bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of a Novel Hec1-Targeted Anticancer Compound against Breast Cancer Cell Lines In Vitro and In Vivo
Authors: Huang Lynn Y.L. , Chang Chia-Chi , Lee Ying-Shuan , Chang Jia-Ming , Huang Jiann-Jyh , Chuang Shih-Hsien , Kao Kuo-Jang , Lau Gillian M.G. , Tsai Pei-Yi , Liu Chia-Wei , Lin Her-Sheng , Lau Johnson Y.N. 
Published: April 2014

Abstract
Current cytotoxic chemotherapy produces clinical benefit in patients with breast cancer but the survival impact is modest. To explore novel cytotoxic agents for the treatment of advanced disease, we have characterized a new and pharmacokinetically improved Hec1-targeted compound, TAI-95. Nine of 11 breast cancer cell lines tested were sensitive to nanomolar levels of TAI-95 (GI50 = 14.29–73.65 nmol/L), and more importantly, TAI-95 was active on a number of cell lines that were resistant (GI50 &gt; 10 μmol/L) to other established cytotoxic agents. TAI-95 demonstrates strong inhibition of in vivo tumor growth of breast cancer model when administered orally, without inducing weight loss or other obvious toxicity. Mechanistically, TAI-95 acts by disrupting the interaction between Hec1 and Nek2, leading to apoptotic cell death in breast cancer cells. Furthermore, TAI-95 is active on multidrug-resistant (MDR) cell lines and led to downregulation of the expression of P-glycoprotein (Pgp), an MDR gene. In addition, TAI-95 increased the potency of cytotoxic Pgp substrates, including doxorubicin and topotecan. Certain clinical subtypes of breast cancer more likely to respond to Hec1-targeted therapy were identified and these subtypes are the ones associated with poor prognosis. This study highlights the potential of the novel anticancer compound TAI-95 in difficult-to-treat breast cancers. Mol Cancer Ther; 13(6); 1419–30. ©2014 AACR.
New Insights into PARP Inhibitors' Effect on Cell Cycle and Homology-Directed DNA Damage Repair
Authors: Jelinic Petar , Levine Douglas A. 
Published: April 2014

Abstract
In preclinical and clinical studies, olaparib and veliparib are the most represented PARP inhibitors (PARPi), which mainly target homologous DNA damage repair pathway-deficient cancer cells. Their off-target effects are not fully understood, especially with regard to cell cycle and homology-directed DNA damage repair. Our objective was to comparatively evaluate olaparib and veliparib in this context and correlate our findings with their therapeutic potential. We used a well-established direct repeat GFP (DR-GFP) reporter assay in U2OSDR-GFP and H1299DR-GFP cells and measured DNA damage repair activity upon drug treatment. Olaparib-treated U2OSDR-GFP cells showed a dramatic decrease in DNA damage repair versus veliparib irrespective of inhibitory potency. We demonstrate that this effect was a result of olaparib's strong effect on the cell cycle. Unlike in veliparib-treated U2OSDR-GFP cells, in olaparib-treated cells S-phase decreased and G2-phase increased sharply, indicating a G2-phase arrest-like state and replicative stress. This was further confirmed by upregulation of p53 and p21 and accumulation of cyclin A. Lack of the same effect in p53-null H1299DR-GFP cells suggested that olaparib's effect is p53 related, which was confirmed in p53-depleted U2OSDR-GFP and p53-null HCT116 cells. Importantly, we also demonstrate that olaparib, but not veliparib, induced a robust phosphorylation of Chk1, a crucial component of the replicative stress response pathway. Our data show olaparib and veliparib differ in their off-target effects; olaparib, unlike veliparib, mitigates DNA damage repair activity via G2 cell-cycle arrest-like effect in a p53-dependent manner. These off-target effects may add to PARPis' anticancer properties. Mol Cancer Ther; 13(6); 1645–54. ©2014 AACR.
Impact of the Middle and Upper Tropospheric Cooling over Central Asia on the Summer Rainfall in the Tarim Basin, China
Authors: Zhao Yong , Huang Anning , Zhou Yang , Huang Danqing , Yang Qing , Ma Yufen , Li Man , Wei Gang 
Published: April 2014

