nils-herrmann/clean_scirepeval huggingface dataset:
Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial

Metformin may reduce the incidence of breast cancer and enhance response to neoadjuvant chemotherapy in diabetic women. This trial examined the effects of metformin on Ki67 and gene expression in primary breast cancer. Non-diabetic women with operable invasive breast cancer received pre-operative metformin. A pilot cohort of eight patients had core biopsy of the cancer at presentation, a week later (without treatment; internal control), then following metformin 500-mg o.d. for 1 week increased to 1-g b.d. for a further week continued to surgery. A further 47 patients had core biopsy at diagnosis were randomized to metformin (the same dose regimen) or no drug, and 2 weeks later had core biopsy at surgery. Ki67 immunohistochemistry, transcriptome analysis on formalin-fixed paraffin-embedded cores and serum insulin determination were performed blinded to treatment. Seven patients (7/32, 21.9%) receiving metformin withdrew because of gastrointestinal upset. The mean percentage of cells staining for Ki67 fell significantly following metformin treatment in both the pilot cohort (P = 0.041, paired t-test) and in the metformin arm (P = 0.027, Wilcoxon rank test) but was unchanged in the internal control or metformin control arms. Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14. By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected. Gene set analysis additionally revealed that p53, BRCA1 and cell cycle pathways also had reduced expression following metformin. Mean serum insulin remained stable in patients receiving metformin but rose in control patients. This trial presents biomarker evidence for anti-proliferative effects of metformin in women with breast cancer and provides support for therapeutic trials of metformin.
Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells

Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.



To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study.



Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro.



Dwelling time had a significant effect on the occurrence of EMT on MCs.
Economic Burden and Epidemiology of Pneumonia in Korean Adults Aged over 50 Years

This study was performed to estimate the direct medical costs and epidemiology of pneumonia in adults of Korea. We conducted a multi-center, retrospective, observational study and collected data targeting for community-acquired pneumonia patients ( ≥ 50 yr) from 11 hospitals. Costs attributable to the treatment of pneumonia were estimated by reviewing resource utilization and epidemiology data (distribution of pathogen, hospital length of stay, overall outcome) were also collected. A total 693 patients were included; average 70.1 ( ± 10.5) aged, 57.3% male and average 1.16 CURB-65 (confusion, blood urea nitrogen, respiratory rate, blood pressure, age > 65 yr) scored. The pathogen was identified in the 32.9% (228 patients); Streptococcus pneumoniae accounted for 22.4% (51 patients) of identified pathogens. The hospital mortality was 3.2% (especially, for S. pneumoniae was 5.9%) and average length of stay was 9 days. The mean total cost for the treatment of pneumonia was US dollar (USD) 1,782 (SD: USD 1,501). Compared to the cost of all caused pneumonia, that of pneumococcal pneumonia was higher, USD 2,049 ( ± USD 1,919), but not statistically significant. Charge of hospitalization accounted the greatest part of total medical costs. The economic burden of pneumonia was high in Korea, and the prevention of pneumonia should be considered as effective strategy.
Insulin infusion improves neutrophil function in diabetic cardiac surgery patients.

Diabetic patients are at increased risk of wound infection after major surgery, but the effect of perioperative glucose control on postoperative wound infection rates after surgery is uncertain. We tested the effect of an insulin infusion on perioperative neutrophil function in diabetic patients scheduled for coronary artery bypass surgery. Participants (n = 26) were randomly allocated to receive either aggressive insulin therapy (AIT) or standard insulin therapy (SIT) during surgery. Blood was drawn for neutrophil testing before surgery, 1 h after the completion of cardiopulmonary bypass, and on the first postoperative day. Neutrophil phagocytic activity decreased to 75% of baseline activity in the AIT group and to 47% of baseline activity in the SIT group (P < 0.05 between groups). No important differences in neutrophil antibody-dependent cell cytotoxicity were found. This study documents a potentially beneficial effect of continuous insulin therapy in diabetic patients who require major surgery.



A continuous insulin infusion and glucose control during surgery improves white cell function in diabetic patients and may increase resistance to infection after surgery.
Adhesive-enhanced sternal closure to improve postoperative functional recovery: a pilot, randomized controlled trial.

We previously established a proof-of-concept in a human cadaveric model where conventional wire cerclage was augmented with a novel biocompatible bone adhesive that increased mechanical strength and early bone stability. We report the results of a single-center, pilot, randomized clinical trial of the effects of adhesive-enhanced closure of the sternum on functional postoperative recovery.



In 55 patients undergoing primary sternotomy, 26 patients underwent conventional wire closure and were compared with 29 patients who underwent adhesive-enhanced closure, which consisted of Kryptonite biocompatible adhesive (Doctors Research Group Inc, Southbury, CT) applied to each sternal edge in addition to conventional 7-wire cerclage. Patients were monitored postoperatively at 72 hours, weekly for 12 weeks, and then after 12 months for incisional pain, analgesic use, and maximal inspiratory capacity measured by spirometry. Standardized assessment tools measured postoperative physical disability and health-related quality of life.



