissues other than the heart-principally in skeletal muscles-and not de-polarization of the heart itself that leads to the discomfort of the procedure. The problem, therefore, of dispensing with anesthesia reduces to that of increasing the efficiency with which electrical energy is delivered to the heart, in order that the extracardiac current flow may be decreased to a tolerable level. Viewed this way, the problem of administering countershock to conscious patients is essentially similar to that of pacing the heart in a tolerable fashion without resort to intra-cardiac electrodes. Both problems have interested us and we have approached both in basically the same way, by using an esopha-geal electrode. Our purpose has been to achieve a greater proximity of the electrodes to the heart. Our technic has been to place one electrode in the esophagus, contiguous with the heart, and the other on the precordium. We hoped that this gain in electrical proximity would sufficiently improve the efficiency of energy delivery so that extracardiac current flow …
Positive expiratory pressure changes aerosol distribution in patients with cystic fibrosis.

We hypothesized that aerosol distribution in the lungs of patients with cystic fibrosis changes with positive expiratory pressure (PEP).



Eight patients were randomized to one of 2 conditions. On one study day, patients inhaled saline aerosol containing 99mtechnetium generated by a Pari LC Plus nebulizer and exhaled through a Pari PEP device. On another day, the same patients exhaled through a low-resistance Pari filter (no PEP). Afterwards, they underwent gamma-camera lung imaging. Images were analyzed for lung deposition fraction, expressed as a percent of the initial nebulizer activity, and deposition pattern, expressed in terms of inner-outer and apical-basal ratios.



Lung deposition fraction was significantly lower with the Pari PEP device; the mean + SD deposition fraction was 6.10 + 3.05% (median 6.20%) with PEP, compared to 10.76 + 4.52% (median 10.32%) (p = 0.0078) without PEP. The inner-outer ratio was 2.01 + 0.69 (median 2.23) with PEP, which was significantly lower than without PEP (2.76 + 1.33, median 2.55) (p = 0.004). The apical-basal ratio was 0.82 + 0.31 (median 0.80) with PEP, which was not significantly different from no PEP (1.00 + 0.49, median 0.90).



These results indicate that less aerosol is deposited in the lungs of patients with cystic fibrosis when the Pari LC Plus nebulizer is used with the Pari PEP device, as described in these experiments. Nevertheless, aerosol administration with this nebulizer and PEP device also results in a proportional redistribution of aerosol to the peripheral airways, compared to nebulization without the PEP device. The clinical relevance of this subtle redistribution of aerosol in cystic fibrosis patients will probably depend on the drug administered and disease severity.
Methods of high integrity RNA extraction from cell/agarose construct

Agarose hydrogels are widely used for three-dimensional cell scaffolding in tissue engineering and cell biology. Recently, molecular profiles have been obtained with extraction of a minimal volume of RNA using fluorescent-tagged quantitative polymerase chain reaction (qPCR), which requires high integrity RNA. However, the agarose interferes considerably with the quantity and quality of the extracted RNA. Moreover, little is known about RNA integrity when the RNA is extracted from cell/agarose construct. Thus, in order to obtain RNA of sufficient integrity, we examined various extraction methods and addressed reproducible methodologies for RNA extraction from cell/agarose constructs using spectrophotometry and microfluidic capillary electrophoresis. With various extraction methods using a mono-phasic solution of phenol and guanidine isothiocyanate, we evaluated quantity and quality of total RNA from cell/agarose construct. Extraction with solution of phenol and guanidine isothiocyanate followed by a silica based membrane filter column gave sufficient RNA integrity number, which allowed us to proceed to fluorescent-tagged qPCR for evaluating various cellular activities. The RNA extraction methods using phenol and guanidine isothiocyanate solution and a silica membrane column can be useful for obtaining high integrity RNA from cell/agarose constructs rich in polysaccharide and extracellular matrix. Our study contributes to further investigation using agarose hydrogels and other materials rich in polysaccharide in the field of cellular and tissue engineering.
Re-transplantation after bortezomib-based therapy.