Abstract
The changes in summer rainfall over the Tarim Basin, China, and the underlying mechanisms have been investigated using the observed rainfall data at 34 stations and the NCEP–NCAR reanalysis data during the period of 1961–2007. Results show that the summer rainfall over the Tarim Basin, which exhibits a significant increasing trend during the last half century, is closely related to the summer middle and upper tropospheric cooling over central Asia. Mechanism analysis indicates that the middle and upper tropospheric cooling over central Asia results in a location farther south of the subtropical westerly jet over western and central Asia with anomalous southerly wind at lower levels and ascending motion prevailing over the Tarim Basin. Such anomalies in the atmospheric circulations provide favorable conditions for the enhanced summer rainfall over the Tarim Basin. Further analysis suggests that the weakened South Asian summer monsoon (SASM) could be potentially responsible for the middle and upper tropospheric cooling over central Asia. This is largely through the atmospheric responses to the diabatic heating effect of the SASM. A weakened SASM can result in an anomalous cyclone in the middle and upper troposphere over central Asia. The western part of the anomalous cyclone produces more cold air advection, which leads to the cooling. This study suggests indirect but important effects of the SASM on the summer rainfall over the Tarim Basin.
Near-Inertial Mixing in the Central Arctic Ocean
Authors: Fer Ilker 
Published: April 2014

Abstract
Observations were made in April 2007 of horizontal currents, hydrography, and shear microstructure in the upper 500 m from a drifting ice camp in the central Arctic Ocean. An approximately 4-day-long time series, collected about 10 days after a storm event, shows enhanced near-inertial oscillations in the first half of the measurement period with comparable upward- and downward-propagating energy. Rough estimates of wind work and near-inertial flux imply that the waves were likely generated by the previous storm. The near-inertial frequency band is associated with dominant clockwise rotation in time of the horizontal currents and enhanced dissipation rates of turbulent kinetic energy. The vertical profile of dissipation rate shows elevated values in the pycnocline between the relatively turbulent underice boundary layer and the deeper quiescent water column. Dissipation averaged in the pycnocline is near-inertially modulated, and its magnitude decays approximately at a rate implied by the reduction of energy over time. Observations suggest that near-inertial energy and internal wave–induced mixing play a significant role in vertical mixing in the Arctic Ocean.
The Impact of Nocturnal Hypoglycemia on Clinical and Cost-Related Issues in Patients With Type 1 and Type 2 Diabetes
Authors: Edelman Steven V. , Blose Jamie S. 
Published: April 2014

Purpose This article provides an overview of the clinical and economic issues associated with hypoglycemia in patients with type 1 and type 2 diabetes mellitus. Current research regarding hypoglycemia is comprehensively reviewed, with special emphasis on nocturnal hypoglycemia, as almost 50% of all severe hypoglycemic episodes occur at nighttime during sleep. Current findings on the economic and human burden of hypoglycemia are presented. Conclusions Poor diabetes self-management leads to an increased risk for hypoglycemia and the development of long-term complications associated with poor glycemic control. Hypoglycemia is also associated with increased health care costs and resources required to treat hypoglycemic events, as well as personal financial costs and loss of productivity at school or work. In addition, fear, anxiety, and worry about hypoglycemic episodes are shown to interfere with patients’ quality of life. Nocturnal hypoglycemia can cause a number of immediate clinical consequences, including convulsions, coma, and even death. Repeated long-term exposure to nocturnal hypoglycemia can blunt counterregulatory mechanisms that maintain glucose levels, leading to reduced cognitive function, impaired awareness of hypoglycemia, and hypoglycemia-associated autonomic failure. Clinicians must be aware of the impact of hypoglycemia, particularly nocturnal hypoglycemia, so that they can prescribe appropriate glucose-lowering therapy and educate patients about the prevention and management of hypoglycemic events to reduce anxiety and improve quality of life.
Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: Therapeutic implications for migraine and other pains
Authors: Burstein Rami , Zhang XiChun , Levy Dan , Aoki K Roger , Brin Mitchell F 
Published: April 2014