No adverse events or sternal complications from the adhesive were observed early or after 12 months. Incisional pain and narcotic analgesic use were reduced in adhesive-enhanced closure patients. Inspiratory capacity was significantly improved, postoperative health-related quality of life scores normalized more rapidly, and physical disability scores were reduced. Computed tomography imaging was suggestive of sternal healing.



Adhesive-enhanced closure is a safe and simple addition to conventional wire closure, with demonstrated benefits on functional recovery, respiratory capacity, incisional pain, and analgesic requirements. A large, multicenter, randomized controlled trial to examine the potential of the adhesive to prevent major sternal complications in higher risk patients is warranted.
Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study.

This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy (HTO) for varus deformity, with or without mesenchymal stem cell (MSC) therapy.



This prospective, comparative observational study was designed to evaluate the effectiveness of MSC therapy. The patients were divided into 2 groups: HTO with platelet-rich plasma (PRP) injection only (n = 23) or HTO in conjunction with MSC therapy and PRP injection (n = 21). Prospective evaluations of both groups were performed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and a visual analog scale (VAS) score for pain. Second-look arthroscopy was carried out in all patients at the time of metal removal.



The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain (PRP only, 74.0 ± 5.7; MSC-PRP, 81.2 ± 6.9; P < .001) and symptoms (PRP only, 75.4 ± 8.5; MSC-PRP, 82.8 ± 7.2; P = .006) relative to the PRP-only group. Although the mean Lysholm score was similarly improved in both groups (PRP only, 80.6 ± 13.5; MSC-PRP, 84.7 ± 16.2; P = .357), the MSC-PRP group showed a significantly greater improvement in the VAS pain score (PRP only, 16.2 ± 4.6; MSC-PRP, 10.2 ± 5.7; P < .001). There were no differences in the preoperative (PRP only, varus 2.8° ± 1.7°; MSC-PRP, varus 3.4° ± 3.0°; P = .719) and postoperative (PRP only, valgus 9.8° ± 2.4°; MSC-PRP, valgus 8.7° ± 2.3°; P = .678) femorotibial angles or weight-bearing lines between the groups. Arthroscopic evaluation, at plate removal, showed that partial or even fibrocartilage coverage was achieved in 50% of the MSC-PRP group patients but in only 10% of the patients in the PRP-only group (P < .001).



MSC therapy, in conjunction with HTO, mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only.
Does acute passive stretching increase muscle length in children with cerebral palsy?

Children with spastic cerebral palsy experience increased muscle stiffness and reduced muscle length, which may prevent elongation of the muscle during stretch. Stretching performed either by the clinician, or children themselves is used as a treatment modality to increase/maintain joint range of motion. It is not clear whether the associated increases in muscle-tendon unit length are due to increases in muscle or tendon length. The purpose was to determine whether alterations in ankle range of motion in response to acute stretching were accompanied by increases in muscle length, and whether any effects would be dependent upon stretch technique.



Eight children (6-14 y) with cerebral palsy received a passive dorsiflexion stretch for 5 × 20 s to each leg, which was applied by a physiotherapist or the children themselves. Maximum dorsiflexion angle, medial gastrocnemius muscle and fascicle lengths, and Achilles tendon length were calculated at a reference angle of 10 ° plantarflexion, and at maximum dorsiflexion in the pre- and post-stretch trials.



All variables were significantly greater during pre- and post-stretch trials compared to the resting angle, and were independent of stretch technique. There was an approximate 10 ° increase in maximum dorsiflexion post-stretch, and this was accounted for by elongation of both muscle (0.8 cm) and tendon (1.0 cm). Muscle fascicle length increased significantly (0.6 cm) from pre- to post-stretch.



The results provide evidence that commonly used stretching techniques can increase overall muscle, and fascicle lengths immediately post-stretch in children with cerebral palsy.
Effects of escitalopram on markers of bone turnover: a randomized clinical trial.

Recent observational studies have suggested that the use of selective serotonin reuptake inhibitors is associated with an increased fracture risk and an accelerated bone loss, although conflicting results have been reported. Furthermore, because many of these studies have been performed in depressed women, confounding by indication may influence these findings.



The objective of the study was to determine whether selective serotonin reuptake inhibitors affect bone metabolism Design: This was a randomized controlled trial.



The study was conducted in four US clinical sites.



Healthy peri- and postmenopausal women participated in the study.



The intervention was escitalopram (10-20 mg/d) for the treatment of vasomotor symptoms.



Serum carboxyterminal collagen crosslinks (CTX) and serum amino-terminal propeptide of type I collagen (P1NP) were measured.



One hundred forty-one peri- or postmenopausal nondepressed women (mean age 53.7 y, SD 4.1) had baseline and 8-week follow-up samples available for analysis and were included in the study (69 escitalopram, 72 placebo). The groups were balanced across a broad range of baseline characteristics, including age, race, body mass index, smoking status, and mood symptoms. The between-group differences in the change in CTX and P1NP from baseline to week 8 were compared by a repeated-measures linear regression model adjusted for race, clinical center, and baseline measurement. Treatment with escitalopram reduced serum P1NP by 1.02 ng/mL on average [95% confidence interval (CI) -5.17, 3.12] compared with a reduction of 1.88 ng/mL (95% CI -4.82, 1.06) in the placebo group (P = .65). Similarly, serum CTX decreased 0.02 ng/mL on average (95% CI -0.05, 0.01) in the escitalopram group compared with 0.00 ng/mL (95% CI -0.02, 0.02) in the placebo group (P = .24). The results were similar when the analysis was restricted to those women whose adherence to study medication was 70% or greater.