Whilst the use of high dose alkylating agents and autologous stem cell transplantation (ASCT) has a fundamental role in consolidating initial anti-tumour induction therapy, its role in salvage therapy consolidation remains to be determined. Bortezomib has been shown to be an effective agent at first and subsequent relapse, with responses equivalent or better than the response to previously used conventional therapies in first-line therapy (Richardson et al, 2005; Laubach et al, 2009). Combining bortezomib re-induction with a second ASCT after maximal anti-tumour response is, therefore, an attractive concept. Accordingly, we undertook a retrospective review of patients proceeding to a second ASCT after bortezomib-based re-induction therapy. Patients undergoing a second ASCT after progression from an initial ASCT and subsequent bortezomib re-induction therapy in 12 centres were identified (n = 40). Detailed information on the patients was obtained through anonymized clinical data retrieval forms, capturing critical patient and disease-specific factors including response to initial induction therapy, response to first ASCT, time to progression, subsequent therapies, bortezomib-based re-induction therapy and response to second ASCT (including the type of transplant and stem cell source). Response to therapy was categorized according to the International Myeloma Working Group criteria (Durie et al, 2006). Kaplan Meier plots were made using the Statistical Package for the Social Sciences (spss) IBM, Chicago, Illinois, USA. There were insufficient cytogenetic data for analysis. A total of 40 patients were identified in this retrospective study. Two patients had planned reduced intensity allogeneic (RIC-Allo) transplants after their second autologous transplant and weren excluded from further analysis. Patient characteristics including age, sex, type of myeloma, therapy prior to their first and second transplants are shown in Table Ia. One patient who relapsed 10 months after their bortezomib therapy was transplanted in relapse. All other patients were transplanted prior to disease progression. Twenty-six patients were treated with a combination of bortezomib and dexamethasone, eight patients had PAD chemotherapy (bortezomib, adriamycin and dexamethasone (Oakervee et al, 2005). Two patients had bortezomib monotherapy, one patient had bortezomib plus intravenous melphalan and one patient had bortezomib plus cyclophosphamide, dexamethasone and idarubicin. The median number of cycles of bortezomib therapy was 4 (range 2–12). Patients receiving PAD chemotherapy also had a median of four cycles
A phase II study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0405.

Amrubicin, a new anthracycline agent, has shown high activity for small-cell lung cancer (SCLC) in previous studies. However, a combination regimen with amrubicin and platinum has been investigated little. On the basis of previous phase I study, we conducted this study to evaluate the efficacy and the safety of amrubicin and carboplatin for elderly patients with SCLC.



Chemotherapy-naive elderly patients with SCLC received amrubicin (35 mg/m(2), days 1-3) and carboplatin [area under the curve (AUC) 4.0, day1] every 3 weeks. The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival and toxicity profile.



From January 2005 to November 2007, 36 patients were enrolled [median age 76 (range 70-83); ECOG performance status of zero and one in 17 and 19 patients, respectively]. One complete response and 31 partial responses were observed (ORR 89%). Median PFS was 5.8 months and median survival time was 18.6 months. Grade 3-4 neutropenia was observed in 97% of the patients and six patients (17%) suffered from grade 3-4 febrile neutropenia. Other toxic effects were moderate and treatment-related death was not observed.



Amrubicin combined with carboplatin is quite effective for SCLC with acceptable toxic effects even for the elderly population. Further evaluation of this regimen is warranted.
Perfusion pressure does not affect neurologic outcome in axillary artery side graft cannulation in type a aortic dissection.

Antegrade selective cerebral perfusion (ASCP) through the right axillary is a safe and effective method for cerebral protection in aortic surgery. In the present study, we evaluated whether or not pressure control in ASCP affected the neurologic outcome.



Sixty-two patients (17 female, 45 male) with a mean age of 53.9 +/- 9.4 years (range, 23-74 years) with a diagnosis of Type A aortic dissection were operated on by using the right axillary artery side graft cannulation technique. ASCP with pressure control was used in the first 37 (59.6%) patients (group 1), whereas ASCP with flow control was used in the consecutive 25 patients (39.4%) (group 2). The groups were compared according to postoperative neurologic outcomes.



The hospital mortality rate was 9.7% with 6 patients. The mean ASCP flows of group 1 was 663 +/- 76 mL/min and 692 +/- 51 mL/min in group 2. This difference was not statistically significant (P = .120). The neurological dysfunction rates were 2.7% in group 1 with 1 patient and 8% in group 2 with 2 patients (P = .560).