Background Meningeal and other trigeminal nociceptors are thought to play important roles in the initiation of migraine headache. Currently, the only approved peripherally administered chronic migraine prophylactic drug is onabotulinumtoxinA. The purpose of this study was to determine how botulinum neurotoxin type A (BoNT-A) affects naïve and sensitized meningeal nociceptors. Material and methods Using electrophysiological techniques, we identified 43 C- and 36 Aδ-meningeal nociceptors, and measured their spontaneous and evoked firing before and after BoNT-A administration to intracranial dura and extracranial suture-receptive fields. Results As a rule, BoNT-A inhibited C- but not Aδ-meningeal nociceptors. When applied to nonsensitized C-units, BoNT-A inhibited responses to mechanical stimulation of the dura with suprathreshold forces. When applied to sensitized units, BoNT-A reversed mechanical hypersensitivity. When applied before sensitization, BoNT-A prevented development of mechanical hypersensitivity. When applied extracranially to suture branches of intracranial meningeal nociceptors, BoNT-A inhibited the mechanical responsiveness of the suture branch but not dural axon. In contrast, BoNT-A did not inhibit C-unit responses to mechanical stimulation of the dura with threshold forces, or their spontaneous activity. Discussion The study provides evidence for the ability of BoNT-A to inhibit mechanical nociception in peripheral trigeminovascular neurons. These findings suggest that BoNT-A interferes with neuronal surface expression of high-threshold mechanosensitive ion channels linked preferentially to mechanical pain by preventing their fusion into the nerve terminal membrane.
Occupied bed days a redundant currency? An evaluation of the first 10 years of an integrated model of care for mentally ill adolescents
Authors: Adrian Nicolette , Smith Jared G 
Published: April 2014

Background: We report on clinical outcomes from the first 10 years of operation of an Adolescent Assertive Outreach Team (AAOT) which forms part of an integrated Tier 4 service offering inpatient, day-patient and intensive community treatment. Method: Prospective data were recorded at pre- and post-treatment for patients accepted for treatment by the AAOT over a 10-year period. Results: A total of 393 adolescents were treated by the AAOT, and 135 received some hospital care as part of their treatment. Contact periods with the team were significantly shorter for those treated wholly in the community. Outcome measures indicated severe pathology at onset with substantial improvement in function regardless of whether treatment involved hospital care or community support only. Conclusions: Adolescent Outreach is a viable and sustainable alternative to inpatient care for some young people referred for admission, reducing but not eliminating the need for acute beds.
Postoperative stiff shoulder after open rotator cuff repair: a 3- to 20-year follow-up study
Authors: Vastamäki H. , Vastamäki M. 
Published: April 2014

Background and Aims: Stiffness after a rotator cuff tear is common. So is stiffness after an arthroscopic rotator cuff repair. In the literature, however, postoperative restriction of passive range of motion after open rotator cuff repair in shoulders with free passive range of motion at surgery has seldom been recognized. We hypothesize that this postoperative stiffness is more frequent than recognized and slows the primary postoperative healing after a rotator cuff reconstruction. We wondered how common is postoperative restriction of both active and passive range of motion after open rotator cuff repair in shoulders with free passive preoperative range of motion, how it recovers, and whether this condition influences short- and long-term results of surgery. We also explored factors predicting postoperative shoulder stiffness. Material and Methods: We retrospectively identified 103 postoperative stiff shoulders among 416 consecutive open rotator cuff repairs, evaluating incidence and duration of stiffness, short-term clinical results and long-term range of motion, pain relief, shoulder strength, and functional results 3–20 (mean 8.7) years after surgery in 56 patients. Results: The incidence of postoperative shoulder stiffness was 20%. It delayed primary postoperative healing by 3–6 months and resolved during a mean 6.3 months postoperatively. External rotation resolved first, corresponding to that of the controls at 3 months; flexion and abduction took less than 1 year after surgery. The mean summarized range of motion (flexion + abduction + external rotation) increased as high as 93% of the controls’ range of motion by 6 months and 100% by 1 year. Flexion, abduction, and internal rotation improved to the level of the contralateral shoulders as did pain, strength, and function. Age at surgery and condition of the biceps tendon were related to postoperative stiffness. Conclusions: Postoperative stiff shoulder after open rotator cuff repair is a common complication resolving in 6–12 months with good long-term results.
Endovascular first strategy for de novo TransAtlantic Inter-Society Consensus C and D femoro-popliteal disease: Mid-term outcomes from a single tertiary referral center
Authors: Grenville Jeffrey Lorne , Tan Kong Teng , Moshonov Hadas , Rajan Dheeraj Kumar 
Published: April 2014