Although the study was limited to 8 weeks, these results suggest that escitalopram does not significantly alter bone metabolism in the short term.
Pharmacokinetics and excretion of 14C-lenvatinib in patients with advanced solid tumors or lymphomas

Lenvatinib is an orally available multi-targeted tyrosine kinase inhibitor with anti-angiogenic and antitumor activity. To get more insight into the disposition of lenvatinib, a mass balance study was performed in patients with advanced solid tumors. A single oral 24 mg (100 μCi) dose of 14C-lenvatinib was administered to six patients, followed by collection of blood, plasma, urine and feces for 7 to 10 days. The collected material was analyzed for total radioactivity, unchanged lenvatinib and selected metabolites. The safety and antitumor effect of a daily oral dose of 24 mg non-labeled lenvatinib were assessed in the extension phase of the study. Peak plasma concentrations of lenvatinib and total radioactivity were reached 1.6 and 1.4 h after administration, respectively, and their terminal phase half-lifes were 34.5 and 17.8 h, respectively. Unchanged lenvatinib systemic exposure accounted for 60 % of the total radioactivity in plasma. Peak concentrations of the analyzed metabolite were over 700-fold lower than the peak plasma concentration of lenvatinib. Ten days after the initial dose, the geometric mean (± CV) recovery of administered dose was 89 % ±10 %, with 64 % ±11 % recovered in feces and 25 % ±18 % in urine. Unchanged lenvatinib in urine and feces accounted for 2.5 % ±68 % of the administered dose, indicating a major role of metabolism in the elimination of lenvatinib. In conclusion, lenvatinib is rapidly absorbed and extensively metabolized, with subsequent excretion in urine and, more predominantly, in feces. Additionally, lenvatinib showed acceptable safety and preliminary antitumor activity.
Glutamic acid decarboxylase autoantibodies are dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes: LADA China study 5

Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects. LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally. Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05). As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies.
Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis

To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity.



Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population.



351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (-2.35 vs -0.68, -2.58 vs -0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (-1.34 vs -0.49 -2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX.



Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity.
A Specific Distress Cutoff Score Shortly After Breast Cancer Diagnosis.

High levels of distress are expected shortly after the diagnosis breast cancer. The Distress Thermometer (DT) is commonly used to screen for distress, using a cutoff score of 4 or 5; however, this score might not be appropriate for detecting distress in women with recently diagnosed breast cancer.



The aims of this study were to establish the optimal DT cutoff score for detecting high distress shortly after breast cancer diagnosis and to correlate this score with the reported problems.



We selected for this study Dutch women who completed the DT and the Hospital Anxiety and Depression Scale within 1 month after breast cancer diagnosis. Receiver operating characteristic analysis of DT scores was performed, with the Hospital Anxiety and Depression Scale being used as the criterion standard for the level of distress. The sensitivity, specificity, positive predictive value, and negative predictive value of each DT score were calculated.



In total, 181 women participated in the study. The optimal DT cutoff score for detecting distress was 7 with a sensitivity of 0.73, specificity of 0.84, positive predictive value of 69%, and negative predictive value of 87%. Emotional problems were the most frequently reported concerns.



We consider a cutoff score of 7, shortly after breast cancer is diagnosed, optimal to identify those women with high distress and therefore at risk of chronic distress.



The findings are clinically important because they can enable healthcare professionals to direct their time and resources to those most in need of their assistance.
Measurement of craniovertebral angle with Electronic Head Posture Instrument: Criterion validity.

This study evaluated the criterion-related validity of the Electronic Head Posture Instrument (EHPI) in measuring the craniovertebral (CV) angle by correlating the measurements of CV angle with anterior head translation (AHT) in lateral cervical radiographs. It also investigated the correlation of AHT and CV angle with the Chinese version of the Northwick Park Questionnaire (NPQ) and Numeric Pain Rating Scale (NPRS). Thirty patients with diagnosis of mechanical neck pain for at least 3 months without referred symptoms were recruited in an outpatient physiotherapy clinic. The results showed that AHT measured with X-ray correlated negatively with CV angle measured with EHPI (r = -0.71, p < 0.001). CV angle also correlated negatively with NPQ (r = -0.67, p < 0.001) and NPRS (r = -0.70, p < 0.001), while AHT positively correlated with NPQ (r = 0.390, p = 0.033) and NPRS (r = 0.49, p = 0.006). We found a negative correlation between CV angle measured with the EHPI and AHT measured with the X-ray lateral film as well as with NPQ and NPRS in patients with chronic mechanical neck pain. EHPI is a valid tool in clinically assessing and evaluating cervical posture of patients with chronic mechanical neck pain.