In this study, we could not find a statistically significant difference in patients treated with ASCP through the right axillary applicated with pressure control versus flow control.
Phase I/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor

This phase I/II dose-escalation study evaluated the efficacy, safety, and pharmacokinetics of pilaralisib (SAR245408), a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, or voxtalisib (SAR245409), a PI3K and mammalian target of rapamycin inhibitor, in combination with letrozole in hormone-receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, non-steroidal aromatase inhibitor-refractory, recurrent or metastatic breast cancer. Maximum tolerated doses (MTDs) were determined using a 3 + 3 design in phase I. Efficacy was evaluated at the MTDs in phase II. Twenty-one patients were enrolled in phase I; MTDs were determined to be pilaralisib tablets 400 mg once daily (QD) or voxtalisib capsules 50 mg twice daily in combination with letrozole tablets 2.5 mg QD. Fifty-one patients were enrolled in phase II; one patient had a partial response in the pilaralisib arm. Rates of progression-free survival at 6 months were 17 and 8 % in the pilaralisib and voxtalisib arms, respectively. The most frequently reported treatment-related grade ≥ 3 adverse events were aspartate aminotransferase increased (5 %) and rash (5 %) in the pilaralisib arm, and alanine aminotransferase increased (11 %) and rash (9 %) in the voxtalisib arm. Pilaralisib and voxtalisib did not interact pharmacokinetically with letrozole. Pilaralisib had a greater pharmacodynamic impact than voxtalisib, as demonstrated by its impact on glucose homeostasis. There was no association between molecular alterations in the PI3K pathway and efficacy. In summary, pilaralisib or voxtalisib, in combination with letrozole, was associated with an acceptable safety profile and limited efficacy in endocrine therapy-resistant HR+ , HER2-negative metastatic breast cancer.
Home-based family intervention increases knowledge, communication and living donation rates: a randomized controlled trial.

Our aim was to develop and test an educational program to support well-informed decision making among patients and their social network regarding living donor kidney transplantation (LDKT). One hundred sixty-three patients who were unable to find a living donor were randomized to standard care or standard care plus home-based education. In the education condition, patients and members of their social network participated in home-based educational meetings and discussed renal replacement therapy options. Patients and invitees completed pre-post self-report questionnaires measuring knowledge, risk perception, communication, self-efficacy and subjective norm. LDKT activities were observed for 6 months postintervention. Patients in the experimental group showed significantly more improvements in knowledge (p < 0.001) and communication (p = 0.012) compared with the control group. The invitees showed pre-post increases in knowledge (p < 0.001), attitude toward discussing renal replacement therapies (p = 0.020), attitude toward donating a kidney (p = 0.023) and willingness to donate a kidney (p = 0.039) and a decrease in risk perception (p = 0.003). Finally, there were significantly more inquiries (29/39 vs. 13/41, p < 0.001), evaluations (25/39 vs. 7/41, p < 0.001) and actual LDKTs (17/39 vs. 4/41, p = 0.003) in the experimental group compared with the control group. Home-based family education supports well-informed decision making and promotes access to LDKT.
Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study.

Exacerbations are among the major factors that may affect the natural history of chronic obstructive pulmonary disease (COPD). The aim was to investigate the clinical characteristics and determinants of COPD exacerbations in our 5-year observational cohort study which had a very low exacerbation frequency. A total of 279 patients with COPD participated in the Hokkaido COPD cohort study, and 268 subjects who had clinical data for multiple visits were analysed. Exacerbation was defined in multiple ways: the patient's subjective complaint, symptom definition, requiring prescription change, requiring antibiotic treatment, or requiring hospital admission. Exacerbation frequency (events per person per year) was 0.78 ± 1.16, 0.24 ± 0.47, 0.20 ± 0.43, 0.13 ± 0.28 and 0.06 ± 0.19 for subjective complaint and symptom, prescription, antibiotic and hospital admission definitions, respectively. Exacerbation events did not significantly affect the annual decline in forced expiratory volume in 1 s. A high St George's Respiratory Questionnaire total score, especially activity score, and a low body mass index were strongly associated with exacerbation-free survival, exacerbation frequency and development of recurrent exacerbations. Despite the low exacerbation frequency in our cohort, impaired health-related quality of life and weight loss were found to be independent risk factors for COPD exacerbations.