Purpose: Describe outcomes after endovascular intervention of TransAtlantic Inter-Society Consensus C and D femoro-popliteal disease. Materials and methods: Retrospective cohort study. Patient demographics, ankle-brachial indices, and lesion details were analyzed from a prospectively maintained database. In all, 980 limbs treated with percutaneous transluminal angioplasty ± stenting of the femoro-popliteal segment between 2005 and 2012 were reviewed. Seventy-six patients representing 83 limbs with de novo TransAtlantic Inter-Society Consensus C and D lesions measuring ≥15 cm continuously were identified (mean age 71.3 ± 12.1 years, 62% male). Results: Twenty-five (30.1%) limbs were treated for severe claudication and 58 (69.9%) for critical limb ischemia. The mean pre-procedural ankle-brachial index was 0.47 ± 0.19. The mean lesion length was 22.9 ± 4.82 cm. Seventy patients representing 77 limbs were available for a mean follow-up length of 19.5 months (range 0–79). The mean post-procedural ankle-brachial index was 0.71 ± 0.28. Primary, assisted-primary, and secondary patency rates were 68.1%, 72.7%, and 83.3% at 6 months, 55.3%, 63.6%, and 58.3% at 12 months, and 38.2%, unavailable, and 10.4% at 24 months, respectively. Conclusions: Angioplasty-first strategy for TransAtlantic Inter-Society Consensus C and D lesions of the femoro-popliteal artery can be safely performed. However, patency drastically decreases after 12 months suggesting further improvements are required to achieve longer-term clinical benefit.
Sideline Coverage
Authors: Gould Sara J. , Cardone Dennis A. , Munyak John , Underwood Philipp J. , Gould Stephen A. 
Published: April 2014

Context: Sidelines coverage presents unique challenges in the evaluation of injured athletes. Health care providers may be confronted with the question of when to obtain radiographs following an injury. Given that most sidelines coverage occurs outside the elite level, radiographs are not readily available at the time of injury, and the decision of when to send a player for radiographs must be made based on physical examination. Clinical tools have been developed to aid in identifying injuries that are likely to result in radiographically important fractures or dislocations. Evidence Acquisition: A search for the keywords x-ray and decision rule along with the anatomic locations shoulder, elbow, wrist, knee, and ankle was performed using the PubMed database. No limits were set regarding year of publication. We selected meta-analyses, randomized controlled trials, and survey results. Our selection focused on the largest, most well-studied published reports. We also attempted to include studies that reported the application of the rules to the field of sports medicine. Study Design: Retrospective literature review. Level of Evidence: Level 4. Results: The Ottawa Foot and Ankle Rules have been validated and implemented and are appropriate for use in both pediatric and adult populations. The Ottawa Knee Rules have been widely studied, validated, and accepted for evaluation of knee injuries. There are promising studies of decision rules for clinically important fractures of the wrist, but these studies have not been validated. The elbow has been evaluated with good outcomes via the elbow extension test, which has been validated in both single and multicenter studies. Currently, there are no reliable clinical decision tools for traumatic sports injuries to the shoulder to aid in the decision of when to obtain radiographs. Conclusion: Clinical decision tools have been developed to aid in the diagnosis and management of injuries commonly sustained during sporting events. Tools that have been appropriately validated in populations outside the initial study population can assist sports medicine physicians in the decision of when to get radiographs from the sidelines.
Past and present in abdominal surgery management for Cushing’s syndrome
Authors: Vilallonga Ramon , Zafon Carles , Fort José Manuel , Mesa Jordi , Armengol Manel 
Published: April 2014

Introduction: Data on specific abdominal surgery and Cushing’s syndrome are infrequent and are usually included in the adrenalectomy reports. Current literature suggests the feasibility and reproducibility of the surgical adrenalectomies for patients diagnosed with non-functioning tumours and functioning adrenal tumours including pheochromocytoma, Conn’s syndrome and Cushing’s syndrome. Discussion: Medical treatment for Cushing’s syndrome is feasible but follow-up or clinical situations force the patient to undergo a surgical procedure. Laparoscopic surgery has become a gold standard nowadays in a broad spectrum of pathologies. Laparoscopic adrenalectomies are also standard procedures nowadays. However, despite the different characteristics and clinical disorders related to the laparoscopically removed adrenal tumours, the intraoperative and postoperative outcomes do not significantly differ in most cases between the different groups of patients, techniques and types of tumours. Tumour size, hormonal type and surgeon’s experience could be different factors that predict intraoperative and postoperative complications. Transabdominal and retroperitoneal approaches can be considered. Outcomes for Cushing’s syndrome do not differ depending on the surgical approach. Novel technologies and approaches such as single-port surgery or robotic surgery have proven to be safe and feasible. Conclusion: Laparoscopic adrenalectomy is a safe and feasible approach to adrenal pathology, providing the patients with all the benefits of minimally invasive surgery. Single-port access and robotic surgery can be performed but more data are required to identify their correct role between the different surgical approaches. Factors such as surgeon’s experience, tumour size and optimal technique can affect the outcomes of this surgery.
Long-term Course in Adolescents after Anterior Cruciate Ligament Reconstruction (ACL)
Authors: Mansson Olle , Sernert Ninni , Kartus Juri T. 
Published: April 2014

Objectives: The risk for further intra-articular damage associated with conservative treatment or delayed ACL reconstruction must be considered against the risk for growth disturbance with early reconstruction and trans-physeal drilling. Long-term follow-ups after surgical treatment of ACL injuries in children are rare. The aims of the present study were to evaluate the results 10-20 years after ACL reconstruction in terms of the presence of osteoarthritis, clinical assessments and health-related quality of life in patients who were adolescents at the time of surgery. Methods: 32 children, aged 12-16 years (11 boys; 21 girls), with symtomatic unilateral ACL rupture, underwent reconstruction using bone-patellar bone-tendon (n=10) or hamstring tendon (n=22) autograft. Twenty-nine patients (91%) underwent clinical, radiographical and health-related quality of life assessments after 10-20 years (mean 175 months). Results: The reconstructed knee had significantly more osteoarthritic changes compared to the non-involved contra lateral knee. Preoperatively the Tegner activity level was 4 (2-8) and the Lysholm knee score was 75 (50-90) points. At follow-up the corresponding values were 4 (1-7) and 84 (34-100) points, (p=n.s; preop v follow-up). The one-leg-hop test was 84% (0-105) preoperatively and 93% (53-126) at follow-up (p=0.003). At follow-up muscle strength measurements diplayed more than 90 % of the non-involved leg in both extension and flexion. The knee laxity measurement was significantly less at follow-up than preoperatively (p=0.001). The SF-36 revealed scores compareable to healthy controls (fig. 1).The EQ 5D was 0.9. The KOOS values were lower in all dimensions compared to an aged matched healthy controls. Conclusion: In the long term, patients who were adolescents at the time of ACL reconstruction reveal significantly more radiographically visible osteoarthritic changes in their operated knee than in their non-involved contralateral knee Clinical outcomes and health-related quality of life are comparable to healthy controls.